Effects of endothelin-1 at pathophysiologic concentrations on coronary perfusion and mechanical function of normal and postischemic myocardium

Julian Donckier, Claude Hanet, Liviu Stoleru, Henri Van Mechelen, Laurence Galanti, Wataru Hayashida, André Keyeux, Jean Marie Ketelslegers, Hubert Pouleur

Research output: Contribution to journalArticle

Abstract

We assess hemodynamic, vascular, and hormonal effects of endothelin-1 (ET-1) at pathophysiologic levels on normal and ischemic myocardium. Thirty conscious chronically instrumented dogs were studied before, during, and after a 10-min coronary artery occlusion (CAO) performed either during ET-1 infusion (2.5 ng/kg min, n = 15) or during placebo infusion (n = 15). ET-1 infusion produced an increase in plasma ET-1 (from 1.3 ± 0.1 to 11.5 ± 1.1 pAf, p < 0.0001) during CAO (pathophysiologic value). Left anterior descending artery (LAD) blood flow (measured by Doppler flow probe) decreased similarly during CAO with ET-1 or placebo (p = 0.0001, NS, ET-1 vs. placebo). Both endocardial and epicardial blood flows in ischemic regions also decreased (p = 0.0001) during CAO but were threefold greater with ET-1 than with placebo (endocardium 42 ± 7 vs. 14 ± 2 ml/min/100 g, p = 0.003). No significant difference in myocardial blood flows between groups was observed in control regions. CAO produced increases (p < 0.005) in heart rate (HR), mean aortic pressure (AOP), and ventricular pressures but no change in atrial pressures. The changes in these parameters were comparable in the ET-1 and placebo groups. Despite the greater residual flow during CAO, however, ET-1 decreased the function of the ischemic zone during reperfusion as assessed by systolic shortening (p < 0.05). Atrial natriuretic factor (ANF), unchanged during CAO with placebo, increased from 38.3 ± 6.1 to 53.3 ± 10 pM with ET-1 (p = 0.02). Thus, ET-1, at pathophysiologic levels, increases collateral blood flow in ischemic myocardium without affecting perfusion of normal myocardium. It decreases postischemic myocardial recovery and directly stimulates ANF release.

Original languageEnglish
Pages (from-to)212-219
Number of pages8
JournalJournal of cardiovascular pharmacology
Volume2
Issue number2
DOIs
Publication statusPublished - Nov 1994
Externally publishedYes

Keywords

  • Atrial natriuretic factor-Myocardium
  • Endothelin-1-Ischemia
  • Stunning

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