Ovariectomy aggravates hypersensitivity reactions to paclitaxel in rats.
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The incidence of hypersensitivity reactions is still a matter of serious concern during chemotherapy with paclitaxel, particularly in patients with ovarian cancer. We recently reported that intravenous injection of paclitaxel causes acute lung injury characterized by vascular hyperpermeability, edema and respiratory dysfunction in rats. In the present study, we investigated the influence of ovariectomy on the paclitaxel-induced acute lung injury in rats. Ovariectomy worsened paclitaxel-induced acute lung injury, which was reversed by 17beta-estradiol. The mRNA expression for endothelial nitric oxide synthase was reduced in lungs of ovariectomized rats. To determine the role for nitric oxide, we examined the effects of several agents that modulate nitric oxide concentration on the pulmonary response to paclitaxel. In ovary-intact rats, a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester exaggerated paclitaxel-induced acute lung injury, while nitric oxide donors such as sodium nitroprusside and isosorbide dinitrate attenuated the lung injury. Sodium nitroprusside was also effective in alleviating the paclitaxel-induced acute lung injury in ovariectomized rats. These findings suggest that ovariectomy enhances the susceptibility to paclitaxel hypersensitivity, in which decrease in estrogen and subsequent reduction in nitric oxide synthesis may be involved. (+info)
Long-term effectiveness of extended-release nitrate for the treatment of systolic hypertension.
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Isosorbide mononitrate (ISMN) is effective in the short-term for decreasing systolic blood pressure, pulse pressure, and pulse wave reflection in patients with systolic hypertension. To determine whether tolerance negates the efficacy of this nitrate in the long-term, a placebo-controlled study was performed in which ISMN was withdrawn briefly in a group of patients (n=16) who had received extended-release ISMN 60 to 120 mg once daily for 16 to 109 months. Blood pressure and wave reflection were determined by 24-hour ambulatory recorder and tonometer, respectively. During a 4-hour delay of the regular morning dose of ISMN, mean systolic blood pressure was higher than with the regular ISMN dosing schedule (P<0.0001). The maximum placebo-active difference was 16+/-4 mm Hg. The corresponding difference in augmentation index (a measure of pulse wave reflection) corrected for heart rate was 25+/-4% (P<0.001). The difference in pulse pressure was 13+/-3 mm Hg (P<0.001). There was no significant difference in diastolic blood pressure. For a subgroup (n=12) in which the effects of a single ISMN dose had been determined at the initiation of regular ISMN therapy, the mean change in augmentation index was of similar magnitude to that observed in their initial study. Thus, tolerance does not seriously diminish the antihypertensive efficacy of ISMN used as adjunct therapy in the chronic treatment of systolic hypertension. This agent lowers systolic blood pressure sufficiently to achieve therapeutic goal in some patients refractory to conventional treatment regimens. (+info)
Myocardial protective effects of nicorandil during percutaneous coronary intervention in patients with unstable angina.
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BACKGROUND: The purpose of the study was to prospectively evaluate the protective effect of nicorandil during percutaneous coronary intervention (PCI) in patients with unstable angina (UAP). METHODS AND RESULTS: Two hundred patients (61+/-10 year-old, male 143) diagnosed with UAP at an emergency medical center were randomly assigned to 2 groups: intravenous isosorbide dinitrate, Group I (n=100), or intravenous nicorandil, Group II (n=100). PCI was performed 12-48 h after infusion of each agent. Serum concentrations of creatine kinase-MB (CK-MB), cardiac troponin T (cTnT), and I (cTnI) were measured before and 6, 12, 24 h after PCI. Patients with non-coronary chest pain, requiring emergency coronary angiogram, temporary pacemaker or glycoprotein IIb/IIIa receptor blocker were excluded. PCI was successfully performed in 96 patients (Group I=54, 61.7+/-8.2 years, 32 males; Group II=42, 60.4+/-11.7 years, 27 males). No significant differences in clinical or coronary angiographic characteristics were observed between the 2 groups. The concentration of CK-MB was elevated in 9 patients (17%) of Group I and 6 (14%) of Group II, cTnT in 16 (30%), 6 (14%) and cTnI in 25 (46%), 9 (21%) after PCI. Elevation of any troponin was less frequent in Group II [28/54 (52%) vs 10/42 (24%) patients, p=0.01]. Major adverse coronary events during the 6-month clinical follow-up occurred in 9 (17%) of Group I and 5 patients of Group II (12%, p=NS). Follow-up echocardiography revealed lower left ventricular ejection fraction in Group I than in Group II (65.4+/-7.2% vs 71.0+/-6.7%, p=0.03). CONCLUSION: Nicorandil has a myocardial protective effect during PCI in patients with UAP. (+info)
Nitroester drug's effects and their antagonistic effects against morphine on human sphincter of Oddi motility.
