Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs
(2023) In FASEB BioAdvances 5(2). p.71-84- 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... (More)
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.
(Less)
- author
- Arlock, Per LU ; Li, Mei LU ; Davis, Benjamin ; Lövdahl, Cecilia ; Liao, Qiuming LU ; Sjöberg, Trygve LU ; Rahman, Awahan ; Wohlfart, Björn LU ; Steen, Stig LU and Arner, Anders LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- action potential, Ca imaging, cardiac transplantation, coronary artery, L-type channels
- in
- FASEB BioAdvances
- volume
- 5
- issue
- 2
- pages
- 71 - 84
- publisher
- The Federation of American Societies for Experimental Biology
- external identifiers
-
- pmid:36816513
- scopus:85145290085
- ISSN
- 2573-9832
- DOI
- 10.1096/fba.2022-00104
- language
- English
- LU publication?
- yes
- id
- 35bacba6-990b-4f27-84ef-343fafd5a60e
- date added to LUP
- 2023-02-09 15:02:32
- date last changed
- 2024-04-16 07:22:41
@article{35bacba6-990b-4f27-84ef-343fafd5a60e,
abstract = {{<p>Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca<sup>2+</sup>-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<sup>2+</sup> transients were attenuated in the brain dead, and linked to lower mRNA expression of L-type calcium channels and a slightly lower I<sub>Ca</sub>,<sub>L</sub>, 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<sup>+</sup> (I<sub>K1</sub>) channel were altered in the brain-dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K<sup>+</sup> currents were detected (I<sub>Kr</sub>, I<sub>Ks</sub>) and were not different between groups. The transient outward K<sup>+</sup> current (I<sub>to</sub>) 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<sup>+</sup> 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.</p>}},
author = {{Arlock, Per and Li, Mei and Davis, Benjamin and Lövdahl, Cecilia and Liao, Qiuming and Sjöberg, Trygve and Rahman, Awahan and Wohlfart, Björn and Steen, Stig and Arner, Anders}},
issn = {{2573-9832}},
keywords = {{action potential; Ca imaging; cardiac transplantation; coronary artery; L-type channels}},
language = {{eng}},
number = {{2}},
pages = {{71--84}},
publisher = {{The Federation of American Societies for Experimental Biology}},
series = {{FASEB BioAdvances}},
title = {{Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs}},
url = {{http://dx.doi.org/10.1096/fba.2022-00104}},
doi = {{10.1096/fba.2022-00104}},
volume = {{5}},
year = {{2023}},
}