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Effects of Nicorandil Versus Nitroglycerin on Arterial Oxygenation During Two-Lung Ventilation and One-Lung Ventilation in Patients With Risk Factors for Myocardial Ischemia: A Prospective, Randomized, Double-Blind Study.
Murakami, C, Kawano, H, Kinoshita, M, Kondo, A, Inoue, M
Journal of cardiothoracic and vascular anesthesia. 2019;(3):702-709
Abstract
OBJECTIVES To compare the effects of nicorandil and nitroglycerin on arterial oxygenation during two-lung ventilation (TLV) and one-lung ventilation (OLV) in patients with risk factors for myocardial ischemia. DESIGN A prospective, randomized, double-blind study. SETTING A tertiary care hospital. PARTICIPANTS Fifty-six patients scheduled for elective video-assisted thoracic surgery were assigned randomly to either the nicorandil group or the nitroglycerin group. INTERVENTIONS Patients in the nicorandil group received a bolus dose of nicorandil, 0.08 mg/kg during induction of anesthesia, followed by a continuous infusion at a rate of 0.08 mg/kg/h. Patients in the nitroglycerin group received a continuous infusion of nitroglycerin at a rate of 1 µg/kg/min from the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Arterial blood gas analysis was performed at the following points: before induction of anesthesia; during TLV; at 5, 10, 20, and 30 minutes after the initiation of OLV. PaO2 at TLV (479.7 ± 57.1 v 408.2 ± 70.9 mmHg, p < 0.001); and at 5 minutes (344.8 ± 85.1 v 282.6 ± 85.8 mmHg, p = 0.012), 20 minutes (215.7 ± 103.0 v 158.2 ± 74.5 mmHg, p = 0.027), and 30 minutes (198.8 ± 103.5 v 147.5 ± 64.1 mmHg, p = 0.039) after OLV was significantly higher in the nicorandil group than in the nitroglycerin group. CONCLUSION This study demonstrated that oxygenation during TLV and OLV was significantly higher in patients receiving nicorandil than in those receiving nitroglycerin.
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Nicorandil Versus Nitroglycerin for Symptomatic Relief of Angina in Patients With Slow Coronary Flow Phenomenon: A Randomized Clinical Trial.
Sani, HD, Eshraghi, A, Nezafati, MH, Vojdanparast, M, Shahri, B, Nezafati, P
Journal of cardiovascular pharmacology and therapeutics. 2015;(4):401-6
Abstract
OBJECTIVE Patients with the coronary slow flow phenomenon frequently experience angina episodes. The present study aimed to compare the efficacy of nicorandil versus nitroglycerin for alleviation of angina symptoms in slow flow patients. METHODS In a single-center, single-blind, parallel-design, comparator-controlled, randomized clinical trial (NCT02254252), 54 patients with slow flow and normal or near-normal coronary angiography who presented with frequent angina episodes were randomly assigned to 1-month treatment with nicorandil 10 mg, 2 times a day (n = 27) or sustained-release glyceryltrinitrate 6.4 mg 2 times a day (n =27). Frequency of angina episodes, pain intensity, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were assessed at baseline and after 1 month of treatment. RESULTS In all, 25 patients in the nicorandil arm and 24 patients in the nitroglycerin arm were analyzed. After 1 month, patients treated with nicorandil had fewer angina episodes (adjusted mean number of episodes per week, nicorandil versus nitroglycerin; 1.68 ± 0.15 vs 2.29 ± 0.15, P = .007, effect size = 14.6%). Patients also reported greater reductions in pain intensity with nicorandil versus nitroglycerin (adjusted mean of self-reported pain score; 3.03 ± 0.29 vs 3.89 ± 0.30, P = .046, effect size = 8.4%). A significantly higher proportion of patients in the nicorandil arm were categorized in CCS class I (76% vs 33.3%, P = .004) or class II (16.0% vs 45.8%, P = .032). CONCLUSION In slow flow patients, nicorandil provides better symptomatic relief of angina than nitroglycerin.
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Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.
Ito, N, Nanto, S, Doi, Y, Kurozumi, Y, Natsukawa, T, Shibata, H, Morita, M, Kawata, A, Tsuruoka, A, Sawano, H, et al
Cardiovascular drugs and therapy. 2013;(4):279-87
Abstract
PURPOSE In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. METHODS We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. RESULTS As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. CONCLUSION Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.
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Long-term prospective randomised clinical and manometric comparison between surgical and chemical sphincterotomy for treatment of chronic anal fissure.
