Excitation and contraction of cardiac muscle and coronary arteries of brain‐dead pigs. Issue 2 (26th December 2022)

• Record Type: Journal Article
• Authors: Arlock, Per; Li, Mei; Davis, Benjamin; Lövdahl, Cecilia; Liao, Qiuming; Sjöberg, Trygve; Rahman, Awahan; Wohlfart, Björn; Steen, Stig; Arner, Anders
• Is Part Of: FASEB bioAdvances. Volume 5:Issue 2(2023)
• Page Start: 71
• Page End: 84
• Publication Date: 2022-12-26
• Subjects: action potential -- Ca2+ imaging -- cardiac transplantation -- coronary artery -- L‐type channels
• DOI: 10.1096/fba.2022-00104
• Languages: English
• ISSNs: 2573-9832

Abstract

Abstract: Excitability and contraction of cardiac muscle from brain‐dead donors critically influence the success of heart transplantation. Membrane physiology, Ca 2+ ‐handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain‐dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole‐cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca 2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L‐type calcium channels and a slightly lower ICa, L, current, as well as to a lower expression of phospholamban. The current–voltage relationship and the current above the equilibrium potential of the inward K + (IK1 ) channel were altered in the brain‐dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K + currents were detected (IKr, IKs ) and were not different between groups. The transient outward K + current (Ito ) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K + channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved. Abstract : A large animal (porcine) model for 12‐hour brain death was used to examine properties of the donor heart. The model mimicked the characteristics of human brain death with catecholaminergic surge and arterial pressure drop. Isolated trabecular preparations and cells revealed shorter action potentials, lower Ca 2+ transients and impaired shortening. Electrophysiology revealed lower L‐type currents and decreased inward rectifier K + currents. Coronary arteries had increased sensitivity to thromboxane activation, but unaltered endothelial relaxation.