Short-term low dose intracoronary diltiazem administered at the onset of reperfusion reduces myocardial infarct size

Abstract

Background: Currently, controversy exists regarding the use of calcium-channel blockers in the treatment of acute myocardial infarction (AMI), due to apparent conflicting results from clinical trials and animal models. One hypothesis to explain such a discrepancy proposes that the timing and duration of drug administration might influence its cardioprotective effect. Pretreatment with calcium-channel blockers or their administration during coronary artery occlusion is associated with the diminished infarct size in animal models. While verapamil failed to reduce infarct size when the drug was given at the onset of reperfusion, similar effects of low dose diltiazem are not known. Methods and Results: This experiment evaluated the effect of intracoronary short term low dose diltiazem administration given immediately with postischemic myocardial reperfusion. Yorkshire swine underwent thoracotomy and 50 min of LAD occlusion, followed by 3 h of reperfusion. In the first group, diltiazem (2.5 mg diluted in 60 cc saline) was infused into the left anterior descending (LAD) over 12 min, beginning with the onset of reperfusion ( n=8). In the second group, animals received saline instead of diltiazem and served as controls ( n=6). Infarct size was 0.13±0.06 g/kg of body weight for diltiazem group, and 0.42±0.04 g/kg for controls ( P=0.01). Conclusions: Short-term low dose diltiazem delivered exclusively during early reperfusion can significantly diminish infarct size in swine. Local intracoronary diltiazem may be valuable adjunct in patients subject to myocardial ischemia/reperfusion during coronary artery bypass grafting, primary angioplasty for AMI, or thrombolysis for AMI if given immediately after restoration of coronary blood flow.