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Biomedical subjects

M Packer

Publications and source records attributed to M Packer.

At least 91 records · Page 5Linked to original sources
PubMed1986

Hormone-electrolyte interactions in the pathogenesis of lethal cardiac arrhythmias in patients with congestive heart failure. Basis of a new physiologic approach to control of arrhythmia.

Congestive heart failure is the most arrhythmogenic disorder in cardiovascular medicine. As left ventricular performance deteriorates and symptoms of dyspnea and fatigue become progressively more severe, nearly all patients with heart failure experience frequent and complex ventricular tachyarrhythmias and nearly half die suddenly during long-term follow-up. This imminent risk of sudden death appears to be present for all patients with congestive heart failure; ambulatory electrocardiographic monitoring and programmed electrical stimulation are not useful in distinguishing patient subsets that are particularly predisposed to fatal arrhythmic events. Although conventional antiarrhythmic agents are widely prescribed as a nonspecific approach to prevent sudden death in these patients, there is little evidence to indicate that these drugs possess clinically important antiarrhythmic activity in patients with congestive heart failure, and these agents frequently serve to exacerbate the heart failure state and the underlying ventricular tachyarrhythmia. A useful approach to the prevention of sudden death in patients with congestive heart failure addresses the reversible causes of lethal ventricular arrhythmias in these individuals. Both experimental and clinical evidence indicates that circulating neurohormones and electrolyte deficits (particularly of potassium and magnesium) interact to provoke malignant ventricular ectopic rhythms and that the prevention of electrolyte depletion and the use of neurohormonal antagonists may exert clinically important antiarrhythmic actions. This physiologic approach may prove to be a more effective means of ameliorating the problem of sudden death than the empiric administration of conventional antiarrhythmic drugs.

Adrenergic beta-Antagonists↗
PubMed1986

Systemic vasoconstrictor effects of oxygen administration in obliterative pulmonary vascular disorders.

Although oxygen is frequently administered to patients with obliterative pulmonary vascular disorders (OPVD) for diagnostic and therapeutic purposes, its hemodynamic effects in these patients have not been systematically evaluated. The response to administration of 50 to 70% oxygen was studied in 14 patients with pulmonary hypertension secondary to OPVD. Mean pulmonary artery pressure decreased (from 62 +/- 5 to 57 +/- 5 mm Hg, p less than 0.01) after oxygen inhalation secondary to a decrease in cardiac index (1.9 +/- 0.2 to 1.8 +/- 0.2 liters/min/m2, p less than 0.01), without changes in pulmonary arteriolar resistance. This decline in forward output appeared to result from a systemic vasoconstrictor effect of oxygen (change in systemic vascular resistance from 1,965 +/- 275 to 2,297 +/- 336 dynes s cm-5, p less than 0.01), which decreased heart rate (from 93 +/- 3 to 89 +/- 2 beats/min, p less than 0.01) by stimulation of baroreceptor reflexes and decreased stroke volume (from 22 +/- 3 to 21 +/- 2 ml/beat/m2, p less than 0.05) by increasing impedance to left ventricular ejection. The decrease in left-sided cardiac output likely led to a decline in venous return to the right side of the heart and, consequently, to a decrease in right atrial and pulmonary arterial pressures. Accordingly, the percent decrease in mean pulmonary artery pressure varied linearly and directly with the percent increase in systemic vascular resistance (r = 0.84), but not with changes in pulmonary arteriolar resistance (r = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Hemodynamic factors limiting the response to transdermal nitroglycerin in severe chronic congestive heart failure.

