Increased Infarct Size in Uremic Rats

Abstract

Abstract. In patients with renal failure, myocardial infarction (MI) is more frequent and the rate of death from acute MI is very high. It has been argued that ischemia tolerance of the heart is reduced in uremia, but direct evidence for this hypothesis has not been provided. It was the purpose of this study (1) to ligate the left coronary artery and to measure the nonperfused area (risk area: total infarction plus penumbra) as well as the area of total infarction in subtotally nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and (2) to examine the effects of potential confounders such as BP, sympathetic overactivity, and salt retention. The left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. For visualizing perfused myocardium, lissamine green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (triphenyltetrazolium chloride stain) were assessed in sections of the left ventricle using image analysis. Groups of SNX rats also received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high salt diet or low salt diet (1.58% versus 0.015%). In surviving animals, the nonperfused area at risk (as the proportion of total left ventricular area), presumably determined by the geometry of vascular supply, was similar in sham-operated and SNX animals (0.38 Ϯ 0.13 versus 0.45 Ϯ 0.09; NS). In contrast, the infarcted area, given as a proportion of the nonperfused risk area, was significantly (P Ͻ 0.003) higher in SNX (0.68 Ϯ 0.09) compared with sham-operated (0.51 Ϯ 0.11) rats and was not altered by any of the above interventions. The finding that a greater proportion of nonperfused myocardium undergoes total necrosis is consistent with the hypothesis of reduced ischemia tolerance of the heart in renal failure. The findings could explain the high rate of death from MI in patients with impaired renal function.The high cardiovascular mortality of renal patients has been widely appreciated since the seminal communication of Lindner (1). This is undoubtedly, at least in part, the consequence of premature and more severe atherosclerosis of the coronary arteries (2,3). Such accelerated atherogenesis recently also was documented in experimental models (4).Not only is the frequency of myocardial infarction (MI) increased in renal patients, there is also convincing evidence that the rate of death from acute MI is dramatically increased. In the observation of Shlipak et al. (5), even moderate renal insufficiency was associated with a substantially elevated risk of death during the first months of follow-up after MI. In a retrospective cohort study on patients with acute MI, Wright et al. (6) found a graded increase of in-hospital mortality with decreasing renal function. Mortality was 2% in patients with normal renal function and 30% in patients with ESRD. Although the authors commented on the "association between reduced use of acute perfusion therapy in these patients and poor survival" (6), there is little doubt that ...

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“…Inadequate capillary density will restrict the ability of the heart to cope with increased oxygen demand. Finally, after ligation of the left coronary, infarcts are larger in animals with experimental uremia, pointing to reduced ischemia tolerance (31).…”

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