Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.
- 1 September 1988
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 63 (3), 621-627
- https://doi.org/10.1161/01.res.63.3.621
Abstract
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 IU/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 micrograms/kg.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 less than 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 (p less than 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 in 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 A2 formation. The mechanism of this anti-ischemic effect is not clear but may involve a metabolic or a cytoprotective effect.This publication has 30 references indexed in Scilit:
- Cardioprotective actions of nisoldipine in postreperfusion myocardial ischemiaAmerican Heart Journal, 1988
- Thromboxane synthetase inhibition with CGS 13080 improves coronary blood flow after streptokinase-induced thrombolysisAmerican Heart Journal, 1987
- Intracoronary Administration of Streptokinase in a Canine Model: Disturbances in Thromboxane A2-Prostacyclin BalanceInvestigative Radiology, 1986
- Prevention of Myocardial Damage in Acute Myocardial Ischemia by Early Treatment with Intravenous StreptokinaseNew England Journal of Medicine, 1985
- Augmented thromboxane A2 generation and efficacy of its blockade in acute myocardial infarctionInternational Journal of Cardiology, 1985
- Thrombolytic TherapyNew England Journal of Medicine, 1984
- Coronary Thrombolysis with Tissue-Type Plasminogen Activator in Patients with Evolving Myocardial InfarctionNew England Journal of Medicine, 1984
- Protection of Ischemic Cat Myocardium By CGS-13080, a Selective Potent Thromboxane A2 Synthesis InhibitorJournal of Cardiovascular Pharmacology, 1983
- Effects of provocation on transcardiac thromboxane in patients with coronary artery diseaseThe American Journal of Cardiology, 1983
- Thromboxane release during pacing-induced angina pectoris: possible vasoconstrictor influence on the coronary vasculature.Circulation, 1980