Lack of correlation between the acute haemodynamic response to intravenous captopril and plasma concentrations of angiotensin II in patients with chronic cardiac failure

Summary We have given a series of incremental intravenous injections of captopril to ten patients with chronic cardiac failure.Small doses of captopril produced significant changes in pulmonary artery end-diastolic pressure and right atrial pressure, up to a total cumulative dose of captopril of 2.5 mg, after which further injections had no significant effect. There were large changes in systemic vascular resistance and blood pressure up to a cumulative dose of captopril of 5.0 mg, after which the injection of larger doses caused no further significant changes.Small doses of intravenous captopril produced large increases in plasma renin activity and plasma angiotensin I concentrations up to a total cumulative dose of captopril of 1.25 mg, after which there were no significant further changes in either plasma renin activity or plasma angiotensin I concentration. However the plasma concentration of angiotensin II fell more slowly, no further change being recorded after a total cumulative dose of captopril of 10 mg.These results suggest that plasma renin activity is not the only determinant of plasma angiotensin II concentrations.     

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of intravenous administration of olprinone hydrochloride on experimental pulmonary hypertension

To examine acute effects of olprinone hydrochloride (CAS 106730-54-0, Coretec) on pulmonary hypertension, hypoxic pulmonary hypertension was produced in 6 adult Beagle dogs. Using this pulmonary hypertension model, single intravenous bolus injections of olprinone at doses of 10, 30 and 100 micrograms/kg were administered at 5-min intervals and hemodynamic parameters were evaluated. Heart rate increased at doses of 30 and 100 micrograms/kg, but did not change at a dose of 10 micrograms/kg. Mean aortic pressure, mean pulmonary arterial pressure, pulmonary vascular resistance and systemic vascular resistance and right ventricular stroke work index did not change at doses of 10 and 30 micrograms/kg, but they decreased significantly at a dose of 100 micrograms/kg. On the other hand, cardiac index and the first derivative value of the left ventricular pressure did not show significant change at all doses. These results indicate the vasodilating effects on peripheral and pulmonary vessels in hypoxic model at high doses of olprinone. Its application in right heart failure accompanied by pulmonary hypertension therefore is expected to yield promising results.     

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.     

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.     

The dopamine congener, ibopamine, in congestive heart failure

The hemodynamic effects of the dopamine congener, ibopamine, were investigated in nine patients with chronic congestive heart failure. A placebo-controlled design was utilized. Placebo and ibopamine in doses of 100, 200, and 300 mg were given orally as a single dose to each patient on 4 successive days. Dopamine at 1, 2, 4, and 6 micrograms/kg/min intravenously, was used as an internal standard. Ibopamine did not significantly change heart rate, systemic and pulmonary arterial pressures, pulmonary capillary wedge pressure, or mean right atrial pressure. Significant decreases of systemic arterial resistance (19%) and total pulmonary arterial resistance (21%), and significant increases of cardiac index (20%) and stroke volume index (16%) were elicited by ibopamine at doses of 200 and 300 mg. Peak effects occurred at 1 to 2 h with a duration of action of less than 4 h. The 2 changes were comparable with those obtained by dopamine 2-4 micrograms/kg/min. Except for mild changes at 30 min postdosing, the inotropic indices of the systolic time intervals were not altered significantly by ibopamine. Ibopamine elicits significant hemodynamic effects in patients with chronic congestive heart failure; in large part, these effects appear to be mediated through vasodilatory properties rather than direct positive inotropy.     

