Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032916.33237.A9
L. Duebener, I. Hagino, T. Sakamoto, L. Mime, C. Stamm, D. Zurakowski, H. Schäfers, R. Jonas
ObjectiveThere is controversy regarding the optimal pH strategy during deep hypothermic bypass in children. We directly visualized the effects of the pH-stat and alpha-stat strategy on cerebral microcirculation (including leukocyte/endothelial cell interactions) in a piglet model using intravital fluorescence microscopy. MethodsTwo groups of 5 piglets (mean weight 9.6±1.3 kg) with a cranial window over parietal cerebral cortex underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass ([CPB] Hct 30%, 100 mL/kg/min), 60-minute circulatory arrest at 15°C, and 40-minute rewarming with alpha-stat (group alpha) or pH-stat (group pH). Plasma was labeled with fluorescein-ITC-dextran for assessment of microvascular diameter. Circulating leukocytes were labeled and observed in postcapillary venules for adhesion before and up to 120 minutes after CPB. Cerebral tissue oxygenation was evaluated by quantification of NADH autofluorescence, which increases during ischemia. ResultsAt the end of normothermic bypass diameter of cerebrocortical microvessels increased to 116±9% (alpha) versus 119±10% (pH) of pre-CPB baseline values. During cooling microvascular diameter decreased in group alpha and significantly increased in group pH (89±11% (alpha) versus 132±13% (pH) at the end of cooling;P <0.001). During the first 10 minutes of rewarming, the cerebral microvascular diameter was significantly larger when the pH stat strategy was used. Tissue oxygenation at the end of cooling was significantly greater in the pH-stat group (P =0.008). On reperfusion, the pH-stat strategy resulted in significantly more rapid return of tissue oxygenation toward baseline although at the end of rewarming the metabolic recovery was complete in both groups. The whole body lactate during early rewarming was significantly less with the pH stat strategy. There was no significant difference between the groups regarding the number of adherent leukocytes throughout the time course of the experiment. ConclusionspH-stat management increases tissue oxygenation during deep hypothermic bypass and after circulatory arrest. Leukocyte/endothelial cell interactions during hypothermic bypass are mild with both alpha-stat and pH-stat.
{"title":"Effects of pH Management During Deep Hypothermic Bypass on Cerebral Microcirculation: Alpha-Stat Versus pH-Stat","authors":"L. Duebener, I. Hagino, T. Sakamoto, L. Mime, C. Stamm, D. Zurakowski, H. Schäfers, R. Jonas","doi":"10.1161/01.CIR.0000032916.33237.A9","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032916.33237.A9","url":null,"abstract":"ObjectiveThere is controversy regarding the optimal pH strategy during deep hypothermic bypass in children. We directly visualized the effects of the pH-stat and alpha-stat strategy on cerebral microcirculation (including leukocyte/endothelial cell interactions) in a piglet model using intravital fluorescence microscopy. MethodsTwo groups of 5 piglets (mean weight 9.6±1.3 kg) with a cranial window over parietal cerebral cortex underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass ([CPB] Hct 30%, 100 mL/kg/min), 60-minute circulatory arrest at 15°C, and 40-minute rewarming with alpha-stat (group alpha) or pH-stat (group pH). Plasma was labeled with fluorescein-ITC-dextran for assessment of microvascular diameter. Circulating leukocytes were labeled and observed in postcapillary venules for adhesion before and up to 120 minutes after CPB. Cerebral tissue oxygenation was evaluated by quantification of NADH autofluorescence, which increases during ischemia. ResultsAt the end of normothermic bypass diameter of cerebrocortical microvessels increased to 116±9% (alpha) versus 119±10% (pH) of pre-CPB baseline values. During cooling microvascular diameter decreased in group alpha and significantly increased in group pH (89±11% (alpha) versus 132±13% (pH) at the end of cooling;P <0.001). During the first 10 minutes of rewarming, the cerebral microvascular diameter was significantly larger when the pH stat strategy was used. Tissue oxygenation at the end of cooling was significantly greater in the pH-stat group (P =0.008). On reperfusion, the pH-stat strategy resulted in significantly more rapid return of tissue oxygenation toward baseline although at the end of rewarming the metabolic recovery was complete in both groups. The whole body lactate during early rewarming was significantly less with the pH stat strategy. There was no significant difference between the groups regarding the number of adherent leukocytes throughout the time course of the experiment. ConclusionspH-stat management increases tissue oxygenation during deep hypothermic bypass and after circulatory arrest. Leukocyte/endothelial cell interactions during hypothermic bypass are mild with both alpha-stat and pH-stat.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"263 1","pages":"I-103-I-108"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77150216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032881.55215.DB
Ken Suzuki, B. Murtuza, N. Suzuki, Mahboob A. Khan, Y. Kaneda, M. Yacoub
BackgroundGraft coronary arteriopathy (GCA) after heart transplantation is a major factor limiting the long-term survival of the recipients. Human cytomegalovirus (HCMV) infection is a possible cause of this disease which is characterized by diffuse intimal thickening resulting from smooth muscle cell migration and proliferation. It has been reported that HCMV immediate-early (IE) proteins, IE1 and IE2, could play an important role in the development of this disease; however, the precise in vivo role of these proteins in causing GCA has not been clarified. Methods and ResultsExcised Lewis rat hearts were transfected with HCMV IE1–72, IE2–86 or control plasmid by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, and transplanted into syngeneic recipients’ abdomens. All cardiac grafts continued to beat well throughout the incubation period in the absence of immunosuppression. Exclusive expression of IE1–72 or IE2–86 protein in coronary artery walls was demonstrated after IE1–72 or IE2–86 gene transfection, respectively. Luminal occlusion as a consequence of intimal thickening of graft coronary arteries developed in the IE2–86 transfected hearts at day 21 after transplantation (30.1±3.4% occlusion, P <0.0001), compared with the IE1–72 and control transfected ones (8.2±1.6 and 6.8±1.1%, respectively). In contrast, there was no significant difference in luminal occlusion between the IE1–72 and control transfected hearts. ConclusionsWe have demonstrated that expression of IE2–86 alone, but not IE1–72, causes intimal hyperplasia after cardiac transplantation. IE2–86 protein may therefore prove to be a useful target in therapies aimed at preventing HCMV-related GCA and improving the long-term result of cardiac transplantation.
{"title":"Human Cytomegalovirus Immediate-Early Protein IE2–86, but not IE1–72, Causes Graft Coronary Arteriopathy in the Transplanted Rat Heart","authors":"Ken Suzuki, B. Murtuza, N. Suzuki, Mahboob A. Khan, Y. Kaneda, M. Yacoub","doi":"10.1161/01.CIR.0000032881.55215.DB","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032881.55215.DB","url":null,"abstract":"BackgroundGraft coronary arteriopathy (GCA) after heart transplantation is a major factor limiting the long-term survival of the recipients. Human cytomegalovirus (HCMV) infection is a possible cause of this disease which is characterized by diffuse intimal thickening resulting from smooth muscle cell migration and proliferation. It has been reported that HCMV immediate-early (IE) proteins, IE1 and IE2, could play an important role in the development of this disease; however, the precise in vivo role of these proteins in causing GCA has not been clarified. Methods and ResultsExcised Lewis rat hearts were transfected with HCMV IE1–72, IE2–86 or control plasmid by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, and transplanted into syngeneic recipients’ abdomens. All cardiac grafts continued to beat well throughout the incubation period in the absence of immunosuppression. Exclusive expression of IE1–72 or IE2–86 protein in coronary artery walls was demonstrated after IE1–72 or IE2–86 gene transfection, respectively. Luminal occlusion as a consequence of intimal thickening of graft coronary arteries developed in the IE2–86 transfected hearts at day 21 after transplantation (30.1±3.4% occlusion, P <0.0001), compared with the IE1–72 and control transfected ones (8.2±1.6 and 6.8±1.1%, respectively). In contrast, there was no significant difference in luminal occlusion between the IE1–72 and control transfected hearts. ConclusionsWe have demonstrated that expression of IE2–86 alone, but not IE1–72, causes intimal hyperplasia after cardiac transplantation. IE2–86 protein may therefore prove to be a useful target in therapies aimed at preventing HCMV-related GCA and improving the long-term result of cardiac transplantation.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"41 1","pages":"I-158-I-162"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76254244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032903.33237.40
B. Podesser, J. Schirnhofer, O. Bernecker, A. Kröner, M. Franz, S. Semsroth, B. Fellner, J. Neumüller, S. Hallström, E. Wolner
BackgroundWhereas the number of patients with reduced left ventricular function after myocardial infarction who need revascularization is increasing, the operative outcome is still inadequate. Consequently, drugs that increase myocardial perfusion and decrease oxygen consumption of the remodeled myocardium are of particular interest to cardiac surgeons. Angiotensin-converting enzyme inhibitors (ACE-I) provide this pharmacologic profile. This study tests the hypothesis whether acute ACE inhibition during cardioplegic arrest improves outcome in failing rat hearts. Methods and ResultsMale Wistar rats (260±15 g) underwent coronary ligation. Ten weeks later the rats had developed heart failure (HF). Hearts were harvested and studied on a red cell-perfused working heart: 60 minutes of ischemia, protected by cold blood cardioplegia (CP) every 20 minutes, and 45 minutes of reperfusion. Rats were randomly assigned to 2 groups, 1 group receiving the ACE-I quinaprilat with CP (QuinaMI, n=11), and 1 group receiving CP only (MI, n=8). Hemodynamic recovery, high-energy phosphates (HEP), and morphometry were analyzed. Groups showed similar degrees of myocardial infarction (44±5 versus 39±4% of LVmass), LVEDP (5.0±1 versus 4±1 mm Hg) and no differences in baseline values such as external heart work (EHW) and coronary flow (CF). At the end of reperfusion, EHW and CF were significantly higher in QuinaMI than MI (P <0.05 and 0.01), LVEDP had returned to baseline in QuinaMI (P <0.01). HEP were significantly higher preserved in QuinaMI than MI (P <0.05). ConclusionsAcute ACE inhibition during CP improves postischemic systolic and diastolic function, coronary perfusion as well as HEP-levels in a rat model of HF. These results may have clinical impact on patients with HF undergoing cardiac surgery.
