Pub Date : 2024-10-01DOI: 10.1097/FJC.0000000000001603
Bu-Yuan Hsiao
Abstract: The aim of this study was to evaluate the potential associations between Sjogren syndrome and outcomes of acute myocardial infarction (AMI) hospitalization. This population-based, retrospective observational study extracted data from the US Nationwide Inpatient Sample between 2005 and 2018. Adults aged 20 years or older hospitalized for AMI were eligible for inclusion. Propensity score matching was applied to balance the characteristics between the comparison groups (ie, with and without Sjogren syndrome). Associations between Sjogren syndrome and in-hospital outcomes were determined using univariate and multivariable logistic regression analyses. A total of 1,735,142 patients were included. After propensity score matching, 4740 patients remained for subsequent analyses (948 had Sjogren syndrome and 3792 did not). After adjustment, patients with Sjogren syndrome had significantly lower in-hospital mortality (adjusted OR: 0.52, 95% CI, 0.36-0.73, P < 0.001), prolonged length of stay (aOR: 0.83, 95% CI, 0.69-0.995, P = 0.044), cardiogenic shock (aOR: 0.58, 95% CI, 0.40-0.83, P = 0.004), cardiac dysrhythmias (aOR: 0.77, 95% CI, 0.66-0.90, P < 0.001), acute kidney injury (aOR: 0.56, 95% CI, 0.45-0.70, P < 0.001), or respiratory failure (aOR: 0.63, 95% CI, 0.48-0.81, P < 0.001) than those without Sjogren syndrome. The stratified analysis revealed that Sjogren syndrome was associated with decreased odds of in-hospital mortality in patients with non-ST elevation myocardial infarction or ST-elevation myocardial infarction. In conclusion, among patients admitted to US hospitals for AMI, the patients with Sjogren syndrome have a lowered probability of in-hospital mortality, certain morbidities, and prolonged length of stay. Further investigations should be conducted to establish a robust understanding of the associations observed.
{"title":"Sjogren Syndrome and Outcomes of Acute Myocardial Infarction: A Propensity Score-Matched Analysis of the Nationwide Inpatient Sample 2005-2018.","authors":"Bu-Yuan Hsiao","doi":"10.1097/FJC.0000000000001603","DOIUrl":"10.1097/FJC.0000000000001603","url":null,"abstract":"<p><strong>Abstract: </strong>The aim of this study was to evaluate the potential associations between Sjogren syndrome and outcomes of acute myocardial infarction (AMI) hospitalization. This population-based, retrospective observational study extracted data from the US Nationwide Inpatient Sample between 2005 and 2018. Adults aged 20 years or older hospitalized for AMI were eligible for inclusion. Propensity score matching was applied to balance the characteristics between the comparison groups (ie, with and without Sjogren syndrome). Associations between Sjogren syndrome and in-hospital outcomes were determined using univariate and multivariable logistic regression analyses. A total of 1,735,142 patients were included. After propensity score matching, 4740 patients remained for subsequent analyses (948 had Sjogren syndrome and 3792 did not). After adjustment, patients with Sjogren syndrome had significantly lower in-hospital mortality (adjusted OR: 0.52, 95% CI, 0.36-0.73, P < 0.001), prolonged length of stay (aOR: 0.83, 95% CI, 0.69-0.995, P = 0.044), cardiogenic shock (aOR: 0.58, 95% CI, 0.40-0.83, P = 0.004), cardiac dysrhythmias (aOR: 0.77, 95% CI, 0.66-0.90, P < 0.001), acute kidney injury (aOR: 0.56, 95% CI, 0.45-0.70, P < 0.001), or respiratory failure (aOR: 0.63, 95% CI, 0.48-0.81, P < 0.001) than those without Sjogren syndrome. The stratified analysis revealed that Sjogren syndrome was associated with decreased odds of in-hospital mortality in patients with non-ST elevation myocardial infarction or ST-elevation myocardial infarction. In conclusion, among patients admitted to US hospitals for AMI, the patients with Sjogren syndrome have a lowered probability of in-hospital mortality, certain morbidities, and prolonged length of stay. Further investigations should be conducted to establish a robust understanding of the associations observed.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"394-399"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1097/FJC.0000000000001615
Catherine X Wright, Attila Feher
{"title":"From Risk to Resilience: Improved Outcomes After Myocardial Infarction in Patients With Sjogren's Syndrome.","authors":"Catherine X Wright, Attila Feher","doi":"10.1097/FJC.0000000000001615","DOIUrl":"10.1097/FJC.0000000000001615","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"389-390"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1097/FJC.0000000000001622
Yan-Feng Liang, Qing-Xin You, Shu-Yue Chen, Lei Ni, Xiang-Lian Meng, Jian-Xiang Gao, Yong-Bo Ren, Han-Jun Song, Jia-Lu Su, Yang Teng, Qing-Yun Gu, Chao Lv, Bo-Yang Yuan, Xuan Wang, Yong-Tai Zheng, Dong-Dong Zhang
Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.
