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)

The presence of monoacylglycerol lipase was established in extracts of acetone-dried powders from rat and bovine brains using thioester substrate analogs. At pH 7.4, the apparent Km and Vmax values for 1-S-decanoyl-1-mercapto-2,3-propanediol were 56 microM and 227 nmol/h/mg protein in bovine gray matter. The divalent metal ions Ca2+ and Mg2+ had no effect on enzymic activity, but Zn2+ at 500 microM produced a 50% inhibition of this enzyme. Free fatty acids also caused a marked inhibition of monoacylglycerol lipase activity. Norepinephrine and 5-hydroxytryptamine slightly stimulated the enzymic activity. Hypoxic-hypoxia and 30-s postdecapitation ischemia resulted in a considerable increase in monoacylglycerol lipase activity of rat brain. However, the increased activity of monoacylglycerol lipase returned to normal after 5 min of ischemia. The increased activity of monoacylglycerol lipase during hypoxic-hypoxia and short-time ischemia may be partially responsible for increased levels of free fatty acids during these processes.
 ...
PMID:Monoacylglycerol lipase. Regulation and increased activity during hypoxia and ischemia. 610 May 9

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
 ...
PMID:Senile dementia of the Alzheimer type. 613 75

Norepinephrine (NE) depletion of the cerebral cortex after lesion of the ipsilateral locus ceruleus (LC) causes abnormalities of cerebral oxidative metabolism when the cortex is stimulated to increased energy demand (Harik, S. I., J. C. LaManna, A. I. Light, and M. Rosenthal (1979) Science 206: 69-71; LaManna, J. C., S. I. Harik, A. I. Light, and M. Rosenthal (1981) Brain Res. 204: 87-101). These abnormalities were exhibited as decreased mitochondrial reducing equivalent flow. One possible cause of this would be the decreased availability of oxidative metabolic substrates in the NE-depleted cortex. We therefore investigated the effect of unilateral LC lesion and the resultant depletion of ipsilateral endogenous NE on glycogen and other energy metabolites in the cerebral cortex of rats under three conditions: (1) at "rest," (2) when energy demand is inncreased markedly by seizures, and (3) during total cerebral ischemia. We report no differences in cerebral metabolites between NE-depleted and control hemispheres at "rest." In seizures and ischemia, however, the increase in the level of adenosine 3':5'-monophosphate (cyclic AMP) and the breakdown of glycogen were impaired considerably in the NE-depleted cortex. The data suggest that depletion of central NE impairs cerebral glycogenolysis in response to increased energy demands and ischemia. Such impairment may be mediated via a cyclic AMP-related mechanism.
 ...
PMID:Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia. 627 95

The accumulation of endogenous catecholamines within the extracellular space of the ischemic myocardium has been studied in the isolated perfused (Langendorff) heart of the rat subjected to various periods of complete ischemia, with subsequent collection of the reperfusate. Catecholamines and deaminated metabolites were measured by radioenzymatic methods, or high pressure liquid chromatography. Ischemic periods of less than 10 minutes are not associated with an increased overflow of catecholamines or metabolites. Longer periods of ischemia are accompanied by the overflow of noradrenaline and its deaminated metabolite 3,4-dihydroxyphenylglycol. This overflow increases with lengthening of the preceding ischemic period (10 minutes: 2.5 +/- 0.6, 20 minutes: 209.8 +/- 17.2, 60 minutes: 1270.5 +/- 148.1 pmol noradrenaline/g heart). Noradrenaline concentration is highest during the first minute of reperfusion, suggesting that the noradrenaline detected during reperfusion is released into the extracellular space of the myocardium during ischemia and is subsequently eluted. Experiments with variation of extracellular calcium concentration and with neuronal uptake (uptake1) blocking agents suggest that different mechanisms of catecholamine release are acting during the course of ischemia. A calcium-independent carrier-mediated efflux of noradrenaline from the nerve terminals is of major importance, using the same carrier as is normally responsible for transporting noradrenaline from the synaptic clefts into the neuronal varicosities. Thus, various uptake1-blocking agents diminish the noradrenaline overflow following ischemic periods of between 10 and 40 minutes. The noradrenaline overflow following longer periods of ischemia is unaffected by uptake1-blocking agents, and additional noradrenaline release at this time is probably consequent upon dissolution of cell membranes. Overflow of adrenaline and dopamine occurs to a minor degree (less than 5% of the corresponding noradrenaline overflow), and only after ischemic periods of more than 15 minutes.
 ...
PMID:Release of endogenous catecholamines in the ischemic myocardium of the rat. Part A: Locally mediated release. 648 89

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Thiopental treatment after global brain ischemia in pigtailed monkeys. 669 50

