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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diltiazem (DTZ), a calcium slow channel blocker, is estimated to be highly effective for myocardial protection and the prevention of perioperative coronary spasms (PCS). However, the use of high doses of DTZ sometimes results in difficulty in coming off cardiopulmonary bypass due to negative chronotropic activity. Nicorandil (NCD) has remarkable coronary vasodilating effect but possesses little negative chronotropic activity. The purpose of this study was to compare NCD with DTZ with respect to effect on myocardial protection during coronary artery bypass grafting (CABG). As parameters, excess lactate (delta XL), redox potential (delta Eh), left and right ventricular stroke work indices (LVSWI, RVSWI), cardiac index (C.I.), systemic vascular resistance index (SVRI.), myocardial isoenzymes (CK-MB, LDH1), number of PCS and recovery time of chronotropic action were used. delta XL, delta Eh, LVSWI, RVSWI, C.I., SVRI, CK-MB, LDH1 were measured at 0, 1, 3, 6, 9, 18 and 24 hours after the removal of aortic cross clamping. The degree of chronotropic action was evaluated by the length of the recovery time to self beat or normal sinus rhythm after the removal of aortic cross clamping. Forty patients who underwent CABG with retrograde cold blood cardioplegia between Dec. 1989 and May 1991 were divided into the NCD group (n = 20), in which 1.1 micrograms/kg/min NCD was continuously administered from the beginning of the operation and the DTZ group (n = 20), in which the initial St. Thomas cardioplegia containing 5 mg/L and subsequent cold blood cardioplegia solution contained DTZ 3.5 mg/L, for a total DTZ dose of less than 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Efficacy of nicorandil on myocardial protection during coronary artery bypass grafting--a comparison with diltiazem]. 140 65

The effect of KRN2391 [N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate] on the cardiovascular system and on myocardial oxygen consumption was compared with that of nicorandil and nifedipine in anesthetized dogs. Intravenous administration of KRN2391 (3-30 micrograms/kg) and nifedipine (1 and 3 micrograms/kg) decreased mean aortic blood pressure and total peripheral vascular resistance, and increased coronary blood flow, cardiac output and stroke volume. Heart rate was not significantly affected by KRN2391, but slightly increased by 1 microgram/kg of nifedipine. Nicorandil (100 and 300 micrograms/kg, intravenously) decreased mean aortic blood pressure, cardiac output, stroke volume and total peripheral vascular resistance, but did not affect heart rate. Nicorandil also showed a tendency to decrease coronary blood flow after an initial increase. All drugs tested decreased the difference in oxygen concentration between arterial and coronary sinus blood, indicating that these drugs increased the oxygen supply to the heart. Myocardial oxygen consumption was significantly decreased by more than 10 micrograms/kg of KRN2391, but was not affected by nifedipine. Nicorandil showed a tendency to decrease the myocardial oxygen consumption, though not significantly. Thus, KRN2391 may be useful to treat ischemic heart disease, because it increases the coronary blood flow and the oxygen supply to the heart, and decreases the afterload and the myocardial oxygen consumption.
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PMID:Comparative cardiovascular effects of KRN2391 and other coronary vasodilators in anesthetized open-chest dogs. 146 70

Acute hemodynamic and coronary vasodilating effects of nicorandol (SG-75, Sigmat; CAS 65141-46-0) and glyceryl trinitrate (GTN, nitroglycerin) were examined in 20 subjects under cardiac catheterization and coronary arteriography. Nicorandil 4 mg i.v. produced significant increases in heart rate, cardiac index and stroke volume index and significant decreases in systolic, diastolic and mean blood pressure, pulmonary capillary wedge pressure, left ventricular enddiastolic pressure, systemic vascular resistance and total pulmonary resistance. Degree of percent changes in these parameters by nicorandil were similar to that by GTN 0.3 mg i.v. Coronary vasodilating effects of both drugs were also at the same degree. Results indicate that nicorandil has cardiovascular and coronary vasodilating effects similar to those of GTN when administered intravenously.
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PMID:Comparison of the acute hemodynamic and coronary vasodilating effects between nicorandil and glyceryl trinitrate. 183 65

Twenty-five patients with congestive heart failure (CHF) underwent a double-blind randomized study of the acute hemodynamic effects of orally administered nicorandil, a newly developed vasodilator drug. A dose range of 10 to 60 mg was studied. Nicorandil, at a dose of 60 mg, caused statistically significant decreases in systemic systolic and diastolic blood pressure, right atrial pressure, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance and systolic and diastolic pulmonary arterial pressure. A brief increase in cardiac index attributable to an increase in stroke volume without a change in heart rate was also observed. A dose of 40 mg produced similar results in cardiac index and systemic and pulmonary vascular resistance, but changes in other hemodynamic parameters were much smaller in magnitude and usually not of statistical significance. No significant hemodynamic response was seen to doses of 10 and 20 mg of nicorandil. Duration of action was short with nearly all hemodynamic parameters returning close to baseline within 3 hours. This rapid decrease in activity occurred in concert with a rapid plasma clearance of nicorandil as determined by serial measurements of plasma drug concentration. This study suggests that first-dose orally administered nicorandil elicits favorable, but brief, hemodynamic effects in CHF at doses greater than or equal to 40 mg.
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PMID:Hemodynamic effects of oral nicorandil in congestive heart failure. 214 Apr 89

