Peripheral hemodynamic effects of captopril in patients with congestive heart failure

In 14 patients with severe congestive heart failure, the effects of captopril on the forearm circulation were evaluated with strain gauge plethysmography. Changes in plasma renin activity, angiotensin II, norepinephrine, epinephrine, bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha concentrations were also measured. To determine whether the prostaglandins contribute to the peripheral hemodynamic response to captopril, the hemodynamic and hormonal measurements were repeated after pretreatment with indomethacin, an inhibitor of prostaglandin synthesis. Ninety minutes after administering a single dose of captopril (25 mg), mean blood pressure and venous pressure decreased (p less than 0.01 and p less than 0.05, respectively), forearm blood flow and maximum venous volume increased (p less than 0.05 for both), and forearm vascular resistance and forearm venous tone decreased (p less than 0.05 for both). Captopril also improved forearm venous distensibility (p less than 0.05). Pretreatment with oral indomethacin (50 mg) significantly blunted all of these captopril-induced hemodynamic changes. The blockage of the renin-angiotensin system by captopril was unaltered by indomethacin pretreatment. Captopril significantly increased plasma bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha (p less than 0.05 for each). Indomethacin pretreatment did not affect the captopril-induced increase in bradykinin, but it did completely eliminate the increase in the prostaglandins. Plasma catecholamines did not change with captopril. These data suggest that the vasodilator prostaglandins play a significant role in captopril's peripheral vasodilative effects in congestive heart failure.     

Acute hemodynamic and hormonal effects of ramipril in chronic congestive heart failure and comparison with captopril

Acute hemodynamic and hormonal responses to ramipril in comparison with captopril were studied in 10 patients with moderate to severe congestive heart failure in an open, randomized study. Both drugs were given to 5 patients each in 2 increasing doses on 2 successive days. After 5 mg of ramipril angiotensin converting enzyme (ACE) activity was significantly decreased during 24 hours with a maximum decrease 4 hours after administration. Mean arterial blood pressure decreased from 84 +/- 5 to 62 +/- 5 mm Hg at 4 hours and 71 +/- 4 mm Hg at 12 hours, respectively, after this dose. Capillary wedge pressure decreased from 19 +/- 1 mm Hg to 13 +/- 1 mm Hg at 4 hours with a maximum increase in cardiac output from 3.8 +/- 0.3 liters/min to 4.4 +/- 0.3 liters/min at 2 hours. No significant cardiac effects were present 8 hours after administration. After 10 mg of ramipril, cardiac and hormonal effects showed a quicker onset of action and longer duration compared with the 5 mg dose. Mean arterial pressure decreased to 61 +/- 6 mm Hg. Similar effects were seen after captopril, but with a significantly shorter duration. Mean arterial pressure decreased from 82 +/- 4 mm Hg to 64 +/- 5 mm Hg after 12.5 mg and to 58 +/- 6 mm Hg after 25 mg of captopril. In patients with congestive heart failure ramipril has the hemodynamic profile of a long-acting and potent ACE inhibitor. Significant cardiac effects are present during 4 to 8 hours and ACE activity is still significantly inhibited 24 hours after a single dose of ramipril.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Elevated plasma norepinephrine (PNE) has been shown to be an important predictor of morbidity and mortality in patients with congestive heart failure (CHF). Moxonidine selectively stimulates imidazoline receptors located in the medulla, which centrally inhibit sympathetic outflow. PNE is suppressed and peripheral vasodilation reduces systemic blood pressure. This study evaluated the acute neurohumoral and hemodynamic effects of a single dose of oral moxonidine in 32 patients (22 men, mean ± SD age 66 ± 10 years) with CHF. All patients were in New York Heart Association functional class III and stabilized on chronic therapy with diuretics, digitalis, and angiotensin-converting enzyme inhibitors. The mean PNE concentration was 509 ± 304 pg/ml at baseline. Patients underwent invasive hemodynamic monitoring after double-blind randomization to either placebo (n = 12), moxonidine 0.4 mg (n = 9), or moxonidine 0.6 mg (n = 11). Moxonidine produced a dose-dependent, vasodilator response compared with placebo. Analysis of the time-averaged change from baseline over 6 hours demonstrated that moxonidine 0.6 mg caused significant reductions in mean systemic arterial pressure (p <0.0001), mean pulmonary arterial pressure (p <0.005), systemic vascular resistance (p <0.05), pulmonary vascular resistance (p <0.01), and heart rate (p <0.05). Stroke volume was unchanged. PNE was reduced substantially (−180 pg/ml at 4 hours, p <0.005) and the reduction was highly correlated with the baseline level (r = −0.968). Moxonidine was well tolerated in this single-dose study and resulted in a modest, dose-dependent, vasodilator response, with substantial reductions in systemic and pulmonary arterial blood pressure. Trials designed to evaluate the clinical efficacy of chronic moxonidine therapy in CHF added to conventional therapy would be appropriate.     

