Effects of ischemia on discontinuous action potential conduction in hybrid pairs of ventricular cells.
BACKGROUND
Acute ischemia often occurs in cardiac tissue that has prior injury, resulting in spatially inhomogeneous distributions of membrane properties and intercellular coupling. Changes in action potential conduction with ischemia, which can be associated with release of catecholamines, may be particularly important in tissue that has discontinuous conduction resulting from prior infarction, hypertrophy, or myopathy.


RESULTS
Isolated guinea pig ventricular myocytes were electrically coupled by a coupling-clamp circuit to a comprehensive computer model of a guinea pig ventricular myocyte to assess alterations in the critical value of coupling conductance required for action potential conduction from the real cell to the model cell when the real cell was exposed to a solution that included hypoxia, acidosis, and an elevated extracellular potassium concentration to simulate acute ischemia. The "ischemic" solution increased critical coupling conductance from 6.2+/-0.1 to 7.4+/-0.2 nS and decreased the associated maximum conduction delay from 31+/-1 to 23+/-1 ms (mean+/-SEM, n=11). The ischemic solution plus 1 micromol/L norepinephrine decreased critical coupling conductance from 5.9+/-0.2 to 5.0+/-0.1 nS and increased maximum conduction delay from 31+/-2 to 54+/-4 ms (mean+/-SEM, n=8).


CONCLUSIONS
The release of catecholamines with ischemia, in a setting of partially uncoupled cells, may play a major role in producing long conduction delays, which may allow reentrant pathways.
Wilders
R
R
Department of Medical Physiology and Sports Medicine, Utrecht University, Utrecht, Netherlands. r.wilders@med.uu.nl
Verheijck
E E
EE
Joyner
R W
RW
Golod
D A
DA
Kumar
R
R
van Ginneken
A C
AC
Bouman
L N
LN
Jongsma
H J
HJ
D000200:Action Potentials; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology*; D006822:Hybrid Cells; D007511:Ischemia / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology
D009638:Norepinephrine