To clarify the continuing controversy concerning the use of transdermal nitroglycerin (TDN), the shortterm hemodynamic responses to sublingual, oral and transcutaneous nitrates were evaluated and compared in 22 patients with severe chronic congestive heart failure. Sixteen patients showed favorable hemodynamic effects with TDN, but the doses needed to achieve this response varied greatly: 10 mg/24 hours in 6 patients, 20 mg/24 hours in 5 patients, 40 mg/24 hours in 3 patients and 60 mg/24 hours in 2 patients. Of the 6 remaining patients, 3 did not respond to high-dose TDN even though they showed marked effects after sublingual and oral nitrate administration; 3 others did not respond to any nitrate formulation by any route. TDN produced immediate increases in cardiac index and decreases in right and left ventricular filling pressure, mean arterial pressure and systemic vascular resistance (p less than 0.01). These effects, however, became rapidly attenuated within 3 to 6 hours; after 18 to 24 hours, only modest decreases in right and left ventricular filling pressures were observed. After removal of TDN treatment, rebound decreases in cardiac index and rebound increases in mean arterial pressure and systemic vascular resistance occurred, but right and left ventricular filling pressures returned to pretreatment values without rebound changes. Isosorbide dinitrate, 40 mg orally, produced hemodynamic effects that were greater in magnitude than effects seen after administration of TDN (p less than 0.05 to 0.01), but 4 patients in whom tolerance to TDN developed showed reversible cross tolerance to oral isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Role of the renin-angiotensin system in the development of hemodynamic and clinical tolerance to long-term prazosin therapy in patients with severe chronic heart failure.

Right heart catheterization was performed before and during long-term therapy with prazosin in 27 patients with severe chronic heart failure who underwent serial hemodynamic studies during 3 to 12 weeks of treatment with the drug. Doses of digoxin and furosemide remained constant during the trial; in addition, 11 of the 27 patients were assigned to concomitant therapy with spironolactone, while the remaining 16 patients did not receive the aldosterone antagonist. First doses of prazosin produced marked increases in cardiac index and marked decreases in mean arterial pressure, left ventricular filling pressure and systemic vascular resistance in both groups of patients (all p less than 0.01), but these effects became rapidly attenuated (p less than 0.01) in both groups after 48 hours and remained attenuated during long-term therapy. After 3 to 12 weeks, values for cardiac index returned to pretreatment levels and did not decrease when the drug was withdrawn; values for mean arterial pressure, left ventricular filling pressure and systemic vascular resistance remained significantly decreased (although attenuated) after 3 to 12 weeks (p less than 0.01) and increased to pretreatment values when the drug was withdrawn. The magnitude and time course of these responses were not altered by concomitant therapy with spironolactone. Complete loss of hemodynamic efficacy (prazosin tolerance) was noted in 14 (58%) of the 24 patients who underwent long-term hemodynamic study and was not accompanied by long-term changes in plasma renin activity or body weight. These data indicate that prazosin produces long-term hemodynamic and clinical benefits in only 30 to 40% of patients with severe chronic heart failure and do not support a role for the renin-angiotensin system in the development of tolerance to alpha-adrenergic blockade. This low response rate explains why most randomized double-blind trials of prazosin in heart failure have not been able to demonstrate a significant difference between patients treated with placebo and those receiving active drug.

Adrenergic alpha-Antagonists↗
PubMed1986

Comparative immediate hemodynamic and hormonal effects of amrinone and captopril in patients with severe chronic heart failure.

To compare the responses to oral inotropic and vasodilator drugs, maximally effective doses of amrinone (300 mg over 3 hours) and captopril (25 mg orally) were administered to 21 patients with severe chronic heart failure, who had not received either agent previously. Despite similar decreases in systemic vascular resistance with both drugs, amrinone produced greater increases in cardiac index (+ 0.56 vs. + 0.41/min/m2, p less than 0.05) and smaller decreases in mean arterial pressure (-11.1 vs. -15.2 mm Hg, p less than 0.05) than did captopril; three patients became symptomatically hypotensive with captopril, but none did so after amrinone. These differences were due to a significant decrease in heart rate with captopril (-6.3 beats/min, p less than 0.01), whereas heart rate increased with amrinone (+ 4.3 beats/min, p less than 0.01); the increases in stroke volume index with both drugs were similar. Despite similar decreases in left ventricular filling pressures, the decrease in mean right atrial pressure with amrinone was greater than with captopril (-5.6 vs. -3.2 mm Hg, p less than 0.01). This difference was the result of the greater decrease in pulmonary arteriolar resistance, and hence in right ventricular afterload, with amrinone than with captopril, (-33% vs. -16%, respectively), p less than 0.01. Despite these superior hemodynamic responses to amrinone, when patients received sequential long-term treatment with both drugs during the follow-up period, only 12% of patients benefitted during therapy with amrinone, whereas 64% improved clinically with captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure.

