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Ischemic Tolerance in Uremic Rabbits

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DOI: 10.4236/wjcd.2015.512041    3,545 Downloads   3,787 Views  

ABSTRACT

Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities; we tested whether experimentally induced prolonged uremia exacer-bated myocardial necrosis in a rabbit preparation of ischemia-reperfusion injury. In addition, we examined if treatment with an angiotensin converting enzyme inhibitor (Enalapril, ENA, 3 mg/Kg, IV) could reduce post-ischemic myocardial damage. Methods: Prolonged uremia was induced by a two-stage subtotal nephrectomy and confirmed by marked increases in serum creatinine and urea levels; after 5 weeks, four groups of rabbits were exposed to 45-min acute coronary occlusion followed by 180-min reperfusion. In treated animals, ENA was administered 5-min before onset of coronary reperfusion. All data from uremic animals were compared with time-matched controls. Results: Cardiac hemodynamics was similar for all groups during the development of kidney failure; heart rate in uremic rabbits was significantly lower for the duration of ischemia-reperfusion. In this animal model, the absence of coronary collateral circulation provides a stable ischemic substrate for evaluation of cellular necrosis. Infarct size (expressed as percent risk zone size) was: control, 48 ± 16; uremia, 36 ± 5; control + ENA, 51 ± 19; and uremia + ENA, 41 ± 16; risk zone size was similar for all animals. Conclusion: The present findings are inconsistent with the view that post-ischemic cardiac injury is greater in animals with pre-existent uremia. In addition, we were unable to show a significant beneficial effect with an angiotensin converting enzyme inhibitor on infarct size in either control or uremic rabbits. It remains to be proven in animal models with comorbidities such as manifest kidney disease that ischemic tolerance can be substantially reduced by either pharmacologic or non-pharmacologic interventions.

Conflicts of Interest

The authors declare no conflicts of interest.

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Kingma, J. , Sénéchal, G. , Rouleau, J. and Kingma, I. (2015) Ischemic Tolerance in Uremic Rabbits. World Journal of Cardiovascular Diseases, 5, 351-360. doi: 10.4236/wjcd.2015.512041.

References

[1] Gansevoort, R.T., Correa-Rotter, R., Hemmelgarn, B.R., Jafar, T.H., Heerspink, H.J., Mann, J.F., Matsushita, K. and Wen, C.P. (2013) Chronic Kidney Disease and Cardiovascular Risk: Epidemiology, Mechanisms, and Prevention. The Lancet, 382, 339-352.
http://dx.doi.org/10.1016/S0140-6736(13)60595-4
[2] Smith, G.L., Lichtman, J.H., Bracken, M.B., Shlipak, M.G., Phillips, C.O., DiCapua, P. and Krumholz, H.M. (2006) Renal Impairment and Outcomes in Heart Failure: Systematic Review and Meta-Analysis. Journal of the American College of Cardiology, 47, 1987-1996.
http://dx.doi.org/10.1016/j.jacc.2005.11.084
[3] Smith, G.L., Masoudi, F.A., Shlipak, M.G., Krumholz, H.M. and Parikh, C.R. (2008) Renal Impairment Predicts Long-Term Mortality Risk after Acute Myocardial Infarction. Journal of the American Society of Nephrology, 19, 141- 150.
http://dx.doi.org/10.1681/ASN.2007050554
[4] Shlipak, M.G., Heidenreich, P.A., Noguchi, H., Chertow, G.M., Browner, W.S. and McClellan, M.B. (2002) Association of Renal Insufficiency with Treatment and Outcomes after Myocardial Infarction in Elderly Patients. Annals of Internal Medicine, 137, 555-562.
http://dx.doi.org/10.7326/0003-4819-137-7-200210010-00006
[5] Wright, R.S., Reeder, G.S., Herzog, C.A., Albright, R.C., Williams, B.A., Dvorak, D.L., Miller, W.L., Murphy, J.G., Kopecky, S.L. and Jaffe, A.S. (2002) Acute Myocardial Infarction and Renal Dysfunction: A High-Risk Combination. Annals of Internal Medicine, 137, 563-570.
http://dx.doi.org/10.7326/0003-4819-137-7-200210010-00007
[6] Dikow, R., Kihm, L.P., Zeier, M., Kapitza, J., Tornig, J., Amann, K., Tiefenbacher, C. and Ritz, E. (2004) Increased Infarct Size in Uremic Rats: Reduced Ischemia Tolerance? Journal of the American Society of Nephrology, 15, 1530-1536.
http://dx.doi.org/10.1097/01.ASN.0000130154.42061.C6
[7] Byrne, C.J., McCafferty, K., Kieswich, J., Harwood, S., Andrikopoulos, P., Raftery, M., Thiemermann, C. and Yaqoob, M.M. (2012) Ischemic Conditioning Protects the Uremic Heart in a Rodent Model of Myocardial Infarction. Circulation, 125, 1256-1265.
http://dx.doi.org/10.1161/CIRCULATIONAHA.111.055392
[8] Bongartz, L.G., Joles, J.A., Verhaar, M.C., Cramer, M.J., Goldschmeding, R., Tilburgs, C., Gaillard, C.A., Doevendans, P.A. and Braam, B. (2012) Subtotal Nephrectomy Plus Coronary Ligation Leads to More Pronounced Damage in Both Organs than Either Nephrectomy or Coronary Ligation. American Journal of Physiology—Heart and Circulatory Physiology, 302, H845-H854.
http://dx.doi.org/10.1152/ajpheart.00261.2011
[9] Kocsis, G.F., Sarkozy, M., Bencsik, P., Pipicz, M., Varga, Z.V., Paloczi, J., Csonka, C., Ferdinandy, P. and Csont, T. (2012) Preconditioning Protects the Heart in a Prolonged Uremic Condition. American Journal of Physiology—Heart and Circulatory Physiology, 303, H1229-H1236.
http://dx.doi.org/10.1152/ajpheart.00379.2012
[10] Maxwell, M.P., Hearse, D.J. and Yellon, D.M. (1987) Species Variation in the Coronary Collateral Circulation during Regional Myocardial Ischemia: A Critical Determinant of the Rate of Evolution and Extent of Myocardial Infarction. Cardiovascular Research, 21, 737-746.
http://dx.doi.org/10.1093/cvr/21.10.737
[11] Ertl, G., Alexander, R.W. and Kloner, R.A. (1983) Interactions between Coronary Occlusion and the Renin-Angiotensin System in the Dog. Basic Research in Cardiology, 78, 518-533.
http://dx.doi.org/10.1007/BF01906463
[12] Remuzzi, G., Perico, N., Macia, M. and Ruggenenti, P. (2005) The Role of Renin-Angiotensin-Aldosterone System in the Progression of Chronic Kidney Disease. Kidney International, 68, S57-S65.
http://dx.doi.org/10.1111/j.1523-1755.2005.09911.x
[13] Swedberg, K., Eneroth, P., Kjekshus, J. and Wilhelmsen, L. (1990) Hormones Regulating Cardiovascular Function in Patients with Severe Congestive Heart Failure and Their Relation to Mortality. CONSENSUS Trial Study Group. Circulation, 82, 1730-1736.
