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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.
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PMID:Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. 109 Mar 93

The present study was designed to evaluate the effects of POCA, a carnitine palmitoyltransferase I (CPT I) inhibitor, and pyruvate, a substrate inhibiting fatty acid (FA) oxidation, on post-ischemic cardiac FA accumulation on the one hand, and hemodynamic recovery and loss of cellular integrity on the other. To this end isolated, working rat hearts, receiving glucose (11 mM) as substrate, were subjected to 45 min of no-flow ischemia and 30 min of reperfusion. Hearts were perfused with or without POCA (10 microM) and/or pyruvate (5 mM). In the control group the FA content increased significantly during ischemia and remained elevated during reperfusion. Administration of POCA did not affect functional recovery and LDH release significantly, but resulted in about two-fold increased FA levels upon reperfusion as compared to glucose-perfused hearts. Pyruvate markedly improved functional recovery. Addition of this substrate did not affect lactate dehydrogenase (LDH) release, but enhanced FA accumulation during reperfusion. The combined administration of pyruvate and POCA nullified the positive effect of pyruvate on hemodynamic recovery, aggravated LDH release, and further enhanced the accumulation of FAs. The adenine nucleotide content of reperfused hearts was comparable for all groups investigated. In conclusion, during transient ischemia POCA and pyruvate markedly increased cardiac FA accumulation through inhibition of the oxidation of FAs released from endogenous lipid pools. No clear relation was found between the FA content of reperfused hearts and post-ischemic functional recovery.
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PMID:Fatty acid accumulation during ischemia and reperfusion: effects of pyruvate and POCA, a carnitine palmitoyltransferase I inhibitor. 181 Oct 59

The human heart in the fasting state extracts free fatty acids (FFA), glucose, lactate, pyruvate, and ketones from circulating blood. The utilization of FFA accounts for most of the oxygen consumed and energy produced at rest. Patients with angiographically demonstrable coronary artery disease and stable angina pectoris have a resting myocardial metabolism similar to that of normal individuals. During atrial pacing in normal persons, there is a significant enhancement of glucose uptake but that of FFA is unchanged, and the oxidation of carbohydrates accounts for more than 60% of the energy produced. In patients with stable angina, myocardial perfusion becomes regionally inadequate during stress. Despite the increase of myocardial glucose utilization, carbohydrate oxidation is negligible. Pyruvate will not be oxidized but in the presence of increased amounts of reduced coenzymes will be reduced to lactate. In addition, a greater amount of alanine will be released by the myocardium through the transamination of pyruvate, with a concomitantly greater uptake of glutamate that serves as the NH2 donor. In addition, glutamate may be used as an anaerobic fuel through conversion to succinate coupled with GTP formation. Although coronary hemodynamics, including myocardial perfusion, return to baseline within a few minutes after stress, a longer time course is needed for myocardial metabolism to become normal. In particular, myocardial utilization of exogenous glucose remains higher well after the normalization of hemodynamic parameters. This is more pronounced in postischemic myocardium, but it also occurs in nonischemic muscle, and glucose is presumably used for rebuilding glycogen stores that were depleted during ischemia.
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PMID:Metabolic markers of stress-induced myocardial ischemia. 202 52

The recovery of both contractile performance and metabolic response of rat heart following 1 h of ischemia after equilibration with glucose + insulin (glucose-ischemia) or with pyruvate (pyruvate-ischemia), was tested in normoxic reperfusion in the presence of glucose + insulin, pyruvate, lactate or acetate. In glucose-ischemia only the reperfusion with pyruvate results in a complete recovery of the contractile force (left ventricular pressure, LVP) (170%) and good recovery of high energy phosphate compounds. Lower LVP and tissue energy charge were found in glucose reperfusion and even less in lactate and acetate reperfusion. Disappearance of the IMP accumulated during ischemia is evident only in the pyruvate reperfusion indicating a higher metabolic recovery. On the contrary in pyruvate-ischemia all types of reperfusion tested were effective in reactivating the contractile force (although acetate to a lesser extent); the contractile activity was accompanied by a good recovery of phosphocreatine, ATP, energy charge and by the decrease of IMP. Large decreases of adenine nucleotides and NADP and lower decreases of NAD are observed during ischemia/reperfusion in both systems. Pyruvate-ischemia is quite similar to, if not worse than glucose-ischemia, for all the metabolic parameters considered, but not worse for the possibility of recovery. Some specific effect of pyruvate should be exerted during the ischemic phase. The mechanism of pyruvate protection is discussed in relationship to: (i) the possible activation of pyruvate dehydrogenase, (ii) the activation of NADPH-dependent peroxide scavenging systems, (iii) the direct scavenging action of pyruvate on H2O2.
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PMID:The protective action of pyruvate on recovery of ischemic rat heart: comparison with other oxidizable substrates. 218 87

