Improvement in functional recovery of stunned canine myocardium by long-term pretreatment with oral propranolol.
We investigated the effect of long-term oral pretreatment with the beta-adrenergic antagonist, propranolol (Inderal LA, 160 mg daily for 8 days) on the functional recovery of myocardium after 15-minute coronary artery occlusion followed by 3 hours of reperfusion in barbital-anesthetized dogs. Propranolol-pretreated dogs (N = 9) displayed a significantly lower left ventricular peak-positive rise in ventricular pressure (dP/dt), heart rate, and rate-pressure product throughout the experiment compared with the control group (N = 15). Subendocardial percent segment shortening as measured by sonomicrometry recovered to 65.4 +/- 7.2% of the preocclusion level after pretreatment with propranolol, whereas the control group recovered to only 11.1% +/- 10.2% after 3 hours of reperfusion. To ascertain the beneficial role of a lower heart rate on the recovery of regional contractile function, a third group of dogs (N = 6) was pretreated with propranolol, but heart rate was maintained at control levels by atrial pacing. The beneficial effects of pretreatment with propranolol were abolished in this group. There were no differences between groups in myocardial perfusion in the normal region as measured by the radioactive microsphere technique. However, in postischemic, reperfused myocardium, there was a significantly higher blood flow to subepicardium, mid-myocardium, and subendocardium after reperfusion in the propranolol-pretreated, unpaced group. Thus long-term oral pretreatment with propranolol enhances the contractile recovery of postischemic, reperfused myocardium. This protective effect of beta-adrenergic blockade is primarily related to the reduction in heart rate and enhanced perfusion in the postischemic region.
al-Wathiqui
M H
MH
Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226.
Farber
N
N
Pelc
L
L
Gross
G J
GJ
Brooks
H L
HL
Warltier
D C
DC
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D011433:Propranolol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology
D011433:Propranolol