Carvedilol improves energy production during acute global myocardial ischaemia

Monteiro, P; Duarte, AI; Moreno, AJ; Gonçalves, L; Providência, LA

http://hdl.handle.net/10400.4/350

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Cardiac mitochondria may become dysfunctional during ischaemia, thus compromising cardiomyocyte function. Carvedilol is an alpha(1)/beta-adrenoceptor antagonist with antioxidant, neuroprotective, cardioprotective and vascularprotective properties, and is used to treat hypertension, myocardial ischaemia and congestive heart failure. However, its impact on mitochondrial function during acute prolonged ischaemia is unknown. We aimed to study the effect of carvedilol on cardiac mitochondrial function during acute ischaemia, using Wistar rat hearts perfused with a Langendorff system, and then submitted to ischaemia in the presence and absence of carvedilol. We determined the electrical potential of the mitochondrial membrane, O(2) consumption by the respiratory chain, energy charge and the activity of the mitochondrial respiratory chain complexes. In our model, carvedilol had a preferential action on phosphorylation, increasing the mitochondrial energy charge (0.76+/-0.03 vs. 0.65+/-0.01 arbitrary units; P<0.05) and decreasing the phosphorylation lag phase (28.64+/-4.23 vs. 62.4+/-11.63 s; P<0.05) during ischaemia. The larger amount of energy available allowed the preservation of the electrical potential (201.2+/-2.45 vs. 186.66+/-3.36 mV;P<0.05), thus improving mitochondrial function during acute prolonged ischaemia