Abd Elhady, HM, Othman, IH, Hablus, MA, Ismail, TA, Aboryia, MH, Selim, MF
South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie. 2009;(4):112-4
Abstract
AIM: To compare surgical and chemical sphincterotomy for treatment of chronic anal fissure. METHODS The 160 patients studied were randomly divided into four equal groups, treated by lateral internal sphincterotomy (group S), local diltiazem ointment (group D), local glyceryl trinitrate ointment (group GTN), or injection of botulinum toxin into the internal anal sphincter (group BT). Anal manometry was performed before and 3 months after treatment. Patients were followed up for 5 years. RESULTS Complete pain relief was achieved in means (+/- standard deviation) of 5.7+/-7.8 days (group S), 15.7+/-5.9 days (group D), 15.6+/-5.9 days (group GTN) and 2.7+/-3.6 days (group BT). The mean times to healing were 4.5+/-1.2 weeks (group 1), 5.1+/-1.1 weeks (group D), 5.0+/-1.1 weeks (group GTN) and 5.1+/-1.3 weeks (group BT). Mean resting and squeeze anal pressures decreased significantly after sphincterotomy. Recurrence rates were 10% in group S, 65% in group D, 57.5% in group GTN and 52.5% in group BT. CONCLUSION Lateral internal sphincterotomy is an easy procedure with satisfactory results, minimal complications and a low recurrence rate. Medical sphincterotomy is safe and easy, with mild complications. Its effect is reversible, and relapse is common. We recommend that medical sphincterotomy be tried before surgery or in patients who are unable or unwilling to undergo surgery.
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Preservation of platelet responsiveness to nitroglycerine despite development of vascular nitrate tolerance.
Holmes, AS, Chirkov, YY, Willoughby, SR, Poropat, S, Pereira, J, Horowitz, JD
British journal of clinical pharmacology. 2005;(4):355-63
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Abstract
AIMS: Organic nitrates, via nitric oxide (NO) release, induce vasodilatation and inhibit platelet aggregation. Development of nitrate tolerance in some vascular preparations may be associated with diminished responsiveness to NO. To date it is not known to what extent vascular tolerance to organic nitrates is associated with acquired platelet hypo-responsiveness to NO. In the current study we compared the acute and chronic effects of sustained release (SR) isosorbide 5' mono-nitrate (ISMN) and transdermal nitroglycerine (TD-NTG) on blood vessels (effects on apparent arterial stiffness) and platelets (effects on responsiveness to NO donors) in patients with stable angina pectoris (SAP). METHODS Patients (n = 34) with SAP entered a blinded randomized crossover study of ISMN (120 mg) vs. intermittent TD-NTG (15 mg 24 h(-1)). Effects of each nitrate on pulse wave reflection (augmentation index (AIx)), platelet response to adenosine di-phosphate (ADP 1 micromol l(-1)), nitroglycerine (NTG 100 micromol l(-1)) and the non-nitrate NO donor sodium nitroprusside (SNP 10 micromol l(-1)), were measured pre-dose, 4 and 8 h post dose, on three occasions: 1) at the end of a pre-nitrate phase, 2) after dosing for 7 days and 3) following 14 days of full dose therapy with either nitrate. RESULTS Acutely, both ISMN and TD-NTG markedly reduced AIx. After 14 days, these effects were significantly attenuated (ANOVA, P = 0.018) but not abolished, indicating development of nitrate tolerance. Neither nitrate preparation affected ADP (1 micromol l(-1))-induced platelet aggregation. Platelet responsiveness to NTG (100 micromol l(-1)) and SNP (10 micromol l(-1)) was not diminished during chronic nitrate therapy, and there was no evidence of 'rebound' hyper-aggregability during 'nitrate-free' periods. CONCLUSIONS Chronic therapy with either ISMN or TD-NTG is associated with development of vascular tolerance. Despite the induction of vascular tolerance, platelet responsiveness to NTG and SNP remains unaffected. Therefore, development of vascular tolerance is unlikely to compromise the anti-aggregatory effects of organic nitrates, or those of endogenous NO.
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The effect of rapid decreases of blood pressure by different mechanisms on coronary flow and flow reserve in normal coronary arteries.
