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PubMed1992

Persistent hemodynamic improvement with short-term nitrate therapy in patients with chronic congestive heart failure already treated with captopril.

To evaluate the therapeutic potential of organic nitrates in patients with chronic congestive heart (CHF) failure already treated with angiotensin-converting enzyme (ACE) inhibitors, the temporal hemodynamic effects of oral isosorbide dinitrate, 40 to 120 mg administered every 6 hours to 11 nitrate responders who had been treated with captopril 89 +/- 32 mg/day, were studied. The administration of isosorbide dinitrate resulted in a significant decline in mean right atrial pressure, from 13 +/- 6 mm Hg at baseline (mean value of measurements performed every 2 hours for 24 hours with captopril therapy) to 9 +/- 4 mm Hg at 1 hour with persistent effect for most of the study period. Mean pulmonary artery pressure decreased from 38 +/- 7 mm Hg at baseline to 29 +/- 9 mm Hg at 1 hour, with effect persisting for 24 hours. Mean pulmonary artery wedge pressure also decreased from 24 +/- 6 to 15 +/- 7 mm Hg at 1 hour and remained significantly reduced for 20 hours. Systemic blood pressure demonstrated a transient decrease lasting 2 hours after initiation of therapy which was asymptomatic in all patients. The results of this study demonstrate a preserved vasodilatory effect of organic nitrates in patients already treated with ACE inhibitors. Nitrates mediated improvement in right and left ventricular filling pressures, and reduction of pulmonary hypertension demonstrates a rationale for the use of these therapeutic methods in combination and suggest the need for long-term evaluation of the effect of nitrate therapy in patients with chronic CHF already treated with ACE inhibitors.

Adult↗
PubMed1982

Hemodynamic effects of vasodilator therapy in severe left heart failure combined with large atrial septal defects.

Two patients presented with severe left heart failure and large secundum atrial septal defects without severe pulmonary hypertension. The acute hemodynamic effects of two commonly used vasodilator agents, isosorbide dinitrate and hydralazine, are described. Although isosorbide dinitrate improved systemic forward cardiac output, it also increased left-to-right intracardiac shunting in both patients. On the other hand, hydralazine dramatically improved systemic toward output and concomitantly diminished left-to-right shunt flow in each patient (43 and 21 percent). The complexities of combined severe left ventricular failure and a large atrial septal defect with left-to-right shunting, and the importance of extensive hemodynamic monitoring at the time of pharmacologic intervention, are discussed.

Blood Pressure↗
PubMed1992

Nitric oxide donors increase mucus gel thickness in rat stomach.

Instillation of the nitric oxide (NO) generator isosorbide dinitrate (0.1-1 mM) into the rat gastric lumen in vivo produced a dose-related increase in mucus gel thickness that was prevented by coadministration of oxyhaemoglobin (10 microM). Isosorbide dinitrate did not induce epithelial cell damage. S-Nitroso-N-acetyl-penicillamine (0.3 mM) and dibutyryl cyclic GMP (1 mM) also increased mucus thickness. These findings, along with the presence of NO synthase in the gastric mucosa, imply a role for NO in vivo in mediation of gastric mucus release.

Animals↗
PubMed1991

Gas chromatographic analysis of isomeric organic mononitrates in plasma.

A specific, sensitive and precise capillary gas chromatographic method using electron-capture detection was developed for the determination of four isomeric vasodilating organic mononitrates, viz. L-isoidide mononitrate (L-IIMN), isosorbide-2-mononitrate (IS-2-MN), isomannide mononitrate (IMMN) and isosorbide-5-mononitrate (IS-5-MN), in rat plasma. With a sample size of 100 microliters of rat plasma, the detection limits were found to be between 0.5 and 2 ng/ml for these mononitrates, and the absolute recovery was found to range from 83 to 90%. The within-day coefficients of variation for the assay of the four isomers were less than 5%, while the between-day coefficients of variation were less than 10%. Because of the short retention times of these isomers in this assay, routine analyses of about sixty plasma samples per day can be carried out. The possibility of in vivo interconversion among these four isomers in rats was investigated after individual administration of each isomer. No interconversion was found based on examination of plasma samples. The gas chromatographic method was applied to the pharmacokinetic studies of these four isomers in rats; at an intravenous dose of 2 mg/kg, the biological half-lives of L-IIMN, IMMN, IS-2-MN and IS-5-MN were found to be 13.2, 25.2, 54.6 and 112 min, respectively.

