硝酸异山梨酯静脉泵入治疗高血压伴心力衰竭

目的:研究硝酸异山梨酯直接静脉泵入治疗高血压心力衰竭的疗效及安全性。方法:将60例高血压伴心力衰竭患者随机分为①硝酸异山梨酯组30例和硝普钠组30例。通过输液泵直接静脉泵入硝酸异山梨酯20 mg(20 ml),②硝普钠组30例静脉滴注硝普钠25 mg 250ml 0.9%氯化钠注射液,两组均根据血压调整剂量。结果:硝酸异山梨酯组疗效略高于硝普钠组,但两组间总有效率比较差异无统计学意义(P>0.05)。硝酸异山梨酯组不良反应发生率11.63%,明显低于硝普钠组(P<0.05)。结论:硝酸异山梨酯原液直接经静脉泵入治疗高血压心力衰竭安全有效。     

尼可地尔治疗冠心病心绞痛31例临床观察

目的：观察尼可地尔与消心痛治疗冠心病心绞痛的疗效。方法：65例冠心病心绞痛患者随机分为2组。尼可地尔为A组31例，消心痛为B组34例，治疗2个月，观察临床症状、心电图变化。结果：治疗2个月后，两组患者心肌缺血发作时间、次数减少。心电图变化差异有显著性（P〈0．05），明显优于消心痛组。结论：尼可地尔改善冠心病稳定型心绞痛患者的心肌缺血效果优于消心痛。     

硝酸异山梨酯静脉滴注对冠心病病人血管内皮功能的影响

目的 :观察硝酸异山梨酯静脉滴注对冠心病病人血管内皮功能的影响。方法 :6 4例冠心病病人随机分为 2组 ,硝酸异山梨酯组 (32例 )予硝酸异山梨酯 2 0mg ,iv ,gtt,qd ;复方丹参组 (32例 )予复方丹参 2 0mL ,iv ,gtt ,qd。均连续用药 4wk。结果 :硝酸异山梨酯组治疗后 6 酮前列腺素F1α(99± 6 9)ng·L- 1]、一氧化氮 [(134± 88) μmol·L- 1]均较治疗前 [(75± 5 8)ng·L- 1,(91± 85 ) μmol·L- 1]上升 ,血组织型纤溶酶原激活物抑制物 [(0 .6 4± 0 .2 7)×10 3AU·L- 1vs (0 .5 4± 0 .2 4 )× 10 3AU·L- 1]、凝血烷B2 [(111± 2 31)ng·L- 1vs (71± 14 6 )ng·L- 1]、内皮素 1[(98± 6 2 )ng·L- 1vs (80± 4 7)ng·L- 1],浓度均下降 (P <0 .0 5 ,P <0 .0 1)。复方丹参组无此变化 (P >0 .0 5 )。结论 :硝酸异山梨酯静脉滴注可改善冠心病病人血管内皮功能     

四逆汤防治冠心病心绞痛的临床研究

目的：观察四逆汤防治冠心病心绞痛的临床疗效。方法：将辨证为阳虚或寒凝的63例冠心病心绞痛患者随机分为四逆汤治疗组(35例)和消心痛对照组(28例),比较两组在症状、ECG、心肌耗氧、心功能等方面的疗效。结果：四逆汤在改善冠心病心绞痛临床症状、ECG、降低心绞痛发作频率、减少硝酸甘油用量等方面与消心痛相似,但在降低心肌耗氧、改善心功能方面,四逆汤较优。结论：四逆汤可用于冠心病心绞痛的防治,是阳虚寒凝型冠心病心绞痛的有效方药。     

静脉注射硝酸酯类对急性心肌梗死早期左心室舒张功能的影响

目的观察硝酸甘油(NTG)及二硝基山梨醇酯(IDN)在急性心肌梗死(AMI)患者对左心室舒张功能的疗效。方法根据超声心动图二尖瓣血流频谱将AMI患者28例分为3组:2>E/A>1(A组);E/A<1(B组);E/A>3(C组)。用二尖瓣和肺静脉血流频谱作为观察指标。结果二尖瓣:静注NTG或IDN后,C组可显著降低E/A比值及E峰下降速率(均P<0.05);而A,B2组患者对上述参数均无影响;肺静脉:静注IDN后,3组均可使肺静脉血流频谱S/D比值显著升高(均P<0.05),Ar负向峰值速率显著下降(均P<0.05);但NTG对这2项参数无明显影响。结论在AMI早期,静脉注射硝酸甘油和二硝基山梨醇酯均可改善左心室舒张功能。     

