%0 Journal Article %1 Srid_2008_1463 %A Sridhar, Arun %A Nishijima, Yoshinori %A Terentyev, Dmitry %A Terentyeva, Radmila %A Uelmen, Rebecca %A Kukielka, Monica %A Bonilla, Ingrid M %A Robertson, Gail A %A Gy�rke, Sandor %A Billman, George E %A Carnes, Cynthia A %D 2008 %J Am J Physiol Regul Integr Comp Physiol %K 4-Aminopyridine, Action Animals; Blockers, Cardiac, Cell Channel Channels, Death, Dogs; Down-Regulation, Electrocardiography; Electrophysiology; Female; Infarction, Male; Myocardial Myocytes, Potassium Potentials, Separation; Sudden, Tachycardia, Ventricular, biosynthesis/drug drug effects; pathology/physiology; pathology; pharmacology; physiology; physiopathology physiopathology; %N 5 %P R1463--R1472 %R 10.1152/ajpregu.90583.2008 %T Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death. %U http://dx.doi.org/10.1152/ajpregu.90583.2008 %V 295 %X Ventricular tachyarrhythmias are the most common cause of sudden cardiac death (SCD); a healed myocardial infarction increases the risk of SCD. We determined the contribution of specific repolarization abnormalities to ventricular tachyarrhythmias in a postinfarction model of SCD. For our methods, we used a postinfarction canine model of SCD, where an exercise and ischemia test was used to stratify animals as either susceptible (VF(+)) or resistant (VF(-)) to sustained ventricular tachyarrhythmias. Our results show no changes in global left ventricular contractility or volumes occurred after infarction. At 8-10 wk postmyocardial infarction, myocytes were isolated from the left ventricular midmyocardial wall and studied. In the VF(+) animals, myocyte action potential (AP) prolongation occurred at 50 and 90\% repolarization (P < 0.05) and was associated with increased variability of AP duration and afterdepolarizations. Multiple repolarizing K(+) currents (I(Kr), I(to)) and inward I(K1) were also reduced (P < 0.05) in myocytes from VF(+) animals compared with control, noninfarcted dogs. In contrast, only I(to) was reduced in VF(-) myocytes compared with controls (P < 0.05). While afterdepolarizations were not elicited at baseline in myocytes from VF(-) animals, afterdepolarizations were consistently elicited after the addition of an I(Kr) blocker. In conclusion, the loss of repolarization reserve via reductions in multiple repolarizing currents in the VF(+) myocytes leads to AP prolongation, repolarization instability, and afterdepolarizations in myocytes from animals susceptible to SCD. These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias.

@article{Srid_2008_1463, abstract = {Ventricular tachyarrhythmias are the most common cause of sudden cardiac death (SCD); a healed myocardial infarction increases the risk of SCD. We determined the contribution of specific repolarization abnormalities to ventricular tachyarrhythmias in a postinfarction model of SCD. For our methods, we used a postinfarction canine model of SCD, where an exercise and ischemia test was used to stratify animals as either susceptible (VF(+)) or resistant (VF(-)) to sustained ventricular tachyarrhythmias. Our results show no changes in global left ventricular contractility or volumes occurred after infarction. At 8-10 wk postmyocardial infarction, myocytes were isolated from the left ventricular midmyocardial wall and studied. In the VF(+) animals, myocyte action potential (AP) prolongation occurred at 50 and 90\% repolarization (P < 0.05) and was associated with increased variability of AP duration and afterdepolarizations. Multiple repolarizing K(+) currents (I(Kr), I(to)) and inward I(K1) were also reduced (P < 0.05) in myocytes from VF(+) animals compared with control, noninfarcted dogs. In contrast, only I(to) was reduced in VF(-) myocytes compared with controls (P < 0.05). While afterdepolarizations were not elicited at baseline in myocytes from VF(-) animals, afterdepolarizations were consistently elicited after the addition of an I(Kr) blocker. In conclusion, the loss of repolarization reserve via reductions in multiple repolarizing currents in the VF(+) myocytes leads to AP prolongation, repolarization instability, and afterdepolarizations in myocytes from animals susceptible to SCD. These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Sridhar, Arun and Nishijima, Yoshinori and Terentyev, Dmitry and Terentyeva, Radmila and Uelmen, Rebecca and Kukielka, Monica and Bonilla, Ingrid M and Robertson, Gail A and Gy�rke, Sandor and Billman, George E and Carnes, Cynthia A}, biburl = {https://www.bibsonomy.org/bibtex/25838dde4f6428cd1487899ac0f2771fd/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpregu.90583.2008}, file = {Srid_2008_1463.pdf:Srid_2008_1463.pdf:PDF}, institution = {Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA.}, interhash = {09c22bde3eeba0916f2a32e3a34cd3d6}, intrahash = {5838dde4f6428cd1487899ac0f2771fd}, journal = {Am J Physiol Regul Integr Comp Physiol}, keywords = {4-Aminopyridine, Action Animals; Blockers, Cardiac, Cell Channel Channels, Death, Dogs; Down-Regulation, Electrocardiography; Electrophysiology; Female; Infarction, Male; Myocardial Myocytes, Potassium Potentials, Separation; Sudden, Tachycardia, Ventricular, biosynthesis/drug drug effects; pathology/physiology; pathology; pharmacology; physiology; physiopathology physiopathology;}, month = Nov, number = 5, pages = {R1463--R1472}, pdf = {Srid_2008_1463.pdf}, pii = {90583.2008}, pmid = {18768760}, timestamp = {2009-06-03T11:21:32.000+0200}, title = {Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death.}, url = {http://dx.doi.org/10.1152/ajpregu.90583.2008}, volume = 295, year = 2008 }