Experimental & Clinical Cardiology最新文献

Background: Intravenous infusion of prostaglandin E1 (PGE1) has been used to treat pulmonary arterial hypertension (PAH); however, the efficacy and safety of inhaled PGE1 is unclear.

Objectives: To investigate the effect of inhaled PGE1 on PAH following corrective surgery for congenital heart disease.

Methods: Sixty patients with postoperative residual PAH following corrective surgery for congenital heart disease were randomly assigned to a control group, a PGE1 infusion group (intravenous PGE1 infusion; 30 ng/kg/min daily for 10 days) or a PGE1 inhalation group (100 μg nebulized PGE1 every 8 h for 10 days). Systolic blood pressure, mean pulmonary arterial pressure, arterial oxygen pressure, oxygen saturation and serum endothelin-1 level were measured before and after the treatment.

Results: At the end of the study, the mean pulmonary arterial pressure in the two PGE1 groups were lower than in the control group (P<0.01), whereas the mean arterial oxygen pressure was higher (P<0.01). Compared with the PGE1 infusion group, the mean pulmonary arterial pressure in the PGE1 inhalation group was lower (P<0.01) whereas the arterial oxygen pressure was higher (P<0.01). The mean endothelin-1 levels in the two PGE1 groups were lower than in the control group (P<0.01), but there was no statistically significant difference in endothelin-1 levels between the PGE1 inhalation and infusion groups (P>0.05).

Conclusions: In pediatric patients with PAH, PGE1 inhalation was associated with a reduction in pulmonary arterial pressure and improvement in arterial blood oxygen levels.

Background: Mitral annulus calcification (MAC) is an important echocardiographic finding that is significantly associated with valvular abnormalities. However, the effect of documented MAC on all-cause mortality is not known. Using a large database, associations between MAC and long-term all-cause mortality were evaluated.

Methods: A retrospective analysis of 3169 echocardiograms, which were performed for clinical reasons in southern California between 1983 and 1998 in patients between 16 and 99 years of age, was performed. Mortality data were extracted from the national mortality database at the end of 2007. Using uni- and multivariate analysis, associations between total mortality and the echocardiographic presence of MAC documented in the final report by the interpreting cardiologist were evaluated.

Results: MAC was significantly associated with all-cause mortality (174 of 334 [52.1%] patients with MAC died versus 709 of 2835 [25.0%] patients without MAC; OR 3.26 [95% CI 2.58 to 4.10]; P<0.001). Using multivariate analysis adjusting for age, left ventricular hypertrophy, sex, abnormal left ventricular systolic function and significant valvular abnormalities, MAC remained independently associated with all-cause mortality (OR 2.50 [95% CI 1.81 to 3.45]; P<0.001).

Conclusion: Using a large echocardiographic database, MAC was found to be independently associated with all-cause mortality. This finding confirms the importance of an abnormal mitral annulus as an important prognostic marker.

Background: Coronary intimal hyperplasia occurs at the site of spasm in patients with vasospastic angina. The migration of vascular smooth muscle cells (VSMCs) from the media has been proposed as a potential mechanism; however, this has not been confirmed with supportive evidence.

Objective: To determine which cell types participate in spasm-induced coronary intimal hyperplasia.

Methods: Morphological changes in spastic coronary artery segments in beagles were examined using electron microscopy and immunohistochemical staining of cell markers at 1 h, 3 h and 6 h, and two and four weeks after spasm provocation.

Results: Small smooth muscle-like cells (SMLCs) were observed in the media of nonspastic coronary segments using electron microscopy. These cells attached side-to-side to large, known VSMCs. At 1 h to 6 h after spasm provocation, SMLCs separated from VSMCs, changed to an amoebic configuration and migrated through cleaved junctions or disrupted portions of the internal elastic lamina into the subendothelial space. The SMLCs expressed alpha-smooth muscle actin and N-cadherin, but not smooth muscle myosin heavy chain-1 and β-actin, suggesting that they were myofibroblasts and not a synthetic phenotype of VSMCs. Intimal hyperplasia was observed in all preparations at two and four weeks after spasm provocation. Furthermore, alpha-smooth muscle actin-positive SMLCs, often amoebic in configuration, were observed in the hyperplastic intima.