The difference in end-products of the nitric oxide, i.e., nitrate-plus-nitrite, in the coronary arterial and venous blood was increased during coronary hypoperfusion of the canine heart (12.8 +/- 0.6 vs. 2.2 +/- 0.2 microM at the baseline). Norepinephrine from sympathetic nerve endings in the heart is released due to ischemic stress, however the relation of norepinephrine with nitric oxide is unknown during ischemia. Neither beta- or alpha 2-adrenoceptor antagonists attenuated the release of nitric oxide during coronary hypoperfusion. An intracoronary infusion of an alpha 1-adrenoceptor antagonist attenuated the release of nitric oxide during coronary hypoperfusion (5.3 +/- 0.4 microM), and the attenuation of alpha 1-adrenoceptor activity further decreased coronary blood flow during hypoperfusion. These findings suggest that alpha 1-adrenoceptor activity contributes to the mechanisms whereby nitric oxide is released from the ischemic myocardium.
 ...
PMID:Roles of alpha 1-adrenoceptor activity in the release of nitric oxide during ischemia of the canine heart. 762 2

In the present study the hypothesis was tested that local noradrenaline release contributes to adenosine formation in myocardial ischemia. Therefore, in ischemic non-working rat hearts either adrenergic receptors or ischemia-evoked noradrenaline release were blocked. Noradrenaline and adenosine were determined in the effluent using HPLC-methods. Following 20 min of stop of perfusion flow both the beta-adrenergic receptor antagonist bisoprolol (91.6 +/- 10.5 nmol/g) and the inhibitor of ischemia-induced noradrenaline release desipramine (108.5 +/- 12.5 nmol/g) caused a suppression of adenosine release (control: 140.9 +/- 7.3 nmol/g). To examine the time-course of the release, further experiments were performed at constant perfusion flow with energy metabolism blocked by cyanide together with removal of glucose from the perfusion buffer. This condition resulted in a nearly simultaneous release of adenosine and noradrenaline from the hearts. The beta-adrenoceptor blocking agents atenolol and bisoprolol postponed the release of adenosine, whereas the alpha-antagonists prazosin and yohimbine had no effect on adenosine release induced by cyanide. None of the adrenergic receptor blockers affected the release of noradrenaline. The inhibitors of the neuronal noradrenaline carrier (uptake1) desipramine, oxaprotiline, and cocaine suppressed the release of noradrenaline during cyanide administration, indicating a carrier-mediated efflux of noradrenaline. Reduction of extracellular noradrenaline by these agents coincided with a delay of adenosine release (cumulative release within 20 min--control: 251.2 +/- 13.9, desipramine: 172.1 +/- 15.3, oxaprotiline 36.5 +/- 5.8, cocaine: 111.8 +/- 23.6 nmol/g). Desipramine and cocaine were also used during administration of exogenous noradrenaline in normoxic hearts, to confirm specificity of their action.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiac noradrenaline release accelerates adenosine formation in the ischemic rat heart: role of neuronal noradrenaline carrier and adrenergic receptors. 786 92

The effects of some components of ischemia on the oscillatory (Vos) and nonoscillatory (V(ex)) potentials and respective currents (Ios and Iex), as well as their mechanisms, were studied in guinea pig isolated ventricular myocytes by means of a single-microelectrode, discontinuous voltage clamp method. Repetitive activations induced not only Vos and Ios, but also V(ex) and Iex. A small decrease in resting potential caused an immediate increase in Vos followed by a gradual increase due to the longer action potential. Immediate and gradual increases in Ios also occurred during voltage clamp steps. A small depolarization increased Vos and V(ex), and facilitated the induction of spontaneous discharge by fast drive. At Vh where INa is inactivated, depolarizing steps induced larger Ios and Iex, indicating the importance of the Na-independent Ca loading. High [K]o decreased the resting potential, but also Vos, V(ex), Ios, Iex, and ICa. In high [K]o, depolarization still increased Vos and V(ex). Norepinephrine (NE) enhanced Vos and V(ex), and also Ios and Iex, during voltage clamp steps. High [K]o antagonized NE effects, and NE those of high [K]o. In conclusion, on depolarization, Vos and Ios immediately increase through a voltage-dependent mechanism; and then Vos and Ios gradually increase, apparently through an increased Ca load related to the longer action potentials and the Na-Ca exchange. The depolarization induced by V(ex) may contribute to increase Vos size. Vos and V(ex) are similarly influenced by different procedures that modify Ca load. The arrhythmogenic events are enhanced by the simultaneous presence of depolarization, faster rate, or NE. Instead, high [K]o decreases Vos and V(ex) by decreasing ICa and opposes the effects of NE. The voltage clamp results show that potentiation and antagonism between different components of ischemia are due primarily to changes in Ca loading and not to changes in action potential configuration.
 ...
PMID:Mechanisms underlying the modulation of arrhythmogenic events by components of ischemia in guinea pig cardiac myocytes. 792 70