背景:虽然心肌梗死后左心室功能下降的患者需要血运重建的人数在增加，但手术效果仍然不理想。因此，增加心肌灌注和减少重塑心肌耗氧量的药物是心脏外科医生特别感兴趣的。血管紧张素转换酶抑制剂(ACE-I)提供了这种药理学特征。本研究验证了心脏骤停时急性ACE抑制是否能改善衰竭大鼠心脏的预后。方法与结果Wistar小鼠(260±15 g)行冠状动脉结扎术。10周后，大鼠出现心力衰竭。摘取心脏，在红细胞灌注的工作心脏上进行研究:缺血60分钟，每20分钟进行一次冷血骤停(CP)保护，再灌注45分钟。将大鼠随机分为2组，1组给予ACE-I喹那普利加CP (QuinaMI, n=11)， 1组只给予CP (MI, n=8)。血流动力学恢复、高能磷酸盐(HEP)和形态学分析。各组心肌梗死程度相似(44±5 vs 39±4% LVmass)， LVEDP(5.0±1 vs 4±1 mm Hg)，基线值无差异，如外心功(EHW)和冠状动脉血流(CF)。再灌注结束时，QuinaMI组EHW和CF显著高于MI组(P <0.05和0.01)，LVEDP已恢复到基线水平(P <0.01)。QuinaMI组HEP保存量显著高于MI组(P <0.05)。结论急性ACE抑制可改善心衰模型大鼠心肌缺血后收缩和舒张功能、冠状动脉灌注及hep水平。这些结果可能对心衰患者接受心脏手术有临床影响。
{"title":"Optimizing Ischemia/Reperfusion in the Failing Rat Heart—Improved Myocardial Protection With Acute ACE Inhibition","authors":"B. Podesser, J. Schirnhofer, O. Bernecker, A. Kröner, M. Franz, S. Semsroth, B. Fellner, J. Neumüller, S. Hallström, E. Wolner","doi":"10.1161/01.CIR.0000032903.33237.40","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032903.33237.40","url":null,"abstract":"BackgroundWhereas the number of patients with reduced left ventricular function after myocardial infarction who need revascularization is increasing, the operative outcome is still inadequate. Consequently, drugs that increase myocardial perfusion and decrease oxygen consumption of the remodeled myocardium are of particular interest to cardiac surgeons. Angiotensin-converting enzyme inhibitors (ACE-I) provide this pharmacologic profile. This study tests the hypothesis whether acute ACE inhibition during cardioplegic arrest improves outcome in failing rat hearts. Methods and ResultsMale Wistar rats (260±15 g) underwent coronary ligation. Ten weeks later the rats had developed heart failure (HF). Hearts were harvested and studied on a red cell-perfused working heart: 60 minutes of ischemia, protected by cold blood cardioplegia (CP) every 20 minutes, and 45 minutes of reperfusion. Rats were randomly assigned to 2 groups, 1 group receiving the ACE-I quinaprilat with CP (QuinaMI, n=11), and 1 group receiving CP only (MI, n=8). Hemodynamic recovery, high-energy phosphates (HEP), and morphometry were analyzed. Groups showed similar degrees of myocardial infarction (44±5 versus 39±4% of LVmass), LVEDP (5.0±1 versus 4±1 mm Hg) and no differences in baseline values such as external heart work (EHW) and coronary flow (CF). At the end of reperfusion, EHW and CF were significantly higher in QuinaMI than MI (P <0.05 and 0.01), LVEDP had returned to baseline in QuinaMI (P <0.01). HEP were significantly higher preserved in QuinaMI than MI (P <0.05). ConclusionsAcute ACE inhibition during CP improves postischemic systolic and diastolic function, coronary perfusion as well as HEP-levels in a rat model of HF. These results may have clinical impact on patients with HF undergoing cardiac surgery.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"434 1","pages":"I-277-I-283"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77529290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032894.55215.32
Y. Baribeau, B. Westbrook, D. Charlesworth, M. Hearne, W. Bradley, C. Maloney
BackgroundReview of the clinical and therapeutic implications of difference in arm blood pressure detected preoperatively in patients having heart surgery. Methods and ResultsProspective study of 53 patients (Group 1) with gradient and comparison with a group of 175 patients without gradient (Group 2). All patients had preoperative carotid duplex interrogation and operative epiaortic scanning. There was no statistical difference regarding age, sex, status, redo, diabetes, ejection fraction, prior myocardial infarct, hyperlipidemia, or creatinine level. Risks factors for Group 1 included peripheral vascular disease (P <0.0001) and cerebrovascular symptoms (P =0.0196). Severe carotid disease (>80% stenosis) was seen in 41.5% of Group 1 and 13.7% of Group 2 (P <0.0001) patients. Severe atherosclerotic proximal aortic disease was found in 39.6% of Group 1 and 10.8% of Group 2 (P <0.0001) patients. There were 7 patients with strokes in Group 1 (13.20%) and 9 in Group 2 (5.14%;P =0.06). Four patients died in Group 1 (7.54%) and 10 died in Group 2 (5.71%;P =0.74). ConclusionBrachial gradient is a marker for increased carotid and proximal atherosclerotic aortic disease. Preoperative arch study at the time of catheterization is strongly recommended, as well as preoperative carotid Doppler and operative epiaortic ultrasound.
{"title":"Brachial Gradient in Cardiac Surgical Patients","authors":"Y. Baribeau, B. Westbrook, D. Charlesworth, M. Hearne, W. Bradley, C. Maloney","doi":"10.1161/01.CIR.0000032894.55215.32","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032894.55215.32","url":null,"abstract":"BackgroundReview of the clinical and therapeutic implications of difference in arm blood pressure detected preoperatively in patients having heart surgery. Methods and ResultsProspective study of 53 patients (Group 1) with gradient and comparison with a group of 175 patients without gradient (Group 2). All patients had preoperative carotid duplex interrogation and operative epiaortic scanning. There was no statistical difference regarding age, sex, status, redo, diabetes, ejection fraction, prior myocardial infarct, hyperlipidemia, or creatinine level. Risks factors for Group 1 included peripheral vascular disease (P <0.0001) and cerebrovascular symptoms (P =0.0196). Severe carotid disease (>80% stenosis) was seen in 41.5% of Group 1 and 13.7% of Group 2 (P <0.0001) patients. Severe atherosclerotic proximal aortic disease was found in 39.6% of Group 1 and 10.8% of Group 2 (P <0.0001) patients. There were 7 patients with strokes in Group 1 (13.20%) and 9 in Group 2 (5.14%;P =0.06). Four patients died in Group 1 (7.54%) and 10 died in Group 2 (5.71%;P =0.74). ConclusionBrachial gradient is a marker for increased carotid and proximal atherosclerotic aortic disease. Preoperative arch study at the time of catheterization is strongly recommended, as well as preoperative carotid Doppler and operative epiaortic ultrasound.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"26 8 1","pages":"I-11-I-13"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82707518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032889.55215.F1
S. Ghostine, C. Carrion, Luiz César Guarita Souza, P. Richard, P. Bruneval, J. Vilquin, B. Pouzet, K. Schwartz, P. Menasché, A. Hagège
BackgroundTransplantation (Tx) of skeletal myoblasts (SM) within an infarcted myocardium improves global left ventricular (LV) function, although a direct systolic effect remains controversial. Methods and ResultsGlobal and regional LV functions were studied in a sheep model (n=16) of infarction before (baseline), and 4 (M4), and 12 (M12) months after in-scar injections of autologous SM or culture medium (CM). LV end-diastolic volume (EDV), ejection fraction (EF), wall motion score (WMS), and systolic myocardial velocity gradient (MVG) across the scar were measured by echocardiography with tissue Doppler imaging. Parameters were similar at baseline between groups. At M4, Tx of SM reduced the postinfarction increase in EDV (72±8 versus 105±13 mL in the CM group, P <0.05) and the decrease in EF (48±5 versus 33±3% in the CM group, P =0.006) although it improved WMS (5.4±1.2 versus 13±2.2 in the CM group, P <0.01) and SMVG (0.60±0.13 versus –0.04±.13 seconds-1 in the CM group, P <0.05). Results were similar at M12. In-scar accumulation of myotubes and SM were detected in all Tx animals up to M12, with co-expression of fast and slow isoforms of the myosin heavy chain (MHC) (30% of the fibers versus 0% in the normal skeletal muscle) and decreased collagen density (30±2% versus 73±3%, P <0.0001). ConclusionFor up to 1 year, Tx of SM limits postinfarction EF deterioration and improves systolic scar function through colonization of fibrosis by skeletal muscle cells with expression of both MHC isoforms, which may confer to the graft the ability to withstand a cardiac-type workload.