Conclusions: On coronary spasm provocation, SMLCs (ie, possible myofibroblasts) resident in the media migrate as a spearhead into the intima and play a role in coronary intimal hyperplasia.

Background: Stent graft placement is an acceptable treatment option for aortic disease, particularly for abdominal aortic aneurysm. At present, the use of stent grafts is expanding beyond current indications for use. Fenestrated stent grafts are used in patients with abdominal aortic aneurysms whose aortic anatomy is unsuitable for repair using standard devices. The success of fenestrated stent graft placement is largely dependent on planning, including obtaining measurements and designing the stent.

Objective: To demonstrate a measurement technique that may be used for the design of fenestrated stent grafts to repair endovascular aneurysms, and to compare these measurements, obtained using archived two-dimensional patient data, with measurements obtained using a three-dimensional (3-D) computer-assisted design model.

Methods: Fenestrated stent grafts were designed and fabricated based on computed tomographic angiography images. 3-D models were constructed using modelling software and rapid prototyping technology incorporated with fused deposition modelling. The stent grafts were trunk-type, with four holes for the visceral branches (celiac axis, superior mesenteric artery, right renal artery and left renal artery). Computed tomography scans of 10 patients with abdominal aortic aneurysms were reviewed. Axial, multiplanar reconstruction and curved multiplanar reconstruction images were used to measure 11 parameters. Sizing of the fenestrated aortic stent grafts was performed independently by an experienced interventional radiologist, and the results were compared with the same measurements calculated using the 3-D aorta model (generated using Materialise Interactive Medical Image Control System software [Materialise NV, Belgium]). Data were reported as the mean of the measurements. Measurements were evaluated using Bland-Altman analysis and concordance correlation coefficients (CCCs).

Results: A total of 10 fenestrated stent grafts were fabricated. The proximal landing section above the celiac axis (one point of the wall being defined as the standard point) was 3 cm, and the distal flared section was 3 cm below the lowest renal artery. Ten computer-assisted design aorta models were successfully constructed. Measurements of the aortic diameter showed high agreement between those obtained using the archived patient computer system stent graft and those obtained using the 3-D aorta model. The CCC for variability was 0.9974. The distance from the standard point to the branch vessels also demonstrated good agreement. The CCC for variability was 0.9999.

Discussion: A direct measurement technique using a standard point was simple to perform and was easily applied to the fabrication process. Preparation time will likely be shortened and the versatility of stent grafts will be improved using this method. It will be possible to produce standardize

Background: The bicuspid aortic valve (BAV) represents the most common cardiac congenital malformation in adults. It is frequently associated with dilation, aneurysm and dissection of the ascending aorta.

Objective: To evaluate left ventricular systolic and diastolic function in subjects with BAVs.

Methods: Thirty-five subjects with BAV (mean [± SD] age 25.9±5.7 years [range 17 to 36 years]; 18 male, 17 female) with either no valvular impairment or mild valvular impairment were recruited along with 30 control subjects (24.5±4.4 years of age [range 15 to 35 years]; 15 male, 15 female) who were matched for age, sex and body surface area. Left ventricular systolic and diastolic function were evaluated using conventional and tissue Doppler echocardiography. Left ventricular systolic and diastolic parameters were compared between the two groups.

