Biochemical and functional effects of nucleoside transport inhibition in the isolated cat heart

Belle, H. Van; Goossens, F.; Wynants, J.

doi:10.1016/0022-2828(89)90719-0

Cited by 30 publications

(4 citation statements)

References 14 publications

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“…More over. in the presence of transport inhibitors, the total release of adenine nucleotide catabolites decreases, particularly that of inosine, whereas the release of adenosine itself is in creased [26][27][28], In our experiments with 8-phenyltheophylline and aminophylline. how ever, the total release was increased in a high ly significant way.…”

Section: Discussionmentioning

confidence: 89%

Increase of Adenosine Release by Adenosine Antagonists in Hearts with Coronary Occlusion and Reperfusion

Bernauer¹

1996

Pharmacology

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In isolated perfused rat hearts with coronary occlusion and reperfusion, the effect of adenosine antagonists on the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated. An antagonist with high selectivity for the A⇓ receptor, 8-phenyltheophylline, was applied and compared with the relatively unspecific antagonist theophylline, used in its water-soluble form aminophylline. Depending on the duration of coronary occlusion, more or less severe tachyarrhythmias occurred during the myocardial ischemia, and particularly during the subsequent coronary reperfusion. Large amounts of the nucleosides and oxypurines were released after reopening the coronary artery. The release was particularly high in hearts with ventricular fibrillation. Both adenosine antagonists increased the release in a highly significant way. The findings let assume that adenosine has perhaps a modulating effect on its own release, which can be blocked by adenosine antagonists.

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Section: Discussionmentioning

confidence: 89%

Increase of Adenosine Release by Adenosine Antagonists in Hearts with Coronary Occlusion and Reperfusion

Bernauer¹

1996

Pharmacology

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“…The collected [78], with permission perfusate of control hearts contained almost exclusively inosine and hypoxanthine. In the soluflazinetreated hearts, the release of nucleosides decreased by about 80% as compared to controls and adenosine accounted for about 30% of the released nucleosides [49]. One hour of LAD occlusion in dogs resulted in a marked decrease in the adenine nucleotide pool, in the energy charge, and in creatine phosphate concentrations in the ischaemic tissue.…”

Section: Biochemistry: Experimentsmentioning

confidence: 82%

“…In the cat hearts, soluflazine prevented the decrease in cardiac output observed after 32 min of normothermic global ischaemia [49]. In the rabbit hearts, R 75 231 improved functional recovery after 20 rain of normothermic global ischaemia [68].…”

Section: Cardiac Functionmentioning

confidence: 96%

Purine metabolism in the heart

Donck

1994

Pharm World Sci

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Adenosine has recently received much attention for the protection it provides against the deleterious effects of ischaemia reperfusion. Whenever the demand for oxygen exceeds its supply, adenosine triphosphate in myocytes is rapidly dephosphorylated to adenosine. Adenosine may then protect the myocardium against ischaemia-reperfusion damage. However, the accumulation of adenosine is limited by its rapid uptake and catabolism in the endothelium and in red blood cells. The strict compartmentalization of the enzyme pathways involved in the metabolism of adenosine, e.g. adenosine production by myocytes, its pharmacological action in the interstitium, its catabolism in the endothelium and in red blood cells, and its carrier-mediated transport across membranes, provides a unique target for pharmacological interventions. Blockade of adenosine uptake may indeed result in prolonged adenosine accumulation specifically in those regions of the heart where it is produced. In recent years considerable evidence has been gathered on the adenosine-mediated cardioprotective actions of nucleoside transport inhibitors.

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“…On the other hand, adenosine-regulating agents which enhance the accumulation of endogenous adenosine may be clinically useful because they work only in conditions in ischemia/reperfusion and only at the site of ischemia. 6 Some recent reports have described the cardioprotective effects of nucleoside transport inhibitor (NTI) as an adenosine-regulating agent. [7][8][9][10][11][12][13][14] NTI prevents the degradation of adenosine by inhibiting the transportation of adenosine into the endothelial cells where it is degraded further to inosine.…”

mentioning

confidence: 99%

The Differential Cardioprotective Effects of Nucleoside Transport Inhibitor on Moderate and Deep Hypothermic Ischemia with Cold Cardioplegia

et al. 2000

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The differences in the cardioprotective effects of nucleoside transport inhibitor (NTI) which is known to accumulate endogenous adenosine, on moderate and deep hypothermic ischemia, were examined. Using the Langendorff model, isolated, perfused rat hearts were arrested with cold cardioplegia and subjected to 90 min of global ischemia followed by 40 min of reperfusion. The temperature during ischemia was maintained at either 10 degrees C (groups 1 and 2) or 25 degrees C (groups 3 and 4). In groups 2 and 4, NTI in the form of R75231, 1 mg/l, was added to the cardioplegic solution. The intramyocardial adenosine triphosphate content at the end of ischemia was significantly lower in the moderate hypothermia groups than in the deep hypothermia groups. In the moderate hypothermia groups, NTI significantly enhanced the adenosine accumulation at the end of ischemia. Moreover, the recovery of both the contractile function and coronary flow rate in group 4 was superior to that in group 3, and was similar to those in groups 1 and 2. The addition of NTI to the cardioplegic solution generated a sufficient cardioprotective effect in moderate hypothermic ischemia, but not in deep hypothermic ischemia. The mechanism of this discrepancy is attributed to the differences in the levels of endogenous adenosine accumulated during ischemia.

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Biochemical and functional effects of nucleoside transport inhibition in the isolated cat heart

Cited by 30 publications

References 14 publications

Increase of Adenosine Release by Adenosine Antagonists in Hearts with Coronary Occlusion and Reperfusion

Increase of Adenosine Release by Adenosine Antagonists in Hearts with Coronary Occlusion and Reperfusion

Purine metabolism in the heart

The Differential Cardioprotective Effects of Nucleoside Transport Inhibitor on Moderate and Deep Hypothermic Ischemia with Cold Cardioplegia

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