Although past reports have identified a variety of prognostic factors in patients with severe chronic heart failure, previous studies have not evaluated the interaction of prognostic variables and drug treatment. We analyzed the association of 30 clinical, hemodynamic, and biochemical variables with survival in 203 consecutive patients with severe heart failure; all variables were assessed just before initiation of treatment with a variety of vasodilator drugs, and all patients were subsequently followed for 6 to 94 months. By regression analysis, pretreatment serum sodium concentration was the most powerful predictor of cardiovascular mortality, with hyponatremic patients having a substantially shorter median survival than did patients with a normal serum sodium concentration (164 vs 373 days, p = .006). The unfavorable prognosis for hyponatremic patients appeared to be related to the marked elevation of plasma renin activity that we noted in these individuals (10.0 +/- 2.0 ng/ml/hr), since hyponatremic patients fared significantly better when treated with angiotensin converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II biosynthesis (median survival 232 vs 108 days, p = .003). In contrast, there was no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low (1.9 +/- 0.3 ng/ml/hr). This interaction between serum sodium concentration, drug treatment, and long-term outcome suggests that the renin-angiotensin system may exert a deleterious effect on the survival of some patients with chronic heart failure, which can be antagonized by converting enzyme inhibition, and provides a clinical counterpart for the similar prognostic role that has been postulated for angiotensin II in experimental preparations of heart failure.

Adult↗
PubMed1986

Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system.

When renal perfusion pressure is reduced in experimentally induced low-output states, glomerular filtration rate is preserved by angiotensin II-mediated efferent arteriolar vasoconstriction, but available evidence in man suggests that angiotensin II supports renal function only to the extent that it preserves systemic blood pressure. We performed simultaneous assessments of cardiac and renal function in 56 patients with severe chronic heart failure before and after 1 to 3 months of converting-enzyme inhibition. Among the 29 patients with a pretreatment renal perfusion pressure under 70 mm Hg, patients with preserved renal function (creatinine clearance greater than 50 ml/min/1.73 m2) had markedly elevated values for plasma renin activity (11.8 +/- 3.8 ng/ml/hr) and showed a significant decline in creatinine clearance after converting-enzyme inhibition (61.1 +/- 3.0 to 45.9 +/- 5.3 ml/min/1.73 m2; p less than .05). In contrast, although similar with respect to all pretreatment demographic, hemodynamic, and clinical variables, patients with a creatinine clearance under 50 ml/min/1.73 m2 had low values for plasma renin activity (3.4 +/- 0.8 ng/ml/hr) and, despite similar drug-induced decreases in systemic blood pressure, showed no change in creatinine clearance after therapy with captopril or enalapril (32.6 +/- 2.5 to 41.4 +/- 3.8 ml/min/1.73 m2). Changes in creatinine clearance varied linearly and inversely with pretreatment values for plasma renin activity (r = - .64, p less than .001); converting-enzyme inhibition effectively abolished the pretreatment difference in renal function seen in the high- and low-renin subgroups. In the 27 patients with a renal perfusion pressure of 70 mm Hg or greater, creatinine clearance did not vary significantly with plasma renin activity and was not altered by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

The role of vasodilator therapy in the treatment of severe chronic heart failure.

The rationale for the use of vasodilating agents in the treatment of congestive heart failure is to reverse the systemic vasoconstriction that characterises patients with this disorder, and which may further limit cardiac performance. Nitrates were the first vasodilators used, followed by arterial vasodilators (hydralazine, minoxidil), alpha-adrenergic blockers (prazosin, trimazosin) and, more recently, calcium antagonists, ACE inhibitors, beta-agonists and phosphodiesterase inhibitors. The choice of vasodilator should be based on consideration of overall benefit-risk profiles. Consideration of pharmacological action together with classification of patients into haemodynamic subsets has been used as a basis from which to initiate vasodilator therapy. However, such a classification may not lead to a logical choice of drug and there is no evidence to suggest that patients so selected do better when given long term treatment with peripherally specific drugs than with agents that are not tailored to pretreatment haemodynamic variables. Moreover, changes in central haemodynamics after administration of specific vasodilator drugs may differ from those expected on the basis of their presumed actions on the peripheral vasculature. Dosage requirements are difficult to predict with many vasodilator drugs. Traditionally, such requirements have been established by titrating vasodilating drugs to achieve an arbitrarily defined haemodynamic response. However, there is little correlation between haemodynamic end-points and clinical efficacy in patients with heart failure, and short and long term haemodynamic responses to vasodilator drugs are not necessarily related. Drug-specific haemodynamic and clinical tolerance occurs during the course of treatment with all vasodilator drugs; the extent and frequency with which it develops differs between agents. Tolerance is thought to arise from a reduction in drug receptor affinity and/or density or activation of counter-regulatory forces (mainly neurohormonal) that limit the magnitude of vasodilatation that can be achieved. Development of tolerance to a single agent does not usually preclude efficacy of other agents. ACE inhibitors have been associated with a relatively low incidence of tolerance. This may relate to their natriuretic effect and ability to decrease the degree of neurohormonal activation, actions not shared by other vasodilators. Tolerance is the principal reason for failure of prazosin and nitrates as therapeutic agents in severe chronic heart failure.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic Disease↗
PubMed1986

