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)

The coronary venous efflux of lactate, inosine and hypoxanthine during pacing-induced angina has been compared with myocardial extraction of the catabolites during exercise-induced angina. Inosine and hypoxanthine were analyzed by enzyme assay after separation by column chromatography. Myocardial lactate extraction at rest (15 +/- 9%, mean +/- SD) was converted to production levels (-34 +/- 26%) during pacing-induced angina (p less than 0.0005) and increased (24 +/- 13%) during exercise (p less than 0.05). The arterial values at rest (850 +/- 330 mumol/1) were unchanged during pacing and increased five-fold during exercise (4380 +/- 1860 mumol/1). The mean myocardial inosine extraction at rest (33 +/- 10%) was transformed to release values (-41 +/- 30%) during pacing (p less than 0.0005) as well as during exercise (-20 +/- 27%) (p less than 0.0005). The hypoxanthine extraction at rest (25 +/- 11%) decreased during pacing (-7.8 +/- 29%) (p less than 0.0025) and exercise (10 +/- 25%) (NS). The slight increase of arterial inosine and hypoxanthine values was not significant. Myocardially produced lactate, a sensitive marker of pacing-induced ischemia, was obscured by elevated arterial concentrations during exercise. However, inosine significantly correlated with lactate during pacing, and was useful in detecting ischemic myocardial energy deficiency during exercise-induced angina.
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PMID:Myocardial release of lactate, inosine and hypoxanthine during atrial pacing and exercise-induced angina. 75 23

During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly. In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased. The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia.
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PMID:Release of nucleosides from canine and human hearts as an index of prior ischemia. 75 70

The rat hearts were subjected to 60-min ischemia by left coronary artery ligation followed by 60-min reperfusion, involving intravenous adenosine inosine or guanosine given in a dose of 1 mg/kg.min-1 in the first 30 minutes of reperfusion. Ischemia and subsequent reperfusion caused a progressive decrease in cardiac output and coronary blood flow. Adenosine was found to enhance coronary blood flow and increase cardiac and stroke outputs. Inosine produced nearly the same, but less pronounced effect. Guanosine increased cardiac output without changing coronary blood flow.
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PMID:[Hemodynamic effects of purine nucleosides in regional ischemia and reperfusion]. 140 75

The effects of a potent adenosine deaminase inhibitor, deoxycoformycin, on purine and amino acid neuro-transmitter release from the ischemic rat cerebral cortex were studied with the cortical cup technique. Cerebral ischemia (20 min) was elicited by four-vessel occlusion. Purine and amino acid releases were compared from control ischemic animals and deoxycoformycin-pretreated ischemic rats. Ischemia enhanced the release of glutamate, aspartate, and gamma-aminobutyric acid into cortical perfusates. The levels of adenosine, inosine, hypoxanthine, and xanthine in the same perfusates were also elevated during and following ischemia. Deoxycoformycin (500 micrograms/kg) enhanced ischemia-evoked release of adenosine, indicating a marked rise in the adenosine content of the interstitial fluid of the cerebral cortex. Inosine, hypoxanthine, and xanthine levels were depressed by deoxycoformycin. Deoxycoformycin pretreatment failed to alter the pattern of amino acid neurotransmitter release from the cerebral cortex in comparison with that observed in control ischemic animals. The failure of deoxycoformycin to attenuate amino acid neurotransmitter release, even though it markedly enhanced adenosine levels in the extracellular space, implies that the amino acid release during ischemia occurs via an adenosine-insensitive mechanism. Inhibition of excitotoxic amino acid release is unlikely to be responsible for the cerebroprotective actions of deoxycoformycin in the ischemic brain.
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PMID:Brain adenosine and transmitter amino acid release from the ischemic rat cerebral cortex: effects of the adenosine deaminase inhibitor deoxycoformycin. 167 Oct 90

