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

Shan Liu, Andrew Richard Kompa, Sirinart Kumfu, Fuyuhiko Nishijima, Darren J Kelly, Henry Krum, Bing Hui Wang

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25 Citations (Scopus)

Abstract

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 ?1 (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.
Original languageEnglish
Pages (from-to)1866 - 1880
Number of pages15
JournalInternational Journal of Cardiology
Volume168
Issue number3
DOIs
Publication statusPublished - 2013

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