Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excitatory amino acid release and neurotoxicity in the ischemic brain may be reduced by endogenously released adenosine which can modulate both glutamate or aspartate release and depress neuronal excitability. The present study reports on the patterns of release of glutamate and aspartate; the inhibitory amino acids GABA and glycine; and of the purine catabolites adenosine and inosine from the rat parietal cerebral cortex during 20 and 60 min periods of middle cerebral artery (MCA) occlusion followed by reperfusion. Aspartate and glutamate efflux into cortical superfusates rose steadily during the period of ischemia and tended to increase even further during the subsequent 40 min of reperfusion. GABA release rose during ischemia and declined during reperfusion, whereas glycine efflux was relatively unchanged during both ischemia and reperfusion. Adenosine levels in cortical superfusates rose rapidly at the onset of ischemia and then declined even though MCA occlusion was continued. Recovery to pre-occlusion levels was rapid following reperfusion. Inosine efflux also increased rapidly, but its decline during reperfusion was slower than that of adenosine.
 ...
PMID:Amino acid and purine release in rat brain following temporary middle cerebral artery occlusion. 782 64

Following our previous results which demonstrated that repeated short periods (2 min) of ischemia are capable of protecting the isolated rat heart from a subsequent global ischemia (30 min), in the present study we have concentrated on the metabolic changes occurring in rat hearts during six 2 min ischemia/3 min reperfusion cycles. Cardiac high-energy phosphates were monitored using 31P-NMR. Phosphocreatine levels fell (50-60%) during each ischemic period, and recovered to 70-80% of their initial values during reperfusion. P(i) rose by 59% during the first ischemic period, but increased less during subsequent ischemias (30% during the 6th occlusion, P < 0.05 vs. the first ischemic period) returning to baseline levels after each reperfusion. [ATP], pH, and [Mg2+] remained almost unaffected, but there was a decrease in HPLC-determined effluent ATP catabolites. The first occlusion led to a 95% drop in contractile function (P < 0.001 vs. baseline), but this recovered to 73% upon reperfusion (P < 0.02 vs. baseline), and was 65% at the end of the protocol. Phosphorylation potential (PP = [ATP]/([ADP].[P(i)]) correlated exponentially with total purine (r = 0.90) and with adenosine + inosine release (r = 0.81), and by the 6th ischemia/reperfusion cycle, exceeded that observed in controls by 21% (P < 0.05). We conclude that repeated short periods of ischemia do not lead to any significant alteration in the absolute myocardial ATP, but are associated with an enhanced cytosolic energy state in the heart, that enables the myocardium to reach a steady albeit lower functional state. Adenosine (+inosine) release may be involved in the regulation of the energy supply-demand balance.
 ...
PMID:NMR evaluation of changes in myocardial high energy metabolism produced by repeated short periods of ischemia. 782 96

Although it is well established that adenosine is released during acute ischemia, little is known of the behaviour of adenosine levels following treatment of coronary lesion by percutaneous transluminal coronary angioplasty (PTCA). Using high performance liquid chromatography, we measured intracoronary adenosine levels before and 5 min after PTCA in ten patients with one-vessel disease and a significant (> 70%) coronary stenosis. Adenosine levels decrease in all patients after PTCA. Nevertheless, more studies are now necessary to evaluate the possible predictive value (with regard to restenosis) of coronary adenosine levels after PTCA.
 ...
PMID:The use of HPLC to evaluate the variations of blood coronary adenosine levels during percutaneous transluminal angioplasty. 785 Sep 94

