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

Dephosphorylation processes of target proteins are critical to the reversible regulation of intracellular signal transduction systems. Further, brain damage such as ischemic insult induces marked changes in protein kinase activity. To study these changes more thoroughly, specific monoclonal antibodies of the A and B subunits of calcineurin (protein phosphatase 2B) were raised, and regional alterations in the immunoreactivity of calcineurin in the rat hippocampus were investigated after a transient forebrain ischemic insult causing selective and delayed hippocampal CA1 pyramidal cell damage. In normal rats it was found that both the calcineurin A and the B subunits showed high immunoreactivity in the dendritic fields of the hippocampal formation. The immunoreactivity of subunit A in the strata oriens, the radiatum of the CA1 subfield and in the stratum lucidum of the CA3 subfield was most intense, whereas the immunoreactivity in the other CA3 subfields and in the dentate gyrus was relatively low. In contrast, the dendritic fields of the hippocampal formation were equally immunoreactive to calcineurin subunit B, although the stratum lucidum of the CA3, where the mossy fibers from the dentate granule cells terminate, showed a very high immunoreactivity of the B subunit. After transient forebrain ischemia in the CA1 subfield, where selective pyramidal cell death occurred two days after this ischemia, a marked loss of immunoreactivity in both subunits was observed, along with morphological pyramidal cell damage. A recovery of the immunoreactivity of A and B subunits in the strata oriens and radiatum was later noted 30 days after ischemia. In the stratum lucidum of the CA3, the immunoreactivity of both the A and B subunits was transiently depressed from 6 to 24 h, followed by a marked immunoreactivity enhancement from four to 30 days after ischemia. Further, in the histologically intact dentate gyrus, both the immunoreactivity of the A and B subunits in the molecular layer were transiently enhanced from four to 14 days after ischemia, particularly in the supragranular layer. The results clearly indicate that the protein dephosphorylation systems were markedly altered in the whole hippocampal formation during the recirculation period following ischemia. Further, the transient depression in the calcineurin immunoreactivity seen in the mossy fiber terminals may reflect modulated synaptic activity of the dentate granule cells, which may play a pivotal role in the delayed and selective death of the CA1 pyramidal cells. Thus, calcineurin appears to be an excellent marker enzyme for the detection of neuronal activity and synaptic plasticity after brain damage, such as an ischemic insult.
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PMID:Alteration in the immunoreactivity of the calcineurin subunits after ischemic hippocampal damage. 132 5

Peroxidative stress, exerted by oxygen free radicals, seems to be an important mechanism of the ischemia-reperfusion myocardial damage. In the present study we evaluated the modifications of sarcoplasmic reticulum function subjected to peroxidation by ferric ions. A subcellular fraction enriched in sarcoplasmic reticulum was obtained from rabbit hearts by homogenization and differential centrifugations. Sarcoplasmic reticulum vesicles were peroxidated through incubation for 5 min at 37 degrees C in presence of ferric cloride (FeCl3) ranging in concentration between 0.3 and 0.9 mM. Peroxidation of sarcoplasmic reticulum vesicles determined a dose-dependent reduction of Ca-uptake (39.2 +/- 10.3, 36.5 +/- 9.9, 28.9 +/- 8.4 and 18.8 +/- 8.2 nmol/min/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; NS, p less than 0.05 and less than 0.01, respectively) which was paralleled by an increase in the production of malondialdehyde, an index of lipid peroxidation (1.0 +/- 1.0, 7.0 +/- 3.2, 14.1 +/- 3.9 and 27.0 +/- 4.7 nmol/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; p less than 0.05, less than 0.01 and less than 0.01, respectively). Depression of Ca-uptake was not accounted for by modifications of Ca-ATPase activity or membrane aspecific permeability to Ca++ ions, since these parameters were not affected by exposure to 0.3-0.9 mM FeCl3. On the contrary, the responsiveness of Ca-release channels to the specific inhibitor ryanodine was greatly altered, even at lower FeCl3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of oxygen free radicals on the function of the cardiac sarcoplasmic reticulum]. 132 20

