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PubMedDate not supplied

The nitroglycerin polymer gel matrix system: a new method for administering nitroglycerin evaluated with plasma nitroglycerin levels.

A new topical dosage form of nitroglycerin has been developed in which nitroglycerin and its vehicle are incorporated in a polymer gel matrix of fixed dimension. Venous plasma nitroglycerin concentrations were measured for 24 h after application of nitroglycerin polymer gel systems measuring 10 cm and containing 2% nitroglycerin (wt/wt) to 10 normal male volunteers. Five of these subjects were subsequently tested with 20-cm2 gel systems of similar composition. With the 10-cm2 nitroglycerin polymer gel system, venous plasma nitroglycerin concentrations were 0.83 +/- 0.26 ng/ml ast 4 h and 0.89 +/- 0.23 ng/ml at 24 h. For the 20-cm2 system, venous plasma nitroglycerin concentrations were 1.83 +/- 0.55 ng/ml at 8 h and 1.81 +/- 0.13 ng/ml at 24 h. The only adverse effect noted was headache, which affected all the subjects tested with the 20-cm2 appliance. The plasma nitroglycerin concentrations obtained with the polymer gel system appear to be in a clinically useful range; thus this new form of topical nitroglycerin should be of benefit to patients in whom sustained plasma nitroglycerin concentrations are desirable, e.g., those patients with chronic congestive heart failure and angina on awakening.

Administration, Topical↗
PubMed1991

Effects of sublingual nitroglycerin in patients receiving transdermal nitroglycerin for coronary artery disease: prevention of cross-tolerance.

The systemic hemodynamic and coronary dilative responses to sublingual nitroglycerin were studied in patients receiving transdermal nitroglycerin. A total of 48 patients with coronary artery disease were divided into 4 groups: 12 patients receiving 1 tablet of sublingual nitroglycerin without transdermal nitroglycerin (Group 1), 12 patients receiving 1 tablet of sublingual nitroglycerin with 12-hour-daily intermittent therapy of transdermal nitroglycerin (Group 2), 12 patients receiving 1 tablet of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 3), and 12 patients receiving 2 tablets of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 4). Before and during administration of sublingual nitroglycerin, aortic pressure, left ventricular pressure, and coronary artery diameter were examined at diagnostic cardiac catheterization in all patients. During sublingual nitroglycerin, the decreases of aortic systolic pressure and left ventricular end-diastolic pressure were greater in Group 1, 2, and 4 than in Group 3. Dilation of coronary arteries by sublingual nitroglycerin tended to be greater in Group 1, 2, and 4 than in Group 3. Thus, the effects of sublingual nitroglycerin for the relief of ischemia might be more prominent in patients with intermittent therapy of transdermal nitroglycerin than in those with continuous therapy. The increased dose of sublingual nitroglycerin for the relief of ischemia might be more effective in patients with continuous therapy of transdermal nitroglycerin.

Administration, Cutaneous↗
PubMed1993

Differences of intravenous nitroglycerin responses in left ventricular systolic and end-diastolic pressures and coronary artery diameters during long-term treatment with cutaneous nitroglycerin patches.

The differences of intravenous nitroglycerin responses in left ventricular (LV) systolic and end-diastolic pressures and in coronary artery diameters (cross-tolerance) were investigated in patients receiving nitroglycerin patches. During diagnostic cardiac catheterization, graded doses of 50, 100, and 150 mcg of intravenous nitroglycerin were given. Left ventricular systolic and end-diastolic pressures and left coronary arteriograms were obtained during each dose. Twenty patients with coronary artery disease were studied. Before cardiac catheterization, 10 received nitroglycerin patch (patch group), and 10 did not (control group). In the control group, graded intravenous nitroglycerin doses of 50, 100, and 150 mcg caused decrease in LV systolic pressure of 18 +/- 7%, 20 +/- 5%, and 23 +/- 6%, respectively. In the patch group, the same intravenous nitroglycerin doses decreased LV systolic pressure by 12 +/- 6% (p < 0.05), 19 +/- 7% (NS), and 18 +/- 6% (p < 0.05), respectively, (p value: vs. control group). At the same intravenous nitroglycerin doses, LV end-diastolic pressures were decreased by 48 +/- 14%, 52 +/- 17%, and 56 +/- 9%, respectively, in the control group. However, there were no significant differences in LV end-diastolic pressure between the two groups for any of the three intravenous nitroglycerin doses. The same intravenous nitroglycerin doses caused increase in diameter of the left anterior descending coronary artery and circumflex coronary artery in the control group, which was attenuated significantly in the patch group. Tolerance may develop in LV systolic pressure and coronary artery diameters, whereas it may not develop in LV end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed2000

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗
PubMed1994

Comparison of tolerance to intravenous nitroglycerin during nicorandil and intermittent nitroglycerin patch in healthy volunteers.

