The effect of intracoronary diltiazem on regional myocardial function and development of infarcts in porcine hearts

Klein, Hermann H.; Pich, Sibylle; Lindert, S.; Nebendahl, Klaus; Kreuzer, H

doi:10.1007/bf01856024

Cited by 4 publications

(1 citation statement)

References 18 publications

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“…The risk region could accurately be delineated by an injected dye because porcine hearts lack significant collateral blood flow [19,20], warranting a clear and sharp border between ischemic and well-perfused myocardium. Ischemia of 75 minutes (series A) was chosen because experiments with ]C diltiazem had suggested that infarct sizes of 40% to 60% could have been expected in this group [21], allowing the assessment of smaller or larger infarctions in the other treatment groups. In series B, the LAD was occluded for 45 minutes since mean infarct sizes of 70% to 75% were obtained in previous control experiments [9,10].…”

Section: Applied Methodsmentioning

confidence: 99%

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

Klein

Pich

Lindert

et al. 1989

Cardiovasc Drug Ther

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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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Applied Methodsmentioning

confidence: 99%

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

Klein

Pich

Lindert

et al. 1989

Cardiovasc Drug Ther

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The periangioplasty polypharmacy: A role for diltiazem?

Turi

1995

Cathet. Cardiovasc. Diagn.

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The paper by Dr. Mclvor and colleagues broadly entitled "Clinical Effects and Utility of Intracoronary Diltiazem" raises significant issues about adjunctive therapy during angioplasty. There is limited published data on parenteral diltiazem use during PTCA; this study describes a small number of patients receiving a fixed dose via intracoronary administration.Intracoronary diltiazem has at least five potential applications during coronary angioplasty. First, it could provide epicardial vasodilation prior to instrumentation: a 10 to 20% increase in luminal diameter in both normal [ I ] and diseased [2] segments has been demonstrated by others and confirmed in this paper, albeit in diseased segments only. Second, it could attenuate ischemia during balloon inflation, allowing for better-tolerated and longer inflations, and potentially limit myocardial necrosis [3]. Careful studies of a number of agents, including nitroglycerin [4], propranolol [ 5 ] , verapamil (61, nifedipine [7], as well as intravenous diltiazem [8,9] have demonstrated reduction of ischemia during balloon occlusion. Third, intracoronary diltiazem could provide treatment for severe coronary vasospasm or no-ref low phenomenon, the latter seen after embolization of clot, debris from degenerated vein grafts, or during routine rotational atherectomy. Fourth, diltiazem could have adjunctive benefit, based on data from intravenous studies, on heart rate control during angioplasty by preventing supraventricular tachycardia and preventing catecholamine mediated sinus tachycardia [lo]. Finally, it may have potential hemodynamic benefits through its vasodilator activity and early improvement in segmental systolic function [ 1 I ] in selected patients.McIvor and colleagues report the effects of intracoronary diltiazem on heart rate, blood pressure, electrical conduction, and coronary artery diameters. In an earlier study, we looked at myocardial ischemia as measured by ST segment changes and chest pain score \ 121, using a much higher dose of intracoronary diltiazem (100 pg/kg) in a randomized comparison with placebo. We found marked reduction of ST segment elevation and chest pain. This was achieved at the penalty of a >40% incidence of significant but transient conduction distrubances, although the dosage was substantially higher than that described in this issue of the Journal. We speculated initially that avoiding infusion into a right coronary artery supplying both the sinus and a-v nodal arteries might eliminate conduction problems, but experienced similar bradyarrhythmias with injection into the LAD and nondominant left circumflex arteries as well.Thus we would like to sound a note of caution regarding the encouraging findings reported by Dr. McIvor and colleagues that intracoronary diltiazem given slowly at low dose appeared to be safe in their 12 patients. The use of intracoronary diltiazem is likely to be considered for severe vasospasm and for no-reflow type ischemia, currently most common with use of the Rotablator. In most laboratories, this pa...

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Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists

Unterberg¹,

Buchwald²,

Mindel³

et al. 1992

Basic Res Cardiol

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Oxygen free radicals have been shown to play a major role in the development of perfusion abnormalities, contractile dysfunction, and irreversible injury in ischemic-reperfused myocardium. The aim of this study was to assess the direct protective effects of radical scavengers, calcium antagonists, and combination of these substances against free radical induced myocyte damage. Viability (% of rod-shaped cells) and adenine nucleotide content (AdN, high-pressure liquid chromatography) of isolated adult rat cardiomyocytes were measured after exposure to hypoxanthine (2 mM) and xanthine oxidase (25 mU/ml). After 90 min, viability of myocytes decreased to 4.2 +/- 3.4% (mean +/- SEM) of pre-exposure control, and AdN decreased from 28.2 +/- 1.8 to 8.09 +/- 1.1 nmol/mg protein. Addition of catalase (1500 U/ml) resulted in the preservation of viability (77 +/- 6% of pre-exposure control, n = 6, mean +/- SEM), and AdN 84 +/- 6%, p less than 0.001. These values are not significantly different from those measured in myocytes not exposed to free radicals (88 +/- 9% and 79 +/- 6%, respectively). Superoxide dismutase (2400 U/ml), dimethylthiourea (10 mM), and desferrioxamine (1 mM) did not preserve either viability or AdN. The calcium antagonist verapamil (10 microM) also preserved myocyte viability significantly (23 +/- 9.7%, p less than 0.05 vs unprotected cells), but failed to prevent the loss of AdN (13.2 +/- 4%, not significant as compared to unprotected cells). Viability and AdN in myocytes treated with nifedipine (10 microM) or diltiazem (10 microM) were not higher than in unprotected cells. All combined treatment forms which included catalase resulted in the preservation of myocyte viability as well as AdN. These data show that only the hydrogen peroxide scavenger catalase protects isolated cardiomyocytes against free radicals generated in the purine catabolic pathway.

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The effect of intracoronary diltiazem on regional myocardial function and development of infarcts in porcine hearts

Cited by 4 publications

References 18 publications

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

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

The periangioplasty polypharmacy: A role for diltiazem?

Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists

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