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Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure

AMERICAN HEART JOURNAL 1999年第2期138卷 285-290页

作者： Weinfeld, MS Chertow, GM Stevenson, LW Harvard Univ Brigham & Womens Hosp Sch Med Cardiovasc DivDept Med Boston MA 02115 USA Harvard Univ Brigham & Womens Hosp Sch Med Renal DivDept Med Boston MA 02115 USA MIT Harvard Mit Div Hlth Sci & Technol Clin Investigator Training Program Beth Israel Deaconess Med Ctr Cambridge MA 02139 USA

Background Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown. Methods we reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of greater than or equal to 2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients. Results ARD, defined as greater than or equal to 25% increase in serum creatinine concentration greater than or equal to 2 mg/dl, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 +/- 16 years vs 51 +/- 13 years;P =.006) and had lower baseline creatinine clearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min;P =.01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70% vs 29%, P =.02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P =.002). Conclusions In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes.

关键词：心房颤动/并发症肌酸酐/血液利尿药/药理学利尿药/治疗应用药物疗法联合肾疾病/病因学肾疾病/病理生理学血管舒张药/药理学血管舒张药/治疗应用成年人老年人女(雌)性人类男(雄)性中年人

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Nitroglycerin is preferable to diltiazem for prevention of coronary bypass conduit spasm

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ANNALS OF THORACIC SURGERY 2000年第3期70卷 883-888页

作者： Shapira, OM Alkon, JD Macron, DSF Keaney, JF Vita, JA Aldea, GS Shemin, RJ Boston Univ Med Ctr Sch Med Dept Cardiothorac Surg Boston MA 02118 USA Boston Univ Sch Med Evans Dept Med Boston MA 02118 USA

Background. Diltiazem is widely used to prevent radial artery spasm after coronary bypass grafting (CABG). However, recent in vitro and in vivo studies have shown that nitroglycerin is a superior conduit vasodilator compared to diltiazem. A clinical comparison of these agents in patients undergoing CABG has not been previously performed. Methods. One hundred sixty-one consecutive patients undergoing isolated CABG with the radial artery were prospectively randomized to 24-hour intravenous infusion of nitroglycerin or diltiazem followed by 6-month treatment with a daily dose of isosorbide mononitrate (n = 84) or diltiazem CD (n = 77). Analyses were performed on "intention-to-treat" basis. Results. Crossovers because of low cardiac output, complete heart block, or sinus bradycardia occurred in 5 patients in the diltiazem group and none in the nitroglycerin group (p = 0.05). Operative mortality (nitroglycerin, 1.2% versus diltiazem, 1.3%), major morbidity (14% versus 16%), perioperative myocardial infarction (1.2% versus 0%), peak serum creatinine phosphokinase MB fraction levels (27 versus 21 U), intensive care unit stay (34 +/- 19 versus 38 +/- 30 hours) and total hospital length of stay (4.7 +/- 1.4 versus 4.7 +/- 1.3 days) were similar (p = not significant for all). Cardiac pacing was required more often in the diltiazem group (28% versus 13%, p = 0.01). Follow-up longer than 2 months was available in 145 patients (90%). Follow-up mortality (nitroglycerin, 1.2%;diltiazem, 1.3%), myocardial infarction (6%, versus 5%), and reintervention (8% versus 6%) rates and average angina class (1.3 +/- 0.7 versus 1.1 +/- 0.4) were similar (p = not significant for all). Thallium stress test obtained in 117 patients showed abnormal perfusion in the radial artery territory in only 4 patients (3%), 2 in each group (P = not significant). Treatment with diltiazem was more costly ($16,340 versus $1,096). Conclusions. Nitroglycerin is preferable to diltiazem for prevention of conduit sp

关键词：住院时间硝酸甘油/投药和剂量硝酸甘油/治疗应用手术后并发症前瞻性研究桡动脉痉挛/预防和控制血管舒张药/投药和剂量血管舒张药/治疗应用男(雄)性中年人

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QRS duration and mortality in patients with congestive heart failure

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AMERICAN HEART JOURNAL 2002年第6期143卷 1085-1091页

作者： Iuliano, S Fisher, SG Karasik, PE Fletcher, RD Singh, SN Vet Affairs Med Ctr Dept Cardiol Washington DC 20422 USA Georgetown Univ Med Ctr Washington DC 20057 USA Vet Affairs Cooperat Studies Program Hines IL USA

Background and Objectives It has been suggested that prolongation of the QRS duration (> 120 ms) is an independent risk factor for mortality in patients with cardiomyopathy. The purpose of this study was to examine the association between QRS duration and survival in patients with heart failure. Methods We performed a retrospective analysis to examine the association between QRS prolongation ( 120 ms) and mortality. The study population included 669 patients with heart failure. Two groups, on the basis of baseline QRS duration < 120 milliseconds or 120 milliseconds, were identified. The groups were compared with respect to total mortality and sudden death. Subgroups were also stratified by right bundle branch block and left bundle branch block, ejection fraction (EF) <30% and greater than or equal to30% to 40%, ischemic and nonischemic cardiomyopathy, amiodarone and placebo. Results Prolonged QRS was associated with a significant increase in mortality (49.3% vs 34.0%, P = .0001) and sudden death (24.8%, vs 17.4%, P = .0004). Left bundle branch block was associated with worse survival (P = .006) but not sudden death. In patients with an EF <30%, QRS prolongation continued to be associated with a significant increase in mortality (51.6% vs 41.1%, P = .01) and sudden death (28.8% vs 21.1%, P = .02). In those with an EF of 30% to 40%, QRS prolongation was associated with a significant increase in mortality (42.7% vs 23.3%, P = .0036) but not in sudden death (13.3% vs 12.0%, P = .625). After adjustment for baseline variables, independent predictors of mortality were found to be prolongation of QRS (P = .0028, risk ratio 1.46) and depressed EF (P = .0001, risk ratio 0.965). Age, type of cardiomyopathy, and drug treatment group were not predictive of mortality. Conclusion QRS prolongation is an independent predictor of both increased total mortality and sudden death in patients with heart failure.

关键词：胺碘酮/治疗应用抗心律失常药/治疗应用束支传导阻滞/死亡率束支传导阻滞/病理生理学猝死心脏/病因学心电描记术预激综合征/死亡率预激综合征/病理生理学预后前瞻性研究回顾性研究危险危险因素血管舒张药/治疗应用老年人女(雌)性人类男(雄)性中年人

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A controlled trial of topical nitroglycerin in a new Zealand white rabbit model of brown recluse spider envenomation

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ANNALS OF EMERGENCY MEDICINE 2001年第2期37卷 161-165页

作者： Lowry, BP Bradfield, JF Carroll, RG Brewer, K Meggs, WJ E Carolina Univ Sch Med Dept Emergency Med Greenville NC 27858 USA

Study objectives: Topical nitroglycerin has been reported to prevent skin necrosis from brown recluse spider bites, but this has never been scientifically tested. This study attempts to assess the effects of topical nitroglycerin on experimental Loxosceles reclusa envenomations. Methods: We performed a randomized, blinded, controlled study in an animal care facility. Twenty-four New Zealand white rabbits were experimentally envenomated by means of subcutaneous injection with 20 mug of brown recluse spider venom. Rabbits were randomized to 1 of 2 experimental groups. The treatment group received 1 in of 2% topical nitroglycerin ointment every 6 hours for 3 days applied directly to the envenomation site. The control group received the vehicle without nitroglycerin. Gross examination of the lesions and measurements of the areas of the lesions were made daily. Creatine phosphokinase (CPK), blood urea nitrogen, creatinine, hemoglobin, and hematocrit levels were measured on days 0, 5, and 10. Lesions were excised after 10 days and examined by a blinded pathologist, who measured the area of necrosis and quantified inflammation and edema using a standard wound-healing score. For all values, mean values plus SD were determined. All comparisons made over multiple time points were assessed for significance by using a repeated-measures analysis of variance followed by Fisher least significant difference and Scheffe post hoc comparisons. A P value of .05 or less was used to determine significance. The Student's t test was used to compare the means of single measures. Significance was determined by using 95% confidence intervals. Comparisons of total area of necrosis were made with the nonparametric Mann-Whitney U test because of the heavy positive skew of the data. Results: Skin necrosis developed in all animals. Mean values of the lesion area were not significantly different over time between the 2 groups of animals. At day 10, the median area of necrosis was 22.3 cm(2) for the

关键词：投药皮肤方差分析蜘蛛毒中毒/血液蜘蛛毒中毒/分类蜘蛛毒中毒/药物疗法蜘蛛毒中毒/病理学血尿素氮肌酸激酶/血液肌酸酐/血液疾病模型动物用药计划表药物评价临床前血细胞比容血红蛋白类/分析炎症坏死硝酸甘油/治疗应用软膏随机分配疾病严重程度指数单盲法统计学非参数时间因素血管舒张药/治疗应用伤口愈合/药物作用动物兔

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Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期35卷 345-351页

作者： Matsubara, T Minatoguchi, S Matsuo, H Hayakawa, K Segawa, T Matsuno, Y Watanabe, S Arai, M Uno, Y Kawasaki, M Noda, T Takemura, G Nishigaki, K Fujiwara, H Gifu Univ Sch Med Dept Internal Med 2 Gifu 500 Japan Gifu Prefectural Hosp Dept Cardiol Gifu Japan

OBJECTIVES This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans. BACKGROUND The ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the KATP channel in the PC effect in humans are still unclear. METHODS Forty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 mu g/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 mu g/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the EGG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined. RESULTS In the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However;the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST. CONCLUSION In human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a KATP channel opener with a nitrate-like effect but not ISDN. This suggests that the Opening of KA

关键词：心绞痛/诊断显像心绞痛/治疗血管成形术气囊冠状动脉冠状血管造影术心电描记术血流动力学注射静脉内缺血预处理心肌/方法硝酸异山梨酯/投药和剂量硝酸异山梨酯/治疗应用尼可地尔/投药和剂量尼可地尔/治疗应用时间因素治疗结果血管舒张药/投药和剂量血管舒张药/治疗应用女(雌)性人类男(雄)性中年人

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DIMETHYL-SULFOXIDE THERAPY IN SUBJECTIVE TINNITUS OF UNKNOWN ORIGIN

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1975年第JAN27期243卷 468-474页

作者： ZUNIGACARO, A MANUEL ARRIARAN CHILDRENS HOSP OTORHINOLARYNGOL SERV SANTIAGO CHILE

In fifteen patients affected by essential nonvibratory tinnitus, local applications in the external auditive canal of 2 ml medicated DMSO spray were made. The spray solution contained DMSO integrated with anti-inflammatory and vasodilatory substances. This application was repeated every four days for a month. At the same time each patient was administered a daily intramuscular injection of a preparation that contained DMSO and a vasodilatory component. The therapeutic effect was evaluated through the subjective modification of the symptom and functional tests of the auditory system. Of the fifteen patients treated, the tinnitus symptom completely disappeared in nine, and did not return during a one-year observation period. The patient's symptoms diminished in two cases, and in four cases the permanent tinnitus became occasional, triggered principally by environmental cold. It is important to note that among the concomitant signs, the five patients with vertigo noted improvement. Hypacusis diminished in three of the six patients affected. Insomnia disappeared in eight and diminished in seven cases. The rise in the average tympanic membrane temperature from 36.8 degrees C before to 37.9 degrees C after treatment was noteworthy. This could indicate an improvement of the blood flow in the inner ear.

关键词：消炎药/治疗应用测听法体温二甲亚砜/治疗应用耳内窥镜检查耳鸣/诊断耳鸣/药物疗法耳鸣/病因学耳鸣/病理生理学鼓膜/病理生理学血管舒张药/治疗应用成年人老年人人类中年人

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Prognostic importance of the oxidized product of catecholamines, adrenolutin, in patients with severe heart failure

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AMERICAN HEART JOURNAL 2003年第5期145卷 926-932页

作者： Rouleau, JL Pitt, B Dhalla, NS Dhalla, KS Swedberg, K Hansen, MS Stanton, E Lapointe, N Packer, M Univ Hlth Network Div Cardiol Toronto ON Canada Mt Sinai Hosp Toronto ON M5G 1X5 Canada Univ Michigan Dept Med Ann Arbor MI 48109 USA St Boniface Gen Hosp Inst Cardiovasc Sci Winnipeg MB R2H 2A6 Canada Gothenburg Univ Dept Med Gothenburg Sweden Columbia Univ Ctr Heart Failure New York NY USA

Objectives The purpose of this study was to assess whether adrenolutin, the inert product of the highly reactive molecules aminochromes, is increased in severe chronic heart failure and whether it is associated with a poor prognosis. Background Experimental evidence suggests that oxidative products of catecholamines, aminochromes, are more cardiotoxic than unoxidized catecholamines and may be increased in heart failure. Methods Adrenolutin was measured at baseline and at 1 and 3 months in 263 patients with chronic New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 22% +/- 7%. Adrenolutin levels were compared with normal levels, and their relation to prognosis was evaluated. Results Baseline adrenolutin was increased (55 +/- 911 pg/mL vs 8.4 +/- 9.1 pg/mL for control, P < .02) and remained increased at 1 month (49 +/- 65 pg/mL). During a mean follow-up of 309 +/- 148 days (22-609 days), 57 patients died. Baseline adrenolutin levels correlated with mortality rates by univariate and multivariate analyses (relative risk 1.06, 95% CI 1.01-1.10 for each 17.9-pg/mL rise, P = .032). Left ventricular ejection fraction (P = .1313) and New York Heart Association class (P = .009) were the only other variables associated with survival. Age, sex, plasma creatinine, plasma N-terminal atrial natriuretic peptide, and plasma norepinephrine levels were not retained in our model. Adrenolutiin levels 1 month after random assignment were not significantly correlated with total mortality rate (P = .061) but were correlated with mortality rate from low output (relative risk 1.14, 95% CI 1.06-1.22, P = .002). Conclusions Plasma adrenolutin is increased in patients with heart failure and correlates with a poor prognosis independent of other important predictors of survival. This finding has potentially important pathophsiologic, prognostic, and therapeutic implications.

关键词：方差分析生物学标记/血液加拿大儿茶酚胺类/血液慢性病吲哚类/血液预后喹啉类/治疗应用参考值每搏输出量血管舒张药/治疗应用老年人女(雌)性人类男(雄)性中年人

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TREATMENT OF ANGINA-PECTORIS - PHARMACOLOGIC APPROACHES

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POSTGRADUATE MEDICINE 1976年第5期60卷 100-106页

作者： ARONOW, WS VET ADM HOSP CARDIOVASC SECTLONG BEACHCA 90822

In choosing a pharmacologic approach to the treatment of angina, the clinician will consider primarily the nitrites, beta-adrenergic blocking agents, and in special circumstances, digitalis. Experience with each of th... 详细信息

关键词：肾上腺素能β受体拮抗剂/治疗应用心绞痛/药物疗法洋地黄糖甙类/治疗应用注射静脉内亚硝酸盐类/治疗应用硝酸甘油/投药和剂量硝酸甘油/治疗应用普萘洛尔/治疗应用时间因素血管舒张药/治疗应用人类

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Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

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AMERICAN HEART JOURNAL 2002年第1期144卷 108-114页

作者： Sondergaard, E Moller, JE Egstrup, K Svendborg Hosp Dept Med Svendborg Denmark

Background It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Halter monitoring. We sought to describe the correlation between daily life ischemia and signs of endothelial dysfunction as assessed by means of brachial vasoreactivity. Methods We included in the study 13 1 patients with documented ischemic heart disease and a serum cholesterol level of greater than or equal to5 mmol/L before the institution of lipid-lowering treatment and dietary intervention. Results Satisfactory 48-hour Halter recordings and ultrasound scans of the brachial artery were obtained in 119 patients. During 5712 hours of ambulatory monitoring, 181 episodes of transient ST-segment depression with a mean duration of 52 +/- 66 minutes were recorded in 3 1 patients. The mean percentage dilatation of the brachial artery after occlusion was 4.38% +/- 5.66%;after nitroglycerin administration, it was 13.86% +/- 7.06%. By means of Spearman correlation analysis, the number of ischemic episodes and degree of flow-mediated vasoclilatation and nitroglycerin-mediated vasoclilatation were significantly negatively correlated (r = -0.249, P =.006 and r = -0.302, P =.02, respectively). In a linear regression model, the presence of ischemic episodes was a significant predictor of impaired flow-mediated vasodilatation (beta = -3.31, P <.01), even after the adjustment for vessel size and classic cardiovascular risk factors. Conclusions These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium.

关键词：肱动脉/病理生理学肱动脉/超声检查心电描记术心电描记术便携式内皮血管/病理生理学心脏功能试验高胆固醇血症/病理生理学高胆固醇血症/治疗心肌缺血/病理生理学心肌缺血/治疗硝酸甘油/治疗应用血管舒张血管舒张药/治疗应用老年人女(雌)性人类男(雄)性中年人

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Cilostazol pharmacokinetics after single and multiple oral doses in healthy males and patients with intermittent claudication resulting from peripheral arterial disease

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CLINICAL PHARMACOKINETICS 1999年第2-Sup期37卷 1-11页

作者： Bramer, SL Forbes, WP Mallikaarjun, S Otsuka Amer Pharmaceut Inc Dept Clin Pharmacokinet Pharmacodynam & Metab Rockville MD 20850 USA

Objective: To study the pharmacokinetics of cilostazol following single oral administration of 50 to 200mg in healthy young males, and after repeated oral administration of 100mg every 12 hours to patients with peripheral arterial disease (PAD). Design: The healthy male single dose study was a single-centre, randomised sequence, open-label, incomplete block, 3-period, 4-treatment, crossover design. The patient study was a single-centre, multiple dose, open-label study. Study Participants: 20 healthy nonsmoking male volunteers were enrolled and successfully completed the single dose study. 26 patients (21 males, 5 females) with intermittent claudication resulting from PAD were enrolled and completed the single/multiple dose study. Main Outcome Measures: Noncompartmental pharmacokinetic parameters, the area under the plasma concentration-time curve from zero to the time of last measurable plasma concentration, and maximum plasma concentration. Results: Peak plasma concentrations of cilostazol occurred about 3 hours after drug administration and then declined biexponentially with concentrations detectable (>20 mu g/L) in the plasma for at least 36 hours postdose. The apparent elimination half-life of cilostazol (approximately 11 hours) was similar after a single dose or after multiple doses, with steady state being reached within 4 days. Cilostazol accumulated 1.7-fold following multiple dose administration. The apparent volume of distribution (V-2/F;2.76 L/kg) suggested extensive distribution of cilostazol in the tissues. The oral clearance of cilostazol (CL/F;0.18 L/h/kg) was much lower than liver blood flow, indicating a low extraction ratio drug, and hence low probability of a significant first-pass effect. None of the administered doses were recovered in the urine as unchanged cilostazol, suggesting that metabolism, rather than urinary excretion, is the major elimination route. Following single oral doses of 50 to 200mg, the plasma concentrations of cilostazol and

关键词：投药口服方差分析曲线下面积交叉研究用药计划表间歇性跛行/药物疗法间歇性跛行/病因学代谢清除率外周血管疾病/并发症外周血管疾病/药物疗法四唑类/投药和剂量四唑类/血液四唑类/药代动力学四唑类/治疗应用组织分布血管舒张药/投药和剂量血管舒张药/血液血管舒张药/药代动力学血管舒张药/治疗应用女(雌)性人类男(雄)性

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