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

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.