Electrophysiologic and extracellular ionic changes during acute ischemia in failing and normal rabbit myocardium.
The incidence of ventricular arrhythmias is higher in failing hearts than in control hearts, especially during acute ischemia. Electrophysiological and extracellular ionic changes during acute ischemia in normal and failing rabbit myocardium were assessed. Heart failure was induced in rabbits by combined volume and pressure overload. In perfused papillary muscles, the onset of electrical uncoupling and changes in action potential duration and conduction velocity during acute ischemia were determined. In Langendorff-perfused rabbit hearts the changes in extracellular potassium concentration ([K+]o) and pH during acute global ischemia were studied. In perfused papillary muscles, during the first 10 min of ischemia, action potential duration at 80% of repolarization decreased more in preparations from failing than from control hearts (from 174 to 104 ms and from 156 to 119 ms respectively (P < 0.001)). Conduction velocity was significantly lower in failing hearts during ischemia (P < 0.005). The onset of electrical uncoupling was similar in failing and control hearts (mean +/- S.E.M., 17 +/- 1 and 15 +/- 1 min respectively, n.s.). Langendorff-perfused hearts [K+]o, after 10 min of ischemia, was 11.0 +/- 0.4 mM in failing and 9.5 +/- 0.3 mM in control hearts (P < 0.01), while the change in pH was the same. After pretreatment with glibenclamide, an ATP sensitive K+ channel blocker, [K+]o reached lower values after 10 min of ischemia in both failing (8.8 +/- 0.5 mM) and control hearts (7.2 +/- 0.4 mM). During ischemia, action potential duration shortening is more pronounced and conduction velocity is lower in failing myocardium than in control myocardium. [K+]o reaches higher values during acute ischemia in failing compared with normal myocardium. These changes are not caused by an earlier activation of IK.ATP. Increased spatial dispersion in electrophysiological parameters and [K+]o over the ischemic border in failing hearts may explain the higher propensity for reentrant arrhythmias during acute regional ischemia in failing hearts.
Vermeulen
J T
JT
Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, Netherlands.
Tan
H L
HL
Rademaker
H
H
Schumacher
C A
CA
Loh
P
P
Opthof
T
T
Coronel
R
R
Janse
M J
MJ
D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000033:anatomy & histology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D010210:Papillary Muscles / Q000502:physiology / Q000503:physiopathology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012016:Reference Values
D015221:Potassium Channels; D011188:Potassium; D005905:Glyburide