Nitroglycerin Group Research Articles

Maternal and Fetal Cardiovascular Effects of Transdermal Glyceryl Trinitrate and Intravenous Ritodrine

In Brief Objective To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. Methods Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. Results Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI −4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. Conclusion At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor. Transdermal glyceryl trinitrate has significantly fewer maternal and fetal cardiovascular side effects than intravenous ritodrine at doses required for tocolysis.

Maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate and intravenous ritodrine

Objective: To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. Methods: Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. Results: Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI −4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. Conclusion: At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor.

This Month in ANESTHESIOLOGY

This Month in ANESTHESIOLOGY

A randomized, double-blind, placebo-controlled, crossover study to assess the immediate effect of sublingual glyceryl trinitrate on the ankle brachial pressure index, claudication, and maximum walking distance of patients with intermittent claudication

Purpose:The goal of the present study was to assess the immediate effect of sublingual glyceryl trinitrate (GTN) in patients with intermittent claudication. Methods: We conducted a randomized, double-blind, placebo-controlled crossover study. Inclusion criteria consisted of history of intermittent claudication, resting ankle brachial pressure index (ABPI) of 1.00 or less, a 20% or greater fall in ABPI after exercise, and maximum walking distance (MWD) of less than 250 m. Patients already receiving nitrates were excluded. In study 1, patients (n = 25) underwent a standard exercise test after randomization to receive either 800 μg of sublingual GTN or placebo. The postexercise ABPI was recorded. Then, the crossover portion of the study was performed. In study 2, patients (n = 22) had their claudication distance and MWD measured. They then were randomized to receive either GTN or placebo spray, and the exercise test was repeated, with the claudication distance and MWD recorded, followed by the crossover portion of the study. Statistical analysis was performed with the Wilcoxon matched pairs signed ranks test and the Mann-Whitney U test. Results:In study 1, the median postexercise ABPIs for placebo and GTN were 0.29 and 0.36 ( P = .0001). In study 2, the median claudication distance for both placebo and GTN groups was 70 m ( P = .59). The median MWD for the placebo and GTN groups was 105 and 125 m ( P = .0084) Conclusion: GTN can decrease the fall in ABPI after exercise and increase the MWD. (J Vasc Surg 1998;28:895-900.)

Lack of correlation between myocardial nitric oxide and cyclic guanosine monophosphate content in both nitrate-tolerant and -nontolerant rats

We studied the effect of nitroglycerin (NTG) on cardiac nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) content in nitrate-tolerant/nontolerant rats in vivo. The effect of the pharmacological blockade of endogenous NO synthesis and the effect of exogenous NO on cardiac cGMP were also examined. Rats were treated with 100 mg/kg of NTG and corresponding vehicle s.c. three times a day for 2.5 days to induce NTG-tolerance/nontolerance. Rats were then administered a single dose of s.c. 100 mg/kg of NTG to test the effect of NTG in tolerant/nontolerant states, respectively. Nontolerant rats treated with vehicle were controls, and nontolerant rats treated with the NO synthesis inhibitor NG-nitro- l-arginine (LNNA, 20 mg/kg) were negative controls. Another group of nontolerant rats treated i.v. with the direct NO donor sodium nitroprusside (SNP, 3 mg/kg) were positive controls. Cardiac NO assessed by electron spin resonance after in vivo spin-trapping increased 100-fold ( P < 0.05) in the positive control, 10-fold ( P < 0.05) in the NTG-tolerant group, and 4-fold ( P < 0.05) in the single NTG group, when compared to controls. In the negative control group, NO was reduced to near the detection limit (four-fold reduction, P < 0.05). Cardiac cGMP measured by radioimmunoassay was increased significantly (two-fold, P < 0.05) only in the positive control group, and there were no differences among the other groups. This shows that: 1) in vivo cardiac bioconversion of NTG to NO is not impaired in nitrate tolerance; and 2) changes in cardiac NO content are not reflected by changes in cGMP content in nitrate-tolerant and -nontolerant rats.