下丘脑室旁核(PVN)在调节心血管活动和血压(BP)方面起着核心作用。我们将胱硫醚-β-合成酶(CBS)抑制剂盐酸羟胺(HA)注入下丘脑室旁核,以抑制内源性硫化氢(H2S),并研究其对高盐诱导的高血压中丝裂原活化蛋白激酶(MAPK)通路的影响。我们将 40 只雄性 Dahl 盐敏感大鼠随机分为 4 组:NS+PVN 车辆组、NS+PVN HA 组、HS+PVN 车辆组和 HS+PVN HA 组,每组 10 只。NS(正常盐)组大鼠食用含 0.3% NaCl 的正常盐饮食,而 HS(高盐)组大鼠食用含 8% NaCl 的高盐饮食。每周一次使用自动血压计闭合尾部袖带进行无创测量,然后计算平均动脉压(MAP)。高血压模型成功建立后,使用 Alzet 渗透压微型泵将 HA 或药物注入双侧 PVN,持续 6 周。我们用酶联免疫吸附法测定了PVN中的H2S水平和血浆去甲肾上腺素(NE)水平。此外,我们还通过 Western 印迹、免疫组化分析或实时 PCR 评估了 MAPK 通路、炎症和氧化应激的参数。在目前的研究中,我们发现PVN中内源性硫化氢水平的降低是高盐诱导的高血压发病的原因之一。这与 MAPK 信号通路的激活、促炎细胞因子和 PVN 中的氧化应激以及交感神经系统的激活有关。
{"title":"The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.","authors":"Yan-Feng Liang, Qing-Xin You, Shu-Yue Chen, Lei Ni, Xiang-Lian Meng, Jian-Xiang Gao, Yong-Bo Ren, Han-Jun Song, Jia-Lu Su, Yang Teng, Qing-Yun Gu, Chao Lv, Bo-Yang Yuan, Xuan Wang, Yong-Tai Zheng, Dong-Dong Zhang","doi":"10.1097/FJC.0000000000001622","DOIUrl":"10.1097/FJC.0000000000001622","url":null,"abstract":"<p><strong>Abstract: </strong>The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"468-478"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1097/FJC.0000000000001636
Giuseppe Biondi-Zoccai, Mattia Galli, George W Booz
{"title":"Finerenone Proves Beneficial for Heart Failure with Preserved Ejection Fraction.","authors":"Giuseppe Biondi-Zoccai, Mattia Galli, George W Booz","doi":"10.1097/FJC.0000000000001636","DOIUrl":"10.1097/FJC.0000000000001636","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malnutrition is known to worsen the prognosis of chronic heart failure. To gain information that may be helpful in establishing appropriate nutritional interventions for chronic heart failure, the present study was performed to investigate the efficacy of nutritional management with two enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat heart failure model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. Additionally, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a heart failure model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic heart failure.
{"title":"Effect of an Enteral Formula Enriched with ω-3 Fatty Acids, Carnitine, and Vitamin D on Body Weight, Heart Weight, and Blood Biochemical Parameters in a Dahl Rat Heart Failure Model.","authors":"Yoshikazu Ryuno, Jun-Ichi Kobayashi, Yudai Fujimoto, Taishi Dotare, Yuya Matsue, Yoshihito Iwanami","doi":"10.1097/FJC.0000000000001637","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001637","url":null,"abstract":"<p><p>Malnutrition is known to worsen the prognosis of chronic heart failure. To gain information that may be helpful in establishing appropriate nutritional interventions for chronic heart failure, the present study was performed to investigate the efficacy of nutritional management with two enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat heart failure model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. Additionally, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a heart failure model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic heart failure.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1097/fjc.0000000000001630
Djemail Ismaili,Johannes Petersen,Carl Schulz,Thomas Eschenhagen,Jussi T Koivumäki,Torsten Christ
Atrial fibrillation (AF) poses a significant therapeutic challenge with drug interventions showing only limited success. Phosphodiesterases (PDE) regulate cardiac electrical stability and may represent an interesting target. Recently, PDE8 inhibition was proposed as an antiarrhythmic intervention by increasing L-type Ca2+ current (ICa,L) and action potential duration (APD). However, the effect size of PDE8 inhibition on ICa,L and APD seems discrepant and effects on force are unknown. We investigated the impact of PDE8 inhibition on force using PF-04957325 in right atrial appendages, obtained from patients in sinus rhythm (SR) and with persistent AF (peAF) undergoing cardiac surgery. A computational model was employed to predict the effects of PDE8 inhibition on APD in SR and peAF. Results showed no increase in force after exposure to increasing concentrations of the PDE8 inhibitor PF-04957325 in either SR or peAF tissues. Furthermore, PDE8 inhibition did not affect the potency or efficacy of norepinephrine-induced inotropic effects in either group. Arrhythmic events triggered by norepinephrine were observed in both SR and peAF, but their frequency remained unaffected by PF-04957325 treatment. Computational modeling predicted that the reported increase in ICa,L induced by PDE8 inhibition would lead to substantial APD prolongation at all repolarization states, particularly in peAF. Our findings indicate that PDE8 inhibition does not significantly impact force or arrhythmogenicity in human atrial tissue.
{"title":"PDE8 Inhibition and Its Impact on ICa,L in Persistent Atrial Fibrillation: Evaluation of PDE8 as a Potential Drug Target.","authors":"Djemail Ismaili,Johannes Petersen,Carl Schulz,Thomas Eschenhagen,Jussi T Koivumäki,Torsten Christ","doi":"10.1097/fjc.0000000000001630","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001630","url":null,"abstract":"Atrial fibrillation (AF) poses a significant therapeutic challenge with drug interventions showing only limited success. Phosphodiesterases (PDE) regulate cardiac electrical stability and may represent an interesting target. Recently, PDE8 inhibition was proposed as an antiarrhythmic intervention by increasing L-type Ca2+ current (ICa,L) and action potential duration (APD). However, the effect size of PDE8 inhibition on ICa,L and APD seems discrepant and effects on force are unknown. We investigated the impact of PDE8 inhibition on force using PF-04957325 in right atrial appendages, obtained from patients in sinus rhythm (SR) and with persistent AF (peAF) undergoing cardiac surgery. A computational model was employed to predict the effects of PDE8 inhibition on APD in SR and peAF. Results showed no increase in force after exposure to increasing concentrations of the PDE8 inhibitor PF-04957325 in either SR or peAF tissues. Furthermore, PDE8 inhibition did not affect the potency or efficacy of norepinephrine-induced inotropic effects in either group. Arrhythmic events triggered by norepinephrine were observed in both SR and peAF, but their frequency remained unaffected by PF-04957325 treatment. Computational modeling predicted that the reported increase in ICa,L induced by PDE8 inhibition would lead to substantial APD prolongation at all repolarization states, particularly in peAF. Our findings indicate that PDE8 inhibition does not significantly impact force or arrhythmogenicity in human atrial tissue.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"42 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1097/fjc.0000000000001634
Tarek Harb,Efthymios Ziogos,Núria Amat-Alarcon,Shenghan Lai,Gary Gerstenblith,Marios Arvanitis,Thorsten M Leucker
Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6 induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).
