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Background: The donor shortage poses a major limitation to use of heart transplantation. Novel strategies such as use of expanded-criteria donors with prolonged ischemia times are being employed to address this need. Recent developments in static hypothermia have allowed for the safe use of cardiac allografts with prolonged ischemic times., Case Report: We present the case of a 68-year-old woman with valvular cardiomyopathy refractory to medical therapy who underwent orthotopic heart transplantation with a cardiac allograft exposed to elevated ischemic times. This was achieved through use of the federally approved SherpaPak Cardiac Transport System for transportation of the allograft. This method of static hypothermic organ preservation allowed for a 330-minute total ischemic time, including 283 minutes of storage within the preservation system. The patient tolerated the procedure well and was discharged on postoperative day 10, with excellent graft function and no evidence of rejection 3 months postoperatively., Conclusions: Though traditionally ischemic times of 240 minutes or less are recommended for cardiac allografts, we demonstrate, to our knowledge, the longest reported ischemic time of 330 minutes via use of a novel method of static hypothermia for organ preservation. The recipient had an excellent outcome postoperatively, demonstrating the potential for this new organ preservation system to expand the donor pool and improve access and use of heart transplantation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Lazaroid, an inhibitor of iron-mediated lipid peroxidation, has been shown to reduce free radical-mediated injury after ischemia and reperfusion. The effect of Lazaroid U-74389G was investigated on ischemia-reperfusion injury of the heart through preservation and transplantation (Tx) in dogs., Methods: Eleven pairs of adult mongrel dogs weighing 8.5 to 12 kg formed the recipient-donor combinations. Following electromechanical arrest of the heart using cardioplegia, the coronary vascular beds were washed out with a cold University of Wisconsin solution followed by 12-hour preservation and orthotopic Tx. Experimental animals were divided into 2 groups; 6 pairs formed the control group, and 5 formed the Lazaroid-treated group in which Lazaroid U-74389G at 10 mg/kg was administered intravenously 30 minutes before reperfusion of the heart. The cardiac function including cardiac output, left ventricular (LV) pressure, and LV dp/dt was assessed 2 hours after Tx by comparing it with the recovery rates (%) from cardiac function of donor dogs. Each transplanted heart was harvested for histological study., Results: The recovery of cardiac function after Tx was significantly better in the Lazaroid-treated group than in the control group. Histologically, myocardial damage, evaluated by both light and transmission electron microscopy, was less evident in the Lazaroid-treated group than in the control group., Conclusion: Early cardiac function following Tx was significantly better and histological damage was less in the Lazaroid-treated group than in the control group, suggesting that Lazaroid U-74389G is effective in preventing ischemia-reperfusion injury after preservation and Tx.

Background: Ischemia-reperfusion injury may result in the local release of proinflammatory cytokines. A newly synthesized organic compound, FR167653, has been characterized as a potent suppressant of interleukin-1beta and tumor necrosis factor-alpha. We investigated the effects of FR 167653 on ischemia-reperfusion injury of canine hearts during preservation and transplantation., Methods: Seventeen pairs of adult mongrel dogs were used. The donor heart was removed, stored in University of Wisconsin solution at 4 degrees C for 12 hours, and then transplanted orthotopically. Recipients were divided into the FR-treated group (FR167653 1 mg/kg/hr, 8 dogs) and the control group (9 dogs). Hemodynamic parameters, including cardiac output, left ventricular pressure (LVP), and the maximum rate of increase of LVP, were assessed after 120 minutes of reperfusion. The heart specimen was then harvested for histopathologic examination., Results: The values of LVP (mm Hg) of the FR-treated and the control groups were 120+/-10 and 79+/-9, respectively. The values of LV dp/dt (mm Hg/sec) in the FR-treated and control groups were 4944+/-414 and 2292+/-380, respectively. There were significant differences in LVP (P < .05) and the maximum rate of increase of LVP (P < .01) between the two groups. The values of cardiac output (L/min) of the FR-treated and control groups were 1.27+/-0.12 and 0.71+/-0.11 of the baseline, respectively, showing a significant difference (P < .05) between the two groups. Histopathologic findings included irregular glycogen distribution in myocardial cells of the control group, although this change was less frequent in the FR-treated group., Conclusion: FR 167653 seems to have a protective effect on tissue subjected to ischemia-reperfusion injury during the acute phase after heart transplantation.

Improvement in preservation and transportation conditions has the potential to enhance organ quality at the time of transplant, optimize patient outcomes, and prolong the acceptable maximum allograft ischemic time. Herein, we describe our initial successful experience with the static hypothermic preservation system (Paragonix) for a donor heart. Our storage period and allograft ischemic time are the longest reported in the literature. A 68-year-old woman with HF was listed for transplantation. A donor heart was procured from a hospital located 3.5 hours away. The donor allograft was secured and packaged using the SherpaPak™ device (Fig. 1) ; total storage period was 283 mins. Heart transplantation was performed in standard fashion. AV conduction and normal sinus rhythm were regained after 7 mins of reperfusion. Total ischemic time was 330 mins, including a warm ischemic time of 20 minutes. The recipient CPB time and aortic cross clamp time were 153 and 50 mins, respectively. The patient recovered well and was discharged on postoperative day 10. At three months post-transplant, the patient continues to have excellent graft function without any evidence of rejection. Historically, Shumway et al. initially obtained donor hearts from operating rooms immediately adjacent to a recipient. Over time, donor distance and allograft ischemic times have increased with advances in cardiac preservation. However, long cold ischemic times may induce PGD, cardiac allograft vasculopathy, and contribute to increased length of stay. Maintaining storage temperatures within the narrow range of 4-8°C is optimal for the preservation of high energy phosphate stores and avoids the risk of cold ischemic injury at temperatures below 2°C. By expanding geographic boundaries and total ischemic times, we believe that regulated static hypothermic preservation is a useful addition to a growing armamentarium of devices and strategies to increase access to transplantation. [ABSTRACT FROM AUTHOR]

Traditionally, after procurement, donor hearts are cooled with ice during transport to the transplant center. However, this can lead to uneven cooling and can result in tissue injury, which may affect subsequent allograft function. The utilization of a hypothermic preservation system (SherpaPak, Paragonix) results in controlled and uniform cooling. This approach may enable longer-distance procurements and may result in better allograft function after transplant. A single center study of heart transplantation using donor hearts transported on ice from 1/1/19-07/16/20 compared to a hypothermic preservation system (Sherpa) from 7/17/20-6/13/21. Patients were assessed for primary graft dysfunction (PGD), defined as requiring any mechanical circulatory support, length of stay (LOS) after transplant, graft function and one year survival. There were a total of 115 patients, 56 (49%) transported with Ice and 59 (51%) with Sherpa. There were no differences in recipient's baseline demographics: mean age (54 years), male (79%), and nonischemic (61%), but a higher use of LVAD in the Ice v Sherpa (18% v. 5%, p=0.03). Donor characteristics were similar: age (35 years), male (68%), white (59%), and cause of death (anoxia 38%, head trauma 41%, stroke 17%). The median post-transplant LOS was 20 days and not different between groups. Despite a longer ischemic time for the Sherpa v Ice transport (255 v. 230 minutes, p=0.021), there were no differences in incidence of PGD (17% v. 14%, p=0.69); median ejection fraction at 6 months (61%) and 12 months (61%); and 1 year patient survival (91% v. 95%, p=0.45), Figure 1a/b. The use of a hypothermic preservation system results in similar one year patient survival and graft function, incidence of PGD, and hospital LOS, despite longer ischemic times. Use of this system safely enables more distant donor heart procurement. [ABSTRACT FROM AUTHOR]