J Physiol 591.17 (2013) pp 4189?Ionic
N license (http://creativecommons.org/licenses/by/3.0/).
J Physiol 591.17 (2013) pp 4189?Ionic mechanisms limiting cardiac repolarization reserve in humans in comparison with dogs?Norbert Jost1,two , L?szlo Vir?g2 , Philippe Comtois10,11 , Bal?zs Ord?g2,9 , Viktoria Szuts2 , Gy?rgy Sepr?nyi3 , a ?a a ?o o e four 1 two 1 1 7 ??a a e a a a Miklos Bitay , Zsofia Kohajda , Istv?n Koncz , Norbert Nagy , Tam?s Sz?l , J?nos Magyar , M?ria Kov?cs2 , e a a L?szlo G. Pusk?s6 , Csaba Lengyel2,five , Erich Wettwer8 , Ursula Ravens8 , P?ter P. N?n?si7 , Julius Gy. Papp1,2 , a ?a ?Andr?s Varro1,2 and Stanley Nattel9,11 aThe Journal of PhysiologyDivision of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary Departments of two Pharmacology and Pharmacotherapy, three Medical Biology, and 4 Cardiac Surgery, Faculty of Medicine, University of Szeged, Szeged, Hungary five 1st Department of Internal Medicine, Faculty of Medicine, University of Szeged, Szeged, Hungary six Laboratory for Functional Genomics, Biological Study Center, Hungarian Academy of Sciences, Szeged, Hungary 7 Division of Physiology, Faculty of Medicine, University of Debrecen, Hungary 8 Division of Pharmacology and Toxicology, Dresden University of Technology, Germany Department of 9 Medicine and ten Physiology, Universit?de Montr l, Quebec, Canada e e 11 Investigation Center, Montreal Heart Institute, Montreal, Quebec, CanadaKey points?Cardiac repolarization, by means of which heart-cells return to their resting state right after having fired, ?Animal models, particularly the dog, are generally made use of to study repolarization properties andis a delicate approach, susceptible to disruption by common drugs and clinical circumstances.responses to drugs, with all the assumption that such findings are relevant to humans. On the other hand, little is recognized regarding the applicability of findings in animals to man. ?Right here, we studied the contribution of various ion-currents to cardiac repolarization in canine and human ventricle. ?Humans showed significantly greater repolarization-impairing effects of drugs blocking the speedy delayed-rectifier current I Kr than dogs, as a result of lower repolarization-reserve contributions from two other essential repolarizing currents (the inward-rectifier I K1 and slow delayed-rectifier I Ks ). ?Our findings clarify variations in cardiac repolarization-processes among species, highlighting the importance of caution when extrapolating results from animal models to man.Abstract The species-specific determinants of repolarization are poorly understood. This study compared the contribution of numerous currents to cardiac repolarization in canine and human ventricle. Traditional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling procedures had been utilized.20-(tert-Butoxy)-20-oxoicosanoic acid In stock Selective I Kr block (50?00 nmol l-1 dofetilide) lengthened AP duration at 90 of repolarization (APD90 ) 3-fold more in human than dog, suggesting smaller sized repolarization reserve in humans.2-Methylindole-4-carboxaldehyde structure Selective I K1 block (10 mol l-1 BaCl2 ) and I Ks block (1 mol l-1 HMR-1556) increased APD90 additional in canine than human appropriate ventricular papillary muscle.PMID:32926338 Ion present measurements in isolated cardiomyocytes showed that I K1 and I Ks densities have been 3- and four.5-fold bigger in dogs than humans, respectively. I Kr density and kinetics were equivalent in human versus dog. I Ca and I to were respectively 30 larger and 29 smaller sized in human, and Na+ a2+ exchange current was comparable. Cardiac mRNA levels for the mainN. Jost and L. Vir?g contributed equal.
