Disease relevance of ADA

• However, ADA did not inhibit dilation induced by gradual stenoses (10.6 +/- 1.4, 24.2 +/- 4.3, 17.5 +/- 6.9%, at each PP, NS vs. vehicle group).(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• Under control, pre-ADA conditions, hypoxia (arterial PO2 19 +/- 2 mmHg) caused left anterior descending (LAD) coronary blood flow to increase from 100 +/- 12 to 382 +/- 47 ml X min-1 X 100 g-1 (+282%) [2].
• The NE-induced hyperemia and the increase in MVo2 were again decreased by ADA [3].
• ADA also attenuated significantly the coronary vasodilatory response to exogenous adenosine and to 20-s ischemia [2].
• Efficacy of ADA was also evaluated by examining its effect on the coronary responses to exogenous adenosine and to 20-s myocardial ischemia [2].

High impact information on ADA

• Aware of the defective lymphopoiesis associated with adenosine deaminase and purine nucleoside phosphorylase deficiencies, we hypothesized that abnormal purine or pyrimidine metabolism might be present in these dogs [4].
• The possible contribution of an endothelial dilator secondary to activation of adenosine receptors on endothelial cells was tested by comparing the response to exogenous intracoronary adenosine infusion with increases in endogenous adenosine produced by inhibition of adenosine kinase and adenosine deaminase [5].
• We employed intracoronary infusion of adenosine deaminase to test the hypothesis that endogenous adenosine contributes to regulation of coronary blood flow following acute reductions in coronary artery pressure [6].
• Additional experiments demonstrated that adenosine deaminase reversibly attenuated myocardial reactive hyperemia following 5- and 10-second coronary occlusions by 30% (P less than 0.05), evidence that the infused enzyme effectively degraded endogenous adenosine [6].
• However, adenosine deaminase did not alter the time course for coronary autoregulation or the steady state autoregulatory flow response over the pressure range between 125 and 75 mm Hg [6].

Chemical compound and disease context of ADA

• Reactive hyperaemic flow response of the circumflex coronary artery was observed following 5, 10, 15, 20 and 30 s coronary occlusions before, during and after infusion of 8-azaguanine and adenine, which are known as adenosine deaminase inhibitors [7].
• Ventricular bigeminy, the most prominent arrhythmia seen in this study, was significantly reduced by adenosine deaminase and BW A1433U [8].
• Effect of adenosine deaminase inhibition with pentostatin on myocardial stunning in dogs [9].
• Interference with adenosine action, by administration of adenosine deaminase plus theophylline, decreased reactive hyperemia by 31.0 +/- 4.0% (p < 0.001) [10].
• Adenosine deaminase attenuates norepinephrine-induced coronary functional hyperemia [3].

Biological context of ADA

• EHNA (3--10 microM in blood) did not inhibit stimulated lipolysis in vivo possibly because of the low ADA activity in fat cells [11].
• ADA completely blocked the norepinephrine-induced vasodilation (n = 6) [12].
• In eight dogs, the NE-induced hyperemia was decreased from +150 to +67%, the change in myocardial oxygen consumption (MVo2) was attenuated from +177 to +101% by ADA, and the increase in HR was reduced from +28 to +16% [3].
• Infusion of ADA confirmed the specificity of the response by blocking the metabolic effect of exogenously infused ADO [13].
• In unstimulated tissues, ADA (n = 7) significantly increased vascular resistance and significantly decreased glucose uptake compared with the effects of a control (boiled deaminase, n = 6) infusion [12].

Anatomical context of ADA

• Blood flow in regions of myocardium supplied by the nonstenotic left anterior descending coronary artery were unchanged following ADA plus 8-PT.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• CONCLUSIONS: Although inhibition of adenosine deaminase effectively enhances ISF adenosine before and during ischaemia, the increase before ischaemia does not "precondition" the myocardium, nor does the augmentation of adenosine during and after ischaemia attenuate necrosis in this model of ischaemia [15].
• The heart was paced (3 V, 0.2 ms and a suitable frequency) via two electrodes attached to the right atrium from 109 +/- 7.3 to 170 +/- 9.8 beats min-4 (means +/- S.E.M.) for 3-4 min, first during an infusion of the solvent, and then during an infusion of a solution of adenosine deaminase (5 U kg-1 min-1) into the circuit [16].
• Pharmacokinetic studies showed pentostatin significantly inhibited adenosine deaminase in canine lymphocytes [17].
• These in vivo experiments clearly demonstrate that alpha-2 adrenoceptor stimulation is able to inhibit beta-stimulated or theophylline plus adenosine deaminase-promoted lipid mobilization from bone marrow fat stores [18].

Associations of ADA with chemical compounds

• Topically applied ADA significantly inhibited intravenously (i.v.) administered adenosine-induced arteriolar dilation [1].
• 8-Phenyltheophylline (8-PT 10 microM) or adenosine deaminase (ADA 10 U/min) was topically superfused onto the heart [1].
• In all groups, the O2 extraction response to increased MVo2 increased and the flow response decreased after ADA [3].
• In six dogs nitroprusside was infused during NE after ADA [3].
• During reactive dilation, the bioassay kidney responded with a large resistance increase which was blocked by theophylline and adenosine deaminase and converted to a decrease by adenosine autoblockade [19].

Analytical, diagnostic and therapeutic context of ADA

• Oxygen consumption in the LAD perfusion field was unchanged by hypoxia before ADA but fell significantly during hypoxia after ADA [2].
• Intracoronary infusion of adenosine deaminase (n = 10) but not vehicle (n = 5) into the LAD during a 15-minute LAD occlusion prevented the attenuation in constriction to stellate stimulation [20].
• Myocardial blood flow was assessed with radioactive microspheres during exercise prior to and during intracoronary infusion of U46619 (0.01 microgram.kg-1 x min-1), in the absence and the presence of adenosine receptor blockade with intravenous 8-phenyltheophylline (5 mg.kg-1) and intracoronary adenosine deaminase (50 units.kg-1) [21].
• The 16 dogs given adenosine deaminase were further subdivided into those perfused with blood deoxygenated by a donor canine lung (group 1, n = 11) and those perfused with blood from a paediatric oxygenator (group 2, n = 5) [22].
• Adenosine kinase, but not 5'-nucleotidase (5'-NTase) or adenosine deaminase activity determined following reperfusion was 76% and 60% higher (P < 0.05) in non-risk and post-ischemic myocardium of MLA pretreated rabbits compared with controls [23].

References