Preserving effect of fructose-1,6-bisphosphate on high-energy phosphate compounds during anoxia and reperfusion in isolated langendorff-perfused rat hearts

1991 ◽  
Vol 23 (1) ◽  
pp. 13-23 ◽  
Author(s):  
G Lazzarino
2005 ◽  
Vol 288 (6) ◽  
pp. H3011-H3015 ◽  
Author(s):  
Kenya Nishizawa ◽  
Paul E. Wolkowicz ◽  
Tadashi Yamagishi ◽  
Ling-Ling Guo ◽  
Martin M. Pike

Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.


1991 ◽  
Vol 261 (6) ◽  
pp. H1919-H1926
Author(s):  
M. Osbakken ◽  
D. N. Zhang ◽  
D. Nelson ◽  
M. Erecinska

Feeding Sprague-Dawley rats for 3 wk a diet containing 1% by weight of cyclocreatine increased the reservoir of the high-energy phosphate compounds but also caused alterations in the levels of the two key amino acids, aspartate and glutamate. Both were decreased by approximately 50% in the presence of an unaltered content of glutamine. In vitro exposure of these hearts to sequential perfusion, global ischemia, and reperfusion in the absence of added amino acids resulted in changes in aspartate, glutamate, and glutamine that were different from those in hearts from control rats. In the cyclocreatine-fed group, aspartate concentration ([aspartate]) and [glutamate] fell after global ischemia, whereas [glutamine] was unaltered. [Glutamine] decreased, however, in the reperfusion period. In control hearts, the predominant effect was a steady decline in glutamine, which was accompanied by either less than 10% (after global ischemia) or 30-50% fall (after reperfusion) in [aspartate] and [glutamate]. The concentration of tissue Pi was smaller in hearts from cyclocreatine-fed rats and appeared to increase more slowly during ischemia. In the presence of rotenone and aminooxyacetate, heart homogenates catalyzed production of glutamate from glutamine, which was markedly stimulated by Pi and inhibited by H+. It is postulated that 1) phosphate-activated glutaminase is an important enzyme that determines cardiac [glutamate], 2) lower [phosphate] in hearts from rats fed cyclocreatine is responsible for the apparently lesser activity of glutaminase, 3) breakdown of the high-energy phosphate compounds and consequent rise in Pi activates glutaminase, and 4) slow breakdown of glutamine during global ischemia is a result of inhibition of glutaminase by H+.


1976 ◽  
Vol 230 (6) ◽  
pp. 1744-1750 ◽  
Author(s):  
TB Allison ◽  
SP Bruttig ◽  
Crass MF ◽  
RS Eliot ◽  
JC Shipp

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.


1977 ◽  
Vol 29 (6) ◽  
pp. 959-977 ◽  
Author(s):  
O. H. Lowry ◽  
S. J. Berger ◽  
M. M.-Y. Chi ◽  
J. G. Carter ◽  
A. Blackshaw ◽  
...  

1997 ◽  
Vol 29 (5) ◽  
pp. 2358-2359
Author(s):  
M. Eugene ◽  
G. Bauza ◽  
L. Esteves-Lima ◽  
L. Le Moyec ◽  
I. Gandjbakhch

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