Inosine is a positive inotropic agent and dilates coronary blood vessels. During ischemia, inosine infusion increases blood flow, resulting in decreased myocardial damage. We wished (a) to determine inosine's effect in isolated rat hearts and (b) to determine if inosine attenuates myocardial dysfunction after transient global ischemia. Developed left ventricular pressure (LVP), LV dP/dt, and coronary perfusion pressure were monitored in hearts receiving Krebs-Henseleit buffer (KHB) (n = 10) or KHB + 2 mM inosine (n = 4). KHB + 2 mM inosine significantly reduced coronary perfusion pressure by 21% but had no effect on developed LVP or LV dP/dt. Hearts receiving KHB (n = 6) or KHB + 2 mM inosine (n = 5) were subjected to 15-min global ischemia followed by 30-min reperfusion with KHB. Recovery of LVP, LV dP/dt, the incidence of arrhythmias, and the time to peak recovery of developed LVP was not different between groups. In two additional hearts, KHB + 2 mM inosine administered during reperfusion had no effect on developed LVP, LV dP/dt, or coronary perfusion pressure. Thus, unlike other preparations, inosine pretreatment did not significantly affect the time course of postischemic functional recovery of rat myocardium.
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PMID:Effect of inosine in the normal and reperfused rat heart. 169 7

Inosine added to the perfusion medium for isolated working rat heart induced a dose-dependent coronary vasodilator and positive functional effect. Inosine increased coronary flow (ml/min) from 11.8 +/- 0.5 (control, n = 16) to 15.6 +/- 0.6 (0.1 mM, n = 10), to 18.2 +/- 1.1 (0.5 mM, n = 6), and to 18.4 +/- 0.8 (1.0 mM, n = 14). Left ventricular systolic pressure was increased (LVSP, mm Hg) from 72.5 +/- 1.1 (control) to 75.4 +/- 1.7 (0.1 mM) to 78.7 +/- 2.1 (0.5 mM) and to 82.6 +/- 1.5 (1.0 mM). and cardiac output (CO, ml/min) from 26.4 +/- 2.0 (control) to 29.6 +/- 2.3 (0.1 mM), to 30.2 +/- 3.5 (0.5 mM), and to 37.4 +/- 2.0 (1.0 mM). At the end of 30-min reperfusion after a 15-min period of global total ischemia (n = 9), the functional parameters were significantly reduced (coronary flow 8.5 +/- 0.4 ml/min, LVSP 63 +/- 1.9 mm Hg, CO 13.6 +/- 1.9 ml/min). When inosine was present in the perfusion medium during the entire experimental protocol, coronary flow and heart function were also enhanced in a dose-dependent manner. The content of cardiac ATP (mumol/g) was decreased at the end of the 15-min ischemic period (1.89 +/- 0.17, n = 7; control 3.85 +/- 0.05, n = 4), and inosine had no effect. At the end of the 30-min postischemic reperfusion period, the ATP pool had recovered to an appreciable extent (3.01 +/- 0.11, n = 9) and was higher when 1.0 mM inosine had been infused (3.44 +/- 0.11, n = 7). Thus, inosine increased coronary flow dose dependently and, as a consequence, the function of the isolated perfused working heart both under control conditions and during the postischemic reperfusion period.
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PMID:Effect of inosine on function and adenine nucleotide content of the isolated working rat heart: studies of postischemic reperfusion. 171 9

This investigation was designed to study the dynamics of energy-related metabolites (i.e., lactate, pyruvate, inosine, and hypoxanthine) in the extracellular fluid (ECF) of the striatum and in cisternal cerebrospinal fluid (CSF) during the first 6 h after middle cerebral artery occlusion (MCAO) using microdialysis. Ischemia induced a dramatic increase in the ECF levels of lactate, inosine, and hypoxanthine, while pyruvate did not change significantly. The major part of these changes occurred during the first 10 min after MCAO. Inosine tended to normalize towards the end, while lactate and hypoxanthine remained elevated throughout the experiment. There was no increase of the energy-related metabolites in CSF during the experiment. It was concluded that lactate, inosine, and hypoxanthine appear to be useful ECF markers of the compromised energy state of the brain during ischemia. Because the metabolites did not appear in CSF during the first 6 h after MCAO, such measurements seem not to be useful for early detection of a disturbance in energy metabolism.
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PMID:Interstitial and cerebrospinal fluid levels of energy-related metabolites after middle cerebral artery occlusion in rats. 192 70