We previously reported in working swine hearts a preferred use of fatty acids during early myocardial reperfusion. The purpose of these studies was to test whether this pattern of substrate oxidation was the result of excess energy demands during mechanical recovery. Two groups of pig hearts (n = 15) were compared. Both received Intralipid with heparin (serum fatty acids, 1.02 +/- 0.05 mumol/ml) to ensure preferred substrate availability and both received [2-14C]pyruvate to monitor myocardial use of a carbohydrate substrate. In one group (n = 8) oxfenicine was administered to suppress fatty acid utilization. Left anterior descending (LAD) coronary flow was maintained at aerobic levels for 30 min, reduced by 60% for 45 min, and restored to aerobic levels for a final 50 min. Ischemia caused the expected decreased in global and regional mechanical performance. Recovery in motion during reflow was less in oxfenicine-treated hearts (73 vs. 32% decrease in systolic shortening from aerobic values in treated and control hearts, P less than or equal to 0.01 and P less than or equal to 0.05, respectively). Pyruvate oxidation declined dramatically in both groups during ischemia but recovered disparately. In control hearts CO2 production remained depressed during reperfusion (NS from ischemic values), whereas in treated hearts it increased 5.5-fold (but did not exceed aerobic values). Tissue levels of acetyl CoA and acetylcarnitine were not statistically different between perfusion beds (aerobic vs. reperfusion) within groups. Oxfenicine reduced levels of acetyl carnitine in both perfusion beds.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of substrate preference for oxidative metabolism during early myocardial reperfusion. 238 16

Bioenergetic and hemodynamic consequences of cellular redox manipulations by 0.2-20 mM pyruvate were compared with those due to adrenergic stress (0.7-1.1 microM norepinephrine) using isolated working guinea-pig hearts under the conditions of normoxia, low-flow ischemia, and reperfusion. 5 mM glucose (+ 5 U/l insulin) + 5 mM lactate were the basal energy-yielding substrates. To stabilize left ventricular enddiastolic pressure, ventricular filling pressure was held at 12 cmH2O under all conditions; this preload control minimized Frank-Starling effects on ventricular inotropism. Global low-flow ischemia was induced by reducing aortic pressure to levels (20-10 cmH2O) below the coronary autoregulatory reserve. Reactants of the creatine kinase, including H+ and other key metabolites, were measured by enzymatic, HPLC, and polarographic techniques. In normoxic hearts, norepinephrine stimulations of inotropism, heart rate x pressure product, and oxygen consumption (MVO2) were associated with a fall in the cytosolic phosphorylation potential [( ATP]/[( ADP].[Pi]] as judged by the creatine kinase equilibrium. In contrast, infusion of excess pyruvate (5 mM) markedly increased [ATP]/[( ADP].[Pi]) and ventricular work output, while intracellular phosphate decreased; MVO2 remained constant under the same conditions. During reperfusion following ischemia, pyruvate effected striking and concentration-dependent increases in MVO2, phosphorylation potential, and inotropism. Pyruvate dehydrogenase flux was augmented during reperfusion hyperemia followed by near-complete recoveries of [ATP]/([ADP].[Pi]), contractile force, heart rate x pressure product, and MVO2 in the presence of 5-10 mM pyruvate. Pyruvate also attenuated ischemic adenylate degradation. Omission of glucose from the perfusion medium rendered pyruvate ineffective in postischemic hearts. Similarly, excess lactate (5-15 mM) or acetate (5 mM) failed to reenergize reperfused hearts and severe depressions of MVO2 and inotropism developed despite the presence of glucose. Apparently, subcellular redox manipulations by pyruvate dissociated stimulated mitochondrial respiration and increased inotropism from low cytosolic phosphorylation potentials. This was evidence against the extramitochondrial [ADP].[Pi]/[ATP] ratio being the primary factor in the control of mitochondrial respiration. The mechanism of pyruvate enhancement of inotropism during normoxia and reperfusion is probably multifactorial. Thermodynamic effects on subcellular [NADH]/[NAD+] ratios are coupled with a rise in the cytosolic [ATP]/[( ADP].[Pi]) ratio at constant (normoxia) or increased (reperfusion) MVO2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pyruvate-enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart. Near-complete prevention of reperfusion contractile failure. 270 62

