Sympathetic stimulation and norepinephrine infusion modulate extracellular potassium concentration during acute myocardial ischemia.
The purpose of this study was to investigate whether sympathetic stimulation modulated the rise in extracellular K+ concentration ([K+]o) evoked by acute myocardial ischemia. In 35 alpha-chloralose-anesthetized dogs, we measured changes in [K+]o during acute myocardial ischemia in the presence and absence of sympathetic stimulation or norepinephrine infusion. A series of four 5-minute occlusions of the distal left anterior descending coronary artery (LAD) was completed in 18 dogs. Thirty minutes of reperfusion separated each LAD occlusion. Four to five K(+)-sensitive electrodes were inserted into the left ventricular midmyocardium that was perfused by the distal LAD. Lead II of the electrocardiogram, arterial pressure, and [K+]o were recorded, and the right atrium was paced at a constant cycle length. The first, second, and fourth LAD occlusions were done in the absence of sympathetic stimulation or norepinephrine infusion. The changes in [K+]o evoked by the first LAD occlusion differed (p < 0.05) from those elicited by the second and fourth occlusions. However, the changes in [K+]o during the second and fourth LAD occlusions were similar (p > 0.2) and served as controls for the responses obtained during the third occlusion. Two minutes before the third LAD occlusion, sympathetic stimulation (4 Hz) or norepinephrine infusion (0.25-0.5 micrograms/kg per minute i.v.) was begun and was continued until 2 minutes after reperfusion. We found that sympathetic stimulation and norepinephrine infusion increased (p < 0.05) myocardial blood flow in both normal and ischemic tissue. The mean response recorded by 23 K(+)-sensitive electrodes in 11 dogs showed that sympathetic stimulation increased (p < 0.001) the [K+]o at 1, 2, 3, 4, and 5 minutes after the onset of LAD occlusion compared with the second and fourth occlusions. In contrast, the mean response recorded by 20 K(+)-sensitive electrodes in seven dogs showed that norepinephrine infusion reduced (p < 0.02) the [K+]o at 4 and 5 minutes after the onset of LAD occlusion. These data show that sympathetic stimulation increased the [K+]o evoked by acute myocardial ischemia, an effect that was not mimicked by the intravenous administration of norepinephrine.
Warner
M R
MR
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Krannert Institute of Cardiology, Indianapolis 46202.
Kroeker
T S
TS
Zipes
D P
DP
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D011188:Potassium; D009638:Norepinephrine