BACKGROUND: Nitrate tolerance is associated with a loss in the hemodynamic response to nitrate during repeated administration. Nicorandil is a new potassium channel agonist with additional nitrate properties. The aim of this study was to determine whether 7-day nicorandil (10 mg orally twice a day) administration attenuates the response to single-dose intravenous nitroglycerin (0.45 mg over 1 minute) in comparison with 7-day intermittent nitroglycerin patch administration (10 mg for 16 of 24 hours). METHODS: This was an open, randomized crossover study performed in 12 healthy volunteers. Blood pressure, heart rate, and their oscillations were measured with use of a noninvasive device. Low-frequency oscillations (66 to 129 mHz) of blood pressure reflect sympathetic activity. Reflex sympathetic activation was measured as after versus before intravenous nitroglycerin difference in low frequency oscillations of blood pressure and heart rate on day 0 and day 7 of each treatment period. Measurements after single-dose intravenous nitroglycerin included the maximum decrease in systolic blood pressure and maximum increase in heart rate and sympathetic activation. Tolerance in each group was assessed as the difference in each parameter between day 7 and day 0. RESULTS: Attenuation of the intravenous nitroglycerin-induced decrease in systolic blood pressure (day 7 - day 0) was - 10 +/- 10 mm Hg during use of the nitroglycerin patch and -2 +/- 11 mm Hg during nicorandil (p = 0.03). Similarly, the change in low frequency oscillations of systolic blood pressure was -79 +/- 144 mm Hg-Hz-1/2 during nitroglycerin administration and 60 +/- 139 mm Hg-Hz-1/2 during nicorandil administration (p = 0.04). CONCLUSION: These results indicate that 7-day administration of nicorandil does not attenuate single-dose intravenous nitroglycerin-induced hemodynamic changes or sympathetic activation. In healthy volunteers and at this dosage (10 mg twice a day), cross tolerance between nicorandil and nitroglycerin does not occur.

Administration, Cutaneous↗
PubMed1984

Effect of nitroglycerin-soluble additives on the stability of molded nitroglycerin tablets.

Nitroglycerin vapor pressures at 25 degrees C were determined for additive-nitroglycerin systems over the additive-nitroglycerin weight ratio range of 0.5 to 3.0 for 16 additives exhibiting solubility in nitroglycerin. The effects of the additives on nitroglycerin chemical stability at 25 degrees C and 50 degrees C were also studied. Tablet stability characteristics, i.e., content uniformity, open-dish stability, and chemical decomposition were evaluated for selected tablet formulations. Most additives lowered the vapor pressure of nitroglycerin sufficiently to stabilize content uniformity when used at additive-nitroglycerin weight ratios near 1. Higher additive levels are needed for significant potency stabilization in open-dish stability tests, but these levels normally decrease the chemical stability of nitroglycerin. However, stabilization of content uniformity, a twofold reduction of potency loss in an open-dish stability test, and chemical stability are possible with at least three of the additives studied.

Absorption↗
PubMed1986

Plasma levels of nitroglycerin generated by three nitroglycerin patch preparations, Nitradisc, Transiderm-Nitro and Nitro-Dur and one ointment formulation, Nitrobid.

Twenty-four healthy male subjects participated in a study comparing plasma concentrations of nitroglycerin generated by single applications of Nitradisc 32 mg, Transiderm-Nitro 50 mg and Nitro-Dur 104 mg patches and from one inch of Nitrobid 2% ointment. The three patch preparations are designed to release 10 mg nitroglycerin systemically over a 24 h period. Nitrobid ointment is intended to deliver 15 mg nitroglycerin per inch of ointment, and to be reapplied at least every 8 h. Blood was taken for nitroglycerin assay up to and including 24 h after each application. Assay for nitroglycerin was performed using a gas chromatography-mass spectrometry technique. Plasma concentrations of nitroglycerin were sustained up to the 24 h mark with all three patch preparations, but not with application of Nitrobid ointment. Nitrobid was associated with a rapid rise in nitroglycerin plasma concentrations maximal 1 h after application. Plasma concentrations of nitroglycerin absorbed from Nitrobid ointment fell below those absorbed from all three patch preparations after 8 h. Clinically, all four formulations were similar with respect to side effects, with headache and dizziness being the most common.

