Assessment of donor heart viability during ex vivo heart perfusion

Abstract

Ex vivo heart perfusion (EVHP) may facilitate resuscitation of discarded donor hearts and expand the donor pool; however, a reliable means of demonstrating organ viability prior to transplantation is required. Therefore, we sought to identify metabolic and functional parameters that predict myocardial performance during EVHP. To evaluate the parameters over a broad spectrum of organ function, we obtained hearts from 9 normal pigs and 37 donation after circulatory death pigs and perfused them ex vivo. Functional parameters obtained from a left ventricular conductance catheter, oxygen consumption, coronary vascular resistance, and lactate concentration were measured, and linear regression analyses were performed to identify which parameters best correlated with myocardial performance (cardiac index: mL·min(-1)·g(-1)). Functional parameters exhibited excellent correlation with myocardial performance and demonstrated high sensitivity and specificity for identifying hearts at risk of poor post-transplant function (ejection fraction: R(2) = 0.80, sensitivity = 1.00, specificity = 0.85; stroke work: R(2) = 0.76, sensitivity = 1.00, specificity = 0.77; minimum dP/dt: R(2) = 0.74, sensitivity = 1.00, specificity = 0.54; tau: R(2) = 0.51, sensitivity = 1.00, specificity = 0.92), whereas metabolic parameters were limited in their ability to predict myocardial performance (oxygen consumption: R(2) = 0.28; coronary vascular resistance: R(2) = 0.20; lactate concentration: R(2) = 0.02). We concluded that evaluation of functional parameters provides the best assessment of myocardial performance during EVHP, which highlights the need for an EVHP device capable of assessing the donor heart in a physiologic working mode.

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

“…Hypothermic machine perfusion can maintain stable oxygen consumption with low lactate accumulation in multiple human and animal models of long‐term perfusion preservation (12‐24 h of perfusion) and models of DCDD donation . Cardiac function after transplantation in these models was excellent, whereas organs preserved by hypothermic static storage in these studies typically failed . Edema formation during the perfusion interval has been reported with this strategy but has not resulted in adverse outcomes after reperfusion …”

“…Additionally, cardiac allografts can be “conditioned” prior to transplantation by addition of therapeutic drugs, cytokines, gene products, or other agents. Perfusion devices also monitor a number of parameters and allow for adjustments of perfusion conditions to optimally preserve the organ . Together, these advantages can lead to improved outcomes of transplants from standard criteria donors, marginal donors and even donors not considered recoverable by hypothermic static storage, such as donation after circulatory determination of death (DCDD).…”

“…Perfusion devices also monitor a number of parameters and allow for adjustments of perfusion conditions to optimally preserve the organ. 32,33 Together, these advantages can lead to improved outcomes of transplants from standard criteria donors, marginal donors and even donors not considered recoverable by hypothermic static storage, such as donation after circulatory determination of death (DCDD). These benefits are summarized in Figure 1.…”

Opportunities for Therapeutic Intervention During Machine Perfusion

“…A variety of criteria have been suggested for assessment of human livers during MP, including the cumulative amount and the rate of bile production during NMP [3] or energy charge during SNMP [24]. In an experimental study on NMP of porcine DCD hearts, one group found that stroke work, ejection fraction and minimum rate of diastolic pressure change were more reliable predictors of organ viability and function than coronary vascular resistance (CVR), myocardial oxygen consumption (MVO 2 ) and venoarterial lactate difference [25]. Barlow et al were the first to show the feasibility of ex-situ NMP to assess the viability and function of declined human pancreas for transplantation based on pancreas blood flow, exocrine function indicated by insulin secretion and endocrine function indicated by lipase and amylase secretion [6].…”

The implications of brain death in donor lung injury: investigation and blockade of the endothelin axis

“…Similar to EVLP techniques described above, it is also possible to assess the effects of endothelin antagonism on cardiac function using an ex-vivo heart perfusion technique. [371] Our group has recently acquired such a device to use in the ovine brain death model.…”