Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City (J.D.S., L.D., N.D., T.B., J.M.C., S.G.D.).
Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes (J.D.S.), University of Utah, Salt Lake City.
Circ Heart Fail. 2019 Aug;12(8):e006085. doi: 10.1161/CIRCHEARTFAILURE.119.006085. Epub 2019 Aug 19.
The coronary vasculature encounters a reduction in pulsatility after implementing durable continuous-flow left ventricular assist device (CF-LVAD) circulatory support. Evidence exists that appropriate pulsatility is required to maintain endothelial cell homeostasis. We hypothesized that coronary artery endothelial function would be impaired after CF-LVAD intervention.
Coronary arteries from patients with end-stage heart failure caused by ischemic cardiomyopathy (ICM; n=16) or non-ICM (n=22) cardiomyopathy were isolated from the left ventricular apical core, which was removed for the CF-LVAD implantation. In 11 of these patients, paired coronary arteries were obtained from an adjacent region of myocardium after the CF-LVAD intervention (n=6 ICM, 5 non-ICM). Vascular function was assessed ex vivo using isometric tension procedures in these patients and in 7 nonfailing donor controls. Maximal endothelium-dependent vasorelaxation to BK (bradykinin; 10-10 M) was blunted (P<0.05) in arteries from patients with ICM compared with non-ICM and donor controls, whereas responses to sodium nitroprusside (10-10 M) were similar among the groups. Contrary to our hypothesis, vasorelaxation responses to BK and sodium nitroprusside were similar before and 219±37 days after CF-LVAD support. Of these patients, an exploratory subgroup analysis revealed that BK-induced coronary artery vasorelaxation was greater (P<0.05) after (87±6%) versus before (54±14%) CF-LVAD intervention in ICM patients, whereas sodium nitroprusside-evoked responses were similar.
Coronary artery endothelial function is not impaired by durable CF-LVAD support and in ICM patients appears to be improved. Investigating coronary endothelial function using in vivo approaches in a larger patient population is warranted.
在实施耐用型持续血流左心室辅助装置(CF-LVAD)循环支持后,冠状脉管系统的搏动性会降低。有证据表明,适当的搏动性是维持内皮细胞稳态所必需的。我们假设 CF-LVAD 干预后,冠状动脉内皮功能会受损。
从缺血性心肌病(ICM;n=16)或非 ICM(n=22)心肌病导致的终末期心力衰竭患者的左心室心尖核心中分离出冠状动脉。在这些患者中,11 例患者的 CF-LVAD 干预后,从心肌的邻近区域获得了配对的冠状动脉(n=6 例 ICM,5 例非 ICM)。在这些患者和 7 例非衰竭供体对照中,使用等长张力程序在体外线粒体功能评估。与非 ICM 和供体对照组相比,ICM 患者的血管对 BK(缓激肽;10-10 M)的最大内皮依赖性血管舒张作用减弱(P<0.05),而各组对硝普钠(10-10 M)的反应相似。与我们的假设相反,CF-LVAD 支持前后 219±37 天,BK 和硝普钠引起的血管舒张反应相似。在这些患者中,探索性亚组分析表明,与 CF-LVAD 干预前(54±14%)相比,ICM 患者的 BK 诱导的冠状动脉血管舒张作用更大(P<0.05),而硝普钠引起的反应相似。
耐用型 CF-LVAD 支持不会损害冠状动脉内皮功能,在 ICM 患者中似乎有所改善。在更大的患者人群中使用体内方法研究冠状动脉内皮功能是有必要的。