Effect of Diltiazem on Experimental Coronary Artery Thrombosis in Dogs

Abstract

The effect of the calcium channel blocker diltiazem on arterial thrombosis was determined in anesthetized dogs subjected to continuous anodal stimulation of the intimal surface of the left circumflex coronary artery (LCCA). Infusion of saline (n = 6) or diltiazem (80 µg/kg plus 20 µg/kg/min i.v.; n = 6) was begun 15min before electrical stimulation. Diltiazem prolonged the P-R interval by 28% and reduced mean arterial blood pressure (ABP) by 9%. All animals developed occlusive thrombosis. Saline- and diltiazem-treated dogs did not differ in the time to occlusion (204 ± 30 and 153 ± 27 min, respectively) and LCCA thrombus mass (25 ± 4 and 24 ± 3 mg, respectively). LCCA flows measured intermittently during thrombogenesis also did not differ between treatment groups, although the frequency of spontaneous flow increases which interrupted the flow declines was reduced 53% by diltiazem. In separate diltiazem-treated dogs (80 µg/kg plus 20 µg/kg/min i.v. for 2 h; n = 7) the ex vivo platelet aggregation response to platelet-activating factor (PAF) was inhibited (-45%), but not the response to collagen. When 5 and 25 µmol/l diltiazem was tested in vitro, again the aggregation response to PAF was reduced (-25 and -81%, respectively) while that to collagen was unaffected. These results demonstrate that diltiazem does not impede thrombus formation in vivo when given at a dose that exerts threshold hemodynamic activity and significantly impairs platelet function.

The Effect of Diltiazem on Microcirculation of Trans-planted Tissue Flaps: Experimental Study on Rabbits

“…In some research studies, diltiazem was not able to prevent thrombosis, but others were found to be contradictory. Diltiazem is unable to prevent thrombosis when determining the dose that eliminates hemodynamic disorders on different animals, especially in the experiments with the creation of a coronary thrombosis model [10][11][12] . In the experimental coronary microemboli model formed on mice, coronary thrombosis symptoms were partially eliminated by intravenous diltiazem detection 13 .…”

Intracoronary Magnesium and Diltiazem Affect to a Similar Extent Certain Hemostatic Factors during Acute Myocardial Infarction in Swine

“…High levels of extra cellular Mg in vitro and intravenous Mg sup plementation ex vivo are associated with a dose-dependent inhibition of platelet aggregability [12,13], There is strong evidence that diltiazem, like Mg, favorably influences hemostasis dur ing ischemia-reperfusion. Most researchers agree that during ischemia-reperfusion diltia zem displays several properties including re duction of platelet aggregation [14,15], sup pression of thromboxane formation [16,17], increases in prostacyclin synthesis [18,19], facilitation of endothelin 1 (ET-1) clearance [20], and abolition of ET-1-induced vasocon striction [21], In contrast to the clinical set ting, animal studies demonstrate that both Mg and diltiazem reduce myocardial infarct size [22,23],…”