胺碘酮治疗无症状心肌缺血伴室性早搏的临床疗效

目的 :观察胺碘酮治疗冠心病无症状心肌缺血 (SMI)伴室性早搏 (VPB)的疗效和安全性。方法 :将 92例患者分成胺碘酮组、硝酸异山梨酯组和普罗帕酮组。疗程 38d ,用DCG观察SMI和VPB改善情况。结果 :与治疗前比较 ,胺碘酮组SMI发作次数明显降低 [(2 3± 1 0 )vs (7 7± 4 3) ,P <0 0 1],持续时间明显缩短 [(3 7± 1 8)minvs (19 4± 12 4 )min ,P <0 0 1],胺碘酮组疗效较硝酸异山梨酯组显著提高 (P <0 0 5 ) ;胺碘酮组治疗VPB有效率 90 6 %,较普罗帕酮疗效好 (P <0 0 5 )。未见严重不良反应。结论 :胺碘酮治疗SMI伴VPB有确切疗效和安全性。     

Bioequivalence of a sustained-release isosorbide dinitrate formulation at steady-state

Isosorbide 2,5-dinitrate and its pharmacologically active metabolites, isosorbide 2-nitrate and isosorbide 5-nitrate, in plasma accumulated to the predicted steady-state after five consecutive oral doses of sustained-release tablets containing 40 mg isosorbide dinitrate at 12-h intervals and after five consecutive oral doses of reference standard-release tablets containing 20 mg at 6-h intervals to 12 subjects in a crossover study. The comparative bioavailability of isosorbide dinitrate, isosorbide 2-nitrate and isosorbide 5-nitrate from the sustained-release tablet was 110 per cent (p greater than 0.05), 89 per cent (p greater than 0.05), and 89 per cent (p less than 0.05), respectively, of that from the reference standard-release tablet. The isosorbide dinitrate plasma level data were the more variable, as expected for a drug of low systemic availability subject to extensive first-pass elimination. The posterior probability that the true bioavailability of isosorbide dinitrate was included within the usually accepted limits of 80-120 per cent was 0.74, a value which is probably insufficient to justify claims of bioequivalence with the reference formulation in respect of extent of availability. In contrast, the posterior probability that the bioavailability of the metabolites isosorbide 2- and 5-nitrate was included within these limits was 0.90 and 0.98, respectively. On the basis of the mononitrate data, these two formulations may be judged bioequivalent in respect of extent of availability despite a formal statistically significant formulation-related effect in the analysis of variance of the isosorbide 5-nitrate bioavailability data. Claims of bioequivalence of isosorbide dinitrate sustained-release formulations may be more economically justified by analysis of the mononitrate plasma concentrations, although concentrations of the formulated parent dinitrate should also be known.     

Isosorbide dinitrate does not interfere with heparin anticoagulation:

The possible nitrate-induced heparin resistance was studied intraoperatively in 40 patients undergoing coronary artery bypass grafting. The patients were randomized to receive a continuous infusion of placebo, nitroglycerin (0.5 μg kg^-1 min^-1) or isosorbide dinitrate (0.5 or 2.5 μg kg^-1 min^-1). After the infusion had been administered, prior to the institution of cardiopulmonary bypass, for at least 60 min, porcine intestine heparin 300 I.U. kg^-1 (as divided in two consecutive doses of 100 and 200 I.U. kg^-1, respectively) was administered to achieve systemic anticoagulation. Activated coagulation time values and plasma heparin anti-X_a activity showed no significant differences between the groups before and after the administration of heparin. It is concluded that in doses given in the present study, organic nitrates do not interfere with the anticoagulation effect of large doses of heparin required for the conduction of cardiopulmonary bypass.     

