Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death.

OBJECTIVE: Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation. METHODS: Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation. Hearts underwent 20 or 36 minutes of warm ischemia time (WIT), 10 minutes of cold cardioplegic arrest, and then were harvested for ex situ heart perfusion (ESHP). Following 15 minutes of ESHP, hearts received either vehicle (VEH) or vehicle containing isolated autologous mitochondria (MITO). A sham nonischemic group (SHAM) did not undergo WIT, mimicking donation after brain death heart procurement. Hearts underwent 2 hours each of unloaded and loaded ESHP perfusion. RESULTS: Following 4 hours of ESHP perfusion, left ventricle developed pressure, dP/dt max, and fractional shortening were significantly decreased (P < .001) in DCD hearts receiving VEH compared with SHAM hearts. In contrast, DCD hearts receiving MITO exhibited significantly preserved left ventricle developed pressure, dP/dt max, and fractional shortening (P < .001 each vs VEH, not significant vs SHAM). Infarct size was significantly decreased in DCD hearts receiving MITO as compared with VEH (P < .001). Pediatric DCD hearts subjected to extended WIT demonstrated significantly preserved fractional shortening and significantly decreased infarct size with MITO (P < .01 each vs VEH). CONCLUSIONS: Mitochondrial transplantation in neonatal and pediatric pig DCD heart donation significantly enhances the preservation of myocardial function and viability and mitigates against damage secondary to extended WIT.

Hybrid Left Heart Bypass Circuit for Repair of the Descending Aorta in an 8-kg Williams Syndrome Patient.

A 1-year old male patient with Williams syndrome and multiple prior interventions presented for surgical repair of his descending aorta (DA) through a left thoracotomy. Concerns for significant bleeding and spinal cord protection led the care team to consider a left heart bypass (LHB) circuit with options for pump sucker use, heat exchange capacity, and the possibility of converting to traditional cardiopulmonary bypass (CPB). A traditional CPB circuit with a roller-head arterial pump was assembled with a bypass line around the cardiotomy venous reservoir (CVR). Excluding the CVR with this line allowed for a closed LHB circuit. A second pump head was integrated to both recirculate the CVR volume and to serve as a means for controlled volume administration to the closed LHB circuit. Pump sucker return directed to the CVR could easily be transfused back to the patient. The patient was placed on the hybrid LHB circuit and cooled to 32°C. DA clamps were placed. Upper body dynamic blood pressure was managed for a target mean of 50 mmHg, the left atrial pressure (LAP) was maintained in the 5-7 mmHg range, and the nonpulsatile lower body blood pressure was targeted at 40-50 mmHg. Cerebral near-infrared spectroscopy (NIRS) helped guide volume and pressure management. The surgeons placed two long-segment patches on the DA, moving clamps as needed. The patient was rewarmed and separated from the hybrid LHB circuit after 82 minutes. Closed circuit LHB can be provided with a roller-head hybrid circuit incorporating an oxygenator for gas exchange, central cooling and warming, and arterial line filtration along with a CVR for pump sucker use and controlled transfusion to the patient.

A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion.

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP. The ESHP circuit consists of an oxygenator, a heart-lung machine, a heater-cooler unit, an anesthesia gas blender, and a collection funnel. Female Yorkshire pig hearts (n = 10) had del Nido cardioplegia (4°C) administered, excised, and attached to the perfusion system. Hearts were perfused retrogradely into the aortic root for 2 hours before converting the system to an isovolumic mode or a working mode for further 2 hours. Blood samples were analyzed to measure metabolic parameters. During the isovolumic mode (n = 5), a balloon inserted in the left ventricular (LV) cavity was inflated so that an end-diastolic pressure of 6-8 mmHg was reached. During the working mode (n = 5), perfusion in the aortic root was redirected into left atrium (LA) using a compliance chamber which maintained an LA pressure of 6-8 mmHg. Another compliance chamber was used to provide an afterload of 40-50 mmHg. Hemodynamic and metabolic conditions remained stable and consistent for a period of 4 hours of ESHP in both isovolumic mode (LV developed pressure: 101.0 ± 3.5 vs. 99.7 ± 6.8 mmHg, p = .979, at 2 and 4 hours, respectively) and working mode (LV developed pressure: 91.0 ± 2.6 vs. 90.7 ± 2.5 mmHg, p = .942, at 2 and 4 hours, respectively). The present study proposed a novel ESHP system that enables comprehensive functional and metabolic assessment of large mammalian hearts. This system allowed for stable myocardial function for up to 4 hours of perfusion, which would offer great potential for the development of translational therapeutic protocols to improve dysfunctional donated hearts.

Mitochondrial transplantation for myocardial protection in ex-situ‒perfused hearts donated after circulatory death.

