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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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| 3. |
- 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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| 5. |
- Noble, Mark I. M., et al.
(författare)
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The beat-to-beat decay of cardiac contractility from highly potentiated levels is bi-exponential
- 2006
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 39:14, s. 2657-2664
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Tidskriftsartikel (refereegranskat)abstract
- In order to determine the mode of beat-to-beat decay of contractility from very high levels, we studied the beat-by-beat decay of cardiac contractility following potentiation. Such decay curves are normally analysed using a mono-exponential decay function, which assumes that a fixed fraction of activator calcium ions is recirculated from one beat to the next. We postulated that there might be deviations from such a mono-exponential expression at high levels of contractility. In single sucrose-gap voltage clamp experiments of isolated ferret papillary muscle, we obtained very high contractility by potentiation due to prolonged depolarisations. We found a bi-exponential decay in 9 of 11 muscles studied, in which the initial decay is much faster than the subsequent slower decay, as judged by residual variance of least-squares exponential fitting and by analysis of covariance using a linear equation (force of beat versus force of previous beat), p = 0.0089. In the slower decay period (physiological range), the decay was identical to that following post-extrasystolic potentiation in the same muscles studied with conventional stimulation. (c) 2005 Elsevier Ltd. All rights reserved.
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| 6. |
- Roscher, Roger, et al.
(författare)
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Effects of dopamine on porcine myocardial action potentials and contractions at 37 degrees C and 32 degrees C
- 2001
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 45:4, s. 421-426
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little information exists on the effects of drugs with cardiovascular action in hypothermia, and some findings have indicated paradoxic effects of dopamine in this setting. As we have not found any data on the electrophysiologic and contractile effects of dopamine on the heart in hypothermia, we decided to study this in pig myocardium, since pigs have a cardiovascular system more similar to that of humans than other animals. METHODS: Excised muscle strips from pig ventricular septum were mounted in an organ bath. After 45 min of equilibration at 37 degrees C or 32 degrees C, resting and action potentials, time to peak contraction and contractile force were recorded during pacing with a frequency of 60/min. Dopamine at 4 microM or 8 microM was added and new recordings were made after 15 min. RESULTS: Cooling to 32 degrees C caused a prolongation of contraction by 48% and the contractile force increased by 39%. The membrane action potential duration at 50% and 90% repolarization levels increased at 32 degrees C by 28% and 16% respectively. Dopamine significantly (P<0.05) increased the contractile force and membrane action potential duration at 50% and 90% repolarization levels both in normothermia and in hypothermia, whereas the duration of the contraction was not significantly changed. CONCLUSION: Cooling to 32 degrees C significantly prolongs the myocardial action potential and the contraction duration. Dopamine increases the contractile force and prolongs the action potential both at 37 degrees C and at 32 degrees C.
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