Sympathetic activation and increased extracellular potassium: synergistic effects on cardiac potassium uptake and arrhythmias.
During acute myocardial ischemia, a combination of increased extracellular K+ concentration and sympathetic nerve activation exists. Using a perfused innervated rat heart model, we studied the influence of increased extracellular K+ concentrations on neural norepinephrine (NE) release, adrenergic stimulation-induced K+ uptake by the heart, and the occurrence of ventricular arrhythmias. Hearts were globally perfused with control (4 mM) or increased concentrations of K+ (7-16 mM). Sympathetic nerve stimulation-induced NE release was analyzed by radioenzymatic assay. Cardiac K+ uptake was assessed by the reduction in K+ concentration in the coronary venous effluent induced by nerve stimulation. Neural NE release was not influenced by increasing K+ from 4 mM to 7, 10, and 13 mM, but was suppressed by 16 mM K+ (-40 +/- 10%). Nerve stimulation induced cardiac uptake of K+, which was blocked by the beta-adrenoceptor antagonist timolol. This stimulated K+ uptake was substantially enhanced by increasing extracellular K+ and was also dependent on the intensity of sympathetic stimulation at 10 mM K+. Sympathetic nerve stimulation, together with a high K+ of 10 mM, was potent in initiating ventricular tachyarrhythmias, and quantitative NE release was well correlated with the frequency of ventricular arrhythmias. Our results demonstrate the synergistic effects of increased extracellular K+ and sympathetic activation, which may be involved in the genesis of ventricular arrhythmias.
Du
X J
XJ
Department of Medicine (RIE), University of Edinburgh, Scotland.
Dart
A M
AM
Riemersma
R A
RA
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000378:metabolism*; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism*; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*
D011188:Potassium; D009638:Norepinephrine