Cardiac hypertrophy is an adaptive response to an increased load imposed on the myocyte which allows the heart to perform increased work while maintaining normal myocardial fiber stress and shortening in systole. A deleterious consequence of pressure-overload hypertrophy is the prolongation of Ca(2+)-sensitive force inactivation (impaired myocardial relaxation) which is related to intrinsic alterations in cytosolic Ca2+ transport and reuptake in diastole. Additional factors appear to adversely modify myocardial relaxation in the hypertrophied heart, including the imposition of ischemia. There is also evidence that the expression and activity of the cardiac tissue renin angiotensin system (RAS) may be modified in the hypertrophied heart and contribute to diastolic dysfunction. Recent studies have demonstrated the presence of increased cardiac angiotensin converting enzyme (ACE) mRNA expression and activity in animal models of hypertrophy, including the aortic-banded rat with compensatory pressure-overload hypertrophy and rats with post-infarction remodeling. In the beating, isovolumic aortic-banded rat heart, the increased intracardiac activation of angiotensin I to II has been shown to be associated with a dose-dependent depression of diastolic relaxation. Preliminary studies suggest that the depression of diastolic function by angiotensin II in the hypertrophied heart can be prevented by the specific inhibition of cardiac ACE. In addition, the well-recognized susceptibility of the hypertrophied heart to severe ischemic diastolic dysfunction also appears to be favorably modified by the inhibition of cardiac ACE activity. The mechanisms responsible for the adverse effects of angiotensin II on diastolic relaxation in the hypertrophied heart are likely to be complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diastolic dysfunction in pressure-overload hypertrophy and its modification by angiotensin II: current concepts. 133 63

We have developed the multiprobe assembly (MPA) by which metabolic, ionic and electrical activities can be monitored from the surface of the brain. In the present study we included optical fibers for the monitoring of intracapillary hemoglobin oxygenation by use of the Erlangen Microlight Guide Spectrophotometer (EMPHO-I) from the surface of the gerbil brain. The newly developed MPA provides simultaneous information about oxygen delivery (oxydeoxy Hb), tissue pO2 level, as well as the intracellular oxygen balance (intramitochondrial redox state). The ionic homeostasis was evaluated by monitoring extracellular K+ and Ca2+ activities reflecting the permeability changes of cation channels as well as the activities of Na+,K(+)-ATPase and other ion linked transport processes. The electrical activities were monitored by a bipolar electrocortical surface probe and DC steady potential. The subjects of the present study were Mongolian gerbils (Meriones unguiculatus) anesthetized and operated according to our routine techniques. After 30 min of recovery from the operation each gerbil was exposed to a short anoxia, graded hypoxia, ischemia as well as spreading depression. The results can be summarized as follows: 1. A clear correlation was recorded between the changes in oxydeoxy Hb spectra, tissue pO2 level and oxidation-reduction state of intramitochondrial NADH under oxygen deficiency situations (hypoxia, ischemia). 2. Blood volume changes under various perturbations monitored by various probes (366 reflectance and EMPHO-I) correlated very well with each other. 3. The degree of inhibition of Na+,K(+)-ATPase induced by oxygen deficiency could be interpreted by changes in extracellular levels of K+ measured by the surface mini-electrode. 4. Brain stimulation induced by spreading depression mechanism led to transient changes in ionic homeostasis and increase in energy requirements. The major HbO2 response was an increase in oxygenation due to the large CBF increase as monitored by the laser Doppler flowmeter. 5. Changes in oxy-deoxy Hb under fast scanning of 500-600 nm during 2-3 seconds of bilateral carotid arterial occlusion provided an indirect index for tissue O2 consumption.
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PMID:Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo. 133 23