梗死心肌内骨骼肌母细胞(SM)移植(Tx)可改善左心室(LV)整体功能，尽管其直接收缩作用仍存在争议。方法和结果在梗死前(基线)、瘢痕内注射自体SM或培养基(CM)后4 (M4)和12 (M12)个月的绵羊模型(n=16)中研究了整体和局部左室功能。采用超声心动图结合组织多普勒成像测量左室舒张末容积(EDV)、射血分数(EF)、壁运动评分(WMS)和收缩心肌速度梯度(MVG)。各组间基线参数相似。在M4时，SM的Tx降低了梗死后EDV的增加(CM组为72±8 mL, CM组为105±13 mL, P <0.05)， EF的降低(CM组为48±5,CM组为33±3%，P =0.006)，尽管它改善了WMS (CM组为5.4±1.2,CM组为13±2.2,P <0.01)和SMVG(0.60±0.13,CM组为-0.04±)。CM组为13 s-1, P <0.05)。M12时的结果相似。所有Tx动物在M12之前都检测到肌管和SM的瘢痕内积累，肌球蛋白重链(MHC)的快速和缓慢亚型共表达(30%的纤维，而正常骨骼肌为0%)，胶原密度降低(30±2%对73±3%，P <0.0001)。结论:在长达1年的时间里，SM的Tx限制了梗死后EF的恶化，并通过表达两种MHC亚型的骨骼肌细胞定殖纤维化改善收缩疤痕功能，这可能赋予移植物承受心脏型负荷的能力。
{"title":"Long-Term Efficacy of Myoblast Transplantation on Regional Structure and Function After Myocardial Infarction","authors":"S. Ghostine, C. Carrion, Luiz César Guarita Souza, P. Richard, P. Bruneval, J. Vilquin, B. Pouzet, K. Schwartz, P. Menasché, A. Hagège","doi":"10.1161/01.CIR.0000032889.55215.F1","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032889.55215.F1","url":null,"abstract":"BackgroundTransplantation (Tx) of skeletal myoblasts (SM) within an infarcted myocardium improves global left ventricular (LV) function, although a direct systolic effect remains controversial. Methods and ResultsGlobal and regional LV functions were studied in a sheep model (n=16) of infarction before (baseline), and 4 (M4), and 12 (M12) months after in-scar injections of autologous SM or culture medium (CM). LV end-diastolic volume (EDV), ejection fraction (EF), wall motion score (WMS), and systolic myocardial velocity gradient (MVG) across the scar were measured by echocardiography with tissue Doppler imaging. Parameters were similar at baseline between groups. At M4, Tx of SM reduced the postinfarction increase in EDV (72±8 versus 105±13 mL in the CM group, P <0.05) and the decrease in EF (48±5 versus 33±3% in the CM group, P =0.006) although it improved WMS (5.4±1.2 versus 13±2.2 in the CM group, P <0.01) and SMVG (0.60±0.13 versus –0.04±.13 seconds-1 in the CM group, P <0.05). Results were similar at M12. In-scar accumulation of myotubes and SM were detected in all Tx animals up to M12, with co-expression of fast and slow isoforms of the myosin heavy chain (MHC) (30% of the fibers versus 0% in the normal skeletal muscle) and decreased collagen density (30±2% versus 73±3%, P <0.0001). ConclusionFor up to 1 year, Tx of SM limits postinfarction EF deterioration and improves systolic scar function through colonization of fibrosis by skeletal muscle cells with expression of both MHC isoforms, which may confer to the graft the ability to withstand a cardiac-type workload.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"29 1","pages":"I-131-I-136"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78784232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032896.55215.A0
C. Stamm, I. Friehs, Douglas B. Cowan, H. Cao-Danh, Yeong-Hoon Choi, L. Duebener, F. McGowan, P. D. del Nido
BackgroundIschemia and adrenergic stimulation of cardiomyocyte cultures have been shown to induce apoptotic cell death. We hypothesized that in a model of contractile dysfunction following ischemia, a commonly used catecholamine such as dopamine augments cardiomyocyte apoptosis via activation of calcium-dependent signaling cascades. Methods and ResultsIsolated perfused rabbit hearts were subjected to 45 minutes of normothermic ischemia with cardioplegic arrest. Hearts were reperfused for 120 minutes with unmodified perfusate (control), perfusate containing 20 nM dopamine, dopamine+2,3-butanedione monoxime (BDM), a MgATPase-inhibitor, or the calcium-sensitizing inotrope ORG 30029. Ischemia-reperfusion alone caused contractile dysfunction without significant myocardial necrosis (left ventricular pressure-volume curves; 1% triphenyltetrazolium chloride staining; creatine kinase release) or apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling [TUNEL] analysis; immunoblotting for poly(ADP-ribose) polymerase [PARP] cleavage; activation of caspases-3, -8, and -9; expression of Bax/Bcl-2). Intracellular calcium [Ca2+]i measured by rhod-2 spectrofluorometry was increased in dopamine-reperfused hearts. Although postischemic dopamine treatment improved contractility, the number of apoptotic cardiomyocytes was significantly higher than in untreated postischemic hearts (32.5±9 versus 5.5±1.6/1000 nuclei, P <0.01). Further evidence of dopamine-stimulated apoptosis included PARP cleavage, activation of mitochondrial-derived caspase-9, and the terminal effector caspase-3. Dopamine also increased cellular content of pro-apoptotic Bax while decreasing anti-apoptotic Bcl-2. Simultaneous treatment with BDM suppressed contractility without affecting [Ca2+]i and did not reduce dopamine-stimulated apoptotic markers. When contractility was increased without elevating [Ca2+]i using ORG 30029, no activation of pro-apoptotic signaling cascades was found. Dopamine infusion in nonischemic hearts did not result in cardiomyocyte apoptosis. ConclusionsPostischemic dopamine treatment of contractile dysfunction activates pro-apoptotic signal cascades, most likely via a calcium-dependent process and mitochondrial damage.