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Elevated plasma norepinephrine (PNE) has been shown to be an important predictor of morbidity and mortality in patients with congestive heart failure (CHF). Moxonidine selectively stimulates imidazoline receptors located in the medulla, which centrally inhibit sympathetic outflow. PNE is suppressed and peripheral vasodilation reduces systemic blood pressure. This study evaluated the acute neurohumoral and hemodynamic effects of a single dose of oral moxonidine in 32 patients (22 men, mean ± SD age 66 ± 10 years) with CHF. All patients were in New York Heart Association functional class III and stabilized on chronic therapy with diuretics, digitalis, and angiotensin-converting enzyme inhibitors. The mean PNE concentration was 509 ± 304 pg/ml at baseline. Patients underwent invasive hemodynamic monitoring after double-blind randomization to either placebo (n = 12), moxonidine 0.4 mg (n = 9), or moxonidine 0.6 mg (n = 11). Moxonidine produced a dose-dependent, vasodilator response compared with placebo. Analysis of the time-averaged change from baseline over 6 hours demonstrated that moxonidine 0.6 mg caused significant reductions in mean systemic arterial pressure (p <0.0001), mean pulmonary arterial pressure (p <0.005), systemic vascular resistance (p <0.05), pulmonary vascular resistance (p <0.01), and heart rate (p <0.05). Stroke volume was unchanged. PNE was reduced substantially (−180 pg/ml at 4 hours, p <0.005) and the reduction was highly correlated with the baseline level (r = −0.968). Moxonidine was well tolerated in this single-dose study and resulted in a modest, dose-dependent, vasodilator response, with substantial reductions in systemic and pulmonary arterial blood pressure. Trials designed to evaluate the clinical efficacy of chronic moxonidine therapy in CHF added to conventional therapy would be appropriate.     

Comparative hemodynamic and clinical effects of long-term treatment with prazosin and captopril for severe chronic congestive heart failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy

Short- and long-term hemodynamic and clinical responses to sequential therapy with prazosin (15 mg/day for 3 to 12 weeks) and captopril (75 to 300 mg/day for 2 to 15 weeks) were compared in 22 patients with severe chronic congestive heart failure. First doses of prazosin produced marked increases in cardiac index and stroke volume index (p less than 0.01), but these effects were lost during long-term treatment. First doses of captopril produced only modest increases in both variables, but these persisted without attenuation during prolonged therapy. Both drugs produced immediate decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure and systemic vascular resistance; these changes became significantly attenuated (p less than 0.01) with prazosin but not with captopril. At the end of treatment, stroke volume index was significantly higher and right and left ventricular filling pressures were significantly lower with captopril than with prazosin (p less than 0.05 to 0.01). Only 8 of the 22 patients (36%) treated with prazosin benefited clinically, whereas 14 of 19 patients (74%) treated with captopril felt that they had improved (p less than 0.05). These differences could not have been predicted by comparing responses to first doses of the 2 drugs. These findings indicate that the choice of 1 vasodilator drug over another in patients with congestive heart failure should be based on studies that compare their long-term rather than short-term hemodynamic and clinical effects.     

