We showed that spironolactone reduced structural damage and prevented renal dysfunction in chronic cyclosporine (CsA) nephrotoxicity. These findings evidenced an aldosterone renal vascular effect under this condition. To investigate aldosterone's role in modulating renal vascular tone, renocortical vasoactive pathways mRNA levels in chronic CsA nephrotoxicity as well as spironolactone's effect on renal function in acute CsA nephrotoxicity were evaluated. Two experimental sets were designed. For chronic nephrotoxicity, rats fed with low-sodium diet were divided into groups receiving vehicle, spironolactone (Sp), CsA, and CsA+Sp, for 21 days. Creatinine clearance, survival percentage, and renocortical mRNA levels of pro-renin, angiotensinogen (Ang), angiotensin receptors (AT(1A), AT(1B), and AT(2)), preproendothelin, endothelin receptors (ET(A), ET(B)), cyclooxygenase-2 (COX-2), and adenosine receptors (Ad(1), Ad(2A), Ad(2B), and Ad(3)) were analyzed. For acute nephrotoxicity, similar groups fed with a standard chow diet for 7 days were included. Serum potassium and sodium, glomerular filtration rate (GFR), and renal blood flow (RBF) were determined. In chronic model, CsA produced pro-renin and ET upregulation, altered adenosine receptors expression, and reduced Ang, AT(1A), AT(1B), ET(B), and COX-2 mRNA levels. Spironolactone protective effect in chronic nephrotoxicity was associated with prevention of pro-renin upregulation and increased AT(2), together with ET(B) reduction. In acute nephrotoxicity, spironolactone completely prevented GFR and RBF reduction induced by CsA. Our results suggest that aldosterone contributes to renal vasoconstriction observed in CsA nephrotoxicity and that renoprotection conferred by spironolactone was related to modification of renocortical vasoactive pathways expression, in which pro-renin normalization was the most evident change in chronic nephropathy. Finally, our data point to spironolactone as a potential treatment to reduce CsA nephrotoxicity in transplant patients.

Forty-four cases of myocardial infarction with cardiac rupture, 88 cases of unruptured myocardial infarction, and 88 cases without myocardial infarction were studied retrospectively. The incidence of cardiac rupture in cases with acute myocardial infarction alone was 5.5% while in hearts having both healed and acute myocardial infarction the incidence was 2.3%. One instance of cardiac rupture was encountered in a heart having only a healed myocardial infarction with subsequent aneurysmal dilation of the healed infarct. Although females represented only 37% of the population having acute myocardial infarction in this institution, they accounted for 55% of the cases of cardiac rupture. On the average the hearts which ruptured following myocardial infarction were lighter and thinner than in the control group of patients having infarction without rupture. Among the clinical correlates possibly associated with postinfarction rupture the most significant finding in the present study is the presence of postinfarction hypertension. In the group of cases with cardiac rupture this was present in 40% while in the control group not having suffered cardiac rupture the comparable figure was 14%. A history of diabetes was found in 18% of the cases of myocardial infarction not having suffered cardiac rupture. A similar history was found in only 9% of the cases having a postinfarction cardiac rupture. This latter incidence is identical with the frequency of diabetes mellitus in the general autopsy population. There is a suggestion that early and severe atherosclerosis may cause earlier heart disease and when infarction occurs provide some protection against rupture. Of interest among the 44 cases of cardiac rupture, none of the patients had cirrhosis, in striking contrast to the 11% incidence of this condition in our general autopsy population.

“Small-for-size” livers arising in the context of liver resection and transplantation are vulnerable to the effects of increased portal flow in the immediate postoperative period. Increased portal flow is an essential stimulus for liver regeneration. If the rise in flow and stimulus for regeneration are excessive; however, liver failure and patient death may result. Somatostatin is an endogenous peptide hormone that may be administered exogenously to not only reduce portal blood flow but also offer direct protection to different cells in the liver. In this review article, we describe key changes that transpire in the liver following a relative size reduction occurring in the context of resection and transplantation and the largely beneficial effects that peri-operative somatostatin therapy may help achieve in this setting.