Effects of Qarlicin on unstable angina pectoris and its relationship with blood lipid and granule membrane protein-140

Objective: To observe the clinical effects of Garlicin on unstable angina pectoris (UAP) and explore how the Garlicin’s effects vary among syndromes as defined by traditional Chinese medicine (TCM).Methods: Fifty-five patients with UAP were randomly divided into the Garlicin group (34 patients) and the control group (21 patients). Each patient was classified according to TCM Syndrome Differentiation as having Cold Syndrome type, Heat Syndrome type, severe blood stasis (SBS) type, and mild blood stasis (MBS) type of UAP. Garlicin 60 mg or nitroglycerin 5 mg was given to the two groups respectively by intravenous drip for 10 days as one therapeutic course. The curative effect was evaluated by symptomatic changes and electrocardiogram. The effective rates as well as indexes such as blood lipid, lipoprotein, apolipoprotein, and granule membrane protein-140 (GMP-140) were compared between groups and types.Results: Garlicin and nitroglycerin group did not differ significantly in effective rate, while that of Garlicin group was higher for the Cold Syndrome type than that of Heat Syndrome type (P < 0. 01). The high density lipoprotein/low density lipoprotein ratio and apolipoprotein A-I level rose markedly in the former type (P < 0.05), while an opposite trend was seen in the Heat Syndrome type. Garlicin was more effective in the SBS type than that in the MBS type, and it markedly decreased GMP-140 in the MBS type.Conclusions: Garlicin is effective in UAP, especially the Cold Syndrome and SBS types. Its mechanism may involve improving blood lipid levels and inhibiting platelet activation.

Long-term follow-up after early intervention with intravenous diltiazem or intravenous nitroglycerin for unstable angina pectoris.

In a double-blind randomized trial in unstable angina it was shown that intravenous diltiazem reduced ischaemic events in the first 48 h after inclusion better than intravenous nitroglycerin. The present study was performed to establish the long-term prognosis of the randomized patients, with respect to their initial treatment assignment. One year follow-up data on ischaemic end-points and anti-ischaemic medication were recorded. Results were available for all of the 121 randomized patients. One hundred and sixty-seven primary endpoint events were recorded, of which 54 occurred in the first 48 h and 113 during the follow-up. Survival analysis showed that event-free survival was significantly better in the diltiazem group (45.0%) than in the nitroglycerin group (34.4%), P=0.04. The incidence rate after 48 h and one year for cardiac death are, respectively, 0% and 4.1%. The trend in anti-ischaemic medication was higher in the nitroglycerin group. For beta-blockers, this trend became significant after 12 months (P=0.03). These results show that the initial benefit obtained by early treatment with intravenous diltiazem was preserved during the first year after the initial hospitalization, and that, despite the high risk of cardiac events in our population, the overall mortality 12 months after inclusion was low.

Vasopressin combined with nitroglycerin increases endocardial perfusion during cardiopulmonary resuscitation in pigs

Although vasopressin increases vital organ blood flow during cardiopulmonary resuscitation (CPR), endocardial perfusion remains suboptimal. This study was designed to assess the effects of vasopressin versus a combination of vasopressin and nitroglycerin on vital organ blood flow in a porcine model of CPR. After 4 min of cardiac arrest, and 3 min of closed-chest compressions, 14 animals were randomly treated with either 0.4 U/kg vasopressin ( n=7) or 0.4 U/kg vasopressin combined with 5 μg/kg nitroglycerin ( n=7). Coronary and cerebral perfusion pressure as well as left ventricular myocardial blood flow was comparable between groups throughout the experiment. Ninety seconds after drug administration, vasopressin combined with nitroglycerin resulted in comparison with vasopressin alone in significantly higher mean (±standard error of the mean) left ventricular endocardial blood flow (78±7 vs 51±5 ml·min −1·100 g −1; P<0.05), and a significantly higher endocardial/epicardial perfusion ratio (0.93±0.09 vs 0.57±0.06; P<0.05). Seven of seven animals in the vasopressin group, and four of seven animals in the vasopressin and nitroglycerin group (NS) were resuscitated successfully and survived the 2-h observation period. We conclude that, when compared with vasopressin therapy alone, combined vasopressin and nitroglycerin improved endocardial perfusion significantly immediately after drug administration during CPR.

