Acute hemodynamic effects of MDL 19205 in mild congestive heart failure

MDL 19205 4-ethyl-1-,3-dihydro-5-(4-pyridinylcarbonyl)-2H-imidazol-2-one, a new cardioactive agent, has been shown to increase myocardial contractile force in animals. It is effective by both oral and intravenous routes. We studied 11 patients with congestive heart failure--in 10 cases owing to coronary artery disease, and in one to cardiomyopathy. All patients had symptoms of NYHA class II or III, left ventricular ejection fractions (LVEF) less than 55%, and left ventricular end-diastolic pressures (LVEDP) greater than 15 mm Hg. Following routine coronary angiography and ventriculography, 0.5 mg/kg MDL 19205 was administered intravenously over 5 min to six patients. Thirty minutes after injection, hemodynamic measurements and ventriculography were repeated. Mean LVEF increased from 42 to 49% (p less than 0.05 for baseline vs. 30 min). In five patients ventriculography was repeated 60 min after placebo administration: LVEF decreased from 45 to 40%. LVEDP decreased from 29 +/- 8 to 16 +/- 8 mm Hg after MDL 19205 administration (p less than 0.05) and remained constant at 24 mm Hg in the placebo group. The small although nonsignificant increase of LVdP/dt after MDL 19205 administration (10 +/- 33%), together with a considerable decrease in LVEDP, was consistent with a positive inotropic effect. LVdP/dt/total pressure developed (VPM), a measure of contractility relatively independent of changes in pre- and afterload, increased from 1.0 +/- 0.3 to 1.3 +/- 0.3 s-1 (p less than 0.05). Neither parameter of contractility (LVdP/dt and VPM) changed significantly in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of MDL 17,043, a new cardiotonic agent, in patients with congestive heart failure: comparison with sodium nitroprusside

MDL 17,043 (MDL), a new cardiotonic agent, was given intravenously at a single dose of 0.5 mg/kg to 14 patients with congestive heart failure (stages II-III). The mean half-life of plasma elimination of the parent compound determined in eight subjects was 81 min. MDL is rapidly metabolized to the sulfoxide with a maximum plasma metabolite concentration reached at 15 min after parent drug infusion and a metabolite half-life of 164 min. In eight patients, the hemodynamic effects of MDL were compared with those of sodium nitroprusside (SN) given at a dose lowering mean blood pressure by 20 mm Hg. Both agents increased cardiac output (p less than 0.001 for MDL, p = 0.06 for SN) and decreased total peripheral resistance values (p less than 0.001 for both) and left ventricular end-diastolic pressure (wedge pressure) (p less than 0.001 for MDL, p less than 0.01 for SN). However, MDL was able to increase left ventricular stroke work, whereas SN failed. As both agents induced comparable changes in loading conditions, it can be assumed that MDL not only acts by peripheral vasodilation but also has a direct positive inotropic action on the heart muscle. Myocardial oxygen uptake, assessed indirectly by tension-time index, was not affected by MDL (p greater than 0.2) despite the improvement in myocardial contractile state, thus making this new agent suitable for the treatment of congestive heart failure secondary to ischemic heart disease.     

Acute hemodynamic effects of beta-blockers in patients with severe congestive heart failure: comparison of celiprolol and esmolol

