Effects of bradycardic agents on ischaemic myocardium and perfusion in anesthetized dogs.
The effects of several new specific bradycardic agents, AQ-A39 and AQ-AH 208, were evaluated in two models of myocardial ischaemia in anesthetized dogs. In the first model, equal bradycardic doses of AQ-AH 208 and propranolol were compared for their effects on coronary collateral blood flow in dogs subjected to an acute coronary artery occlusion. AQ-AH 208 produced a significant (P less than 0.05) increase (35%) in transmural collateral perfusion whereas propranolol had no effect. Atrial pacing to control heart rate only partially negated the beneficial effect of AQ-AH 208 on collateral flow. In the second model of ischaemia, AQ-AH 208 and AQ-A39 were evaluated for their effects on subendocardial segment shortening (% SS) and regional myocardial blood flow in dogs subjected to 15 minutes of coronary artery occlusion, followed by 3 hours of reperfusion. Both compounds produced similar decreases in heart rate (24%) and increases in the endocardial/epicardial distribution of collateral blood flow. During occlusion and throughout reperfusion, AQ-AH 208 and AQ-A39 resulted in a significant improvement in % SS in the ischaemic-reperfused region. These results suggest that specific bradycardic agents may have potential for therapeutic use in certain types of myocardial ischaemia by several different mechanisms.
Gross
G J
GJ
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Daemmgen
J W
JW
D000768:Anesthesia, General; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D054833:Isoindoles; D008297:Male; D010797:Phthalimides / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D054833:Isoindoles; D010797:Phthalimides; D011433:Propranolol; C030532:falipamil