The impact of vasodilators on random-pattern skin flap survival in the rat following mainstream smoke exposure.

This study demonstrates that acute mainstream cigarette smoke exposure is deleterious to dorsal random-pattern skin flap survival in the rat. Three vasodilators were also studied for their ability to mediate flap survival after smoke exposure. Sprague-Dawley rats (10 per group) were exposed to two cigarettes per day over a 14-day period. This is an exposure equivalent to that of an average cigarette smoker. Dorsal McFarlane caudally based random-pattern skin flaps (4 x 10 cm) were created on day 7 of the smoke exposure. Enteral phenoxybenzamine (0.56 mg per kilogram per day), enteral nifedipine (10 mg per kilogram per day), and topical nitroglycerin (1.3 cm or 7.5 mg per day) were administered after creation of the dorsal skin flaps in two doses daily during smoke exposure. Fluorescein was used to delineate areas of viability accurately. A pad digitizer was utilized to calculate designated skin flap areas to +/-1.0 mm2. Experimental animals demonstrated a 23% decrease (p < 0.01) in skin flap area survival compared with the control animals. The phenoxybenzamine group demonstrated a 5.5% increase in flap area survival (p=0.068), the nifedipine group demonstrated a 4.1% increase in flap area survival (p=0.049), and the nitroglycerin group demonstrated an 8.9% increase in flap area survival (p=0.049). These data suggest that phenoxybenzamine appears to affect skin flap survival marginally after smoke exposure. However, nifedipine and nitroglycerin improve random-pattern skin flap survival significantly after mainstream cigarette smoke exposure in the rat. These results imply that pharmacological intervention with vasodilators may ultimately prove clinically useful for random-pattern skin flap salvage in the cigarette-smoking patient.

Controlled delivery of vascular endothelial growth factor promotes neovascularization and maintains limb function in a rabbit model of ischemia

Purpose: Vascular endothelial growth factor (VEGF) modulates new blood vessel development and growth and has been suggested as a potential therapeutic agent that could alleviate debilitating claudication in patients. The objective of this study was to determine whether controlled, local delivery of a low dose of VEGF from an osmotic pump could promote neovascularization, limb perfusion, and functional improvements in the hind limbs of rabbits rendered partially ischemic by surgery. The effects of VEGF were compared with those of the vasodilator nitroglycerin (NTG) and to saline administered similarly. Methods: Thirty rabbits were randomly assigned to either VEGF (n = 10), NTG (n = 10), or saline (n = 10) treatment groups. Partial ischemia was induced in each left hind limb by surgical ligation of the common and superficial femoral arteries, leaving the internal iliac artery intact. The right limb of each animal served as a nonischemic control. Immediately after vessel ligations, a 28-day osmotic pump was implanted to deliver VEGF (0.22 μg/kg/day), NTG (17.8 μg/kg/day), or saline solution into the common iliac artery just proximal to the ligation site. Comparative vascularity between ischemic and nonischemic limbs within treatment groups and between groups was evaluated by (1) capillary counts from representative fields of hematoxylin and eosin stained muscle tissue taken from hind limbs at day 40; (2) digitized arteriograms of ischemic legs at day 40, which were used to quantify the complexity of vascular branching (fractal dimension index) and the total extent of vascularization (vascular density index); (3) measuring capillary refill times in ischemic limbs; and (4) observations of functional and trophic changes in ischemic limbs. Statistical differences between treatment groups were evaluated by one-way ANOVA. Results: Complexity of vascular branching and vascular density were significantly greater ( p < 0.001) in VEGF-treated ischemic limbs compared with NTG- and saline-treated ischemic limbs. By postoperation day 14, all VEGF-treated ischemic limbs had restored capillary refill ( p < 0.001), new hair growth, and greatly improved limb function and appearance. Saline-treated limbs exhibited ischemic changes, with poor capillary refill and negligible limb function. Capillary refill in NTG-treated ischemic limbs did not differ significantly from saline-treated limbs. Ischemic VEGF-treated limbs had significantly more capillaries compared with both ischemic and nonischemic limbs in saline-treated animals ( p < 0.05). Ischemic NTG-treated limbs also had significantly more capillaries compared with ischemic limbs in saline-treated animals ( p < 0.05). Because of high variability, however, capillary counts in VEGF-treated ischemic limbs did not differ significantly from those of contralateral nonischemic limbs, or from capillary counts in either ischemic or nonischemic limbs of NTG-treated rabbits. Conclusions: Controlled release of microgram quantities of VEGF significantly enhanced neovascularization and vascular perfusion in ischemic limbs compared with controls in this rabbit model of partial ischemia. In addition, VEGF-treated ischemic limbs demonstrated near-normal function and appearance, whereas NTG- and saline-treated ischemic controls remained noticeably impaired. This novel approach of VEGF delivery may prove clinically useful either alone or combined with revascularization procedures. (J Vasc Surg 1998;27:886-95.)

