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)

A new antianginal agent, nicorandil, was tested in an isolated perfused rat heart model. Hearts were subjected to 30 min of low-flow, global ischemia followed by 30 min of reperfusion in the presence or absence of nicorandil. Nicorandil (1,500 micrograms/l) significantly improved isovolumic left ventricular minute-work during reperfusion compared to untreated hearts. Nicorandil also prevented the rebound in cardiac phosphocreatine levels and the loss of total adenine nucleotides as a result of ischemia and reperfusion. The salient effect of nicorandil was independent of any alterations in the release of endogenous prostacyclin. These results suggest that nicorandil may possess a unique cytoprotective effect on the ischemic-reperfused myocardium.
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PMID:Protective effect of nicorandil on postischemic function and tissue adenine nucleotides following a brief period of low-flow global ischemia in the isolated perfused rat heart. 252 51

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

Nicorandil therapy was compared with placebo therapy in 11 patients with chronic stable angina pectoris. A computer-assisted treadmill exercise test was performed after administration of either 10 or 30 mg of nicorandil. Analysis of variance showed a significant difference among placebo and nicorandil treatments (p less than 0.01). Ten milligrams of nicorandil prolonged time to onset of ischemia 36% (p less than 0.05) but increased the exercise duration only 15%. Thirty milligrams of nicorandil prolonged time to onset of ischemia 82% (p less than 0.01) and exercise duration 45% (p less than 0.01). Both time to onset of ischemia and exercise duration increased progressively from the 10-mg to the 30-mg dose (p less than 0.05). Heart rate at rest was significantly higher and systolic pressure at rest significantly lower with 30 mg of nicorandil than with placebo. After administration of 30 mg of nicorandil there was a significant reduction in ST depression associated with a slight decrease in the double product at the end of Bruce stage 2 exercise. The peak double product was greater after administration of 30 mg of nicorandil than after placebo, indicating an increased myocardial oxygen supply to the ischemic area. The plasma concentration of nicorandil averaged 78 +/- 83 ng/ml with the 10 mg and 313 +/- 142 ng/ml with 30 mg. There was an increase in exercise duration of more than 1 minute in 8 of 9 patients who had plasma nicorandil concentrations greater than 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris. 294 20

The effects of two antianginal drugs, nicorandil and isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple coronary occlusions in barbital-anesthetized dogs. The preparation consisted of three 5 min occlusions of the left anterior descending coronary artery interspersed by 30 min of reperfusion. An equihypotensive dose of nicorandil (7.5 micrograms/kg/min) or ISDN (12.5 micrograms/kg/min) was infused 15 min before and during the second occlusion period. Hemodynamics, myocardial segment shortening (%SS), tissue blood flow, and myocardial oxygen consumption were determined throughout. Uptake of free fatty acids (FFA), glucose, and lactate were determined during control and ischemic periods. At the end of the final 30 min reperfusion period, biopsy samples of transmural tissue were taken for analysis of phosphocreatine, adenine nucleotides, and total tissue water content. No major hemodynamic changes were produced by either drug except for a 5 to 10 mm Hg decrease in mean aortic pressure. Compared with untreated and ISDN-treated hearts, hearts of dogs treated with nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent ischemia. This was accompanied by an attenuation of the increase in oxygen extraction and CO2 production in the ischemic zone by nicorandil, but not by ISDN. Nicorandil, but not ISDN, improved %SS during reperfusion. Endocardial ATP and total adenine nucleotides were preserved in both nicorandil- and ISDN-treated hearts. Tissue edema was also attenuated by both compounds. Thus, nicorandil improved both function and metabolism during recurrent myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of adenine nucleotides and increase in tissue water.
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PMID:Salutary action of nicorandil, a new antianginal drug, on myocardial metabolism during ischemia and on postischemic function in a canine preparation of brief, repetitive coronary artery occlusions: comparison with isosorbide dinitrate. 295 76

The effects of nicorandil and nifedipine on ischemia--reperfusion-induced myocardial infarct size following a 2-h occlusion and 30-min reperfusion period of the left anterior descending coronary artery (LAD) were compared in anesthetized dogs. Myocardial blood flow was measured using the radioactive microsphere technique, and infarct size was determined using triphenyl tetrazolium chloride histochemical stain. Vehicle, nicorandil (100-micrograms/kg bolus followed by 25 micrograms/kg/min), or nifedipine (10-micrograms/kg bolus followed by 1 microgram/kg/min) was administered intravenously 10 min after LAD occlusion and infused throughout the occlusion and reperfusion periods. Nicorandil and nifedipine reduced mean arterial blood pressure similarly (15 mm Hg) during infusion. However, neither drug altered collateral blood flow to the ischemic region during occlusion. In all three groups, left ventricular mass, area at risk mass, percentage of the left ventricle at risk, and retrograde flow during occlusion were similar. As compared with the control group, nicorandil reduced myocardial infarct size as determined by absolute mass, percentage of the area at risk infarcted, and percentage of the left ventricle infarcted. Nifedipine had no significant effect on infarct size. This beneficial effect of nicorandil was not related to an improvement in myocardial blood flow or a change in global hemodynamics.
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PMID:Effects of nicorandil and nifedipine on protection of ischemic myocardium. 620 83

Following trials in Japan, Nicorandil (SG-75) has been introduced as a new antianginal drug with coronary dilatory properties. The effects of 20 mg SG-75 administered sublingually were studied in 9 patients with coronary artery disease and reproducible pacing-induced myocardial ischemia (MIS) (rise in left ventricular enddiastolic pressure, changes in ST-segment, and angina). Changes in heart rate, arterial pressure and angiographic left ventricular ejection parameters, contractility, parameters derived from left ventricular function (ejection fraction, cardiac index, stroke work index) and cardiac work (left ventricular stroke work index, left ventricular work), myocardial oxygen consumption, cardiac efficiency (LVeff), and regional wall motion (RWM) were investigated for the following hemodynamic phases: 7th and 14th minute after SG-75, the immediate postpacing phase without medication (PPP), and the postpacing phase under the influence of SG-75 (PPP + SG). In the 7th and 14th minute after SG-75 and in the absence of stress, there was no variation from control values (p less than 0.05). In the 15th and 16th minute after SG-75 (serum-level control), under pacing stress equivalent to that measured in the PPP, the MIS observed in the absence of medication did not now occur. Moreover, in the PPP + SG-75 phase the following mean parameter changes were noted: ejection fraction +21%, cardiac index +37%, left ventricular stroke work index +48%, left ventricular work +52%, and LVeff +60%; RWM also improved. Prophylaxis of ischemia and improved hemodynamics under the influence of SG-75 were probably due to a decrease in preload (left ventricular enddiastolic pressure -41%) and afterload (stroke volume ratio -29%). Similar changes might have been expected after nitroglycerin, if given under equivalent conditions. Since no harmful effects, either subjective or objective, were apparent during or after application of SG-75, this seems to be a promising drug for the antianginal therapy of the future.
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PMID:[Efficacy of nicorandil (SG-75), a substance with nitro-properties and long-term effects in coronary patients: improvement of LV-function and wall motility without pacing-induced myocardial ischemia]. 621 3

Experiments were designed to assess whether (1) nicorandil given before global low-flow ischemia or (2) included in low-flow continuous cardioplegia improved the recovery of cardiac function in the isolated rat heart. The first investigated the effect of nicorandil (2, 10, or 100 mumol/L), given for 3 minutes before 30 minutes of normothermic global ischemia, on recovery after 30 minutes of reperfusion. In aerobically perfused hearts, doses of 10 and 100 mumol/L significantly increased coronary flow; the dose of 100 mumol/L exerted a negative inotropic effect. These doses shortened the time to contractile arrest (282 +/- 18 and 276 +/- 22 seconds versus 354 +/- 16 seconds in the control hearts with unmodified ischemia; p < 0.05 in both instances). Nicorandil also improved the postischemic recovery of coronary flow (79.1% +/- 1.7% and 78.0% +/- 1.6%, respectively, versus 71% +/- 1.8%; p < 0.05). However, there was no significant improvement in recovery of contractile function, creatine kinase leakage, or tissue adenosine triphosphate and creatine phosphate contents. Second, pretreatment with nicorandil (10 mumol/L) was shown to increase susceptibility of the hearts to reperfusion-induced ventricular fibrillation from 0% (n = 8) in control hearts to 50% in the drug-treated group (p < 0.05). Third, nicorandil (10 mumol/L) was added to cardioplegic and noncardioplegic solutions infused into the coronary tree throughout 100 minutes of low-flow (0.7 ml/min) ischemia: in eight of nine control hearts electrical activity was maintained throughout, whereas in all nicorandil-treated hearts electrical activity was suppressed for at least part of the time. Nicorandil also reduced the prevalence of ischemic contracture to 0% during continuous infusion of cardioplegic solution (compared with 30% in nicorandil-free control hearts) and improved the recovery of contractile function after 40 minutes of reperfusion. Thus, in the noncardioplegia groups, left ventricular developed pressure recovered to 77.8% +/- 4.0% versus 51.7% +/- 2.6% in control hearts (p < 0.05) and in the cardioplegia groups to 96.2% +/- 4.2% versus 79.7% +/- 5.5% (p < 0.05). Ventricular compliance (the ventricular volume required to achieve a left ventricular end-diastolic pressure of 4 mm Hg) was better preserved in the nicorandil-containing noncardioplegia group (133 +/- 6 microliters) than in the control group (88 +/- 10 microliters; p < 0.05). In conclusion, nicorandil has been shown to (1) reduce ischemic contracture, (2) lessen the effects of ischemic arrest, and (3) improve the postischemic recovery of contractile function. In this species and preparation it may, however, enhance vulnerability to reperfusion-induced arrhythmias.
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PMID:Protective effect of nicorandil as an additive to the solution for continuous warm cardioplegia. 747 35