Characterization of the dose-concentration-dependent hemodynamic effects of nifedipine in heart failure

The hemodynamic effects of increasing oral doses of nifedipine (10 to 30 mg) were studied in 12 patients who had low output heart failure. With each set of hemodynamics, serum concentrations of nifedipine were measured to determine the concentration/response relationships. Eleven of twelve patients responded acutely to nifedipine, defined as a reduction in systemic vascular resistance (SVR), and an augmentation in cardiac index (CI) and stroke volume index (SVI). The differential dose effects (X +/- SD) for SVR and SVI for baseline (N = 11), 10 mg (N = 10), 20 mg (N = 3) and 30 mg (N = 4) were: 1913 +/- 486, 1102 +/- 221, 1128 +/- 166, 803 +/- 176 and 17.9 +/- 4.8, 23.8 +/- 4.5, 31 +/- 0.42, 33 +/- 3.5, respectively. All nifedipine doses reduced SVR and increased CI and SVI compared with baseline (P less than .001). The increase in CI and SVI was significantly correlated to the mg/kg dose of nifedipine (r = 0.79; P less than .001). Nifedipine administration resulted in no significant change in central venous pressure, pulmonary capillary wedge pressure, or pulmonary vascular resistance. No relationship could be demonstrated between serum concentrations of nifedipine and any hemodynamic effect. Conclusions drawn were: (1) the afterload reduction effects of nifedipine are acutely efficacious in a large portion of patients with heart failure and this activity supercedes the negative inotropic effects of the drug at doses between 10 and 30 mg; (2) the magnitude of the hemodynamic effects are dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Milrinone. A preliminary review of its pharmacological properties and therapeutic use

Milrinone is a bipyridine derivative of amrinone, with approximately 10 to 75 times greater positive inotropic potency, and separate direct vasodilatory properties. As with amrinone, the relative importance of these properties to treatment of congestive heart failure still remain controversial. The mode of action of milrinone appears to be due in part to selective inhibition of a specific cardiac phosphodiesterase with a subsequent increase in intracellular cyclic adenosine monophosphate and alteration in intracellular and extracellular calcium transport. Clinical experience has involved both short and long term treatment of a limited number of patients with moderate to severe congestive heart failure refractory to conventional therapy. Milrinone has usually been administered as intravenous bolus doses (12.5 to 75 micrograms/kg) and/or continuous intravenous infusion (0.5 microgram/kg/min), or orally (30 to 40 mg/day in divided doses). Milrinone rapidly improves cardiac performance by enhancing myocardial contractility, and by decreasing systemic vascular resistance (afterload), left ventricular filling pressure (preload), and pulmonary arterial pressure. Exercise performance improvement occurs with enhancement of left ventricular performance but without a significant increase in myocardial oxygen consumption or significant decrease in mean arterial pressure. Milrinone has been compared with dobutamine, nitroprusside and captopril in preliminary short term studies in patients with severe congestive heart failure. Milrinone significantly increased stroke work index and decreased left ventricular filling pressure compared to nitroprusside. When compared with dobutamine, both drugs improved cardiac index (to a similar degree), but milrinone significantly reduced right atrial pressure, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure. One small study suggests that short term effects of intravenous milrinone may be superior to those of oral captopril, and it appears that the addition of captopril to milrinone therapy may produce a synergistic haemodynamic effect. Preliminary long term studies suggest that tolerance to the haemodynamic effects of milrinone does not occur, and that the drug is well tolerated and without the thrombocytopenic effects, fever and gastrointestinal complications observed with amrinone. However, it has not been demonstrated that milrinone improves the prognosis of the disease or the overall mortality and its propensity to produce arrhythmias has not been fully agreed upon.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cumulative hemodynamic response to short-term treatment with flosequinan (BTS 49465), a new direct-acting vasodilator drug, in severe chronic congestive heart failure

