Effect of the cardioselective ATP-sensitive potassium channel inhibitor HMR 1883 in a porcine model of cardiopulmonary resuscitation.
OBJECTIVE
HMR 1883 (the free acid form of HMR 1098) selectively inactivates myocardial ATP sensitive potassium channels, which may be a potential important therapeutic approach to prevent life-threatening arrhythmias. This study was designed to assess the effects of HMR 1883 combined with adrenaline on haemodynamic variables, blood gases, and cardiac arrhythmias in a porcine cardiac arrest model.


METHODS
After 8 min of untreated cardiac arrest, followed by 1 min of cardiopulmonary resuscitation (CPR), 12 pigs weighing 30-40 kg were assigned randomly to receive either 45 microg/kg adrenaline alone (n=6), or 45 microg/kg adrenaline combined with 3 mg/kg HMR 1883 (n=6), followed by up to three defibrillation attempts 2 min later. Five minutes after return of spontaneous circulation, cardiac arrest was induced for 1 min, with the CPR protocol following as described above. All animals subsequently underwent four cardiac arrest intervals of 1, 2, 3, and 4 min duration which were separated by four episodes of 5 min of return of spontaneous circulation.


RESULTS
Haemodynamic variables, cardiac arrhythmias in the acute resuscitation phase between termination of chest compressions and return of spontaneous circulation, and after return of spontaneous circulation in both groups were comparable throughout the experiment. Survival rates throughout the experiment were comparable between groups. Arterial blood gases, electrolyte, glucose, and lactate levels in both groups during the experiment indicated comparable severe metabolic acidosis, with increasing levels after each episode of simulated refibrillation, and subsequent return of spontaneous circulation.


CONCLUSIONS
Combining HMR 1883 with adrenaline during CPR resulted in comparable haemodynamic variables, return of spontaneous circulation rates, cardiac arrhythmias, lactate and glucose levels compared with adrenaline alone. This indicates that injection of HMR 1883 was safe under these conditions.
Krismer
Anette C
AC
Department of Anaesthesiology and Critical Care Medicine, The Leopold-Franzens-University, Anichstrasse 35, 6020 Innsbruck, Austria. anette.krismer@uibk.ac.at
Wenzel
Volker
V
Voelckel
Wolfgang
W
Witkiewicz
Markus
M
Strohmenger
Hans Ulrich
HU
Raedler
Claus
C
Lindner
Karl H
KH
D000818:Animals; D001784:Blood Gas Analysis; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000627:therapeutic use; D006323:Heart Arrest / Q000150:complications* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology*; D023421:Models, Animal; D026902:Potassium Channel Blockers; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000517:prevention & control*
D026902:Potassium Channel Blockers; D013449:Sulfonamides; C114623:clamikalant; D013890:Thiourea; D004837:Epinephrine