http://dx.doi.org/10.1161/01.CIR.82.5.1730
[14] Ertl, G., Kloner, R.A., Alexander, R.W. and Braunwald, E. (1982) Limitation of Experimental Infarct Size by an Angiotensin-Converting Enzyme Inhibitor. Circulation, 65, 40-48.
http://dx.doi.org/10.1161/01.CIR.65.1.40
[15] Mehta, P.M., Alker, K.J. and Kloner, R.A. (1988) Functional Infarct Expansion, Left Ventricular Dilation and Isovolumic Relaxation Time after Coronary Occlusion: A Two-Dimensional Echocardiographic Study. Journal of the American College of Cardiology, 11, 630-636.
http://dx.doi.org/10.1016/0735-1097(88)91542-2
[16] De Graeff, P.A., Van Gilst, W.H., Bel, K., de Langen, C.D., Kingma, J.H. and Wesseling, H. (1987) Concentration-Dependent Protection by Captopril against Myocardial Damage during Ischemia and Reperfusion in a Closed Chest Pig Model. Journal of Cardiovascular Pharmacology, 9, S37-S42.
http://dx.doi.org/10.1097/00005344-198700002-00009
[17] Parlakpinar, H., Ozer, M.K. and Acet, A. (2011) Effects of Captopril and Angiotensin II Receptor Blockers (AT1, AT2) on Myocardial Ischemia-Reperfusion Induced Infarct Size. Cytokine, 56, 688-694.
http://dx.doi.org/10.1016/j.cyto.2011.09.002
[18] Daniell, H.B., Carson, R.R., Ballard, K.D., Thomas, G.R. and Privitera, P.J. (1984) Effects of Captopril on Limiting Infarct Size in Conscious Dogs. Journal of Cardiovascular Pharmacology, 6, 1043-1047.
http://dx.doi.org/10.1097/00005344-198411000-00009
[19] Brenner, B.M., Cooper, M.E., de Zeeuw, D., Keane, W.F., Mitch, W.E., Parving, H.H., Remuzzi, G., Snapinn, S.M., Zhang, Z. and Shahinfar, S. (2001) Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. The New England Journal of Medicine, 345, 861-869.
http://dx.doi.org/10.1056/NEJMoa011161
[20] Edner, M., Benson, L., Dahlstrom, U. and Lund, L.H. (2015) Association between Renin-Angiotensin System Antagonist Use and Mortality in Heart Failure with Severe Renal Insufficiency: A Prospective Propensity Score-Matched Cohort Study. European Heart Journal, 36, 2318-2326.
http://dx.doi.org/10.1093/eurheartj/ehv268
[21] Fried, L.F., Emanuele, N., Zhang, J.H., Brophy, M., Conner, T.A., Duckworth, W., Leehey, D.J., McCullough, P.A., O’Connor, T., Palevsky, P.M., Reilly, R.F., Seliger, S.L., Warren, S.R., Watnick, S., Peduzzi, P. and Guarino, P. (2013) Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. The New England Journal of Medicine, 369, 1892-1903.
http://dx.doi.org/10.1056/NEJMoa1303154
[22] Brochu, E., Lacasse, S., Lariviere, R., Kingma, I., Grose, J.H. and Lebel, M. (1999) Differential Effects of Endothelin-1 Antagonists on Erythropoietin-Induced Hypertension in Renal Failure. Journal of the American Society of Nephrology, 10, 1440-1446.
[23] Freundlich, M., Quiroz, Y., Zhang, Z., Zhang, Y., Bravo, Y., Weisinger, J.R., Li, Y.C. and Rodriguez-Iturbe, B. (2008) Suppression of Renin-Angiotensin Gene Expression in the Kidney by Paricalcitol. Kidney International, 74, 1394-1402.
http://dx.doi.org/10.1038/ki.2008.408
[24] Daleau, P., Boudriau, S., Michaud, M., Jolicoeur, C. and Kingma Jr., J.G. (2001) Preconditioning in the Absence or Presence of Sustained Ischemia Modulates Myocardial Cx43 Protein Levels and Gap Junction Distribution. Canadian Journal of Physiology and Pharmacology, 79, 371-378.
http://dx.doi.org/10.1139/y01-004
[25] Currie, R.W., Tanguay, R.M. and Kingma Jr., J.G. (1993) Heat-Shock Response and Limitation of Tissue Necrosis during Occlusion/Reperfusion in Rabbit Hearts. Circulation, 87, 963-971.
http://dx.doi.org/10.1161/01.CIR.87.3.963
[26] Kingma Jr., J.G., Simard, D., Rouleau, J.R., Tanguay, R.M. and Currie, R.W. (1996) Effect of 3-Aminotriazole on Hyperthermia-Mediated Cardioprotection in Rabbits. American Journal of Physiology: Heart and Circulatory Physiology, 270, H1165-H1171.
