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)

Hyperkalaemia-induced hypopolarization of the sarcolemnal membrane during standard crystalloid cardioplegic arrest potentiates calcium influx during reperfusion and is associated with depletion of high-energy phosphate reserves. Adenosine has been shown to induce fast cardiac arrest whilst preserving membrane hyperpolarization in an isolated rat heart model. In this study we compared the efficacy of adenosine, both as an arresting agent and as an ultrastructural, haemodynamic and high-energy phosphate preserving agent, in an in situ global ischemia model in the baboon with St. Thomas' Hospital solution No. 2 (ST2; n = 8) and with Krebs-Henseleit buffer (KHB; n = 7). The addition of 10 mM adenosine to the non-cardioplegic KHB (ADO; n = 8) improved haemodynamic recovery significantly in terms of cardiac index (91.6% +/- 7.2 vs 59.9% +/- 9.9) and stroke volume index (101.6% +/- 8.9 vs 55.6 +/- 10.0) and was not statistically distinguishable from the ST2 with regard to cardiac index (91.6% +/- 7.2 vs 94.8% +/- 5.8), stroke volume index (101.6% +/- 8.9 vs 114.0% +/- 8.3) or left ventricular dP/dt (73.1% +/- 9.9 vs 87.0% +/- 12.4). Adenosine triphosphate was best preserved with ADO (103.5% +/- 21.1 vs 67.9% +/- 9.3 and 48.5% +/- 8.7) although this was not statistically significant. This suggests therefore that the mechanism of cardioprotection by adenosine occurs by means other than its role as high-energy phosphate precursor.
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PMID:Adenosine cardioplegia: reducing reperfusion injury of the ischaemic myocardium? 175 47

Adenine nucleotide metabolism is greatly altered by myocardial anoxia or ischemia, both of which induce depletion of ATP and of the total adenine nucleotide pool. The depletion occurs at variable rates depending upon the nature of the model and the severity and conditions of the injury. In ischemia, the decrease in both ATP and the adenine nucleotide pool is due to an inadequate rate of production of high-energy phosphate relative to the demand of the heart for energy. In the process of capturing the high-energy phosphate of ADP, AMP is produced via myokinase and is degraded to nucleosides and ultimately to bases. In the early phase of ischemia, ADO and INO are the chief metabolites produced. A small quantity of XAN and large quantities of HX accumulate with time until eventually HX replaces INO as the principal metabolite of the pool. The biology of myocardial ischemic cell damage in the dog heart is summarized with respect to the depletion of ATP and total adenine nucleotide pool. Myocytes can survive with about 25% of the ATP of control tissue but exhibit a variety of defects that persist for minutes to days. At the onset of irreversibility, the dead tissue invariably exhibits virtually no ATP and a 65% or greater depletion in the total adenine nucleotide pool. It is not known whether these changes in ATP and the pool are directly or indirectly related to the development of irreversibility. In any event, the transition to cell death appears to be gradual.
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PMID:Nucleotide metabolism and cellular damage in myocardial ischemia. 258 8

Small mesenteric arteries supplying partially isolated jejunal segments were totally occluded for 5 minutes and then released. With video microscopy, blood flow was calculated from measurements of submucosal arteriolar diameter and red blood cell velocity. For the first 30 minutes of reperfusion, the serosa was superfused with a Ringer's vehicle containing either adenosine (ADO; 10(-4) M), acetylcholine (ACh; 10(-5) M), or prostacyclin (PGI2; 3 x 10(-7) M). Thereafter, the substances were removed from the suffusate, and superfusion continued with vehicle alone for an additional 10-30 minutes. These concentrations were equieffective for causing vasodilation. During the first minute of reperfusion, blood flow increased more than 300% of baseline in all groups. Within the subsequent 30 minutes, blood flow fell to 45 +/- 3% of baseline with vehicle alone, which demonstrates the no-reflow phenomenon. While either ADO, ACh, or PGI2 was in the suffusate, vasodilation was persistent. After washout of these substances, the postocclusion blood flows were significantly higher with each treatment than with vehicle alone, which shows that each substance had a positive action. However, with ADO, blood flow was 121 +/- 7% of baseline after washout, whereas with ACh or PGI2, it was 64 +/- 10% or 69 +/- 5% of baseline after washout. This property of ADO was observed if the mucosa was superfused with a Ringer's solution or with a bile salt solution, which suggests that ADO might have similar properties in situ. After 60 minutes of reperfusion, the intestinal villi were short, thick, and edematous with epithelial necrosis and crypt degeneration. ADO attenuated most of these histological changes to a greater extent than either PGI2 or ACh. Furthermore, ADO reduced a biochemical index of neutrophil infiltration; tissue myeloperoxidase concentration was increased to 169 +/- 14% of baseline with vehicle but was increased to 120 +/- 8% with ADO. Overall, these observations suggest that ADO protects the intestine from ischemia-reperfusion injury by causing vasodilation and by inhibiting neutrophil function. The vasodilatory effect probably is a minor component because other vasodilators (ACh and PGI2) had minimal protective effects in these conditions.
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PMID:Attenuation of no-reflow phenomenon, neutrophil activation, and reperfusion injury in intestinal microcirculation by topical adenosine. 266 71

Evidence supports the involvement of adenosine receptor stimulation and activation of K(ATP) channels in ischemic preconditioning of human myocardium. It is unknown, however, whether protection mediated by adenosine receptors is dependent upon the K(ATP) channel in the human heart. The purpose of this study was to determine whether adenosine-mediated protection against a simulated ischemia-reperfusion injury in human myocardium is dependent upon K(ATP) channels. Isolated human right atrial trabeculae were placed in tissue baths at 37 degrees C, oxygenated with a modified Tyrode solution, and field stimulated at 1 Hz. Trabeculae were subjected to 45 min of normothermic simulated ischemia (hypoxic, substrate-free buffer with pacing at 3 Hz.) and 60 min of reperfusion (I/R trabeculae). Trabeculae were preconditioned with simulated ischemia (IPC trabeculae) or adenosine receptor stimulation (adenosine, 125 micromol/l) for 5 min (ADO trabeculae) prior to simulated ischemic-reperfusion injury. Inhibition of the K(ATP) channel with glibenclamide (10 micromol/l) was combined with adenosine pretreatment (ADO+GLI trabeculae) or alone (GLI trabeculae) prior to simulated ischemic-reperfusion injury. Developed force (DF) at end reperfusion (mean+/-S.E.) was compared to baseline developed force, and tissue creatine kinase (CK) activity at end reperfusion was measured. I/R trabeculae showed 27+/-2% of baseline DF, whereas IPC trabeculae or ADO trabeculae showed 50+/-4% and 43+/-3% of baseline DF, respectively. ADO+GLI trabeculae showed 25+/-2% and GLI trabeculae showed 23+/-4% of baseline DF. Tissue CK activity was enhanced in the IPC and ADO trabeculae (433+/-63 U/g wet myocardium, and 415+/-28 U/g wet myocardium, respectively). I/R trabeculae had 196+/-26 U/g wet myocardium and ADO+GLI trabeculae had 277+/-38 U/g wet myocardium at end reperfusion. The results suggest that ischemic preconditioning and adenosine receptor stimulation confer functional protection against simulated ischemic-reperfusion, and adenosine mediated protection is eliminated by K(ATP) channel inhibition in human myocardium.
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PMID:Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive K+ channel. 904 32

In order to examine the relationship between local adenosine concentrations before, during, and after ischemia and the extent of ischemic myocardial damage, measurements of interstitial fluid (ISF) nucleosides were made using microdialysis probes implanted in the ischemic region of isoflurane anesthetized Micropigs undergoing 60' coronary artery occlusion (CAO) and 3 h of reperfusion (REP). Nucleoside concentrations in the dialysate collected from the microdialysis probes were used as an index of ISF levels. Dialysate nucleoside concentrations (ADO, inosine and hypoxanthine), myocardial infarct size, and myocardial blood flow (MBF) were determined in control animals (n = 6), animals preconditioned with a single 10' cycle of CAO and REP (PC, n = 6), and those treated with the adenosine deaminase inhibitor pentostatin (n = 6, 0.2 mg/Kg i.v. 30' prior to CAO). The brief PC occlusion resulted in a transient but significant increase in dialysate ADO (6.7 +/- 1.8 microM vs. 0.67 +/- 0.1 microM at baseline). Pentostatin administration had no significant effect on either dialysate nucleosides or MBF at baseline. During the 60' CAO, dialysate ADO increased in control animals. In PC animals, however, dialysate ADO during CAO was lower than control. Pretreatment with pentostatin resulted in a six-fold augmentation in dialysate ADO during the 60 min CAO when compared to the control values (110.62 +/- 30.2 microM vs. 16.31 +/- 2.1 microM at 60 min of ischemia). Pentostatin also resulted in a significant reduction in the accumulation of inosine and hypoxanthine, indicating inhibition of adenosine deaminase activity. There were no significant differences in MBF between groups at any time point. Following 3 h REP, infarct size was 35.4 +/- 5.5%, 8.1 +/- 1.5% and 8.3 +/- 1.8% of the region at risk in control, PC, and pentostatin groups, respectively. These data suggest that marked increase in ISF ADO during CAO, may be as effective in reducing INF as a modest increase in ISF ADO prior to prolonged CAO.
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PMID:Effects of ischemia, preconditioning, and adenosine deaminase inhibition on interstitial adenosine levels and infarct size. 934 31

Approximately 30% of patients suffer supraventricular dysrhythmias after cardiac bypass. While the heart can be constructively preconditioned to maintain function against subsequent ischemic insult using a variety of stimuli across many species, preconditioning in experimental animals is associated with decreased postischemic reperfusion cardiac dysrhythmias. This mode of therapeutic preconditioning has not been previously examined in human atrial myocardium. We therefore hypothesized that preconditioning provides both antidysrhythmic and functional protection to human atria. To study this, human atrial trabeculae were suspended in organ baths, paced at 1 Hz, while force development and ectopy were recorded before and after simulated ischemia. The study consisted of five groups: (1) control trabeculae (n = 12), (2) trabeculae exposed to dysrhythmogenic stimuli (phenylephrine 50 microM and isoproterenol 25 microM (n = 8)), (3) trabeculae exposed to ischemia-reperfusion (I/R) injury and then drug stimulated (n = 10), (4) trabeculae preconditioned with adenosine (ADO 125 microM) then drug stimulated (n = 10), and (5) trabeculae preconditioned with ischemic preconditioning (IPC) then drug stimulated (n = 6) each at end reoxygenation. Differences between groups were assessed using X2 analysis and ANOVA (Bonferroni/Dunn). Results demonstrated that human atrial trabeculae did not exhibit dysrhythmia at baseline or when stimulated with alpha and beta agonists. After I/R, control trabeculae exhibited stimulated reperfusion dysrhythmia, while trabeculae preconditioned with either ADO or transient ischemia exhibited decreased stimulated dysrhythmia (each P < 0.05 vs. I/R). Functionally, I/R decreased developed force (DF) to 16 +/- 2% of baseline (%BDF) while ADO pretreatment increased postischemic DF to 41 +/- 3% BDF (P < 0.05 vs. I/R) while IPC increased DF to 49 +/- 3% BDF (P < 0.05 vs. I/R). We conclude that (1) human atrial trabeculae can ve functionally preconditioned with either ADO or IPC, and (2) protective preconditioning/ cardioprotection does extend to dysrhythmia control and is therapeutically accessible in human atrial myocardium.
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PMID:Therapeutic antidysrhythmic and functional protection in human atria. 969 14

Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate was infused 1 h before (1 g. kg(-1). h(-1)) and 2 h during (0.5 g. kg(-1). h(-1)) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruvate group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.
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PMID:Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. 1060 Aug 44

Ingestion of low levels of ethanol 24 h before [ethanol preconditioning (EPC)] ischemia and reperfusion (I/R) prevents postischemic leukocyte rolling (LR) and adhesion (LA), effects that were abolished by adenosine A(2) receptor (ADO-A(2)R) antagonists or nitric oxide (NO) synthase (NOS) inhibitors. The aims of this study were to determine whether NO derived from endothelial NOS (eNOS) during the period of ethanol exposure triggered entrance into this preconditioned state and whether these events were initiated by an ADO-A(2)R-dependent mechanism. Ethanol or distilled water vehicle was administered to C57BL/6J [wild type (WT)] or eNOS-deficient (eNOS-/-) mice by gavage. Twenty-four hours later, the superior mesenteric artery was occluded for 45 min. LR and LA were quantified by intravital microscopy after 30 and 60 min of reperfusion. I/R increased LR and LA in WT mice, effects that were abolished by EPC or NO donor preconditioning (NO-PC). NO-PC was not attenuated by coincident administration of an ADO-A(2)R antagonist. I/R increased LR and LA in eNOS-/- mice to levels comparable with those noted in WT animals. However, EPC only slightly attenuated postischemic LR and LA, whereas NO-PC remained effective as a preconditioning stimulus in eNOS-/- mice. Preconditioning with an ADO-A(2)R agonist (which we previously demonstrated prevents I/R-induced LR and LA in WT animals) failed to attenuate these postischemic adhesive responses in eNOS-/- mice. Our results indicate that EPC is triggered by NO formed secondary to ADO-A(2)R-dependent eNOS activation during the period of ethanol exposure 24 h before I/R.
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PMID:Role of eNOS-derived NO in the postischemic anti-inflammatory effects of antecedent ethanol ingestion in murine small intestine. 1709 34