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)

Ischemia/reperfusion (I/R), a phenomenon that is associated with conditions such as organ transplantation, trauma, vascular disease, and stroke, involves the recruitment of activated and adherent leukocytes that subsequently mediate tissue injury. Endothelial cell adhesion molecules such as P-selectin mediate I/R-induced leukocyte recruitment and allow the adherent leukocytes to damage the vascular wall and parenchymal cells. This study examines the influence of dypiridamole (persantine) on hemorrhagic shock (H/S)-induced P-selectin expression. H/S was induced in C57BL/6 mice by withdrawing blood to drop the mean arterial blood pressure to 30 to 35 mm Hg for 45 minutes. The mice were resuscitated by infusing the shed blood and Ringer's lactate (50% shed blood volume). In vivo P-selectin expression was determined using a dual monoclonal antibody technique in the heart, lung, liver, kidneys, stomach, small bowel, and colon of a control group, a hemorrhagic shock group, and a hemorrhagic shock group that was pretreated with Persantine (Boehringer, Ingelheim, Ingelheim, Germany). H/S significantly (P < 0.01) increased P-selectin expression in all regional vascular beds of untreated mice. Persantine treatment largely prevented the H/S-induced P-selectin expression in the same vascular beds. Persantine significantly attenuates the upregulation of P-selectin in the hemorrhagic shock model.
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PMID:Persantine attenuates hemorrhagic shock-induced P-selectin expression. 1114 78

Dipyridamole nuclear myocardial perfusion test is a safe and effective alternative to exercise nuclear perfusion testing for detecting myocardial ischemia. It is the procedure of choice in selected patients who are unable to exercise adequately. Intravenous dipyridamole causes coronary vasodilation with resultant maldistribution and heterogeneity of coronary flow in the presence of significant coronary artery disease. True ischemia, causing symptoms or ST-segment depression, is uncommon, in part because there is no increase in myocardial oxygen demand. A patient in whom myocardial ischemia developed, manifested by ST-segment elevation, during dipyridamole stress testing is described. Scintigraphic images illustrated a myocardial perfusion defect, which was consistent with coronary angiographic findings. This case report addresses the importance of dipyridamole-induced ST-segment elevation, its correlation with angiographic findings, and the need for continued hemodynamic and electrocardiographic monitoring in patients following dipyridamole infusion.
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PMID:Dipyridamole-induced ST-segment elevation indicative of transmural myocardial ischemia--a case report. 1151 95

A 31-year-old man was admitted to our hospital for further evaluation of heart failure symptoms. Crow-Fukase syndrome was diagnosed on the basis of findings of polyneuropathy, hepatomegaly, monoclonal hypergammaglobulinemia, and hypertrichosis. Dipyridamole-stress thallium-201 perfusion imaging, contrast left ventriculography, and coronary angiography revealed a markedly dilated and dysfunctioning left ventricle, extensive reversible ischemia with fixed defect, and multiple coronary lesions. Histopathology of myocardial biopsy specimens demonstrated ischemia-induced myocardial necrosis. These findings suggested that ischemic cardiomyopathy, probably due to inflammatory reactions of coronary arteries in Crow-Fukase syndrome, was responsible for the heart failure symptoms and left ventricular dysfunction in this patient.
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PMID:Crow-Fukase syndrome with ischemic cardiomyopathy. 1151 11

In patients with diabetes and coronary artery disease, the potential negative role of sulfonylurea drugs is under intensive investigation. We assessed the effects of treatment with glibenclamide or insulin on the extension of left ventricular myocardial dysfunction induced by acute ischemia. Nineteen consecutive patients with type 2 diabetes and coronary artery disease entered the study. Each patient was randomly assigned to either insulin or glibenclamide therapy. Treatment was crossed over after 12 weeks and maintained for another 12 weeks. At the end of each treatment, left ventricular myocardial function at rest and during dipyridamole infusion was studied by two-dimensional echocardiography under the same conditions of metabolic control. Glibenclamide or insulin treatment did not influence the rest values of left ventricular dimensions, left ventricular ejection fraction (LVEF), or wall motion score index (WMSI). Dipyridamole infusion, in patients receiving glibenclamide treatment, decreased LVEF (43 +/- 7 vs. 37 +/- 12%, P < 0.005) and increased WMSI (1.4 +/- 0.28 vs. 1.98 +/- 0.24, P < 0.001) compared with baseline values; during insulin treatment, LVEF (46 +/- 8 vs. 45 +/- 11%, NS) and WMSI (1.4 +/- 0.29 vs. 1.6 +/- 0.4, NS) did not change significantly. Peak stress LVEF was higher (45 +/- 11 vs. 37 +/- 12%, P < 0.001) and WMSI lower (1.6 +/- 0.4 vs. 1.98 +/- 0.24, P < 0.001) in patients receiving insulin. The results indicate that in patients with type 2 diabetes and coronary artery disease, ischemic myocardial dysfunction induced by dipyridamole infusion is less severe during treatment with insulin than with glibenclamide. Restitution of a preconditioning mechanism in insulin-treated patients may be the potential beneficial mechanism.
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PMID:Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes. 1187 84