Various evidence suggest that myocardial ischemia is a major factor in the progression of hypertrophic cardiomyopathy (HCM). In this study, we investigated the effects of nicorandil on left ventricular (LV) systolic and diastolic function in 12 symptomatic patients with HCM using echocardiography and radionuclide angiography. Nicorandil (6 mg), when administered intravenously, produced no significant changes in any parameter, including LV filling dynamics. However, accelerated LV peak early filling velocity (0.51 +/- 0.13 to 0.59 +/- 0.14 m/sec, p < 0.01), and reduced peak velocity in atrial contraction (0.54 +/- 0.17 to 0.50 +/- 0.15 m/sec, p < 0.05) were observed by Doppler echocardiography after 4 weeks of oral administration of 10 mg nicorandil 3 times daily. This oral administration did not affect heart rate, blood pressure, LV outflow gradient, or LV systolic function. The same favorable results were observed in a wall motion analysis with radionuclide angiography: peak filling rate (PFR) in global LV (3.21 +/- 0.76 to 3.52 +/- 0.87 end-diastolic volume (EDV)/sec, p < 0.02), and apical (4.73 +/- 1.18 to 5.42 +/- 1.55 EDV/sec, p < 0.01) and lateral (4.78 +/- 1.60 to 5.52 +/- 1.51 EDV/sec, p < 0.05) segments was increased, and the time to peak filling rate (TPF) in septal (245 +/- 31 to 203 +/- 40 msec, p < 0.01) and lateral (222 +/- 54 to 193 +/- 34 msec, p < 0.05) segments was reduced. These findings indicate that nicorandil has beneficial effects on LV diastolic function in HCM. These favorable effects may be due to the improvement of subendocardial ischemia.
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PMID:Effects of nicorandil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy. 760 50

The cardioprotective effect of nicorandil, an opener of ATP-sensitive potassium channels, was studied in the isolated perfused hearts of the spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. The hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. Controls received no drug. In the nicorandil group, the hearts were treated with 0.03 to 0.3 mmol/L nicorandil for 15 min before ischemia. Left ventricular developed pressure (LVDP) and end diastolic pressure (LVEDP) at 30 min of reperfusion were significantly lower and larger, respectively, in SHR than in WKY rats. Nicorandil improved LVDP and decreased LVEDP at 30 min of reperfusion in both SHR and WKY rats dose-dependently. The hypertensive heart in the early stage is already susceptible to reperfusion-cardiac dysfunction. Nicorandil has a beneficial effect on the post-ischemic dysfunction in both SHR and WKY rats.
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PMID:Effect of nicorandil on cardiac dysfunction during reperfusion in normotensive and spontaneously hypertensive rats. 779 82

New nitro ester 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones show marked inhibitory activity against ischemia-induced electrocardiographic changes, with only limited systemic hemodynamic effects, and are reported in the present study. These new nitro vasodilators are potent inhibitors of the electrocardiographic T-wave and S-T segment elevation induced by intravenous or intracoronary administration of Arg-vasopressin or methacholine in the anesthetized rat. The most active compounds are up to 300- and 600-fold more potent than glyceryl trinitrate or Nicorandil, respectively. These nitro esters relax in a concentration-dependent manner the isolated rabbit aorta, at higher concentrations (2-40-fold) than glyceryl trinitrate, and reduce the mean arterial blood pressure at doses 7-300-fold higher than those required by glyceryl trinitrate to exert a similar hypotensive effect. Remarkably, these compounds retain their anti-ischemic and hemodynamic profile after oral (po) administration. These new nitro ester derivatives, endowed with a marked antianginal activity, which is not associated with concurrent and pronounced falls in systemic blood pressure, represent the leads of a new class of selective nitrovasodilators having a preferential action on large coronary vessels, which could be clinically relevant in the treatment of coronary artery diseases.
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PMID:New antianginal nitro esters with reduced hypotensive activity. Synthesis and pharmacological evaluation of 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones. 783 24


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