Effect of diltiazem on experimental coronary artery thrombosis in dogs

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 micrograms/kg plus 20 micrograms/kg/min i.v.; n = 6) was begun 15 min 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 micrograms/kg plus 20 micrograms/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 mumols/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.