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 Similar articles in PubMed 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 Snabaitis, A. K. Articles by Chambers, D. J. Search for Related Content PubMed PubMed Citation Articles by Snabaitis, A. K. Articles by Chambers, D. J.

(Circulation. 1997;96:3148-3156.)
© 1997 American Heart Association, Inc.

Articles

Comparison of Polarized and Depolarized Arrest in the Isolated Rat Heart for Long-term Preservation

A. K. Snabaitis, BSc; M. J. Shattock, PhD; ; D. J. Chambers, PhD

From Cardiac Surgical Research and Cardiovascular Research (M.J.S.), The Rayne Institute, St Thomas' Hospital, London, UK.

Correspondence to Dr D.J. Chambers, Cardiac Surgical Research, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. E-mail d.chambers{at}umds.ac.uk

Background Hypothermic hyperkalemic cardioplegic solutions are currently used for donor heart preservation. Hyperkalemia-induced depolarization of the resting membrane potential (E_m) may predispose the heart to Na⁺ and Ca²⁺ loading via voltage-dependent "window currents," thereby exacerbating injury and limiting the safe storage duration. Alternatively, maintaining the resting E_m with a polarizing solution may reduce ionic movements and improve postischemic recovery; we investigated this concept with the reversible sodium channel blocker tetrodotoxin (TTX) to determine (1) whether polarized arrest was more efficacious than depolarized arrest during hypothermic long-term myocardial preservation and (2) whether TTX induces and maintains polarized arrest.

Methods and Results The isolated crystalloid-perfused working rat heart preparation was used in this study. Preliminary studies determined an optimal TTX concentration of 22 µmol/L and an optimal storage temperature of 7.5°C. To compare depolarized and polarized arrest, hearts were arrested with either Krebs-Henseleit (KH) buffer (control), KH buffer containing 16 mmol/L K⁺, or KH buffer containing 22 µmol/L TTX and then stored at 7.5°C for 5 hours. Postischemic recovery of aortic flow was 13±4%, 38±2%, and 48±3%* (*P<.05 versus control and 16 mmol/L K⁺), respectively. When conventional 3 mol/L KCl-filled intracellular microelectrodes were used, E_m gradually depolarized during control unprotected ischemia to -55 mV before reperfusion, whereas arrest with 16 mmol/L K⁺ caused rapid depolarization to -50 mV, where it remained throughout the 5-hour storage period. In contrast, in 22 µmol/L TTX-arrested hearts, E_m remained more polarized, at -70 mV, for the entire ischemic period.

Conclusions Blockade of cardiac sodium channels by TTX during ischemia maintained polarized arrest, which was more protective than depolarized arrest, possibly because of reduced ionic imbalance.

Key Words: cardioplegia • electrophysiology • depolarizing

This article has been cited by other articles:

				S. E. Anderson, H. Liu, A. Beyschau, and P. M. Cala Effects of cold cardioplegia on pH, Na, and Ca in newborn rabbit hearts Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1090 - H1097. [Abstract] [Full Text] [PDF]

				G. P. Dobson and M. W. Jones Adenosine and lidocaine: a new concept in nondepolarizing surgical myocardial arrest, protection, and preservation J. Thorac. Cardiovasc. Surg., March 1, 2004; 127(3): 794 - 805. [Abstract] [Full Text] [PDF]

				D. J. Chambers Nicorandil cardioplegia or procaine cardioplegia? Eur. J. Cardiothorac. Surg., October 1, 2003; 24(4): 670 - 670. [Full Text] [PDF]

				H. Irie, J. Gao, G. R. Gaudette, I. S. Cohen, R. T. Mathias, A. E. Saltman, and I. B. Krukenkamp Both Metabolic Inhibition and Mitochondrial KATP Channel Opening Are Myoprotective and Initiate a Compensatory Sarcolemmal Outward Membrane Current Circulation, September 9, 2003; 108(90101): II-341 - 347. [Abstract] [Full Text] [PDF]

				D. J. Chambers Mechanisms and alternative methods of achieving cardiac arrest Ann. Thorac. Surg., February 1, 2003; 75(2): S661 - 666. [Abstract] [Full Text] [PDF]

				E. M. Hoenicke, X. Sun, R. G. Strange Jr, and R. J. Damiano Jr Donor heart preservation with a novel hyperpolarizing solution: Superior protection compared with University of Wisconsin solution J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 746 - 754. [Abstract] [Full Text] [PDF]

				D. J. Chambers and D. J. Hearse Developments in cardioprotection: ""polarized"" arrest as an alternative to ""depolarized"" arrest Ann. Thorac. Surg., November 1, 1999; 68(5): 1960 - 1966. [Abstract] [Full Text] [PDF]

				A. K. Snabaitis, M. J. Shattock, and D. J. Chambers LONG-TERM MYOCARDIAL PRESERVATION: EFFECTS OF HYPERKALEMIA, SODIUMCHANNEL, AND Na+/K+/2Cl- COTRANSPORTINHIBITION ON EXTRACELLULAR POTASSIUM ACCUMULATION DURING HYPOTHERMIC STORAGE J. Thorac. Cardiovasc. Surg., July 1, 1999; 118(1): 123 - 134. [Abstract] [Full Text] [PDF]