[27] Anavekar, N.S., McMurray, J.J., Velazquez, E.J., Solomon, S.D., Kober, L., Rouleau, J.L., White, H.D., Nordlander, R., Maggioni, A., Dickstein, K., Zelenkofske, S., Leimberger, J.D., Califf, R.M. and Pfeffer, M.A. (2004) Relation between Renal Dysfunction and Cardiovascular Outcomes after Myocardial Infarction. The New England Journal of Medicine, 351, 1285-1295.
http://dx.doi.org/10.1056/NEJMoa041365
[28] de Mattos, A.M., Siedlecki, A., Gaston, R.S., Perry, G.J., Julian, B.A., Kew, C.E., Deierhoi, M.H., Young, C., Curtis, J.J. and Iskandrian, A.E. (2008) Systolic Dysfunction Portends Increased Mortality among Those Waiting for Renal Transplant. Journal of the American Society of Nephrology, 19, 1191-1196.
http://dx.doi.org/10.1681/ASN.2007040503
[29] Go, A.S., Chertow, G.M., Fan, D., McCulloch, C.E. and Hsu, C.Y. (2004) Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. The New England Journal of Medicine, 351, 1296-1305.
http://dx.doi.org/10.1056/NEJMoa041031
[30] Braam, B., Joles, J.A., Danishwar, A.H. and Gaillard, C.A. (2014) Cardiorenal Syndrome—Current Understanding and Future Perspectives. Nature Reviews Nephrology, 10, 48-55.
http://dx.doi.org/10.1038/nrneph.2013.250
[31] Bongartz, L.G., Cramer, M.J., Doevendans, P.A., Joles, J.A. and Braam, B. (2005) The Severe Cardiorenal Syndrome: “Guyton Revisited”. European Heart Journal, 26, 11-17.
http://dx.doi.org/10.1093/eurheartj/ehi020
[32] Ronco, C., McCullough, P., Anker, S.D., Anand, I., Aspromonte, N., Bagshaw, S.M., Bellomo, R., Berl, T., Bobek, I., Cruz, D.N., Daliento, L., Davenport, A., Haapio, M., Hillege, H., House, A.A., Katz, N., Maisel, A., Mankad, S., Zanco, P., Mebazaa, A., Palazzuoli, A., Ronco, F., Shaw, A., Sheinfeld, G., Soni, S., Vescovo, G., Zamperetti, N. and Ponikowski, P. (2010) Cardio-Renal Syndromes: Report from the Consensus Conference of the Acute Dialysis Quality Initiative. European Heart Journal, 31, 703-711.
http://dx.doi.org/10.1093/eurheartj/ehp507
[33] Brown, J.H., Lappin, T.R., Elder, G.E., Bridges, J.M. and McGeown, M.G. (1990) The Metabolism of Erythropoietin in the Normal and Uraemic Rabbit. Nephrology Dialysis Transplantation, 5, 855-859.
http://dx.doi.org/10.1093/ndt/5.10.855
[34] Oreopoulos, A.K., Balaskas, E.V., Rodela, H., Anderson, G.H. and Oreopoulos, D.G. (1993) An Animal Model for the Study of Amino Acid Metabolism in Uremia and during Peritoneal Dialysis. Peritoneal Dialysis International, 13, S499-S507.
[35] Bagcivan, I., Kilicarslan, H., Sarac, B., Gokce, G., Yildirim, S., Ayan, S. and Sarioglu, Y. (2003) The Evaluation of the Effects of Renal Failure on Erectile Dysfunction in a Rabbit Model of Chronic Renal Failure. BJU International, 91, 697-701.
http://dx.doi.org/10.1046/j.1464-410X.2003.04179.x
[36] Lazarus, J.M., Hampers, C.L., Lowrie, E.G. and Merrill, J.P. (1973) Baroreceptor Activity in Normotensive and Hypertensive Uremic Patients. Circulation, 47, 1015-1021.
http://dx.doi.org/10.1161/01.CIR.47.5.1015
[37] Tomiyama, O., Shiigai, T., Ideura, T., Tomita, K., Mito, Y., Shinohara, S. and Takeuchi, J. (1980) Baroreflex Sensitivity in Renal Failure. Clinical Science, 58, 21-27.
http://dx.doi.org/10.1042/cs0580021
[38] Levin, A., Singer, J., Thompson, C.R., Ross, H. and Lewis, M. (1996) Prevalent Left Ventricular Hypertrophy in the Predialysis Population: Identifying Opportunities for Intervention. American Journal of Kidney Diseases, 27, 347-354.
http://dx.doi.org/10.1016/S0272-6386(96)90357-1
[39] Michea, L., Villagran, A., Urzua, A., Kuntsmann, S., Venegas, P., Carrasco, L., Gonzalez, M. and Marusic, E.T. (2008) Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats. Hypertension, 52, 295-300.
http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.109645