Voudris, V, Avramides, D, Gatzov, P, Malakos, J, Skoularigis, J, Manolis, A, Gavras, H, Gavras, I, Cokkinos, DV
American journal of hypertension. 2003;(12):1000-5
Abstract
BACKGROUND Changes in mean blood pressure (MBP) alter coronary blood flow (CBF). We evaluated the acute effects of three hypotensive medications on CBF parameters in angiographically normal coronary arteries. METHODS We performed CBF measurements using the Doppler wire at rest and during hyperemia produced by intracoronary adenosine (18 microg) as follows: 1) in the normal left circumflex coronary artery in 20 patients with coronary artery disease (measurements were performed without drugs, and after intravenous infusion of nitroprusside [0.5 to 2 microg/kg/min] and nitroglycerin [10 to 90 microg/min]; drugs were titrated to decrease MBP 20% to 25% below the control values, and heart rate was held constant using right atrial pacing); and 2) in the normal left anterior descending coronary artery in 19 patients without coronary artery disease (measurements were performed before and after intravenous clonidine infusion [150 microg in 5 min]; time-averaged peak velocity [APV], CBF, and coronary flow reserve [CFR] were measured). RESULTS Similar decreases in MBP were obtained in the two patient groups. Lumen diameter at the site of Doppler measurements increased after all medications (P <.005), whereas CBF did not change significantly. The CFR decreased after nitroprusside (1.79 +/- 0.48 v 2.54 +/- 0.45, P=.000), did not change significantly after nitroglycerin (2.74 +/- 0.43 v 2.54 +/- 0.45, P =.097), and increased after clonidine (3.12 +/- 0.70 v 2.76 +/- 0.75, P =.006). CONCLUSIONS In normal coronary arteries the infusion of three hypotensive medications to produce the same decreases in MBP is associated with different effects on CFR (increase with clonidine, decrease with nitroprusside, and no change with nitroglycerin).
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Nicardipine or nitroglycerin in patients with failed percutaneous coronary angioplasty: effect on myocardial diastolic function.
Casthely, PA, Bunik, T, Casthely, PA, Yoganathan, T, Komer, C, Mekhjian, H
Journal of cardiothoracic and vascular anesthesia. 2003;(5):604-12
Abstract
OBJECTIVE To evaluate whether intracoronary vasodilators can improve diastolic function in 32 patients with failed percutaneous transluminal coronary angioplasty (PTCA). DESIGN Clinical trial. SETTING Single-institution, academic hospital. PARTICIPANTS Failed PTCA patients undergoing emergency coronary artery bypass grafting surgery. INTERVENTIONS Patients were divided into 2 groups: group A received 0.1 mg of intracoronary nicardipine, and group B received 20 microg of intracoronary nitroglycerin. Both drugs were administrated via a coronary dilatation perfusion catheter inserted in the catheterization laboratory by the cardiologist. Subsequently, they were continuously infused via the side port of the introducer of the pulmonary artery catheter and titrated to keep systolic blood pressure at about two thirds of the control value. Transesophageal echocardiography (Power Vision/6000, 9-mm 5MHZ Probe; Toshiba, Elmsford, NY) was used in this study. MEASUREMENTS AND MAIN RESULTS Left ventricular ejection fraction, cardiac index, tissue Doppler imaging velocity of the left ventricle and mitral annulus, and troponin levels were measured before and after administration of the 2 vasodilators and after cardiopulmonary bypass. Diastolic dysfunction was found preoperatively in all the patients and responded only to intracoronary nicardipine. Ea of mitral annulus velocity significantly increased in group A patients from 7.5 +/- 0.02 to 11.8 +/- 0.01 (p < 0.005) and decreased in group B patients from 8.0 +/- 0.03 to 7.5 +/- 0.02 after nicardipine or nitroglycerin administration. Left ventricular ejection fraction and cardiac index increased significantly (p < 0.005) only after nicardipine administration. Troponin levels were significantly lower in group A than in group B patients (p < 0.005). CONCLUSION Intracoronary nicardipine improves diastolic function and myocardial flow velocity in patients with failed PTCA undergoing emergency coronary artery bypass graft surgery.
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[Clinical effect and mechanism of nitroglycerin patch on arresting preterm labor].
He, Q, Sha, J, Gu, Q, Gu, H, Chen, X, Yang, Z, Ning, H
Zhonghua fu chan ke za zhi. 2002;(3):134-5
Abstract
OBJECTIVE To observe the effect of nitroglycerin patch on treatment of preterm labour and to identify the mechanism responsible for arrest of preterm labour with nitroglycerin patch. METHODS Sixty women diagnosed as threatened preterm labour were divided into two groups: group of nitroglycerin patch therapy (n = 30), and group of magnesium sulfate and salbutamol sulfate therapy (n = 30). Nitroglycerin patch was applied to the abdomen of patients. Measurement of cortictrophin-releasing hormone (CRH) levels in maternal plasma was performed by radioimmunoassay. RESULTS The mean time of pregnancy prolongation was 25 days in the nitroglycerin patch group, and 8 days in the magnesium sulfate and salbutamol sulfate group. The mean level of CRH concentration in nitroglycerin patch group before treatment was (257 +/- 61) ng/L, and it was decreased sharply to (38 +/- 17) ng/L after treatment. Those were (248 +/- 60) ng/L and (56 +/- 22) ng/L respectively in the magnesium sulfate and salbutamol sulfate group. CONCLUSION Reduction of CRH secretion may be the mechanism of nitroglycerin patch on preterm labour therapy. It may act as an effective, safe, well-tolerated, and non-invasive method for treatment of preterm labour.
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Effects of race and hypertension on flow-mediated and nitroglycerin-mediated dilation of the brachial artery.
Gokce, N, Holbrook, M, Duffy, SJ, Demissie, S, Cupples, LA, Biegelsen, E, Keaney, JF, Loscalzo, J, Vita, JA
Hypertension (Dallas, Tex. : 1979). 2001;(6):1349-54
Abstract
Black Americans have increased morbidity and mortality rates from cardiovascular disease, greater prevalence of hypertension, and altered responses to vasodilator medications compared with those of white Americans. Hypertension and black race have been linked to impaired vascular function in the microcirculation. To examine these effects and their interaction in the conduit vasculature, we examined vasomotor responses of the brachial artery by using high-resolution vascular ultrasound in 228 subjects (48% hypertensive, 54% black). Subjects had no history of diabetes mellitus and were matched for age and gender. Flow-mediated dilation (8.5+/-5.3% versus 11.7+/-6.3%, P<0.001) and nitroglycerin-mediated vasodilation (14.9+/-6.0 versus 18.5+/-7.8, P=0.003) were both impaired in hypertensive compared with normotensive individuals. Multivariate analysis identified higher systolic blood pressure (P=0.003) and larger baseline vessel (P<0.001) size as independent predictors of lower flow-mediated dilation. Race did not significantly influence flow-mediated dilation. In contrast, blacks had a greater vasodilator response to nitroglycerin compared with whites (17.7+/-7.5% versus 15.0+/-6.2%, respectively; P=0.02). By multivariate analysis, black race (P=0.004), smaller vessel size (P=0.001), lower serum glucose (P=0.02), lower systolic blood pressure (P=0.02), and lower serum total cholesterol (P=0.04) were independent predictors of higher nitroglycerin-mediated dilation. Thus, hypertension is associated with impaired NO-mediated vasodilation in the conduit brachial artery. Overall, race did not influence flow-mediated dilation, but black race was associated with an enhanced response to sublingual nitroglycerin. This later observation provides further evidence of racial differences in the responses to medical therapy that may be relevant to the treatment of patients with cardiovascular disease.
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A double-blind, randomized study of the effect of immediate intravenous nitroglycerin on the incidence of postprocedural chest pain and minor myocardial necrosis after elective coronary stenting.
Kurz, DJ, Naegeli, B, Bertel, O
American heart journal. 2000;(1 Pt 1):35-43
Abstract
BACKGROUND Anginal chest pain without creatine kinase (CK) elevation is frequently observed in the first hours after coronary stenting. Possible causes of ischemic episodes are microembolism, side branch occlusion, coronary vasospasm, and disturbances of microvascular circulation. In a prospective, double-blind, randomized trial, we tested the effect of intravenous nitroglycerin on the incidence of angina and minor myocardial necrosis (MMN), as detected by cardiac troponin I increase, after elective coronary stenting. METHODS AND RESULTS One hundred patients were randomly assigned to intravenous nitroglycerin (group A: n = 50, goal dose 100 microgram/min) or placebo (group B: n = 50, NaCl 0.9%) during 12 hours after stenting. Patients with acute myocardial infarction, known intolerance to nitrates, and hemodynamic instability during angioplasty were excluded. The 2 groups were comparable in respect to baseline and interventional variables, except for age (group A: 60 +/- 9 years, group B: 56 +/- 10 years; P =.04). The incidence of chest pain was not influenced by nitroglycerin (group A: 18%, group B: 22%; P = not significant). However, the occurrence of MMN was significantly reduced by nitroglycerin (group A: 5%, group B: 19%, P =.036). A rise in CK with significant CK-MB fraction was observed in only 2 patients in group B (both less than twice upper limit). Only 4 of the 10 patients with MMN also had chest pain. CONCLUSIONS Routine use of intravenous nitroglycerin after coronary stenting significantly reduced the occurrence of minor myocardial necrosis. However, the incidence of postprocedural chest pain remained unchanged.