The present study was designed to investigate, in patients with severe heart failure, the dose-dependent acute hemodynamic effects of celiprolol versus those of esmolol. Celiprolol is a beta 1 -receptor blocker with vasodilating properties, whereas esmolol is an ultra-short-acting beta 1 -blocker. Included were 14 patients with decompensated chronic heart failure (NYHA class IV) due to coronary heart disease (n = 8) or to dilated cardiomyopathy (n = 6). Each patient received both celiprolol and esmolol in random fashion. The beta-blockers were administered in four dose tiers, with an increase in dosage every 15 min. Hemodynamic measurements were obtained with a Swan-Ganz thermodilution catheter. Administration of celiprolol (5, 10, 20, and 50 microg/kg) took place intravenously. After intravenous administration of a loading dose of 500 microg/kg, we continuously infused esmolol at increasing doses, which were individually titrated for each patient. Mean infusion rates of esmolol were as follows: 40, 75, 140, and 230 micromol/kg per minute. Celiprolol and esmolol induced a comparable dose-dependent decrease in heart rate to a minimum of -10% below baseline. Esmolol caused a significant dose-dependent decrease (-25% below baseline at the highest dose level) in cardiac index (CI). After administration of celiprolol, CI decreased only transiently (-10% below baseline at the second and third dose level) and did not differ from the baseline at the highest dose level. For treatment of severe heart failure, initiation of intravenous beta-blocker therapy with low doses of a beta 1 -blocker with vasodilating effects may have hemodynamic advantages over conventional beta-blockade.     

Acute hemodynamic effects of moderate doses of nebivolol versus metoprolol in patients with systolic heart failure

OBJECTIVES: To determine the acute hemodynamic effect of moderate doses of nebivolol (vasodilating beta1-selective blocker) vs. metoprolol tartrate (non-vasodilating beta1-selective blocker) in systolic heart failure (SHF). MATERIAL AND METHODS: 20 stable patients with SHF (left ventricular (LV) ejection fraction < or = 35%) underwent right heart catheterization. Once a reproducible baseline was obtained, patients were randomized to 5 mg nebivolol PO (n = 10) or metoprolol tartrate 50 mg PO (n = 10). Hemodynamic studies were repeated hourly for the first 4 hours and at 6 hours. RESULTS: Both agents caused bradycardia. Nebivolol caused additionally a decrease in systemic vascular resistance (SVR) and no significant change in pulmonary capillary wedge pressure (PCWP), and cardiac output (CO). In contrast, metoprolol caused a deterioration of LV systolic function characterized by a decrease in cardiac output, and an increase in SVR and PCWP. CONCLUSIONS: Treatment initiation with moderate doses of nebivolol is not associated with the adverse hemodynamic effects of metoprolol in patients with SHF. These findings suggest that a long up-titration period may not be necessary with nebivolol.     

Short-term hemodynamic effects of intravenous methyldopa in patients with congestive heart failure

The acute hemodynamic effects of intravenous methyldopa were studied in six patients with chronic congestive heart failure (New York Heart Association class IV) at 4-6 hours after a 750-mg bolus (period A) and 6-12 hours after a maintenance infusion of 1-2 mg/minute (period B). For period A, the most consistent and striking finding was a significant (48%) fall in pulmonary wedge pressure (33 +/- 6 to 17 +/- 2 mm Hg; p less than 0.05). Stroke volume increased 39% (23 +/- 3 to 32 +/- 4 ml/m2; p less than 0.05), while peripheral vascular resistance decreased 15% (3331 +/- 363 to 2841 +/- 241 dynes.s.cm-5; p less than 0.05). Heart rate fell from 97 +/- 7 to 76 +/- 3 beats/minute (p less than 0.05) with a nonsignificant decline in mean right atrial pressure (18 +/- 4 to 9 +/- 1 mm Hg). These hemodynamic changes were either sustained or enhanced during period B. Concomitant clinical improvement was also noted. As an agent with potent vasodilatory and antiadrenergic properties, methyldopa permitted a rise in stroke volume by virtue of unloading and possible inhibition of sympathetic activity that led to increased density of beta-adrenergic receptors of the heart (up-regulation). Significant reduction of ventricular filling pressure was attributed to venodilation and probable improved diastolic function. In selected patients with severe congestive heart failure, particularly underscored by excessive sympathetic tone, methyldopa may be considered as an alternative agent to improve cardiac performance and clinical symptomatology.     