{"title":"Dopamine Treatment of Postischemic Contractile Dysfunction Rapidly Induces Calcium-Dependent Pro-Apoptotic Signaling","authors":"C. Stamm, I. Friehs, Douglas B. Cowan, H. Cao-Danh, Yeong-Hoon Choi, L. Duebener, F. McGowan, P. D. del Nido","doi":"10.1161/01.CIR.0000032896.55215.A0","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032896.55215.A0","url":null,"abstract":"BackgroundIschemia and adrenergic stimulation of cardiomyocyte cultures have been shown to induce apoptotic cell death. We hypothesized that in a model of contractile dysfunction following ischemia, a commonly used catecholamine such as dopamine augments cardiomyocyte apoptosis via activation of calcium-dependent signaling cascades. Methods and ResultsIsolated perfused rabbit hearts were subjected to 45 minutes of normothermic ischemia with cardioplegic arrest. Hearts were reperfused for 120 minutes with unmodified perfusate (control), perfusate containing 20 nM dopamine, dopamine+2,3-butanedione monoxime (BDM), a MgATPase-inhibitor, or the calcium-sensitizing inotrope ORG 30029. Ischemia-reperfusion alone caused contractile dysfunction without significant myocardial necrosis (left ventricular pressure-volume curves; 1% triphenyltetrazolium chloride staining; creatine kinase release) or apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling [TUNEL] analysis; immunoblotting for poly(ADP-ribose) polymerase [PARP] cleavage; activation of caspases-3, -8, and -9; expression of Bax/Bcl-2). Intracellular calcium [Ca2+]i measured by rhod-2 spectrofluorometry was increased in dopamine-reperfused hearts. Although postischemic dopamine treatment improved contractility, the number of apoptotic cardiomyocytes was significantly higher than in untreated postischemic hearts (32.5±9 versus 5.5±1.6/1000 nuclei, P <0.01). Further evidence of dopamine-stimulated apoptosis included PARP cleavage, activation of mitochondrial-derived caspase-9, and the terminal effector caspase-3. Dopamine also increased cellular content of pro-apoptotic Bax while decreasing anti-apoptotic Bcl-2. Simultaneous treatment with BDM suppressed contractility without affecting [Ca2+]i and did not reduce dopamine-stimulated apoptotic markers. When contractility was increased without elevating [Ca2+]i using ORG 30029, no activation of pro-apoptotic signaling cascades was found. Dopamine infusion in nonischemic hearts did not result in cardiomyocyte apoptosis. ConclusionsPostischemic dopamine treatment of contractile dysfunction activates pro-apoptotic signal cascades, most likely via a calcium-dependent process and mitochondrial damage.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"10 1","pages":"I-290-I-298"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89394847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032880.55215.92
Ken Suzuki, B. Murtuza, I. Sammut, N. Latif, J. Jayakumar, R. Smolenski, Y. Kaneda, Y. Sawa, H. Matsuda, M. Yacoub
BackgroundHeat shock protein 72 (HSP72) is known to provide myocardial protection against ischemia-reperfusion injury by its chaperoning function. Target molecules of this effect are presumed to include not only structural proteins but also other self-preservation proteins. The details, however, remain unknown. Manganese superoxide dismutase (Mn-SOD) is an enzyme that preserves mitochondria, a key organelle for cellular respiration, from reperfusion injury and limits mitochondria-related apoptosis. We hypothesized that Mn-SOD would play a role in HSP72-mediated cardioprotection. Methods and ResultsRat hearts were transfected with human HSP72 by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, resulting in global myocardial overexpression of HSP72. After ischemia-reperfusion injury, cardiac function (left ventricular systolic pressure, maximum dP/dt, minimum dP/dt, and coronary flow) was improved in the HSP72-transfected hearts compared with control-transfected ones, corresponding with less leakage of creatine kinase and mitochondrial aspartate aminotransferase. Postischemic Mn-SOD content and activity in the HSP72-transfected hearts were enhanced in comparison with the controls (content: 96.9±4.1 versus 85.5±2.5% to the preischemic level, P =0.038; activity: 93.9±2.2 versus 82.2±3.7%, P =0.022), associated with improved mitochondrial respiratory function (postischemic percent respiratory control index; NAD+-linked: 81.3±3.8 versus 18.5±4.4%; FAD-linked: 71.8±5.5 versus 20.7±5.3%, P <0.001). In addition, incidence of postischemic cardiomyocyte apoptosis was attenuated in the HSP72-transfected hearts (4.0±1.1 versus 10.3±3.3%, P =0.036), correlating with an increased Bcl-2 level and reduced up-regulation of caspase-3. ConclusionsThese data suggest that the enhanced Mn-SOD activity during ischemia-reperfusion injury, which is associated with mitochondrial protection and apoptosis reduction, is a possible mechanism of HSP72-induced cardioprotection.