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AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility. METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry. A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group, isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually. RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95+/-7.49 mmHg to 5.92+/-4.04 mmHg (P<0.05) evidently after application of PTN. BPOS increased from 7.37+/-5.58 mmHg to 16.60+/-13.87 mmHg, SOCA increased from 54.09+/-38.37 mmHg to 100.70+/-43.51 mmHg, SOF increased from 7.15+/-3.20 mmHg to 10.38+/-2.93 mmHg and CBDP increased 3.75+/-1.95 mmHg to 10.49+/-8.21 mmHg (P<0.01) evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN, SOCA and SOF decreased separately from 100.64+/-44.99 mmHg to 66.17+/-35.88 mmHg and from 10.70+/-2.76 mmHg to 9.04+/-1.71 mmHg (P<0.05) markedly. CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant. (+info)
Quantitative coronary angiogram analysis: nifedipine retard versus angiotensin-converting enzyme inhibitors (JMIC-B side arm study).
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This study was performed to compare the effects of nifedipine retard and angiotensin-converting enzyme (ACE) inhibitors on the progression of coronary atherosclerosis by means of quantitative coronary angiogram. Coronary angiogram was performed before the start of the study and during the 3-year treatment period. This study was conducted on the assumption that possible coronary vasodilation, which may be caused by nifedipine, was excluded by administration of sufficient isosorbide dinitrate. The changes from the baseline in the minimum lumen diameter of the coronary artery in all measured segments were negligible in the nifedipine group (+0.02+/-0.27 mm; P=0.543), whereas they were significantly reduced in the ACE inhibitor group (-0.12+/-0.27 mm; P<0.001), with a significant difference observed between the groups (P=0.002). The number of progressors in the nifedipine group was significantly lower than that in the ACE inhibitor group (P=0.019), and there was also a significant difference between the groups in the number of patients in whom > or =1 lesion developed after treatment (P=0.040). However, the changes of minimum lumen diameter stratified by baseline percent diameter stenosis demonstrated that progression of coronary atherosclerosis was suppressed in the nifedipine group for lesions with a percent diameter stenosis of < or =40 but was suppressed in both groups for those with a percent diameter stenosis of > or =41. This study suggests that nifedipine retard and ACE inhibitors may be effective in suppression of progression of coronary atherosclerosis, and that nifedipine in particular may be effective for mild to moderate stenosis. (+info)
Hemodynamic assessment of intravenous Isosorbidi Dinitras in coronary heart disease.
