Ischemic Tolerance in Uremic Rabbits
نویسندگان
چکیده
Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities; we tested whether experimentally induced prolonged uremia exacerbated 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.
منابع مشابه
Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance.
BACKGROUND Recent studies suggest that the late phase of ischemic preconditioning (PC) can be mimicked by pretreatment with NO donors. The ability of clinically relevant NO donors to induce PC against infarction, however, has not been evaluated. Furthermore, it is unknown whether tolerance to the hemodynamic actions of nitrates also extends to their PC effects. METHODS AND RESULTS Conscious r...
متن کاملPresence of toxic substances which inhibit erythropoiesis in serum of uremic nephrectomized rabbits.
The presence of toxic substances which inhibit erythropoiesis in uremic sera is still undetermined. We examined the effect of aceton-methylalcohol extracts of serum of nephrectomized rabbits with uremia on the erythropoiesis. The percentage red cell iron utilization was markedly reduced in nephrecto mized rabbits with uremia. The administration of aceton-methylalcohol extracts of uremic rabbit ...
متن کاملThe uremic myocardium and ischemic tolerance: a world of difference.
Uremia is associated with an increased prevalence of ischemic heart disease. Already, at the start of dialysis, the prevalence of coronary artery disease is 38%.1 The frequency of myocardial infarction in renal patients is high and the outcome is poor.2 Despite significant improvement of therapeutic modalities, the unadjusted 2-year mortality for dialysis patients after acute myocardial infarct...
متن کاملAcute Administration of Estradiol Protects against Spinal Ischemic-Reperfusion Injury in Male Rabbits
Introduction: Postoperative neurological deficit is the most devastating complication after thoracoabdominal aortic aneurysm repair. Despite demonstrated neuroprotective effects of estradiol, its protective efficacy against spinal cord ischemia-reperfusion and underlying mechanisms are not yet elucidated. Methods: Two groups, each of 10 New Zealand white male rabbits, were studied. Control g...
متن کامل