Corticotropin-releasing hormone: A biochemical predictor of preterm delivery in a pilot randomized trial of the treatment of preterm labor

We assessed the ability of maternal plasma corticotropin-releasing hormone measurements to predict preterm delivery in the setting of a pilot study comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for preterm labor and to determine the effect of these tocolytics on maternal plasma corticotropin-releasing hormone concentrations. Twenty-six consecutive patients with preterm labor were randomized to tocolytic treatment with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13). Plasma corticotropin-releasing hormone immunoreactivity levels were higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by treatment. Two women in each of the treatment groups delivered within 7 days of the initiation of treatment, two women in the glyceryl trinitrate group were changed to albuterol because of persistence of contractions. Glyceryl trinitrate treatment was associated with significantly fewer maternal side effects. Neither treatment altered umbilical artery Doppler ultrasonographic findings. Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol but may be no more efficacious than albuterol for the treatment of preterm labor. Biologic markers such as plasma corticotropin-releasing hormone levels may be an important method of identifying women at high risk of preterm delivery.

Perinatal transmission of human papillomavirus in infants: relationship between infection rate and mode of delivery

To determine the efficacy of nitroglycerin in easing fetal extraction in elective cesarean deliveries in comparison with placebo and to collect maternal and fetal pharmacologic data after administration of nitroglycerin. This randomized, double-blind clinical and descriptive pharmacokinetic study was carried out at the gynecology departments at Virchow Hospital and Charité Hospital (both university hospitals of Humboldt University, Berlin, Germany) between June 1994 and July 1996 in patients scheduled for elective cesarean delivery under general anesthesia. At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg of nitroglycerin or a physiologic saline solution was administered as an intravenous bolus. Intraoperatively, maternal and neonatal pulse rates and blood pressure were monitored closely. The surgeons estimated reduction in uterine tone and the ease of fetal extraction by means of defined scales. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and from umbilical blood. Ninety-seven patients were included in the statistical evaluation of the study; 32 received 0.25 mg of nitroglycerin, 34 received 0.5 mg of nitroglycerin, and 31 received placebo. The evaluation of the surgeons' estimation revealed no significant difference in ease of fetal extraction (statistical power 0.7) and no significant reduction in uterine tone under treatment with both nitroglycerin dosages in comparison with placebo. Only substance-specific maternal side effects were noted. The neonates' conditions were not affected by administration of nitroglycerin. The median fetal-maternal ratio of venous nitroglycerin plasma levels was approximately 1:400 in the 0.25-mg nitroglycerin group and 1:160 in the 0.5-mg nitroglycerin group. Approximately 11-12 times more nitroglycerin was detected in the venous umbilical branch than in the arterial branch. Administration of nitroglycerin leads to no clinically relevant easing of fetal extraction, at least not in elective cesarean deliveries after the 34th week of gestation. With regard to pharmacokinetics, the measured median fetal-maternal venous nitroglycerin concentration was 1:400 in the 0.25-mg group and 1:160 in the 0.5-mg group.