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This study investigates the systemic hemodynamic effects of intravenous Isosorbidi Dinitras, Isoket (ISDN) in 20 patients with coronary arterial disease to test the validity of the hypothesis concerning the relief of myocardial ischemia. Patients were eligible for the study if they had angina with coronary angiographic records or if they were cases of post-myocardial infarction. Before and after ISDN infusion the following measurements were recorded or calculated: heart rate (HR); systolic, diastolic and mean aortic pressure (ASP, ADP, AP); systolic and mean pressure of the left ventricle (LVSP, LVP); end-diastolic pressure in the LV (LVEDP); left ventricular contractility (dp/dt max); the double products (DP, HR x LVSP) and myocardial perfusion pressure in the LV (LVPP). After ISDN the ASP, AP and LVEDP decreased while HR, ADP, dp/dt and DP showed no significant changes. However, LVEDP was significantly decreased from 20 +/- 7 to 12 +/- 5 mmHg (P less than 0.01) with increased LVPP from 49 +/- 12 to 56 +/- 13 mmHg (P less than 0.01), which may be favourable for the relief of myocardial ischemia. There was no significant change of dp/dt max with decreased LVEDP after ISDN. It is suggested that the left ventricle can maintain normal performance at lower intracardial volume (preload) in these patients. (+info)
The effect of a combined treatment with propranolol and isosorbide-5-mononitrate on Doppler ultrasound parameters in patients with cirrhosis and portal hypertension.
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OBJECTIVES: The objectives of this study were to compare the effect of the treatment with propranolol to that with propranolol and isosorbide-5-mononitrate in portal hypertension, as assessed by Doppler ultrasound parameters in patients with cirrhosis. METHODS: A prospective study of two groups, each of 30 patients with cirrhosis Child-Pugh A was performed. In one group 40 mg/day propranolol were administered for 6 months and in the other, a combined treatment with propranolol 40 mg/day and isosorbide-5-mononitrate 40 mg/day was administered for 6 months. In all patients the presence of esophageal varices was confirmed by upper gastrointestinal endoscopy and abdominal ultrasonography and Doppler ultrasonography of the portal vein was performed. The patients were monitored for: the velocity of blood flow in the portal vein, the cross sectional area of the portal vein and the portal vein congestion index. Data analysis used t-Student test, Pearson and Spearman correlation. A p value of <0.05 was considered to be significant. RESULTS: A significant decrease of all parameters after 6 months was observed in the group with combined therapy with propranolol and isosorbide-5-mononitrate (p<0.05). The relative decrease of the cross sectional area of the portal vein and of the portal vein congestion index was more important when patients had higher initial values of the two parameters, indicating an increased hemodynamic impairment (Pearson, p<0.001). In patients treated only with propranolol, the relative decrease correlated with its initial value for all parameters. CONCLUSION: The combined therapy with propranolol and isosorbide-5-mononitrate proved to be superior to the mono-therapy with propranolol in decreasing the hemodynamic parameters in portal hypertension, probably by an additive effect. (+info)
Use of simultaneous pressure and velocity measurements to estimate arterial wave speed at a single site in humans.
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It has not been possible to measure wave speed in the human coronary artery, because the vessel is too short for the conventional two-point measurement technique used in the aorta. We present a new method derived from wave intensity analysis, which allows derivation of wave speed at a single point. We apply this method in the aorta and then use it to derive wave speed in the human coronary artery for the first time. We measured simultaneous pressure and Doppler velocity with intracoronary wires at the left main stem, left anterior descending and circumflex arteries, and aorta in 14 subjects after a normal coronary arteriogram. Then, in 10 subjects, serial measurements were made along the aorta before and after intracoronary isosorbide dinitrate. Wave speed was derived by two methods in the aorta: 1) the two-site distance/time method (foot-to-foot delay of pressure waveforms) and 2) a new single-point method using simultaneous pressure and velocity measurements. Coronary wave speed was derived by the single-point method. Wave speed derived by the two methods correlated well (r = 0.72, P < 0.05). Coronary wave speed correlated with aortic wave speed (r = 0.72, P = 0.002). After nitrate administration, coronary wave speed fell by 43%: from 16.4 m/s (95% confidence interval 12.6-20.1) to 9.3 m/s (95% confidence interval 6.5-12.0, P < 0.001). This single-point method allows determination of wave speed in the human coronary artery. Aortic wave speed is correlated to coronary wave speed. Finally, this technique detects the prompt fall in coronary artery wave speed with isosorbide dinitrate. (+info)