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Implication de la vasopressine dans l'hypoperfusion tissulaire au cours du choc cardiogénique compliquant l'infarctus du myocarde

Abstract : 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. Permanent left coronary artery ligation (LCA) is the most widely used model of heart failure in rat. A shock state is characterized by an increase of lactate production, a marker of global tissue dysoxia to which mesenteric hypoperfusion may notably contribute. The aim of the first study was to evaluate the relationship between CS and mesenteric perfusion assessed by near infrared spectroscopy (NIRS) in a rat model. The second study aimed to investigate the implication of vasopressin on hemodynamic and tissue perfusion at the early phase (24h) of CS complicating AMI. All animals had the same surgery with LCA ligation (AMI) or not (Sham). From the whole cohort of 103 male Wistar rats, the mesenteric oxygenation (SmO2) was compared in several animals between AMI with cardiogenic shock (left ventricular ejection fraction (LVEF) ≤ 40% and elevated lactate level) and selected Sham and AMI with normal lactate level (non-shocked). After surgery, SmO2 decreased notably in all groups. SmO2 remained low at Day 1 (D1) only in AMI with CS, while it returned close to preoperative value in Sham and AMI without shock. The mean arterial pressure was lower, and the decrease of cardiac output was higher in AMI with CS compared to non-shocked AMI. SmO2 determination had an excellent predictive value for CS (area under the receiver operating characteristic curve: 0.955 [95%CI: 0.854;1], p=0.003) with a 100% sensitivity and 88% specificity for a 35% SmO2 threshold. In order to study AMI-induced AHF and vasopressin stimulation, a LVEF ≤ 40% was prerequisite for the selection of animals in AMI groups and six groups of rats were studied: Sham without treatment, AMI without treatment (AMI), rats treated with terlipressin (Sham-TLP and AMI-TLP) or SR-49059, a V1a receptor antagonist, (Sham-SR and AMI-SR). To assess CS, a tissue hypoperfusion as evidenced by lactate > 2.2 mmol/L or mesenteric hypoxia (SmO2 < 35%) was required. Among 103 operated rats, 67 were ligatured and exhibited mortality of 40%, 0% and 33% respectively for AMI, AMI-SR and AMI-TLP (p=0.057). All animals were sacrificed at D1 after hemodynamic and biochemical assessments. Incidence of CS was decreased to 25% in AMI-SR versus 72% in AMI or AMI-TLP (p=0.038). Plasma copeptin at D1 was increased in AMI and AMI-SR but not in AMI-TLP. The maximal contractile response to vasopressin, evaluated in vitro on aortic rings, was similarly decreased in AMI and TLP-treated rats (AMI-TLP and Sham-TLP) compared to Sham but also severely altered in animals treated by the antagonist, the latest exhibiting a competitive binding profile. To conclude, CS occurs likely when LVEF is below 40% after LCA ligation. In this model, CS is associated with a significant decrease in mesenteric oxygenation. Thus, combined to reduced LVEF, SmO2 could allow a non-invasive assessment of shock at the bench side. Increased vasopressin secretion seems involved in the early phase of AMI, which may result in mesenteric hypoperfusion and lactate production. Tissue perfusion was improved by V1a antagonist treatment, without major effect on arterial pressure, while it was impaired by treatment with terlipressin, associated to a huge increase in arterial pressure. The role of vasopressin in tissue hypoperfusion during the early phase of CS seems crucial.
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Philippe Gaudard. Implication de la vasopressine dans l'hypoperfusion tissulaire au cours du choc cardiogénique compliquant l'infarctus du myocarde. Médecine humaine et pathologie. Université Montpellier, 2020. Français. ⟨NNT : 2020MONTT004⟩. ⟨tel-02869670⟩

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