Administration, Topical↗
PubMed1998

Converting i.v. nitroglycerin therapy to nitroglycerin ointment therapy: a comparison of two methods.

BACKGROUND: Methods of converting treatment with i.v. nitroglycerin to treatment with nitroglycerin ointment 2% vary greatly and may affect the length of time patients remain in the ICU, nursing time, and possible recurrent angina. To date, no randomized, controlled studies have evaluated the methods used for conversion. OBJECTIVE: To evaluate two methods of conversion. METHODS: Two hundred patients receiving i.v. nitroglycerin at doses of 10 to 100 micrograms/min were randomized to two methods of conversion: (1) Apply nitroglycerin ointment and stop i.v. nitroglycerin 30 minutes later. (2) Decrease the dose of i.v. nitroglycerin by 10 micrograms/min every 15 minutes, apply one half the dose of nitroglycerin ointment when the original i.v. dose has been decreased by one half, and apply the full dose of the ointment when the i.v. nitroglycerin is stopped. The primary end point was the time patients remained in the ICU after the conversion. Secondary end points included time to hospital discharge, estimate of nursing time, and selected clinical end points. Kaplan-Meier and Cox regression analyses were used to evaluate time patients remained in the ICU and nursing time. Clinical outcomes were analyzed by using a chi-square test. RESULTS: Use of the first method reduced median time before transfer from the ICU by 23 minutes and median nursing time by 45 minutes. Analysis of all clinical outcomes showed no differences between the two methods. CONCLUSIONS: Use of the first method was associated with a reduction in the time patients remained in the ICU before transfer to another unit and savings in nursing time, but the two methods did not differ according to clinical outcomes.

Administration, Cutaneous↗
PubMed1981

Relation of time course of plasma nitroglycerin levels to echocardiographic, arterial pressure and heart rate changes after sublingual administration of nitroglycerin.

Despite the widespread use of nitroglycerin, a relation between plasma nitroglycerin concentrations and the associated cardiovascular effects has not been well established. It was hypothesized that nitroglycerin levels may help predict the hemodynamic responses. With use of a recently developed nitroglycerin assay technique, the relation between the time course of plasma nitroglycerin levels and echocardiographic changes after sublingual administration of 0.6 mg of the drug was evaluated in 12 normal volunteers. Mean plasma nitroglycerin levels were maximal at 2 (1.1 +/- 0.3 ng/ml) and 5 (1.4 +/- 0.6 ng/ml) minutes, when the changes in mean heart rate (+17 +/- 7 and +12 +/- 3 min-1) and decreases in echocardiographic left ventricular diastolic (-4.2 +/- 0.8 mm at 5 minutes) and systolic (-3.1 +/- 0.6 mm at 5 minutes) dimensions were also maximal. Parallel changes were noted in left atrial dimension, ventricular velocity of circumferential fiber shortening and systolic blood pressure, but not in diastolic blood pressure. These findings demonstrate the existence of a close relation between plasma nitroglycerin levels and variables that reflect the known responses to this drug.

Administration, Oral↗
PubMed1984

Sustained beneficial hemodynamic responses to large doses of transdermal nitroglycerin in congestive heart failure and comparison with intravenous nitroglycerin.

The hemodynamic effects of a new transdermal preparation of nitroglycerin were evaluated in 9 patients with chronic congestive heart failure (CHF). A graded infusion of nitroglycerin was administered initially to establish the dose-response relation for nitroglycerin and estimate the dose of topical nitroglycerin to be applied. Significant hemodynamic improvement was observed 0.5 to 1.0 hour after the cutaneous application of the nitroglycerin-impregnated polymer. The peak effect occurred at 6 hours, with the left ventricular filling pressure decreasing from 24 +/- 2 to 18 +/- 1 mm Hg (mean +/- standard error of the mean) (p less than 0.01) and the cardiac index increasing from 2.0 +/- 0.2 to 2.6 +/- 0.2 liters/min/m2 (p less than 0.01). The systemic vascular resistance decreased from 1,860 +/- 198 to 1,531 +/- 162 dynes s cm-5 (p less than 0.01). Heart rate and mean arterial pressure were unchanged. Significant hemodynamic benefit was observed for 24 hours, and no rebound deterioration occurred upon withdrawal of the drug. The average dose of transdermal nitroglycerin applied was 51 +/- 6 cm2 (1.7 +/- 0.2 mg/kg; 6 of the 9 patients received 64 cm2). Thus, topical application of a new nitroglycerin-impregnated polymer induces an improvement in cardiac performance that is sustained for 24 hours in patients with chronic CHF. However, substantial doses of the drug may be required to produce a satisfactory hemodynamic response in most patients with CHF.

