Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective study the significance of silent ischemia was evaluated in 66 patients with a clinical diagnosis of unstable angina (no requirement for reversible ST-T changes during pain on 12-lead electrocardiograms before entry), and the results of continuous 2-channel electrocardiographic (ECG) recordings, begun within 24 hours of admission, were compared with other clinical and ECG predictors of adverse outcome. Ischemic changes were detected in 7 patients (11%) during a mean of 41 hours of recording. There were 37 episodes of transient ST-segment change (16 ST elevation, 21 ST depression) of which 11 (30%) were symptomatic and 26 (70%) were silent. All 7 patients had at least 1 silent episode and 5 also had symptomatic episodes during the recording but only 2 patients had exclusively silent episodes. During a mean follow-up of 13.3 months, 3 patients died, 5 had a nonfatal myocardial infarction and 32 required revascularization. Although transient myocardial ischemia during the continuous ECG recording, whether silent or symptomatic, was a specific predictor of subsequent nonfatal myocardial infarction or death (specificity 92%), its sensitivity for these events was low (25%). In contrast, recurrent rest pain (greater than or equal to 1 episode) occurred in all patients with these serious adverse events (sensitivity 100%, specificity 49%). Transient ischemia occurs infrequently during continuous ECG recordings in patients with unstable angina not selected by reversible ST-T changes on a 12-lead electrocardiogram at entry. Recurrent rest pain after hospital admission is a more sensitive predictor of serious events in this group.
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PMID:Clinical significance of silent ischemia in unstable angina pectoris. 218 94

Transient ischemia does not induce myocardial necrosis but may be associated with prolonged contractile dysfunction ("stunned" myocardium). It has been suggested that alteration of the excitation-contraction coupling system (sarcoplasmic reticulum) could be responsible for this phenomenon. We tested this hypothesis by characterizing sarcoplasmic reticulum (SR) function in an isolated rat heart model of "stunned" myocardium (hearts reperfused after 10 min of normothermic global ischemia). At the end of the ischemic period oxalate-supported Ca-uptake was depressed either in the whole homogenate or in isolated SR (to 47% and 22% of control values, respectively). During reperfusion Ca-uptake of the whole heart homogenate recovered almost completely whereas slight but significant depression persisted in isolated SR (48 +/- 2 vs 67 +/- 4 nmol/min x mg, P less than 0.01). In the presence of ruthenium red or ryanodine, two inhibitors of SR Ca-release channels, Ca-uptake was stimulated. Both in the whole heart homogenate and in isolated SR, such stimulation was remarkably smaller after reperfusion than in control conditions (P less than 0.001) suggesting reduced conductivity state of the SR Ca-release channels. Ca-stimulated, magnesium-dependent ATPase activity was remarkably reduced during ischemia and postischemic reperfusion induced only incomplete recovery (93 +/- 18 vs 169 +/- 14 nmol ATP/min x mg protein, P less than 0.05). We conclude that complex modifications of SR function occur in the "stunned" myocardium and could contribute to the contractile impairment found in this condition.
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PMID:Sarcoplasmic reticulum function in the "stunned" myocardium. 247 59

Transient ischemia arising from proximal events in epicardial coronary arteries causes important symptoms, such as angina pectoris, and is usually studied in the hospital with provocative tests. However, Holter monitoring of ST-segment disturbances in patients out of the hospital has shown frequent asymptomatic evidence of ischemia that is surprisingly prolonged and that is not associated with the obvious tachycardia of exercise or stress. Positron emission tomography has been developed to measure the regional myocardial uptake of a cation (rubidium-82) in order to assess repeatedly the directional changes in regional coronary blood flow during these events. This method has been used to show that both symptomatic and asymptomatic episodes of ST depression are reliably associated with disturbances in regional myocardial perfusion. The daily activities of patients have been analyzed and reproduced in the hospital to assess the effects of cold stimulation, mental arithmetic, cigarette smoking, and exercise. Physical exercise was associated with angina, ST-segment change, and regional abnormalities of myocardial perfusion, including decreased perfusion in poststenotic segments. The other tests caused the same disturbances in myocardial perfusion; these perfusion disturbances were mostly asymptomatic and surprisingly prolonged, with periods of recovery that were two to five times longer than the ST-segment disturbance and the pain. Current studies using a structured diary indicate that the episodes of transient ischemia occurring out of the hospital are more frequently associated with different levels of mental arousal than with any other activity. Physical exercise is a relatively infrequent cause of transient ischemia. The examination of coronary blood flow using provocative tests derived from the patients' own activities out of the hospital have confirmed that, irrespective of the pattern of angina, patients have frequent episodes of asymptomatic transient ischemia that are surprisingly prolonged and that these episodes occur in response to previously unsuspected ordinary daily activities. The disturbances in coronary blood flow usually include a regional decrease in myocardial perfusion that can only be explained by pathophysiologic events in the proximal epicardial coronary arteries.
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PMID:Clinical problems in coronary disease are caused by wide variety of ischemic episodes that affect patients out of hospital. 405 Aug 20