Results: In subjects with BAVs, the ratio of mitral early diastolic velocity to late diastolic velocity was lower (0.95±0.4 versus 1.27±0.9; P=0.001), the ratio of mitral early diastolic velocity to myocardial early diastolic velocity was higher (10.1±3.2 versus 6.5±2.4; P=0.001) and the myocardial early diastolic velocity was lower (8.4±2.1 versus 15.3±3.6; P<0.001) compared with control subjects. In addition, the myocardial performance index was higher in subjects with BAVs than in control subjects (P=0.03). The left ventricular ejection fraction was also lower (53±11% versus 64±13%; P<0.001). No other statistically significant differences were observed between the two groups with regard to left ventricular systolic and diastolic parameters. In addition, the number of mitral valve prolapses and atrial septal aneurysms was higher in subjects with BAVs.

Conclusion: BAVs may be associated with left ventricular systolic and diastolic dysfunction.

Cyclophilin A (CypA) is a ubiquitously distributed protein present both in intracellular and extracellular spaces. In atherosclerosis, various cells, including endothelial cells, monocytes, vascular smooth muscle cells and platelets, secrete CypA in response to excessive levels of reactive oxygen species. Atherosclerosis, a complicated disease, is the result of the interplay of different risk factors. Researchers have found that CypA links many risk factors, including hyperlipidemia, hypertension and diabetes, to atherosclerosis that develop into a vicious cycle. Furthermore, most studies have shown that secreted CypA participates in the developmental process of atherosclerosis via many important intracellular mechanisms. CypA can cause injury to and apoptosis of endothelial cells, leading to dysfunction of the endothelium. CypA may also induce the activation and migration of leukocytes, producing proinflammatory cytokines that promote inflammation in blood vessels. In addition, CypA can promote the proliferation of monocytes/macrophages and vascular smooth muscle cells, leading to the formation of foam cells and the remodelling of the vascular wall. Studies investigating the roles of CypA in atherosclerosis may provide new direction for preventive and interventional treatment strategies in atherosclerosis.

Background: It is well known that nitrates can induce paradoxical myocardial ischemia.

Methods and results: Fifty patients (median age 73 years; range 67 to 78 years; 80% male) with healed myocardial infarcts were selected. All patients underwent resting single-photon emission computed tomography (SPECT) and resting baseline gated-SPECT using sestamibi or thallium-201 after the sublingual administration of 5 mg isosorbide dinitrate (ISD). Forty-eight per cent (24 of 50) of the patients demonstrated ISD-induced peri-infarct ischemia as observed by SPECT. Compared with patients without ISD-induced ischemia, patients with ISD-induced ischemia presented larger infarcts as determined by the extent of perfusion defects (mean [± SD] 27±12 pixels versus 11±9 pixels; P<0.0001), lower ejection fractions (39±17% versus 50±15%; P<0.02) and a higher incidence of severe coronary artery disease (P<0.04). At five years, the survival probability on Kaplan-Meier analysis was 42% and 96% for patients with and without ISD-induced ischemia, respectively (HR 5.6 [95% CI 1.6 to 20]; P=0.009).

Conclusions: Nitrates may have low efficacy in improving blood flow through the coronary vessels that supply large myocardial infarcts with high-resistance microvascular damage. At the same time, nitrates induce dilation and blood pressure decrease in remotely patent or mildly stenotic vessels. The blood pressure gradient elicited between the high- and low-resistance coronary vessels may provide the force for a blood flow steal from the viable zones of the infarct toward the healthy myocardium. The resultant nitrate-induced paradoxical ischemia could be a silent marker of myocardial instability and adverse outcomes in elderly patients with healed myocardial infarcts.

Background/objectives: Previous studies using isolated mitochondria have provided new insight into the mechanisms and interventions for ischemia and reperfusion (I/R) injury. In in vitro experiments involving isolated mitochondria, hypoxia and reoxygenation (H/R) has been widely used to mimic I/R injury. However, in in vitro H/R mitochondrial experiments, the effects of various substrates on mitochondrial oxidative phosphorylation are unclear. In the present study, the effects of in vitro I/R injury on mitochondrial oxidative phosphorylation under different substrate conditions were investigated.