The effects of preconditioning, adenosine and dipyridamole in protecting the systolic and diastolic alterations of myocardial stunning in rabbit hearts were studied. Isovolumic left ventricular developed pressure (LVDP), and end diastolic pressure (LVEDP) were measured. The time constant of relaxation (T) was calculated. Isolated rabbit hearts were subject to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. LVDP and LVEDP stabilized to 55 +/- 5% and 320 +/- 28% of control values respectively (stunned group) T increased early in reperfusion (from 48.2 +/- 3.9 to 97.2 +/- 10 ms P < 0.05) but returned to control value late in reperfusion. When hearts were preconditioned by a single cycle of 5 min of ischemia LVDP and LVEDP stabilized at 89 +/- 3% and 162 +/- 34% of preischemic values respectively (P < 0.05 with respect to stunned group). The change in T was attenuated (62 +/- 6 ms at 5 min of reperfusion, P < 0.05 with respect to stunned group). Hearts treated either with adenosine (800 micrograms/min) or the nucleoside transport blocker dipyridamole (4 micrograms/min) previously to the ischemia, recovered their LVDP to 86 +/- 1% and 82 +/- 3% of preischemic values, respectively (P < 0.05 with respect to stunned group). Adenosine and dipyridamole also attenuated the increase in LVEDP (195 +/- 12% and 197 +/- 10% respectively, P < 0.05 with respect to stunned group).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenosine and dipyridamole mimic the effects of ischemic preconditioning. 786

Adenosine is now widely accepted as the major inhibitory neuromodulator in the central nervous system besides GABA. It has been suggested to be an endogenous neuroprotective metabolite. In situations of metabolic stress, e.g. ischemia adenosine decreases energy demand and increases energy supply. Of particular relevance in this context is its modulation of glutamate release. A shift of this adenosine-glutamate balance in favor of adenosine helps to restore function at the cellular, organ and organism level. Adenosine A1 receptor agonists and metabolic inhibitors, e.g. of transport, deaminase and xanthine oxidase have been demonstrated to be effective in different animal models of ischemia. Nimodipine, a L-type channel calcium antagonist currently in clinical trials for stroke and dementia syndromes, has now been shown to be a potent adenosine transport inhibitor in clinically relevant concentrations. Increase of adenosinergic neuromodulation may well be one of several future therapeutic strategies in neuroprotection.
 ...
PMID:Adenosine--an endogenous neuroprotective metabolite and neuromodulator. 788 4

A new method for the rapid determination of plasma adenosine concentrations was developed by using high-performance liquid chromatography with a column switching technique and fluorometric detection. Several "stop solutions" were used to prevent the enzymatic degradation and cellular uptake and release of adenosine in blood samples. Red blood cells and certain denatured proteins were separated by centrifugation. Subsequently, the supernatant was transferred directly into autosample vials and adenosine was reacted with chloroacetaldehyde to form a strong fluorescent, 1-N6-ethenoadenosine. The adenosine derivative was injected directly and separated on a shielded hydrophobic phase column coupled with a C18 reverse-phase column using a column switching valve. Macromolecules and other interfering substances were excluded by the shielded hydrophobic phase column and bypassed to waste. Then, the adenosine derivative and other retained compounds were switched onto the reverse-phase column for further separation and subsequently to the fluorescence detector. The system reduces the analysis time and contamination of the column and hence allows a shorter cleanup time and a longer column lifetime. Adenosine as low as 30 fmol (signal-to-noise ratio, S/N = 3) can be detected by this method. The percentage of recovery of adenosine in plasma treated with adenosine deaminase was above 90%. This method is very rapid (without tedious sample preparation) and sensitive for determining adenosine in canine blood and should prove to be useful in analyzing the effects of ischemia and reperfusion on arterial and coronary venous adenosine concentrations in blood or perfusate samples released from the ischemic or hypoxic myocardium.
 ...
PMID:Determination of plasma adenosine by high-performance liquid chromatography with column switching and fluorometric detection. 788 74