Transient ischemia on Holter monitoring is a major determinant of outcome in unstable angina. In this study we investigated whether analysis of heart rate variability (HRV) may further improve the prognostic yield of Holter monitoring in this clinical setting. We performed 24-hour Holter monitoring in 75 patients with unstable angina (59 men, aged 62 +/- 9 years) within 12 hours of hospital admission. Number and duration of myocardial ischemic episodes, and both time domain and frequency domain HRV measures were obtained from Holter recordings. In-hospital major cardiac events (death or myocardial infarction) occurred in 7 patients (9%). Episodes of ST-segment depression on Holter monitoring were found in 6 of 7 patients (86%) with and in 26 of 68 patients (38%) without events (p <0.05). There were no differences between patients with or without events in both time domain (standard deviation [SD] of all normal RR intervals in the entire 24-hour electrocardiographic recording (SDNN), SD of the mean RR intervals for all 5-minute segments (SDANN-i), mean of SD of all RR intervals for all 5-minute segments (SDNN-i), percentage of differences between adjacent RR intervals >50 ms (pNN50), and square root of the mean squared differences of successive RR intervals) (RMSSD), and frequency domain (ultra low, very low, low, and high frequency) HRV indexes. However, the low-frequency/high-frequency (LF/HF) ratio was significantly higher in patients with cardiac events (2.12 +/- 1.4 vs 1.48 +/- 0.5, p = 0.01). Moreover, when considering only the 32 patients with myocardial ischemic episodes on Holter monitoring, the LF/HF ratio was again higher in the 6 patients with than the 26 patients without major cardiac events (2.45 +/- 1.5 vs 1.31 +/- 0.3, p <0.01). Multivariate logistic regression, including clinical and angiographic variables, showed that transient ischemia on Holter monitoring was the only independent determinant of outcome (odds ratio = 12.2, p = 0.03), with the LF/HF ratio being only slightly over statistical significance (odds ratio for 0.1 increments = 2.8, p = 0.08). Our data confirm that transient ischemia on Holter monitoring is a powerful predictor of cardiac events in unstable angina and indicates that an imbalance in cardiac autonomic tone toward a prevalence of sympathetic activity increases the risk of events in this group of patients.
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PMID:Usefulness of the addition of heart rate variability to Holter monitoring in predicting in-hospital cardiac events in patients with unstable angina pectoris. 926 16

We investigated the combined effect of increased brain topical K+ concentration and reduction of the nitric oxide (NO.) level caused by nitric oxide scavenging or nitric oxide synthase (NOS) inhibition on regional cerebral blood flow and subarachnoid direct current (DC) potential. Using thiopental-anesthetized male Wistar rats with a closed cranial window preparation, brain topical superfusion of a combination of the NO. scavenger hemoglobin (Hb; 2 mmol/L) and increased K+ concentration in the artificial cerebrospinal fluid ([K+]ACSF) at 35 mmol/L led to sudden spontaneous transient ischemic events with a decrease of CBF to 14+/-7% (n=4) compared with the baseline (100%). The ischemic events lasted for 53+/-17 minutes and were associated with a negative subarachnoid DC shift of -7.3+/-0.6 mV of 49+/-12 minutes' duration. The combination of the NOS inhibitor N-nitro-L-arginine (L-NA, 1 mmol/L) with [K+]ACSF at 35 mmol/L caused similar spontaneous transient ischemic events in 13 rats. When cortical spreading depression was induced by KCl at a 5-mm distance, a typical cortical spreading hyperemia (CSH) and negative DC shift were measured at the closed cranial window during brain topical superfusion with either physiologic artificial CSF (n=5), or artificial CSF containing increased [K+]ACSF at 20 mmol/L (n=4), [K+]ACSF at 3 mmol/L combined with L-NA (n=10), [K+]ACSF at 10 mmol/L combined with L-NA (five of six animals) or [K+]ACSF at 3 mmol/L combined with Hb (three of four animals). Cortical spreading depression induced longlasting transient ischemia instead of CSH, when brain was superfused with either [K+]ACSF at 20 mmol/L combined with Hb (CBF decrease to 20+/-20% duration 25+/-21 minutes, n=4), or [K+]ACSF at 20 mmol/L combined with L-NA (n=19). Transient ischemia induced by NOS inhibition and [K],ACSF at 20 mmol/L propagated at a speed of 3.4+/-0.6 mm/min, indicating cortical spreading ischemia (CSI). Although CSH did not change oxygen free radical production, as measured on-line by in vivo lucigenin-enhanced chemiluminescence, CSI resulted in the typical radical production pattern of ischemia and reperfusion suggestive of brain damage (n=4). Nimodipine (2 microg/kg body weight/min intravenously) transformed CSI back to CSH (n=4). Vehicle had no effect on CSI (n=4). Our data suggest that the combination of decreased NO. levels and increased subarachnoid K+ levels induces spreading depression with acute ischemic CBF response. Thus, a disturbed coupling of metabolism and CBF can cause ischemia. We speculate that CSI may be related to delayed ischemic deficits after subarachnoid hemorrhage, a clinical condition in which the release of Hb and K+ from erythrocytes creates a microenvironment similar to the one investigated here.
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PMID:Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-L-arginine induces cortical spreading ischemia when K+ is increased in the subarachnoid space. 974 Jan 1