Influence of renal function on the hemodynamic and clinical responses to long-term captopril therapy in severe chronic heart failure.

To evaluate the influence of renal function on the efficacy of converting-enzyme inhibition in patients with severe chronic heart failure, we measured the long-term hemodynamic and clinical responses to captopril in 101 consecutive patients with heart failure grouped according to pretreatment serum creatinine concentration (group I, less than 1.4 mg/dL; group II, 1.4 to 2.8 mg/dL; and group III, greater than 2.8 mg/dL). After 1 to 3 months of treatment, patients with preserved renal function (group I) had greater increases in stroke volume index and greater decreases in left ventricular filling pressure and systemic vascular resistance than did patients with renal impairment (groups II and III) (p less than 0.05). Clinical improvement paralleled these hemodynamic benefits; only 2 of 12 patients with severe renal insufficiency (group III) improved clinically compared with 29 of 40 patients with preserved renal function (group I) and 29 of 49 patients with mild-to-moderate renal impairment (group II), (p less than 0.005). Therapy-limiting rash and dysgeusia occurred most frequently in patients with renal impairment. Our findings support an important role for the kidneys in mediating the beneficial actions of captopril in patients with severe congestive heart failure.

Adult↗
PubMed1986

Adverse effects of converting-enzyme inhibition in patients with severe congestive heart failure: pathophysiology and management.

Although converting-enzyme inhibition is of established value in the management of patients with severe chronic congestive heart failure, troublesome adverse reactions occur frequently during the course of treatment and may cause physicians to interrupt effective therapy. The three most common adverse reactions that are seen in patients with heart failure following treatment with captopril and enalapril (symptomatic hypotension, functional renal insufficiency, hyperkalaemia) are predictable consequences of interfering with the homeostatic functions of the renin-angiotensin system, which evolved millions of years ago to preserve life in sodium-depleted states. It is not surprising, therefore, that these untoward effects can be prevented or reversed by increasing the dietary intake of salt or reducing the dose of concomitantly administered diuretics; their occurrence rarely requires discontinuation of drug therapy. Recognition of this link between sodium balance and the adverse effects of converting-enzyme inhibition is important, because most patients with severe heart failure who experience such untoward reactions can nevertheless be expected to improve clinically during long-term therapy, if effective treatment is not interrupted.

Acute Kidney Injury↗
PubMed1985

Coupling factor activity of the purified pea mitochondrial F1-ATPase.

The pea cotyledon mitochondrial F1-ATPase was released from the submitochondrial particles by a washing procedure using 300 mM sucrose/2 mM Tricine (pH 7.4). The enzyme was purified by DEAE-cellulose chromatography and subsequent sucrose density gradient centrifugation. Using polyacrylamide gel electrophoresis under non-denaturing conditions, the purified protein exhibited a single sharp band with slightly lower mobility than the purified pea chloroplast CF1-ATPase. The molecular weights of pea mitochondrial F1-ATPase and pea chloroplast CF1-ATPase were found to be 409 000 and 378 000, respectively. The purified pea mitochondrial F1-ATPase dissociated into six types of subunits on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Most of these subunits had mobilities different from the subunits of the pea chloroplast CF1-ATPase. The purified mitochondrial F1-ATPase exhibited coupling factor activity. In spite of the observed differences between CF1 and F1, the mitochondrial enzyme stimulated ATP formation in CF1-depleted pea chloroplast membranes. Thus, the mitochondrial F1 was able to substitute functionally for the chloroplast CF1 in reconstituting photophosphorylation.

Adenosine Triphosphate↗
PubMed1985

Therapeutic application of calcium-channel antagonists for pulmonary hypertension.

Calcium-channel antagonists may provide an effective approach to the treatment of pulmonary hypertensive disorders. Biochemical evidence suggests that pulmonary vasoconstriction results from the transmembrane flux of calcium into vascular smooth muscle; accordingly, the pulmonary pressor responses in experimental hypoxic pulmonary hypertension can be attenuated by verapamil and nifedipine. In patients with chronic obstructive lung disease, nifedipine decreases pulmonary artery pressures and pulmonary vascular resistance in proportion to the severity of hypoxemia before treatment. However, little pulmonary vasodilator effect is seen when hypoxemia is corrected by inhalation of oxygen, and systemic arterial oxygen desaturation can occur after nifedipine in patients breathing room air; most importantly, long-term studies in patients with chronic lung disease are lacking. In selected patients with primary pulmonary hypertension and other obliterative diseases of the pulmonary vasculature, nifedipine produces short- and long-term hemodynamic improvement at rest and during exercise, and these benefits are frequently paralleled by amelioration of dyspnea and fatigue. However, in patients in whom right ventricular function has been severely compromised by chronic pressure overload, both verapamil and nifedipine may exert notable depressant effects on right ventricular performance, despite the decrease in right ventricular afterload that would be expected to accompany a decrease in pulmonary vascular resistance. These negative inotropic actions may result in serious deleterious clinical reactions. Although calcium-channel antagonists represent a promising approach to the management of patients with pulmonary hypertension, the long-term efficacy and safety of these drugs in this disorder remain to be established.

Animals↗
PubMed1985

Comparative effects of captopril and isosorbide dinitrate on pulmonary arteriolar resistance and right ventricular function in patients with severe left ventricular failure: results of a randomized crossover study.

We compared the short-term hemodynamic effects of isosorbide dinitrate (40 mg orally) and captopril (25 mg orally) in 18 patients with severe chronic heart failure in a randomized, crossover study conducted on consecutive days. Captopril and isosorbide dinitrate produced similar decreases in systemic vascular resistance, but whereas nitrate therapy decreased pulmonary arteriolar resistance significantly, captopril did not; the difference between the two drugs was highly significant (-25% vs -5%, p less than 0.001). Left ventricular filling pressures declined similarly with both captopril (-10.5 mm Hg) and with isosorbide dinitrate (-9.3 mm Hg), but because pulmonary arteriolar resistance fell significantly with nitrate therapy, mean right atrial pressure decreased more with isosorbide dinitrate than with captopril (-5.4 vs -2.8 mm Hg, respectively; p less than 0.001). Although systemic resistance declined similarly with both drugs, cardiac index increased more with nitrate therapy than during converting-enzyme inhibition (+0.47 vs +0.23 L/min/m2) (p less than 0.01), and therefore mean arterial pressure fell less with isosorbide dinitrate than with captopril (-10.5 mm Hg vs -16.7 mm Hg); p less than 0.05); two patients developed symptomatic hypotension with captopril, whereas none did so with the nitrate. The difference in the effects of the two drugs on cardiac index was not due to differences in their effects on heart rate, since heart rate fell similarly with both drugs, and thus both drugs produced similar increases in stroke volume index. These data indicate that, in patients with severe chronic heart failure, nitrates exert favorable dilating effects on the pulmonary circulation not shared by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1985

Mechanisms of nitrate action in patients with severe left ventricular failure: conceptual problems with the theory of venosequestration.

