Department of Anesthesiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Institute for Cardiovascular Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Int J Mol Sci. 2024 Oct 12;25(20):10975. doi: 10.3390/ijms252010975.
Endothelial dysfunction (ED) is closely associated with most cardiovascular diseases. Experimental models are needed to analyze the potential impact of ED on cardioprotection in constant pressure Langendorff systems (CPLS). One cardioprotective strategy against ischemia/reperfusion injury (I/RI) is conditioning with the lipid emulsion Intralipid (IL). Whether ED modulates the cardioprotective effect of IL remains unknown. The aim of the study was to transfer a protocol using a constant flow Langendorff system for the induction of ED into a CPLS, without the loss of smooth muscle cell functionality, and to analyze the cardioprotective effect of IL against I/RI under ED. In isolated hearts of male Wistar rats, ED was induced by 10 min perfusion of a Krebs-Henseleit buffer containing 60 mM KCl (K+), and the vasodilatory response to the vasodilators histamine (endothelial-dependent) and sodium-nitroprusside (SNP, endothelial-independent) was measured. A CPLS was employed to determine cardioprotection of pre- or postconditioning with 1% IL against I/RI. The constant flow perfusion of K+ reduced endothelial response to histamine but not to SNP, indicating reduced vasodilatory functionality of endothelial cells but not smooth muscle cells. Preconditioning with IL reduced infarct size and improved cardiac function while postconditioning with IL had no effect. The induction of ED neither influenced infarct size nor affected the cardioprotective effect by preconditioning with IL. This protocol allows for studies of cardioprotective strategies under ED in CLPS. The protection by preconditioning with IL seems to be mediated independently of a functional endothelium.
内皮功能障碍 (ED) 与大多数心血管疾病密切相关。需要实验模型来分析 ED 对恒压 Langendorff 系统 (CPLS) 中心脏保护的潜在影响。一种针对缺血/再灌注损伤 (I/RI) 的心脏保护策略是使用脂质乳剂 Intralipid (IL) 进行预处理。ED 是否调节 IL 的心脏保护作用尚不清楚。本研究的目的是将使用恒流 Langendorff 系统诱导 ED 的方案转移到 CPLS 中，同时不丧失平滑肌细胞功能，并分析 ED 下 IL 对 I/RI 的心脏保护作用。在雄性 Wistar 大鼠的离体心脏中，通过灌注含有 60mM KCl (K+) 的 Krebs-Henseleit 缓冲液 10 分钟来诱导 ED，并测量血管扩张剂组胺 (内皮依赖性) 和硝普钠 (SNP，内皮非依赖性) 的血管扩张反应。采用 CPLS 来确定 1%IL 对 I/RI 的预处理或后处理的心脏保护作用。K+ 的恒流灌注降低了内皮对组胺的反应，但对 SNP 没有影响，表明内皮细胞的血管扩张功能降低，但平滑肌细胞没有。IL 的预处理可减少梗死面积并改善心功能，而 IL 的后处理则没有效果。ED 的诱导既不影响梗死面积，也不影响 IL 预处理的心脏保护作用。该方案允许在 CPLS 中研究 ED 下的心脏保护策略。IL 预处理的保护似乎独立于功能正常的内皮细胞。