Methods: Hypoxia was achieved following complete consumption of oxygen by mitochondria isolated from rat heart tissue in an experimental chamber. The H/R protocol involved 30 min hypoxia followed by 15 min reoxygenation in a chamber opened to the atmosphere. Mitochondrial respiration and respiratory control ratio (RCR) were measured.

Results: When pyruvate/malate were used as substrates, H/R significantly decreased state 3 respiration (28.2±12 nmol O2/min/mg protein) and RCR (2.7±0.8) compared with the control (121.4±32.5 nmol O2/mg protein/min and 7.8±1.2, respectively). In contrast, when succinate was used without rotenone, H/R significantly increased state 3 respiration (57.0±11.2 nmol O2/mg protein/min) and RCR (2.0±0.3) compared with the control (48.2±12.3 nmol O2/mg protein/min and 1.3±0.2, respectively).

Conclusions: The present study demonstrated that mitochondrial oxidative phosphorylation can be modulated by H/R in vitro depending on substrate conditions.

Objective: To explore the effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization (CME) in rats.

Methods: Forty rats were randomly divided into four groups (n=10 each): a sham operation (control) group, CME plus saline (CME) group, CME plus metoprolol (metoprolol) group and caspase-9 inhibitor Z-LEHD-FMK (ZLF) group. CME was induced by injecting 3000 polyethylene microspheres (42 μm diameter) into the left ventricle during a 10 s occlusion of the ascending aorta. Echocardiography, terminal deoxynucleotidyl transferase dUTP nick end labelling and Western blotting were used to evaluate cardiac function, apoptosis and activation of caspase-9/caspase-3, respectively, 6 h after CME.

Results: The echocardiographic parameters of left ventricular function were significantly decreased in the CME group compared with the control group (P<0.05); however, the metoprolol group and ZLF group showed significantly improved cardiac function compared with CME alone (P<0.05). Compared with the control group, the myocardial apoptosis rate and the levels of activated caspase-9 and -3 increased significantly in the CME group (P<0.05). Again, these effects were ameliorated by metoprolol and ZLF (P<0.05).

Conclusions: The present study demonstrates that metoprolol and ZLF can protect the rat myocardium during CME by inhibiting apoptosis and improving cardiac function, likely by inhibiting apoptosis/ mitochondrial apoptotic pathway. These results suggest that antiapoptotic therapies may be useful in treating CME.

Background: Patients hospitalized for decompensated heart failure (DHF) frequently experience worsening of renal function (WRF), leading to volume overload and resistance to diuretics.

Objective: To investigate whether albumin levels and whole-body impedance ratio, as an indicator of water distribution, were associated with WRF in patients with DHF.

Methods: A total of 80 patients hospitalized for DHF were consecutively included in the present longitudinal study. WRF during hospitalization was defined as an increase of ≥0.3 mg/dL (≥26.52 μmol/L) or 25% of baseline serum creatinine. Clinical and echocardiographic characteristics were assessed at baseline. Whole-body bioelectrical impedance was measured using tetrapolar and multiple-frequency equipment to obtain the ratio of impedance at 200 kHz to that at 5 kHz. Serum albumin levels were also evaluated. Baseline characteristics were compared between patients with and without deteriorating renal function using a t test or χ(2) test. Subsequently, a logistic regression analysis was performed to obtain the independent variables associated with WRF.

Results: The incidence of WRF during hospitalization was 26%. Independent risk factors associated with WRF were low serum albumin (RR=0.11; P=0.04); impedance ratio >0.85 (RR=5.3; P=0.05), systolic blood pressure >160 mmHg (RR=12; P=0.02) and maximum dose of continuous intravenous furosemide required >80 mg/day during hospitalization (RR=5.7, P=0.015).

Conclusions: WRF is frequent in patients with DHF. It results from the inability to effectively regulate volume status because hypoalbuminemia induces water loss from the vascular space (high impedance ratio), and high diuretic doses lower circulatory volumes and reduce renal blood flow, leading to a decline in renal filtration function.