Abstract
To test the hypothesis that a critical stenosis prevents delayed preconditioning against stunning, studies were conducted in pigs chronically instrumented with occluders and segment-shortening crystals. In the setting of a critical stenosis, a preconditioning stimulus of repetitive brief occlusions resulted in infarction. Thereafter, a single 10-min occlusion was used as the preconditioning stimulus. Delayed preconditioning against stunning was documented on subsequent days by the deficit-of-function following brief repetitive occlusions. In contrast to experiments in the naïve heart, the deficit-of-function improved on the day after a single 10-min occlusion (from 60 ± 14 to 24 ± 6 arbitrary units, p = 0.003) and similar improvement occurred when reperfusion was performed through a critical stenosis (32 ± 6 units, p = 0.02 vs. naïve and p = 0.34 vs. no stenosis). Delayed preconditioning also reduced the frequency of ventricular fibrillation and produced a fourfold increase in both calcium-dependent and calcium-independent NOS activity. Thus, a critical stenosis did not prevent delayed preconditioning against stunning.
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Baker, C. S., Rimoldi, O., Camici, P. G., Barnes, E., Chacon, M. R., Huehns, T. Y., et al. (1999). Repetitive myocardial stunning in pigs is associated with the increased expression of inducible and constitutive nitric oxide synthases. Cardiovascular Research, 43, 685–697.
Bolli, R. (2000). The late phase of preconditioning. Circulation Research, 87, 972–983.
Bolli, R., Manchikalapudi, S., Tang, X. -L., Takano, H., Qiu, Y., Guo, Y., et al. (1997). The protective effect of late preconditioning against myocardial stunning in conscious rabbits is mediated by nitric oxide synthase. Evidence that nitric oxide acts both as a trigger and as a mediator of the late phase of ischemic preconditioning. Circulation Research, 81, 1094–1107.
Canty Jr., J. M., Suzuki, G., Banas, M. D., Verheyen, F., Borgers, M., & Fallavollita, J. A. (2004). Hibernating myocardium: chronically adapted to ischemia but vulnerable to sudden death. Circulation Research, 94, 1142–1149.
De Curzon, O. P., Ghaleh, B., Tissier, R., Giudicelli, J. F., Hittinger, L., & Berdeaux, A. (2001). Myocardial stunning in exercise-induced ischemia in dogs: lack of late preconditioning. American Journal of Physiology Heart and Circulatory Physiology, 280, H302–H310.
De Zeeuw, S., Van Den Doel, M. A., Duncker, D. J., & Verdouw, P. D. (1999). New insights into cardioprotection by ischemic preconditioning and other forms of stress. Annals of the New York Academy of Sciences, 874, 178–191.
Fallavollita, J. A., Trojan, C., & Canty Jr., J. M. (2000). Transmural distribution of Fdg uptake in stunned myocardium. American Journal of Physiology Heart and Circulatory Physiology, 279, H102–H109.
Guo, Y., Jones, W. K., Xuan, Y. T., Tang, X. L., Bao, W., Wu, W. J., et al. (1999). The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible no synthase gene. Proceedings of the National Academy of Sciences USA, 96, 11507–11512.
Heusch, G. (2001). Nitroglycerin and delayed preconditioning in humans: yet another new mechanism for an old drug? Circulation, 103, 2876–2878.
Kapadia, S. J., Terlato, J. S., & Most, A. S. (1997). Presence of a critical coronary artery stenosis does not abolish the protective effect of ischemic preconditioning. Circulation, 95, 1286–1292.
Kim, S. J., Kim, Y. K., Takagi, G., Huang, C. H., Geng, Y. J., & Vatner, S. F. (2002). Enhanced iNOS function in myocytes one day after brief ischemic episode. American Journal of Physiology Heart and Circulatory Physiology, 282, H423–H428.
Kloner, R. A., Bolli, R., Marban, E., Reinlib, L., & Braunwald, E. (1998). Medical and cellular implications of stunning, hibernation, and preconditioning: an NHLBI workshop. Circulation, 97, 1848–1867.
Kloner, R. A., Shook, T., Przyklenk, K., Davis, V. G., Junio, L., Matthews, R. V., et al. (1995). Previous angina alters in-hospital outcome in timi 4. A clinical correlate to preconditioning? Circulation, 91, 37–45.
