Subtotal nephrectomy accelerates pathological cardiac remodeling post-myocardial infarction: Implications for cardiorenal syndrome

Abstract

Background To further understand the pathophysiology of concomitant cardiac and renal dysfunction, we investigated molecular, structural and functional changes in heart and kidney that occur when a kidney insult (5/6 nephrectomy-STNx) follows myocardial infarction (MI). Methods Male Sprague Dawley rats (n = 43) 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 followed by STNx/Sham surgery 4 weeks later. Cardiac and renal function was assessed prior to STNx/Sham surgery and again 10 weeks later. Hemodynamic parameters were measured prior to sacrifice. Results Compared to the MI + Sham group, STNx further accelerated the reduction in left ventricular (LV) ejection fraction by 21% (p < 0.01), and increased tau logistic by 38% (p < 0.01) in MI + STNx animals. Heart weight/body weight (BW) and lung weight/BW ratios were 39% (p < 0.001) and 16% (p < 0.01) greater in MI + STNx compared to MI + Sham animals. Similarly, myocyte cross-sectional area (p < 0.001), cardiac interstitial fibrosis (p < 0.01) and collagen I (p < 0.01) were increased in the LV non-infarct zone of the myocardium in the MI + STNx group. These changes were associated with significant increases in atrial natriuretic peptide (p < 0.001), transforming growth factor β1(p < 0.05) and collagen I (p < 0.05) gene expression in MI + STNx animals. In comparison with the Sham + STNx group, renal tubulointerstitial fibrosis was increased by 64% in MI + STNx animals (p < 0.001), with no further deterioration in renal function. Conclusions STNx accelerated cardiac changes post-MI whilst MI accelerated STNx-induced renal fibrosis, supporting bidirectional interactions in cardiorenal syndrome (CRS). This animal model may be of use in assessing the impact of therapies to treat CRS. © 2013 Elsevier Ireland Ltd. All rights reserved.