Adult↗
PubMed1984

Plasma nitroglycerin concentrations and hemodynamic effects of sublingual, ointment, and controlled-release forms of nitroglycerin.

After a sublingual test dose, 12 healthy men aged 21 to 29 yr were treated with controlled-release transdermal nitroglycerin skin patches designed to deliver 10 mg/day nitroglycerin and with nitroglycerin ointment (2%) (1-in amount from the tube spread over 50 cm2) for 24 hr in a double-blind crossover study. Assessment was by measurement of nitroglycerin in plasma, blood pressure, and pulse rate. The mean plasma concentration of nitroglycerin during ointment dosing was approximately 200% to 400% that during skin patch dosing. Levels during ointment dosing were closer to those from sublingual dosing than were those during skin patch dosing. Blood pressure and pulse rate changes were much the same during both transdermal treatments. Calculations showed that delivery of nitroglycerin from the skin patches would have to be over 40 to 80 cm2 of the skin to achieve nitroglycerin exposure of the order of that induced by 1 in of ointment spread over 50 cm2 or from sublingual dosing.

Administration, Oral↗
PubMed2001

Different mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt in patients with unexplained syncope: important role of epinephrine in nitroglycerin-induced syncope.

INTRODUCTION: A reduction in left ventricular volume and an increase in epinephrine levels have been reported in tilt-induced neurally mediated syncope. To compare the mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt and to investigate the role of catecholamines, the temporal changes in plasma levels of norepinephrine and epinephrine and in left ventricular volume were measured. METHODS AND RESULTS: The first study population consisted of 90 patients with syncope of unknown etiology and 12 control subjects. The second study population consisted of 43 patients with unexplained syncope. In the first study, head-up tilt (80 degree angle) was conducted for 40 minutes, and norepinephrine and epinephrine levels were measured. In the second study, all patients were randomly allocated to either isoproterenol test (20 patients) or nitroglycerin test (23 patients) for 20-minute head-up tilt. Isoproterenol infusion was given at a rate of 1 to 3 microg/min. Intravenous infusion of nitroglycerin was started at 250 microg/hour with increasing dosages up to 1,500 microg/hour. Norepinephrine and epinephrine were measured in peripheral venous blood. Left ventricular volumes were measured by echocardiography with patients in the supine position and during head-up tilt every 1 minute. End-diastolic volume and end-systolic volume were calculated. In the first study, 61 patients demonstrated a positive response and 29 patients demonstrated a negative response. Plasma norepinephrine changes during head-up tilt were not significantly different, whereas epinephrine levels were significantly higher in the positive patients than in the negative and control subjects (148 +/- 118 pg/mL vs 66 +/- 31 pg/mL and 55 +/- 27 pg/mL). Thirteen of the 20 patients given isoproterenol and 15 of the 23 patients given nitroglycerin showed a positive head-up tilt (65.0% vs 65.2%; P = NS). During isoproterenol and nitroglycerin infusion head-up tilt, epinephrine in the positive group determined by the nitroglycerin test was significantly higher than that in the other three groups (103 +/- 38 pg/mL vs 60 +/- 33 pg/mL, 31 +/- 21 pg/mL, and 50 +/- 52 pg/mL). In contrast, end-systolic volume was significantly smaller in the positive group than in the other three groups based on findings of the isoproterenol test. CONCLUSION: The findings suggest that nitroglycerin triggers head-up tilt-induced syncope by increasing epinephrine levels, whereas isoproterenol induces syncope by decreasing left ventricular volume.

Adolescent↗
PubMed1983

Myocardial salvage by intravenous nitroglycerin in conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension.