Loss of inhibitory GABAergic modulation may induce hyperexcitability of neuronal elements and potentiate their vulnerability to excitotoxic injury. It has been also found that the adenosine system interacts with the GABAergic system during ischemia and anoxia where the adenosine receptors as well as the GABAergic receptors may conscript the same intracellular pathway to increase tolerance to ischemia. Therefore, it was aimed to study whether dipyridamole (CAS 58-32-2), an adenosine uptake inhibitor, or adenosine (CAS 58-61-7) could affect the rat brain gamma-aminobutyric acid (GABA, CAS 56-12-2) level after induction of cerebral ischemia, and to test their effect on the lactate dehydrogenase (LDH) activity of the ischemic rat brain. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by reperfusion for other 60 min. Dipyridamole was administered alone and in combination with adenosine and the effect of the drugs on the brain GABA level as well as on LDH activity was determined. The results show that dipyridamole could protect the brain of rats against the ischemic insult, while adenosine when administered separately failed to influence the selected parameters. Protection of the rat brain by dipyridamole might be related to the elevated level of GABA.
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PMID:Influence of inhibition of adenosine uptake on the gamma-aminobutyric acid level of the ischemic rat brain. 1208 19

Increased dispersion of the QT interval has been observed during pacing or exercise stress testing in patients with coronary artery disease (CAD). It has not been established whether this phenomenon is a consequence of ischemia. Therefore, we sought to evaluate whether dipyridamole-induced myocardial ischemia, as directly detected by echocardiographic monitoring of regional contractile function, would affect QT dispersion. Twenty-four patients with nonsignificant and 34 patients with significant CAD but no previous myocardial infarction underwent dipyridamole stress echocardiography while not taking medications. QT dispersion was measured on a 12-lead electrocardiogram at baseline and at various times after dipyridamole infusion. Dipyridamole infusion did not influence QT dispersion in patients without CAD. QT dispersion was similarly unaffected in patients with CAD in whom dipyridamole did not induce wall motion abnormalities. In contrast, in patients with positive dipyridamole stress test findings, QT dispersion increased from 60 +/- 17 ms at baseline to 94 +/- 25 ms during peak infusion (p <0.0001), with a time course mirroring that of development of contractile abnormalities. QT dispersion returned to 63 +/- 25 ms upon relief of ischemia by administration of aminophylline. The increase in QT dispersion was significantly related to the extent of contractile dysfunction induced by dipyridamole. Although ST-segment depression occurred in only 40% of patients with positive dipyridamole stress test findings, 88% of such patients had an increase in QT dispersion. Analysis of the receiver-operating characteristic curve showed that a QT dispersion increase of > or =20 ms identified positive findings for dipyridamole stress echocardiography with 68% sensitivity and 91% specificity. Thus, QT dispersion is acutely affected by myocardial ischemia induced by the administration of dipyridamole. Measurement of QT dispersion may improve detection of stress-induced ischemia on surface electrocardiograms.
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PMID:Effects of acute myocardial ischemia on QT dispersion by dipyridamole stress echocardiography. 1258 49

Adenosine is formed during conditions that deplete ATP, such as ischemia. Adenosine deaminase converts adenosine into inosine, and both adenosine and inosine can be beneficial for postischemic recovery. This study investigated adenosine and inosine release from astrocytes and neurons during chemical hypoxia or oxygen-glucose deprivation. In both cell types, 2-deoxyglucose was the most effective stimulus for depleting cellular ATP and for evoking inosine release; in contrast, oxygen-glucose deprivation evoked the greatest adenosine release. alpha,beta-Methylene ADP, an inhibitor of ecto-5'nucleotidase, significantly reduced adenosine release from astrocytes but not neurons. Dipyridamole, an inhibitor of equilibrative nucleoside transporters, inhibited both adenosine and inosine release from neurons. Erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase, reduced neuronal inosine release evoked by oxygen-glucose deprivation but not by 2-deoxyglucose treatment. These data indicate that (1). astrocytes release adenine nucleotides that are hydrolyzed extracellularly to adenosine, whereas neurons release adenosine per se, (2). inosine is formed intracellularly and released via nucleoside transporters, and (3). inosine is formed by an adenosine deaminase-dependent pathway during oxygen-glucose deprivation but not during 2-deoxyglucose treatment. In summary, the metabolic pathways for adenosine formation and release were cell-type dependent whereas the pathways for inosine formation were stimulus dependent.
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PMID:Stimulus- and cell-type-specific release of purines in cultured rat forebrain astrocytes and neurons. 1500 86