The present investigation was conducted to study systemic and regional haemodynamic effects of nicorandil, a potent coronary vasodilator, after intravenous or local intracoronary administration in anaesthetized or conscious pigs. Intravenous infusions of nicorandil for 10 min in both anaesthetized (15, 30, 75 and 150 micrograms.kg-1.min-1) and conscious (20, 40 and 80 micrograms.kg-1.min-1) pigs reduced arterial blood pressure, stroke volume, left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance, but increased heart rate and maxLVdP/dt. Since nicorandil decreased LVEDP at doses which did not affect arterial blood pressure, the drug may be considered as a more potent venodilator than arterial dilator. Nicorandil increased cardiac output only in conscious animals due to a more marked tachycardia (85% after 80 micrograms.kg-1.min-1) than in anaesthetized animals (30% after 75 micrograms.kg-1.min-1). The nicorandil-induced increase in heart rate and maxLVdP/dt, being substantially attenuated in conscious pigs after treatment with propranolol, can be ascribed to a reflex activation of the sympathetic nervous system following the fall in arterial pressure. Although cardiac output did not change in anaesthetized animals, intravenous infusions of nicorandil did cause a redistribution of blood flow in favour of organs such as the heart, adrenals, spleen, small intestine and brain at the expense of that to the stomach and kidneys; hepatic artery and skeletal muscle blood flow did not change. The increase in myocardial blood flow, primarily to the subepicardial layers, was associated with an enhancement in coronary venous oxygen content and was also notices after intracoronary infusions of nicorandil (0.6, 1.5, 3 and 6 micrograms.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nicorandil-induced changes in the distribution of cardiac output and coronary blood flow in pigs. 296 Sep 4

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

We studied the acute haemodynamic dose response of nicorandil, a combined nitrate and potassium channel opener, in patients evaluated for chest pain. Single dose oral nicorandil (5, 10, 20, or 30 mg) or placebo was given to 42 right-heart catheterized patients using a randomized block design. Persistent, significant (P < 0.05) haemodynamic changes occurred primarily after 30 mg. Arterial systolic pressure fell significantly after all doses and remained reduced (maximum, 31 mmHg) up to 6 h after 30 mg; heart rate increased significantly up to 1 h. Individual haemodynamic sensitivity varied and three patients (1, 10 mg; 2, 30 mg) developed transient symptomatic hypotension associated with bradycardia. Pulmonary artery systolic pressure (diastolic was unchanged) declined significantly (maximum, 5 mmHg) up to 6 h after 30 mg whereas pulmonary capillary wedge (baseline normal) and mean right atrial pressures decreased transiently. Cardiac index (baseline normal) declined slightly (significantly after 30 mg); however, stroke volume index and stroke work index were significantly and persistently reduced after all doses. Total systemic vascular resistance declined slightly after 30 mg. Individual plasma nicorandil concentrations were variable and systemic bioavailability was reduced compared with values reported in healthy subjects. Nicorandil demonstrated cardiac unloading actions. Variable plasma concentrations, haemodynamic effects, and patient sensitivity warrant low initial doses with individual dose titration, especially if cardiac filling pressures are low.
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PMID:Dose-related haemodynamic effects and pharmacokinetics of oral nicorandil in patients evaluated for chest pain. 807 66

The coronary and systemic hemodynamic effects of the novel nitrate ester ITF 296 were investigated in conscious, resting dogs and compared with nitroglycerin and nicorandil. ITF 296 at 1-25 micrograms/kg i.v. elicited selective, long-lasting, and dose-dependent increases in large epicardial coronary artery diameter (CD) without affecting coronary blood flow (CBF) or coronary vascular resistance (CVR). Blood pressure (BP) and heart rate (HR) were also unaltered. At 125 micrograms/kg, ITF 296 further increased CD but simultaneously reduced CVR and mean aortic pressure and increased CBF and HR. Nitroglycerin 1-25 micrograms/kg induced a shorter and less selective dilatation of large coronary conductance arteries, as it was accompanied by a decrease in CVR at all doses used. Nicorandil produced a selective increase in left circumflex CD only at the lowest dose used (10 micrograms/kg), whereas higher doses were effective on both CD and CVR. ITF 296 significantly reduced left ventricular end-diastolic pressure and increased stroke volume (SV) and cardiac output (CO) at doses that did not alter HR or BP, indicating an increase in cardiac efficiency. In contrast, the increases in CO produced by nitroglycerin and nicorandil were dependent on the augmentation of HR, because SV was unchanged at all doses used. Nitroglycerin dose-dependently decreased BP, whereas ITF 296 reduced BP only at the highest dose used. In conclusion, ITF 296 induces a selective, flow-independent dilatation of large coronary conductance arteries without affecting the tone of small coronary resistance vessels or systemic hemodynamics over a broad range of doses. An equally selective effect was elicited by nicorandil only at the lower dose used, whereas no selective effect of nitroglycerin on the diameter of coronary conductance arteries was seen at the doses utilized in this study.
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PMID:Effect of the new nitrate ester ITF 296 on coronary and systemic hemodynamics in the conscious dog: comparison with nitroglycerin and nicorandil. 883 21

