Effects of Diltiazem (CRD-401) on Developed Coronary Collaterals in the Dog

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Abstract
The effect of diltiazem (CRD-401) on coronary collaterals was studied in the dog. The anterior descending branch of the left coronary artery was occluded for 4 to 6 weeks by an ameroid constrictor. In these dogs, the retrograde flow (RF) from the peripheral coronary artery and peripheral coronary pressure (PCP) were significantly higher than those in acute coronary-ligated dogs, suggesting the development of large supraepicardial intercoronary anastomoses. Diltiazem (100 μg/kg i.v.) increased circumflex blood flow (CBF) for several min, while nitroglycerin (10 μg/ kg i.v.) increased CBF transiently after which CBF decreased to below control values. Diltiazem (100 μg/kg) and nitroglycerin (10 μg/kg) increased RF/MAP (mean aortic pressure) and PCP/MAP and these increases lasted longer than that of CBF. Diltiazem also increased RF in doses of 100 μg/kg or 20 μg/kg/min. Therefore, diltiazem possesses the property of dilating coronary collaterals thus causing redistribution of intramyocardial blood flow. In acute preparations, however, both diltiazem and nitroglycerin showed no significant changes in PCP/MAP and RF/MAP.