Animals↗
PubMed1992

Effect of direct vasodilation with hydralazine versus angiotensin-converting enzyme inhibition with captopril on mortality in advanced heart failure: the Hy-C trial.

To compare the benefit of angiotensin-converting enzyme inhibition and direct vasodilation on the prognosis of advanced heart failure, 117 patients evaluated for cardiac transplantation who had severe symptoms and abnormal hemodynamic status at rest were randomized to treatment with either captopril or hydralazine plus isosorbide dinitrate (Hy-C Trial). Comparable hemodynamic effects of the two regimens were sought by titrating vasodilator doses to match the hemodynamic status achieved with nitroprusside and diuretic agents, attempting to achieve a pulmonary capillary wedge pressure of 15 mm Hg and a systemic vascular resistance of 1,200 dynes.s.cm-5. Treatment with the alternate vasodilator was started because of poor hemodynamic response or side effects (40% of patients in the captopril group and 22% in the hydralazine group). Adequate hemodynamic response in patients with a serum sodium level less than 135 mg/dl was more likely with hydralazine than with captopril (71% vs. 33%, p = 0.04). Isosorbide dinitrate was prescribed in 88% of the hydralazine-treated patients and 84% of the captopril-treated patients. The hemodynamic improvements from each regimen were equivalent. After 8 +/- 7 months of follow-up, the actuarial 1-year survival rate was 81% in the captopril-treated patients and 51% in the hydralazine-treated patients (p = 0.05). The improved survival with captopril resulted from a lower rate of sudden death, which occurred in only 3 of 44 captopril-treated patients compared with 17 of 60 hydralazine-treated patients (p = 0.01). In the subset of patients who continued treatment with the initial vasodilator, results were similar to those for the entire treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Long-term oral nitrate therapy prevents chronic ventricular remodeling in the dog.

OBJECTIVES: The purpose of this experiment was to assess the long-term effects of oral nitrate therapy on ventricular remodeling in a canine model of discrete myocardial damage. BACKGROUND: A progressive increase in left ventricular mass and volume has been documented after experimental and clinical myocardial infarction. This ventricular remodeling has been associated with the development of congestive heart failure. Nitrate therapy, especially when combined with hydralazine, is effective in the management of clinical heart failure. Moreover, nitrates inhibit infarct expansion, one of the earliest manifestations of ventricular remodeling. Whether nitrates can attenuate chronic left ventricular remodeling is unknown. METHODS: Dogs with discrete myocardial necrosis produced 24 h earlier by transmyocardial direct current shock were randomized to receive isosorbide mononitrate, 30 mg twice daily (n = 10), or no treatment (n = 4); the latter group was augmented by 13 control dogs from a prior study in which an identical protocol was used. Ventricular structure was assessed with nuclear magnetic resonance imaging at baseline and at 1 and 16 weeks after myocardial damage. RESULTS: Left ventricular mass increased at 1 week in the control group (mean +/- SD 68.1 +/- 10.7 g to 80.1 +/- 12.1 g, p = 0.0001) but not in the nitrate-treated group (70.2 +/- 7.7 g to 69.6 +/- 7.3 g, p = NS). No change in left ventricular volume was observed in either group during the 1st week after myocardial damage. After 16 weeks of follow-up left ventricular mass had increased by 12.7 +/- 7.1 g (p = 0.001) in the control group and had decreased by 1.2 +/- 7.7 g in the nitrate group. Left ventricular volume was increased at 16 weeks by 14.2 +/- 10.3 ml in the control group but was decreased by 3.7 +/- 7.5 ml in the nitrate group. Isosorbide mononitrate produced transient hemodynamic effects with a return of most measured variables toward baseline within 2 h after administration of the drug. At 1 week there was no intergroup difference in rest hemodynamic variables assessed 12 h after drug administration. At 16 weeks, pulmonary capillary wedge pressure (15 +/- 4 vs. 8 +/- 3 mm Hg, p = 0.0001), pulmonary artery pressure (24 +/- 5 vs. 16 +/- 3 mm Hg, p = 0.0001) and right atrial pressure (10 +/- 3 vs. 6 +/- 3 mm Hg, p = 0.008) were all higher in the control group. CONCLUSIONS: Long-term oral nitrate therapy attenuates the early and late manifestations of ventricular remodeling after myocardial damage in the dog. Hemodynamic observations suggest the possibility that drug-induced preload or afterload reduction does not completely explain this effect.

Administration, Oral↗
PubMed1993

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Acetylcholine↗
PubMed1995

Functional evaluation of internal mammary artery bypass grafts in the early and late postoperative periods.

