The nonselective beta-blocker carvedilol suppresses apoptosis in human cardiac tissue: a pilot study.
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).


CONCLUSIONS
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.
Usta
Engin
E
Department of Thoracic, Cardiac and Vascular Surgery, Tübingen University Hospital, Tübingen, Germany. engin.usta@gmx.de
Mustafi
Migdat
M
Straub
Andreas
A
Ziemer
Gerhard
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D000906:Antibodies / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D004867:Equipment Design; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015425:Myocardial Reperfusion; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010447:Peptide Hydrolases / Q000494:pharmacology; D010477:Perfusion / Q000295:instrumentation; D010865:Pilot Projects; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000276:immunology; D011412:Propanolamines / Q000494:pharmacology*; D013194:Staining and Labeling
D000319:Adrenergic beta-Antagonists; D000906:Antibodies; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D010447:Peptide Hydrolases; D053148:Caspase 3