Recent investigations of SMI occurring during daily life have advanced our understanding of the pathophysiology of myocardial ischemia. These contributions have directed our attention away from "chest pain" alone and physical exertion as the central provoking factor toward transient myocardial ischemia and its broader triggers and consequences. Transient myocardial ischemic episodes, the majority of which are silent, are found in a subset of patients with any clinical manifestations of CAD (eg, stable angina, unstable angina, myocardial infarction, and sudden death), as well as in those patients with CAD who are and have been totally asymptomatic. These episodes are an independent predictor of increased risk for future cardiac events. Most medical therapy and revascularization therapies have the potential to prevent or relieve these silent episodes; however, we do not yet know which method is superior in reducing SMI episodes or preventing future cardiac events. Furthermore, the benefit of reducing SMI versus the cost and potential morbidity of these chosen therapies is not known. At least three trials are now underway to examine some of these concerns (Table 2). Focus on pain relief alone does not appear to be an adequate approach to alter outcome in patients with CAD and may prove insufficient to control SMI. Until these issues are resolved, we believe a conservative approach to the management of patients with CAD is warranted. Documentation of ischemia (painful or painless) is essential. Three general principles should be kept in mind. First, the presence of detectable ischemia is of central importance. This information should be used in the overall risk assessment of the patient. Second, the level of concern or aggressiveness of treatment should be based on the risk associated with the ischemic abnormalities documented (Table 3). The exercise stress test is the most useful to begin this process. The detection of ischemic-type ST-segment depression, either silent or painful, at a low workload (eg, less than or equal to 120 beats per minute or less than or equal to 6.5 metabolic equivalents [METS]) implies high risk for adverse outcome. Likewise, these ST-segment changes occurring in leads that reflect multiple coronary artery distribution, of greater than 2 mm in magnitude and persisting for greater than 6 minutes, are all markers for high risk. Thallium redistribution defects occurring at low work loads, in multiple areas, associated with increased lung uptake and enlargement of the cardiac pool all imply high risk.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Treatment strategies for daily life silent myocardial ischemia: a correlation with potential pathogenic mechanisms. 135 7

A number of studies have addressed the response to calcium antagonists, used alone or combined with other therapy, in patients with silent myocardial ischemia (SMI). Nifedipine, the first calcium antagonist to be studied, was shown to be superior to pindolol in patients with effort angina. Although both nifedipine and diltiazem significantly reduced episodes of ST depression, compared with placebo, in patients with stable effort angina, the addition of nifedipine to diltiazem removed the beneficial effect of diltiazem in another study. Studies have shown a reduced incidence of ischemic episodes during nicardipine treatment in patients with ambulatory ischemia, predominantly SMI, and rest angina due to coronary artery spasm. Other workers similarly reported that verapamil was superior to both placebo and propranolol in reducing painful and painless ischemia in patients with angina at rest. It has been demonstrated that, compared with placebo, nifedipine reduced ischemic episodes by 50% and also markedly reduced total ischemic time in totally asymptomatic men with coronary artery disease and SMI. It was suggested that the well-documented increase in SMI occurring between 0600 and 1200 h was reduced, but not eliminated, by nifedipine. Diltiazem may also attenuate the circadian variation in SMI. Nifedipine has been shown to be particularly effective in SMI when combined with a beta-blocker. This has been substantiated in a large group of patients; both drugs reduced the number of episodes of SMI when used as monotherapy, and the combination decreased the incidence by 95%. These findings collectively indicate that calcium antagonists are effective in reducing or preventing SMI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical effects of calcium antagonists in silent ischemia. 136 8

To determine the incidence and characteristics of ventricular dysrhythmias (premature ventricular contractions greater than 30/min, ventricular tachycardia greater than or equal to 3 beats, and ventricular fibrillation) and whether a relationship exists between ventricular tachycardia and myocardial ischemia in patients undergoing coronary artery bypass graft surgery, we continuously monitored 50 patients for 10 perioperative days using two-lead electrocardiography. Electrocardiographic changes consistent with ischemia were defined as a reversible ST depression greater than or equal to 1.0 mm, or ST elevation greater than or equal to 2.0 mm from baseline, lasting at least 1 minute. Ventricular dysrhythmias developed in 10% of patients preoperatively and in 16% intraoperatively before bypass surgery. The highest incidence occurred postoperatively, with ventricular dysrhythmias developing in 66% of patients (22% to 44% of patients on any postoperative day 0 to 7). Premature ventricular contractions were greater than 30/hr in 6% of patients preoperatively, in 8% intraoperatively before bypass, and in 34% postoperatively (6% to 23% of patients on any postoperative day). Twenty-nine patients (58%) developed 76 verified episodes of greater than or equal to 3 beats of ventricular tachycardia. Ventricular tachycardia occurred in 6% of patients preoperatively (four episodes), in 8% of patients intraoperatively prior to bypass (four episodes), and 54% of patients postoperatively (5% to 21% on any postoperative day). No patient developed ventricular fibrillation. All postoperative ventricular tachycardia episodes (after tracheal extubation) were asymptomatic. Postoperatively, 48% of patients developed ischemia, compared with 12% preoperatively and 10% intraoperatively before bypass surgery. Only 5 of 68 (7%) postoperative ventricular tachycardia episodes occurred within 3 hours of an ischemia episode.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventricular dysrhythmias in patients undergoing coronary artery bypass graft surgery: incidence, characteristics, and prognostic importance. Study of Perioperative Ischemia (SPI) Research Group. 137 Mar 63