[40] Kingma, J.G., Simard, D., Voisine, P. and Rouleau, J.R. (2014) Impact of Chronic Kidney Disease on Myocardial Blood Flow Regulation in Dogs. Nephron Experimental Nephrology, 126, 175-182.
http://dx.doi.org/10.1159/000362090
[41] Papazova, D.A., van Koppen, A., Koeners, M.P., Bleys, R.L., Verhaar, M.C. and Joles, J.A. (2014) Maintenance of Hypertensive Hemodynamics Does Not Depend on ROS in Established Experimental Chronic Kidney Disease. PLoS ONE, 9, e88596.
http://dx.doi.org/10.1371/journal.pone.0088596
[42] Hatamizadeh, P., Fonarow, G.C., Budoff, M.J., Darabian, S., Kovesdy, C.P. and Kalantar-Zadeh, K. (2013) Cardiorenal Syndrome: Pathophysiology and Potential Targets for Clinical Management. Nature Reviews Nephrology, 9, 99-111.
http://dx.doi.org/10.1038/nrneph.2012.279
[43] Hoshida, S., Yamashita, N., Kawahara, K., Kuzuya, T. and Hori, M. (1999) Amelioration by Quinapril of Myocardial Infarction Induced by Coronary Occlusion/Reperfusion in a Rabbit Model of Atherosclerosis: Possible Mechanisms. Circulation, 99, 434-440.
http://dx.doi.org/10.1161/01.cir.99.3.434
[44] Hartman, J.C. (1995) The Role of Bradykinin and Nitric Oxide in the Cardioprotective Action of ACE Inhibitors. The Annals of Thoracic Surgery, 60, 789-792.
http://dx.doi.org/10.1016/0003-4975(95)00192-N
[45] Hoshida, S., Yamashita, N., Kuzuya, T. and Hori, M. (2000) Differential Effects of Long-Term Renin-Angiotensin System Blockade on Limitation of Infarct Size in Cholesterol-Fed Rabbits. Atherosclerosis, 149, 287-294.
http://dx.doi.org/10.1016/S0021-9150(99)00334-2
[46] Downey, J.M. and Cohen, M.V. (1995) Signal Transduction in Ischemic Preconditioning. Zeitschrift fur Kardiologie, 84, 77-86.
[47] Kingma, J.G. (2014) Conditioning Strategies Limit Cellular Injury? World Journal of Cardiovascular Diseases, 4, 539-547.
http://dx.doi.org/10.4236/wjcd.2014.411065
[48] Ludman, A.J., Yellon, D.M. and Hausenloy, D.J. (2010) Cardiac Preconditioning for Ischaemia: Lost in Translation. Disease Models & Mechanisms, 3, 35-38.
http://dx.doi.org/10.1242/dmm.003855
[49] Kingma Jr., J.G., Vincent, C., Rouleau, J.R. and Kingma, I. (2006) Influence of Acute Renal Failure on Coronary Vasoregulation in Dogs. Journal of the American Society of Nephrology, 17, 1316-1324.
http://dx.doi.org/10.1681/ASN.2005101084
[50] Jones, S.P., Tang, X.L., Guo, Y., Steenbergen, C., Lefer, D.J., Kukreja, R.C., Kong, M., Li, Q., Bhushan, S., Zhu, X., Du, J., Nong, Y., Stowers, H.L., Kondo, K., Hunt, G.N., Good-child, T.T., Orr, A., Chang, C.C., Ockaili, R., Salloum, F.N. and Bolli, R. (2015) The NHLBI-Sponsored Consortium for Preclinical Assessment of Cardioprotective Therapies (CAESAR): A New Paradigm for Rigorous, Accurate, and Reproducible Evaluation of Putative Infarct-Sparing Interventions in Mice, Rabbits, and Pigs. Circulation Research, 116, 572-586.
http://dx.doi.org/10.1161/CIRCRESAHA.116.305462
[51] Mehta, P.M., Przyklenk, K. and Kloner, R.A. (1990) Cardioprotective Effects of Captopril in Myocardialischaemia/Reperfusion and Infarction. European Heart Journal, 11, 94-99.
http://dx.doi.org/10.1093/eurheartj/11.suppl_B.94
[52] Andrade, T.U., Pinto, V.D., Medeiros, A.R., Abreu, G.R., Moyses, M.R., Sampaio, K.N. and Bissoli, N.S. (2007) Effect of Enalapril Treatment on the Sensitivity of Cardiopulmonary Reflexes in Rats with Myocardial Infarction. Clinical and Experimental Pharmacology and Physiology, 34, 606-611.
http://dx.doi.org/10.1111/j.1440-1681.2007.04613.x
[53] Arnold, A.C., Okamoto, L.E., Gamboa, A., Shibao, C., Raj, S.R., Robertson, D. and Biaggioni, I. (2013) Angiotensin II, Independent of Plasma Renin Activity, Contributes to the Hypertension of Autonomic Failure. Hypertension, 61, 701-706.
http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.00377

  
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