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J Thorac Cardiovasc Surg 1999;117:980-986
© 1999 Mosby, Inc.

CARDIOPULMONARY SUPPORT AND PHYSIOLOGY

DELAYED MYOCARDIAL PRECONDITIONING BY 1-ADRENOCEPTORS INVOLVES INHIBITION OF APOPTOSIS

From the Departments of Surgery^a and Physiology,^c Medical College of Virginia/Virginia Commonwealth University, Richmond, Va, and the Department of Cardiothoracic Surgery,^b MCP-Hahnemann University of Health Sciences, Philadelphia, Pa.

Received for publication Aug 17, 1998. Revisions requested Oct 30, 1998. Revisions received Nov 30, 1998. Accepted for publication Dec 23, 1998. Address for reprints: Kourosh Baghelai, MD, 1200 East Broad St, PO Box 981239, Richmond, VA 23298.

Objective: Previous studies have demonstrated that 1-adrenoceptor activation increases myocardial resistance to ischemic injury 24 hours later. Here we tested the hypothesis that delayed protection is associated with limited infarction and involves altered expression of pro-apoptotic and/or anti-apoptotic proteins.
Methods: Rabbits were treated with phenylephrine or an equivalent volume of vehicle (n = 6 per group). Twenty-four hours after pretreatment, isolated hearts were perfused with a bovine erythrocyte suspension in modified Krebs solution, subjected to 45 minutes of global ischemia (37°C), and reperfused for 120 minutes. Infarct size was determined by triphenyltetrazolium chloride staining. Apoptosis was quantified by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling. Left ventricular tissue from separate groups of animals (n = 5 per group), 24 hours after pretreatment with phenylephrine or vehicle but without ischemia and reperfusion, was analyzed by Western blotting for content of the anti-apoptotic protein, bcl_x, and pro-apoptotic protein, bax.
Results: Isolated hearts after phenylephrine pretreatment had increased end-reperfusion developed pressures (56.8 ± 4.9 vs 36.2 ± 3.9 mm Hg for vehicle, P = .008) and decreased elevated end-diastolic pressures (26.7 ± 4.5 vs 42.3 ± 5.0 mm Hg for vehicle, P = .04). Phenylephrine pretreatment abrogated infarction (9.9 ± 2.4% vs 42.6 ± 6.3% for vehicle, P = .002) and reduced the number of apoptotic nuclei (24 ± 4.8 vs 51 ± 4.6 for vehicle, P = .038). Analysis by Western blotting showed that the ratio of bcl_x to bax protein increased in phenylephrine-pretreated hearts (2.65 ± 0.5 vs 1.0 ± 0.1 for vehicle, P = .008).
Conclusion: Delayed myocardial protection to infarction mediated by 1-adrenoceptor activation involves an increased bcl_x/bax ratio, thereby limiting apoptotic cell death.

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