Hemodynamic effects of a constant intravenous infusion of piroximone in patients with severe congestive heart failure

The hemodynamic effects and serum levels of piroximone (MDL 19,205), a new inotropic agent with vasodilating properties, were measured in 10 patients with chronic severe congestive failure during a constant 48-h infusion. The initial five patients (group A) received piroximone at 10 micrograms/kg/min; however, because a sustained increase in heart rate greater than or equal to 25% from baseline developed in two patients and an episode of paroxysmal supraventricular tachycardia developed in another, the last 5 patients (group B) received an 8 micrograms/kg/min infusion. Because the steady-state hemodynamic alterations of group A prior to the onset of tachyarrhythmias were similar to those of group B, these results were combined. A significant increase in cardiac output from 3.65 +/- 0.31 (SE) to 5.20 +/- 0.49 L/min and decrease in pulmonary capillary wedge pressure (27 +/- 2 to 20 +/- 2 mm Hg), right atrial pressure (18 +/- 2 to 11 +/- 2 mm Hg), and systemic vascular resistance (1811 +/- 172 to 1293 +/- 80 dynes.s.cm-5) occurred (all p less than 0.05) without a significant change in mean arterial pressure. The peak plasma piroximone level was lower in the eight patients who did not develop a sustained increase in heart rate greater than or equal to 25% above baseline (2.1 +/- 0.5 micrograms/ml; range 1.6-2.9 micrograms/ml) than in the two who did (5.0 and 5.8 micrograms/ml). The latter two patients had the highest serum creatinine levels in the study population.(ABSTRACT TRUNCATED AT 250 WORDS)     

硝普钠治疗老年充血性心力衰竭的疗效观察

目的：观察静脉应用硝普钠治疗老年充血性心力衰竭的疗效及安全性。方法：采用整群抽样的方法随机抽取2家社区卫生服务中心收治的98例老年充血性心力衰竭患者,在常规治疗的基础上采用抽签法随机分为硝普钠组和硝酸甘油组,硝普钠和硝酸甘油开始剂量分别为6.25μg/min和5μg/min,均由微量注射泵经静脉泵入,根据血压及临床表现调整剂量持续静脉泵入。结果：硝普钠组总有效率为96.0%,硝酸甘油组为78.7%,两组比较,硝普钠组明显优于硝酸甘油组（P〈0.01）。结论：硝普钠能改善心脏的收缩与舒张功能,对老年充血性心力衰竭患者疗效显著,不良反应较少,对常规治疗效果不佳的老年充血性心力衰竭患者,可应用硝普钠治疗。     

Acute hemodynamic and hormonal effects of central versus peripheral sympathetic inhibition in patients with congestive heart failure

Indoramin, an alpha 1 antagonist, and guanabenz, an alpha 2 agonist, were given to 10 patients with severe congestive heart failure to compare the hemodynamic and hormonal effects of a reduction in sympathetic tone obtained through inhibition of postsynaptic alpha 1 receptors versus the decrease in sympathetic activity achieved by stimulating central or presynaptic peripheral alpha 2 adrenoceptors. Both drugs produced similar reduction in systemic arterial pressure. However, only indoramin significantly decreased systemic and pulmonary vascular resistances from 1529 +/- 526 to 1071 +/- 356 and from 721 +/- 422 to 412 +/- 257 dynes X s X cm-5, respectively, and increased stroke index from 26.6 +/- 9.5 to 33.3 +/- 9.5 ml/m2 (all p less than 0.01). Heart rate fell significantly only after guanabenz. Plasma norepinephrine, unchanged after indoramin, fell in each patient after guanabenz; the mean value decreased from 746 +/- 332 to 461 +/- 255 pg/ml (p less than 0.01). Plasma renin activity increased only after indoramin. The data demonstrate: (a) a decrease in sympathetic activity due to blockade of alpha 1 adrenoreceptors produces marked peripheral and pulmonary vasodilation; (b) noradrenergic transmitter release in heart failure is regulated by alpha 2 receptors; (c) an alpha 2-mediated decrease in sympathetic activity and in plasma norepinephrine has a bradycardic effect but does not produce a vasodilator effect. Although the acute hemodynamic effects of indoramin were more prominent than those of guanabenz, the more favorable neurohumoral effects of guanabenz suggest the possibility of long-term benefit in the treatment of heart failure.     

