Collateral blood flow following acute coronary artery occlusion: comparison of a new intracellular calcium antagonist (KT-362) and diltiazem.
The effects of a new intracellular calcium antagonist, KT-362 (150 and 300 micrograms/kg per min), on hemodynamics and collateral function (retrograde pressure and flow, radioactive microspheres) distal to an acute coronary artery occlusion were studied in anesthetized dogs and compared with the effects of the structurally related classical calcium channel blocker, diltiazem (15 and 30 micrograms/kg per min), and a saline-treated control group. In the saline series, there were no changes in systemic hemodynamics or coronary collateral blood flow over the 90-min ischemic period. KT-362 reduced mean aortic pressure, heart rate, and dP/dt whereas diltiazem only decreased aortic blood pressure. When blood pressure was controlled by a distal aortic cuff, heart rate was significantly reduced in both groups and dP/dt was reduced in the KT-362 series and increased in diltiazem-treated dogs. In both drug-treated groups, retrograde pressure and flow were significantly increased only when aortic pressure was controlled. Regional myocardial tissue blood flow in the nonischemic or ischemic region did not change significantly after KT-362 treatment despite its hypotensive actions, and in the presence of a constant aortic pressure, transmural collateral blood flow and the ischemic/nonischemic blood flow ratio tended to increase. In contrast, diltiazem treatment resulted in a significant decrease in the ischemic/nonischemic blood flow ratio in the absence of blood pressure control. In the presence of constant aortic pressure, blood flow to the nonischemic area was markedly increased by diltiazem whereas subendocardial blood flow was significantly increased in the ischemic area.(ABSTRACT TRUNCATED AT 250 WORDS)
Farber
N E
NE
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D013841:Thiazepines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D013841:Thiazepines; C051271:KT 362; D004110:Diltiazem