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

C W White; E Ambrose; A Müller; Y Li; H Le; J Thliveris; R C Arora; T W Lee; I M C Dixon; G Tian; J Nagendran; L V Hryshko; D H Freed

doi:10.1111/ajt.13574

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

Am J Transplant. 2016 Mar;16(3):773-82. doi: 10.1111/ajt.13574. Epub 2016 Jan 18.

Authors

C W White^{1

2

3}, E Ambrose^{2

3}, A Müller⁴, Y Li², H Le², J Thliveris⁵, R C Arora^{1

2}, T W Lee⁶, I M C Dixon^{2

3}, G Tian^{3

7}, J Nagendran⁸, L V Hryshko^{2

3}, D H Freed^{2

3

4

8

9}

Affiliations

¹ Cardiac Surgery, University of Manitoba, Winnipeg, Canada.
² Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Canada.
³ Departments of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada.
⁴ Department of Physiology, University of Alberta, Edmonton, Canada.
⁵ Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.
⁶ Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Canada.
⁷ National Research Council Institute for Biodiagnostics, Winnipeg, Canada.
⁸ Cardiac Surgery, University of Alberta, Edmonton, Canada.
⁹ Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.

PMID: 26780159
DOI: 10.1111/ajt.13574

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 (5°C; N = 6, 25°C; N = 5, and 35°C; N = 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 (5°C = 483 ± 53, 25°C = 722 ± 60, 35°C = 906 ± 36 mL/min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 5°C = 91 ± 6, 25°C = 64 ± 16, 35°C = 57 ± 7 pg/mL/g, p = 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 5°C = 3.2 ± 0.5, 25°C = 1.8 ± 0.2, 35°C = 1.7 ± 0.3, p = 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 5°C = 3.9 ± 0.8, 25°C = 6.2 ± 0.4, 35°C = 6.5 ± 0.6 mL/minute/g, p = 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts.

Keywords: basic (laboratory) research / science; heart (allograft) function / dysfunction; heart transplantation / cardiology; ischemia reperfusion injury (IRI); organ perfusion and preservation; organ procurement; organ procurement and allocation; organ transplantation in general donors and donation: donation after circulatory death (DCD); translational research / science.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Heart / physiology*
Heart Arrest, Induced
Heart Transplantation
Hypothermia / prevention & control*
Myocardial Ischemia / therapy*
Myocardial Reperfusion / methods*
Organ Preservation / methods*
Recovery of Function*
Swine
Tissue and Organ Harvesting / methods*

Grants and funding

Canadian Institutes of Health Research/Canada