Chávez E, García N, Pavón N

Language: Spanish
References: 10
Page: 77-81
PDF size: 147.91 Kb.

ABSTRACT

Introduction: The results presented in this study indicate that the immunosuppressor cyclosporine A acts as a cardioprotective drug. Methods: This effect was analyzed during development of reperfusion-induced arrhythmias after 5 min period of coronary ligation in hearts of rats under anesthesia. Results: The results indicate that cyclosporine inhibits Ca²⁺-induced mitochondrial damage; furthermore, when given before coronary occlusion, at a dose of 20 mg/kg, effectively protects against the high incidence of arrhythmias and the fall in blood pressure induced by reperfusion. In addition, it inhibits the delivery of lactic dehydrogenase and creatine kinase enzymes to the plasma. Conclusions: We propose that the protective effect could be related with its well documented action to restrain Ca²⁺-induced damage of mitochondrial functions.

REFERENCES

1. Jennings RB, Reimer KA, Steenbergen C: Miocardial ischemia revisited: The osmolar load, membrane damage, and reperfusion. J Mol Cell Cardiol 1986; 18: 769-780.

2. Bolli R, et al: Direct evidence that oxigen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. Proc Natl Acad Sci USA 1989; 86: 4695-4699.

3. Bernier M, et al: Reperfusion arrhythmias, dose-related protection by anti-free radical interventions. Am J Physiol 265, H1344-H1352, 1989.

4. Opie LA, Coetzee WA: Role of calcium ions in reperfusion arrhythmias relevance to pharmacological intervention. Cardiovasc. Drug Ther 2, 1989, 623-633.

5. Julia PL, et al: Studies of controlled reperfusion after ischemia. XXI Reperfusate composition: Superiority of blood cardioplegia damage-importance of endogenous oxygen free radical savensis in red blood cells. J Thorac Vardiovasc Surg 1991; 101: 303-313.

6. García N, García JJ, Correa F, Chávez E: The permeability transition pore as a pathway for the release of mitochondrial DNA. Life Sci 2005; 76: 2873-2880.

7. García N, Zazueta C, Carrillo R, Correa F, Chávez E: Copper sensitizes the mitochondrial permeability transition to carboxyatractyloside and oleate. Mol Cell Biochem 2000; 209: 119-123.

8. Halestrap AP, Clarke SJ, Javadov SA: Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc Res 61, 372-385.

9. Chavez E, Zazueta C: Cyclosporin, from clinical to basic research. Curr Top Pharm 1998: 4: 183-192.

10. Zazueta C, Sánchez C, García N, Correa F: Posible involvement of the adenine nucleotide translocase in the activation of the permeability transition pore induced by cadmium Int. J Biochem Cell Biol 2000; 32: 1093-1101.