We have developed a novel in vivo proton MR spectroscopy magnetization transfer method for detection of lactate in ischemic tissue in the presence of interfering fat proton resonances. Pyruvate is magnetically labeled with a saturation pulse and, when converted to lactate, the lactate retains the label. Difference of spectra obtained with and without a saturation pulse contain no fat resonances. High-resolution spectra (determined with a GE 1.5 T Signa) of low lactate levels were obtained in vivo by water suppression using a 2662 composite RF pulse and slice-selective gradients. Spectral subtraction was performed in real time allowing the monitoring of a buildup of the intensity of the lactate peak. Pyruvate-lactate saturation transfer techniques should find wide applicability in the study of ischemia.
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PMID:Lactate observation in vivo by spectral editing in real time. 306 99

In the present study the hemodynamic and metabolic effects of pyruvate (5 mM), added as cosubstrate to glucose (11 mM) perfused, transiently ischemic, isolated working rat hearts, were evaluated. During 2 h of normoxic perfusion pyruvate improved functional stability, prevented depletion of glycogen and triacylglycerol stores, and increased non-esterified fatty acid (NEFA) levels, even at relatively high workloads. The elevated NEFA levels are in line with the notion that pyruvate competes with endogenously produced fatty acids for oxidative energy production. After 45 min of global ischemia pyruvate was found (a) to affect markedly the relative contribution of ATP, ADP and AMP to the total adenine nucleotide content and (b) to stimulate the degradation of glycogen and to enhance the accumulation of lactate, suggesting enhanced anaerobic ATP production. After restoration of flow pyruvate reduced the incidence of fibrillation and markedly improved recovery of cardiac output at both normal and high workload. Pyruvate did neither attenuate the release of lactate dehydrogenase, a marker for cell death, nor improve the conservation of the total adenine nucleotide and ATP content of hearts reperfused for 30 min. The latter findings indicate that hemodynamic recovery during reperfusion in the presence of pyruvate is neither related to the absolute tissue content of ATP nor to a reduction of irreversible cell damage, and suggest that pyruvate exerts its advantageous hemodynamic effects rather by improving the condition of reversibly damaged cells during reperfusion.
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PMID:Effects of pyruvate on post-ischemic myocardial recovery at various workloads. 326 1

Acute changes associated with anhepatic and revascularized state were analyzed in relation to mitochondrial energy metabolism in rabbits. Fifteen minutes after the induction of anhepatic state, the ketone body ratio in the arterial blood decreased markedly from 0.833 to 0.229. The ketone body concentration also decreased to 24% of the normal value. The blood ketone body ratio and concentration remained low during the next 45 min. Pyruvate and lactate levels and the pyruvate/lactate ratio in the arterial blood changed very little during the 60-min anhepatic state. In a revascularization model following a 15-min anhepatic state, the ketone body concentration rose rapidly and then declined gradually, finally attaining a constant level at 30 min. The decreased blood ketone body ratio recovered to 0.55 at 30 min, and achieved steady state thereafter. Mitochondrial phosphorylative activity and hepatic energy charge showed almost normal levels 60 min after revascularization following the 15-min anhepatic state. These results indicate that the rapid metabolic alterations associated with the anhepatic and revascularized state can be accurately determined by measuring the arterial blood ketone body ratio, and they suggest that the ketone body ratio may serve as a convenient parameter for the evaluation of liver viability in pathological states such as operative ischemia or liver transplantation.
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PMID:Acute responses of blood ketone body ratio following devascularization and revascularization of rabbit liver. 365 57

Insulin treatment of hearts during aerobic reperfusion following transient ischemia in the working rat heart preparation significantly improved the recovery of myocardial function. This improvement was reflected both by a shorter time required for the heart to resume beating, and to increase heart rate and peak systolic pressure after resumption of beating. The beneficial effects of insulin may be related to improved energy metabolism secondary to small increases in pyruvate production during the early phase of reperfusion. It was also associated with an increased rate of restoration of cellular K+. Pyruvate addition to the perfusate also improved resumption of spontaneous beating of the heart and restoration of normal rate and pressure development. This effect of pyruvate was also associated with increased cellular levels of K+. Both insulin and pyruvate may improve ATP production during the first few minutes of reperfusion when glycolysis and oxidation of fatty acids are inhibited, but ATP levels were not increased after 30 min of reperfusion.
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PMID:Energy metabolism during reperfusion following ischemia. 701 2


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