BACKGROUND: Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. To establish a pharmacologic strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the antiapoptotic properties of the nonselective beta-blocker carvedilol during simulated cardioplegia and reperfusion ex vivo. METHODS: Cardiac biopsies were retrieved before induction of cardiopulmonary bypass from the auricle of the right atrium of patients undergoing elective coronary artery bypass grafting. Biopsies were exposed to ex vivo conditions of varying periods of cardioplegia/reperfusion (30/10 minutes, 60/20 minutes, 120/40 minutes). Group I was the untreated control (n = 15), group II was the treated control (cardioplegia/reperfusion, n = 15), and group III was the experimental group (cardioplegia/reperfusion plus carvedilol, n = 15). Immunostaining for antibodies to activated caspase 3 and poly(ADP-ribose) polymerase 1 (PARP-1) cleavage was used to detect apoptosis. RESULTS: The percentage of apoptotic cardiomyocytes was significantly lower (P < .05) in group I than in group II, revealing a time-dependent increase. In group III, carvedilol treatment suppressed apoptosis significantly (P < .05). CONCLUSION: Carvedilol significantly suppresses apoptosis in our ex vivo setting. This finding warrants further studies to evaluate the potential beneficial effects of carvedilol in suppressing ischemia/reperfusion injury in clinical settings.
BACKGROUND: Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. To establish a pharmacologic strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the antiapoptotic properties of the nonselective beta-blocker carvedilol during simulated cardioplegia and reperfusion ex vivo. METHODS: Cardiac biopsies were retrieved before induction of cardiopulmonary bypass from the auricle of the right atrium of patients undergoing elective coronary artery bypass grafting. Biopsies were exposed to ex vivo conditions of varying periods of cardioplegia/reperfusion (30/10 minutes, 60/20 minutes, 120/40 minutes). Group I was the untreated control (n = 15), group II was the treated control (cardioplegia/reperfusion, n = 15), and group III was the experimental group (cardioplegia/reperfusion plus carvedilol, n = 15). Immunostaining for antibodies to activated caspase 3 and poly(ADP-ribose) polymerase 1 (PARP-1) cleavage was used to detect apoptosis. RESULTS: The percentage of apoptotic cardiomyocytes was significantly lower (P < .05) in group I than in group II, revealing a time-dependent increase. In group III, carvedilol treatment suppressed apoptosis significantly (P < .05). CONCLUSION:Carvedilol significantly suppresses apoptosis in our ex vivo setting. This finding warrants further studies to evaluate the potential beneficial effects of carvedilol in suppressing ischemia/reperfusion injury in clinical settings.
Authors: João Manoel Rossi Neto; Carlos Gun; Rui Fernando Ramos; Antonio Flavio Sanchez de Almeida; Mario Issa; Vivian Lener Amato; Jarbas J Dinkhuysen; Leopoldo Soares Piegas Journal: Rev Bras Cir Cardiovasc Date: 2013 Oct-Dec
Authors: Michael J Jacka; Gordon Guyatt; Richard Mizera; Janet Van Vlymen; Dario Ponce de Leon; Thomas Schricker; Mohd Yani Bahari; Bonan Lv; Lalitha Afzal; Maria Pilar Plou García; Xinmin Wu; Lília Nigro Maia; Maribel Arrieta; Purnima Rao-Melacini; Philip J Devereaux Journal: Anesth Analg Date: 2018-04 Impact factor: 5.108