Acute hemodynamic and coronary effects of captopril in chronic cardiac failure

The acute effects of captopril on haemodynamics, coronary flow and myocardial metabolism were studied in 12 patients with chronic severe cardiac failure (primary cardiomyopathy: 10 cases; ischaemic: 2 cases) in functional Classes III or IV of the NYHA. All patients were male and their average age was 51.3 +/- 14.1 years (range 27 to 68 years). Measurements were carried out under basal conditions and 90 minutes after a single dose of 50 mg (5 cases) or 100 mg (7 cases) of captopril. Captopril administration leads to an increase in cardiac index from 2.05 +/- 0.32 to 2.34 +/- 0.35 l/min/m2 (p less than 0.05) and a greater increase in systolic index from 23.9 +/- 6.7 to 29.8 +/- 6.9 ml/syst/m2 (p less than 0.01), because the heart rate decreased slightly (p less than 0.05). These changes were the result of a decrease in afterload: mean aortic pressure fell from 85 +/- 11.8 to 68 +/- 19.6 mmHg (p less than 0.01) and systemic arterial resistance fell from 2 886 +/- 745 to 2 010 +/- 610 dynes/cm-5/sec/m-2 (p less than 0.01). Captopril also led to a fall in venous tone, i.e. pre-load: left ventricular end diastolic pressure fell from 26.9 +/- 6.1 to 20.8 +/- 6.6 mmHg: p less than 0.01. There was no change in contractility as shown by the absence of variation of the V.max (0.92 +/- 0.18 under basal conditions, and 0.90 +/- 0.15 after 90 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous hemodynamic improvement or stabilization and associated biopsy findings in patients with congestive cardiomyopathy

The hemodynamic courses of 56 patients with congestive cardiomyopathy (CCM) were investigated. Fourteen patients died within 24 months after diagnosis. The hemodynamic courses of the remaining 42 patients were investigated in subsequent examinations by determination of left ventricular ejection fraction (LVEF), mean pulmonary arterial pressure at maximal workload, and peak systolic pressure/end-systolic volume index. During the study interval of 32.2 +/- 20.0 months the conditions of 20 patients (48%) deteriorated, according to their hemodynamic status, and at least five of these died of terminal heart failure. Surprisingly, the conditions of 22 patients (52%) improved or stabilized. One of these died of leukemia. Seven patients in the latter group with initial LVEFs of 0.30 or less experienced an average increase from 0.22 to 0.51. Retrospectively consideration of age, alcohol intake, exercise capacity, and hemodynamic status were not helpful in predicting the course of the disease. In 38 patients endomyocardial biopsy samples could be obtained at the time of diagnosis. Reduced myofibril volume fraction (less than 60%) had prognostic significance for both hemodynamic deterioration and death (sensitivity 23/24 = 96%), while 14 of 15 patients whose conditions improved or stabilized had a myofibril volume fraction of 60% or more (specificity 14/15 or 93%, p less than .002). A relationship between hemodynamic status and the myofibril volume fraction could not be found. Individual patients with CCM differ significantly with respect to course of the disease. A distinct separation of the patients by means of morphologic criteria is possible. This makes it more likely that the pathogenesis of the disease is not unique.     

Acute hemodynamic effects of right ventricular pacing site and pacing mode in patients with congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy

The hemodynamic effects of pacing in patients with congestive heart failure (CHF) remain controversial. Early studies reported that pacing from the right ventricular (RV) apex improved acute hemodynamic parameters in patients with left ventricular systolic dysfunction, but these findings were not confirmed in subsequent controlled studies. More recently, it has been proposed that pacing from the RV side of the ventricular septum improves hemodynamic function compared with intrinsic conduction or apical pacing. Either dual-chamber or ventricular pacing have been evaluated, again with inconsistent findings. To assess the effects of pacing site and mode on acute hemodynamic function, we evaluated 21 subjects with CHF and intrinsic conduction disease. Hemodynamics were compared in AAI, VVI, and DDD modes with pacing from the RV apex or high septum. The pacing rate was constant in each patient and the order of testing was randomized. In the absence of ventricular pacing (AAI mode), the mean systemic arterial pressure was 85 +/- 11 mm Hg, the right atrial pressure was 11 +/- 4 mm Hg, the pulmonary capillary wedge pressure was 18 +/- 8 mm Hg and the cardiac index was 2.4 +/- 0.7 L/min/m(2). Compared with AAI pacing, there were no improvements in any hemodynamic parameter with DDD pacing from either RV site. Hemodynamic function worsened with VVI pacing from both RV sites. Subgroup analyses of patients with dilated cardiomyopathy, with prolonged PR interval, or with significant mitral regurgitation also failed to demonstrate an improvement with pacing. We conclude that pacing mode but not RV pacing site affects acute hemodynamic function. Pacing in the DDD mode prevents the deleterious effects of VVI pacing in this patient population.     

Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure

The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril arid teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 ± 240 to 1,715 ± 170 dynes·s·cm^?5 (p < 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 ± 8 to 86 ± 5 mm Hg, p < 0.001) and left ventricular filling pressure (30 ± 2 to 21 ± 2 mm Hg, p < 0.001). Coronary sinus thermodilution blood flow parallelled perfusion pressure but did not significantly vary overall (160 ± 20 to 133 ± 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 ± 8.8 to 41.3 ± 7.9 g·m/m², p < 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 ± 1.0 to 10.4 ± 1.0 ml/100 ml, NS) or calculated myocardial oxygen consumption (16.4 ±1.9 to 13.9 ± 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 ± 703 to 7,087 ± 514 beats·mm Hg, p < 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 ± 3 to 26 ± 6, p < 0.05), reflecting greater left ventricular work without increased oxygen demand.Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.     

Acute and chronic effects of ramipril and captopril in congestive heart failure

We studied the acute and long-term effects of ramipril and captopril in 12 patients with moderate to severe congestive heart failure using an open, parallel design. Drug doses were titrated. Compared with baseline values, maximal haemodynamic and humoral effects after the first dose of both angiotensin converting enzyme inhibitors were similar, but the effects of ramipril (5 mg) demonstrated a slower onset of action and a significantly longer duration than captopril (12.5 mg). After 3 months of treatment a single dose of 5 mg ramipril showed the same 24-hour haemodynamic profile as after the first dose, but the hypotensive effect was less marked. There was no plasma accumulation of ramiprilat. Serum creatinine and potassium remained stable, except for one patient whose renal function deteriorated on captopril treatment. Complex ventricular arrhythmias occurred in 11 patients and were unaffected after treatment with ramipril or captopril. Two patients died suddenly during ramipril therapy and one patient during captopril therapy. In summary, ramipril is an effective, long-acting angiotensin converting enzyme inhibitor, producing long-term haemodynamic effects in patients with congestive heart failure. Using an individualised dosage scheme, neither long-lasting hypotension nor deterioration of renal function occurred. No effect on ventricular arrhythmias was seen.     

Amrinone: Acute electrophysiologic and hemodynamic effects in patients with congestive heart failure

Amrinone is an effective inotropic agent, but its electrophysiologic effects in humans have not been previously determined. Fifteen patients with congestive heart failure (CHF) New York Heart Association functional class II to IV, underwent an electrophysiologic study after withdrawal of all other cardioactive drugs before and after 10 to 20 μg/kg/min of intravenous amrinone (doses that increased cardiac index and decreased pulmonary capillary wedge pressure and systemic vascular resistance, p < 0.002). Amrinone caused no change in PR, QRS, QTc, AH or HV intervals or maximal corrected sinus node recovery time and had no significant effect on the ventricular effective refractory periods. Amrinone decreased the atrial effective refractory period from 256 ± 40 to 240 ± 38 ms (p = 0.015), and the atrioventricular (AV) nodal functional refractory period from 374 ± 65 to 356 ± 64 ms (p < 0.05), and enhanced maximal 1:1 AV nodal conduction from 371 ± 46 to 334 ± 47 ms (p = 0.006). Nine patients had baseline HV prolongation; this was not affected by amrinone. The frequency of inducible ventricular tachycardia was not significantly affected by amrinone. Holter recordings (24 to 48 hours) were obtained from 10 patients before and after acute oral amrinone dosing (75 to 150 mg every 8 hours). There was no change in the number of ventricular premature contractions per 24 hours (2,197 ± 3,305 vs 2,616 ± 2,436) or number of runs of ventricular tachycardia per 24 hours (10 ± 12 vs 12 ± 13); however, the number of ventricular couplets per 24 hours increased from 22 ± 34 to 52 ± 55 (p = 0.054). Thus, amrinone is safe to use in patients with intraventricular conduction disturbances. It shortens the atrial effective and AV nodal functional refractory period and enhances AV nodal conduction, and it has minimal effects on ventricular arrhythmogenesis during acute drug administration.     

Acute hemodynamic effects of digoxin alone or in combination with other vasoactive agents in patients with congestive heart failure.

