Effects of endothelin-1 at pathophysiologic concentrations on coronary perfusion and mechanical function of normal and postischemic myocardium.
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 pM, 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Donckier
J
J
Division of Endocrinology, University Hospital of Mont-Godinne, Yvoir, Belgium.
Hanet
C
C
Stoleru
L
L
Van Mechelen
H
H
Galanti
L
L
Hayashida
W
W
Keyeux
A
A
Ketelslegers
J M
JM
Pouleur
H
H
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001806:Blood Urea Nitrogen; D002395:Catecholamines / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D004285:Dogs; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011188:Potassium / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects
D002395:Catecholamines; D016232:Endothelins; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D011188:Potassium