Abstract 11507: Subtotal Nephrectomy Accelerates Pathological Cardiac Remodelling Post Myocardial Infarction: Recapitulating the Phenotype of Cardiorenal Syndrome?
Introduction: A close relationship exists between chronic kidney disease and chronic heart failure, with failure of one organ having detrimental effects on the other (cardiorenal syndrome, CRS). The aim of this study was to investigate the pathophysiological changes that occur when a kidney insult (induced by 5/6 nephrectomy - STNx) follows that of myocardial infarction (MI) on heart and kidney structure and function.
Study design: Male Sprague Dawley rats (n=24) were randomized into four groups: Sham-operated MI + Sham-operated STNx (Sham+Sham), MI + Sham-operated STNx (MI+Sham), Sham-operated MI + STNx (Sham+STNx) and MI+STNx. MI/Sham surgery was performed initially; STNx/Sham surgery was performed 4 weeks post-MI, and animals were followed for a further 10 weeks post-STNx.
Results: Heart weight/body weight and lung weight/body weight ratios were significantly greater in MI+STNx vs MI+Sham animals at week 14 (P<0.0001 and P=0.005 respectively), despite no difference in infarct size (34.0±2.9% and 33.5±1.6% respectively). Left ventricular ejection fraction was further decreased from 39.7±2.3% in MI+Sham animals to 30.7±1.3% in MI+STNx animals (P=0.005). Significant increases in cardiomyocyte cross-sectional area were observed in MI+STNx animals compared to MI+Sham animals (P=0.0008). MI+STNx animals also had greater interstitial fibrosis in the peri-infarct zone of the heart compared to MI+Sham animals (P=0.052). Despite lower blood pressure in the MI+STNx animals, greater interstitial fibrosis in the non-infarct zone of the kidney was observed in MI+STNx animals compared to Sham+STNx animals (P=0.001).
Conclusions: Subtotal nephrectomy accelerates pathophysiological cardiac changes whilst MI causes more severe renal fibrosis in the present study, supporting bi-directional interactions in cardiorenal syndrome. This pre-clinical model furthers our understanding of underlying pathophysiology of this condition.
- © 2011 by American Heart Association, Inc.