Pharmacologic tolerance develops rapidly to the hemodynamic effects of many vasodilator drugs used in the treatment of congestive heart failure. We evaluated the responses to 3 days of therapy with a new long-acting vasodilator drug, flosequinan (BTS 49465), in 16 patients with severe chronic heart failure. On each of the 3 days, flosequinan (100 or 150 mg orally) produced marked increases in cardiac index and decreases in left ventricular filling pressure, mean right atrial pressure, and systemic vascular resistance (all p less than 0.01) without significant changes in heart rate. Whereas the effects of flosequinan on right and left ventricular filling pressures on the first and third days were similar, cardiac index was higher and systemic vascular resistance was lower after the third dose than after the first dose of the drug, indicating the occurrence of a cumulative vasodilator effect on arterial resistance vessels. Since all hemodynamic changes persisted for longer than 24 h after each dose of the drug, the daily administration of flosequinan also produced a progressive improvement in the hemodynamic state recorded before each dose of the drug. These data indicate that pharmacologic tolerance does not develop to the effects of flosequinan during short-term therapy with the drug in patients with severe chronic heart failure. Instead, further hemodynamic improvement may occur because of a cumulative vasodilator effect that results from the drug's prolonged duration of action.     

Circulatory and myocardial effects of different sodium antagonistic drugs in comparison to the calcium antagonist verapamil

The hemodynamic effects of intravenous class I and class IV antiarrhythmic drugs were investigated at different doses in comparison. In open-chest rats hemodynamic measurements in the intact circulation and isovolumic registrations 5 min after infusion of flecainide (2, 4, 8 mg/kg), disopyramide (1, 2, 4, 8 mg/kg), quinidine (5 and 10 mg/kg) and verapamil (0.35, 0.7, 1.5 mg/kg) were compared to saline controls. After clinically usual doses all investigated drugs had no effects on stroke volume, cardiac output, dp/dtmax and systemic resistance. The isovolumic pressure generating capacity of the left ventricle was not decreased at these doses. High intravenous doses of the drugs, however, caused a significant depression of myocardial performance (pressure generating capacity). Furthermore, flecainide decreased mean aortic pressure and heart rate, while disopyramide had no significant effect on the peripheral circulation. Blocking of the autonomic system (1 mg/kg propranolol and 0.1 mg/kg atropine) did not change significantly the action of disopyramide. Quinidine lowered heart rate and pressures. Verapamil reduced the heart rate and tended to decrease the mean aortic pressure. Besides the negative inotropic action of high doses the different hemodynamic profiles of class I and class IV antiarrhythmic drugs might be of importance for intravenous application in patients with left ventricular dysfunction.     

Infusion of atrial natriuretic peptide to patients with congestive heart failure

Atrial natriuretic peptides (ANP) exert vasodilating and natriuretic actions. The present study was undertaken to test the effect of low dose infusions of synthetic ANP on hemodynamic and humoral variables of patients with severe heart failure. Eight patients, aged 26 to 71 years, with severe congestive heart failure due to ischemic heart disease or idiopathic dilated cardiomyopathy were included in the study. Synthetic human (3-28) ANP was infused at doses ranging from 0.5 to 2 micrograms/min for up to 3 h. Pulmonary capillary wedge pressure fell from 24 +/- 1 to 16 +/- 2 mm Hg (mean +/- SEM) (p less than 0.01) and cardiac index tended to rise from 2 +/- 0.2 to 2.3 +/- 0.2 L/min/m2 (NS), while blood pressure and heart rate did not change. One patient experienced a marked drop in pulmonary capillary wedge and arterial blood pressure that necessitated the administration of saline. ANP infusion did not alter plasma renin activity or plasma aldosterone, norepinephrine, or vasopressin levels. It decreased plasma epinephrine levels from 0.472 +/- 0.077 to 0.267 +/- 0.024 nmol/L (p less than 0.05). Plasma ANP levels were markedly elevated in all patients before initiating the infusion. They had no predictive value for the hemodynamic response to exogenous ANP. No correlation was observed between the hemodynamic effects of ANP and those induced by the subsequently administered converting enzyme inhibitor captopril, which seemed to improve cardiac function more consistently.(ABSTRACT TRUNCATED AT 250 WORDS)     

SC-36602, a new antiarrhythmic agent: comparison of its cardiovascular profile with that of other antiarrhythmic drugs

The cardiovascular profile of SC-36602, a new class 1A/1B antiarrhythmic agent, was compared to those of disopyramide, lidocaine, mexiletine, flecainide, encainide, lorcainide, and quinidine. These drugs were compared at their respective canine antiarrhythmic doses in a hemodynamic evaluation using anesthetized dogs. In another test using anesthetized dogs, the cardiovascular effects of cumulative doses of SC-36602 were assessed. The direct negative inotropic potential of each drug was also determined using isolated cat papillary muscles. In the hemodynamic study, SC-36602 and quinidine did not cause significant myocardial depression, measured as a decrease in the maximal first derivative of the left ventricular pressure. (Heart rate and diastolic filling pressure were not controlled in order to mimic clinical conditions). SC-36602, mexiletine, flecainide, and quinidine increased heart rate. SC-36602 and mexiletine caused a small increase in mean arterial pressure, whereas disopyramide and quinidine decreased it. Disopyramide was the only drug studied that increased left ventricular end-diastolic pressure. SC-36602, quinidine, and mexiletine increased index of cardiac effort. Disopyramide caused a decrease in the latter. Disopyramide, flecainide, encainide, and lorcainide lengthened the ECG intervals. Cumulative intravenous doses of SC-36602 up to 50 mg/kg produced significant decreases in mean arterial pressure, increases in heart rate, and increases in P-R and QRS intervals of the ECG relative to placebo-matched controls. SC-36602 had the least direct negative inotropic action of the drugs studied, as measured in isolated papillary muscles. These data suggest SC-36602, when compared to the other antiarrhythmic drugs studied, has the least amount of hemodynamic side-effects at its antiarrhythmic dose.     

Hemodynamic actions of corticotropin-releasing hormone and proopiomelanocortin derivatives in septic patients

Proopiomelanocortin (POMC) derivatives and mRNA of POMC have been detected in cardiomyocytes and vascular smooth muscle cells. Increased plasma levels of POMC derivatives have been found in septic patients during cardiovascular deregulation; therefore, we evaluated whether corticotroph-type (ACTH, β-endorphin, β-lipotropin) or melanotroph-type (α-melanocyte-stimulating hormone and N-acetyl-β-END) POMC derivatives have influences on patients' hemodynamics during sepsis. Seventeen septic patients were monitored by pulmonary artery catheter and corticotropin-releasing hormone (CRH) tests were performed by intravenous administration of 100 μg CRH. Before, 15, 30, 45, and 60 minutes after CRH administration, hemodynamic variables were measured, and plasma concentrations of POMC derivatives were determined. After CRH administration, heart rate, cardiac index, and stroke index increased, and the systemic vascular resistance index decreased; moreover, a correlation between ACTH concentration and stroke index as well as an inverse correlation between (α-melanocyte-stimulating hormone concentration and systemic vascular resistance index was observed. CRH and ACTH may have opposite effects on the blood pressure (mean arterial pressure). Immediately after CRH injection mean arterial pressure decreased. ACTH (in contrast to β-endorphin or β-lipotropin), released into the cardiovascular compartment 15 minutes after CRH injection, might have raised mean arterial pressure as compatible with the correlation between ACTH levels and stroke index. (α-melanocyte-stimulating hormone appears to have a vasodilative effect during sepsis.     

The acute hemodynamic, hormonal, and pharmacokinetic properties of oral spirapril in patients with moderate to severe heart failure.