We studied the effect of nitroglycerin-induced decreases in mean arterial pressure (MAP) on myocardial salvage. Two hours after occlusion of the left anterior descending coronary artery, 65 conscious dogs were randomly allocated to receive 4 hr intravenous infusions of saline (group 1, 19 dogs), or nitroglycerin in doses to decrease MAP by 10% (group 2, 18 dogs), 25% (group 3, 14 dogs), and 50% (group 4, 14 dogs), respectively. At 7 days, 41 dogs were killed for measurement of infarct size; 24 dogs, given 7 to 10 micron radioactive microspheres for flow calculations, were killed 6 hr after occlusion. Boundaries of the occluded bed were defined by postmortem coronary arteriography. Infarct and occluded bed masses were measured by planimetry of weighed transverse sections of the left ventricle. Compared with saline infusions in group 1, nitroglycerin infusions produced sustained reductions (p less than .001) in mean left atrial pressure and MAP in all dogs, but heart rate was unchanged. The decreases in MAP achieved in groups 2, 3, and 4 were 10% (range, 5% to 19%), 23%, and 39%, respectively, with average levels of 96 (range, 83 to 113), 83, and 64 mm Hg, respectively. Despite similar masses of the occluded bed and left ventricle among the four groups, infarct size was significantly smaller (p less than .025) in group 2 compared with groups 1, 3, or 4, expressed both as percent of the left ventricle (6% vs 14% vs 13% vs 15%) and as percent of the occluded bed (13% vs 37% vs 34% vs 44%). Myocardial salvage (expressed as percent of the occluded bed) with nitroglycerin correlated inversely with the percent of decrease in MAP (r = -.77, p less than .001). Collateral blood flow increased (p less than .005) throughout the occluded bed in group 2 compared with group 1 but was unchanged in groups 3 and 4. In contrast, coronary vascular resistance decreased (p less than .025) in all nitroglycerin groups. These results suggest that perfusion pressure is an important determinant of myocardial salvage during nitroglycerin therapy. An increase in the dose of nitroglycerin to decrease MAP by more than 10%, and to levels below 96 mm Hg, might offset its potential for myocardial salvage in the conscious dog.

Animals↗
PubMed1983

Effect of buccal nitroglycerin on pulmonary artery pressure at rest and during exercise: a comparison with sublingual nitroglycerin in patients with coronary artery disease.

60 patients with ischemic heart disease and angina pectoris, aged 42 to 74 years (mean 59), were included in this randomized study. All suffered from coronary disease demonstrated by ECG changes and/or positive exercise test results. Twenty percent of the patients had coronary angiograms revealing significant CAD. All patients had had typical angina pectoris episodes for a period of 22 +/- 10 months at a frequency of 4 +/- 2 attacks a week. A positive response to sublingual nitroglycerin was observed in all patients. The patients were randomly assigned to four groups (1 mg, 2.5 mg, or 5.0 mg buccal nitroglycerin and a control group with 0.8 mg sublingual nitroglycerin). Exercise testing was done by bicycle ergometer in the recumbent position at maximal work loads in 3-min periods; hemodynamic measurements were performed using a pulmonary artery catheter (Grandjean). Pulmonary artery pressure, heart rate, systemic blood pressure, and ST-segment changes in the ECG were recorded before administration of the drug as well as 5, 15, 30, 60, 120, and 180 s after administration. Exercise tests were performed 3, 30, and 180 min after administration. The study demonstrates that buccal Synchron nitroglycerin has immediate hemodynamic and clinical effects, documented by the reduction in pulmonary artery pressure values at rest and exercise and the increase in exercise tolerance and cardiac output. The best antianginal effects were achieved with the dosage of 2.5 mg buccal nitroglycerin. We conclude that buccally administered nitroglycerin has early effects similar to those of nitroglycerin administered sublingually; the hemodynamic and clinical effects, however, persist over a minimum of 180 min.

Blood Pressure↗
PubMed1977

Polymer sorption of nitroglycerin and stability of molded nitroglycerin tablets in unit-dose packaging.

The sorption of nitroglycerin by thermoplastic polymers and the stability of molded nitroglycerin tablets in strip packaging were studied. The polymers investigated varied greatly in their affinity for nitroglycerin, the order of decreasing affinity being: vinyls greater than low density polyethylene greater than ionomers greater than high density polyethylene. With the proper choice of packaging, molded nitroglycerin tablets stabilized with povidone maintained acceptable potency for up to 2 years at 26 degrees when strip packaged in unit doses. Chemical decomposition (hydrolysis) of nitroglycerin also was investigated. Povidone accelerated the decomposition of nitroglycerin; at high temperature, decomposition was a significant factor in tablet stability for tablets containing povidone.

