Twenty-four-hour Normothermic Ex Vivo Heart Perfusion With Low Flow Functional Assessment in an Adult Porcine Model.

BACKGROUND: Cold static storage and normothermic ex vivo heart perfusion are routinely limited to 6 h. This report describes intermittent left atrial (LA) perfusion that allows cardiac functional assessment in a working heart mode. METHODS: Using our adult porcine model, general anesthesia was induced and a complete cardiectomy was performed following cardioplegic arrest. Back-table instrumentation was completed and normothermic ex vivo heart perfusion (NEHP) was initiated in a nonworking heart mode (Langendorff). After 1 h of resuscitation and recovery, LA perfusion was initiated and the heart was transitioned to a coronary flow-only working heart mode for 30 min. Baseline working heart parameters were documented and the heart was returned to nonworking mode. Working heart assessments were performed for 30 min every 6 h for 24 h. RESULTS: Twenty-four-hour NEHP on 9 consecutive hearts (280 ±â€…42.1 g) was successful and no significant differences were found between working heart parameters at baseline and after 24 h of perfusion. There was no difference between initial and final measurements of LA mean pressures (5.0 ±â€…3.1 versus 9.0 ±â€…6.5 mm Hg, P  = 0.22), left ventricular systolic pressures (44.3 ±â€…7.2 versus 39.1 ±â€…9.0 mm Hg, P  = 0.13), mean aortic pressures (30.9 ±â€…5.8 versus 28.1 ±â€…8.1 mm Hg, P  = 0.37), and coronary resistance (0.174 ±â€…0.046 versus 0.173 ±â€…0.066 mL/min/g, P  = 0.90). There were also no significant differences between lactate (2.4 ±â€…0.5 versus 2.6 ±â€…0.4 mmol/L, P  = 0.17) and glucose (173 ±â€…75 versus 156 ±â€…70 mg/dL, P  = 0.37). CONCLUSIONS: A novel model using intermittent LA perfusion to create a coronary flow-only working heart mode for assessment of ex vivo cardiac function has been successfully developed.

Twenty-Four Hour Normothermic Ex Vivo Heart Perfusion With Hemofiltration In an Adult Porcine Model.

BACKGROUND: Historically, cardiac transplantation relied on cold static storage at 5 °C for ex vivo myocardial preservation. Currently, machine perfusion is the standard of care at many transplant centers. These storage methods are limited to 12 hours. We sought to evaluate the efficacy of hemofiltration and filtrate replacement in adult porcine hearts using normothermic heart perfusion (NEVHP) for 24 hours. METHODS: We performed 24-hour NEVHP on 5 consecutive hearts. After anesthetic induction, sternotomy, cardioplegia administration, explantation, and back-table instrumentation, NEVHP was initiated in beating, unloaded mode. After 1 hour, plasma exchange was performed, and hemofiltration was initiated. Heart function parameters and arterial blood gasses were obtained hourly. RESULTS: All hearts (n = 5) were viable at the 24-hour mark. The average left ventricular systolic pressure at the beginning of the prep was 36.6 ± 7.9 mm Hg compared with 27 ± 5.5 mm Hg at the end. Coronary resistance at the beginning of prep was 0.79 ± 0.10 mm Hg/L/min and 0.93 ± 0.28 mm Hg/L/min at the end. Glucose levels averaged 223 ± 13.9 mg/dL, and the lactate average at the termination of prep was 2.6 ± 0.3 mmol/L. CONCLUSIONS: We successfully perfused adult porcine hearts at normothermic temperatures for 24 hours with results comparable to our pediatric porcine heart model. The next step in our research is NEVHP evaluation in a working mode using left atrial perfusion.

Successful Porcine Renal Transplantation After 60 Minutes of Donor Warm Ischemia: Extracorporeal Perfusion and Thrombolytics.

