title: Carvedilol improves energy production during acute global myocardial ischaemia.
abstract: 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.
authors.affiliation: Basic Research Unit in Cardiology, Cardiology Department, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.forename: Ana I
authors.initials: AI
authors.lastname: Duarte
authors.forename: António
authors.initials: A
authors.lastname: Moreno
authors.forename: Lino M
authors.initials: LM
authors.lastname: Gonçalves
authors.forename: Luís A
authors.initials: LA
authors.lastname: Providência
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol