Successful Resuscitation of Porcine Hearts After 12 and 24 h of Static Cold Storage With Normothermic Ex Situ Perfusion.

Background: Heart transplantation is always an emergency because the transplant needs to occur within 6 h after procurement to prevent primary graft dysfunction. Static cold storage (SCS) is the gold-standard preservation method. This study describes the outcomes of hearts preserved after prolonged SCS (12 and 24 h); those are then resuscitated with a novel normothermic ex situ heart perfusion (NEHP) system. Methods: Anesthetized piglets (n = 10) were used as heart donors. Hearts were procured and stored at 5 °C CoStorSol following standard SCS protocols. Two groups were studied: SCS-12 h and SCS-24 h. After SCS, 8 h of NEHP (37 °C blood-based perfusate) was performed at 0.7-1.0 mL/min/g of cardiac tissue. NEHP parameters were monitored continuously. Results were corroborated with 3 additional hearts transplanted orthotopically in healthy recipients (n = 3) after SCS (24 h) + NEHP (5 h). Recipients were observed for 90 min after weaning off cardiopulmonary bypass support. Results: All hearts (after 12 and 24 h of SCS) regained normal function and metabolism within 10 min and retained it throughout 8 h of NEHP. No differences were observed in NEHP parameters and histopathology between groups. Three hearts were successfully transplanted after a total ~30 h of preservation (24 h of SCS + 5 h of NEHP + 1 h of second cold ischemia time). The 3 recipients were weaned off cardiopulmonary bypass with mild vasopressor support. Conclusions: NEHP has the potential to routinely resuscitate porcine hearts that have undergone SCS for up to 24 h, restoring them to viable function. By objectively assessing heart function before transplant, NEHP may enhance the success rate of transplants. If these resuscitated hearts can be successfully transplanted, it would support the effectiveness of NEHP in ensuring heart viability.

Extending heart preservation to 24†h with normothermic perfusion.

Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts (n = 42) of different sizes (6-55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions (n = 15); (2) NEHP + plasma exchange (n = 5); (3) NEHP + hemofiltration (n = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration (n = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion (n = 7). All hearts with NEHP + interventions (n = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group (n = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies.

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.