Response to changing plasma concentrations of isosorbide-bound NO2 during acute and sustained treatment with isosorbide dinitrate in patients with coronary artery disease

BACKGROUND: The mechanisms behind development of tolerance to nitrate effects during sustained, asymmetric isosorbide dinitrate (ISDN) therapy are not fully understood. HYPOTHESIS: The study was undertaken to investigate the changes of the relationships between left ventricular (LV) function and plasma concentrations of ISDN and its vasoactive metabolites (2- and 5-ISMO) during acute and sustained, asymmetric ISDN therapy. METHODS: Left ventricular function and plasma concentrations of ISDN, 2- and 5-isosorbide mononitrates (P-ISDN, P-2- and 5-ISMO) were measured at rest and at supine exercise before and for 4 h after peroral 30 mg ISDN in 15 patients with coronary artery disease, all with initial exercise pulmonary artery wedge pressure (PAWP) > 25 mmHg. Seven patients were untreated (acute group), while eight received 30 mg ISDN b.i.d. for 2 weeks before the invasive study. P-ISDN and the concentration of available isosorbide-bound nitrate (NO2) in plasma (P-ISDN.2 + P-2-ISMO + P-5-ISMO) (P-NO2) were used as measures of the nitric oxide (NO) offer to the tissues. RESULTS: Throughout the study, after administration of medication, all plasma concentrations, in particular P-ISDN, were higher in the chronic than in the acute group. Peak P-ISDN was reached after 15 min in the chronic group and after 25 min in the acute group, while P-2- and 5-ISMO reached maximum only after 40 min in both groups. At rest, the full effect on PAWP was observed after 10 min in both groups, but at markedly higher levels of P-ISDN and P-NO2 in the chronic group. Afterward, no further changes in PAWP were observed. During exercise, 1 h after medication, PAWP and stroke index to PAWP ratio (SI/PAWP) were normal in both groups. Thereafter, at slowly declining P-NO2, PAWP rose and SI/PAWP declined toward the initial level in the chronic group, but remained unchanged in the acute group, in spite of higher P-NO2 and greater NO release in the former. CONCLUSIONS: Patients receiving sustained, asymmetric 30 mg ISDN b.i.d. dosing had the same immediate beneficial effects on LV function during exercise after a morning dose as did untreated patients. However, in spite of higher P-NO2 and higher rate of NO release during sustained treatment, the effects deteriorated gradually 2 to 3 h after medication. The changes in metabolism and/or distribution of isosorbide-bound NO2 may possibly be part of the tolerance induced by long-term treatment, even with asymmetric dosing.     

COMPARING BALLOON DIAMETER ON PERFORMING ENDOSCOPIC PAPILLARY BALLOON DILATATION WITH ISOSORBIDE DINITRATE DRIP INFUSION FOR REMOVAL OF BILE DUCT STONES

Background: Endoscopic papillary balloon dilatation (EPBD) is one of the methods to remove bile duct stones. EPBD might preserve the function of the sphincter of Oddi despite the potential risk of acute pancreatitis. There are only a few reports of EPBD reducing the risk of acute pancreatitis and, at same time, preserving the function of the sphincter of Oddi. Methods: We performed EPBD for bile duct stone removal in 60 patients using two balloons with different diameters. Patients were randomized to EPBD with a 6 mm balloon (n = 30) or an 8 mm balloon (n = 30). In both groups, isosorbide dinitrate (ISDN) was infused in a rate of 5 mg/h while low pressure EPBD were being performed. The pressure of the sphincter of Oddi was observed before and after the EPBD procedures. Also, serum amylase level after EPBD was observed for both groups. Results: Serum amylase level of the 6 mm group was signi?cantly higher than that of the 8 mm group (P < 0.05). Acute pancreatitis occurred in two patients ( 6.7%) in the 6 mm group whereas no case was observed for the 8 mm group. The rates of duct clearance were 93% in the 6 mm group and 100% in the 8 mm group. Stone removals were dif?cult in seven cases with 6 mm balloon dilatations due to the narrow ori?ces of the papilla. In the 6 mm group, there was no signi?cant difference between the basal sphincter of Oddi pressure (BSOP) and the phasic sphincter of Oddi pressure (PSOP) before and after EPBD. However in the 8 mm group, the BSOP observed after the EPBD procedure was signi?cantly higher than BSOP before the treatments. Within this group, BSOP values after EPBD were preserved by approximately 80% of the BSOP values before the treatments. In contrast, there was no signi?cant difference in PSOP before and after the treatments. Regarding the stone numbers, no signi?cant difference was observed in BSOP before and after the treatments for the 6 mm group with less than two stones. Also, as for stone size, no signi?cant difference was observed in BSOP before and after the treatments for the 6 mm group with stones of less than 6 mm in diameter. Conclusion: We are now conducting EPBD with ISDN infusion using a 6 mm balloon for a patient who has less than two stones with size not exceeding 6 mm in diameter. An 8 mm balloon is used for a patient with more than two stones or a stone greater than 6 mm in size.