Does the opening of ATP-sensitive K+ channels modify ischaemia-induced ventricular arrhythmias in anaesthetised dogs?
These experiments were designed to determine whether there is any change in the severity of ventricular arrhythmias resulting from coronary artery occlusion in anaesthetised mongrel dogs if ATP-sensitive potassium channels were already open at the time of coronary occlusion. To achieve this we locally infused the K(ATP) channel opener levcromakalim, in a total dose of 3 microg/kg, and given by slow infusion over a 30 min period directly into a side branch of the left anterior descending coronary artery. This dose increased blood flow in that main artery by 30% (and by 7% in the adjacent left circumflex artery). The degree of inhomogeneity of electrical activation, measured from the left ventricular wall distal to the occlusion site, was unaffected by levcromakalim administration but there was significant epicardial ST-elevation, perhaps indicating K+ egression from cells. Following coronary artery occlusion there was no marked difference in the severity of arrhythmias between control and levcromakalim-treated dogs, except for an increased number of episodes of ventricular tachycardia due entirely to effects in two of the nine treated dogs. We conclude that opening cardiac K(ATP) channels with levcromakalim, at this one dose level, and administered directly to the left ventricular wall, does not significantly modify arrhythmia severity during ischaemia. These results cannot be extrapolated to studies in which such drugs markedly reduce coronary perfusion pressure.
Vegh
A
A
Department of Pharmacology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Papp
J G
JG
György
K
K
Kaszala
K
K
Parratt
J R
JR
D000255:Adenosine Triphosphate / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate