Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral A-delta and C fibers are activated during the production of ischemic or tourniquet pain; however, individual metabolic or molecular factors responsible for neural activation are not known. To elucidate these mechanisms the in vitro corneal nerve preparation was used. Electrophysiologic effects of individual metabolic perturbations associated with ischemia (hypoxia, hypoglycemia, lactic acid, and decreased pH) were investigated on A-delta and C fiber nociceptors. Increased tonic action potential activity occurred in C fibers but not in A-delta fibers after ischemia. The conduction velocity of C fibers was 0.85 +/- 0.2 m/s (mean +/- SD). Under control conditions (n = 43) there was very little fluctuation in the baseline action potential frequency (+/- 3.2%). Hypoxia (n = 12) resulted in a 213 +/- 3.4% (mean +/- SD) increase in C fiber action potential frequency relative to control (P less than 0.001, ANOVA). L-glucose substitution for D-glucose (n = 8) increased C fiber discharge frequency by 653 +/- 28% relative to control (P less than 0.001) as did the combination of hypoxia and L-glucose substitution (n = 6) by 671 +/- 14%. Comparison of hypoxia versus hypoxia and hypoglycemia conditions did not show them to be statistically different (P greater than 0.5). Lactate (10-1000 micrograms/ml) at a pH of 6.9 or 7.4 did not alter the action potential discharge frequency in corneal C fibers (n = 5, P greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of C fibers by metabolic perturbations associated with tourniquet ischemia. 155 Feb 87

Isolated working rat hearts perfused with Krebs-Hensleit buffer were arrested and made ischemic. After 22 min, the hearts were reperfused with buffer, yielding restoration of function. Nucleotide levels rose and fell in the cardiac tissue as ischemia was imposed; the changes were consistent with the energy needs of the tissue. ATP concentrations in the tissues fell by 75% during ischemia, AMP levels were low initially and subsequently rose 5-fold, and ADP levels were essentially unchanged. Upon reperfusion ATP levels rebounded, although not to initial values, and AMP returned to initial values. During ischemia, there was a 10-fold or greater rise in inosine, hypoxanthine, and xanthine levels which fell to normally low levels upon reperfusion. Lactate dehydrogenase (LDH) activity rose during ischemia and returned to baseline upon reperfusion. Changes in LDH isozyme distribution suggest that, during ischemia, there is an increased proportion of liver-associated forms which returns to normally low levels upon reperfusion. Glutamate oxalacetate transaminase activity rose slightly at 5 min of ischemia, but, by 22 min of ischemia, it had fallen to 60% of initial values. Upon reperfusion, activity rose and, by 15 min, had reached 127% of initial values. On the other hand, there is no significant change in levels of extractable creatine kinase or isocitrate dehydrogenase activities as a result of the various conditions imposed on the hearts. As an index of protein oxidation, carbonyl levels in extractable protein rose during ischemia and were over four times the initial values at 5 min of reperfusion but, with continued reperfusion, declined to approximately 150% of initial values at 15 min.
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PMID:Biochemical effects of ischemia on isolated, perfused rat heart tissues. 157 15

The regional, functional as well as metabolic consequences of inotropic stimulation on myocardium subjected to prolonged moderate ischemia were investigated. In 35 enflurane-anesthetized swine the left anterior descending coronary artery was cannulated and perfused at constant flow. The vein paralleling the left anterior descending coronary artery was cannulated for measurement of lactate and oxygen content. Transmural biopsies from the anterior myocardium were taken for the measurement of ATP, creatine phosphate, and glycogen. After control measurements, flow was adjusted to reduce regional contractile function (expressed as a work index, determined by sonomicrometry) by approximately 50%. After either 5, 25, 40, or 85 minutes of moderate ischemia, dobutamine was infused for 5 minutes into the ischemic region. In a separate group of five swine also subjected to 85 minutes of ischemia followed by infusion of dobutamine and 2 hours of reperfusion, triphenyltetrazolium chloride staining and light microscopy were used to identify infarcted tissue. Moderate ischemia (regional myocardial blood flow, 0.21 +/- 0.07 ml.min-1.g-1, determined by radiolabeled microspheres) was associated with a reduction of creatine phosphate after 5 minutes (from 9.35 +/- 2.54 to 6.43 +/- 1.06 mumol/g wet wt, p less than 0.05) and a further reduction after 25 minutes (3.18 +/- 0.69 mumol/g wet wt, p less than 0.05). Thereafter, creatine phosphate recovered despite continued ischemia (after 40 minutes, 4.95 +/- 1.37 mumol/g wet wt; after 85 minutes, 5.78 +/- 2.27 mumol/g wet wt). Lactate consumption during control conditions was reversed to production after 5 minutes of ischemia, which moderated during more prolonged ischemia. Without changing regional myocardial blood flow, infusion of dobutamine increased the work index significantly at any time point but also caused worsening of metabolic markers of ischemia. Nevertheless, even after 85 minutes of ischemia followed by the infusion of dobutamine and 2 hours of reperfusion, there was no evidence of necrosis. This experimental model provides a means of characterizing the mechanisms of short-term hibernation.
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PMID:Recruitment of an inotropic reserve in moderately ischemic myocardium at the expense of metabolic recovery. A model of short-term hibernation. 157 42

