Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death

Abstract

The resuscitation of hearts donated after circulatory death (DCD) is gaining widespread interest; however, the method of initial reperfusion (IR) that optimizes functional recovery has not been elucidated. We sought to determine the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-min standoff period was observed and then hearts were reperfused for 3 min at three different temperatures (58C; N ¼ 6, 258C; N ¼ 5, and 358C; N ¼ 7) with a normokalemic adenosine-lidocaine crystalloid cardioplegia. Hearts then underwent normothermic EVHP for 6 h during which time myocardial function was assessed in a working mode. We found that IR coronary blood flow differed among treatment groups (58C ¼ 483 AE 53, 258C ¼ 722 AE 60, 358C ¼ 906 AE 36 mL/ min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 58C ¼ 91 AE 6, 258C ¼ 64 AE 16, 358C ¼ 57 AE 7 pg/mL/g, p ¼ 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 58C ¼ 3.2 AE 0.5, 258C ¼ 1.8 AE 0.2, 358C ¼ 1.7 AE 0.3, p ¼ 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 58C ¼ 3.9 AE 0.8, 258C ¼ 6.2 AE 0.4, 358C ¼ 6.5 AE 0.6 mL/minute/g, p ¼ 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts.Abbreviations: C a O 2 , oxygen content in arterial blood (aortic root); C v O 2 , oxygen content in venous blood (pulmonary artery); CBF, coronary blood flow; CVR, coronary vascular resistance; DCD, donation after circulatory death; dP/dt maximum, maximum rate of pressure change in the left ventricle; dP/dt minimum, minimum rate of pressure change in the left ventricle; EVHP, ex vivo heart perfusion; MVO 2 , myocardial oxygen consumption; P a O 2 , partial pressure of oxygen in arterial blood (aortic root); P v O 2 , partial pressure of oxygen in venous blood (pulmonary artery)

Hearts transplanted after circulatory death in children: Analysis of the International Society for Heart and Lung Transplantation registry

“…While this study was not aimed at improving the tolerability of DCD hearts to warm ischemia and performing ex vivo perfusion of hearts for transplantation, there is much research being performed internationally that may eventuate more widespread utilization of DCD HT. 27,28 White et al found that evading profound hypothermia during ischemic reperfusion improves the recovery of DCD hearts. 28 Continuous myocardial perfusion with lukewarm blood cardioplegia solution has been shown to minimize myocardial inflammation.…”

“…27,28 White et al found that evading profound hypothermia during ischemic reperfusion improves the recovery of DCD hearts. 28 Continuous myocardial perfusion with lukewarm blood cardioplegia solution has been shown to minimize myocardial inflammation. 29 Additionally, catecholamines are released by the adrenal medulla and myocardial ischemia associated with warm ischemic time may cause the adrenal medulla to release additional catecholamines intrinsic to the body.…”

Enhanced myocardial protection in cardiac donation after circulatory death using Intralipid® postconditioning in a porcine model

“…5 We have previously shown that controlled initial reperfusion of the DCD heart can result in optimization of functional recovery compared with standard recovery techniques. 6,7 These studies focused on the initial reperfusion period of the donor heart, without subsequent further intervention during EVHP. Nevertheless, pharmacologic postconditioning, which is known to enhance innate endogenous protective cellular mechanisms within the myocardium resulting in improved recovery after IR injury, has not been well explored in the DCD context.…”

“…A previously optimized initial reperfusion protocol with normokalemic adenosine-lidocaine cardioplegic solution and avoidance of hypothermia during initial reperfusion was used as a control/standard treatment. 6,7 We hypothesized that ILE postconditioning would enhance mechanical function of DCD hearts and reduce oxidative and cellular damage even with a previously optimized procurement and preservation protocol. We further hypothesized that ILE postconditioning would elicit all protective signalling features in this large animal modelmimicking conditions closer to the human heart-that we previously reported in small rodent hearts.…”

“…Results Intralipid Ò postconditioning reduced cell membrane damage as assessed by the mean (standard deviation) leakage of myocardial glutathione disulfide (39 (9) nmolÁmg -1 protein vs 19 (7) nmolÁmg -1 protein; P = 0.006), protected LV tissue from protein carbonylation (3.4 [0.6] nmolÁmg -1 protein vs 5.3 [0.9] nmolÁmg -1 protein; P = 0.006), decreased myeloperoxidase activity (35 [8] nmolÁmin -1 Ámg -1 protein vs 75 [11] nmolÁmin -1 Ámg -1 protein; P\0.001), and increased inotropy (maximum rate of rise of LV pressure 2001 [345] mmHgÁsec -1 vs 1584 [192] mmHgÁsec -1 ; P = 0.044). Intralipid Ò postconditioning triggered reactive oxygen species signalling at early reperfusion and activated protection signalling (Akt, signal transducer and activator of transcription 3, and glycogen synthase kinase 3b) in LV tissue, recapitulating all features of ILE-mediated protection reported in small rodent hearts.…”