In common with halogenated anaesthetics, nicorandil, a new KATP channel opener, has been shown to have cardioprotective and vasodilator effects. Recent studies have also suggested that the vasodilator and protective effects of halogenated anaesthetics are mediated partly via KATP channel opening. This study examined the effects of concurrent administration of nicorandil and isoflurane on haemodynamic state and ventricular function before, during and after 15 min of ischaemia. We studied left ventricular function in 40 anaesthetized rabbits using ultrasonomicrometry. Measurements were obtained before, during and after 15 min of regional ischaemia. Regional ventricular function was assessed in terms of systolic shortening (SS%) and preload recruitable work area (PRWA, the area beneath the regional stroke work vs end-diastolic length relationship) during reperfusion. Four groups were studied: group F (n = 10) received a bolus dose of fentanyl 100 micrograms kg-1 and then 400 micrograms kg-1 h-1 throughout; group 1 (n = 10) received 2.05% end-tidal concentration of isoflurane (1 MAC); group FN (n = 10) received fentanyl, a bolus does of nicorandil 100 micrograms kg-1 and then 25 micrograms kg-1 min-1, 15 min before occlusion; and group IN (n = 10) received isoflurane and nicorandil. Isoflurane decreased left ventricular systolic pressure and ventricular contractility (+dP/dtmax, slope of preload recruitable stroke work, and SS%). Nicorandil increased -dP/dtmax in group FN. Post-ischaemic regional left ventricular contractility in group I did not differ from that in group F, however, groups receiving nicorandil recovered to a greater extent. Group IN showed better recovery compared with all other groups when ventricular contractility was assessed by PRWA normalized to pre-occlusion values (mean 99.3 (SEM 10.5)% vs 73.4 (7.5)%, 50.2 (5.8)% and 52.4 (3.7)% at 120 min reperfusion in groups FN, I and F, respectively). Tissue ATP and lactate contents did not differ between groups. We conclude that concurrent administration of nicorandil and isoflurane enhanced post-ischaemic recovery compared with isoflurane anaesthesia or nicorandil and fentanyl administration.
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PMID:Beneficial effect of concomitant administration of isoflurane and nicorandil. 930 92

Nicorandil, a new KATP channel opener, is used in clinical practice for anti-anginal therapy. It exhibits vasodilator properties as does the halogenated anaesthetic isoflurane. We have examined the cardiovascular effects of increasing concentrations of isoflurane after administration of nicorandil in 10 adult beagle dogs anaesthetized with thiopental and whose lungs were ventilated mechanically. During surgery, anaesthesia was maintained with 1.0-1.5% isoflurane. A left thoracotomy was performed and the heart suspended in a pericardial cradle. Monitoring included: ECG; aortic, left ventricular, arterial, central venous and pulmonary artery pressures; cardiac output; coronary flow; and segmental length in the apical region. After surgery, isoflurane anaesthesia was set at an end-tidal concentration of 1.05% (1 MAC) and measurements obtained; these were repeated with 1.4%, 1.75%, 2.1% and 1.05% isoflurane concentrations after appropriate stabilization periods. Nicorandil (100 micrograms kg-1 bolus, 25 micrograms kg-1 min-1 infusion) was begun and a second dose-response study of isoflurane was obtained as before. Blood samples were obtained for measurement of concentrations of nicorandil. Systolic ventricular function was assessed by systolic shortening (%SS) and preload recruitable stroke work (PRSW). Increasing isoflurane concentration produced decreases in heart rate, systolic pressure, cardiac output, %SS and PRSW. Nicorandil produced a slight decrease in systolic arterial pressure (10 and 15 mm Hg after 1.05% and 2.05% isoflurane) and a slight increase in heart rate (10 and 5 beat min-1 after 1.05% and 2.05% isoflurane). Preload, assessed by end-diastolic length, decreased. Coronary blood flow increased with infusion of nicorandil. Left ventricular function was not affected by infusion of nicorandil. We conclude that nicorandil has only minor vaso/venodilatory effects in the presence of isoflurane. Ventricular function was not altered by infusion of nicorandil.
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PMID:Cardiovascular effects of concomitant administration of isoflurane and nicorandil in dogs. 964 Jan 55


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