Renal and cardiac function during α 1 -β-blockade in congestive heart failure

The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and &#103 -blockade. The need for control of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined &#102 1 - &#103 -blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function. Methods : Fourteen patients treated for moderate to severe CHF with diuretics and ACE inhibitors were investigated at baseline, after 4 months of maximum carvedilol treatment and after withdrawal of carvedilol. Results : Carvedilol lowered blood pressure and heart rate but increased left and right ventricular ejection fractions without changing cardiac output or pulmonary blood volume. At the same time, a minor fall was seen in glomerular filtration rate (GFR), but renal blood flow was unchanged and effective renal plasma flow slightly increased. Carvedilol also lowered the plasma levels of angiotensin II and aldosterone. All changes were reversed after withdrawal of carvedilol. Conclusions : Carvedilol augments ACE-inhibitor-induced vasodilation by lowering blood pressure, and angiotensin II beside reducing heart rate. The heart adapts to the haemodynamic alterations without changes in cardiac output and pulmonary blood volume. GFR is slightly lowered despite no changes in renal blood flow and a slight increase in effective renal plasma flow. The study emphasizes the need for control of renal function during treatment with carvedilol in patients with CHF.     

卡维地洛在充血性心力衰竭治疗中的应用

目的研究新型β-受体阻滞剂国产卡维地洛(Carvedilol)对充血性心力衰竭患者心功能及神经内分泌激素的影响。方法40例住院慢性充血性心力衰竭患者,双盲随机分为安慰剂组及治疗组。治疗组在常规治疗基础上加服卡维地洛,安慰剂组在常规治疗基础上加服用等量安慰剂片。观察心率、血压、6 min步行距离、心功能级别、超声心动图测量左室射血分数(LVEF)、左室内径(LVDd),血浆去甲肾上腺素(NE)、肾素(PRA)、血管紧张素Ⅱ(AngⅡ)及血生化指标,并分别于治疗后1个月,3个月复查。结果心力衰竭患者血浆中NE、PRA、AngⅡ水平均较正常安慰剂组明显升高(P<0.01),且心衰越重,升高越明显。治疗组经治疗后血浆NE、PRA、AngⅡ水平均较治疗前明显下降(P<0.01),且心衰恶化发生率亦明显低于安慰剂组,严重心脏事件发生率亦较安慰剂组降低了76%(P=0.028),6 min步行距离、心功能级别均有明显改善,LVEF明显提高,LVDd缩小。结论卡维地洛能降低心衰患者血循环去甲肾上腺素、肾素及血管紧张素水平,改善慢性充血性心力衰竭患者的生活质量,改善心功能。     

卡维地洛与美托洛尔治疗高原慢性充血性心力衰竭疗效的对比研究

目的 比较卡维地洛与美托洛尔治疗高原慢性心力衰竭(CHF)的疗效.方法 90例CHF患者随机分成3组:常规治疗组(20例)给予血管紧张素转化酶抑制剂、利尿剂、地高辛等常规心力衰竭治疗.美托洛尔组(34例)、卡维地洛组(36例)在上述治疗基础上分别给予美托洛尔50 mg,2次/d;卡维地洛25 mg,2次/d口服.随访半年,治疗前、后采用超声心动图测定患者心功能并进行疗效观察.结果 治疗后美托洛尔组、卡维地洛组左心室舒张末期内径(LVEDD)[分别为(57.3±6.5)、(57.2±6.9)mm]和左心室收缩末期内径(LVSED)[分别为(46.6±7.0)、(44.0±6.9)mm]显著低于常规治疗组[分别为(64.7±9.1)、(53.4±9.8)mm],左心室射血分数(LVEF)显著高于常规治疗组[分别为(47.5±8.1)%、(52.9±8.5)%、(42.8±9.2)%](P均＜0.05).卡维地洛组LVEF改善优于美托洛尔组(P＜0.05).死亡情况:常规治疗组4例,美托洛尔组1例,卡维地洛组无死亡.美托洛尔组、卡维地洛组病死率均明显低于常规治疗组(P均＜0.05).结论 美托洛尔、卡维地洛均可明显改善高原CHF患者心功能.卡维地洛疗效及耐受性略优于美托洛尔.

Abstract：

Objective To compare the effect of carvedilol and motoprolol on high altitude chronic congestive heart failure (CHF). Methods Ninety patients with high altitude chronic CHF were divided into three groups randomly:Twenty patients in the regular treatment group treated with angiotensin-converting enzyme inhibitor (ACEI) ,diuretics and digoxin; motoprolol (50 mg twice daily) was given in the motoprolol group( 34cases) additional to regular treatment; carvedilol (25 mg twice daily) was given in the carvedilol group(36cases ) additional to regular treatment. All the patients were followed up for six months and measured the changes of cardiac function by echocardiography. Results Left ventricular end-diastolic dimension (LVEDD) was ( 57. 3 ± 6. 5 ) mm and (57.2 ± 6. 9) mm in the carvedilol group and the motoprolol group respectively, and left ventricular end-systolic dimension (LVESD) was (46. 6 ± 7.0) mm and (44. 0 ± 6. 9 ) mm in the carvedilol group and the motoprolol group respectively, which were all significantly smaller than that in the regular treatment group ([64.7 ±9. 1]mm and [53.4 ±9.8]mm for LVEDD and LVESD,respectively) (Ps ＜0.05). Left ventricular ejection fraction (LVEF) in the carvedilol group and the motoprolol group ( [47.5 ± 8. 1] % and [52. 9 ±8.5] % ,respectively) was higher than that in regular treatment group( [42. 8 ±9. 2]% ) (Ps ＜0. 05).The improvement of LVEF in the carvedilol group was better than that in the motoprolol group (P ＜ 0. 05 ). One case died in the motoprolol group and no death in the carvedilol group,4 cases died in the regular treatment group,the mortality in the motoprolol group and the carvedilol group was significantly lower than that in the regular treatment group. Conclusion Carvedilol and motoprolol significantly improved cardiac function in high latitude CHF patients,and the effect of Carvedilol is slightly better than that of motoprolol.     

Effect of angiotensin converting enzyme inhibition on renal function in the treatment of heart failure

Renal hemodynamics in heart failure and the effects of angiotensin converting enzyme (ACE) inhibition on renal function are reviewed. The incidence of renal dysfunction in patients with congestive heart failure is relatively high; however, the incidence of progression of renal dysfunction during treatment with ACE inhibitors is low. The mild reduction in renal function initially observed represents the physiologic expression of blocking both the systemic and the intrarenal compensatory activities of the renin-angiotensin system. Despite small changes in blood urea nitrogen and serum creatinine noted following initiation of enalapril therapy in the two studies described, there was no further clinically significant increase in blood urea nitrogen and serum creatinine noted during continued treatment in the majority of patients, irrespective of baseline renal function. The use of enalapril as adjunctive therapy with digitalis and diuretics in patients with congestive heart failure, with appropriate adjustment of the dosages of these agents, may benefit many patients.     

Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons

Underlying causes and precipitating causes of congestive heart failure (CHF) should be treated when possible. Older persons with CHF and normal left ventricular (LV) ejection fraction should have maintenance of sinus rhythm, treatment of hypertension and myocardial ischemia, slowing of the ventricular rate below 90 beats/minute, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE) inhibitors should be administered if CHF persists despite diuretics and beta blockers. If persons are unable to tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite diuretics, beta blockers, and ACE inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. Calcium channel blockers should be used if CHF persists despite administration of diuretics and the person is unable to tolerate beta blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and diltiazem may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF in sinus rhythm with normal LV ejection fraction.     

卡维地洛对充血性心力衰竭患者QT离散度的影响

目的　探讨充血性心力衰竭 (CHF)患者 QT间期离散度 (QTd)的变化及卡维地洛对其影响。方法　选择CHF患者 80例和 30例健康人作 QTd测量 ,80例 CHF患者随机分为卡维地洛治疗组 (32例 )和常规治疗组 (48例 ) ,比较 2组治疗前后 QTd的变化。结果　 CHF患者的 QTd明显高于健康人 (P<0 .0 1) ;卡维地洛组治疗后 CHF患者的QTd明显缩短 (P<0 .0 1) ;CHF伴有严重室性心律失常者与不伴有者相比 ,QTd明显延长 (P<0 .0 1)。结论　 QTd在CHF患者明显延长 ,且能预测恶性心律失常的发生。卡维地洛能缩短 CHF患者 QTd。     

卡维地洛对扩张型心肌病心力衰竭患者心功能及运动耐量的改善作用

Thispaperaimstostudytheeffectofcarvedilolonthecardiacfunction，andexercisetoleranceinpatientswithheartfailure（HF）ofDCM．１Subjectsandmethods１．１Subjects６０casesofpatientsconsistentwiththediagnosticcriteriaofWHO／ISFC，１９９５，withcardiacfunctionofgradeII～III，wererandomlydividedintocarvediloltreatedgroup（thetestgroup）andthecontrolgroupwith３０patientsineach．Thetestgroupwascomposedof１７malesand１３females，aging３４～７４years，meanly（５６．０±１０．０）years，withcardiacfu…     

Effect of cordaron on systolic and diastolic functions of the left ventricle in patients with a mixed form of chronic low cardiac output and cardiac arrhythmias

AIM: To study effects of cordaron on central hemodynamics reflecting systolic and diastolic functions of the left ventricle (LV) in patients with a mixed form of chronic cardiac failure--a systolic dysfunction and LV diastolic dysfunction type I. MATERIAL AND METHODS: 14 patients with a mixed form of chronic heart failure (CHF) and cardiac arrhythmia were followed up for 6 months. All the patients received ACE inhibitors, diuretics, nitrates and, additionally, cordaron in a supporting dose 200-300 mg/day. Control of central hemodynamics was made with echocardiography before, 1, 3 and 6 months of therapy. RESULTS: For 6 months of therapy LV ejection fraction increased by 16%. LV diastolic function improved, primarily, due to a rise of the E max (by 52% for 6 months of therapy). This reflected early diastolic filling of the LV. Improvement of LV diastolic function was associated with heart rate decrease. CONCLUSION: Cordaron used in addition to ACE inhibitors, diuretics, nitrates improves both systolic and diastolic LV function in patients with a mixed form of CHF.     

Pathophysiological roles of endogenous endothelin-1 in dogs with chronic heart failure produced by rapid right ventricular pacing.

This study was designed to analyze the pathophysiological role of the endogenous endothelin (ET) system and the therapeutic approach to congestive heart failure (CHF) with ET(A)/ET(B) receptor antagonists in a canine CHF model. After 3 weeks of rapid right ventricular pacing (240 beats/min), concentrations of immunoreactive ET-1 in dogs increased approximately 2-fold in plasma and in the left and right ventricles but not in the lung. There were no meaningful changes in the density and affinity of total ET receptors, or in the ratio of ET(A) to ET(B) receptors. To clarify the functional role of endogenous ET, we examined the effects of acute injection of J-104132 (1 and 3 mg/kg i.v.), an ET(A)/ET(B) receptor antagonist, on cardiovascular and renal function in dogs with CHF. Compared with vehicle, J-104132 at both doses significantly decreased pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure (MAP), and increased cardiac output (CO) and renal blood flow. J-104132 had no effects on heart rate and cardiac contractility. In addition, we examined whether J-104132 has an additive effect in the presence of enalaprilat. J-104132 (1 mg/kg i.v.) administered after enalaprilat (0.05 mg/kg i.v.) induced further decreases in MAP, PCWP and PAP, and further increases in CO, resulting in further decreases in total peripheral resistance. These results indicate that the endogenous ET system is exaggerated in CHF and has a detrimental effect on cardiac function. Therefore, J-104132 given alone or as combination therapy may play a beneficial role in the treatment of CHF in humans.     

Effect of captopril and the nonpeptide angiotensin II antagonists, SK&F 108566 and EXP3174, on renal function in dogs with a renal artery stenosis.

Treatment with an angiotensin converting enzyme (ACE) inhibitor can result in acute renal failure in patients with a renal artery stenosis. In the present study the effects of the selective nonpeptide angiotensin II antagonists, SK&F 108566 ((E)-alpha-[[2-Butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl] methylene]-2-thiophenepropanoic acid) and EXP3174 (2-n-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl) methyl]imidazole-5-carboxylic acid hydrochloride) (the active metabolite of DuP 753, losartan) were compared with the ACE inhibitor, captopril, in the anesthetized dog which had been uninephrectomized and the remaining renal artery clamped to reduce renal blood flow (RBF) by approximately 50%. All three agents resulted in dose-dependent reductions in mean arterial pressure (MAP), glomerular filtration rate (GFR) and RBF. The maximum responses to captopril and SK&F 108566 were similar with MAP, RBF and GFR all decreasing approximately 30%. EXP3174 also resulted in decreases in GFR and RBF of approximately 30%; however, there was a smaller (approximately 17%) decrease in MAP. The data indicate that the possible bradykinin enhancing activity of ACE inhibitors may not provide any moderating activity of ACE inhibitor-induced reduction in GFR observed in dogs with a renal artery stenosis.     

Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure

Advances in the treatment of heart failure may require manipulation of neurohumoral responses to cardiac impairment in addition to the established strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since new treatments are likely to be used in conjunction with ACE inhibition therapy, the effects of the combination of agents need to be assessed. Adrenomedullin (ADM) is a peptide with potent vasodilator and natriuretic actions. ADM and an ACE inhibitor (captopril) were administered for 3 h both separately and together in eight sheep with heart failure. Both ADM and captopril alone reduced arterial pressure, left atrial pressure (greater with captopril) and peripheral resistance, and increased cardiac output (greater with ADM). Compared with either treatment separately, combined ADM+captopril produced directionally similar but significantly greater changes in all haemodynamic variables (particularly falls in blood pressure). ADM increased renal sodium and creatinine excretion and creatinine clearance, and maintained urine output. Captopril and ADM+captopril reduced creatinine excretion and creatinine clearance, while urine volume and sodium excretion were not significantly altered. Plasma renin activity rose with all active treatments, whereas angiotensin II levels rose during ADM, but fell during captopril and ADM+captopril. Aldosterone was reduced by all active treatments. ADM+captopril reduced plasma noradrenaline (norepinephrine). In conclusion, short-term co-treatment with ADM and an ACE inhibitor produced significantly greater decreases in ventricular filling pressures and cardiac afterload, and increases in cardiac output, compared with either treatment alone. Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone.     

Clinical Pharmacology of Carvedilol

BACKGROUND: There is now a wealth of data supporting the use of beta-blockers in heart failure and the additional pharmacological properties of carvedilol are thought to play an important role in the therapeutic efficacy of carvedilol in this disease. METHODS AND RESULTS: Carvedilol is licensed for the treatment of essential hypertension, chronic stable angina, and mild to moderate chronic heart failure. This article provides an up-to-date review of the clinical pharmacology of carvedilol, with particular emphasis on its clinical effects in heart failure. CONCLUSION: Carvedilol is a multiple-action neurohormonal antagonist that offers nonselective beta-blockade, alpha-1 blockade, antioxidant, anti-ischemic mortality, and anti-proliferative properties. In addition to reductions in hospitalization and mortality rates, benefits of carvedilol in heart failure include dramatic improvements in left ventricular function and other parameters of cardiac remodeling.     

Renal response to pentobarbital anesthesia in rats: effect of interrupting the renin-angiotensin system

The influence of interrupting the renin-angiotensin system on the renal hemodynamic response to barbiturate anesthesia was assessed in conscious, trained, chronically catheterized rats. Anesthesia induced by pentobarbital caused a marked reduction in mean arterial pressure, heart rate, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Pretreatment of rats with captopril, an inhibitor of angiotensin I converting enzyme, prevented the impairment of renal hemodynamics by pentobarbital without restoring blood pressure. GFR remained at 100 to 110% of control values in captopril-pretreated rats receiving pentobarbital, but was reduced by pentobarbital (90-120 min after induction) to 75 +/- 5% in rats which did not receive captopril. ERPF showed similar changes. An antagonist of angiotensin II receptors, 1-sarcosine-8-isoleucine-angiotensin II, did not prevent the anesthesia-induced decrements in GFR and ERPF (GFR was reduced to 78 +/- 6% and ERPF to 68 +/- 4% at 90-120 min after pentobarbital). This failure of the antagonist of angiotensin II receptors to protect renal hemodynamics may have been due to its intrinsic agonist activity on the renal vasculature. This is suggested by the fact that, in captopril-pretreated rats, which maintained renal hemodynamics in response to pentobarbital, addition of 1-sarcosine-8-isoleucine-angiotensin II caused a reduction in GFR and ERPF and an elevated blood pressure. At 100 min after administration of pentobarbital, plasma renin activity was elevated compared to a conscious control group (3.57 +/- 0.42 vs. 1.94 +/- 0.34 ng angiotensin l/ml X hr, P less than .05). It is concluded that the renin-angiotensin system mediates an impairment of renal hemodynamics during pentobarbital anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of capsaicin-sensitive sensory neurons by carvedilol, a nonselective beta-blocker, in spontaneous hypertensive rats

We performed a study in spontaneous hypertensive rats (SHR) to determine whether carvedilol, a nonselective beta-adrenoceptor antagonist, activates capsaicin-sensitive sensory neurons (CSSNs), thereby promoting the release of calcitonin gene-related peptide (CGRP), a neuropeptide with an important role in maintenance of cardiovascular homeostasis. Carvedilol given intravenously at a dose of 0.3 mg/kg transiently decreased the mean arterial blood pressure (MABP) and increased renal tissue blood flow with increases in CGRP levels in plasma and kidney. These effects induced by carvedilol were not seen in animals pretreated with capsazepine, an antagonist of capsaicin. Although 1.0 mg/kg cavedilol markedly decreased MABP, it neither increased renal tissue blood flow nor CGRP levels in plasma and kidney. Prazosin, a selective alpha(1)-adrenoceptor antagonist, and bisoprolol, a selective beta(1)-adrenoceptor antagonist, decreased MABP with capsazepine, showing no antagonistic action in either cases, and these agents increased neither renal tissue blood flow nor levels of CGRP in plasma and kidney. Both ICI 118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol], a selective beta(2)-adrenoceptor antagonist, at a dose of 0.25 mg/kg and capsaicin mimicked effects induced by 0.3 mg/kg carvedilol. Administration of 1.0 mg/kg ICI 118,551 produced effects similar to those induced by 1.0 mg/kg carvedilol. These observations strongly suggested that the low dose of carvedilol might activate CSSNs in SHR to increase the release of CGRP, thereby decreasing blood pressure with an increase in renal tissue blood flow. The effects induced by carvedilol seemed to be mediated by its beta(2)-adrenoceptor blockade activity.     

Systemic and renovascular hypertension.

To ascertain the contribution of systemic hypertension in the progression of renal failure, we have studied the effects of pharmacological treatment of hypertension in rats with the remnant kidney model of renal insufficiency, streptozotocin diabetes, or nephrotoxic serum nephritis. Treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril lowered systemic blood pressure in the remnant kidney and diabetic animals, but did not lower blood pressure in rats with nephrotoxic serum nephritis. Proteinuria was reduced in all three models, and creatinine clearance improved in the remnant kidney and diabetic animals, when compared with untreated controls. In the remnant kidney and diabetic models systemic blood pressure was lowered to a similar degree by treatments with a calcium blocker, with no improvement in either proteinuria, or glomerular filtration rate. Further studies of the long-term effects of enalapril have been undertaken in rats with the two kidney one clip model of hypertension. Rats treated with enalapril had a lower blood pressure and improved survival over one year of treatment, compared with untreated rats. After 1 year of treatment however the clipped kidney was small and fibrotic, and non functional. Following withdrawal of enalapril therapy there was no functional improvement of the clipped kidney. The possibility that ACE inhibitors have a specific intra-renal effect reducing the rate of progression of renal disease now needs confirmation in human studies. In renovascular hypertension however, intra-renal changes induced by ACE inhibitors may cause irreversible renal damage.     

充血性心力衰竭患者血浆一氧化氮和内皮素含量及其临床意义

目的：探讨血浆一氧化氮（ＮＯ）和内皮素（ＥＴ）的改变在充血性心力衰竭（ＣＨＦ）病程中的临床意义。方法：检测３５例ＣＨＦ患者外周静脉血和肺动脉血中ＮＯ、ＥＴ、血管紧张素转换酶（ＡＣＥ）的含量。以２０例健康体检者作为对照组。结果：ＣＨＦ患者外周静脉和肺动脉血浆中ＮＯ、ＥＴ含量显著高于健康对照组（Ｐ均＜０．０５）;血浆ＡＣＥ水平呈现相同的变化;血浆ＥＴ增加的幅度大于ＮＯ,因此,ＣＨＦ患者ＮＯ／ＥＴ比值降低（Ｐ＜０．０５）。这些变化在患者的肺动脉中比外周静脉中更明显（Ｐ均＜０．０５）,与心力衰竭的严重程度有关。结论：血浆ＮＯ水平增高,ＮＯ／ＥＴ比值降低是ＣＨＦ的病理生理特征之一,反映了心力衰竭时血管内皮细胞的功能紊乱     

依那普利与卡维地洛联合治疗慢性充血性心力衰竭

目的：评价依那普利与卡维地洛联合应用治疗慢性充血性心力衰竭的疗效和安全性。方法：110例充血性心力衰竭患者随机分为依那普利联合卡维地洛组（68例）、依那普利组（42例）。在心衰标准用药基础上，依那普利、卡维地洛均由小剂量开始，逐渐递增至目标剂量。全部病例在治疗后12个月进行心脏超声检查，以评价治疗前后左室功能和容积。结果：治疗后心功能和6min步行距离较治疗前明显改善（P〈0．01），两组的左室射血分数（LVEF）均有增加，左室收缩末期容积（LVESV）和左室舒张末期容积（LVEDN）均有减少，但依那普利联合卡维地洛组与单独依那普利组比较，差异有显著性，（P〈0．05）。两组均未发生肝、肾功能损害，无血脂、电解质和血糖变化。结论：依那普利与卡维地洛联合治疗轻中度慢性充血性心力衰竭安全、有效。     

常见抗心力衰竭药物副反应的观察与护理

回顾调查了76例充血性心力衰竭患住院期间服常用药副反应的发生情况，对洋地黄类、血管紧张素转换酶抑制剂类、硝酸酯类及利尿药致副反应的特点进行了分析，提出在护理充血性心力衰竭患时应注意：及时发现、积极防治洋地黄的毒性反应，血管紧张素转换酶抑制剂类药物致咳嗽的鉴别，硝酸酯类宜密切观察血压变化，使用利尿剂要监测血尿酸及观察药物作用等。     

Primary pulmonary hypertension: activation of sympathico-adrenal system and free radical oxidation. Positive effects of carvedilol therapy

AIM: To study the condition of the sympathico-adrenal system (SAS), synthesis of cAMP dependent on beta2-adrenoreceptors and parameters of free radical oxidation in patients with primary pulmonary hypertension (PPH); to examine efficacy of non-selective beta- and alpha1-adrenoblocker carvedilol in PPH patients. MATERIAL AND METHODS: Twenty patients with PPH had 6-minute walk test, ECG monitoring with assessment of heart rhythm variability (HRV). Tests for noradrenalin and adrenalin concentration in blood plasma, cAMP synthesis by blood lymphocytes in basal conditions and under stimulation with isoproterenol and forskolin, free radical oxidation were made initially, 1 and 6 months later. Ten patients received carvedilol in addition to standard therapy, 10 patients served control. RESULTS: PPH patients had higher NA in the blood, low cAMP synthesis, high malonic aldehyde, low activity of glutathionperoxidase, increased activity of superoxidedismutase and catalase of erythrocytes. The most pronounced changes in the above parameters were observed in patients with PPH FC III-IV. HRV declined in progression of cardiac failure. 6-months of combined treatment with carvedilol increased the distance of 6-min walk. Carvedilol had no effect on HRV, it reduced NA, stimulated cAMP synthesis, demonstrated no antioxidant activity. CONCLUSION: In PPH there is activation of SAS and desensitization of beta2-AR cells, oxidative stress develops. Addition of carvedilol to standard therapy with PPH improves clinical condition due to adrenoblocking properties of the drug.     

The effects of enoximone on renal function in patients with congestive heart failure

Enoximone is an investigational cardiotonic agent with positive inotropic and vasodilatory properties. In this protocol the effects of enoximone on parameters of renal function in patients (n = 14) with New York Heart Association class II or III congestive heart failure were determined after intravenous (IV) treatment (2 mg/kg) and after chronic oral administration (150 mg t.i.d.), either alone or with added furosemide (40 mg b.i.d.). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction, mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) were determined each time. Plasma volume (PV) was determined at baseline and after oral enoximone and after oral enoximone plus furosemide. Significant reductions in GFR (18%) and ERPF (20%) were observed after IV treatment but not after oral treatment with or without furosemide. MAP also was lowered significantly by 14% after IV administration but not after oral treatments. PV after oral enoximone plus furosemide was reduced significantly (31%) compared with baseline. These results demonstrate that enoximone produces acute reductions in GFR and ERPF when given intravenously but has no effect on parameters of renal function when given orally, either alone or with furosemide.