Nitroglycerin and other organic nitrates exert a number of favorable effects on the circulation of patients with severe congestive heart failure, and these effects mediate the short- and long-term hemodynamic and clinical improvement that follows treatment with these drugs. Although these agents are potent dilators of systemic venous capacitance vessels, present evidence indicates that they do not exert their beneficial hemodynamic and clinical effects by decreasing venous return to the heart. Rather, their ability to dilate pulmonary and systemic resistance vessels offsets any decrease in cardiac output that might be expected to occur from a decrease in venous return. Of equal importance, the increase in output of the left side of the heart that results from drug-induced pulmonary and systemic vasodilation prevents any decrease in venous return to the right side of the heart that might be expected to accompany an increase in systemic venous capacitance. The net effect of these two interacting forces is not only to keep cardiac output and venous return constant but also to translocate blood volume from the pulmonary circulation and left ventricle to the systemic vessels. In addition, nitrates also relieve subendocardial ischemia and favorably alter pressure-volume relationships in the left ventricle. These observations support the conclusion that the complex cardiovascular responses to organic nitrates in patients with congestive heart failure cannot be adequately summarized by the single concept of preload reduction.

Arteries↗
PubMed1985

Hemodynamic and clinical significance of the pulmonary vascular response to long-term captopril therapy in patients with severe chronic heart failure.

Exercise capacity in patients with left heart failure is closely related to the performance of the right ventricle and the pulmonary circulation. To determine the significance of changes in pulmonary resistance during long-term vasodilator therapy, hemodynamic studies were performed before and after 1 to 3 months of treatment with captopril in 75 patients with severe chronic left heart failure. Patients were grouped according to the relative changes in pulmonary and systemic resistances during long-term therapy: patients in Group I (n = 24) showed greater decreases in pulmonary arteriolar resistance (PAR) than in systemic vascular resistance (SVR) (% delta PAR/% delta SVR greater than 1.0), whereas patients in Group II showed predominant systemic vasodilation (% delta PAR/% delta SVR less than 1.0). Despite similar changes in systemic resistance, patients in Group I showed greater increases in cardiac index, stroke volume index and left ventricular stroke work index (p less than 0.01 to 0.001) but less dramatic decreases in mean systemic arterial pressure (p less than 0.02) than did patients in Group II. Despite similar changes in left ventricular filling pressure, patients in Group I showed greater decreases in mean pulmonary artery and mean right atrial pressures (p less than 0.02 to 0.01) than did patients in Group II. Pretreatment variables in Groups I and II were similar, except that plasma renin activity was higher (8.7 +/- 2.1 versus 3.0 +/- 0.6 ng/ml per h) and serum sodium concentration was lower (133.1 +/- 0.9 versus 137.1 +/- 0.6 mEq/liter) in Group II than in Group I (both p less than 0.05). Both groups improved clinically after 1 to 3 months, but symptomatic hypotension occurred more frequently in Group II than in Group I (36 versus 8%) (p less than 0.005). These findings indicate that changes in the pulmonary circulation modulate alterations in both right and left ventricular performance during the treatment of patients with left heart failure. Hyponatremic patients are likely to experience symptomatic hypotension with captopril because they are limited in their ability to increase cardiac output as a result of an inadequate pulmonary vasodilator response to the drug.

Adult↗
PubMed1985

Usefulness of plasma renin activity in predicting haemodynamic and clinical responses and survival during long term converting enzyme inhibition in severe chronic heart failure. Experience in 100 consecutive patients.

The relation between plasma renin activity before treatment and the haemodynamic and clinical responses to converting enzyme inhibition was determined in 100 consecutive patients with severe chronic heart failure who were treated with captopril or enalapril. Initial doses of captopril produced significant increases in cardiac index and decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure, heart rate, and systemic vascular resistance that varied linearly with the pretreatment value for plasma renin activity. In contrast, there was no relation between the pretreatment activity and the magnitude of haemodynamic improvement after 1-3 months of treatment with the converting enzyme inhibitors, and, consequently, a similar proportion of patients with a high (greater than 6 ng/ml/h; greater than 4.62 mmol/l/h), intermediate (2-6 ng/ml/h; 1.54-4.62 mmol/l/h), and low (less than 2 ng/ml/h; less than 1.54 mmol/l/h) pretreatment value improved clinically during long term treatment (64%, 60%, and 64% respectively). Long term survival after one, two, and three years was similar in the three groups. Estimating the degree of activation of the renin-angiotensin system by measuring pretreatment plasma renin activity fails to predict the long term haemodynamic or clinical responses to converting enzyme inhibitors in patients with severe chronic heart failure, and thus appears to be of limited value in selecting those patients likely to benefit from treatment with these drugs.

Adult↗