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Comparative study on the enhancement of ischemic tolerance by intracoronary pretreatment with three calcium antagonists in pig hearts

  • Calcium Antagonists
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Summary

The effect of intracoronary (IC) pretreatment with different calcium antagonists (diltiazem, nifedipine, verapamil) on the development of infarcts was investigated in two experimental series including 35 open-chest pigs. The left anterior descending coronary artery (LAD) was distally ligated for 75 minutes (series A) or for 45 minutes (series B) and was reperfused for 24 hours. Infarct size was determined as the ratio of infarcted myocardium (tetrazolium stain) to the risk region (dye technique). In series A, 20 pigs were pretreated immediately before occlusion with either IC diltiazem (n=5, 4 mg/2 min), IC nifedipine (n=5, 0.4 mg/2 min), IC verapamil (n=5, 1 mg/2 min), or isotonic sodium chloride solution (n=5). In series B, IC diltiazem (n=5, 4 mg/2 min), IC verapamil (n=5, 1 mg/2 min), or isotonic saline solution (n=5) were administered 8 minutes prior to ischemia. The IC infusion of all calcium antagonists (series A) depressed left ventricular peak pressure, diastolic blood pressure, and dp/dt max and increased heart rate and coronary venous oxygen saturation. The development of infarcts was significantly delayed by IC diltiazem and IC verapamil. Mean infarct sizes (series A) amounted to 62% in the diltiazem group, 88% in the nifedipine group, 40% in the verapamil group, and 94% in the control group. In series B, where a time period of 8 minutes elapsed between pretreatment and induction of ischemia, mean infarct sizes after 45 minutes of ischemia and 24 hours of reperfusion amounted to 47% in the diltiazem group, 4% in the verapamil group, and 76% in control experiments. The better protection of verapamil in series B can mainly be ascribed to its longer lasting regional depression compared to diltiazem.

In conclusion, at the given drug concentrations, IC verapamil and IC diltiazem enhanced the ischemic tolerance to a greater extent than IC nifedipine (series A). When a time period of 8 minutes had elapsed between IC treatment and the onset of ischemia (series B), verapamil still exhibited a protective effect on the treated myocardium, which can mainly be ascribed to its long-lasting negative inotropic action.

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Authors and Affiliations

  1. Department of Cardiology, University of Göttingen, Federal Republic of Germany

    Hermann H. Klein, Sibylle Pich, Stefanie Lindert, Klaus Nebendahl & Heinrich Kreuzer

  2. Department of Experimental Animal Research, University of Göttingen, Federal Republic of Germany

    Hermann H. Klein, Sibylle Pich, Stefanie Lindert, Klaus Nebendahl & Heinrich Kreuzer

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  1. Hermann H. Klein
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  2. Sibylle Pich
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  4. Klaus Nebendahl
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  5. Heinrich Kreuzer
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Additional information

This study was supported by a grant from the Deutsche Forschungs-gemeinschaft, SFB 330 Organprotektion. The paper contains parts of the “Habilitationschrift” of Dr. H. H. Klein.

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Klein, H.H., Pich, S., Lindert, S. et al. Comparative study on the enhancement of ischemic tolerance by intracoronary pretreatment with three calcium antagonists in pig hearts. Cardiovasc Drug Ther 2, 815–821 (1989). https://doi.org/10.1007/BF00133213

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