This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Engelman, D. T. Articles by Das, D. K. Search for Related Content PubMed Articles by Engelman, D. T. Articles by Das, D. K.

(Circulation. 1995;92:417-422.)
© 1995 American Heart Association, Inc.

Articles

Improved 4- and 6-Hour Myocardial Preservation by Hypoxic Preconditioning

Daniel T. Engelman, MD; Chang-zhi Chen, MD; Masazumi Watanabe, MD; Richard M. Engelman, MD; John A. Rousou, MD; Joseph E. Flack, III, MD; David W. Deaton, MD; Nilanjana Maulik, PhD; Dipak K. Das, PhD

From the Departments of Surgery, University of Connecticut School of Medicine, Farmington, Conn, and Baystate Medical Center, Springfield, Mass.

Correspondence to Dr Daniel T. Engelman, Surgical Research Center, University of Connecticut School of Medicine, 263 Farmington Ave, Farmington, CT 06030-1110.

Background A brief hypoxic episode can precondition myocardium against a subsequent ischemic-reperfusion injury. The present study sought to determine whether intracellular ionic alterations, induced expression of heat-shock proteins (hsps), and/or catalase are involved in the cellular mechanisms by which hypoxic preconditioning can preserve postischemic function in a model of prolonged hypothermic storage.

Methods and Results Two groups of isolated working rat hearts were studied: control (CON) and hypoxically preconditioned (HP) hearts. Hearts were arrested at 4°C with St Thomas' cardioplegic solution and immersion-stored for either a 4- or 6-hour period. Myocardial function (ie, heart rate, aortic flow, coronary flow, developed pressure, and its first derivative dP/dt_max) was determined at baseline, after preconditioning, and during reperfusion. At similar time points, myocardial [Na⁺]_i, [K⁺]_i, [Mg²⁺]_i, and [Ca²⁺]_i were measured using an atomic absorption spectrophotometer, and the induction of hsp 70 and catalase mRNAs was assayed using Northern blot analysis. After 4 and 6 hours of hypothermic storage, aortic flow, dP/dt_max, and [K⁺]_i were increased, whereas [Na⁺]_i and [Ca²⁺]_i were decreased significantly in the HP group compared with the CON group. Steady state mRNA levels of catalase and hsp 70 were increased from baseline levels only in the HP group, with a peak (2.8- and 2.4-fold versus baseline) after 4 hours of storage.

Conclusions Our results indicate that intracellular ionic alterations and upregulation of catalase and hsp 70 gene expression may contribute to the mechanisms underlying hypoxic preconditioning, leading to improved postischemic function during prolonged hypothermic storage of hearts.

Key Words: hypoxia • ischemia • cardioplegia • reperfusion • preconditioning

This article has been cited by other articles:

				H. Kasahara, E. Tanaka, N. Fukuyama, E. Sato, H. Sakamoto, Y. Tabata, K. Ando, H. Iseki, Y. Shinozaki, K. Kimura, et al. Biodegradable gelatin hydrogel potentiates the angiogenic effect of fibroblast growth factor 4 plasmid in rabbit hindlimb ischemia J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1056 - 1062. [Abstract] [Full Text] [PDF]

				M. Kirsch, S. Bertrand, J.-P. Garnier, C. Fernandez, C. Baufreton, A. Astier, and D. Loisance Pretreatment with a potassium-channel opener before prolonged cardiac storage: an evaluation in an experimental brain death model Ann. Thorac. Surg., June 1, 1999; 67(6): 1623 - 1629. [Abstract] [Full Text] [PDF]

				J. C. Cleveland Jr, D. R. Meldrum, R. T. Rowland, A. Banerjee, and A. H. Harken Preconditioning and Hypothermic Cardioplegia Protect Human Heart Equally Against Ischemia Ann. Thorac. Surg., January 1, 1997; 63(1): 147 - 152. [Abstract] [Full Text]