Author + information
- Received December 13, 1985
- Revision received March 26, 1986
- Accepted May 2, 1986
- Published online November 1, 1986.
- Colin A. Campbell, PhD*,
- Robert A. Kloner, MD, PhD, FACC*,§,‡,
- Kevin J. Alker* and
- Eugene Braunwald, MD, FACC†
- ↵§Address for reprints: Robert A. Kloner, MD, PhD, Wayne State University School of Medicine, Division of Cardiology, Harper Hospital, 3990 John R, Detroit, Michigan 48201.
Reocclusion after successful coronary reperfusion occurs in 15 to 35% of patients receiving thrombolytic therapy for acute myocardial infarction. The present study was designed to simulate the clinical situation of reocclusion and determine whether verapamil might be effective in reducing myocardial necrosis and preserving high energy phosphates in this setting. Pentobarbital-anesthetized, open chest dogs underwent occlusion of the left anterior descending coronary artery for 2 hours followed by 1 hour of reperfusion and a further 4 hours of coronary artery occlusion. Treatment with verapamil (intravenous bolus dose of 0.2 mg/kg body weight followed by infusion of 0.56 ± 0.14 mg/kg per h) was begun 1 hour after occlusion and infusion was continued for the remainder of the experiment. The dose of verapamil was adjusted to lower mean arterial pressure to approximately 90 mm Hg. The area at risk was determined by intraatrial injection of monastral blue dye and the area of necrosis was assessed by triphenyltetrazolium chloride staining. In vivo myocardial needle biopsy for determination of adenosine triphosphate and creatine phosphate was performed at the end of the experiment.
The area of the left ventricle at risk was similar in both groups (control [n = 8], 20.2 ± 1.6% versus ve-rapamil-treated [n = 9], 23.1 ± 2.9%; p = NS). The area of necrosis expressed as a percent of the area at risk was reduced in the verapamil-treated group compared with the control group (43.3 ± 5.0% versus 63.1 ± 6.8%, p < 0.05). At the termination of the experiment, the adenosine triphosphate and creatine phosphate were significantly higher in both the epicar-dium and endocardium of the ischemic area in the verapamil-treated group compared with the control group.
In conclusion, verapamil reduced or at least delayed the necrosis in an experimental model of reocclusion after an initial period of reperfusion and was associated with a preservation of high energy phosphate content.
- Received December 13, 1985.
- Revision received March 26, 1986.
- Accepted May 2, 1986.
- American College of Cardiology Foundation