We utilized the closed cranial window technique in the anesthetized rat to determine changes in CSF concentrations of adenosine, inosine, and hypoxanthine and pial arteriolar diameter during transient (20 min) forebrain ischemia and reperfusion. After mock CSF under the cranial window was allowed to equilibrate with cerebral interstitial fluid, endogenous adenosine concentration was found to be 0.16 +/- 0.05 microM, while inosine and hypoxanthine were 0.35 +/- 0.17 and 1.23 +/- 0.47 microM, respectively. The concentration of adenosine in CSF increased 4.2-fold during ischemia and 13.8-fold during the first 5 min of reperfusion. Inosine and hypoxanthine concentrations were also significantly increased during ischemia and reperfusion. After 1 h of reperfusion, CSF adenosine and inosine levels had decreased from peak value but remained significantly above preischemic values. In contrast, hypoxanthine remained at peak concentrations even after 60 min of reperfusion. Preischemic arteriolar diameter was 42.6 +/- 11.3 microns and was not significantly changed after 20 min of ischemia. However, during the first 5 min of reperfusion, arteriolar diameter increased significantly (p less than 0.05), coincident with peak adenosine concentrations. By 60 min of reperfusion, arteriolar diameter had returned to baseline. These results indicate that during the postischemic period, adenine nucleosides and hypoxanthine in CSF are elevated and could affect reperfusion.
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PMID:Adenosine release and changes in pial arteriolar diameter during transient cerebral ischemia and reperfusion. 193 92

Using Langendorff rat hearts, we tested whether 1. adenosine as a cardioplegic agent, and 2. inosine administered during reperfusion could prevent and treat ischemic injury, respectively. For cardioplegic arrest (37 degrees C), buffer supplemented with 20 mM K+ (K), K + 1 mM adenosine (KA), or none (Control, C), was infused for 3 min at 3 ml/min. Arrest time was 260 +/- 16 s (C), 22 +/- 4 s (K) and 10 +/- 2 s (KA, p less than 0.02 vs K). During 20 min total ischemia, resting tension increased only in C, and remained elevated after 20 min reperfusion. In treated hearts resting tension rose somewhat and returned to baseline. Developed tension: heart rate (g/min) after reperfusion was superior with KA:C (3,180 +/- 830), K (4,380 +/- 390), and KA (6,250 +/- 740, p less than 0.05 vs. K.). Our electrophysiological studies suggest that adenosine increases K(+)-permeability and thereby arrests the sinus node. It did not affect high-energy phosphates. We also tested whether inosine could regenerate nucleotides. We perfused hearts with buffer containing glucose +/- pyruvate. After 15 min no-flow, hearts were reperfused for 45 min with 20 microM inosine and 0.5 mM ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. Inosine decrease the ATP/ADT ratio by 15% (p less than 0.05) and increased the IMP level 2 times (p less than 0.01) whom pyruvate was absent. It increased the effluent adenosine concentration 6 times (p less than 0.005). Inosine administration +/- pyruvate did not affect function recovery, heart rate or coronary flow. Thus adenosine as adjunct to K(+)-cardioplegia shortened arrest time, and was also beneficial for post-ischemic recovery. Inosine given during reperfusion failed to improve heart function. Both treatments hardly affected cardiac adenine nucleotide levels.
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PMID:Prevention and treatment of ischemic injury with nucleosides. 202 58

Reports on enhanced nucleotide regeneration by purines during reperfusion are conflicting. We have, therefore, evaluated the effects of inosine or adenine, administered after ischemia, on adenine nucleotide levels and function in isolated rat hearts. The hearts were perfused with a Tyrode solution, containing 10 mM D-glucose, with or without 5 mM pyruvate. After 15 minutes without flow, the hearts were reperfused for 45 minutes with 20 microM purine and 0.5 mM D-ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. The purines decreased the ATP/ADP ratio by 10-15% (p less than 0.05) if pyruvate was absent. The IMP level in the inosine/glucose group exceeded that in all other groups by a factor of two (p less than 0.001). Inosine increased the adenosine concentration in the effluent sixfold (p less than 0.005). The hypoxanthine concentration rose up to four times following adenine treatment (p less than 0.05). The administration of purine, with or without pyruvate, did not affect mechanical recovery, heart rate or coronary flow. We conclude that inosine and adenine failed to improve cardiac function and hardly affected nucleotide levels in the reperfused heart.
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PMID:Effects of inosine and adenine on nucleotide levels in the post-ischemic rat heart, perfused with and without pyruvate. 210 91


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