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)

The purpose of this study was to compare the effects of nicorandil [SG-75; 2-nicotinamidoethyl nitrate (ester)] and nitroglycerin on the distribution of blood flow between subendocardium and subepicardium [endocardial/epicardial blood flow ration (endo/epi)] distal to a proximal flow-limiting coronary artery stenosis in anesthetized dogs. Myocardial blood flow distribution was determined by use of 15-micron radioactive microspheres. Various indices of reactive hyperemia (peak flow, duration, volume) and poststenotic coronary pressures were used to assess the severity of ischemia in the area distal to the stenosis. Partial ischemia was produced by a 10-s total left circumflex coronary occlusion followed by 110 s of reflow to 50-60% of the control flow. Microspheres were injected during steady-state conditions during the partial reflow period. In the absence of drug, coronary artery stenosis produced marked underperfusion of the subendocardium (endo/epi, 0.55 +/- 0.05). Following administration of nicorandil (60 micrograms/kg i.v.) or nitroglycerin (15 micrograms/kg i.v.), the endo-epi during a subsequent partial reflow (stenosis present) period was significantly increased (0.67 +/- 0.06). The duration of reactive hyperemia and reactive hyperemic flow were also decreased by both compounds following release of the stenosis. These results suggest that nicorandil and nitroglycerin reduce subendocardial ischemia distal to a flow-limiting coronary artery stenosis. This beneficial effect may partially explain the efficacy of these two compounds in the therapy of angina pectoris.
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PMID:Enhanced subendocardial perfusion distal to a flow-limiting coronary artery stenosis in dogs: comparative effects of nicorandil, a potential new antianginal agent, and nitroglycerin. 241 11

Nitrates are beneficial in post-myocardial infarction patients with stable, unstable, and Prinzmetal's variant angina and as adjunctive therapy in congestive heart failure. They are available in multiple formulations that differ in chemical structure, pharmacokinetics, onset and duration of activity, and peak effect; all of these variables may condition the choice of nitrate preparation and routes of administration. Other conditions, such as different types of angina, intensity of symptomatology, psychological attitude, patient's compliance, and cost of treatment, have to be taken into account. The potential problem of nitrate tolerance requires further evaluation and can be prevented or reversed with intermittent-dosing regimens. Up-to-date nitrates continue to be a mainstay in the treatment of patients with myocardial infarction, especially if complicated by painful or silent ischemia.
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PMID:Chronic treatment after acute myocardial infarction: which drug for which patient? Nitrates. 248 40

To investigate the antiischemic efficacy and development of tolerance to transdermal nitroglycerin, 14 patients with chronic, stable angina pectoris were studied using continuous ambulatory electrocardiographic monitoring. Patients demonstrated initial hemodynamic responsiveness to sublingual nitroglycerin and were titrated to a maximally tolerated dose of 30 to 60 mg/24 hours (52 +/- 5 mg). Two crossover phases were use in a randomized, double-blind, placebo-controlled manner: continuous nitroglycerin therapy (patches containing active drug worn for 24 hours) and intermittent nitroglycerin therapy (12-hour active drug followed by a 12-hour nitrate-free period). There were no differences in frequency or duration of ischemic episodes between the placebo days of each phase. A significant effect in frequency of episodes was observed between placebo and treatment days of continuous therapy (p less than 0.05). Nonsignificant reductions in frequency and duration of ischemic episodes also occurred during intermittent therapy. The major antiischemic effect of transdermal nitroglycerin therapy occurred during the first day of treatment but was lost by 48 hours. Reductions in frequency and duration of ischemic episodes (p less than 0.05) were present on day 1 of continuous therapy but ischemic episodes returned to placebo levels by day 2, suggesting the development of tolerance. Intermittent therapy did not prevent the development of tolerance on day 2 of treatment. The results demonstrate that the use of high doses of transdermal nitroglycerin in patients with chronic, stable coronary artery disease produced a beneficial reduction in the frequency and duration of ischemia. However, the antiischemic benefit was lost between 24 nd 48 hours after the onset of continuous and intermittent therapy, presumably due to tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin. 210 35

The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 micrograms/kg followed by 25 micrograms/kg/min, i.v.) or nifedipine (3 micrograms/kg followed by 1 microgram/kg/min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (approximately 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil, or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine. 258 Jan 37

To return to the patient's syncopal episode, it is clearer now that he probably did have a vasovagal reaction. An hour had elapsed since administration of morphine, making that etiology unlikely. The patient showed no evidence of heart block or acute ischemia. While nitrate induced hypotension may have contributed to his faint, that would not have explained his bradycardia. Worth noting is the fact that he developed nausea and lost consciousness as an arterial puncture was about to be performed. Had he been asked, the patient might have recalled other incidents of vasovagal fainting. A combination of factors may cause a brief syncopal episode in the ICU. Sorting out the causes of vasovagal syncope may be difficult if not impossible, and a syncopal episode may set a chain of events into motion that further complicates the situation. The patient with an acute, especially inferior MI who received intravenous medications is particularly prone to vagal-like reactions. Patients with nausea or extreme anxiety should be watched carefully and their symptoms treated.
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PMID:Vasovagal syncope. 280 52

To monitor free radical scavenging properties of drugs, the 'stable' radical 2,2,6,6-tetramethylpiperidino-1-oxyl (TEMPO) was used. The sydnonimine molsidomine (SIN-1) effectively reduced the ESR signal whereas the nitrate isosorbidemononitrate (ISMN) did not. Thiol reagents like 2-mercaptopropionylglycine (MPG) or glutathione (GSH) only were effective in the presence of Fe2+ or Fe3+. Protein-bound iron in hemoglobin proved about four times more effective in reducing ESR signal height by thiols. It is suggested that the decrease in thiol content adds to the lack in protein bound iron of hemoglobin to induce the burst of free radicals in hypoxia (ischemia) and reperfusion.
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PMID:Free radical scavenging drugs, assessed by ESR studies: influence of hemoglobin. 285 30

Nitrate tolerance is defined as an attenuation or even loss of hemodynamic and anti-ischemic effects during continuous nitrate medication. The blunted response may be due to the development of pseudotolerance and true pharmacologic tolerance. Pseudotolerance is the result of volume and salt retention, as well as the stimulation of counter-regulatory mechanisms which may alter the baseline hemodynamics of a patient during nitrate therapy. Far less important are changes in nitrate pharmacokinetics. True pharmacological tolerance may also be of practical importance. Diminished uptake of nitrates into the vascular smooth muscle cell, a decrease in intracellular SH groups, inhibition of the guanylate-cyclase, and stimulation of a specific phosphodiesterase may result in a decrease of cyclic GMP formation and hence to a decrease in nitrate induced vasodilatation. Tolerance development may be prevented by intermittent nitrate administration providing intervals with low plasma and tissue nitrate levels. In consequence, nitrates should be used predominantly for treatment of ischemic episodes, but 24-hour anti-ischemic action for the prevention of ischemia can be better achieved by treatment with a beta-blocker and/or a calcium antagonist. Nitrates should be added in times of maximum susceptibility to ischemia, while allowing nitrate levels to fall at other times.
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PMID:[Nitrate tolerance]. 290 73

Patients with silent myocardial ischemia can be classified as one of three clinical types: those who are totally asymptomatic (type 1), those who are asymptomatic after a myocardial infarction (type 2), and those who demonstrate both asymptomatic and symptomatic episodes (type 3). Total ischemic activity may be similar in any given patient, but the ratio of symptomatic to asymptomatic episodes will differ. Prognosis appears dependent on the degree of total ischemic activity plus the extent of coronary artery disease and left ventricular dysfunction. The effects of therapy can be monitored with exercise testing and/or Holter monitoring. Using the latter technique, the largest multicenter study to date, the Nifedipine Total Ischemia Awareness Program, has demonstrated the advantages of adding a calcium antagonist to nitrate and/or beta-blocker therapy regimens in order to maximize the reduction in total ischemic activity in angina patients.
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PMID:Total ischemic burden. Implications for prognosis and therapy. 291 87

Post-infarction angina includes a syndrome of ischemic chest pain occurring either at rest or during minimal activity 24 hours or more following an acute MI. It develops in approximately 10 to 15 per cent of patients and is particularly common in non Q-wave infarcts involving the anterior myocardial wall. Post-infarction angina may result from ischemia either within the infarct zone or at a distance and frequently portends a poor long term prognosis. Platelet aggregation, coronary vasospasm, and thrombus formation at the site of a ruptured atherosclerotic plaque are each involved in its pathogenesis. The initial treatment of post-infarction angina includes identification and correction of factors that increase myocardial demand including congestive heart failure and arrhythmias. beta-Adrenergic blockers, calcium channel blockers, and nitrate preparations constitute the first line of medical therapy. The role of heparin is controversial, yet it continues to be used in clinical practice. Although thrombolytic agents are currently being investigated, early experience suggests that they may accelerate clinical stabilization and allow time for elective revascularization when required. Antiplatelet therapy with aspirin has proven benefit in the long term management of unstable angina. Patients unresponsive to medical therapy should be considered for intra-aortic balloon pump placement and early coronary angiography. Revascularization with either coronary angioplasty or coronary artery bypass grafting may then be performed as dictated by the overall clinical status, available facilities, and coronary anatomy.
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PMID:Management of post-infarction angina. 304 72

Recent evidence suggests that traditional approaches to the use of nitroglycerin (NTG) in patients with chronic stable angina should be reconsidered. Studies of the time to onset of hemodynamic effects of sublingual NTG suggest that the first detectable effect, on left ventricular end-diastolic pressure, occurs at a mean of 90 seconds after administration. By timing the duration of exertional angina after formal exercise testing, one can show that, on average, chest pain is gone within 2 minutes. Thus, in many patients, it is unlikely that sublingual NTG can further shorten episodes of exertional angina. The value of sublingual NTG is greater when patients exercise beyond the onset of pain, when patients have more protracted episodes of exertional pain and when there is a need to resume immediately the activity that brought on the angina. With respect to angina prophylaxis, the pioneering studies of Parker and co-workers have now been amply confirmed. Continuous nitrate administration by oral, transdermal or intravenous routes results in substantial, albeit incomplete, tolerance. Tolerance occurs even when high plasma concentrations are achieved and persist over time. Tolerance can eliminate responsiveness to sublingual NTG. Preliminary evidence suggests that tolerance to the antianginal effects of NTG at maximal exercise may be more marked than tolerance to the effects of NTG on silent ischemia at submaximal activity levels. The significance of this dissociation in time course and its implications are unclear at this time. Three potential strategies exist for avoiding NTG tolerance in patients with chronic stable angina. Administration of a thiol donor has been shown to reverse some hemodynamic manifestations of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitroglycerin in chronic stable angina pectoris. 312 May 61


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