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  • 1
    ISSN: 1573-7241
    Keywords: diltiazem ; nifedipine ; verapamil ; infarct size ; pigs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-742X
    Keywords: ischemia ; infarction ; infarct size ; cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated whether reperfusion results in an increase of ultrastructurally determined myocardial injury in pig hearts. The left anterior descending coronary artery (LAD) was distally occluded in 12 pigs for 35–45 minutes and then reperfused for 3 hours. At the end of ischemia, as well as after 3 hours of reperfusion, one transmural biopsy was removed from the center of the risk region and subdivided into four specimens, representing the subendocardial (I), subendo-midmyocardial (II), subepi-midmyocardial (III), and subepicardial layers (IV). The degree of injury was assessed by electronmicroscopy and was scored as reversible (1), an almost equal mixture of reversible and irreversible (2), and totally irreversible (3) damage. In addition, infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic (dye technique) myocardium. Infarct sizes ranged from 29.3% to 93% (mean 61.2%). The scores of injury of the four tissue layers before and after reperfusion did not differ significantly: layer I, 2.4 ± 0.8/2.3 ± 0.9; layer II, 2.2 ± 0.9/2.0 ± 0.9; layer III, 1.8 ± 0.9/2.0 ± 0.9; and layer IV, 1.6 ± 0.9/1.3 ± 0.6. The means of the four layers were almost identical at the end of ischemia (2.1 ± 0.8) and after 3 hours of reperfusion (2.0 ± 0.6). A linear regression analysis with 95% confidence limits of the score values before and after reperfusion indicated that maximally 25% of a mean final infarct size of about 50% may be due to lethal reperfusion injury. This study suggests that cell death in regional ischemia and reperfusion occurs predominantly during ischemia and not during reperfusion.
    Type of Medium: Electronic Resource
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