Regional hemodynamic effects of clonidine in congestive heart failure

Regional and central hemodynamic variables were ascertained in 10 patients with congestive heart failure before and after the oral administration of clonidine. Following the 0.2 mg dose, renal, hepatic, and limb blood flow remained unaltered, whereas a reduction was noted in heart rate (10%), mean systemic (14%), and pulmonary capillary wedge pressures (27%). Cardiac index and systemic vascular resistance fell slightly, however the changes were not statistically significant. Higher dose clonidine (0.4 mg) elicited similar regional hemodynamic effects whereas systemic vascular resistance significantly diminished (21%) and cardiac index remained unchanged. In congestive heart failure, the central antihypertensive agent, clonidine, effects a significant reduction in preload (left ventricular filling pressure) and afterload (systemic blood pressure) without markedly altering other central and regional hemodynamic variables.     

Acute hemodynamic effects of nilvadipine, a new calcium channel blocker, in patients with congestive heart failure.

The acute hemodynamic effects of nilvadipine, a newly synthesized calcium channel blocker, were studied in 12 patients with congestive heart failure. Hemodynamic measurements were made before and 15, 30, and 60 min after oral administration of 6 mg nilvadipine. Substantial reductions in systemic vascular resistance (-28.8 +/- 6.3%, p less than 0.01) and forearm vascular resistance (-52.0 +/- 6.2%, p less than 0.01) after nilvadipine administration were associated with increases in cardiac index (31.1 +/- 8.3%, p less than 0.01) and forearm blood flow (105.2 +/- 27.4%, p less than 0.01). Mean arterial and pulmonary arterial pressures were decreased by 12.2 +/- 3.0% (p less than 0.01) and 14.7 +/- 5.0% (p less than 0.05), respectively, after nilvadipine administration; however, heart rate remained unchanged. Decreases in mean arterial pressure correlated with the baseline arterial pressure (y = 0.58x - 41.6, r = 0.75, p less than 0.01). Pulmonary capillary wedge pressure decreased by 33.1 +/- 9.1% (p less than 0.01) after nilvadipine administration. However, right atrial pressure and the venous stiffness constant remained unchanged, and the venous pressure-volume curve was not shifted significantly. Therefore, the decrease in pulmonary capillary wedge pressure was attributed primarily to afterload reduction. Nilvadipine holds promise as a vasodilator for the therapy of congestive heart failure.     

果糖二磷酸钠与硝普钠合用治疗老年心力衰竭

目的 :观察果糖二磷酸钠 (FDP)与硝普钠合用治疗老年心力衰竭的疗效。方法 :将 73例老年心力衰竭病人分为FDP +硝普钠组 3 7例 ,给FDP5 .0 g,静脉滴注 ,bid× 7d ,硝普钠 12 .5～ 2 5mg·d- 1,以 2 5～ 5 0 μg·min- 1速度静脉滴注 ,qd× 7d ;硝普钠组 3 6例给硝普钠 ,用法同FDP +硝普纳组。结果 :总有效率FDP +硝普纳组为 81% ,硝普钠组为 75 % ,组间疗效比较 ,P <0 .0 5。 2组心功能参数均较治疗前高 ,FDP +硝普钠组的峰射血率、峰充盈率高于硝普钠组 (P <0 .0 1)。结论 :FDP与硝普钠合用治疗老年心力衰竭疗效优于单用硝普钠 ,FDP有改善老年人心脏收缩和舒张功能的作用。     

