Background— The formation of angiotensin-(1-7) from either angiotensin (Ang) I or Ang II in failing human hearts is not well understood. Methods and Results— Angiotensinase activity in left and right ventricular membranes from 14 idiopathic dilated cardiomyopathy (IDC), 8 primary pulmonary hypertension (PPH), and 13 nonfailing human hearts was measured with either 125 I-Ang I or 125 I-Ang II as substrate. Ang-(1-7)–forming activity from 125 I-Ang I was inhibited by thiorphan. With 125 I-Ang II as substrate, Ang-(1-7) formation was inhibited by the ACE2-specific inhibitor C16. Western blotting with an anti-ACE2 antibody confirmed the presence of ACE2. Angiotensinase activity with 125 I-Ang I as substrate was increased in failing IDC left ventricles (LVs) compared with nonfailing LVs ( P <0.001). Ang-(1-7)–forming activity with 125 I-Ang II as substrate was increased in both failing LVs and right ventricles (RVs) of IDC hearts and only in failing RVs of PPH hearts (PPH LV, 51.12±5.25; PPH RV, 89.97±11.21; IDC LV, 139.7±21.96; and IDC RV, 192.7±5.43; NF LV, 32.89±5.38; NF RV 40.49±10.66 fmol/min per milligram ( P <0.05 PPH RV versus PPH LV; P <0.05 PPH RV versus NF RV; P <0.001 IDC LV versus NF LV; P <0.001 IDC RV versus NF RV). Conclusions— Ang-(1-7)–forming activity from both Ang I and Ang II was increased in failing human heart ventricles but was mediated by at least two different angiotensinases. The first, which demonstrated substrate preference for Ang I, was neutral endopeptidase (NEP)-like. The second was ACE2, as demonstrated by Western blotting and inhibition of activity with C16.

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Background— In patients with sickle cell trait or disease, reduced life expectancy and a tendency for complications are believed to negatively affect likelihood of survival after open heart surgery. The aim of this study was to review retrospectively the perioperative results of patients undergoing cardiac surgery at our institution. Methods and Results— Between January 1995 and December 2006, 47 patients with either sickle cell disease or sickle cell trait underwent open heart surgery at our institution. The average age of the 29 male and 18 female patients was 20 years. Patient outcomes were analyzed through the use of the institutional database. Clinical and echocardiographic follow-up was complete in all patients except 3, with a mean follow-up period of 46 months. Current status could be confirmed in 32 patients. The most common operations included the treatment of congenital and valvular heart diseases. There were no coronary artery bypass grafting procedures. Average weight of the patients was 45 kg. Exchange transfusion was performed both preoperatively and during surgery. Mean preoperative hemoglobin S concentration was 30.4±3.2% and decreased to 8.1±2.6% while on pump. Average on-pump hematocrit value was 25.4±3.7%; in the postoperative period, it increased to 32.7±4.9%. Mean cardiopulmonary bypass and cross-clamp times were 95 and 69 minutes, respectively. None of the patients had sickling crisis or acidosis. Postoperative complications included exploration for hemorrhage in 3 patients (6.4%), stroke in 2 patients (4.3%), renal failure in 2 patients (4.3%), and prolonged ventilation in 1 patient (2.1%). Average hospital stay was 8.3 days (range, 4 to 27 days). Early in-hospital death occurred in 1 patient (2.1%); currently, 31 patients (66%) remain alive and free of cardiac symptoms. Conclusion— Heart valve surgery and surgery for congenital heart diseases can be performed safely in patients with sickle cell disease or sickle cell trait with acceptable outcome and survival rates.