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- Arlock, Per, et al.
(författare)
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Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs
- 2023
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Ingår i: FASEB BioAdvances. - : Wiley. - 2573-9832. ; 5:2, s. 71-84
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Arlock, Per, et al.
(författare)
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Ion currents of cardiomyocytes in different regions of the Göttingen minipig heart
- 2017
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Ingår i: Journal of Pharmacological and Toxicological Methods. - : Elsevier BV. - 1056-8719 .- 1873-488X. ; 86, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Göttingen minipig is a promising model for pharmacological safety assessment and for translational research in cardiology. We have examined the main ion currents in cardiomyocytes of the minipig heart. Methods Cardiac cells were isolated from different cardiac regions (endo-, mid- and epicardial left ventricle and right ventricle) from Göttingen minipigs and examined using the whole cell patch clamp technique combined with pharmacological interventions. Results The inward rectifier (IK1), the delayed rectifier (IK), with the rapid and slow components, (IKr, IKs) and the L-type Ca2 + channel (ICa,L) were identified in the different regions of the heart, whereas the Ca2 +-independent transient outward current (Ito1) was observed in only a few cells. IK1 was similar in the cardiac regions with a slightly lower value in the epicardial cells. IKs was smaller in epi- and endo-cardial regions. Discussion The equivalents of the main human cardiac ion currents are present in the minipig cardiomyocytes with the exception of the Ca2 +-independent Ito1. The study provides further evidence that the minipig is a valid model for investigating cardiovascular pharmacology.
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