New engineering treatment of bovine pericardium confers outstanding resistance to calcification in mitral and pulmonary implantations in a juvenile sheep model.

OBJECTIVE: To conduct a test of noninferiority for CardioCel (Admedus, Brisbane, Australia), a chemically engineered bovine pericardium over autologous pericardium treated intraoperatively with glutaraldehyde in a chronic juvenile sheep model of pulmonary valve (PV) and mitral valve (MV) reconstruction. METHODS: We replaced the posterior leaflet of the MV and of 1 PV cusp with patches in ewes aged 10 months. There were 2 groups: CardioCel (n = 6) and control (n = 4). All valves were competent. Echocardiography was performed before euthanasia. The collected data were function, macroscopy, histology, and calcium contents. The primary end points were thickening and calcium content. RESULTS: All animals survived until sacrifice after 7 months. The valves had normal echo. The macroscopic aspect of the valves was excellent. Examination of the slides for both groups revealed a continuous endothelium on both sides of the patch and a layer of new collagen developed on both sides between patch and endothelium and interstitial cells and smooth muscle cell in these layers. The patch had not thickened but the 2 layers of new collagen for the PV showed a median thickening of 37% in the CardioCel group and 111% in the control group (P = .01), and for the MV a thickening of 108% and 251%, respectively, was seen (P = .01). The median calcium content in the PV was 0.24 µg/mg (range, 0.19-0.30) in the CardioCel group versus 0.34 µg/mg (range, 0.24-0.62) in controls (P = .20). In the MV it was 0.46 µg/mg (range, 0.30-1.0) in the CardioCel group and 0.47 µg/mg (range, 0.29-1.9) in controls (P = 1.0). CONCLUSIONS: In this growing lamb model the CardioCel patch allowed accurate valve repair at both systemic and pulmonary pressure. The mechanical properties of CardioCel after 7 months were preserved with a more controlled healing than the treated autologous pericardium and without calcification.

Impact of levosimendan on brain injury patterns in a lamb model of infant cardiopulmonary bypass.

BACKGROUND: The effects of levosimendan (Levo) on injury patterns in the immature brain following cardiopulmonary bypass (CPB) are unknown. METHODS: Eighteen 3- to 4-wk-old anesthetized lambs, instrumented with vascular catheters and aortic and right carotid artery flow probes, were allocated to non-CPB, CPB, or CPB+Levo groups (each n = 6). After 120 min CPB with 90 min aortic cross-clamp, CPB animals received dopamine, and CPB+Levo animals both dopamine and Levo, for 4 h. All lambs then underwent brain magnetic resonance imaging, followed by postmortem brain perfusion fixation for immunohistochemical studies. RESULTS: In CPB lambs, aortic (P < 0.05) and carotid artery (P < 0.01) blood flows fell by 29 and 30%, respectively, between 2 and 4 h after cross-clamp removal but were unchanged in the CPB+Levo group. No brain injury was detectable with magnetic resonance imaging in either CPB or CPB+Levo lambs. However, on immunohistochemical analysis, white matter astrocyte density of both groups was higher than in non-CPB lambs (P < 0.05), while white matter microglial density was higher (P < 0.05), but markers of cortical oxidative stress were less prevalent in CPB+Levo than CPB lambs. CONCLUSION: While Levo prevented early postoperative falls in cardiac output and carotid artery blood flow in a lamb model of infant CPB, this was associated with heterogeneous neuroglial activation and manifestation of markers of oxidative stress.

Mechanisms of a reduced cardiac output and the effects of milrinone and levosimendan in a model of infant cardiopulmonary bypass.

OBJECTIVES: A low cardiac output state is an important cause of morbidity after pediatric cardiopulmonary bypass. The objectives of our study were to define the early precipitants of the reduced cardiac output and to investigate the effects on these of milrinone and levosimendan in a model of pediatric cardiopulmonary bypass. DESIGN: Experimental study. SETTING: : Research laboratory at a university-affiliated, tertiary pediatric center. SUBJECTS: Eighteen piglets. INTERVENTIONS: Piglets, instrumented with systemic, pulmonary arterial, and coronary sinus catheters, pulmonary and circumflex arterial flow probes, and a left ventricular conductance-micromanometer-tipped catheter, underwent cardiopulmonary bypass with aortic cross-clamp and cardioplegic arrest. At 120 mins, they were assigned to control, milrinone, or levosimendan groups and studied for a further 120 mins. MEASUREMENTS AND MAIN RESULTS: In controls, between 120 and 240 mins, cardiac output decreased by 15%. Systemic vascular resistance was unchanged, but pulmonary vascular resistance increased by 19%. Systemic arterial elastance increased by 17%, indicating increased afterload. End-systolic elastance was unchanged, and coronary sinus oxygen tension decreased by 4.0 +/- 1.7 mm Hg. In animals receiving milrinone cardiac output was preserved, and in animals receiving levosimendan cardiac output increased by 14%. Both drugs prevented an increase in arterial elastance and pulmonary vascular resistance after cardiopulmonary bypass. Systemic vascular resistance decreased by 31% after levosimendan, and end-systolic elastance increased by 48%, indicating improved contractility. Both agents prevented a decrease in coronary sinus oxygen tension. CONCLUSIONS: Increased afterload, which is not matched by an equivalent elevation in contractility, contributes to the reduced cardiac output early after pediatric cardiopulmonary bypass in this model. This increase is prevented by milrinone and levosimendan. Both agents exert additional beneficial effects on pulmonary vascular resistance and myocardial oxygen balance, although levosimendan has greater inotropic properties.