Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiarrhythmic effectiveness of N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) has been investigated in 10 patients with ischemic heart disease and frequent premature ventricular contractions (PVCs). Each patient received a random succession of treatment with the drug (1020 mg) and with a reference substance (solvent of COP) both administered i.m. twice a day over a 3-day period. In each patient a Holter ECG was recorded in the basal state and during the last 24 h of each treatment. Heart rate, PQ and QTc showed no changes. On the contrary, PVCs were significantly lower (P less than 0.01) with COP than with the reference substance. The drug showed a prevailing effect during daytime. Results are discussed in view of experimental observations suggesting that COP has a "membrane effect".
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PMID:Antiarrhythmic effectiveness of creatinol O-phosphate in man. 9 66

In a double-blind investigation N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was checked versus a reference substance (solvent of COP) on volunteers affected by ischemic heart disease with persistent ventricular premature beats (VPB). COP was able to reduce VPB by 50--100% in 85% of the volunteers treated with this drug. This fact and the virtual absence of side-effects of COP lead the authors to the conclusion that COP merits more extensive investigations in this field in view of its clinical employment alone or in association with specific antiarrhythmic agents.
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PMID:Activity of creatinol O-phosphate on persistent ventricular premature beats in ischemic heart disease. Double blind clinical trial. 39 59

The authors report a case of spontaneous rupture of spleen inaugurating the symptomatology of a pheochromocytoma. After presenting the observation, clinical problems are considered with a deceptive abdominal symptomatology and myocardial ischemia that could be part of an "adrenergic myocarditis"; the mechanism of ruptured spleen is analyzed. The diagnosis approach is discussed through a reliability study of various explorations: computed tomography has a sensitivity ranging from 93 to 97% which approaches 100% when associated with magnetic resonance, methyl-iodo-benzyl-guanidine scanning seems to be provided with similar reliability. During checking up for pheochromocytoma spreading, ectopic location was not found, but a cold thyroid nodule was detected which allowed suspecting a SIPPLE syndrome. The three-stage surgical approach was required by symptomatology, hemostasis splenectomy, lateral pheochromocytoma excision after a short preparation by blocking alpha and beta, and then total thyroidectomy after extemporaneous confirmation of the existence of a medullary carcinoma of the thyroid. This pathologic association leading to a SIPPLE syndrome is listed as part of the multiple endocrine neoplasias of type II (MEN II).
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PMID:[Spontaneous rupture of the spleen disclosing pheochromocytoma]. 226 21

Thallium myocardial imaging is a useful technique to evaluate myocardial perfusion and myocardial viability in ischemic heart disease. However, myocardial imaging using single photon emission computed tomography (SPECT) and gamma-emitting radiopharmaceuticals has been recently developed for more precise evaluation of myocardial infarction and ischemia. The present study evaluates animal experiments and the clinical applications of these new myocardial imaging techniques. Areas considered on 1) myocardial necrosis assessed using 111In-antimyosin, 2) myocardial fatty acid metabolism assessed using 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and 3) myocardial sympathetic neural activity assessed using 123I-metaiodobenzyl guanidine (MIBG). Dual energy SPECT using these new agents and thallium gives precise characterization of the myocardial tissue in the infarcted and ischemic area.
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PMID:Newly developed myocardial imaging by using single photon emission computed tomography (SPECT). 236 19

Alterations in cardiac sympathetic innervation may result in QT interval prolongation and predispose to sudden arrhythmias and death. Sudden cardiac death occurs in diabetic patients who have autonomic neuropathy, but the cause is uncertain. In 30 patients with insulin-dependent diabetes mellitus who had no evidence of ischemic heart disease, cardiac autonomic neuropathy, determined by clinical tests, was found in 17. The corrected QT interval (QTc), measured using Bazett's formula at rest and peak exercise, was prolonged (greater than 440 msec) in 12 of these patients at rest and in 15 at peak exercise. Prolonged QTc intervals were found only in patients who had definite cardiac autonomic neuropathy. As a group, the QTc interval (mean +/- SD) in the diabetic patients with cardiac autonomic neuropathy was prolonged compared to that in patients without cardiac autonomic neuropathy at rest (447 +/- 28 vs. 405 +/- 9 ms; P less than 0.0001) and peak exercise (468 +/- 23 vs. 402 +/- 23 ms; P less than 0.0001). There was a direct linear relationship between the extent of cardiac autonomic neuropathy and the QTc interval (r = 0.71; P less than 0.001). One of the patients with cardiac autonomic neuropathy and prolonged QTc intervals had a nonuniform loss of adrenergic neurons in his heart demonstrated by meta-iodobenzyl-guanidine scintigraphy, indicating sympathetic imbalance; he subsequently died unexpectedly. These data suggest that diabetic cardiac autonomic neuropathy may result in sympathetic imbalance and QTc interval prolongation, predisposing these patients to sudden arrhythmias and death.
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PMID:QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy. 381 2

The purpose of this study was to clarify any association between clinically detectable silent myocardial ischemia (SMI) and myocardial 123I-metaiodobenzyl-guanidine (MIBG) uptake. Subjects of this study were (1) patients with SMI with diabetes (n = 15), (2) patients with angina pectoris with diabetes (n = 15), (3) patients with SMI without diabetes (n = 8) and (4) normal subjects (n = 23). Subjects underwent planar and single photon-emission-computed tomography (SPECT) imaging 15 min and 3 hours after injection of 123I-MIBG. H/M ratio was significantly lower in diabetic SMI (2.1 +/- 0.3) and non-diabetic SMI (2.3 +/- 0.3) than control subjects (2.6 +/- 0.3). The inferior-to-anterior wall count ratio (I/A) in diabetic SMI group was the lowest among all groups (p < 0.05). A significant difference was observed in relative regional uptake in the inferior segment of the distal left ventricle between SMI and angina group in patients with diabetes mellitus (p < 0.05). The decreased MIBG uptake in the inferior wall may be an important sign of cardiac sympathetic dysfunction, suggesting the abnormalities in cardiac nervous system play an important role in the mechanism of diabetic silent myocardial ischemia.
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PMID:[Characteristics of regional sympathetic innervation in diabetic patients with silent myocardial ischemia assessed by 123I-metaiodobenzylguanidine imaging]. 869 17

Studies in different preparations have suggested that Na+/H+ exchange is one mechanism causally involved in cell death in myocardial ischemia and reperfusion. The time delay of cell death by pretreatment with the Na+/H+-exchange inhibitor HOE642, cariporide (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), was investigated in regionally ischemic, reperfused porcine hearts. HOE642 (1 mg/kg) was injected intravenously in 14 thoracotomized pigs 10 min before occlusion of the left anterior descending coronary artery (45 min of ischemia, six pigs; 70 min of ischemia, six pigs; 90 min of ischemia, two pigs). Ischemia was followed by 24 h of reperfusion. Six animals (45 min of ischemia) served as controls. Infarct size was determined as a ratio of infarcted (tetrazolium stain, histology) to ischemic myocardium (dye technique), and regional myocardial function was assessed by sonomicrometry. HOE642 did not affect global hemodynamic parameters. In the pretreated group with 45 min of ischemia, HOE642 significantly decreased histochemical infarct size from 51.2 +/- 12.6% (control group) to 13.2 +/- 12% (p < 0.005) and histologic infarct size from 44.5 +/- 9% to 17.1 +/- 7% (p < 0.005). Recovery of regional systolic shortening after 24 h of reperfusion was improved from 2 +/- 6% (control group) to 12 +/- 7% (p = 0.02). In addition, myocardial contracture and increase in heart rate during early reperfusion were attenuated. When ischemia was prolonged to 70 min after pretreatment with HOE642, infarct size, recovery of systolic shortening, myocardial contracture, and increase in heart rate did not differ from those of the control group. Pretreatment with HOE642 increased the tolerance to ischemia/reperfusion by approximately 20-25 min. Inhibition of Na+/H+ exchange appears to be very promising in the clinical treatment of acute myocardial ischemia and reperfusion.
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PMID:Time delay of cell death by Na+/H+-exchange inhibition in regionally ischemic, reperfused porcine hearts. 926 52