Skeletal muscle ischemia results in energy depletion and intracellular acidosis. Reperfusion is associated with impaired adenine nucleotide resynthesis, edema formation, and myocyte necrosis. The purpose of these studies was to define the time course of cellular injury and adenine nucleotide depletion and resynthesis in postischemic skeletal muscle during prolonged reperfusion in vivo. The isolated canine gracilis muscle model was used. After 5 h of ischemia, muscles were reperfused for either 1 or 48 h. Lactate and creatine phosphokinase (CPK) release during reperfusion was calculated from arteriovenous differences and blood flow. Adenine nucleotides, nucleosides, bases, and creatine phosphate were quantified by high-performance liquid chromatography, and muscle necrosis was assessed by nitroblue tetrazolium staining. Reperfusion resulted in a rapid release of lactate, which paralleled the increase in blood flow, and a delayed but prolonged release of CPK. Edema formation and muscle necrosis increased between 1 and 48 h of reperfusion (P less than 0.05). Recovery of energy stores during reperfusion was related to the extent of postischemic necrosis, which correlated with the extent of nucleotide dephosphorylation during ischemia (r = 0.88, P less than 0.001). These results suggest that both adenine nucleotide resynthesis and myocyte necrosis, which are protracted processes in reperfusing skeletal muscle, are related to the extent of nucleotide dephosphorylation during ischemia.
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PMID:Prolonged adenine nucleotide resynthesis and reperfusion injury in postischemic skeletal muscle. 159 Apr 58

The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers.
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PMID:Effect of ischemia on protein synthesis in the septic liver. 170 61

The effects of L-propionylcarnitine on mechanical function, creatine phosphate and ATP content, and lactate dehydrogenase leakage were studied in isolated perfused rat hearts exposed to global no-flow ischemia for 30 min followed by reperfusion for 20 min. Five and 10 mM L-propionylcarnitine resulted in a 100% recovery of left ventricular-developed pressure, whereas the recovery was only 40% in the hearts perfused without this agent. Ischemia-reperfusion caused a 85% loss of creatine phosphate and a 77% loss of ATP, which was prevented by 10 mM L-propionylcarnitine. Five millimolar L-propionylcarnitine protected the heart from the loss of creatine phosphate but not from the loss of ATP. Ten millimolar L-propionylcarnitine failed to improve the postischemic left ventricular-developed pressure, when it was added to the perfusate only after ischemia. L-propionylcarnitine alleviated the decrease of coronary flow in the reperfused hearts. Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine. This adverse effect was, however, transient. L-Propionylcarnitine provides protection for the postischemic reperfused heart in a dose-dependent manner. The optimal time for administration is before the ischemic insult. High doses of this compound may perturb cell membrane integrity. Moreover, the present data point to an intracellular, metabolic, and perhaps anaplerotic mechanism of action of L-propionylcarnitine in cardiac ischemia-reperfusion injury.
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PMID:Protection of the reperfused heart by L-propionylcarnitine. 175 78

The effect of AMG-1 [6(5-hydroxy-2-methylpyridylamino)-9 ribofranosylpurine] on mouse brain energy metabolism in complete brain ischemia induced by decapitation and on neurological deficit and histopathological changes after occlusion of the middle cerebral artery (MCAO) in rats were studied. The results indicate that AMG-1 has an effect of improving the status of energy metabolism in complete brain ischemia in mice. Lactate concentration was greatly reduced and the ATP and phosphocreatine levels were significantly elevated. Treatment with AMG-1 or nimodipine was performed before and after MCAO. The score of neurological deficit was significantly decreased as compared with the vehicle treated group. The extent of ischemic neuronal injury was determined by histopathological examination. AMG-1 and nimodipine seemed to attenuate the MCAO-induced neuronal damage. In as much as AMG-1 can improve the status of brain energy metabolism, neurological deficit and neuronal damage after ischemic insult, AMG-1 may have a beneficial effect for the treatment of cerebral ischemic damage.
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PMID:[Effects of AMG-1 on energy metabolism and neuronal damage of ischemic brain in mice and rats]. 182 85