Donation from uncontrolled circulatory determination of death donors (uDCD) is impractical in United States because of the time needed to organize procurement before irreversible organ damage. Salvaging organs after prolonged warm ischemic time (WIT) may address this limitation. We evaluated the combination of extracorporeal support (ECS) and thrombolytics in a porcine uDCD renal transplant model. Nonanticoagulated uDCD sustained 60 min of WIT, and two groups were studied. Rapid recovery (RR)-uDCD renal grafts procured using the standard quick topical cooling and renal flush, and ECS-assisted donation (E-uDCD), 4 hr ECS plus thrombolytics for in situ perfusion before procurement. All kidneys were flushed and cold stored, followed by transplantation into healthy nephrectomized recipients without immunosuppression. Delayed graft function (DGF) was defined as creatinine more than 5.0 mg/dl on any postoperative day. Twelve kidneys in E-uDCD and 6 in RR-uDCD group were transplanted. All 12 E-uDCD recipients had urine production and adequate function in the first 48 hr, but two grafts (16.7%) had DGF at 96 hr. All six recipients from RR-uDCD group had DGF at 48 hr and were killed. Creatinine and blood urea nitrogen (BUN) levels were significantly lower in E-uDCD compared with RR-uDCD group at 24 hr (2.9 ± 0.7 mg/dl vs. 5.2 ± 0.9 mg/dl) and 48 hr (3.2 ± 0.9 mg/dl vs. 7.2 ± 1.0 mg/dl); BUN levels at 24 and 48 hr were 28.3 ± 6.7 mg/dl vs. 39.5 ± 7.5 mg/dl and 23.9 ± 5.0 mg/dl vs. 46 ± 12.9 mg/dl, respectively. Thrombolytics plus ECS precondition organs in situ yielding functional kidneys in a porcine model of uDCD with 60 min of WIT. This procurement method addresses logistical limitations for uDCD use in the United States and could have a major impact on the organ donor pool.

In vivo testing of a novel blood pump for short-term extracorporeal life support.

BACKGROUND: Centrifugal pumps are used increasingly for temporary mechanical support for the treatment of cardiogenic shock. However, centrifugal pumps can generate excessive negative pressure and are afterload sensitive. A previously developed modified roller pump mitigates these limitations both in vitro and in preliminary animal experiments. We report the results of intermediate-term testing of our evolving pump technology, known as the BioVAD. METHODS: The BioVAD was implanted in 6 adult male sheep (62.5±3.9 kg), with drainage from the left atrium and reinfusion into the descending aorta. The sheep were monitored for 5 days. Heparin was given during the initial implantation, but no additional anticoagulants were given. Data collected included hemodynamic status, pump flow and pressures, laboratory values to monitor end-organ function and hemolysis, pathologic specimens to evaluate for thromboembolic events and organ ischemia, and explanted pump evaluation results. RESULTS: All animals survived the planned experimental duration and there were no pump malfunctions. Mean BioVAD flow was 3.57±0.30 L/min (57.1 mL/kg/min) and mean inlet pressure was -30.51±4.25 mm Hg. Laboratory values, including plasma free hemoglobin, creatinine, lactate, and bilirubin levels, remained normal. Three animals had small renal cortical infarcts, but there were no additional thromboembolic events or other abnormalities seen on pathologic examination. No thrombus was identified in the BioVAD blood flow path. CONCLUSIONS: The BioVAD performed well for 5 days in this animal model of temporary left ventricular assistance. Its potential advantages over centrifugal pumps may make it applicable for short-term mechanical circulatory support.

A novel rotary pulsatile flow pump for cardiopulmonary bypass.

It has been suggested that pulsatile blood flow is superior to continuous flow (CF) in cardiopulmonary bypass (CPB). However, adoption of pulsatile flow (PF) technology has been limited because of practicality and complexity of creating a consistent physiologic pulse. A pediatric pulsatile rotary ventricular pump (PRVP) was designed to address this problem. We evaluated the PRVP in an animal model and determined its ability to generate PF during CPB. The PRVP (modified peristaltic pump, with tapering of the outlet of the pump chamber) was tested in four piglets (10-12 kg). Cannulation was performed with right atrial and aortic cannulae, and pressure sensors were inserted into the femoral arteries. Pressure curves were obtained at different levels of flow and compared with both the animal's baseline physiologic function and a CF roller pump. Pressure and flow waveforms demonstrated significant pulsatility in the PRVP setup compared with CF at all tested conditions. Measurement of hemodynamic energy data, including the percentage pulsatile energy and the surplus hydraulic energy, also revealed a significant increase in pulsatility with the PRVP (p < 0.001). The PRVP creates physiologically significant PF, similar to the pulsatility of a native heart, and has the potential to be easily implemented in pediatric CPB.

