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)

Although microvascular occlusion has been considered a basis for pathophysiology of the myocardium during the crisis of sickle cell anemia, the status of the left ventricle in uncertain. To determine if left ventricular performance is affected by crisis, 11 patients were evaluated noninvasively by the systolic time interval method on the first day of crisis and serially until recovery. There were no significant differences in the time intervals over this period. In addition, since the serum CPK-MB isoenzyme was not elevated during crisis and evidence of acute injury was not present on ECG, myocardial necrosis appeared unlikely. Four patients on subsequent admission exhibited systolic time interval values similar to the earlier crisis. To determine if there were chronic changes in cardiac function, subjects with sickle cell hemoglobin were studied between crises. Those under 23 years of age were not dissimilar from a group of normals and a group of patients with chronic blood loss anemia A significant abnormality of the PEP/LVET ratio was observed in subjects over 23 years of age. Similar observations were made on echocardiography, with subjects over the age of 23 demonstrating an abnormal ejection fraction compared to the younger group, despite enhanced end-diastolic diameter. Thus, it is suggested that the chronic hemolytic process in subjects with sickle cell anemia may effect cumulative myocardial alterations, resulting in chronic cardiac malfunction in the apparent absence of acute ischemia during crises.
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PMID:Left ventricular performance during and after sickle cell crisis. 43 33

12 patients suffering from chronic coronary insufficiency with signs of ischemia in the ECG, were treated orally with 200 mg of acebutolol t.i.d. for a period of 3 weeks. The following parameters were examined at the beginning of the therapy as well as at the end of every week: number of stenocardiac attacks, characteristics of pain, nitroglycerin consumption, B.P., H.R., respiratory rate, ECG, maximal exercise test, PEP, LVET, PEP/LVET at rest and immediately after effort. The treatment with acebutolol was effective inducing an improvement of subjective symptoms (reduction of stenocardiac crises, intensity and duration of angor, trinitrin pearls consumption) and an increase of effort tolerance. The utility of the therapy was also proved by the reduction of the systolic pressure and by the following decrease of hemodynamic overload and, therefore, of the heart muscle's work. This positive effect is due to the reduction of the myocardial oxygen consumption, modulated among others by the bradycardiac action of the drug. The cardioselectivity of acebutolol avoided to cause peripherical disorders usually observed with other non selective beta blocking drugs.
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PMID:[Effects of the administration of acebutolol in patients with chronic angina of effort]. 730 53

The changes in systolic time intervals (STI) LVET, PEP/LVET) between rest conditions, maximal exercise and after seven minutes after upright bicycle stress test were measured in 31 consecutive subjects: 14 "control" normal subjects, and 17 subjects with ischemic heart disease. The purpose of this investigation was to evaluate the specificity and sensitivity of the stress - STI in the identification of patients with positive exercise ECG and of patients with markedly positive exercise ECG that shown a late recovery persistent ischemia. The changes of STI are different in the control group and in ischemic heart disease group pts with negative exercise stress test and pts with positive or markedly positive exercise ecg. In the literature the usefulness of stress STI in the diagnosis of coronary disease is not univocally accepted. Our results indicate that STI are not a parameters that have an available correlation ith the stress myocardial ischemia even at distance of haemodynamic variations of maximal exercise and recovery and in presence of late recovery persistent ischemia.
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PMID:[The stress systolic time intervals in the diagnosis of ischaemic heart disease. Study of the recovery in patients with persistent ischemia (author's transl)]. 734 10

RheothRx Injection, an aqueous solution of a nonionic block copolymer (poloxamer 188) formulated for intravenous administration, was investigated as an inhibitor of red blood cell (RBC)-induced platelet aggregation at plasma concentrations of 0.05-5mgmL-1. Platelet aggregation was determined by measuring the fall in single platelet counts after mechanical agitation of 2mL aliquots of citrated whole blood in a 37 degrees C shaking waterbath. Inhibition of RBC-induced platelet aggregation of > 95% was observed for poloxamer 188 at a concentration of 1mgmL-1, and 41% inhibition was observed at 0.05mgmL-1. Poloxamer 188 was observed to be a more effective inhibitor of RBC-induced platelet aggregation than 2-chloradenosine (2-ClAd) or phosphoenolpyruvate/pyruvate kinase (PEP/PK). Studies using platelet rich plasma (PRP) showed that platelet aggregation could not be induced by shaking in the absence of RBC, though aggregation was induced by the addition of exogenous adenosine diphosphate (ADP). Poloxamer 188 did not inhibit ADP-induced platelet aggregation. We propose that poloxamer 188 protects RBC from mechanical trauma by non-specific adsorption of copolymer to the RBC surface (via the hydrophobic polyoxypropylene moiety), and that this effect prevents mechanical damage and hence leakage of ADP from RBC. RheothRx Injection has been shown to have value in the treatment of acute ischemic disorders such as myocardial infarction. The observation of significant inhibition of RBC-induced platelet aggregation at clinically relevant concentrations suggests that RheothRx Injection may have antithrombotic properties in vivo, and may therefore have potential not only in acute ischemia but also to prevent thrombosis within vascular prostheses or to prevent rethrombosis after angioplasty or endarterectomy.
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PMID:Inhibition of red blood cell-induced platelet aggregation in whole blood by a nonionic surfactant, poloxamer 188 (RheothRx injection). 750 70