We evaluated the effects of a single oral dose of 5 mg of isradipine compared to placebo in a randomized, double-blind, crossover study using gated radionuclide angiography at rest and during exercise in 20 patients with stable chronic angina. Isradipine improved both anginal symptomatology and ST-segment depression during exercise, with a concomitant favorable effect on the isotopic parameters exploring systolic and diastolic left ventricular function. There was a marked increase of the ejection fraction during exercise with isradipine compared to placebo (61 +/- 14% vs. 55 +/- 15%, respectively, p less than 0.001) as well as a significant improvement in the peak ejection rate and the peak filling rate at rest [2.56 +/- 0.62 vs. 2.16 +/- 0.54 end diastolic volume (EDV) per second and 2.14 +/- 0.59 vs. 1.87 +/- 0.37 EDV/s, respectively] and during exercise (3.49 +/- 0.97 vs. 3.10 +/- 1.07 EDV/s and 4.05 +/- 1.34 vs. 3.65 +/- 1.25 EDV/s, respectively). We conclude that isradipine has a beneficial effect on the clinical and electrocardiographic signs of exercise-induced ischemia, leading to a significant improvement of the systolic and diastolic parameters of left ventricular function. Therefore, isradipine is potentially a useful treatment for patients with exertional angina and hypertension, alone or associated with beta blocker medication.
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PMID:Effects of oral isradipine on left ventricular function at rest and during exercise in patients with stable chronic angina: a double-blind, placebo-controlled crossover study. 137 79

Data from previous studies are debatable regarding whether Holter monitors are a reliable electrocardiographic indicator of ischemia, for which the 12-lead electrocardiogram (ECG) is the standard. Simultaneous 12-lead and Holter ECGs were performed on 30 patients with typical angina pectoris during coronary angiography or exercise testing. ST depression recorded by both methods was directly compared, using the 12-lead ECG as the reference. The Holter tapes were also scanned by two automated ST analysis programs and the results were compared to 12-lead ECGs. Only 66 of the 178 12-lead ECG ST depression events were also present on the Holter recordings (37.1% Holter sensitivity). ST depression was underestimated by the Holter recordings compared to the 12-lead ECGs (p < 0.0001). The majority (67.0%) of ST depression events identified by one computer program were false positive events. The degree of ST depression was overestimated compared to 12-lead ECGs by the second program (p = 0.0033). Holter-detected ST depression may not be a reliable ECG indicator of myocardial ischemia.
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PMID:Comparison of ST depression recorded by Holter monitors and 12-lead ECGs during coronary angiography and exercise testing. 140 18

The purpose of this study is to determine why precordial ST elevation (V1 lead) occurs during acute occlusion of the right coronary artery (RCA). Nineteen patients with vasospastic angina, in whom ergonovine administration into RCA provoked spasms, were divided into 2 groups by precordial ST change during spasms. Group I (n = 6) had precordial ST elevation; group II (n = 13) had no precordial ST elevation. A subgroup, IIA was comprised 6 patients in group II with spasms in the RCA proximal segment (segment number less than 2 of AHA coronary classification). None had left coronary dominancy. There was no difference in collateral flow during spasms. Location of spasms in group I was in the RCA proximal segment, and was significantly more proximal compared to group II. There was no difference in sigma ST in II, III, aVF between group I and II or IIA. Max ST elevation time by which duration of ischemia was estimated was significantly longer in group I than in group IIA. Three patients in group I displayed precordial ST depression before elevation, in all of whom in sigma ST in II, III, aVF was higher during precordial ST elevation than during depression. During acute occlusion in the RCA proximal segment, precordial ST elevation is caused by ischemia of the right ventricular anterior wall. Furthermore, precordial ST elevation can occur in a patient with RCA dominance, even if ischemic injury in the left ventricular infero-posterior wall increases progressively.
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PMID:Precordial ST segment elevation in acute ischemia caused by right coronary artery occlusion. 140 44


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