Impact of Reperfusion Calcium and pH on the Resuscitation of Hearts Donated After Circulatory Death

Christopher White; Emma Avery; Alison Müller; Sanaz Hatami; Yun Li; Hoa Le; James Thliveris; Rakesh Arora; Trevor Lee; Ian Dixon; Ganghong Tian; Jayan Nagendran; Larry Hryshko; Darren Freed

doi:10.1016/j.athoracsur.2016.05.084

Impact of Reperfusion Calcium and pH on the Resuscitation of Hearts Donated After Circulatory Death

Ann Thorac Surg. 2017 Jan;103(1):122-130. doi: 10.1016/j.athoracsur.2016.05.084. Epub 2016 Aug 12.

Authors

Christopher White¹, Emma Avery², Alison Müller³, Sanaz Hatami³, Yun Li², Hoa Le², James Thliveris⁴, Rakesh Arora⁵, Trevor Lee⁶, Ian Dixon², Ganghong Tian⁷, Jayan Nagendran⁸, Larry Hryshko², Darren Freed⁹

Affiliations

¹ Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada; Department of Surgery, University of Alberta, Edmonton, Canada.
² Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada.
³ Department of Physiology, University of Alberta, Edmonton, Canada.
⁴ Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada.
⁶ Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
⁷ National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada.
⁸ Department of Surgery, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada.
⁹ Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada; Department of Surgery, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dhfreed@ualberta.ca.

PMID: 27526656
DOI: 10.1016/j.athoracsur.2016.05.084

Abstract

Background: Hearts donated after circulatory death may represent an additional donor source. The influx of sodium and calcium ions across the sarcolemma play a central role in the pathogenesis of ischemia-reperfusion injury; however, this process may be inhibited if the initial reperfusion solution is rendered hypocalcemic and acidic. We sought to determine the calcium concentration and pH of the initial reperfusion solution that yielded optimal functional recovery of hearts donated after circulatory death during ex vivo heart perfusion.

Methods: Pigs were anesthetized, mechanical ventilation was discontinued, and a 15-minute standoff period was observed after circulatory arrest. Hearts were reperfused with a normothermic cardioplegia of varying calcium concentrations (part 1 [50 μmol/L, n = 4; 220 μmol/L, n = 9; 500 μmol/L, n = 4; and 1,250 μmol/L, n = 5]) and pH (part 2 [7.9, n = 5; 7.4, n = 9; 6.9, n = 8; and 6.4, n = 6]). Myocardial function was then assessed in a physiologic working model 1 hour after initiation of normothermic ex vivo heart perfusion.

Results: The calcium concentration and pH of the cardioplegic solution affected the development of myocardial edema (part 1: 50 μmol/L = 5.8% ± 0.9%; 220 μmol/L = 4.3% ± 0.4%; 500 μmol/L = 7.0% ± 0.6%; and 1,250 μmol/L = 6.6% ± 0.8% weight gain, p = 0.015; part 2: 7.9 = 3.6% ± 0.4%, 7.4 = 4.3% ± 0.4%, 6.9 = 3.7% ± 0.6%, and 6.4 = 6.4% ± 1.3% weight gain, p = 0.056) and the recovery of myocardial function (cardiac index part 1: 50 μmol/L = 2.6 ± 0.6; 220 μmol/L = 6.0 ± 0.8; 500 μmol/L = 2.3 ± 0.5; and 1,250 μmol/L = 1.9 ± 0.6 mL · m^-1 · g^-1, p < 0.001; part 2: 7.9 = 1.5 ± 0.7; 7.4 = 6.0 ± 0.8; 6.9 = 8.4 ± 1.8; and 6.4 = 3.1 ± 0.8 mL · m^-1 · g^-1, p = 0.003) during ex vivo heart perfusion.

Conclusions: Initial reperfusion of hearts donated after circulatory death with a hypocalcemic and moderately acidic cardioplegia minimizes edema and optimizes functional recovery during subsequent ex vivo heart perfusion.

MeSH terms

Animals
Calcium / metabolism*
Cardioplegic Solutions / pharmacology*
Disease Models, Animal
Heart Arrest, Induced / methods*
Heart Transplantation*
Hydrogen-Ion Concentration
Myocardial Reperfusion Injury / metabolism*
Myocardial Reperfusion Injury / prevention & control
Myocardium / metabolism*
Swine
Tissue and Organ Procurement*

Substances

Cardioplegic Solutions
Calcium