OBJECTIVES: Chronic renal dysfunction severely increases cardiovascular risk. Adverse cardiac remodeling is suggested to play a major role as predisposition for increased cardiac ischemic vulnerability. The aim of the present study was to examine the role of adverse cardiac remodeling in cardiac sensitivity to acute ischemia/reperfusion damage in a rat model for renal dysfunction. METHODS: Munich Wistar Fromter (MWF) rats, developing spontaneous progressive renal dysfunction and mild hypertension, were compared to healthy Wistar rats, and to nonproteinuric spontaneously hypertensive rats (SHRs). In MWF rats, renal dysfunction and mild hypertension were confirmed. Hearts were analyzed for adverse cardiac remodeling, including myocyte hypertrophy, capillary density, and interstitial fibrosis, by histology. In parallel, sensitivity to cardiac ischemia/reperfusion damage was obtained from infarct size measured after 30-min coronary artery occlusion, followed by 24 h of reperfusion. RESULTS: Infarcts were larger in MWF rats [56 ± 3% of risk area (P = 0.04)], but at a similar extent in SHRs [52 ± 4% (P = 0.16)], when compared to Wistar rats (45 ± 4%). However, whereas SHRs showed pronounced adverse cardiac remodeling, MWF rats did not: no left ventricular hypertrophy (myocyte size MWF rats +29%; SHRs +72%), no lower capillary density (MWF rats +34%; SHRs-13%), and no interstitial fibrosis (MWF rats-16%; SHRs +70%). CONCLUSION: Data indicate that chronic renal dysfunction in MWF rats is associated with elevated cardiac sensitivity to acute ischemia/reperfusion damage, as reflected by larger infarcts. Comparing results to SHRs suggests that this higher susceptibility could not be attributed to hypertension or adverse cardiac remodeling.

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doi.org/10.1097/HJH.0b013e32835f7482, hdl.handle.net/1765/68916
Journal of Hypertension
Department of Cardiology

Szymanski, M., Hillege, H., Danser, J., Garrelds, I., & Schoemaker, R. (2013). Elevated sensitivity to cardiac ischemia in proteinuric rats is independent of adverse cardiac remodeling. Journal of Hypertension, 31(5), 966–974. doi:10.1097/HJH.0b013e32835f7482