Ji. Shapiro et al., ACUTE AND CHRONIC HYPOKALEMIA SENSITIZE THE ISOLATED HEART TO HYPOXICINJURY, American journal of physiology. Heart and circulatory physiology, 43(5), 1998, pp. 1598-1604
We examined the effects of acute and/or chronic hypokalemia on respons
es to 30 min of hypoxia and recovery in the isolated, perfused heart m
odel. We found that both acute hypokalemia and chronic hypokalemia imp
aired contractility [expressed as maximum slope of pressure increase o
ver time (dP/dt): 501 +/- 49 and 529 +/- 48 vs. 1,302 +/- 118 mmHg/s,
P < 0.01] and recovery of ATP concentrations (determined with P-31 NMR
spectroscopy: 30 +/- 6 and 40 +/- 10 vs. 67 +/- 5% initial, P < 0.05)
at 30 min of recovery. Moreover, the combination of acute hypokalemia
and chronic hypokalemia had additive effects (dP/dt 166 +/- 15 mmHg/s
and ATP 21 +/- 7% initial, both P < 0.01). We also measured cytosolic
calcium with surface fluorescence spectroscopy after indo 1 loading.
Acute hypokalemia and acute hypokalemia + chronic hypokalemia increase
d cytosolic calcium (averaged throughout the cardiac cycle) during and
after hypoxia (390- to 460-nm ratio at 30 min of recovery: 0.46 +/- 0
.07 and 0.65 +/- 0.07 vs. 0.18 +/- 0.03, P < 0,01), whereas:control an
d chronic hypokalemia hearts had only small changes with hypoxia and r
ecovery. Finally, when we examined mitochondria isolated from hearts p
erfused under experimental conditions, we found that chronic hypokalem
ia-alone mitochondria and chronic hypokalemia + acute hypokalemia mito
chondria had marked impairment of state 3 respiration compared with co
ntrol hearts (52 +/- 13 and 50 +/- 9 vs. 128 +/- 10 natm.min(-1).mg pr
otein(-1) with succinate as substrate, P < 0.01), whereas acute hypoka
lemia mitochondria demonstrated only subtle changes. These data sugges
t that both acute hypokalemia and chronic hypokalemia impair cardiac r
esponses to hypoxia. The mechanism may involve impairment of calcium m
etabolism, but cytosolic calcium alterations do not explain all of the
metabolic and functional effects of acute hypokalemia and chronic hyp
okalemia in the setting of hypoxia.