PhyMedExp, Université Montpellier, INSERM, CNRS, 34295 Montpellier, France.
CHU de Montpellier, 34090 Montpellier, France.
Int J Mol Sci. 2023 Jan 10;24(2):1325. doi: 10.3390/ijms24021325.
Acute heart failure (AHF) due to acute myocardial infarction (AMI) is likely to involve cardiogenic shock (CS), with neuro-hormonal activation. A relationship between AHF, CS and vasopressin response is suspected. This study aimed to investigate the implication of vasopressin on hemodynamic parameters and tissue perfusion at the early phase of CS complicating AMI. Experiments were performed on male Wistar rats submitted or not to left coronary artery ligation (AMI and Sham). Six groups were studied Sham and AMI treated or not with either a vasopressin antagonist SR-49059 (Sham-SR, AMI-SR) or agonist terlipressin (Sham-TLP, AMI-TLP). Animals were sacrificed one day after surgery (D) and after hemodynamic parameters determination. Vascular responses to vasopressin were evaluated, ex vivo, on aorta. AHF was defined by a left ventricular ejection fraction below 40%. CS was defined by AHF plus tissue hypoperfusion evidenced by elevated serum lactate level or low mesenteric oxygen saturation (SmO) at D. Mortality rates were 40% in AMI, 0% in AMI-SR and 33% in AMI-TLP. Immediately after surgery, a sharp decrease in SmO was observed in all groups. At D, SmO recovered in Sham and in SR-treated animals while it remained low in AMI and further decreased in TLP-treated groups. The incidence of CS among AHF animals was 72% in AMI or AMI-TLP while it was reduced to 25% in AMI-SR. Plasma copeptin level was increased by AMI. Maximal contractile response to vasopressin was decreased in AMI (32%) as in TLP- and SR- treated groups regardless of ligation. Increased vasopressin secretion occurring in the early phase of AMI may be responsible of mesenteric hypoperfusion resulting in tissue hypoxia. Treatment with a vasopressin antagonist enhanced mesenteric perfusion and improve survival. This could be an interesting therapeutic strategy to prevent progression to cardiogenic shock.
急性心肌梗死（AMI）引起的急性心力衰竭（AHF）可能涉及心源性休克（CS）和神经激素激活。AHF、CS 和血管加压素反应之间的关系受到怀疑。本研究旨在探讨血管加压素对 AMI 并发 CS 早期血流动力学参数和组织灌注的影响。实验在雄性 Wistar 大鼠中进行，分为左冠状动脉结扎（AMI 和 Sham）和未结扎（AMI 和 Sham）。研究了 6 组 Sham 和 AMI 治疗或不治疗血管加压素拮抗剂 SR-49059（Sham-SR，AMI-SR）或激动剂特利加压素（Sham-TLP，AMI-TLP）。手术后一天（D）测定血流动力学参数后处死动物。评估血管加压素的血管反应，在体外用主动脉进行。AHF 定义为左心室射血分数低于 40%。CS 定义为 AHF 加组织低灌注，表现为血清乳酸水平升高或肠系膜氧饱和度（SmO）降低。AMI 组死亡率为 40%，AMI-SR 组为 0%，AMI-TLP 组为 33%。手术后立即，所有组的 SmO 急剧下降。在 D，Sham 和 SR 治疗组的 SmO 恢复，而 AMI 和 TLP 治疗组的 SmO 仍然较低，且进一步降低。在 AMI 或 AMI-TLP 治疗的 AHF 动物中，CS 的发生率为 72%，而在 AMI-SR 治疗的动物中降低至 25%。AMI 增加了血浆 copeptin 水平。AMl 组的血管加压素最大收缩反应降低（32%），TLP 和 SR 治疗组也是如此。AMI 早期发生的血管加压素分泌增加可能导致肠系膜低灌注，导致组织缺氧。血管加压素拮抗剂的治疗增强了肠系膜灌注，提高了生存率。这可能是一种预防心源性休克进展的有前途的治疗策略。