Pharmacologic stress myocardial perfusion imaging is being performed with increasing frequency over exercise stress. Dipyridamole and adenosine have a high side-effect profile, provide higher than needed coronary artery flow rates, and use a relatively complicated method of administration. Based on preclinical animal work, three selective adenosine A2A receptor agonists, regadenoson (CVT3146), binodenoson (MRE0470 or WRC0470), and apadenoson (BMS068645 or ATL146e), may overcome these limitations and are now in Phase III studies as pharmacologic stress agents. For single-photon emission CT imaging, binodenoson and regadenoson were concordant with adenosine images for detection and quantitation of ischemia. Despite the high A2A selectivity of binodenoson and regadenoson in preclinical studies, subjective side effects attributable to other adenosine receptor subtypes were still observed in human studies and are similar to or slightly lower than adenosine. There have been no reports of atrioventricular block or bronchospasm with either regadenoson or binodenoson in published trials.
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PMID:Advances in pharmacologic agents in imaging: new A2A receptor agonists. 1652 38

Bone marrow cell transplantation has been proposed as a novel therapeutic option for patients with coronary artery disease. This study investigated whether autologous bone marrow-derived mononuclear cell injection into the ischemic myocardium of patients with severe angina pectoris could safely reduce anginal symptoms, improve myocardial perfusion, and increase left ventricular (LV) function. In a total of 20 patients (63 +/- 10 years old; 16 men) with angina pectoris, myocardial segments with stress-induced ischemia as assessed by gated single-photon emission computed tomography were injected with 30 to 100 million mononuclear cells. Anginal symptoms, Canadian Cardiovascular Society class, and quality of life were assessed at 3 and 6 months of follow-up. At baseline and 3 months of follow-up, an exercise test, gated single-photon emission computed tomography, and magnetic resonance imaging were performed to assess exercise capacity, myocardial perfusion, and LV function. Intramyocardial injection of autologous bone marrow-derived mononuclear cells was safe. The Canadian Cardiovascular Society class improved from 3.5 +/- 0.5 at baseline to 2.4 +/- 0.6 after 3 months (p <0.01) and 2.4 +/- 0.6 after 6 months (p <0.01). The quality-of-life score improved from 52 +/- 10% to 71 +/- 10% at 3 months (p <0.01) to 73 +/- 15% at 6 months (p <0.01). The exercise capacity increased from 79 +/- 31% to 84 +/- 29% (p <0.05). Magnetic resonance imaging revealed an increased LV ejection fraction from 51 +/- 11% to 54 +/- 10% (p <0.01) and a reduced LV end-systolic volume from 97 +/- 50 to 88 +/- 42 ml (p <0.01). The wall motion score index improved from 0.36 +/- 0.32 to 0.24 +/- 0.28 (p <0.01). The number of segments with stress-induced ischemia decreased from 5.1 +/- 3.2 to 2.3 +/- 2.6 (p<0.01). In conclusion, autologous bone marrow-derived mononuclear cell injection in patients with ischemia is safe, reduces anginal symptoms, improves myocardial perfusion, and increases LV function.
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PMID:Usefulness of intramyocardial injection of autologous bone marrow-derived mononuclear cells in patients with severe angina pectoris and stress-induced myocardial ischemia. 1663 5

Dipyridamole increases adenosine levels and augments coronary collateralization in patients with coronary ischemia. This pilot study tested whether a 6-month course of sustained-release dipyridamole/aspirin improves coronary flow reserve and left ventricular systolic function in patients with ischemic cardiomyopathy. Six outpatients with coronary artery disease and left ventricular ejection fraction (LVEF) <40% were treated with sustained-release dipyridamole 200 mg/aspirin 25 mg twice daily for 6 months. Myocardial function and perfusion, including coronary sinus flow at rest and during intravenous dipyridamole-induced hyperemia, were measured using velocity-encoded cine magnetic resonance stress perfusion studies at baseline, 3 months, and 6 months. There was no change in heart failure or angina class at 6 months. LVEF increased by 39%+/-64% (31.0%+/-13.3% at baseline vs 38.3%+/-10.7% at 6 months; P=.01), hyperemic coronary sinus flow increased more than 2-fold (219.6+/-121.3 mL/min vs 509.4+/-349.3 mL/min; P=.01), and stress-induced relative myocardial perfusion increased by 35%+/-13% (9.4%+/-3.4% vs 13.9%+/-8.5%; P=.004). Sustained-release dipyridamole improved hyperemic myocardial blood flow and left ventricular systolic function in patients with ischemic cardiomyopathy.
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PMID:Effect of chronic sustained-release dipyridamole on myocardial blood flow and left ventricular function in patients with ischemic cardiomyopathy. 1754 6


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