热休克蛋白72 (HSP72)通过其伴随功能对心肌缺血再灌注损伤提供保护。据推测，这种作用的靶分子不仅包括结构蛋白，还包括其他自我保护蛋白。然而，具体细节仍不得而知。锰超氧化物歧化酶(Mn-SOD)是一种保护线粒体(细胞呼吸的关键细胞器)免受再灌注损伤和限制线粒体相关凋亡的酶。我们假设Mn-SOD在hsp72介导的心脏保护中发挥作用。方法与结果采用冠状动脉内灌注日本血凝病毒脂质体转染人HSP72大鼠心脏，引起心肌中HSP72的过表达。缺血再灌注损伤后，与对照组相比，hsp72转染心脏的心功能(左室收缩压、最大dP/dt、最小dP/dt和冠状动脉血流)得到改善，肌酸激酶和线粒体天冬氨酸转氨酶的渗漏减少。与对照组相比，hsp72转染的心肌缺血后Mn-SOD含量和活性均有所提高(含量:96.9±4.1 vs 85.5±2.5%，P =0.038;活度:93.9±2.2 vs 82.2±3.7%，P =0.022)，与线粒体呼吸功能改善相关(缺血后百分比呼吸控制指数;NAD+连锁:81.3±3.8 vs 18.5±4.4%;fad相关:71.8±5.5 vs 20.7±5.3%，P <0.001)。此外，hsp72转染的心脏缺血后心肌细胞凋亡发生率降低(4.0±1.1 vs 10.3±3.3%，P =0.036)，这与Bcl-2水平升高和caspase-3上调减少有关。结论缺血再灌注损伤时Mn-SOD活性的增强与线粒体保护和细胞凋亡减少有关，可能是hsp72诱导心肌保护的机制之一。
{"title":"Heat Shock Protein 72 Enhances Manganese Superoxide Dismutase Activity During Myocardial Ischemia-Reperfusion Injury, Associated With Mitochondrial Protection and Apoptosis Reduction","authors":"Ken Suzuki, B. Murtuza, I. Sammut, N. Latif, J. Jayakumar, R. Smolenski, Y. Kaneda, Y. Sawa, H. Matsuda, M. Yacoub","doi":"10.1161/01.CIR.0000032880.55215.92","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032880.55215.92","url":null,"abstract":"BackgroundHeat shock protein 72 (HSP72) is known to provide myocardial protection against ischemia-reperfusion injury by its chaperoning function. Target molecules of this effect are presumed to include not only structural proteins but also other self-preservation proteins. The details, however, remain unknown. Manganese superoxide dismutase (Mn-SOD) is an enzyme that preserves mitochondria, a key organelle for cellular respiration, from reperfusion injury and limits mitochondria-related apoptosis. We hypothesized that Mn-SOD would play a role in HSP72-mediated cardioprotection. Methods and ResultsRat hearts were transfected with human HSP72 by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, resulting in global myocardial overexpression of HSP72. After ischemia-reperfusion injury, cardiac function (left ventricular systolic pressure, maximum dP/dt, minimum dP/dt, and coronary flow) was improved in the HSP72-transfected hearts compared with control-transfected ones, corresponding with less leakage of creatine kinase and mitochondrial aspartate aminotransferase. Postischemic Mn-SOD content and activity in the HSP72-transfected hearts were enhanced in comparison with the controls (content: 96.9±4.1 versus 85.5±2.5% to the preischemic level, P =0.038; activity: 93.9±2.2 versus 82.2±3.7%, P =0.022), associated with improved mitochondrial respiratory function (postischemic percent respiratory control index; NAD+-linked: 81.3±3.8 versus 18.5±4.4%; FAD-linked: 71.8±5.5 versus 20.7±5.3%, P <0.001). In addition, incidence of postischemic cardiomyocyte apoptosis was attenuated in the HSP72-transfected hearts (4.0±1.1 versus 10.3±3.3%, P =0.036), correlating with an increased Bcl-2 level and reduced up-regulation of caspase-3. ConclusionsThese data suggest that the enhanced Mn-SOD activity during ischemia-reperfusion injury, which is associated with mitochondrial protection and apoptosis reduction, is a possible mechanism of HSP72-induced cardioprotection.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"44 1","pages":"I-270-I-276"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72585071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032898.55215.0D
P. Moustakidis, H. Maniar, B. Cupps, T. Absi, Jie Zheng, J. Guccione, T. Sundt, M. Pasque
BackgroundLeft ventricular aneurysm (LVA) is a significant complication of myocardial infarction that may lead to global left ventricular (LV) dysfunction. However, the exact mechanism underlying the abnormal function has not been elucidated. In this study we tested the hypothesis that changes in LV geometry cause both an increase in wall stress and a change in the temporal distribution of stress in the LVA border zone (BZ) during systole. MethodsTransmural anteroapical infarcts were created in adult Dorsett sheep (n=8) and were allowed to mature into LVAs for 10 weeks. Animals were imaged subsequently using MRI with simultaneous recording of intraventricular pressures. Cardiac models were constructed from the MRI images at end-diastole, isovolumic systole, peak-systole and end-systole. Two short-axis slices, 1 basal and 1 apical were analyzed. The apical slice included the septal and anterior component of the aneurysm as well as the corresponding BZs and normal myocardium. Regional wall stresses were calculated using finite element analysis and compared with stresses in corresponding regions from normal control sheep (n=7). ResultsIn the LVA group, stress was significantly increased in the BZ at the end-diastolic, isovolumic, peak-systolic, and end-systolic instants (P <0.001 for all). In addition the temporal distribution of stress was significantly altered with maximum stress occurring at peak instead of isovolumic systole. ConclusionsGeometric changes in the LVA hearts increased wall stress and altered its temporal distribution in the BZ region. Correlation of this finding with the corresponding regional blood flow, oxygen consumption, and mechanical systolic performance may help elucidate the mechanism underlying the observed global LV dysfunction.