Although digitalis preparations have been in use for greater than 200 years, it is only within the last 2 decades that the central hemodynamic and neurohumoral effects occurring over several hours following intravenous administration of digoxin have been investigated in patients with congestive heart failure (CHF). Although digoxin has been shown to stimulate myocardial contractility in tissue preparations, its positive inotropic activity does not consistently translate into improvements in hemodynamic measurements in humans. Digoxin given intravenously results in increased cardiac index and decreased heart rate, left ventricular filling pressure, and right atrial pressure, as well as in acute attenuation of neurohumoral abnormalities, in patients with chronic CHF who have abnormal baseline hemodynamic measurements. Unlike other drugs with positive inotropic activity, however, digoxin does not influence hemodynamics in normal volunteers or in CHF patients in whom hemodynamics have been normalized with other therapies. These differing effects may be related to the drug's diverse peripheral vascular effects in CHF patients in whom vasodilation may occur in comparison with those that occur in normal subjects in whom the peripheral vasoconstrictor effects may prevent the inotropic effects of the drug from being translated into an increase in cardiac output. The hemodynamic effects of digoxin in patients with chronic CHF due primarily to diastolic dysfunction have not been fully investigated. Intravenous digoxin produces hemodynamic effects in patients with CHF associated with acute myocardial infarction, but these changes are small compared with those resulting from the administration of dobutamine. Digoxin does not appear to influence hemodynamic measurements in patients with right ventricular dysfunction unless concomitant left ventricular failure is present. In patients with chronic left ventricular dysfunction, the hemodynamic effects of intravenous digoxin and vasodilators are enhanced when these agents are given in combination.     

静脉滴注L-精氨酸对充血性心力衰竭患者的急性血流动力学效应

目的：评价充血性心力衰竭患静脉滴注L－精氨酸（L－arg）的急性血流动力学效应,探讨L－arg治疗心力衰竭的机制。方法：36例心力衰竭患（心功能Ⅳ级1例,Ⅲ级24例,Ⅱ1级11例）,以20％L－arg100ml加入5％葡萄糖溶液100ml,1h内恒速静脉滴注,每日1次,连续7d。记录用药后心率、血压变化,并对其中11例患（心功能Ⅲ级8例,Ⅱ级3例）采用有创检查观察血流动力学效应,同时测定用药后血液和尿液一氧化氮（NO）。结果：静脉滴注L－arg5min收缩压、舒张压、收缩压与心率乘积均有显降低（P＜0．05）,最大效应时间10－60min,心率无变化。血流动力学检查结果表明,静脉滴注L－arg可使平均动脉压和体循环阻力、肺动脉压、肺毛细血管嵌压、肺血管阻力显降低（P＜0．05－0．01）,心指数和左心室作功指数显增加（P＜0．01）。用药后尿液NO显升高。结论：心力衰竭患静脉滴注L－arg增加了体内NO,血流动力学明显改善。     

Correlations of hemodynamic parameters with plasma catecholamines in patients with congestive cardiomyopathy

Noradrenaline and adrenaline blood levels, as well as central hemodynamics (Swan-Ganz semi-floating balloon-tipped catheter), were measured at rest and during moderate exercise in 8 male patients suffering with idiopathic congestive cardiomyopathy (COCM), and in 12 healthy male control subjects. The stroke volume and the cardiac output in COCM were, on the average, one-half that of the control subjects; adrenaline, noradrenaline, pulmonary capillary wedge pressure, as well as the roentgenographically determined heart volume (at rest) in COCM were, on the average, increased more than twice the control values. The noradrenaline and adrenaline responses in COCM reached at the 25-W exercise level the response of controls at the 150-W level. Direct correlations were observed between the cate-cholamine responses and the capillary wedge pressure as well as the heart volume; inverse correlations existed between the catecholamines and the stroke volume or the cardiac output. The results may be indicative of a causal relationship between the reduced function of the left heart and a compensatorily increased sympathetic activity, but they are not at all conclusive for a definite cause-effect response. The differences in catecholamine levels and the correlations are more significant for noradrenaline during both exercise and rest, whereas for adrenaline significance only occurred during exercise. The noradrenaline and adrenaline levels may serve as indicators (especially in the chronic stage) in the diagnosis of reduced left ventricular function.