Myocardial ischemia, electrolyte changes, and fluctuations in autonomic tone may play an important role in the presentation of malignant ventricular arrhythmias. beta-Adrenoceptor blocking agents have been shown to decrease the incidence of ventricular fibrillation and sudden cardiac death in patients with coronary artery disease. Therefore we investigated the changes in myocardial metabolism and transcardiac electrolytes during simulated ventricular tachycardia before and after beta-adrenergic blockade. Six patients with normal coronary arteries (group 1) and 12 patients with documented coronary artery disease (group 2) were included in the study. The right ventricle was paced with electrode catheters to a constant cycle length of 400 msec for 3 minutes. Blood samples were withdrawn simultaneously from the coronary sinus and femoral artery to determine the transcardiac differences in metabolic variables and electrolytes before the pacing, at the end of the pacing, and 2 minutes thereafter. After pacing, the patients were given intravenous propranolol (0.15 mg/kg), and the protocol was repeated. Intraarterial blood pressure and electrocardiogram were monitored continuously. There was a rapid decline of the mean arterial blood pressures after initiation of the pacing in both study groups, whereafter the pressures began to rise. Propranolol somewhat blunted the blood pressure recovery, especially in group 2. Norepinephrine levels increased during the pacing in both patient groups, and the increase was accentuated by beta-adrenergic blockade. The femoroarterial coronary sinus difference in lactate turned negative, and pH, PCO2 and potassium differences increased in group 2 during pacing. However, the myocardial energy state remained relatively good as estimated from the nonsignificant change in the transcardiac differences of the plasma adenosine catabolites. There were no changes in the metabolic variables or transcardiac electrolytes in group 1 patients during pacing. Propranolol did not prevent the metabolic ischemia, but it did prevent the pacing-induced decrease in coronary sinus potassium and increase in transcardiac potassium difference. Propranolol also decreased arterial levels of free fatty acids and their extraction in group 2 patients during pacing. In conclusion, blood pressure decay during simulated ventricular tachycardia is followed by instantaneous sympathoadrenergic activation. In patients with coronary artery disease, this process is accompanied by metabolic ischemia and net transfer of extracellular potassium into the intracellular space. The metabolic and electrolyte changes may result in alterations of electrophysiologic millieau, thereby also modifying the clinical characteristics of ventricular tachycardia. Propranolol decreases arterial levels of free fatty acids and prevents changes in transcardiac electrolytes observed in coronary artery disease patients during simulated ventricular tachycardia. These effects of propranolol may be of clinical significance.
 ...
PMID:Changes in myocardial metabolism and transcardiac electrolytes during simulated ventricular tachycardia: effects of beta-adrenergic blockade. 801 90

The effect of myocardial ischemia and its major metabolic changes, such as anoxia, acidosis, and hyperkalemia, on exocytotic noradrenaline release was investigated in rat, guinea pig, and human cardiac tissue. Noradrenaline release was evoked by electrical field stimulation, and the effect of each experimental intervention on stimulation-evoked noradrenaline release (S2) was intraindividually compared with the release induced by a control stimulation (S1). In perfused hearts, 10 minutes of global ischemia caused a reduction of noradrenaline overflow in rat hearts (mean S2/S1, 0.31), whereas the overflow was increased in guinea pig hearts (S2/S1, 1.89). This species-dependent effect may be caused by quantitatively different responses to facilitating and suppressing factors of noradrenaline release in both species. Anoxia and substrate-free perfusion increased noradrenaline overflow in guinea pig hearts (S2/S1, 2.40) but had no significant effect in rat hearts (S2/S1, 0.75). Acidosis (pH 6.0) resulted in a suppression of noradrenaline release in rat hearts (S2/S1, 0.16), whereas it had only a minor inhibiting effect in guinea pig hearts (S2/S1, 0.67). Hyperkalemia had a comparable effect in both species (S2/S1 at 15 mmol/L K+, 1.17 in rat and 1.14 in guinea pig; and S2/S1 at 20 mmol/L K+, 0.64 in rat and 0.41 in guinea pig). To obtain results regarding the modulation of noradrenaline release in human myocardium, human atrial tissue was incubated, and the effect of anoxia, acidosis, and hyperkalemia on stimulation-evoked noradrenaline release was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of myocardial ischemia on stimulation-evoked noradrenaline release. Modulated neurotransmission in rat, guinea pig, and human cardiac tissue. 839 25


<< Previous 1 2 3 4 5 6 Next >>