{"title":"Altered Left Ventricular Geometry Changes the Border Zone Temporal Distribution of Stress in an Experimental Model of Left Ventricular Aneurysm: A Finite Element Model Study","authors":"P. Moustakidis, H. Maniar, B. Cupps, T. Absi, Jie Zheng, J. Guccione, T. Sundt, M. Pasque","doi":"10.1161/01.CIR.0000032898.55215.0D","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032898.55215.0D","url":null,"abstract":"BackgroundLeft ventricular aneurysm (LVA) is a significant complication of myocardial infarction that may lead to global left ventricular (LV) dysfunction. However, the exact mechanism underlying the abnormal function has not been elucidated. In this study we tested the hypothesis that changes in LV geometry cause both an increase in wall stress and a change in the temporal distribution of stress in the LVA border zone (BZ) during systole. MethodsTransmural anteroapical infarcts were created in adult Dorsett sheep (n=8) and were allowed to mature into LVAs for 10 weeks. Animals were imaged subsequently using MRI with simultaneous recording of intraventricular pressures. Cardiac models were constructed from the MRI images at end-diastole, isovolumic systole, peak-systole and end-systole. Two short-axis slices, 1 basal and 1 apical were analyzed. The apical slice included the septal and anterior component of the aneurysm as well as the corresponding BZs and normal myocardium. Regional wall stresses were calculated using finite element analysis and compared with stresses in corresponding regions from normal control sheep (n=7). ResultsIn the LVA group, stress was significantly increased in the BZ at the end-diastolic, isovolumic, peak-systolic, and end-systolic instants (P <0.001 for all). In addition the temporal distribution of stress was significantly altered with maximum stress occurring at peak instead of isovolumic systole. ConclusionsGeometric changes in the LVA hearts increased wall stress and altered its temporal distribution in the BZ region. Correlation of this finding with the corresponding regional blood flow, oxygen consumption, and mechanical systolic performance may help elucidate the mechanism underlying the observed global LV dysfunction.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"17 1","pages":"I-168-I-175"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84705034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032873.55215.4C
T. Timek, P. Dagum, D. Lai, F. Tibayan, D. Liang, G. Daughters, M. Hayase, N. Ingels, D. C. Miller
BackgroundAcute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR. MethodsRadiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8±1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates. ResultsThe average degree of mitral regurgitation increased from 0.0±0.0 to 2.1±0.7 (P =0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group (0.1±0.2 for both conditions). The change in MAA throughout the cardiac cycle before ischemia was 17±4% in control animals, but only 5±2% (P =0.0002) in the Tailor ring group. Unlike the control animals, there was no increase in MAA (5.4±0.8 and 5.5±0.7 cm2, respectively; p=NS) nor dilatation of the muscular annulus (6.2±0.3 and 6.2±0.4, respectively; p=NS) during ischemia with the Tailor ring. Mitral SL dimension increased slightly with ischemia (2.3±0.2 versus 2.2±0.2 cm, P =0.03). Although posterior leaflet motion was limited, as observed with complete rings, normal annular flexion was maintained with the Tailor ring before and during acute ischemia. ConclusionsThe Tailor partial annuloplasty ring prevented acute IMR probably by limiting SL diameter dilatation during acute ischemia. In this animal model of acute IMR, a partial, flexible posterior annuloplasty ring is as effective as a complete ring.
