Excitation and contraction of cardiac muscle and coronary arteries of brain‐dead pigs

Abstract

Excitability and contraction of cardiac muscle from brain‐dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+‐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 Ca2+ 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.

Pharmacological and mechanical properties of isolated pig coronary veins

“…We present a first detailed analysis of the mechanical and pharmacological properties of pig coronary veins, in comparison to coronary arteries. The pig coronary arteries have previously been examined in studies on, e.g., vascular aging (Murohara et al, 1991), transplantation (Arlock et al, 2023), endothelial function (Matsumoto et al, 1993) and exercise (Parker et al, 1994), whereas the properties of the veins are poorly understood. The two examined vessels in the present study (left anterior descending coronary artery and the adjacent coronary vein) are located on the surface of the heart in the anterior interventricular sulcus.…”

“…Previous work on the coronary artery of the pig has characterized agonist responses and demonstrated substance P-induced endothelial relaxation [e.g., (Qin et al, 2020;Arlock et al, 2023)]. In contrast, very little is known regarding the coronary veins.…”