Person:

Pigula, Frank A.

Carbon monoxide (CO) at low concentrations imparts protective effects in numerous preclinical small animal models of brain injury. Evidence of protection in large animal models of cerebral injury, however, has not been tested. Neurologic deficits following open heart surgery are likely related in part to ischemia reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB) induced significant alterations in metabolic demands, including a decrease in the oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise in cerebral blood pressure that ultimately resulted in increased cell death in the neocortex and hippocampus that was completely abrogated in piglets preconditioned with a low, safe dose of CO. Moreover CO-treated animals maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures with no change in systemic hemodynamics or metabolic intermediates. Collectively, our data demonstrate that inhaled CO may be beneficial in preventing cerebral injury resulting from DHCA and offer important therapeutic options in newborns undergoing DHCA for open heart surgery.

Background: Systemic vasodilation using α‐receptor blockade has been shown to decrease the incidence of postoperative cardiac arrest following stage 1 palliation (S1P), primarily when utilizing the modified Blalock‐Taussig shunt. We studied the effects of a protocol in which milrinone was primarily used to lower systemic vascular resistance (SVR) following S1P using the right ventricular to pulmonary artery shunt, measuring its effects on oxygen delivery (DO 2) profiles and clinical outcomes. We also correlated Fick‐based assessments of DO 2 with commonly used surrogate measures. Methods and Results: Neonates undergoing S1P were treated according to best clinical judgment prior to (n=32) and following (n=24) implementation of a protocol that guided operative, anesthetic, and postoperative management, particularly as it related to SVR. A majority of the subjects (n=51) received a modified right ventricular to pulmonary artery shunt. In a subset of these patients (n=21), oxygen consumption (VO 2) was measured and used to calculate SVR, DO 2, and oxygen debt. Neonates treated with the protocol had significantly lower SVR (P=0.02), serum lactate (P<0.001), and Sa‐vO 2 difference (P<0.001) and a lower incidence of CPR requiring extracorporeal membrane oxygenation (E‐CPR, P=0.02) within the first 72 postoperative hours. DO 2 was closely associated with SVR (r2=0.78) but correlated poorly with arterial (SaO2) and venous (SvO2) oxyhemoglobin concentrations, the Sa‐vO 2 difference, and blood pressure. Conclusions: A vasodilator protocol utilizing milrinone following S1P effectively decreased SVR, improved serum lactate, and decreased postoperative cardiac arrest. DO 2 correlated more closely with SVR than with Sa‐vO 2 difference, highlighting the importance of measuring VO 2 in this population. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02184169.

Objectives: Although mitral valve repair is rarely required in neonates, this population is considered to be at high risk for adverse outcomes. The aim of this study was to review the indications for surgery, mechanisms, repair techniques, and mid-term outcomes of neonatal mitral valve repair. Methods: The demographic, procedural, and outcome data were obtained for all neonates who underwent mitral valve repair from 2005 to 2012. The primary endpoints included mortality, transplantation, and mitral valve reoperation. Results: Twenty patients were included during the study period. Median age at operation was 11 days (range: 3–25). Eleven patients (55%) presented with mitral stenosis, three had regurgitation (15%), and six had mixed mitral disease (30%). Nineteen of 20 patients had mild or less regurgitation on immediate postoperative imaging. During a median follow-up of 5 months (1 month–4.8 years), six patients died at a median of 33 months (7–41 months) from repair and one patient required orthotopic heart transplantation. Six patients required mitral valve reoperation, five for mitral valve re-repair, and one for mitral valve replacement. Freedom from death, transplantation, or mitral valve replacement was 84.2 ± 8.4% at 1 month, 71.3 ± 11% at 6 months, 64.1 ± 12% at 1 year, and 51.3 ± 15% at 2 years and was worse for patients presenting with mitral regurgitation compared to stenosis or mixed mitral valve disease. Conclusion: Although mitral valve repair can be performed with acceptable immediate postoperative result, this procedure carries a high burden of late death and mitral valve reoperations.

Background: Neonates undergoing open-heart surgery are particularly at risk of postoperative bleeding requiring blood transfusion. Aprotinin has attained high efficacy in reducing the requirement for a blood transfusion following a cardiopulmonary bypass, but is seldom studied in the neonatal age group. The aim of this study was to compare the efficacy and adverse effects of aprotinin and tranexamic acid in neonates undergoing open-heart surgery at a single centre. Methods: Between October 2003 and March 2008, perioperative data of 552 consecutive neonatal patients undergoing open-heart surgery in Children’s Hospital Boston were reviewed. Among them, 177 did not receive antifibrinolytic therapy (Group A); 100 were treated with tranexamic acid only (Group B); and 275 patients received aprotinin with or without tranexamic acid (Group C). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained identical. Postoperative complications and in-hospital mortality were the primary study endpoints. Results: Body weight and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores were statistically comparable among the three groups. No statistically significant differences were observed between the duration of hospitalization, chest tube drainage, reexploration for bleeding, and kidney function impairment. In Group C, less blood was transfused within 24 hours than in GroupB. Operative mortality was similar among the three groups. Conclusion: No further risk and kidney injury were observed in the use of aprotinin in neonatal cardiac surgery, aprotinin demonstrated a reduced requirement for blood transfusion compared with tranexamic acid. Our data provide reasonable evidence that aprotinin and tranexamic acid are safe and efficacious as antifibrinolytic modalities in neonatal patients undergoing cardiac surgery.

A soft robotic sleeve modeled on the structure of the human heart assists cardiovascular function in an ex vivo and in vivo porcine model of heart failure.