Role of the l-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction

The role of nitric oxide in hypoxic fetoplacental vasoconstriction (HFPV) was investigated using dually perfused human placental cotyledons. Standard medium (Earle's salt solution with added dextran and L-arginine) was equilibrated with 95 per cent O 2 and 5 per cent CO 2 (maternal side) and 94 per cent N 2 and 6 per cent CO 2 (fetal side). Part 1 consisted of perfusion for 1 h, then maternal perfusate equilibrated with a 95 per cent N 2 and 5 per cent CO 2 for 20 min (hypoxia), and then the original perfusion conditions resumed for 40 min. In part 2, this sequence was repeated with standard medium alone ( n=6), or with added N-nitro- l-arginine methyl ester (L-NAME) ( n=6), nitroglycerin ( n=6), or l-NAME and nitroglycerin ( n=6). When standard medium was used throughout, basal fetal perfusion pressure (30 ± 2 mmHg) and the hypoxia-induced increase in perfusion pressure (18 ± 1 mmHg) did not change significantly between parts I and 2. l-NAME increased basal perfusion pressure from 33 ± 3 to 56 ± 2 mmHg whereas perfusion pressure remained unchanged with l-NAME and nitroglycerin or nitroglycerin alone. The hypoxic vasoconstriction observed during part 1 in the L-NAME (I4 ± 3 mmHg) and the L-NAME with nitroglycerin groups (18 ± 2 mmHg) was abolished during part 2 (to - 4 ± I and 0.4 ± 0.5 mmHg, respectively) whereas nitroglycerin alone significantly blunted the response (21 ± 3 to 6 ± 1 mmHg). Results suggest that a reduction in basal NO release mediates hypoxic fetoplacental vasoconstriction in the perfused human placental cotyledon in vitro.

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

Cardiopulmonary effects of enoximone or dobutamine and nitroglycerin on mitral valve regurgitation and pulmonary venous hypertension

Objective: To compare the cardiovascular and pulmonary effects of the phosphodiesterase III inhibitor enoximone (EN) or a combination of dobutamine (DOB) and nitroglycerin (NTG) before and after mitral valve repair or replacement. Design: Prospective, randomized, controlled clinical study. Setting: University hospital. Participants: Twenty patients with mitral regurgitation and pulmonary venous hypertension scheduled for elective mitral valve surgery. Interventions: Patients fulfilling the inclusion criteria of the study were randomly allocated into a group treated with EN (group 1, n = 10) or DOB and NTG (group 2, n = 10). A cardiopulmonary status was obtained after induction of anesthesia and mechanical ventilation during stable hemodynamic conditions (control). Then the patients received either EN (bolus dose 1.0 mg/kg followed by a continuous infusion of 10 μg/kg/min) or DOB (8.0 μg/kg/min) and NTG (1.0 pg/kg/min) according to the randomization. After a period of 20 minutes, all parameters were measured again. The study drugs were stopped, and cardiac surgery was performed. Infusions of EN (without additional loading dose) or DOB and NTG were started again in the above-described doses 10 minutes before separation from cardiopulmonary bypass (CPB). Respiratory and hemodynamic measurements were made 20 minutes after weaning from CPB and 60 minutes after admission of the patient to the intensive care unit. Measurements and Main Results: Both groups were comparable regarding preoperative and control data. Before mitral valve surgery, cardiac output (CO) and heart rate (HR) increased by 46% ( p < 0.05) and 31% ( p < 0.01) during infusion of EN with minor changes of mean systemic arterial pressure (PSA) and gas exchange. Mean pulmonary arterial pressure (P PA) decreased from 32 ± 11 mmHg to 23 ± 11 mmHg ( p < 0.05). Similar alterations were observed in group 2 (ΔCO + 26%, p < 0.05, ΔHR + 39%, p < 0.01); however, P PA and calculated pulmonary vascular resistance remained unchanged. After separation from CPB, EN and DOB-NTG achieved comparable effects on CO, HR, and P SA, but P PA as significantly lower in group 1. In addition, venous admixture and alveolo-arterial oxygen tension gradient were lower in EN-treated patients. Conclusion: Enoximone or DOB and NTG have comparable effects on CO, P SA, and HR in mitral regurgitation and pulmonary hypertension, but EN is more effective in reducing P PAwithout deterioration of gas exchange.