BACKGROUND: Donation after circulatory death (DCD) offers an additional source of cardiac allografts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts. METHODS: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a cessation of mechanical ventilation. After 20 minutes of warm ischemia, cardioplegia was administered. The hearts were then reperfused on an ex-situ blood perfusion system. After 15 minutes of reperfusion, hearts received either vehicle alone (vehicle [VEH], 10 ml; n = 8) or vehicle containing autologous mitochondria (vehicle with mitochondria as a single injection [MT], 5 × 109 in 10 ml, n = 8). Another group of hearts (serial injection of mitochondria [MTS]; n = 6) received a second injection of mitochondria (5 × 109 in 10 ml) after 2 hours of ex-situ heart perfusion and reperfused for an additional 2 hours. A Sham group (sham hearts; n = 6) did not undergo any warm ischemia. RESULTS: At the end of 4 hours of reperfusion, MT and MTS groups showed a significantly increased left ventricle/ventricular peak developed pressure (p = 0.002), maximal left ventricle/ventricular pressure rise (p < 0.001), fractional shortening (p < 0.001), and myocardial oxygen consumption (p = 0.004) compared with VEH. Infarct size was significantly decreased in MT and MTS groups compared with VEH (p < 0.001). No differences were found in arterial lactate levels among or within groups throughout reperfusion. CONCLUSIONS: Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing a possible option for expanding the heart donor pool.

Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine.

This study used a swine model of mildly hypothermic prolonged circulatory arrest and found that the addition of 2.4% inhaled hydrogen gas to inspiratory gases during and after the ischemic insult significantly decreased neurologic and renal injury compared with controls. With proper precautions, inhalational hydrogen may be administered safely through conventional ventilators and may represent a complementary therapy that can be easily incorporated into current workflows. In the future, inhaled hydrogen may diminish the sequelae of ischemia that occurs in congenital heart surgery, cardiac arrest, extracorporeal life-support events, acute myocardial infarction, stroke, and organ transplantation.

A novel wall water system for cardiopulmonary bypass may reduce the risk of aerosolized infection.

OBJECTIVE: Oxygenators for cardiopulmonary bypass require water flow for their integral heat exchanger. Heater-cooler units are nearly universally used for this requirement. Heater-cooler units pose the risk of aerosolized infection. The Centers for Disease Control and Prevention recommended discontinuing use of Stöckert 3T heater-cooler units (LivaNova PLC, London, United Kingdom) in October 2016 because of this risk. We aimed to reduce the risk of aerosolized infection posed by heater-cooler units by eliminating those devices from our operating rooms. METHODS: The cardiac surgery division collaborated with in-house specialties to engineer a novel wall water system. The design called for service to 4 operating rooms with the actual water mixing valve in an operating room closet. Remote temperature control was mounted next to the heart-lung machine. Primary safety systems built into the water system include 5 µm filtration, pressure regulating and relief valves, flow quantifiers, limits to the hot and chilled input temperatures, and a novel bridge near the heart-lung machine that allows the perfusionist to test the system before patient use and to quickly disconnect the patient in case of system malfunction. In addition, all water line connections can be made with the tubing drained and never under pressure. RESULTS: This novel wall water system has successfully provided heat exchanger water flow on 625 patients undergoing congenital heart surgery requiring cardiopulmonary bypass during its first 9 months of use. CONCLUSIONS: Wall water systems are an option for oxygenator heat exchangers that allow for improved heat exchange performance while reducing the risk of heater-cooler unit-associated infection during cardiac surgery.

Comparison of two pediatric cases requiring the use of bivalirudin during cardiopulmonary bypass.

INTRODUCTION: Comparison of two pediatric cases at our institution that utilized bivalirudin for anticoagulation on cardiopulmonary bypass (CPB); a bilateral lung transplant (BLT) and a ventricular assist device (VAD) implantation. METHODS: The same bivalirudin protocol was utilized in both cases with an initial bolus of 1 mg/kg administered by the anesthesia team, a 50 mg bolus in the pump prime at the time of the initial patient bolus and an initial infusion rate of 2.5 mg/kg/h, with titration as needed during CPB to maintain kaolin-activated clotting time (K-ACT) values >400 s. RESULTS: The BLT experienced high K-ACT levels (>720 s) for the majority of the case despite decreasing the bivalirudin infusion rate to 0.5 mg/kg/h. The VAD implantation case required the bivalirudin infusion rate to be increased to 5.0 mg/kg/h throughout the case due to low K-ACTs. CONCLUSION: The literature strongly supports a specific infusion rate1-7 (2.5 mg/kg/h) for bivalirudin anticoagulation during extracorporeal circulation. Clinicians must consider the loss of clotting factors and the administration of blood products while adjusting the bivalirudin infusion during bypass. We have now elected to maintain an infusion rate of ≥0.5 mg/kg/h for bivalirudin anticoagulation at our center, based on institutional experience, though consideration for a higher infusion rate for an added margin of safety should be considered. It is imperative to have a well-developed protocol for the management of these cardiopulmonary bypass patients and we offer our one-page timeline of events to help guide other pediatric centers looking to use bivalirudin anticoagulation.