Transient ischemia is known to lead to a long-lasting depression of cerebral metabolic rate and blood flow and to an attenuated metabolic and circulatory response to physiological stimuli. However, the corresponding responses to induced seizures are retained, demonstrating preserved metabolic and circulatory capacity. The objective of the present study was to explore how a preceding period of ischemia (15 min) alters the release of free fatty acids (FFAs) and diacylglycerides (DAGs), the formation of cyclic nucleotides, and the influx/efflux of Ca(2+), following intense neuronal stimulation. For that purpose, seizure activity was induced with bicuculline for 30 s or 5 min at 6 h after the ischemia. Extracellular Ca(2+) concentration (Ca(2+)(e)) was recorded, and the tissue was frozen in situ for measurements of levels of FFAs, DAGs, and cyclic nucleotides. Six hours after ischemia, the FFA concentrations were normalized, but there was a lowering of the content of 20:4 in the DAG fraction. Cyclic AMP levels returned to normal values, but cyclic GMP content was reduced. Seizures induced in postischemic animals showed similar changes in Ca(2+)(e), as well as in levels of FFAs, DAGs, and cyclic nucleotides, as did seizures induced in nonischemic control animals, with the exception of an attenuated rise in 20:4 content in the DAG fraction. We conclude that, at least in the neocortex, seizure-induced phospholipid hydrolysis and cyclic cAMP/cyclic GMP formation are not altered by a preceding period of ischemia, nor is there a change in the influx/efflux of Ca(2+) during seizure discharge or in associated spreading depression.
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PMID:Alterations in lipid and calcium metabolism associated with seizure activity in the postischemic brain. 1108 Feb 5

Depression is a frequent but often unrecognized and under treated complication of stroke that has scarcely been investigated in animal models particularly regarding treatment issues. Using the Forced Swim Test (FST) and testing spontaneous motor activity, we studied whether a transient focal cerebral ischemia modifies mice behaviours and antidepressant drug effects. We first evaluated whether FST realized 2 days or 1 week after brain reperfusion may be routinely used in male Swiss mice previously submitted to a 15, 30 or 60-min transient occlusion of the right middle cerebral artery. We then evaluated behavioural changes up to 5 weeks in mice previously submitted to a 15-min ischemia. Behaviours according to the administration of imipramine or fluvoxamine at 1 and 5 weeks after a 15-min ischemia were finally evaluated. Transient ischemia was associated with a decrease in immobility in the FST performed 2 days after reperfusion while no changes were observed in 1 and 5 weeks post-ischemia groups. Changes were related neither to brain ischemia duration nor to infarct volume. At both 1 and 5 weeks after brain ischemia, a dramatic decrease in the antidepressant response to imipramine related to a decrease in climbing behaviour was observed while the effects of fluvoxamine were improved through an increase in both climbing and swimming. Behaviours in the FST were unrelated to any spontaneous motor activity changes. Responses to anti-depressant drugs are strongly modified in mice previously submitted to brain ischemia. Present results underline that not all antidepressant drugs are appropriate after ischemic stroke.
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PMID:Brain ischemia changes the long term response to antidepressant drugs in mice. 2123 93

Oxygen-glucose deprivation (OGD) leads to depression of evoked synaptic transmission, for which the mechanisms remain unclear. We hypothesized that increased presynaptic [Ca2+]i during transient OGD contributes to the depression of evoked field excitatory postsynaptic potentials (fEPSPs). Additionally, we hypothesized that increased buffering of intracellular calcium would shorten electrophysiological recovery after transient ischemia. Mouse hippocampal slices were exposed to 2 to 8 min of OGD. fEPSPs evoked by Schaffer collateral stimulation were recorded in the stratum radiatum, and whole cell current or voltage clamp recordings were performed in CA1 neurons. Transient ischemia led to increased presynaptic [Ca2+]i, (shown by calcium imaging), increased spontaneous miniature EPSP/Cs, and depressed evoked fEPSPs, partially mediated by adenosine. Buffering of intracellular Ca2+ during OGD by membrane-permeant chelators (BAPTA-AM or EGTA-AM) partially prevented fEPSP depression and promoted faster electrophysiological recovery when the OGD challenge was stopped. The blocker of BK channels, charybdotoxin (ChTX), also prevented fEPSP depression, but did not accelerate post-ischemic recovery. These results suggest that OGD leads to elevated presynaptic [Ca2+]i, which reduces evoked transmitter release; this effect can be reversed by increased intracellular Ca2+ buffering which also speeds recovery.
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PMID:Raised Intracellular Calcium Contributes to Ischemia-Induced Depression of Evoked Synaptic Transmission. 2693 14