Effects of Sodium Nitroprusside and Nitroglycerin on the Venous Capacitance during Induced Hypotension in Halothane Anesthetized Dogs

Background : Since a change in venous capacitance significantly alters venous return and thus affects cardiac output, it is important to know the effects of vasodilators on venous capacitance. The purpose of this study was to examine the effects of sodium nitroprusside and nitroglycerin on venous capacitance during induced hypotension in halothane anesthetized dogs. Methods : Fourteen mongrel dogs(SNP group: 7, NTG group: 7), weighing 10∼15 kg, were anesthetized with N2O 1.5L/min-O2 1.5L/min-halothane 0.5vol%. Each dog received only one drug. In dogs anesthetized with N2O-O2-halothane, mean arterial pressure(MAP) was decreased by 15%(mild hypotension) and 30%(deep hypotension) of control value by sodium nitroprusside(SNP) and nitroglycerin (NTG), respectively. Venous capacitance was assessed before and during induced hypotension by measuring mean circulatory filling pressure(MCFP). MCFP was measured after arresting the circulation by tightening of superior vena cava and inferior vena cava snares simultaneously. Results : As compared with MCFP before induced hypotension, MCFP was significantly decreased by SNP at deep hypotension and NTG at mild hypotension and deep hypotension. As compared with MCFP at mild hypotension, MCFP at deep hypotension was significantly decreased by NTG and SNP, respectively. Conclusions : These results suggest that NTG has potent venodilating effect at mild and deep induced hypotension, whereas SNP has venodilating effect only at deep induced hypotension. (Korean J Anesthesiol 1997; 32: 887∼894)

Successful treatment of shoulder pain syndrome due to supraspinatus tendinitis with transdermal nitroglycerin. A double blind study

We have conducted a prospective double blind randomized and placebo controlled clinical study in 20 patients with shoulder pain syndrome caused by supraspinatus tendinitis to determine whether transdermal nitroglycerin (NTG) has analgesic action in this condition. In a randomized manner we used a 5-mg NTG (Nitroplast®) patch per day over 3 days or similar placebo patches applied in the most painful area. Patients were evaluated before treatment was initiated and after 24 and 48 h. The assessment was made blindly by the same clinical investigator. The follow-up showed a significant decrease in intensity of pain at 24 h (7.05 ± 0.4 to 4.5 ± 0.5) and 48 h (2 ± 0.3) in the NTG group ( P < 0.003). No changes were observed in the placebo group. The mean pain duration, activity of the extremity and hours of sleep also improved in the NTG group, with no significant modification in the placebo group. Two patients experienced headache as a side effect 24 h after treatment was started. Patients in the NTG group remained free of symptoms when they were assessed 15 days later. We conclude that NTG is useful in the treatment of shoulder pain syndrome caused by supraspinatus tendinitis and that this treatment could be a useful approach to the management of this common disturbance and probably also in other tendon musculoskeletal disorders.

Effect of nitroglycerin on spinal cord ischemia after thoracic aortic cross-clamping

Thoracic aortic cross-clamping with the use of sodium nitroprusside (SNP) has been shown to cause a decrease in spinal cord perfusion pressure and an increased incidence of paraplegia. Nitroglycerin is frequently used in this setting. This study investigated the effects of nitroglycerin and SNP on spinal cord ischemia. Three-groups of 8 mongrel dogs underwent thoracic aortic cross-clamping for 45 minutes. Proximal pressure was maintained between 95 and 100 mm Hg with SNP, nitroglycerin, or phlebotomy. All animals were neurologically evaluated 24 hours later by a blinded observer, and the findings were confirmed by histopathologic study. Statistical analysis (p value of less than 0.05) of measured hemodynamic data was by analysis of variance and of Tarlov scores, the Mann-Whitney U test. Distal aortic pressures (p < 0.001), Tarlov scores, and spinal cord perfusion pressures (p < 0.01 and p < 0.05 for SNP group and nitroglycerin group, respectively) were significantly higher in the phlebotomy group compared with the SNP and NTG groups. Cerebrospinal fluid pressures were significantly lower in the phlebotomy group compared with the SNP group (p < 0.001). The use of either NTG or SNP was associated with a high incidence of paraplegia. Nitroglycerin appears to be no safer than SNP when used during thoracic aortic cross-clamping.