In vitro testing of a novel blood pump designed for temporary extracorporeal support.

Extracorporeal blood pumps are used as temporary ventricular assist devices or for extracorporeal membrane oxygenation. The ideal pump would be intrinsically self-regulating, carry no risk of cavitation or excessive inlet suction, be afterload insensitive, and valveless thus reducing thrombogenicity. Currently used technology, including roller, centrifugal, and pneumatic pulsatile pumps, does not meet these requirements. We studied a nonocclusive peristaltic pump (M-Pump) in two mock circulatory loops and compared the performance to a frequently used centrifugal pump and a modified prototype of the M-Pump (the BioVAD). The simple resistance loop consisted of the investigated pump, a fixed height reservoir at 150 mm Hg, and a variable inflow reservoir. The pulsatile circulation used a mock patient simulator with adjustable resistance elements connected to a pneumatic pulsatile pump. The M-Pump intrinsically regulated flow with changing preload, was afterload insensitive, and did not cavitate, unlike the centrifugal pump. The BioVAD also demonstrated these features and could augment output with the use of vacuum assistance. A nonocclusive peristaltic pump may be superior for short-term extracorporeal circulatory assist by mitigating risks of excessive inlet suction, afterload sensitivity, and thrombosis.

Preliminary in vivo testing of a novel pump for short-term extracorporeal life support.

BACKGROUND: Blood pumps used for temporary circulatory support have limitations. We propose a novel device designed for short-term extracorporeal support that is intrinsically volume responsive, afterload insensitive, and incapable of cavitation or excessive hemolysis. After in vitro testing, we performed the initial in vivo implantations and assessments. METHODS: The BioVAD prototype (MC3, Inc, Ann Arbor, MI) was implanted in 6 adult male sheep (60.2±2.8 kg) through the left ventricular apex and descending thoracic aorta. Arterial, left and right atrial, and pump inlet and outlet pressures and BioVAD flow were measured and recorded. The animals were volume loaded to assess volume responsiveness, and the inlet lines were abruptly clamped during maximum support to observe for cavitation. An acute heart failure model was created with rapid ventricular pacing, and the animals were supported for 4 hours. RESULTS: Peak flow was 3.19±0.56 L/min and increased to 3.71±0.53 L/min with 20 mm Hg vacuum-assisted drainage. Without manual changes in pump settings, pump flow increased 17.5% with volume loading. During acute venous line occlusion, there was no evidence of cavitation, and inlet suction was minimal. Hemodynamics were maintained for 4 hours during acute heart failure. CONCLUSIONS: The BioVAD provided adequate flow in an acute in vivo model. Its design may be superior for short-term extracorporeal support.

A novel, low cost, disposable, pediatric pulsatile rotary ventricular pump for cardiac surgery that provides a physiological flow pattern.

Research is underway to develop a novel, low cost, disposable pediatric pulsatile rotary ventricular pump (PRVP) for cardiac surgery that provides a physiological flow pattern. This is believed to offer reduced morbidity and risk exposure within this population. The PRVP will have a durable design suitable for use in short- to mid-length prolonged support after surgery without changing pumps. The design is based on proprietary MC3 technology which provides variable pumping volume per stroke, thereby allowing the pump to respond to hemodynamic status changes of the patient. The novel pump design also possesses safety advantages that prevent retrograde flow, and maintain safe circuit pressures upon occlusion of the inlet and outlet tubing. The design is ideal for simple, safe and natural flow support. Computational methods have been developed that predict output for pump chambers of varying geometry. A scaled chamber and pump head (diameter = 4 in) were prototyped to demonstrate target performance for pediatrics (2 L/min at 100 rpm). A novel means of creating a pulsatile flow and pressure output at constant RPM was developed and demonstrated to create significant surplus hydraulic energy (>10%) in a simplified mock patient circuit.