Blockade of the Na+/H+ exchange has been shown to diminish the serious consequences of myocardial ischemia. The aim of this investigation was to alter the structure of the common benzoylguanidine NHE inhibitors in such a way that the 3-methylsulfonyl and 4-alkyl group form a ring. The new benz-fused five-, six-, and seven-membered ring sulfones were prepared by internal Heck reaction. Benz-fused five-membered ring sulfones could also be prepared by internal aldol-type condensation using ketones or nitriles as acceptor groups. In the final step, the carboxyl groups were converted to acylguanidines preferentially by guanidine treatment of the esters or acid chlorides. The compounds were tested as their methanesulfonate salts. The inhibition of the Na+/H+ antiport activity was determined by observing the uptake of 22Na+ into acidified rabbit erythrocytes. Additionally, the inhibition of the antiport activity was assessed also by the platelet swelling assay (PSA), in which the swelling of human platelets was induced by the incubation in the presence of a weak organic acid. On average, the IC50 values in the PSA turned out to be about 10-fold higher than in the erythrocyte assay primarily due to a higher Na+ concentration in the PSA; however, the order of the compounds' potency was not substantially altered. The new compounds were found to be highly active with peak values ranging within the cariporide and EMD 96785 standards.
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PMID:Bicyclic acylguanidine Na+/H+ antiporter inhibitors. 973 99

The abilities of 2-(2-methylphenyl)-5,7-dimethoxy-4-quinolyl carbonylguanidine dihydrochloride (CAS 181048-29-3, MS-31-050) and 2-phenyl-8-(2-methoxyethoxy)-4-quinolyl carbonylguanidine bismethanesulfonate (CAS 181048-36-2, MS-31-038) in inhibiting Na(+)-H+ exchange, ischemia- and reperfusion-induced injury were determined and compared with those of 4-isopropyl-3-methylsulfonylbenzoyl guanidine methanesulfonate (CAS 159138-81-5, IMGM), a selective inhibitor of Na(+)-H+ exchange. MS-31-050 and IMGM exhibited comparable inhibitory effects on Na(+)-dependent pH recovery and antiarrhythmic effects during ischemia in anesthetized rats. In rats subjected to ischemia and reperfusion, MS-31-050 (10 mg/kg i.v.) significantly reduced the infarct size when given prior to the onset of ischemia. However, postischemic treatment with either MS-31-050 or IMGM failed to protect reperfused hearts. In contrast, MS-31-038 reduced the infarct size dramatically from 65.4 +/- 7.4% in control to 29.9 +/- 11.6% at 3 mg/kg and 9.8 +/- 3.4% at 10 mg/kg even when administered before the onset of reperfusion. These results suggest the beneficial effects of Na(+)-H+ exchange inhibitors on myocardial ischemia/reperfusion injury.
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PMID:Effects of MS-31-038, a novel Na(+)-H+ exchange inhibitor, on the myocardial infarct size in rats after postischemic administration. 1033 48

Cariporide, HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na(+)-H+ exchange (NHE) subtype 1 inhibitor, has cardioprotective effects including an antifibrillatory effect on the coronary ischemia/reperfusion induced arrhythmias not only in in vitro, but also in vivo animal hearts, which might be induced by intracellular Ca2+ overload following myocardial ischemia. This antifibrillatory effects on reperfusion arrhythmias were observed even when the drug was administered after induction of coronary ischemia or even when the drug was administered simultaneously with reperfusion. Other NHE inhibitors also have similar antiarrhythmic and antifibrillatory effects as cariporide and these drugs had almost no deleterious effects on the heart rate and blood pressure, nor ECG parameters. The antifibrillatory mechanism of NHE inhibitors may be due to their NHE inhibition as judged by the doses used, and they may become useful for treating or preventing arrhythmias in patients with coronary artery diseases.
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PMID:[Na+/H+ exchange inhibitors for ischemic diseases]. 1177 53


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