This Article Full Text Full Text (PDF) 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 Stowe, D. F. Articles by Smart, S. C. Search for Related Content PubMed PubMed Citation Articles by Stowe, D. F. Articles by Smart, S. C. Related Collections Contractile function Biochemistry and metabolism Calcium cycling/excitation-contraction coupling Energy metabolism Ischemic biology - basic studies Transplantation CV surgery: coronary artery disease CV surgery: valvular disease

(Circulation. 2000;102:1172.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Reduced Cytosolic Ca²⁺ Loading and Improved Cardiac Function After Cardioplegic Cold Storage of Guinea Pig Isolated Hearts

David F. Stowe, MD, PhD; Srinivasan G. Varadarajan, MD; Jianzhong An, MD; Steven C. Smart, MD

From the Anesthesiology Research Laboratory, Departments of Anesthesiology, Medicine (Cardiovascular Diseases), and Physiology, and Cardiovascular Research Center, Medical College of Wisconsin, and Veterans Affairs Medical Center, Milwaukee.

Correspondence to David F. Stowe, MD, PhD, Medical College of Wisconsin, M4280, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail dfstowe{at}mcw.edu

Background—Hypothermia is cardioprotective, but it causes Ca²⁺ loading and reduced function on rewarming. The aim was to associate changes in cytosolic Ca²⁺ with function in intact hearts before, during, and after cold storage with or without cardioplegia (CP).

Methods and Results—Guinea pig hearts were initially perfused at 37°C with Krebs-Ringer’s (KR) solution (in mmol/L: Ca²⁺ 2.5, K⁺ 5, Mg²⁺ 2.4). One group was perfused with CP solution (Ca²⁺ 2.5, K⁺ 18, Mg²⁺ 7.2) during cooling and storage at 3°C for 4 hours; another was perfused with KR. LV pressure (LVP), dP/dt, O₂ consumption, and cardiac efficiency were monitored. Cytosolic phasic [Ca²⁺] was calculated from indo 1 fluorescence signals obtained at the LV free wall. Cooling with KR increased diastolic and phasic [Ca²⁺], whereas cooling with CP suppressed phasic [Ca²⁺] and reduced the rise in diastolic [Ca²⁺]. Reperfusion with warm KR increased phasic [Ca²⁺] 86% more after CP at 20 minutes and did not increase diastolic [Ca²⁺] at 60 minutes, compared with a 20% increase in phasic [Ca²⁺] after KR. During early and later reperfusion after CP, there was a 126% and 50% better return of LVP than after KR; during later reperfusion, O₂ consumption was 23% higher and cardiac efficiency was 38% higher after CP than after KR.

Conclusions—CP decreases the rise in cardiac diastolic [Ca²⁺] observed during cold storage in KR. Decreased diastolic [Ca²⁺] and increased systolic [Ca²⁺] after CP improves function on reperfusion because of reduced Ca²⁺ loading during and immediately after cold CP storage.

Key Words: contractility • cardioplegia • calcium • hypothermia

This article has been cited by other articles:

				I. Khaliulin, S. J. Clarke, H. Lin, J. Parker, M.-S. Suleiman, and A. P. Halestrap Temperature preconditioning of isolated rat hearts - a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore J. Physiol., June 15, 2007; 581(3): 1147 - 1161. [Abstract] [Full Text] [PDF]

				A. K. S. Camara, M. Aldakkak, J. S. Heisner, S. S. Rhodes, M. L. Riess, J. An, A. Heinen, and D. F. Stowe ROS scavenging before 27{degrees}C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2021 - C2031. [Abstract] [Full Text] [PDF]

				S. S. Rhodes, K. M. Ropella, A. K. S. Camara, Q. Chen, M. L. Riess, P. S. Pagel, and D. F. Stowe Ischemia-reperfusion injury changes the dynamics of Ca2+-contraction coupling due to inotropic drugs in isolated hearts J Appl Physiol, March 1, 2006; 100(3): 940 - 950. [Abstract] [Full Text] [PDF]

				J. An, A. K. S. Camara, S. S. Rhodes, M. L. Riess, and D. F. Stowe Warm ischemic preconditioning improves mitochondrial redox balance during and after mild hypothermic ischemia in guinea pig isolated hearts Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2620 - H2627. [Abstract] [Full Text] [PDF]

				A. K. S. Camara, M. L. Riess, L. G. Kevin, E. Novalija, and D. F. Stowe Hypothermia augments reactive oxygen species detected in the guinea pig isolated perfused heart Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1289 - H1299. [Abstract] [Full Text] [PDF]

				M. L Riess, A. K.S Camara, L. G Kevin, J. An, and D. F Stowe Reduced reactive O2 species formation and preserved mitochondrial NADH and [Ca2+] levels during short-term 17 {degrees}C ischemia in intact hearts Cardiovasc Res, February 15, 2004; 61(3): 580 - 590. [Abstract] [Full Text] [PDF]

				J. An, A. K.S. Camara, Q. Chen, and D. F. Stowe Effect of low [CaCl2] and high [MgCl2] cardioplegia and moderate hypothermic ischemia on myoplasmic [Ca2+] and cardiac function in intact hearts Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 974 - 985. [Abstract] [Full Text] [PDF]

				Q. Chen, A. K.S Camara, S. S Rhodes, M. L Riess, E. Novalija, and D. F Stowe Cardiotonic drugs differentially alter cytosolic [Ca2+] to left ventricular relationships before and after ischemia in isolated guinea pig hearts Cardiovasc Res, October 1, 2003; 59(4): 912 - 925. [Abstract] [Full Text] [PDF]

				S. S. Rhodes, K. M. Ropella, S. H. Audi, A. K. S. Camara, L. G. Kevin, P. S. Pagel, and D. F. Stowe Cross-bridge kinetics modeled from myoplasmic [Ca2+] and LV pressure at 17{degrees}C and after 37{degrees}C and 17{degrees}C ischemia Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1217 - H1229. [Abstract] [Full Text] [PDF]

				L. G. Kevin, A. K. S. Camara, M. L. Riess, E. Novalija, and D. F. Stowe Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H566 - H574. [Abstract] [Full Text] [PDF]

				J. An, S. G. Varadarajan, A. Camara, Q. Chen, E. Novalija, G. J. Gross, and D. F. Stowe Blocking Na+/H+ exchange reduces [Na+]i and [Ca2+]i load after ischemia and improves function in intact hearts Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2398 - H2409. [Abstract] [Full Text] [PDF]

				J. An, S. G. Varadarajan, E. Novalija, and D. F. Stowe Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca2+ responses in intact hearts Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1508 - H1523. [Abstract] [Full Text] [PDF]

				S. G. Varadarajan, J. An, E. Novalija, S. C. Smart, and D. F. Stowe Changes in [Na+]i, compartmental [Ca2+], and NADH with dysfunction after global ischemia in intact hearts Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H280 - H293. [Abstract] [Full Text] [PDF]

				Q. Chen, A. K. S. Camara, J. An, M. L. Riess, E. Novalija, and D. F. Stowe Cardiac preconditioning with 4-h, 17{degrees}C ischemia reduces [Ca2+]i load and damage in part via KATP channel opening Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H1961 - H1969. [Abstract] [Full Text] [PDF]