Hearts Donated After Circulatory Death and Reconditioned Using Normothermic Regional Perfusion Can Be Successfully Transplanted Following an Extended Period of Static Storage

Abstract

Background: There has been an increased interest in donation after circulatory death (DCD) to expand donor pool for cardiac transplantation. Normothermic regional perfusion (NRP) allows in situ assessment of DCD hearts, allowing only acceptable organs to be procured. We sought to determine if extended cold storage was possible for DCD hearts following NRP and to compare hearts stored using standard cold storage with a novel cardioprotective solution designed for room temperature storage. Methods and Results: Donor pigs underwent hypoxic cardiac arrest (DCD) followed by 15 minutes of warm ischemia and resuscitation on NRP. They were then randomly assigned to static storage with histidine-tryptophan-ketoglutarate (HTK) at 4°C (HTK group, n=5) or SOM-TRN-001 at 21°C (SOM group, n=5). Conventional beating-heart donations were used as controls (n=4). Fourteen transplants were successfully performed. HTK hearts showed initial dysfunction following reperfusion; however, they demonstrated significant recovery up to 3 hours post-transplant. No significant differences were seen between HTK and control hearts post-transplantation (cardiac index: control 49.5±6% and HTK 48.5±5% of baseline). SOM improved myocardial preservation; hearts showed stable contractility after transplantation (cardiac index: 113.0±43% of NRP function) and improved diastolic function compared with HTK. Preservation in SOM also significantly reduced proinflammatory cytokine production and release following transplantation and partially prevented endothelial dysfunction. Conclusions: DCD hearts stored using a standard preservation solution demonstrated comparable post-transplantation myocardial function to standard controls. Thus, short periods of cold storage following successful NRP and documented adequate function is an acceptable strategy for DCD hearts. Preservation in SOM at room temperature is feasible and can improve cardiac recovery by minimizing endothelial dysfunction and tissue injury.

Ice, ice, maybe? Is it time to ditch the igloo cooler? Benefits of machine perfusion preservation of donor hearts

“…The ability to affect donor organ physiology is extensive, not only by adjustments of perfusion parameters, but also infusion of inotropes, substrates, or hormonal manipulation, for example . Donor organ evaluation during perfusion may even include echocardiography or cardiac catheterization . Device operation is more complex than for hypothermic perfusion preservation devices and usually requires additional team members than just the recovering surgeon.…”

“…48 Donor organ evaluation during perfusion may even include echocardiography or cardiac catheterization. 49,50 Device operation is more complex than for hypothermic perfusion preservation devices and usually requires additional team members than just the recovering surgeon. While devices are relatively mobile, they may require special accommodations when transported by air or ground.…”

Heart donation and transplantation after circulatory determination of death: expert guidance from a Canadian consensus building process

“…4,5 In the UK, the definition of death is brain-based; as long as NRP does not restore brainstem perfusion after death has been confirmed then it is consistent with laws for death determination 6 and NRP. 8 Canadian Blood Services and Trillium Gift of Life Network collaborated to organize a two-day consensus building process, held on 15-16 October 2018, for relevant stakeholders to develop expert guidance for the possible implementation of DCD heart donation in Canada.…”

Commentary: The next chapter in donor heart preservation: Modulation of preservation biology by targeted molecular therapies

“…Current clinical DCD logistics involve cardioplegic arrest of the donor heart with subsequent mechanical normothermic perfusion ex vivo or in vivo using regional perfusion techniques. 10 The heart is Inflammasome inhibition improves murine DCD heart function. Translation to clinical practice requires identifying FDA-approved NLRP3 inhibitors and showing efficacy in large animal and human hearts.…”

“…Current clinical DCD logistics involve cardioplegic arrest of the donor heart with subsequent mechanical normothermic perfusion ex vivo or in vivo using regional perfusion techniques. 10 The heart is then assessed and/or transported for a variable time and then rearrested for implant into the recipient. Future experimental model will likely benefit from modeling this process because the duration of normothermic perfusion, ex vivo versus in vivo perfusion, and the influence of 2 cold cardioplegic arrest episodes all likely influence transplanted graft function.…”