Adenosine is an endogenous nucleoside that can modulate the function of cells involved in the inflammatory response, such as polymorphonuclear leukocytes (PMN) and monocytes. Production and release of cytokines by activated mononuclear phagocytes is an important event in the pathogenesis of ischemia-reperfusion injury, a pathologic phenomenon that is associated with excessive ATP catabolism and subsequent local release of adenosine. The "retaliatory" metabolite adenosine has been shown to interfere with PMN function, thereby attenuating the deleterious consequences of ischemia and reperfusion. In this study, we demonstrate that adenosine inhibits the production of TNF-alpha, IL-6, and IL-8 by LPS-activated human monocytes with a differential potency. The A2 receptor-specific adenosine analogues 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine (NECA) were most effective in attenuating LPS-induced cytokine production, whereas the A1-selective adenosine analogue N6-cyclopentyladenosine (CPA) was less effective, indicating that inhibition of cytokine production by adenosine is primarily an A2 receptor-mediated event. The observed inhibitory effects were not restricted to endotoxin-induced cytokine production, because adenosine also inhibited TNF-alpha production by monocytes stimulated with the proinflammatory cytokine IL-1 beta. Again, 2-chloroadenosine and NECA reduced IL-beta-induced TNF-alpha production more potently than CPA. In contrast, adenosine enhanced production of IL-6 and IL-8 by monocytes stimulated with IL-1 beta. Furthermore, only 2-chloroadenosine, but not NECA, strongly inhibited cytokine-induced IL-6 and IL-8 production. These results suggest an additional A2 receptor-mediated mechanism of retaliatory action of adenosine under pathologic conditions where cytokine production by activated mononuclear phagocytes is involved, such as ischemia-reperfusion injury and septic shock.
 ...
PMID:Differential regulatory effects of adenosine on cytokine release by activated human monocytes. 793 Jun 19

The powerful vasoconstrictor autacoid thromboxane A2 (TxA2) has pathological roles in many diseases including pre-eclampsia or pregnancy induced hypertension (PIH). Adenosine and other purines are released by tissues during ischemia as occurs in the utero-placental circulation during PIH. These substances, particularly adenosine, may modulate TxA2 constrictor responses. We therefore characterized TxA2 receptors in the umbilical artery in vitro using the competitive antagonist GR32191. Also examined was the Ca2+ channels' involvement in adenosine-induced inhibition of TxA2 vasoconstriction. Results showed that TxA2 receptors on umbilical arteries are identical to those present in platelets, the placenta and umbilical vein. Adenosine was found to inhibit equally constriction involving either voltage or receptor operated Ca2+ channels.
 ...
PMID:Modulation by adenosine of thromboxane A2 receptor-mediated constriction in the human umbilical artery. 795 95

The effects of indomethacin (10 mg/kg) on the release of the transmitter amino acids, glutamate, aspartate, GABA, and of the purines, adenosine and inosine, from the cerebral cortex was studied in a four-vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison with the control group, indomethacin significantly attenuated the ischemia-evoked release of glutamate and aspartate, but not of GABA. Adenosine levels in the cortical superfusates were significantly elevated following indomethacin administration. As indomethacin is a potent inhibitor of adenosine uptake, these results suggest that, by blocking adenosine uptake, indomethacin could elevate extracellular adenosine levels and depress glutamate and aspartate efflux as a consequence of the activation of adenosine A1 receptors.
 ...
PMID:Indomethacin modulates ischemia-evoked release of glutamate and adenosine from the rat cerebral cortex. 795 50

Restoration of the ATP level after brief ischemia is limited by slow de novo ATP synthesis and substrate loss in a salvage pathways for ATP synthesis, and complete recovery requires several days in the stunned heart. Adenosine is a substrate for myocardial ATP synthesis. We measured myocardial ATP in both ex vivo and in vivo experiments by 31P magnetic resonance spectroscopy (31P-MRS) and investigated the time course of ATP content recovery after application of adenosine. Guinea-pig perfused hearts were subjected to 30 min of global ischemia and reperfused for 3 h with 50 microM adenosine. The ATP level increased from 54 +/- 5% to 117 +/- 4% of the pre-ischemic value (p < 0.01). In dogs, we occluded the left anterior descending coronary artery for 40 min to produce regional ischemia. Afterwards, we administered 100 mumol/h adenosine into the left ventricle for 2 h. ATP levels increased from 63 +/- 4% to 77 +/- 5% of the pre-ischemic value with adenosine (p < 0.05). However, ATP levels did not increase for a few hours after reperfusion both ex vivo and in vivo. Our 31P-MRS studies demonstrated that brief ischemia depressed ATP levels and that administration of adenosine accelerated ATP formation in post-ischemic hearts.
 ...
PMID:Time course of the recovery of adenosine triphosphate content with adenosine in post-ischemic hearts--a 31P magnetic resonance spectroscopy study. 796 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>