The acute hemodynamic, hormonal, and pharmacokinetic responses to the oral angiotensin-converting enzyme (ACE) inhibitor spirapril were studied in 15 patients with moderate to severe congestive heart failure in a baseline controlled dose-ranging study. Doses of 0.3, 1.0, 1.5, 3.125, and 6.25 mg were investigated for 24 h in three groups of five patients each. All doses demonstrated a significant reduction in serum ACE, even after 24 h. Significant reductions in mean arterial pressure, systemic vascular resistance, and pulmonary capillary wedge pressure were observed with doses greater than 1.0 mg spirapril. Maximal significant hemodynamic effects occurred approximately 4-6 h after drug administration. The plasma concentrations of spirapril and its metabolite spiraprilate were dose-dependent. After administration of spirapril, the quick rise to the peak level of spiraprilate suggests rapid metabolism of spirapril into spiraprilate and a slow elimination of this metabolite. No severe hypotension or other serious side effects occurred in the patients studied. The results indicate that spirapril may be expected to be an effective drug in the treatment of congestive heart failure. From our findings we conclude that 1.5 mg spirapril is an optimal starting dose in patients with moderate to severe congestive heart failure.     

Pharmacokinetics and haemodynamic effects of tocainide in patients with acute myocardial infarction complicated by left ventricular failure.

The pharmacokinetics and haemodynamic effects of tocainide, an orally active structural analogue of lignocaine, were studied in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (mean age 65 years) with acute myocardial infarction complicated by mild left ventricular failure were studied, following a single dose of tocainide (250 mg) by intravenous infusion, over 30 min. Heart rate, systemic arterial pressure, pulmonary artery pressure and cardiac output were monitored. Plasma tocainide levels were estimated by gas chromatography. The mean plasma level of tocainide achieved was 2.95 micrograms/ml (15.37 mmol/l). The mean plasma half-life was 15.6 h. The mean cardiac index was reduced 5 min after completion of the infusion, from 2.24 1 min-1 m-2 (+/- 0.40) to 2.07 1 min-1 m-2 (+/- 0.29) (P less than 0.01). At 90 min the cardiac index had returned to pre-treatment levels. Small changes were seen in the heart rate, arterial blood pressure and the pulmonary artery pressure but these changes were not statistically significant. The pharmacokinetics of tocainide were not significantly altered in patients with acute myocardial infarction complicated by mild left ventricular failure.     

Hemodynamic and electrophysiologic effects of combined infusion of lidocaine and propafenone in humans

The hemodynamic and electrophysiologic effect of a combined intravenous infusion of lidocaine (100 mg bolus followed by 2 mg/min infusion) and propafenone (1 or 2 mg/kg) in patients with a history of ventricular arrhythmia was studied. Lidocaine infusion alone significantly increased the mean pulmonary artery (+28%) and pulmonary capillary wedge (+17%) pressure, with no effect on cardiac index. Lidocaine alone produced no consistent change in any measured electrophysiologic parameter, except slight QTc shortening (-2%, P less than .05). Propafenone alone, particularly at the higher dose (2 mg/kg), produced significant increases in mean blood pressure (+14%), right atrial pressure (+78%), pulmonary artery pressure (+50%), pulmonary capillary wedge pressure (+65%), systemic vascular resistance (+29%), and pulmonary vascular resistance (+61%) and a decrease in cardiac index (-12%). Significant prolongation of PR (+9%), AH (+29%), and HV (+23%) intervals, atrial functional refractory period (+12%), ventricular effective (+7%) and functional (+6%) refractory period, and Wenckebach cycle length (+13%) also occurred after the administration of propafenone alone. Only the effects on atrioventricular (AV) node were observed at the lower dose of propafenone (1 mg/kg). Combined infusion of lidocaine with propafenone produced a mild, statistically insignificant additional negative inotropic effect but reversed the prolongation in atrial and ventricular refractoriness produced by propafenone alone. Thus, the data show that lidocaine attenuates certain electrophysiologic effects of propafenone, which might alter its antiarrhythmic efficacy, while producing mild additive negative inotropic effects that may be of hemodynamic significance.     

Haemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril

Objective: Levosimendan in a new inodilator drug that sensitises troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40–50%.The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug. Methods: The haemodynamic effects of levosimendan, given with or without captopril, were evaluated by using 2-dimensional echocardiography, repeated blood pressure measurements and by ambulatory ECG recordings. Twenty-four male patients with stable NYHA II-III heart failure (EF<40%) after a previous myocardial infarct were given, in randomised order, a single IV infusion of levosimendan or placebo. The infusions were repeated after 2 weeks treatment with upto 50 mg b.i.d. of captopril. Twelve patients received levosimendan 1 mg and twelve received 2 mg. Results: Mean CO was increased from 6.0 to 6.81·min^–1 in patients receiving 1 mg levosimendan compared to placebo, but only from 6.3 to 6.51·min^–1 in patients receiving 2 mg. The increase in CO was statistically significant when all levosimendan patients were compared to placebo. Heart rate did not change after either dose. Mean stroke volume increased significantly after 1 mg but not after 2 mg of levosimendan. The addition of captopril did not change the effects of levosimendan. No additional decrease in systolic or diastolic blood pressure was observed when levosimendan and captopril were given concomitantly. Conclusion: It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.     

硝苯地平与卡托普利单用及联合应用对低氧性肺动脉高压的作用

目的 :探讨硝苯地平与卡托普利单用及联用对低氧性肺动脉高压 (PAH)的作用。方法 :30例慢性阻塞性肺疾病 (COPD)合并肺心病病人 ,通过Swan_Ganz导管分别观察了硝苯地平 2 0mg舌下含服与卡托普利 2 0mg静脉注射 ,单用或 2药联用 3组各 10例对平均肺动脉压 (MPAP)等血流动力学参数的影响。结果 :硝苯地平无明显降低MPAP、肺血管阻力 (PVR)的作用 (P >0 .0 5) ,但却显著降低体循环平均压 (MAP )、动脉血氧分压Pao2 (P <0 .0 1,P <0 .0 5)。卡托普利可显著降低MPAP和PVR(P <0 .0 5) ,对MAP和Pao2 无明显的影响。 2药联用可更显著地降低MPAP、PVR (P <0 .0 1)。结论 :卡托普利是治疗低氧性PAH的一个有效药物 ,与硝苯地平联用有协同作用     

Effects of captopril on pulmonary haemodynamics

Summary The effects of oral captopril on pulmonary haemodynamics were studied in two groups of 6 patients, one of subjects with chronic respiratory failure (PaO₂ 52±5.1 mmHg, PaCO₂ 54±2.1 mmHg), and the others with chronic heart failure and high plasma renin activity. Two potential mechanisms of its actions were assessed, namely inhibition of hypoxic vasoconstriction and inhibition of the possible effects of angiotensin II on the pulmonary circulation. There were significant (p<0.05) decreases in mean arterial pressure, pulmonary wedge pressure and in systemic arterial resistance associated with improvement in cardiac index in both groups. In the chronic respiratory failure group there was no change in blood gases, mean pulmonary arterial pressure or pulmonary vascular resistance. An increase in driving pressure (p<0.05) indicated that captopril had had no effect on pulmonary haemodynamics. In chronic heart failure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure were decreased by a similar extent, so that driving pressure and pulmonary vascular resistance were not changed. It is concluded that oral captopril did not inhibit hypoxic vasoconstriction, and that it modified pulmonary haemodynamics in chronic heart failure patients with high renin activity only as a consequence of reduction in systemic afterload. Presented in part at the annual meeting of the American Thoracic Society, Kansas City, in May 1983     

心力衰竭时静注氨力农的血流动力学与血药浓度的关系

对8例心力衰竭患者静注国产氨力农1mg/kg,继以7.5μg/(kg·min)静滴6h。由漂浮导管测定血流动力学变化,HPLC法测血药浓度的改变。结果:心指数在血药浓度为1.05μg/mL左右时增加较大(最大增幅为23.8％),但不随浓度的继续上升而增高,两者有一定相关性(r=0.72,P<0.05)。肺动脉压和肺楔嵌压显著下降,但与血药浓度变化无关。提示该药的扩血管作用较明显,但可能存在耐受性。