Prolonged (24-hour) Normothermic ex vivo Heart Perfusion Facilitated by Perfusate Hemofiltration

Abstract

Currently, normothermic ex vivo heart perfusion (NEVHP) is limited to 6-12 hours. NEVHP for 24 hours or more would allow organ treatment, assessment of organ function, and nearperfect recipient matching. We present a model of NEVHP using continuous hemofiltration (HFn) with sustained myocardial viability up to 24 hours. Twenty hearts from 6-10 kg piglets were procured and maintained on our NEVHP circuit. HFn hearts (n = 10) underwent NEVHP with HFn, whereas controls (n = 10) used NEVHP alone. All HFn vs. four controls were viable at 24 h (p = 0.004). At end perfusion, HFn hearts had higher left ventricular systolic pressure (51.5 ± 6.8 mm Hg, 38.3 ± 5.2 mm Hg, p = 0.05), lower coronary resistance (0.83 ± 0.11 mm Hg/mL/min, 1.18 ± 0.21mmHg/mL/min, p < 0.05), and lower serum lactate levels (2.9 ± 0.4 mmol/L, 4.1 ± 0.6 mmol/L, p < 0.0001) when compared to control hearts. HFn hearts also had less extensive myocardial damage and significantly less edema than control hearts with lower weight gain and wet-dry ratios. Using our circuit, NEVHP for 24 hours is possible with HFn and allows for preservation of myocardial function, improved tissue viability, decreased tissue edema, and less myocardial injury.

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

“…The surgical procedure was previously described by Tchouta et al and Johnson et al 14,15 A brief description is as follows. All animals underwent general anesthesia using Telazol (tiletamine and zolazepam; 7 mg/kg) combined with xylazine (3 mg/kg) and were given antibiotics (nafcillin 25 mg/kg and gentamicin 2.25 mg/kg) before surgical incision.…”

“…Representative 1 cm 3 samples from all 4 heart chambers were examined and scored by a blinded veterinary pathologist using a previously described myocardial injury scoring system. 15 Injury scores range from 0 to 3 based on myofiber degeneration, myocardial hemorrhage, interstitial edema, and endothelial changes, with 0 representing no damage and 3 representing being severe. Average tissue injury scores were reported.…”

Thoracic organ machine perfusion: A review of concepts with a focus on reconditioning therapies

“…For ESHP, Johnson et al reports that in comparison to controls, hearts subjected to continuous hemofiltration during ESHP showed decreased edema, reduced histological damage scoring, and a lack of increase in coronary resistance. It may be that hemofiltration removed edema-inducing factors which decreased coronary occlusion, therefore mitigating anaerobic respiration and myocardial damage over the course of the run (130). The prospect of hemofiltration in combatting induced edema has also been studied in the context of the lungs, where hyper concentration of the perfusate by continuous hemofiltration without fluid replacement was able to mediate up to a third reduction in gained lung fluid, though did not affect P/F ratios (131).…”

Artificial Intelligence-Assisted Strain Echocardiography in an Ex Vivo Heart

“…We developed a prolonged normothermic ex vivo heart perfusion (NEVHP) model that maintains cardiac function for 24 hours or longer. 2,3 These studies have led to successful transplantation following 24 hours of NEVHP. Prolonged NEVHP requires meticulous antisepsis.…”

“…The heart was connected to a perfusion circuit. 3 Reperfusion and rewarming were initiated in the nonworking heart mode and, following recovery, the circuit was transitioned to working mode (Figure 1 and Video 2, Supplemental Digital Content). Imaging was performed after prolonged NEVHP with the heart immersed in saline (Supplementary Figure S1, http://links.lww.com/ ASAIO/B56).…”