We measured the changes in heart rate (HR) variability estimated from the standard deviation of the R-R intervals to evaluate cardiac parasympathetic tone noninvasively before and during activation of muscle metaboreflex induced by postexercise muscle ischemia. Eight healthy male subjects performed sustained handgrip at 50% maximal voluntary contraction followed by forearm occlusion. Mean arterial pressure, cardiac stroke volume, and ratio of cardiac preejection period to left ventricular ejection time (PEP/LVET) were also measured. During the 2-min occlusion after 60 s of handgrip with voluntary respiration, HR variability and mean arterial pressure were significantly increased from baseline (54.4 +/- 6.1 to 80.1 +/- 12.8 ms and 81 +/- 1 to 99 +/- 3 mmHg, respectively) and PEP/LVET was decreased from resting level of 0.404 +/- 0.022 to 0.363 +/- 0.036. During occlusion and recovery, HR did not change from baseline level in any experiment. There was no influence of occlusion itself or of cessation of exercise per se on any parameters. Although overall enhanced HR variability was seen, probably due to lower breathing frequency and larger tidal volume, similar results were also obtained from an experiment with controlled respiration, showing that the increase in HR variability was not due to the changes in tidal volume or breathing frequency during occlusion. In conclusion, the HR variability is increased during activation of the muscle metaboreflex induced by postexercise muscle ischemia in humans. This finding shows that the parasympathetic cardiac tone is enhanced during activation of the muscle metaboreflex in humans and balances enhanced cardiac sympathetic activity to result in an unchanged HR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of parasympathetic cardiac activity during activation of muscle metaboreflex in humans. 789 21

This study tests the hypothesis that glycolytic regulation of KATP channel activity is altered in myocardial hypertrophy. Left ventricular (LV) subendocardial myocytes were isolated from cats with normal or left ventricular hypertrophied hearts (LVH). Saponin-permeabilized open cell-attached patch configurations of normal and LVH cells were exposed to an exogenous ATP consuming system containing hexokinase and 2-deoxyglucose. Phosphoenol pyruvate (PEP, substrate for the last ATP producing step in glycolysis) was applied extracellularly; ADP was present. In both cell types, KATP channels were activated in the absence of PEP, inhibited when PEP was added and activated again when PEP was removed, indicating the cells retained metabolic integrity and generated ATP in the proximity of their KATP channels. Single channel conductance in the absence of PEP was similar (70 pS, normal; 66 pS, LVH). However, LVH KATP channels showed enhanced activity (P0=0.50+/-0.03); normal (0.41+/-0.03) in PEP absence (P<0. 05). PEP responsiveness was reduced in LVH, with IC50, PEP increased to 23 microM; (11 microM normal). Lactate failed to activate KATP channels in both cell types. The concentration-P0 response curves obtained during exposure of open cells to exogenous ATP also revealed reduced responsiveness to ATP of LVH KATP channels (IC50, ATP=283 microM LVH; 93 microM normal). Our data indicate myocardial hypertrophy increases the maximal activity of KATP channels in the absence of ATP and reduces their responsiveness to ATP, including locally generated glycolytic ATP. These alterations in metabolic regulation of myocardial electrophysiology may contribute to diversity of action potential shortening in hypertrophied hearts during acute ischemia.
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PMID:Hypertrophy decreases cardiac KATP channel responsiveness to exogenous and locally generated (glycolytic) ATP. 934 77

The aim was to assess the capabilities of a two-segment myocardial recording to recognize patients with an underlying chronic ischemic process as a fast screening from controls, prior to the usual segment-to-segment tissue Doppler echocardiographic assessment of ischemia. Ischemia generates systolic and relaxation abnormalities. A flow Doppler index of global systolic and diastolic myocardial performance was recently drawn from time durations studied by coupling isovolumic relaxation (IR) to preejection (PEP)/ejection (ET) ratio (PEP/ET). We derived a similar tissue Doppler approach to the period preceding the left ventricular filling: PEP', the ejectional inward wall motion representing ET' and the prefilling (PreFg) period ranging from the end of ET' to the onset of the outward wall motion approximating IR, were measured and ratios calculated between variables. Spectral tissue Doppler was applied to septal and posterior walls of 28 patients with proven chronic coronary artery disease and preserved left ventricular function and of 12 age-matched controls. Data were compared with global flow data. Global information did not differentiate both groups, save for IR (sensitivity 32%, specificity 57%). In patients, tissue Doppler mean values of single variables (P=0.004-0.0006) and ratios (P=0.03-0.002) significantly differed from controls. Moreover, septal ET' differentiated 13 patients with one-vessel (219+/-34 ms) from 10 with two-vessel disease (158+/-70 ms, P=0.01). Sensitivity and specificity of a septal ET'<190 ms for a two-vessel disease were 80%. The two-segment tissue Doppler echocardiographic study provided a rapid screening of patients versus controls and helped to predict the number of diseased vessels.
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PMID:Myocardial time intervals preceding left ventricular filling in chronic coronary artery disease: value of a decreased septal ejection time. 1272 3

