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(Circulation Research. 2006;99:1270.)
© 2006 American Heart Association, Inc.

Integrative Physiology

Obligatory Role of Cardiac Nerves and ₁-Adrenergic Receptors for the Second Window of Ischemic Preconditioning in Conscious Pigs

Raymond K. Kudej, You-Tang Shen, Athanasios P. Peppas, Cheng-Hsiung Huang, Wei Chen, Lin Yan, Dorothy E. Vatner, Stephen F. Vatner

From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine (R.K.K., Y.-T.S., A.P.P., W.C., L.Y., D.E.V., S.F.V.), UMDNJ-New Jersey Medical School, Newark; Department of Clinical Sciences (R.K.K.), Tufts University School of Veterinary Medicine, North Grafton, Mass; Department of Surgery (C.-H.H.), National Yang-Ming University School of Medicine, Taipei Veterans General Hospital, Taiwan.

Correspondence to Stephen F. Vatner, MD, Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, 185 S. Orange Avenue, MSB G-609, Newark, NJ 07103. E-mail vatnersf{at}umdnj.edu

We tested the hypothesis that cardiac nerves may mediate ischemic preconditioning. Pigs were chronically instrumented to measure aortic, left atrial and left ventricular pressures, and regional myocardial function (wall thickening). Hemodynamic variables, area at risk, and tissue blood flows (radioactive microspheres) were similar among groups. Myocardial infarct size following 60 minutes coronary artery occlusion and 4 days reperfusion, expressed as a fraction of the area at risk, was 42±4.0%, in innervated pigs and similar in pigs with regional cardiac denervation (CD, 41±2.5%). Infarct size in innervated pigs during the first window of preconditioning (first window) was markedly reduced (6±1.8%, P<0.01), as it was in the second window of preconditioning (second window) (16±3.3%, P<0.01). Although infarct size was still reduced in pigs with CD and first window preconditioning (9±1.8%, P<0.01), the protective effects of second window were abrogated in pigs with CD resulting in an infarct size of 38±5.6%. In another group of innervated pigs during pharmacological ₁-adrenergic receptor (AR) blockade, infarct size was also not reduced during the second window (48±3.2%). Additionally, Western blot analysis of inducible nitric oxide synthase and cyclooxygenase-2 proteins demonstrated significant (P<0.05) upregulation following the second window in innervated pigs, but not in pigs with CD or ₁-AR blockade. Thus, the mechanism of protection during the second window, but not the first window, appears to be dependent on cardiac nerves and ₁-AR stimulation.

Key Words: myocardial infarction • sympathetic nervous system • nitric oxide • regional wall motion • coronary artery occlusion

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