Coronary vasomotion during dynamic exercise: Influence of intravenous and intracoronary nicardipine

Our aim was to evaluate the influence of a calcium channel blocking agent of the dihydropyridine group (nicardipine) on coronary vasomotion during dynamic exercise. Coronary vasomotion plays an important role in the pathophysiology of myocardial ischemia. Twenty-nine patients with coronary artery disease were studied at rest and during bicycle exercise with the use of biplane quantitative coronary angiography. Twelve patients without pretreatment (group 1) served as control subjects. Seventeen patients (group 2) received nicardipine, either 0.2 mg by intracoronary injection (n = 9) or 2.5 mg intravenously (n = 8) before exercise. In the control group there was exercise-induced vasoconstriction (-29%, p < 0.001) of the stenotic segment but coronary vasodilation (+22%, p < 0.05) of the normal vessel segment. In group 2, nicardipine induced coronary vasodilation of both the normal (+16%, p < 0.001) and the stenotic vessel segment (+35%). During subsequent exercise there was some additional vasodilation of normal (+4%, p = NS) and stenotic arteries (+5%, p = NS). There was no difference between either intracoronary or intravenous nicardipine with regard to vasodilation. Application of sublingual nitroglycerin was associated with significant vasodilation of the normal vessel segment in groups 1 (+18%, p < 0.05) and 2 (+15%, p < 0.001). The stenotic vessels showed a significant increase in percent cross-sectional area after nitroglycerin in groups 1 (+12%, p = NS) and 2 (+51%, p < 0.001). Exertional angina pectoris occurred less frequently in group 2 (18%) than in group 1 (67% [p < 0.005 vs. group 2]); group 2 also had a smaller increase in mean pulmonary artery pressure (+14 vs. +21 mm Hg, p < 0.05). Exercise induces vasoconstriction of stenotic, but vasodilation of normal, coronary vessel segments. Intravenous and intracoronary nicardipine prevent vasoconstriction of stenotic coronary arteries during exercise and exert a significant anti-ischemic effect. The combination of two anti-ischemic drugs, nitroglycerin and nicardipine, has an additive effect on coronary vasomotion that is seen only in the stenotic vessel segment. Thus, the anti-ischemic action of nicardipine is mainly due to a primary effect on coronary vasomotor response rather than to secondary effects such as changes in loading conditions.

Comparison of hemodynamic effects and plasma cyclic guanosine monophosphate of nicorandil and nitroglycerin in patients with congestive heart failure

Hemodynamic tolerance has been observed within several hours of continuous infusion of nitroglycerin (NTG). We examined the hemodynamic parameters as well as femoral arterial and venous cyclic guanosine monophosphate (cGMP) concentrations during intravenous infusion of NTG or nicorandil, a nitrate and potassium channel opener, in patients with congestive heart failure. Doses of NTG or nicorandil were titrated to achieve a ≥25% reduction in pulmonary capillary wedge pressure (PCWP) within 1 hour, and the infusion was maintained at a constant rate for 24 hours. The reduction in PCWP and mean arterial blood pressure was identical after a 1-hour infusion of either NTG or nicorandil. In the NTG group, PCWP and mean blood pressure were not significantly different from the baseline value at 12 hours, but in the nicorandil group PCWP and mean blood pressure remained significantly lower than the preinfusion value for 24 hours. The cGMP production with NTG (assessed by the difference between the plasma arterial and venous cGMP level) paralleled the changes in PCWP, suggesting that the plasma arteriovenous cGMP difference is a biochemical indicator of nitrate tolerance. Although the sustained decrease in PCWP was observed in the nicorandil group, cGMP production with nicorandil was also attenuated at 24 hours of continuous infusion. These findings suggest that the absence of the hemodynamic tolerance of nicorandil, a nitrate and potassium channel opener, is likely due to its action as a potassium channel opener, and not to its nitrate activity.