Lambiase, P. D., Edwards, R. J., Cusack, M. R., Bucknall, C. A., Redwood, S. R., & Marber, M. S. (2003). Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment. Journal of the American College of Cardiology, 41, 1174–1182.
Leesar, M. A., Stoddard, M. F., Dawn, B., Jasti, V. G., Masden, R., & Bolli, R. (2001). Delayed preconditioning-mimetic action of nitroglycerin in patients undergoing coronary angioplasty. Circulation, 103, 2935–2941.
McFalls, E. O., Hou, M., Bache, R. J., Best, A., Marx, D., Sikora, J., et al. (2004). Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium. American Journal of Physiology Heart and Circulatory Physiology, 287, H1328–H1334.
Murry, C. E., Jennings, R. B., & Reimer, K. A. (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 74, 1124–1136.
Scholz, D., & Schaper, W. (2005). Preconditioning of arteriogenesis. Cardiovascular Research, 65, 513–523.
Schott, R. J., Rohmann, S., Braun, E. R., & Schaper, W. (1990). Ischemic preconditioning reduces infarct size in swine myocardium. Circulation Research, 66, 1133–1142.
Schulz, R., Post, H., Sakka, S., Wallbridge, D. R., & Heusch, G. (1995). Intraischemic preconditioning: increased tolerance to sustained low-flow ischemia by a brief episode of no-flow ischemia without intermittent reperfusion. Circulation Research, 76, 942–950.
Schulz, R., Post, H., Vahlhaus, C., & Heusch, G. (1998). Ischemic preconditioning in pigs: a graded phenomenon. Its relation to adenosine and bradykinin. Circulation, 98, 1022–1029.
Shen, Y. -T., & Vatner, S. F. (1996). Differences in myocardial stunning following coronary artery occlusion in conscious dogs, pigs, and baboons. American Journal of Physiology, 270, H1312–H1322.
Shinmura, K., Kodani, E., Xuan, Y. T., Dawn, B., Tang, X. L., & Bolli, R. (2003). Effect of aspirin on late preconditioning against myocardial stunning in conscious rabbits. Journal of the American College of Cardiology, 41, 1183–1194.
Sun, J. -Z., Tang, X. -L., Knowlton, A. A., Park, S. -W., Qiu, Y., & Bolli, R. (1995). Late preconditioning against myocardial stunning: an endogenous protective mechanism that confers resistance to postischemic dysfunction 24 H after brief ischemia in conscious pigs. The Journal of Clinical Investigation, 95, 388–403.
Takano, H., Manchikalapudi, S., Tang, X. -L., Qiu, Y., Rizvi, A., Jadoon, A. K., et al. (1998). Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. Circulation, 98, 441–449.
Tang, X. -L., Qiu, Y., Park, S. -W., Sun, J. -Z., Kalya, A., & Bolli, R. (1996). Time course of late preconditioning against myocardial stunning in conscious pigs. Circulation Research, 79, 424–434.
Vahlhaus, C., Neumann, J., Luss, H., Wenzelburger, F., Tjan, T. D., Hammel, D., et al. (2005). Ischemic preconditioning by unstable angina reduces the release of Ck-Mb following CABG and stimulates left ventricular HSP-72 protein expression. Journal of Cardiac Surgery, 20, 412–419.
Wu, Z. K., Iivainen, T., Pehkonen, E., Laurikka, J., & Tarkka, M. R. (2002). Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization. Circulation, 106, 3091–3096.
Acknowledgements
I would like to thank Edward O. McFalls, M.D., Ph.D. and Joseph Sikora for performing the myocardial NOS activity assays, Elaine Granica for her expert technical assistance with conduct and analysis of these studies, and Anne Coe for her assistance with the completion of this manuscript. I would also like to thank John M. Canty, Jr., M.D. for his helpful comments on the draft of this manuscript. This study is supported by the Department of Veterans Affairs; the American Heart Association; and the National Heart, Lung and Blood Institute.
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Fallavollita, J.A. Determinants of Delayed Preconditioning Against Myocardial Stunning in Chronically Instrumented Pigs. J. of Cardiovasc. Trans. Res. 2, 71–80 (2009). https://doi.org/10.1007/s12265-008-9081-6
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DOI: https://doi.org/10.1007/s12265-008-9081-6