Author(s)

John G. Kingma^*, Guylaine Sénéchal, Jacques R. Rouleau, Iris Kingma

Faculté de Médecine Pavillon Ferdinand Vandry, Avenue de la Médecine, Université Laval Québec, Québec Canada.

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.

Myocardial Infarct Size, Ischemia, Reperfusion, Uremia

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.