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(Circulation. 2005;112:I-219 – I-223.)
© 2005 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

Myocyte Volume and Function in Response to Osmotic Stress

Observations in the Presence of an Adenosine Triphosphate-Sensitive Potassium Channel Opener

Shinichi Mizutani, MD; Sandip M. Prasad, MD; Angela D. Sellitto, MS; Richard B. Schuessler, PhD; Ralph J. Damiano, Jr, MD; Jennifer S. Lawton, MD

From the Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo.

Correspondence to Jennifer S. Lawton, MD, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8234, St Louis, MO 63110. E-mail lawtonj{at}msnotes.wustl.edu

Background— Hypothermic hyperkalemic cardioplegia results in significant myocyte swelling and impaired contractility. These detrimental effects may be eliminated by the addition of an adenosine triphosphate-sensitive potassium (K_ATP) channel opener. This study evaluated the hypothesis that a K_ATP channel opener (diazoxide) would benefit volume homeostasis by limiting volume and subsequent contractility changes during osmotic stress.

Methods and Results— Isolated rabbit ventricular myocyte volume and contractility were evaluated using video microscopy and field stimulation after exposure to osmotic stress at 37°C. Myocytes were exposed to Tyrode’s physiological solution for 20 minutes and test solution for 20 minutes, and then reexposed to Tyrode’s for 20 minutes. Test solutions included control Tyrode’s (1T) and osmotically altered Tyrode’s (2.6T, 0.9T, and 0.6T) solutions with or without the K_ATP channel opener diazoxide. Severe osmotic stress (2.6T and 0.6T) resulted in significant cell shrinkage and swelling, respectively. This was unchanged by the addition of diazoxide. Mild hyposmotic stress (0.9T) resulted in significant cell swelling that was eliminated by the addition of diazoxide. Cell swelling was associated with reduced contractility.

Conclusions— Cell swelling, but not shrinkage, was detrimental to myocyte contractility. Diazoxide eliminated volume change due to mild hyposmotic stress, similar to that previously noted with hyperkalemic cardioplegia, but did not alter volume change secondary to severe osmotic stress.

Key Words: contractility • myocytes • stress