Nicorandil protects cardiac mitochondria against permeability transition induced by ischemia-reperfusion

Ischemia followed by reperfusion is known to negatively affect mitochondrial function by inducing a deleterious condition termed mitochondrial permeability transition. Mitochondrial permeability transition is triggered by oxidative stress, which occurs in mitochondria during ischemia-reperfusion as a result of lower antioxidant defenses and increased oxidant production. Permeability transition causes mitochondrial dysfunction and can ultimately lead to cell death. A drug able to minimize mitochondrial damage induced by ischemia-reperfusion may prove to be clinically effective. We aimed to analyze the effects of nicorandil, an ATP-sensitive potassium channel agonist and vasodilator, on mitochondrial function of rat hearts and cardiac HL-1 cells submitted to ischemia-reperfusion. Nicorandil decreased mitochondrial swelling and calcium uptake. It also decreased reactive oxygen species formation and thiobarbituric acid reactive substances levels, a lipid peroxidation biomarker. We thus confirm previous reports that nicorandil inhibits mitochondrial permeability transition and demonstrate that nicorandil inhibits this process by preventing oxidative damage and mitochondrial calcium overload induced by ischemia-reperfusion, resulting in improved cardiomyocyte viability. These results may explain the good clinical results obtained when using nicorandil in the treatment of ischemic heart disease.

Evaluation of the effects of nicorandil and its molecular precursor (without radical NO) on proliferation and apoptosis of 786-cell

Nicorandil is a nitric oxide (NO) donor used in the treatment of angina symptoms. It has also been reported to protect cells and affect the proliferation and death of cells in some tissues. The molecules that interfere with these processes can cause dysfunction in healthy tissues but can also assist in the therapy of some disorders. In this study we examined the effect of nicorandil and of the molecular precursor that does not have the NO radical (N-(beta-hydroxyethyl) nicotinamide) on the cell proliferation and death of human renal carcinoma cells (786-O) under normal oxygenation conditions. The molecular precursor was used in order to analyze the effects independents of NO. In the cytotoxicity test, nicorandil was shown to be cytotoxic at very high concentrations and it was more cytotoxic than its precursor (cytotoxic at concentrations of 2,000 and 3,000 μg/mL, respectively). We propose that the lower cytotoxicity of the precursor is due to the absence of the NO radical. In this study, the cells exposed to nicorandil showed neither statistically significant changes in cell proliferation nor increases in apoptosis or genotoxicity. The precursor generated similar results to those of nicorandil. We conclude that nicorandil causes no changes in the proliferation or apoptosis of the cell 786-O in normal oxygenation conditions. Moreover, the lack of NO radical in the precursor molecule did not show a different result, except in the cell cytotoxicity. © 2013 Springer Science+Business Media Dordrecht.

Clinical effect of intravenous thrombolysis combined with nicorandil therapy in patients with acute ST-segment elevation myocardial infarction

Purpose: To evaluate the effectiveness of intravenous thrombolysis in combination with nicorandil in the treatment of acute ST-segment elevation myocardial infarction (STEMI). Methods: Patients who developed acute STEMI and underwent intravenous thrombolysis in the hospital were selected and divided into observation group (n = 128) and control group (n = 114). Besides thrombolytic therapy, the observation group was also given 20 mg of nicorandil. The control group received conventional thrombolytic therapy only. Clinical effects and rehabilitation of patients were observed. Results: Cardiac troponin I (cTNI) level of the observation group was 4.0 ± 1.5, 8.3 ± 2.8 and 9.8 ± 3.9 after 4, 12 and 24 h, respectively, which is much lower than 5.8 ± 1.4, 11.4 ± 2.7 and 13.2 ± 4.2 in the control group (p < 0.05). ST-segment resolution of observation group was higher (44 ± 14, 52 ± 17, 69 ± 21 and 80 ± 18) % at different time points, compared with the control group (p < 0.05). The proportion of patients with Curtis-Walker score > 3 points, and ventricular wall motion score (4.70 %; 1.38 ± 0.11) in the observation group were both lower than those of the control group (21.00 %; 1.43 ± 0.15) (p < 0.05). The difference in adverse cardiac events between the observation group (N = 6, 4.70 %) and control group (N = 12, 10.50 %) was not statistically significant (p > 0.05) Conclusion: Combining intravenous thrombolysis with nicorandil therapy can enhance myocardial perfusion level, reduce myocardial damage, improve cardiac function and decrease risk of arrhythmia for acute STEMI patients.

Factores asociados a fenómeno de no reflujo coronario en pacientes adultos llevados a angioplastia

Introducción: La disminución de flujo en los vasos coronarios sin presencia de oclusión, es conocido como fenómeno de no reflujo, se observa después de la reperfusión, su presentación oscila entre el 5% y el 50% dependiendo de la población y de los criterios diagnósticos, dicho suceso es de mal pronóstico, aumenta el riesgo de morir en los primeros 30 días posterior a la angioplastia (RR 2,1 p 0,038), y se relaciona con falla cardiaca y arritmias, por eso al identificar los factores a los cuales se asocia, se podrán implementar terapias preventivas. Metodología: Estudio de casos y controles pareado por médico que valoró el evento, para garantizar que no existieron variaciones inter observador, con una razón 1:4 (18:72), realizado para identificar factores asociados a la presencia de no reflujo en pacientes llevados a angioplastia, entre noviembre de 2010 y mayo de 2014, en la Clínica San Rafael de Bogotá, D.C. Resultados: La frecuencia del no reflujo fue del 2.89%. El Infarto Agudo de Miocardio con elevación del ST (IAMCEST) fue la única variable que mostró una asociación estadísticamente significativa con este suceso, valor de p 0,002, OR 8,7, IC 95% (2,0 – 36,7). Discusión: El fenómeno de no reflujo en esta población se comportó de manera similar a lo descrito en la literatura, siendo el IAMCEST un factor fuertemente asociado.