Cardioprotective effects of normothermic reperfusion with oxygenated potassium cardioplegia: a possible mechanism.
Na(+)/K(+) pump activation induced by normothermic reperfusion with high potassium cardioplegia may exert a protective effect on reperfusion-induced myocardial damage. We investigated (1) temperature dependency and extracellular potassium dependency of the Na(+)/K(+) pump current (Ip), (2) effects of high potassium or ouabain during reperfusion on the post-ischemic left ventricular (LV) function. Ip-voltage relation was constructed at 5.0 and 20 mM of KCl (37 degrees C) using a whole-cell clamp technique in guinea pig myocytes. Ip at -40 mV was measured at 37, 27 and 18 degrees C (KCl: 5.0 mM). Isolated rat hearts were Langendorff-perfused and subjected to 20 min of global ischemia (37 degrees C) followed by 35 min of reperfusion (37 degrees C). The post-ischemic recovery of LV developed pressure (%LVDP) was assessed in the four reperfusate groups (4.8 mM KCl, 10 mM KCl, 20 mM KCl, or 4.8 mM KCl plus 50 microM ouabain during the first 10 min of reperfusion). The 4.8 mM KCl and 10.0 mM KCl groups were compared under metabolic inhibition (glucose-free, NaCN, or hypoxia) during reperfusion. The Ip-voltage relation shifted upward when extracellular KCl was increased from 5.0 to 20 mM. Ip was significantly greater at 37 degrees C than at 18 degrees C (114.3+/-17.2 vs. 22.7+/-1.2 pA, respectively). %LVDP was significantly greater at the 10.0 mM KCl group than at the 4.8 mM KCl group (54.9+/-5.5% vs. 34.2+/-5.9%, respectively). Metabolic inhibition abolished the difference between the two groups. Ouabain significantly decreased %LVDP (15.9+/-1.6%). Potassium-induced cardiac arrest during normothermic reperfusion may exert a cardioprotective effect by inducing Na(+)/K(+) pump activation, which may be supported by aerobic metabolism during reoxygenation rather than by energy saving during cardiac arrest.
Yamamoto
Hiroshi
H
Department of Cardiovascular Surgery, Akita University School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan. h-yama@cvs.med.akita-u.ac.jp
Magishi
Katsuaki
K
Goh
Kazutomo
K
Sasajima
Tadahiro
T
Yamamoto
Fumio
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002314:Cardioplegic Solutions / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006324:Heart Arrest, Induced / Q000379:methods*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D017680:Potassium Compounds / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D002314:Cardioplegic Solutions; D004791:Enzyme Inhibitors; D017680:Potassium Compounds; C018369:potassium cardioplegic solution; D010042:Ouabain; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen