Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In isolated perfused rat hearts with occlusion of the left coronary artery the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated with and without exogenous addition of adenosine deaminase. In the control experiments large amounts of the adenine nucleotide catabolites appeared in the perfusate during coronary reperfusion. The greater part was represented by adenosine and inosine. During the coronary occlusion itself only a minor increase in the release of adenine nucleotide catabolites was observed, compared with the basal release before the coronary occlusion. Depending on the duration of the coronary occlusion more or less severe tachyarrhythmias occurred during the reperfusion of the previously ischaemic myocardium. Reperfusion-induced ventricular fibrillation was associated with a significant increase in the release of adenine nucleotide catabolites, compared with non-fibrillating hearts. In the presence of exogenously-added adenosine deaminase the release of adenine nucleotide catabolites from reperfused hearts was further increased. Adenosine itself, however, almost completely disappeared from the perfusate. In adenosine-deaminase treated hearts the incidence of reperfusion-induced fibrillation increased, thereby contributing to the enhanced release of adenine nucleotide catabolites. However, the release was also increased by the enzyme when only the fibrillating hearts were considered, suggesting that rapid elimination of adenosine from the interstitial space also directly increases the release of adenine nucleotide catabolites from the heart.
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PMID:Effect of exogenous adenosine deaminase on arrhythmias and the release of adenine nucleotide catabolites in isolated rat hearts with coronary occlusion and reperfusion. 181 Nov 71

The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with 125I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. 125I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior descending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 +/- 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 +/- 0.38, P less than 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 +/- 0.36 vs. circumflex zone = 1.45 +/- 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distal: circumflex epicardial flow ratio declined vs. control 1 (0.98 +/- 0.14) during adenosine deaminase infusion (0.87 +/- 0.17, P less than 0.05). The distal:circumflex endocardial flow ratio during adenosine deaminase (0.72 +/- 0.20) was unchanged vs. control 1 (0.76 +/- 0.22) but was less than control 2 (0.80 +/- 0.18, P less than 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s).
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PMID:Role of adenosine in the maintenance of coronary vasodilation distal to a severe coronary artery stenosis. Observations in conscious domestic swine. 686 Dec 96

Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and has been demonstrated to augment endogenous adenosine levels during regional and global myocardial ischemia. Based on the rationale that increasing endogenous adenosine during ischemia may be cardioprotective, the objective of this study was to determine if adenosine deaminase inhibition with pentostatin could improve postischemic contractile dysfunction (stunning) in open-chest anesthetized dogs. All animals underwent 15 min of coronary occlusion followed by 3 h of reperfusion preceded by an intravenous bolus of either 0.2 mg/kg of pentostatin (n = 8) or saline (n = 7). Sonomicrometers were placed in the ischemic area and were used to measure systolic wall thickening before, during, and after occlusion of the left anterior descending artery. Myocardial blood flow was measured with tracer labeled microspheres at baseline, 10 min of occlusion and at 1 h of reperfusion. Both groups were equally dyskinetic during occlusion (-21 +/- 5% of baseline thickening in the controls and -28 +/- 8% in the pentostatin group). The pentostatin group, however, demonstrated better contractile function at all time points during reperfusion, which was significantly different from the control group at 3 h of reperfusion. The improvement in regional function in the pentostatin group was not due to significant disparities in hemodynamic variables, size of the region at risk, or in collateral blood flow. These results indicate that pentostatin can ameliorate the severity of myocardial stunning, an effect we propose is due to increasing endogenous levels of adenosine during the ischemic interval. Although significant improvement was detected with pentostatin, the improvement was modest compared to controls, suggesting that the utility of inhibiting adenosine deaminase to modify regional mechanical stunning is limited.
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PMID:Effect of adenosine deaminase inhibition with pentostatin on myocardial stunning in dogs. 764 20

Adenosine receptor activation has been assumed to play a role in the cardioprotective effect of ischemic preconditioning. The actions of adenosine are terminated by the naturally occurring substance adenosine deaminase. We determined whether 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, could mimic the effect of preconditioning in nonpreconditioned rats and potentiate the salutary effect of preconditioning in preconditioned rats. We assessed the effect of DCF on myocardial infarct size and the incidence of ventricular arrhythmias in four groups of anesthetized rats: control (nonpreconditioned) + vehicle, control + DCF, preconditioned + vehicle, and preconditioned + DCF. All rats underwent 90 minutes of coronary artery occlusion followed by 4 hours of reperfusion, while preconditioned rats received three cycles of 3-minute episodes of ischemia and 5 minutes of reperfusion before the 90-minute occlusion. Following 4 hours of reperfusion, area at risk was determined by intravenous injection of blue dye during a brief coronary occlusion, and area of necrosis was determined by incubation of heart slices in triphenyltetrazolium chloride. In the nonpreconditioned control rats receiving vehicle, myocardial infarct size expressed as a percentage of the area at risk averaged 44.8 +/- 7.6%. Pretreatment with DCF had no effect on infarct size (49.4 +/- 4.9%) in the nonpreconditioned control rats. Both the preconditioned+vehicle (19.2 +/- 7.8%) and the preconditioned + DCF (17.9 +/- 5.1%) groups had a significant reduction in infarct size (p < 0.05 versus control + vehicle and control + DCF), with no significant difference in infarct size between the two preconditioned groups. The incidence of ventricular tachycardia (VT) during the 90 minutes of ischemia was significantly attenuated in both preconditioned groups (p < 0.05 versus controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine deaminase inhibition is not cardioprotective in the rat. 824 84

Body core temperature in the normothermic range alters infarct size in rabbits. Moreover, temperature may modulate the protection by adenosine during a coronary artery occlusion. We investigated the effect of core temperature within the normothermic range (35-39 degrees C) on myocardial infarct size produced by a 45-min coronary occlusion in open-chest swine (n = 10), and we determined whether adenosine blockade with 8-phenyltheophylline and adenosine deaminase increased infarct size in the normothermic range (n = 9). After 4 h of reperfusion the area at risk and infarct size were determined with Evans blue dye and triphenyltetrazolium chloride. Infarct size strongly correlated with temperature (r2 = 0.71, P = 0.0001) so that at 35 degrees C no infarction occurred and with each 1 degree C increase in temperature 20% of the area at risk became infarcted. In contrast, neither the low levels of collateral flow (0.03 +/- 0.01 ml.min-1.g-1) nor the rate-pressure product correlated with infarct size. In the normothermic range, adenosine blockade had no effect on infarct size. The data demonstrate that temperature can exert a profound effect on infarct size but fail to demonstrate a protective effect on endogenous adenosine at normothermic temperatures. Our findings emphasize the need for stringent control of core temperature during investigation of interventions aimed at reducing infarct size.
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PMID:Effect of temperature on myocardial infarction in swine. 896 56

In the perfused guinea-pig heart reactive hyperaemia (RH) after occlusion of coronary flow (1-60 s) was inhibited by 100-60% with NG-nitro-L-arginine (100 microM) and to a lesser extent (by 35%) after 8-phenyltheophylline (10 microM), but not by indomethacin (5 microM). Inhibition of adenosine deaminase by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (5 microM) not only increased the concentration of adenosine in the coronary perfusate, but also prolonged the duration of RH. RH induced cardiac generation of prostacyclin, nitric oxide and adenosine as indicated by the appearance of 6-keto-PGF1 alpha, cyclic GMP, adenosine, inosine, hypoxanthine, xanthine and urate in the perfusate. Only NO and adenosine, but not prostacyclin, were responsible for RH. RH after short-term (1-10 s) coronary occlusion was mediated by NO, whereas adenosine and NO maintained RH that followed after longer (20 s-10 min) periods of cardiac ischaemia. Prostacyclin never participated in the mediation of RH.
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PMID:Ischaemic cardiac hyperaemia: role of nitric oxide and other mediators. 908 46