Glycolytic ATP production is not essential for Na+-K+ ATPase function and contractile recovery during postischemic reperfusion in isolated rat hearts

Normalization of intracellular sodium (Na[Formula: see text]) after postischemic reperfusion depends on reactivation of the sarcolemmal Na+-K+-ATPase. To evaluate the requirement of glycolytic ATP for Na+-K+-ATPase function during postischemic reperfusion, 5-s time-resolution23Na NMR was performed in isolated perfused rat hearts. During 20 min of ischemia, Na[Formula: see text] increased approximately twofold. In glucose-reperfused hearts with or without prior preischemic glycogen depletion, Na[Formula: see text]decreased immediately upon postischemic reperfusion. In glycogen-depleted pyruvate-reperfused hearts, however, the decrease of Na[Formula: see text] was delayed by ∼25 s, and application of the pyruvate dehydrogenase (PDH) activator dichloroacetate (DA) did not shorten this delay. After 30 min of reperfusion, Na[Formula: see text]had almost normalized in all groups and contractile recovery was highest in the DA-treated hearts. In conclusion, some degree of functional coupling of glycolytic ATP and Na+-K+-ATPase activity exists, but glycolysis is not essential for recovery of Na[Formula: see text] homeostasis and contractility after prolonged reperfusion. Furthermore, the delayed Na+-K+-ATPase reactivation observed in pyruvate-reperfused hearts is not due to inhibition of PDH.

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Dynamics of myocardial adaptation to low-flow ischemia and hypoxemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.6.h2300 ◽

1996 ◽

Vol 271 (6) ◽

pp. H2300-H2305

Author(s):

G. Merati ◽

S. Allibardi ◽

L. D. Monti ◽

J. W. de Jong ◽

M. Samaja

Keyword(s):

Low Flow ◽

Control Performance ◽

Perfusion Medium ◽

Atp Production ◽

Lactate Release ◽

Rat Hearts ◽

O2 Supply ◽

Developed Pressure ◽

Myocardial Adaptation ◽

Isolated Rat

We investigated whether one or more factors control performance in O2-limited hearts. For this purpose, we measured the dynamics of myocardial adaptation to reduced O2 supply with a specially designed setup, analyzing early changes after reduction in either flow of the perfusion medium or its PO2. For 10 min, 38 isolated rat hearts underwent low-flow ischemia or hypoxemia, matched for O2 supply. Early during ischemia, developed pressure declined at a rate of 311 +/- 25 mmHg/s; lactate release increased and then leveled off to 3.4 +/- 0.7 mumol/min within 2 min. During hypoxemia, pressure dropped initially, as observed during ischemia. However, it then increased before slowly decreasing. Lactate release during hypoxemia peaked at 13.0 +/- 2.3 mumol/min after 2 min, leveling off to 3.5 +/- 1.3 mumol/min. Glycogen decreased by 52 and 81% in ischemic and hypoxemic hearts, respectively (P < 0.05). Reexposure to ischemia or hypoxemia induced comparable changes in both groups. We conclude that, at the beginning of ischemia, a single factor does limit myocardial performance. This variable, which remains undisturbed for 10 min, is presumably O2 availability. In contrast, approximately 20 s after induction of hypoxemia, glycolytic ATP production can partially override low O2 availability by providing most of the energy needed. During repeated restriction of O2 supply, O2 availability alone limits performance during both ischemia and hypoxemia.

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Glutathione disulfide as an index of oxidative stress during postischemic reperfusion in isolated rat hearts

Molecular and Cellular Biochemistry ◽

10.1007/bf00926745 ◽

1995 ◽

Vol 144 (1) ◽

pp. 85-93 ◽

Cited By ~ 4

Author(s):

Robert J. A. M. Verbunt ◽

Willem G. van Dockum ◽

E. M. Lars Bastiaanse ◽

Janneke M. Egas ◽

Arnoud van der Laarse

Keyword(s):

Oxidative Stress ◽

Glutathione Disulfide ◽

Postischemic Reperfusion ◽

Rat Hearts ◽

Isolated Rat

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Substrate competition in postischemic myocardium. Effect of substrate availability during reperfusion on metabolic and contractile recovery in isolated rat hearts.

