Role of KATP channels in repetitive induction of ventricular fibrillation.
OBJECTIVE
Patients with sustained ventricular tachyarrhythmias are at high risk for sudden cardiac death. The mechanisms leading to multiple temporally related episodes of ventricular fibrillation (VF) are not yet fully elucidated, and treatment options are limited. We investigated whether K(ATP)-channels could be involved in triggering VF.


METHODS
We determined postarrhythmic changes of monophasic action potentials (MAP) after repetitive induction of VF in 32 Langendorff-perfused rabbit hearts.


RESULTS
Postarrhythmic action potential duration (APD) was significantly shorter compared with baseline (100 +/- 12 ms vs. 140 +/- 8 ms, P < 0.05). With increasing numbers of VF and shortening of recovery intervals between VF episodes (2 min) inducibility of VF increased, and abbreviation of APD became more prominent (90 +/- 5 ms vs. 130 +/- 4 ms, P < 0.05). Pre-treatment with the selective K(ATP) blocking agent HMR 1883 led to a significant increase of postarrhythmic APDs compared with control hearts (100 +/- 12 ms vs. 118 +/- 3 ms, P = 0.0013). Moreover, HMR 1883 significantly reduced inducibility of VF and increased the rate of successful defibrillation.


CONCLUSIONS
Repetitive episodes of VF result in postarrhythmic abbreviation of APDs, a phenomenon thought to be of potential relevance for incessant tachyarrhythmias in patients. Prevention of postarrhythmic MAP-shortening by HMR 1883 might be useful in suppressing VF.
Bauer
Alexander
A
Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. alexander_bauer@med.uni-heidelberg.de
Becker
Ruediger
R
Dreyhaupt
Jens
J
Voss
Frederik
F
Kraft
Patricia
P
Kelemen
Kamilla
K
Senges-Becker
Julia C
JC
Katus
Hugo A
HA
Schoels
Wolfgang
W
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012008:Recurrence; D013449:Sulfonamides / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013449:Sulfonamides; C117780:mitochondrial K(ATP) channel; C114623:clamikalant; D013890:Thiourea