Reactive oxygen species (ROS) are implicated in reperfusion injury after transient focal cerebral ischemia. The antioxidant enzyme Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS after ischemia. Recently, we reported that denatured Tat-SOD fusion protein is transduced into cells and skin tissue. Moreover, PEP-1 peptide, which has 21 amino acid residues, is a known carrier peptide that delivers full-length native proteins in vitro and in vivo. In the present study, we investigated the protective effects of PEP-1-SOD fusion protein after ischemic insult. A human SOD gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-SOD fusion protein. The expressed and purified fusion proteins were efficiently transduced both in vitro and in vivo with a native protein structure. Immunohistochemical analysis revealed that PEP-1-SOD injected intraperitoneally (i.p.) into mice can have access into brain neurons. When i.p.-injected into gerbils, PEP-1-SOD fusion proteins prevented neuronal cell death in the hippocampus caused by transient forebrain ischemia. These results suggest that the biologically active intact forms of PEP-1-SOD provide a more efficient strategy for therapeutic delivery in various human diseases related to this antioxidant enzyme or to ROS, including stroke.
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PMID:In vivo protein transduction: biologically active intact pep-1-superoxide dismutase fusion protein efficiently protects against ischemic insult. 1547 17

The neuroprotective potency of N-PEP-12, a novel, proprietary compound consisting of biopeptides and amino acids was investigated. Lesion models have been applied in neuronal cultures of embryonic chicken cortex, pre-treated with N-PEP-12 from the first day onwards. On day 8 in vitro neurons were lesioned and cell viability was measured 24 and 48 hours later. To simulate acute brain ischemia, cytotoxic hypoxia was induced by sodium cyanide or by iodoacetate and excitotoxicity by L-glutamate. Ionomycin for up to 48 hours induced calcium overload. The cytoskeleton was disrupted by addition of colchicine. N-PEP-12 shows dose-dependent neuroprotection in all different models. The effect size depends on the recovery time but also on the extent of the lesion. In cases of mild to moderate lesion pronounced dose-dependent effects could be demonstrated. This indicates that chronic exposure to N-PEP-12 is able to prevent neuronal cell death associated to conditions occurring during normal aging and neurological disorders like ischemic stroke, hypoxia, brain trauma, or AD.
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PMID:N-PEP-12--a novel peptide compound that protects cortical neurons in culture against different age and disease associated lesions. 1575 Jun 82

In the present study, we investigated the chronological alterations in SOD1 and its copper chaperone (chaperone for superoxide dismutase, CCS) immunoreactivities and their neuroprotective effects against neuronal damage in the gerbil hippocampus after 5 min of transient forebrain ischemia. SOD1 and CCS immunoreactivities were significantly increased in the stratum pyramidale of the CA1 region at 24 and 12 h after ischemic insult, respectively. At 24 h after ischemic insult, the SOD1 and CCS immunoreactivities were colocalized in the CA1 pyramidal cells of the stratum pyramidale. Thereafter, their immunoreactivities were significantly decreased in the CA1 region. To elucidate the effects of CCS or CCS/SOD1, we constructed the expression vectors PEP-1-SOD and PEP-1-CCS. In the CCS-treated group and the CCS/SOD1-treated group, 43.9 and 78.9% pyramidal cells, respectively, compared to the sham-operated group, were stained with cresyl violet 5 or 7 days after ischemic insult. The distribution pattern of active astrocytes and microglia in the PEP-CCS/SOD1-treated group 5 days after ischemic insult was similar to that of the sham-operated group. In addition, the SOD activity in the PEP-CCS- or PEP-CCS/SOD1-treated group was maintained by 10 days after ischemic insult. The SOD activity was higher in the PEP-CCS/SOD1-treated group vs the CCS-treated group. These results suggest that the enhanced expression of SOD1 and CCS may be related to compensatory mechanisms against ischemic damage and that cotreatment with CCS and SOD1 has a greater neuroprotective effect than treatment with CCS or SOD1 in isolation.
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PMID:Copper chaperone for Cu,Zn-SOD supplement potentiates the Cu,Zn-SOD function of neuroprotective effects against ischemic neuronal damage in the gerbil hippocampus. 1769 34


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