Despite various techniques of hypothermia it is still difficult to provide optimal myocardial preservation in neonatal cardiac surgery. The early effects of moderate and deep hypothermia were examined in neonatal pig hearts by studying metabolism over time and the tolerance of the hearts to global ischemia. The latter was measured by the time to onset of ischemic contracture, an indicator of irreversible ischemic damage. After control right ventricular biopsies were done, 56, 3-day-old neonatal hearts were excised and placed in one of four temperature-regulated baths (37 degrees C, 25 degrees C, 19 degrees C, 12 degrees C). A compliant left ventricular balloon measured onset time to ischemic contracture (TIC) (2 mm Hg increase in pressure). Biopsies were also done at 15 and 30 minutes of ischemia. Progressive hypothermia significantly (p less than 0.001) prolonged TIC but resulted in an increased standard error of the mean (SEM). Lactate accumulation was the least in deep hypothermia (12 degrees C, 19 degrees C) (p less than 0.05) and intermediate with moderate hypothermia (25 degrees C), and all were less (p less than 0.01) than that at normothermia. The decline of adenosine triphosphate was slowed more by hypothermia than normothermia. These observations can be used to improve current methods of myocardial preservation in neonatal hearts.
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PMID:Comparison of mild and deep hypothermia: do they provide similar protection in all neonatal hearts? 186 86

Despite hypothermia, pediatric cardiac surgeons continue to experience difficulties in providing adequate myocardial protection in newborns. This study examines the effects of deep hypothermia on neonatal heart tolerance to ischemia by measuring metabolic responses and the time to onset of ischemic contracture, or "stone heart." After control right ventricular biopsy specimens were obtained, hearts of newborn pigs (n = 36) were excised and placed in temperature-regulated baths: 37.5 degrees +/- 0.5 degrees C (n = 9), 19.0 degrees +/- 0.5 degrees C (n = 14), and 12.0 degrees +/- 0.5 degrees C (n = 13). With a compliant balloon in the left ventricle to measure pressure, time to onset of ischemic contracture (greater than 2-mm Hg rise) was recorded, and sequential biopsies were done. Data indicated hypothermia significantly (p less than 0.001) prolonged time to onset of ischemic contracture from 29.5 +/- 1.7 minutes (mean +/- standard error of the mean) at normothermia to 150.0 +/- 6.4 minutes at 19 degrees C and to 283.8 +/- 46.4 minutes at 12 degrees C. Lactate buildup at 30 minutes of ischemia was significantly reduced by 70% with hypothermia. Decline in adenosine triphosphate level was significantly reduced by 50% (19 degrees C) and 75% (12 degrees C) with hypothermia. More importantly, a subgroup of hearts in each hypothermia group (n = 5 per group) was identified by 38% to 48% lower adenosine triphosphate stores before ischemia compared with the group means.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Not all neonatal hearts are equally protected from ischemic damage during hypothermia. 192 15

The functional significance of cardiac ATP-sensitive potassium channels remains controversial because of the discrepancy between the low levels of ATP at which activation of the channels occurs and the much higher levels of ATP maintained during myocardial ischemia. We studied the effects of (+)-lactate, which accumulates in large quantity as a result of increased glycolysis during ischemia, on ATP-sensitive potassium channels in adult guinea pig ventricular myocytes using the whole-cell patch-clamp technique. Lactate at 20-40 mM in the internal solution activated ATP-sensitive potassium channels and shortened action potential duration. Activation of the channels occurred even in the presence of 2-5 mM ATP in the internal solution and was dependent on intracellular free magnesium levels. Our results suggest that intracellular lactate may play a significant role in activating cardiac ATP-sensitive potassium channels and shortening action potential duration even at ATP levels similar to those resulting from moderate to severe myocardial ischemia.
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PMID:Lactate activates ATP-sensitive potassium channels in guinea pig ventricular myocytes. 193 61


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