OBJECTIVES: We sought to determine whether internal mammary artery grafts adapt to an increase in myocardial flow demand and whether they restore maximal flow reserve. BACKGROUND: Although mammary grafts are now considered the graft of choice for coronary artery bypass surgery, there is still controversy about whether they can provide adequate flow at periods of peak myocardial demand. METHODS: Of 28 patients with a mammary graft anastomosed to the left anterior descending coronary artery, 15 were studied early (mean [+/- SD] 8 +/- 2 days) and 13 late (19 +/- 15 months) after operation by quantitative angiography and selective intravascular Doppler analysis at baseline, during pacing and after injection of papaverine and isosorbide dinitrate into the graft. Eleven patients with a normal left anterior descending artery served as control subjects. RESULTS: At baseline, mean graft diameter (2.39 +/- 0.41 vs. 2.42 +/- 0.45 mm) and bypass flow (38 +/- 22 vs. 30 +/- 12 ml/min) were similar in the early and late postoperative periods. Significant and similar vasodilation was observed in mammary grafts after administration of papaverine (+6 +/- 5% vs. +9 +/- 6%) and nitrates (+14 +/- 7% vs. +16 +/- 9%) both early and late after bypass surgery. Graft diameter increased during pacing late (+6 +/- 3%, p < 0.05) but not early after operation. Bypass flow increased similarly during pacing in both groups, but maximal flow reserve induced by papaverine was significantly lower in mammary grafts studied early (2.70 +/- 0.62) than those studied late (3.66 +/- 0.81, p < 0.01) and in normal coronary arteries (4.05 +/- 0.96, p < 0.001). CONCLUSIONS: An increase in myocardial blood flow induced by pacing resulted in vasodilation of mammary grafts in the late but not in the early postoperative period. Significant vasodilation of mammary grafts after papaverine and isosorbide dinitrate administration was observed both early and late after operation. However, bypass flow reserve after papaverine injection was significantly lower in the early postoperative period but normalized over time. This finding seems unrelated to the conduit; rather, it appears to be related to the periphery and could be the result of injury to the microvasculature during operation.

Blood Flow Velocity↗
PubMed1994

Rest technetium-99m sestamibi tomography in combination with short-term administration of nitrates: feasibility and reliability for prediction of postrevascularization outcome of asynergic territories.

OBJECTIVES: This study investigated the role of nitrate technetium-99m sestamibi imaging in predicting the postrevascularization outcome of chronically hypoperfused asynergic territories. BACKGROUND: Rest technetium-99m sestamibi myocardial scintigraphy underestimates the presence of viable myocardium in asynergic territories. Stimulation that improves coronary blood flow could increase tracer uptake in hibernating territories. METHODS: Nineteen patients with a previous myocardial infarction and left ventricular dysfunction scheduled for revascularization underwent quantitative technetium-99m sestamibi tomography under baseline conditions and during isosorbide dinitrate infusion. Global and regional function were assessed, respectively, before and after revascularization by radionuclide angiocardiography and two-dimensional echocardiography. RESULTS: Seven patients (group A) showed postrevascularization regional function recovery, and 12 (group B) showed no significant changes. In group A, nitrate infusion induced a decrease in the extent of the global uptake defect ([mean +/- SD] -37.4 +/- 21.6% of baseline value); in group B, no change or a slight increase was observed (+5.8 +/- 8.4%, p < 0.0005 vs. group A). The nitrate-induced changes in the extent of uptake defect correlated with postrevascularization changes in ejection fraction (r = -0.94, SEE 7.6). After revascularization, 11 asynergic vascular territories showed improvement (hibernating), and 34 remained unchanged (fibrotic). With administration of nitrates, 10 hibernating territories had a decrease in the extent of uptake defect, whereas only 4 of 34 of the fibrotic territories showed a nitrate-induced uptake improvement. CONCLUSIONS: Short-term administration of isosorbide dinitrate immediately before injection of technetium-99m sestamibi increases tracer uptake in some chronically hypoperfused asynergic territories. This finding correlates with the observation of post-revascularization functional recovery. Nitrate technetium-99m sestamibi myocardial scintigraphy could be a promising method for the noninvasive detection of viable hibernating myocardium.

Coronary Angiography↗
PubMed1996

Flow-mediated vasodilation during pacing of the free epigastric artery bypass graft early and late postoperatively.

OBJECTIVES: The free epigastric artery bypass graft is proposed as an alternative conduit to the saphenous vein graft, known for its high rate of attrition. The aim of our study was to assess its endothelial function in vivo. BACKGROUND: The endothelium of arterial bypass grafts plays a role in both the performance and the patency of such grafts. METHODS: We studied 73 epigastric grafts early (mean +/- SD 10 +/- 3 days) and 36 late (12 +/- 5 months) after coronary bypass surgery with quantitative angiography at rest, after 2 min of atrial pacing (130 beats/min) and after injection of isosorbide dinitrate (1 to 2 mg) into the graft. RESULTS: At rest, mean epigastric graft diameter was lower in the late than in the early postoperative period (2.26 +/- 0.39 vs. 2.61 +/- 0.49 mm, p < 0.001). Early after operation, epigastric grafts with a small or an intermediate runoff, but not those with a large runoff, were capable of vasodilation with nitrates (+0.09 +/- 0.10 mm). Late after operation, vasodilation after administration of isosorbide dinitrate was similar in epigastric grafts with a large runoff and in those with a small or intermediate runoff (+ 0.23 +/- 0.09 vs. +0.23 +/- 0.18 mm). Significant vasodilation during pacing was observed late (+4 +/- 9%, p < 0.01) but not early postoperatively, except in a subset of patients with grafts capable of vasodilation after nitrates. A correlation between the response to nitrates and the response during pacing was observed early (r = 0.579, p < 0.001) and late postoperatively (r = 0.530, p = 0.02). CONCLUSIONS: Flow-mediated vasodilation during pacing was observed in most epigastric grafts late, but not early, after operation. This endothelium-dependent dilation was correlated with the importance of the vasodilation observed with nitrates (endothelium-independent), which was related to the importance of the runoff only in the early postoperative period. The ability of epigastric grafts late postoperatively to dynamically adapt their dimensions to an acute increase in demand could contribute to the good functional results of this new alternative arterial graft.

Cardiac Catheterization↗
PubMed1995

Coronary artery response to cold-pressor test is impaired early after operation in heart transplant recipients.

OBJECTIVES: The aim of the present study was to evaluate the coronary vasomotor response to the cold-pressor test within 3 months after heart transplantation. BACKGROUND: Normal epicardial coronary arteries dilate in response to sympathetic stimulation evoked by the cold-pressor test. In transplant recipients, abnormal coronary vasomotion has been described shortly after operation. METHODS: Fourteen heart transplant recipients were compared 52 +/- 15 days (mean +/- SD) after operation with 10 control subjects. All had angiographically normal epicardial coronary arteries. Coronary blood flow velocity was measured with a Doppler catheter placed in the proximal left anterior descending coronary artery. Four segments in each patient were analyzed by quantitative coronary angiography to assess the diameter changes during the cold-pressor test and after intracoronary injection of isosorbide dinitrate. RESULTS: Coronary flow velocity increased similarly during the cold-pressor test in control subjects and in transplant recipients, from 7.5 +/- 2.3 to 11.0 +/- 3.9 cm/s and from 10.3 +/- 3.2 to 13.7 +/- 4.8 cm/s (both p < 0.01). In control subjects, 39 of 40 segments analyzed dilated during the cold-pressor test. In transplant recipients, 48 of 56 segments analyzed did not change or constricted. The mean epicardial coronary diameter increased significantly during the cold-pressor test in control subjects (+13 +/- 6%, p < 0.001), whereas it did not change significantly in transplant recipients (-2 +/- 9%, p = NS). In transplant recipients, isosorbide dinitrate elicited coronary vasodilation similar to that in control subjects. CONCLUSIONS: These data indicate that in human transplanted denervated hearts, coronary vasodilation in response to sympathetic stimulation by cold exposure is impaired shortly after operation.

Adult↗
PubMed2006

Relation of coronary hypersensitivity to serotonin in cardiac transplant recipients to vessel wall morphology and effect of vitamin C.

Coronary hypersensitivity to serotonin promotes platelet aggregation, entailing the progression of the atherosclerotic process. This abnormality is a common finding in cardiac transplant recipients and may be triggered by reactive oxygen species, which plays a main role in the inflammatory process. Hence, this study aimed to determine the influence of intimal hyperplasia on this abnormality and its reversibility after acute supplementation with the superoxide anion scavenger vitamin C. Therefore, intracoronary injections of serotonin (3 microg), bradykinin (600 ng), and nitroglycerin (isosorbide dinitrate 200 microg) were administered to 21 cardiac transplant recipients (1 year after transplantation) with normal coronary angiographic results; the serotonin injections were repeated after intracoronary vitamin C supplementation (40 mg/min for 14 minutes). In the segments in which serotonin effects were the most pronounced, the diameter changes were measured by quantitative angiography, and vessel wall morphology was studied by intravascular ultrasound (IVUS). The IVUS examination revealed moderate to severe intimal thickening (total area - luminal area/total area) in 9 patients (group 1) of 25 +/- 2%, compatible with the early stage of graft vasculopathy. In this group, hypersensitivity to serotonin remained unchanged after intracoronary vitamin C supplementation, from -21 +/- 3% (percentage from baseline) to -25 +/- 3%, whereas in the other 12 patients with mild intimal thickening (9 +/- 1%; group 2), hypersensitivity to serotonin was attenuated from -20 +/- 5% to -4 +/- 6% (p <0.01). In contrast, the responses to bradykinin and isosorbide dinitrate were similar in the 2 groups. In group 1, plasma levels of high-sensitivity C-reactive protein and proinflammatory cytokines (interleukin-6 and -8) were significantly enhanced. For all the patients studied, the effect of vitamin C on the response to serotonin was significantly correlated with the intimal thickening. In conclusion, at 1 year after transplantation, morphologic changes compatible with the early stage of the graft vasculopathy are accompanied by hypersensitivity to serotonin unresponsive to vitamin C, despite a relatively preserved endothelial function (unaltered response to bradykinin).

Adult↗
PubMed1996

Organic nitrates: new formulations and their clinical advantages.

The organic nitrates have been used for more than a century in the management of patients with myocardial ischemia. The most commonly used agents at this time include nitroglycerin, isosorbide dinitrate, and isosorbide-5-mononitrate. These agents all exert their therapeutic effects through biodegradation to nitric oxide, which stimulates guanylate cyclase in vascular smooth muscle cells with the production of cyclic guanosine monophosphate. The latter induces vasodilation by reducing the availability of ionized calcium to the contractile proteins. Tolerance to the organic nitrates occurs when the agents are administered in an attempt to provide therapeutic effects throughout 24 hours each day. There are probably several mechanisms responsible for nitrate tolerance, but there is no evidence at this time that concurrent medications will modify the development of tolerance. The only available method at this time is to give these agents intermittently to provide a period of washout. In so doing, it is possible to provide therapeutic nitrate effects for approximately 12 hours throughout each 24-hour period.

Cardiovascular Diseases↗
PubMed1996

Comparison of subgroups assigned to medical regimens used to suppress cardiac ischemia (the Asymptomatic Cardiac Ischemia Pilot [ACIP] Study).

This report focuses on the subset of 235 patients from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study receiving randomly assigned medical therapy to treat angina and suppress ischemia detected on ambulatory electrocardiography: 121 patients received the sequence of atenolol and nifedipine, and 114 diltiazem and isosorbide dinitrate. After 12 weeks of therapy, the primary end point (absence of ambulatory electrocardiographic (ECG) ischemia and no clinical events) was reached in 47% of atenolol/nifedipine- versus 31% of diltiazem/isosorbide dinitrate-treated patients (adjusted p = 0.03). A trend to increased exercise time to ST depression was seen in the atenolol and nifedipine versus diltiazem and isosorbide dinitrate regimens (median treadmill duration 5.8 vs 4.8 minutes; p = 0.04). However, when adjusted for baseline imbalances in ambulatory ECG ischemia, the 2 medical combinations were similar in suppression of ambulatory ECG ischemia. In both medication regimens, an association between mean heart rate and ischemia on ambulatory electrocardiography after 12 weeks of treatment was observed so that patients on either regimen with a mean heart rate > 80 beats/min had ischemia detectable almost twice as often as those with a mean heart rate < 70 beats/min (p < 0.001).

Angina Pectoris↗
PubMed1981

Intraaortic balloon counterpulsation: its influence alone and combined with various pharmacological agents on regional myocardial blood flow during experimental acute coronary occlusion.

We investigated the separate and combined effects of pharmacological and intraaortic balloon pump (IABP) support on regional myocardial blood flow in an experimental model of acute myocardial ischemia. Chloralose-anesthetized dogs were ventilated with an oxygen-air mixture, and cardiac output, arterial pressure, and heart rate were held constant. Treatment was begun 20 minutes following permanent ligation of the left anterior descending coronary artery (LAD). We evaluated the following pharmacological interventions: 25% hypertonic mannitol, isosorbide dinitrate, methyl-prednisolone sodium succinate, and propranolol. We measured left ventricular hemodynamics and intramyocardial blood flow by the radioactive microsphere technique prior to treatment and at 15-minute intervals thereafter. Compared with control measurements 20 minutes following LAD ligation, collateral blood flow to ischemic myocardium tended to decrease with no treatment. Treatments with the four pharmacological interventions and with IABP alone produced no significant improvement in collateral blood flow to ischemic myocardium 15 minutes following treatment. In contrast, mannitol, isosorbide dinitrate, and propranolol, each combined with IABP support, produced significant improvements in collateral flow within the same time periods. In nonischemic myocardium, combined pharmacological and IABP treatment did not enhance myocardial blood flow above that obtained with the pharmacological agents alone. The most effective combination of mechanisms for improving the ischemic region's myocardial blood flow appeared to be a reduction of extravascular coronary flow resistance coupled with a simultaneous increase in diastolic arterial pressure.

Animals↗
PubMed2003

A study of the efficacy of cervical ripening with nitric oxide donor versus placebo for cervical priming before second-trimester termination of pregnancy.

This was a double-blind randomized control study to evaluate the efficacy of cervical priming by nitric oxide donor before second-trimester induced abortion. One-hundred healthy women with a singleton pregnancy between 14 and 20 weeks of gestation were randomized into either 40 mg isosorbide mononitrate or placebo, given intravaginally 12 h before induction. This was followed by intravaginal misoprostol induction. The induction-abortion interval, abortion rate, side effects and the woman's acceptability of the priming agent were recorded. All women completed the study and there was no severe complication recorded. There was no significant difference in the induction-abortion interval and abortion rate between the two groups. Isosorbide mononitrate group reported significantly more side effects of headache. More than 90% of the women in both groups found the priming agent acceptable. The application of intravaginal nitric oxide donors prior to the prostaglandins induction did not significantly improve the second-trimester induced-abortion process.

Abortifacient Agents, Steroidal↗
PubMed2001

Influence of nitrovasodilators and cyclooxygenase inhibitors on cerebral vasoreactivity in conscious rabbits.

Since the nitric oxide (NO) and cyclooxygenase pathways have been suggested to have important roles in most vasodilations, our aim was to study the influence of cyclooxygenase inhibitors and nitrovasodilators on cerebrovascular reserve capacity. Corticocerebral blood flow was measured by hydrogen polarography during hypercapnia and acetazolamide stimuli in conscious rabbits. The measurements were repeated in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin as nitric oxide synthase (NOS) and cyclooxygenase inhibitors. The effects of nitroglycerin and isosorbide-5-nitrate were also tested. L-NAME completely, while indomethacin markedly inhibited the hypercapnic corticocerebral blood flow response. Nitroglycerin and isosorbide-5-nitrate significantly attenuated hypercapnia elicited corticocerebral blood flow increase. The different treatments reduced only moderately the acetazolamide-induced corticocerebral blood flow response. These results lend support to the hypothesis that antithrombotic and antiinflammatory medication (cyclooxygenase inhibitors) and nitrovasodilator treatments could interfere with the measurement of cerebrovascular reactivity resulting in underestimation of the cerebrovascular reserve capacity in patients taking these drugs.

Acetazolamide↗
PubMed1995

Late endothelial function of free and pedicled internal mammary artery grafts.

The internal mammary artery has greater long-term patency than the saphenous vein when used for coronary bypass grafting. Therefore, bilateral use of the internal mammary artery for grafting with the right internal mammary artery used as a "free" graft may result in improved graft survival. The study objectives were to compare the endothelial-dependent and -independent vasodilatory response in free and pedicled internal mammary artery grafts in patients who had previously undergone coronary surgery. Free (group 1, n = 8) and pedicled (group 2, n = 7) internal mammary artery grafts were studied by comparing the response to selective infusion of the endothelial-dependent vasodilator substance P (1.4 up to 22.4 pmol/min in doubling dose increments) followed by isosorbide dinitrate (2 mg over 2 minutes), in patients undergoing coronary angiography, 1 month to 6 years after coronary surgery. Maximal dilatory response to substance P was 8.7% +/- 1.8% in pedicled grafts compared with 8.8% +/- 2.3% in free grafts (p = not significant), with the dose response for both groups being similar. Infusion of isosorbide dinitrate produced only minimal further dilatation in both groups. No significant difference was found in endothelium-dependent and -independent vasodilatory response between free and pedicled internal mammary artery grafts, suggesting that the use of the free right internal mammary artery and other arterial grafts may enhance graft survival.

Adult↗