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1.
Augmentation pressure is influenced by ventricular contractility/relaxation dynamics: novel mechanism of reduction of pulse pressure by nitrates.
Fok, H, Guilcher, A, Li, Y, Brett, S, Shah, A, Clapp, B, Chowienczyk, P
Hypertension (Dallas, Tex. : 1979). 2014;(5):1050-5
Abstract
Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 μg sublingually, n=20) and locally by intracoronary infusion (1 μg/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg (P<0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each P<0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced (P<0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg (P<0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation.
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2.
Reduced retinal vessel response to flicker stimulation but not to exogenous nitric oxide in type 1 diabetes.
Pemp, B, Garhofer, G, Weigert, G, Karl, K, Resch, H, Wolzt, M, Schmetterer, L
Investigative ophthalmology & visual science. 2009;(9):4029-32
Abstract
PURPOSE Various studies have shown that retinal vessels in patients with diabetes mellitus have a reduced capacity to adapt to changes in perfusion pressure and to stimulation with flickering light. Structural and functional changes in retinal vessels in diabetes could lead to a general reduction of vasodilator and/or vasoconstrictor capacity. To gain more insight into this topic, we compared the response of retinal vessel diameters to systemic glyceryl trinitrate (GTN) and stimulation with diffuse luminance flicker in patients with diabetes and healthy control subjects. METHODS Twenty patients with type 1 diabetes mellitus featuring no or mild nonproliferative diabetic retinopathy and 20 healthy, age-matched subjects were included in this study. A vessel analyzer was used for measurement of diameters of retinal arteries and veins. The response of diameters was measured continuously during stimulation with flickering light, as well as immediately after sublingual application of 0.8 mg GTN. RESULTS The response of retinal vessels to flickering light was significantly reduced in the patients with diabetes (arteries: 2.9% in diabetes versus 7.0% in control subjects, P < 0.002; veins: 4.6% in diabetes versus 6.8% in control subjects, P = 0.020). GTN-induced vasodilatation was not different between the patients with diabetes and the healthy control subjects (P >or= 0.70). CONCLUSIONS The present study confirmed reduced response of retinal vessels to stimulation with flickering light in diabetes. The response of retinal vessels to a direct NO-donor, however, was maintained. This result indicates that abnormal flicker-induced vasodilatation in diabetes is not a consequence of generally reduced retinal vascular reactivity (ClinicalTrials.gov number, NCT00432029).
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Endothelial function in post-menopausal women: effect of folic acid supplementation.
Paradisi, G, Cucinelli, F, Mele, MC, Barini, A, Lanzone, A, Caruso, A
Human reproduction (Oxford, England). 2004;(4):1031-5
Abstract
BACKGROUND Higher than normal homocysteine levels are associated with an increased incidence of adverse cardiovascular events in post-menopausal women, perhaps via hyperhomocysteinaemia-induced vascular endothelial damage. Because folic acid supplementation reduces homocysteine levels, we attempted to evaluate whether folic acid supplementation may affect endothelial function in post-menopausal women. METHODS Brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerin-induced dilatation (endothelium-independent) before and after a methionine load were analysed in 15 healthy post-menopausal women. Plasma levels of folate, homocysteine, glucose, insulin and lipids were measured, as was blood pressure. All studies were repeated after 1 month supplementation with 7.5 mg/day of folic acid. RESULTS After folate, endothelial function rose 37% over pre-folic acid supplementation value (P < 0.001), and flow-mediated dilation before folic acid was reduced by 62% subsequent to methionine loading (P < 0.0001); this reduction was still present after folic acid, but was only 19% (P < 0.001). Nitroglycerin-induced dilatation did not change in response to methionine loading before or after folic acid supplementation. Among the other cardiovascular risk factors studied, only high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol showed significant changes after folic acid supplementation, with a 6% increase (P < 0.03) and a 9% decrease (P < 0.03) respectively. CONCLUSIONS Although preliminary, these results indicate that folic acid supplementation may improve endothelial function and lipid profile in post-menopausal women, thus contributing to reduce their cardiovascular risk.
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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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Randomized clinical trials to determine the role of topical glyceryl trinitrate in peripheral intravenous nutrition.
Dobbins, BM, Catton, JA, Tighe, MJ, Miller, GV, Martin, IG, McMahon, MJ
The British journal of surgery. 2003;(7):804-10
Abstract
BACKGROUND The contribution of glyceryl trinitrate (GTN) to prevention of peripheral vein thrombophlebitis (PVT) during peripheral intravenous nutrition delivered by fine-bore midline intravenous catheter is unclear. The aim of this study was to establish its role. METHODS Two consecutive randomized clinical trials were conducted. In trial 1 patients were randomized to receive standard peripheral intravenous nutrition containing heparin and hydrocortisone with or without the placement of a topical GTN patch (triple therapy or dual therapy). In trial 2 patients were randomized to receive standard peripheral intravenous nutrition with either dual therapy or topical GTN alone (monotherapy). RESULTS Dual therapy was as effective as triple therapy in preventing PVT (incidence 10 of 37 versus 11 of 39 patients respectively). Dual therapy reduced the incidence and increased the time to onset of PVT compared with monotherapy (14 of 41 versus 22 of 35 patients respectively, P = 0.012; median 17.3 (95 per cent confidence interval (c.i.) 13.4 to 21.1) versus 8.9 (95 per cent c.i. 6.7 to 11.0) days, P = 0.007). CONCLUSION Use of a topical GTN patch confers no benefit when peripheral intravenous nutrition is delivered via a fine-bore midline intravenous catheter.
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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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Changes in coronary vessel resistance during postischemic reperfusion and effectiveness of nitroglycerin.
Kalweit, GA, Schipke, JD, Godehardt, E, Gams, E
The Journal of thoracic and cardiovascular surgery. 2001;(5):1011-8
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Abstract
OBJECTIVE Microvascular incompetence after ischemia and reperfusion may compromise the normal postischemic coronary perfusion and additionally jeopardize the recovery of the myocytes. We investigated whether such a form of acute endothelial dysfunction occurs in the routine operative setting despite the use of protective measures. For this purpose, we measured pressure-flow relations in the coronary vasculature during heart operations before and after ischemia and after reperfusion and their reaction to the nitric oxide donor nitroglycerin. METHODS Forty-eight patients with a low risk profile scheduled for routine coronary artery bypass surgery were included. During normothermic extracorporeal circulation, the fibrillating heart was completely excluded from bypass by clamping of the ascending aorta and snaring of the caval veins. It was relieved of blood by opening the right atrium and venting the left atrium and ventricle to avoid distention. The coronary vessels were perfused under controlled flow, and the perfusion pressures were monitored. This protocol was performed in 24 patients before and immediately after ischemia and after a reperfusion period. RESULTS Compared with the preischemic control, vascular resistance was decreased by 17% (P <.003) immediately after ischemia but increased again by 46% (P <.0001) during an average of 25 minutes of reperfusion and, even more important, by 23% (P <.028) in comparison with the preischemic values. In two groups of 12 patients, nitroglycerin was added to the perfusate either in a dosage of 3 microg. kg. min(-1) or as a bolus injection of 2 mg. Low-dose nitroglycerin did not reduce the elevated postreperfusion resistances significantly, but bolus injection did (P <.0002). Coronary vessel resistance increased during reperfusion in particular in patients with a history of hypertension. CONCLUSION Coronary vasoconstriction during postischemic reperfusion is regularly present in the routine operative setting in cardiac surgery, despite myocardial protection measures. The amount of vasoconstriction varies considerably and is particularly increased in patients with hypertension. The nitric oxide donor nitroglycerin can normalize the elevated resistances, but only in high dosages. This demonstrates a preserved ability of vascular smooth muscle to relax. The phenomenon had no sequelae in our low-risk patients having elective operations. However, it may gain significance in the case of severe left heart hypertrophy and in patients at risk with both a postoperative low-output syndrome and reduced mean arterial pressures during reperfusion.
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Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study.
Gori, T, Burstein, JM, Ahmed, S, Miner, SE, Al-Hesayen, A, Kelly, S, Parker, JD
Circulation. 2001;(10):1119-23
Abstract
BACKGROUND In healthy humans, continuous treatment with nitroglycerin (GTN) causes nitric oxide synthase dysfunction, probably through the reduced bioavailability of tetrahydrobiopterin. Recent studies proposed that folic acid is involved in the regeneration of tetrahydrobiopterin in different disease states. Therefore, we investigated whether folic acid administration would prevent this phenomenon. We also sought to determine if folic acid supplementation could prevent the development of tolerance to GTN. METHODS AND RESULTS On the first visit, 18 healthy male volunteers (aged 19 to 32 years) were randomized to receive either oral folic acid (10 mg once a day) or placebo for 1 week in a double-blind designed study. All subjects also received continuous transdermal GTN (0.6 mg/h). On the second visit, forearm blood flow was measured with venous occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 microgram/min), N-monomethyl-L-arginine (1, 2, and 4 micromol/min), and GTN (11 and 22 nmol/min). Folic acid prevented GTN-induced endothelial dysfunction, as assessed by responses to intraarterial acetylcholine and N-monomethyl-L-arginine (P<0.01). Moreover, in the subjects treated with folic acid plus transdermal GTN, responses to intraarterial GTN were significantly greater than those observed after transdermal GTN plus placebo (P<0.05). CONCLUSION Our data demonstrate that supplemental folic acid prevents both nitric oxide synthase dysfunction induced by continuous GTN and nitrate tolerance in the arterial circulation of healthy volunteers. We hypothesize that the reduced bioavailability of tetrahydrobiopterin is involved in the pathogenesis of both phenomena. Our results confirm the view that oxidative stress contributes to nitrate tolerance.
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Diltiazem versus nitroglycerin for myocardial protection following coronary artery bypass grafting as assessed by dobutamine stress echocardiography.
Lassnigg, A, Wutte, M, Grubhofer, G, Chevtchik, O, Podesser, B, Simon-Kupilik, N, Wild, T, Hiesmayr, M, Seitelberger, R
Wiener klinische Wochenschrift. 2001;(11-12):439-45
Abstract
BACKGROUND Perioperative infusion of the calcium channel antagonist diltiazem reduces the occurrence and extent of postoperative myocardial ischemia. However, recent reports also mention nitroglycerin as the drug of choice to prevent conduit spasm after coronary bypass grafting. The diagnosis of myocardial ischemia in the perioperative setting is still problematic. Dobutamine stress echocardiography (DSE) is an established technique that combines inotropic stimulation with real-time myocardial imaging and delineates normal and abnormal regional contraction patterns. We assessed the perioperative anti-ischemic effects of diltiazem and nitroglycerin during hemodynamic stress using DSE. METHODS 50 adult patients were included in a prospective randomized study. Diltiazem or nitroglycerin was used from the onset of extracorporeal circulation until 24 h postoperatively. Dobutamine stress echocardiography was performed in a stepwise fashion 2 to 3 h after elective coronary artery bypass grafting. RESULTS In 42 of 49 patients, dobutamine stress echocardiography either reached a level of 40 micrograms/kg/min dobutamine or achieved the target heart rate. One patient improved in terms of segmental wall motion abnormalities and three patients developed new abnormalities without corresponding electrocardiographic changes. Analysis of ischemia-sensitive parameters showed lower creatine kinase MB (p = 0.032) and troponin I levels (p = 0.1) in the diltiazem group 24 h postoperatively. Heart rate was significantly lower in the diltiazem group (p = 0.0003). CONCLUSIONS Under conditions of hemodynamic stress, DSE revealed no significant difference between diltiazem and nitroglycerin with regard to renewed ischemia.