Cardioprotective Actions of Nisoldipine in Postreinfusion Myocardial Ischemia

Mentley, Richard K.; Lefer, Allan M.

doi:10.1111/j.1749-6632.1988.tb33394.x

Cited by 1 publication

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“…The degree of myocardial protection achieved with t-PA and CGS-13080 is quite striking, and is greater than that obtained using the calcium channel blocker nisoldipine in this same model. 32 In summary, occlusion of the LAD coronary artery in cats for two hours followed by reperfusion for four hours results in a significant degree of necrotic myocardial tissue. Administration of the thrombolytic agent t-PA or the thromboxane synthetase inhibitor CGS-13080 alone did not exert a clear-cut degree of myocardial salvage.…”

Section: Discussionmentioning

confidence: 98%

Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.

Lefer

Mentley

Sun

1988

Circulation Research

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We studied the effects of a thrombolytic agent (t-PA) and a thromboxane synthetase inhibitor (CGS-13080) in a model of myocardial ischemia and reperfusion. Occlusion of the left anterior descending coronary artery for 2 hours followed by 4 hours of reperfusion in anesthetized cats results in a large washout of creatine kinase into the blood (32 ±7 lU/mg protein) and an area of necrotic tissue comprising 52±5% of the area at risk and 9±0.6% of the left ventricle. Intravenous administration of t-PA (500 IU/kg • min) for 30 minutes alone at reperfusion or infusion of CGS-13080 (500 figlkg • hr) had no effect on washout of creatine kinase or extent of necrotic tissue development. Administration of the same doses of both t-PA and CGS-13080 together markedly attenuated creatine kinase release to 10 ± 2 IU/mg protein (p<0.01) and reduced the area of necrotic tissue to 9 ± 2% of the area at risk and only 1.3 ± 0.3% of the left ventricle (/?<0.001). No significant sustained effects of these agents were observed on mean arterial blood pressure, heart rate, or the pressure rate index in these experiments. Thus, t-PA and CGS-13080 exert synergistic effects hi preserving myocardial integrity in cats subjected to acute myocardial ischemia followed by reperfusion. The mechanism of this beneficial effect does not appear to be via reduced myocardial oxygen demand, increased myocardial oxygen supply, or enhanced inhibition of thromboxane A 2 formation. The mechanism of this anti-ischemic effect is not clear but may involve a metabolic or a cytoprotective effect. (Circulation Research

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Section: Discussionmentioning

confidence: 98%