Affiliation:
1. From the Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham.
Abstract
Abstract
The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca
2+
(Ca
2+
i
). The mechanism is undetermined but may involve disturbances in Na
+
homeostasis. We tested this hypothesis by interleaving
23
Na and
31
P nuclear magnetic resonance (NMR) measurements of Na
+
i
and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H
2
O
2
and Fe
3+
. In separate experiments, K
+
i
and Ca
2+
i
were measured with
39
K and
19
F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na
+
i
increases and substantial K
+
i
depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca
2+
i
occurred before substantial Na
+
i
accumulation or K
+
i
depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H
2
O
2
and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na
+
i
and K
+
i
, whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H
2
O
2
but has similar protective effects. In conclusion, pyruvate effectively protects against H
2
O
2
/Fe
3+
, largely by direct H
2
O
2
scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na
+
homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na
+
i
accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca
2+
i
was not supported.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Reference63 articles.
1. Burton KP. Superoxide dismutase enhances recovery following myocardial ischemia. Am J Physiol. 1985;248:H637-H643.
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