硝普钠与多巴胺持续静脉泵入治疗充血性心力衰竭的护理

目的：探讨持续静脉泵入血管活性药物;硝普钠与多巴胺治疗充血性心力衰竭（CHF）的临床护理特点。方法：选择硝普钠与多巴胺静脉泵入治疗CHF患者60例（治疗组）,观察其临床效果及护理特点,同时以常规治疗的59例CHF病人做为对照组。结果：治疗组显效率76．7％,对照组显效率25．4％,组明显优于对照组（P＜0．01）。平均住院天数治疗组为15天,对照组为26天,治疗组住院天数较对照组明显缩短（P＜0．01）。结论：应用血管活性药物,治疗CHF的方法是极为有效的;在治疗过程中应严密观察病情变化并随时依据病情调整药物剂量。     

Peripheral hemodynamic and humoral effects of oral zofenopril calcium (SQ. 26,991) in patients with congestive heart failure

In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginine-vasopressin (AVP) were also measured. Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility. Zofenopril also decreased ANP levels in a manner directly related to peripheral venodilatation (r = .64; P less than .05) and modified arginine-vasopressin (AVP) proportionally to the fall in blood pressure observed in response to drug administration (%SBP/%AVP: r = .64, P less than .05; %DBP/%AVP: r = .67, P less than .05). Hemodynamic and humoral responses to zofenopril occurred without any significant unwanted adverse reaction, even in patients with greater pressor reduction. We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration.     

Acute haemodynamic effects of ibopamine in patients with severe congestive heart failure.

Ten patients with congestive heart failure (CHF), in III and IV NYHA Class, were treated orally with a single dose of ibopamine ranging from 1.2-3.3 mg/kg, and were studied using the Swan-Ganz catheter and thermodilution technique. Cardiac index (CI) and stroke volume index (SVI) were increased, and mean pulmonary pressure (PAP), systemic vascular resistances (SVR) were lowered. Ibopamine increased CI (+33%) and SVI (+26%), and decreased PAP (-17%) and SVR (-24%). All changes were statistically significant. The maximum haemodynamic effect occurred 180 min after ibopamine administration. Blood pressure and heart rate were unaffected. Tolerability was good. This study shows that ibopamine when orally administered to human subjects improves cardiac performance and further investigations on its use as a therapeutic agent in the long term treatment of CHF are recommended.     

Global and regional hemodynamic effects of ramipril in congestive heart failure

Global and regional hemodynamic changes were assessed in 11 patients with congestive heart failure following the introduction of the novel angiotensin-converting enzyme inhibitor (ACEI), ramipril. All patients were stabilized on digitalis, furosemide, and a fixed diet, central hemodynamics and hormones having been stable over 2 control days. Ramipril resulted in significant falls in converting enzyme activity, angiotensin II, and aldosterone, with a rise in renin. Changes in regional blood flow were assessed 2 h following the first dose of ramipril at the time of maximal increase in global cardiac output (+27%, p less than 0.05), but prior to the maximal fall in systemic arterial pressure. Despite the fall in systemic arterial pressure, blood flow increases were noted in the renal (+93%, p less than 0.05), coronary (+10%), and cerebral (+5%) regions, while forearm blood flow was unchanged. Glomerular filtration rate fell (29%) and was associated with small rises of plasma creatinine and acute sodium retention. After 7 weeks of therapy we noted improvement in functional class (p less than 0.05), exercise time, and left ventricular ejection fraction. We conclude that during inhibition of angiotensin-converting enzyme activity by ramipril in patients with congestive heart failure, blood flow to the kidneys, heart, and brain is increased or preserved despite hypotension. Long-term therapy is associated with beneficial clinical effects.     

The hemodynamic effects of ibopamine, a dopamine congener, in patients with congestive heart failure

Ten patients with congestive heart failure underwent noninvasive and invasive hemodynamic testing before and sequentially after the administration of ibopamine to determine the cardiovascular effects of this oral dopamine congener. Single doses of 200, 400 and 600 mg were administered to all patients and 5 repeated doses of 200 or 400 mg were studied in 8. Hemodynamic effects occurred as early as 30 minutes and lasted up to 4 hours after dosing. In general, ibopamine elicited statistically significant dose-related increases in cardiac output and reductions in the derived resistance of the systemic and pulmonary circulations. A biphasic response in central and peripheral pressures was observed; up to 1 hour after administration, ibopamine elevated mean right and left atrial pressures and pulmonary and systemic arterial pressures with a significant reduction of these measurements beyond 1 hour. It did not alter heart rate. Repeated doses qualitatively affected hemodynamics similar to the initial dose and did not appear to be accompanied by short-term tolerance. While oral ibopamine elicits some favorable hemodynamic effects in humans with cardiac failure, the biphasic hemodynamic response is generally undesirable in the majority of these patients.     

Acute haemodynamic effects of felodipine in congestive heart failure

Summary The haemodynamic effects of felodipine 0.1 mg/kg p.o., a new arteriolar dilator, were studied in 7 patients with severe congestive heart failure of NYHA Class IV (Group A) and in 3 patients in Class II–III (Group B). In Group A, measurements were made before and 1 and 4 h after felodipine administration. There was a substantial fall in systemic arterial pressure, which was not associated with a compensatory tachycardia. In fact, there was a fall in heart rate from 92 to 82 beats/min 1 h after drug administration. The pulmonary capillary wedge pressure was reduced from 22 to 14 mm Hg and the cardiac index and stroke volume index rose significantly. Consequently, there was a marked reduction in systemic vascular resistance. In Group B measurements were performed at rest and during exercise before and 1 h after felodipine. The pulmonary wedge capillary pressure during exercise was lower than in the control situation. Coronary sinus flow was increased and there was a pronounced fall in coronary vascular resistance. The results would suggest that felodipine, by virtue of its ventricular unloading potency, might be a valuable drug in the treatment of congestive heart failure.     

硝普钠联合硝酸甘油对急性左心衰竭患者的效果分析

目的研究硝普钠联合硝酸甘油治疗急性左心衰竭的效果分析。方法选取2016年1月～2018年1月我院心内科收治的急性左心衰竭患者58例,根据用药方法不同分两组,各29例,对照组患者给予常规对症支持治疗和硝普钠治疗,观察组患者在对照组的基础上加用硝酸甘油,对比分析两组患者的治疗效果以及心衰症状改善耗费时间和不良反应发生率情况。结果观察组患者治疗总有效率100.0%高于对照组的总有效率82.76%,差异有统计学意义(P 0.05)。观察组的心衰症状改善耗费时间短于对照组,差异有统计学意义(P 0.05);观察组的不良反应发生率低于对照组,两组的不良反应均较为轻微,差异有统计学意义(P 0.05)。结论硝普钠联合硝酸甘油抢救急性左心衰竭效果确切,促进心衰症状的缓解,减少药物不良反应,值得推广。     

Acute haemodynamic and neurohumoral effects of intravenous nisoldipine in patients with severe congestive heart failure

Summary Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continous infusion of 0.2 g · kg^–1 · min^–1. Haemodynamic measurements were performed at baseline and after 30 min.The mean arterial pressure fell from 91 to 73 mm Hg, pulmonary capillary wedge pressure from 31 to 26 mm Hg and systemic vascular resistance from 1695 to 1040 dyn · s · cm^–5.The cardiac index (2.2 to 2.71 · min^–1 · m^–2, and stroke volume index (25 to 33 ml · m^–2) were markedly increased. There was no reflex tachycardia as the heart rate dropped from 92 to 85 beats · min^–1. Plasma renin activity and norepinephrine concentration did not change significantly.The findings indicate that nisoldipine acts as a strong vasodilator and that it has a beneficial acute haemodynamic effect in patients with severe left heart failure irrespective of its aetiology.     

Systemic and regional hemodynamic effects of perindopril in congestive heart failure.

The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.