{"title":"Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells.","authors":"Tarek Harb,Efthymios Ziogos,Núria Amat-Alarcon,Shenghan Lai,Gary Gerstenblith,Marios Arvanitis,Thorsten M Leucker","doi":"10.1097/fjc.0000000000001634","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001634","url":null,"abstract":"Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6 induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"42 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1097/fjc.0000000000001631
Carl Schulz,Thomas Eschenhagen,Torsten Christ
Human induced pluripotent stem cells (hiPSC) and atrial hiPSC-derived cardiomyocytes (hiPSC-CM) have entered the arena of preclinical AF research. A central question is whether they reproduce the physiological contribution of atrial selective potassium currents (such as the ultrarapid potassium current, IKur) to repolarization. Of note, two studies in single atrial hiPSC-CM reported prolongation of action potential duration by IKur block indicating that IKur might in fact represent a valuable target for the treatment of human AF. However, the results and interpretation are at odds with the literature on IKur block in human atria and the results of clinical studies. We believe that the discrepancies indicate that experiments in single atrial CM (both adult atrial CM and atrial hiPSC-CM) might be misleading. Under particular experimental conditions, atrial hiPSC-CMs may not closely resemble the electrophysiology of the human atrium. Therefore, we recapitulate here methodological issues evaluating potential value of the IKur as an antiarrhythmic target when investigated in animal models, in human atrial tissues and finally in atrial hiPSC-CM.
人类诱导多能干细胞(hiPSC)和心房 hiPSC 衍生心肌细胞(hiPSC-CM)已进入临床前房颤研究领域。一个核心问题是它们是否能再现心房选择性钾电流(如超快速钾电流IKur)对复极化的生理贡献。值得注意的是,有两项针对单心房 hiPSC-CM 的研究报告称,IKur 阻断可延长动作电位持续时间,这表明 IKur 实际上可能是治疗人类房颤的一个有价值的靶点。然而,这些结果和解释与有关人类心房 IKur 阻滞的文献和临床研究结果不一致。我们认为,这些差异表明,在单个心房 CM(包括成人心房 CM 和心房 hiPSC-CM)中进行的实验可能会产生误导。在特定的实验条件下,心房 hiPSC-CM 可能与人类心房的电生理学并不十分相似。因此,我们在此概述了评估 IKur 作为抗心律失常靶点在动物模型、人类心房组织和心房 hiPSC-CM 中的潜在价值的方法学问题。
{"title":"Atrial hiPSC-CM as a pharmacological model to evaluate anti-AF drugs: Some lessons from IKur.","authors":"Carl Schulz,Thomas Eschenhagen,Torsten Christ","doi":"10.1097/fjc.0000000000001631","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001631","url":null,"abstract":"Human induced pluripotent stem cells (hiPSC) and atrial hiPSC-derived cardiomyocytes (hiPSC-CM) have entered the arena of preclinical AF research. A central question is whether they reproduce the physiological contribution of atrial selective potassium currents (such as the ultrarapid potassium current, IKur) to repolarization. Of note, two studies in single atrial hiPSC-CM reported prolongation of action potential duration by IKur block indicating that IKur might in fact represent a valuable target for the treatment of human AF. However, the results and interpretation are at odds with the literature on IKur block in human atria and the results of clinical studies. We believe that the discrepancies indicate that experiments in single atrial CM (both adult atrial CM and atrial hiPSC-CM) might be misleading. Under particular experimental conditions, atrial hiPSC-CMs may not closely resemble the electrophysiology of the human atrium. Therefore, we recapitulate here methodological issues evaluating potential value of the IKur as an antiarrhythmic target when investigated in animal models, in human atrial tissues and finally in atrial hiPSC-CM.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"43 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1097/FJC.0000000000001633
Sabrina Dunham, Patrick M Wieruszewski, James E Gerrald
Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality utilized in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most utilized anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on co-factors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of co-factors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. Additionally, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.
{"title":"Bivalirudin in Extracorporeal Membrane Oxygenation.","authors":"Sabrina Dunham, Patrick M Wieruszewski, James E Gerrald","doi":"10.1097/FJC.0000000000001633","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001633","url":null,"abstract":"<p><strong>Abstract: </strong>Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality utilized in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most utilized anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on co-factors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of co-factors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. Additionally, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}