背景:绵羊急性后外侧缺血可导致缺血性二尖瓣反流(IMR)。虽然完全环成形术可以预防急性IMR，但部分环成形术可能提供更多的生理性修复，但尚未在IMR的动物模型中进行测试。方法对13只羊的左室、二尖瓣环和小叶进行透射线标记。7只羊作为对照，6只羊植入St. Jude Tailor部分柔性环(5只29 mm, 1只31 mm)。8±1天后，在急性左室后外侧缺血(旋动脉球囊闭塞)前后和期间，对动物进行双翼透视和超声心动图研究。根据三维标记坐标计算二尖瓣环面积(MAA)、隔侧环直径(SL)、环周长和小叶边缘间距。结果急性缺血时，对照组的平均二尖瓣反流度由0.0±0.0增加到2.1±0.7 (P =0.0006)，而Tailor组的平均二尖瓣反流度不变(两组均为0.1±0.2)。缺血前整个心脏周期MAA的变化在对照组为17±4%，而在Tailor环组仅为5±2% (P =0.0002)。与对照动物不同，MAA没有增加(分别为5.4±0.8和5.5±0.7 cm2);p=NS)和肌环扩张(分别为6.2±0.3和6.2±0.4);p=NS)。二尖瓣SL尺寸随缺血轻微增加(2.3±0.2 vs 2.2±0.2 cm, P =0.03)。虽然后小叶运动受限，如完整环观察到的，但在急性缺血之前和期间，裁缝环保持正常的环状屈曲。结论局部环成形术可能通过限制急性缺血时SL直径的扩张来预防急性IMR。在这个急性IMR动物模型中，一个部分的、灵活的后环成形术环与一个完整的环一样有效。
{"title":"Will a Partial Posterior Annuloplasty Ring Prevent Acute Ischemic Mitral Regurgitation?","authors":"T. Timek, P. Dagum, D. Lai, F. Tibayan, D. Liang, G. Daughters, M. Hayase, N. Ingels, D. C. Miller","doi":"10.1161/01.CIR.0000032873.55215.4C","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032873.55215.4C","url":null,"abstract":"BackgroundAcute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR. MethodsRadiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8±1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates. ResultsThe average degree of mitral regurgitation increased from 0.0±0.0 to 2.1±0.7 (P =0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group (0.1±0.2 for both conditions). The change in MAA throughout the cardiac cycle before ischemia was 17±4% in control animals, but only 5±2% (P =0.0002) in the Tailor ring group. Unlike the control animals, there was no increase in MAA (5.4±0.8 and 5.5±0.7 cm2, respectively; p=NS) nor dilatation of the muscular annulus (6.2±0.3 and 6.2±0.4, respectively; p=NS) during ischemia with the Tailor ring. Mitral SL dimension increased slightly with ischemia (2.3±0.2 versus 2.2±0.2 cm, P =0.03). Although posterior leaflet motion was limited, as observed with complete rings, normal annular flexion was maintained with the Tailor ring before and during acute ischemia. ConclusionsThe Tailor partial annuloplasty ring prevented acute IMR probably by limiting SL diameter dilatation during acute ischemia. In this animal model of acute IMR, a partial, flexible posterior annuloplasty ring is as effective as a complete ring.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"376 1","pages":"I-33-I-39"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78065147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032886.55215.15
C. Davos, P. Davlouros, R. Wensel, D. Francis, L. Davies, P. Kilner, A. Coats, M. Piepoli, M. Gatzoulis
BackgroundSustained ventricular tachycardia (VT) and sudden cardiac death (SCD) remain devastating late complications after repair of Tetralogy of Fallot (ToF). Although heart rate variability (HRV) and baroreflex sensitivity (BRS) are recognized as independent markers of autonomic activity and strong predictors of SCD in major cardiovascular disease, little is known about their role in patients with tertralogy. Methods and ResultsWe measured HRV and BRS in 45 ToF patients (27 male, age 35±12 years, 26±7 years after repair) and 45 matched healthy controls. Subjects underwent 20 minute of resting measurements of heart rate (ECG) and noninvasive beat-to-beat blood pressure recording (Finapres), with 5 minutes of 0.1Hz controlled breathing followed by cardiac MRI. BRS was computed by spectral analysis and the sequence and controlled breathing methods. All HRV time and frequency domain variables were measured. All BRS and HRV variables were significantly reduced in patients compared with controls (P <0.001 in all). HRV tended to increase with years from repair. BRS decreased with previous palliation and increasing patient age. Both HRV and BRS decreased with pulmonary regurgitation, elevated right ventricular end systolic volumes and reduced right and left ventricular ejection fraction. Finally, there was an inverse relation between QRS duration (predictor of sustained VT and SCD) and indices of HRV but no relation with indices of BRS. ConclusionThere is global impairment of autonomic nervous system regulation late after repair of tetralogy with marked reduction of BRS and HRV. This seems to relate to previous surgical intervention/s, their timing and current right and left-sided hemodynamics. Reduced HRV also related to markers of sustained VT and SCD, suggesting possible common pathogenic mechanisms. Further studies are required to examine the prognostic significance of impaired BRS and HRV in these patients.
{"title":"Global Impairment of Cardiac Autonomic Nervous Activity Late After Repair of Tetralogy of Fallot","authors":"C. Davos, P. Davlouros, R. Wensel, D. Francis, L. Davies, P. Kilner, A. Coats, M. Piepoli, M. Gatzoulis","doi":"10.1161/01.CIR.0000032886.55215.15","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032886.55215.15","url":null,"abstract":"BackgroundSustained ventricular tachycardia (VT) and sudden cardiac death (SCD) remain devastating late complications after repair of Tetralogy of Fallot (ToF). Although heart rate variability (HRV) and baroreflex sensitivity (BRS) are recognized as independent markers of autonomic activity and strong predictors of SCD in major cardiovascular disease, little is known about their role in patients with tertralogy. Methods and ResultsWe measured HRV and BRS in 45 ToF patients (27 male, age 35±12 years, 26±7 years after repair) and 45 matched healthy controls. Subjects underwent 20 minute of resting measurements of heart rate (ECG) and noninvasive beat-to-beat blood pressure recording (Finapres), with 5 minutes of 0.1Hz controlled breathing followed by cardiac MRI. BRS was computed by spectral analysis and the sequence and controlled breathing methods. All HRV time and frequency domain variables were measured. All BRS and HRV variables were significantly reduced in patients compared with controls (P <0.001 in all). HRV tended to increase with years from repair. BRS decreased with previous palliation and increasing patient age. Both HRV and BRS decreased with pulmonary regurgitation, elevated right ventricular end systolic volumes and reduced right and left ventricular ejection fraction. Finally, there was an inverse relation between QRS duration (predictor of sustained VT and SCD) and indices of HRV but no relation with indices of BRS. ConclusionThere is global impairment of autonomic nervous system regulation late after repair of tetralogy with marked reduction of BRS and HRV. This seems to relate to previous surgical intervention/s, their timing and current right and left-sided hemodynamics. Reduced HRV also related to markers of sustained VT and SCD, suggesting possible common pathogenic mechanisms. Further studies are required to examine the prognostic significance of impaired BRS and HRV in these patients.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"16 1","pages":"I-69-I-75"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74110720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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