TY - JOUR
T1 - Effects of endothelin-1 at pathophysiologic concentrations on coronary perfusion and mechanical function of normal and postischemic myocardium
AU - Donckier, Julian
AU - Hanet, Claude
AU - Stoleru, Liviu
AU - Van Mechelen, Henri
AU - Galanti, Laurence
AU - Hayashida, Wataru
AU - Keyeux, André
AU - Ketelslegers, Jean Marie
AU - Pouleur, Hubert
PY - 1994/11
Y1 - 1994/11
N2 - 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.
AB - 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.
KW - Atrial natriuretic factor-Myocardium
KW - Endothelin-1-Ischemia
KW - Stunning
UR - http://www.scopus.com/inward/record.url?scp=0028044790&partnerID=8YFLogxK
U2 - 10.1097/00005344-199411000-00006
DO - 10.1097/00005344-199411000-00006
M3 - Article
C2 - 7511749
AN - SCOPUS:0028044790
SN - 0160-2446
VL - 2
SP - 212
EP - 219
JO - Journal of cardiovascular pharmacology
JF - Journal of cardiovascular pharmacology
IS - 2
ER -