Circulation Research ◽

10.1161/01.res.75.6.1103 ◽

1994 ◽

Vol 75 (6) ◽

pp. 1103-1112 ◽

Cited By ~ 17

Author(s):

C Tamm ◽

R Benzi ◽

I Papageorgiou ◽

I Tardy ◽

R Lerch

Keyword(s):

Substrate Availability ◽

Rat Hearts ◽

Contractile Recovery ◽

Postischemic Myocardium ◽

Substrate Competition ◽

Isolated Rat

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Contribution of prostaglandins to reperfusion-induced ventricular failure in isolated rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.251.1.h133 ◽

1986 ◽

Vol 251 (1) ◽

pp. H133-H140 ◽

Cited By ~ 6

Author(s):

M. Karmazyn

Keyword(s):

Coronary Flow ◽

Initial Period ◽

Hydrolysis Product ◽

Contractile Force ◽

Ventricular Contractility ◽

Endogenous Prostaglandin ◽

Resting Tension ◽

Rat Hearts ◽

Contractile Recovery ◽

Isolated Rat

This study was carried out to investigate the possible contribution of endogenous prostaglandin (PG) production to failure of contractile recovery following reperfusion of hypoperfused isolated rat hearts. A 90% reduction in coronary flow rate for 60 min resulted in a time-dependent depression of contractile force and an elevation in resting tension. Reperfusion produced a slight (approximately 11%) recovery of contractile force, whereas resting tension remained elevated. Reperfusion was a potent stimulus for PG (as assessed by 6 keto-PGF1 alpha) release and resulted in levels that were significantly higher than those observed prior to ischemia. When PG synthesis was inhibited by the nonsteroidal anti-inflammatory drugs ibuprofen, indomethacin, or acetylsalicylic acid (ASA), recovery of ventricular contractility on reperfusion was significantly higher than that seen in the absence of drugs. Ibuprofen was the most effective, producing an average recovery of 70% (P less than 0.05 from control). Indomethacin and ASA produced approximately a 40% (P less than 0.05) and 35% (P less than 0.05) recovery of contractile force, respectively. The improved recovery in contractility was significantly depressed by the addition of low concentrations of prostacyclin (PGI2) and PGF2 alpha, whereas PGE2 and 6 keto-PGF1 alpha, the hydrolysis product of PGI2, were ineffective. The effects on resting tension were inconsistent. PG release during reperfusion was unrelated either to the length of the initial period of reduced coronary flow or the degree of contractile recovery; it was attenuated either by a reduction in or by an elevation of Ca concentration. These results indicate that endogenous PGs mediate, at least in part, reperfusion-associated failure of ventricular function.

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Glutathione disulfide as an index of oxidative stress during postischemic reperfusion in isolated rat hearts

Molecular and Cellular Biochemistry ◽

10.1007/bf00944612 ◽

1995 ◽

Vol 146 (2) ◽

pp. 187-187

Author(s):

Robert J. A. M. Verbunt ◽

Willem G. van Dockum ◽

E. M. Lars Bastiaanse ◽

Janneke M. Egas ◽

Arnoud van der Laarse

Keyword(s):

Oxidative Stress ◽

Glutathione Disulfide ◽

Postischemic Reperfusion ◽

Rat Hearts ◽

Isolated Rat

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Recovery of glycolysis and oxidative metabolism during postischemic reperfusion of hypertrophied rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.2.h798 ◽

1996 ◽

Vol 271 (2) ◽

pp. H798-H805 ◽

Cited By ~ 4

Author(s):

B. O. Schonekess ◽

M. F. Allard ◽

G. D. Lopaschuk

Keyword(s):

Oxidative Metabolism ◽

Glucose Oxidation ◽

Mechanical Function ◽

Lactate Oxidation ◽

Atp Production ◽

Postischemic Reperfusion ◽

Palmitate Oxidation ◽

Abdominal Aortic ◽

Rat Hearts ◽

And Control

We investigated the source and extent of recovery of ATP production during postischemic reperfusion of isolated working hearts from abdominal aortic-banded rats. Rates of glycolysis, glucose oxidation, lactate oxidation, and palmitate oxidation were measured in hypertrophied and control hearts [perfused with (in mM) 11 glucose, 0.5 lactate, and 1.2 palmitate] during and after 30 min of no-flow ischemia. In the initial aerobic period glycolytic rates were 1.87-fold higher in hypertrophied hearts compared with control hearts (P < 0.05), with rates of carbohydrate and palmitate oxidation being similar. During reperfusion, hypertrophied hearts recovered 40% of preischemic function compared with 71% in control hearts. Rates of glycolysis during reperfusion of hypertrophied hearts remained accelerated compared with control hearts (2.01-fold higher, P < 0.05), whereas oxidative metabolism returned to preischemic values in both groups. The efficiency of converting ATP production into mechanical work decreased to 29% of preischemic values in hypertrophied hearts during the postischemic reperfusion compared with a decrease to only 59% of preischemic values in control hearts. This suggests that the recovery of glycolysis and oxidative metabolism in the hypertrophied heart during postischemic reperfusion is not impaired, but rather the efficiency of converting ATP produced into mechanical function decreases.

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