Adsorption↗
PubMed1997

Chronic splanchnic hemodynamic effects of low-dose transdermal nitroglycerin versus low-dose transdermal nitroglycerin plus spironolactone in patients with cirrhosis.

We studied the hemodynamic changes following a four-week administration of either low-dose transdermal nitroglycerin (a constant release of 5 mg of nitroglycerin/day) (N = 10) or low-dose transdermal nitroglycerin plus spironolactone (100 mg/day) (N = 9) in patients with cirrhosis and portal hypertension. Two patients in the latter group did not undergo repeat measurements after dropping out because of severe headaches or developing ascites during the study. Transdermal nitroglycerin induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-11.7 +/- 14.9%, P < 0.05), which was associated with a significant reduction of cardiac output (-10.5 +/- 7.3%). Nitroglycerin plus spironolactone induced a significant reduction in the HVPG (-18.3 +/- 16.0%, P < 0.05) associated with a significant reduction of cardiac output (-13.8 +/- 5.6%), right atrial pressure (-35.0 +/- 30.0%), mean arterial pressure (-7.5 +/- 6.8%), and plasma volume (-10.2 +/- 7.0%). The difference of the mean HVPG reduction between the groups was insignificant. A decrease in the HVPG greater than 10% was observed in six of 10 patients (60%) and in five of seven patients (71.4%), defined as "responders," at four weeks. The difference in percentage of responders between the groups was insignificant. We found that in some cirrhotic patients, low-dose transdermal nitroglycerin is potentially useful in the treatment of portal hypertension. Spironolactone as an adjunct to low dose transdermal nitroglycerin did not demonstrate therapeutic advantages in the treatment of portal hypertension in cirrhotics. That there were nonresponders indicates that there are variable responses in splanchnic hemodynamics to these drugs.

Administration, Cutaneous↗
PubMed1975

Reduction in myocardial ischemia with nitroglycerin or nitroglycerin plus phenylephrine administered during acute myocardial infarction.

Nitroglycerin reduces ischemic injury during acute myocardial infarction (AMI) in dogs--an effect that is potentiated when drug-induced hypotension and tachycardia are prevented with phenylephrine. To determine the effectiveness of nitroglycerin, alone or with phenylephrine, during AMI in man, 12 patients (five or whom had left heart failure) were evaluated by summing ST-segment abnormalities (sigmaST) from 35 precordial electrodes. The seven patients without heart failure did not benefit consistently from nitroglycerin alone; however, addition of phenylephrine to abolish nitroglycerin-induced arterial pressure reduction uniformly diminished sigmaST (4.9 to 3.2 mv; P less than 0.05). In patients with heart failure, nitroglycerin alone consistently reduced ischemia (5.8 to 4.4 mv, P less than 0.05); addition of phenylephrine often partially reversed this effect. Thus, administration of nitroglycerin, alone or with phenylephrine, can reduce myocardial ischemic injury during AMI in man; however, the response to phenylephrine depends on the presence or absence of left ventricular failure before treatment.

Acute Disease↗
PubMed1986

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

The study of venodilator tolerance to nitroglycerin has been complicated by reflex compensation and by problems in analyzing venous tone in the presence of multiple determinants of venous pressure. We assessed venous tone as total effective vascular compliance (TEVC) under autonomic blockade in six dogs, in the nontolerant state, and during a 5 day infusion of nitroglycerin (1.5 micrograms/kg/min). Under long-term treatment, baseline TEVC was unaffected and the nitroglycerin dose-response relationship for TEVC was shifted to greater than 10-fold higher doses, whereas baseline mean arterial pressure (MAP) was lowered by 17 +/- 3 mm Hg without any shift in nitroglycerin responsiveness. This lowering of MAP was observed only after autonomic blockade. In six additional dogs instrumented with aortic flow probes, nitroglycerin (1.5 micrograms/kg/min) induced a 15 +/- 1% decline in peripheral vascular resistance (PVR) under autonomic blockade, but with reflexes intact these dogs showed no change in PVR and a 21 +/- 10% increase in norepinephrine release rate. We conclude that modest long-term exposure to nitroglycerin results in tolerance to its venodilating effects, whereas arteriolar action is maintained. This tolerance-induced shift in action from venous toward arteriolar dilation is normally masked by compensatory reflexes.

Animals↗