PubMed Health⌕ Search

Biomedical subjects

M Packer

Publications and source records attributed to M Packer.

108 records · Page 6Linked to original sources
PubMed1985

Hemodynamic changes mimicking a vasodilator drug response in the absence of drug therapy after right heart catheterization in patients with chronic heart failure.

We suspected that patients with severe chronic heart failure may show hemodynamic changes after cardiac catheterization in the absence of drug therapy that could complicate assessment of the hemodynamic effects of new vasodilator and inotropic agents. To evaluate this phenomenon prospectively, hemodynamic variables were measured in 21 patients with heart failure 30 min and 2, 6, 24, and (in 12 patients) 48 hr after right heart catheterization, during which time therapy was not altered. During the first 2 hr we noted a significant increase in cardiac index and decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure, and systemic vascular resistance (p less than .01); a further decline in left ventricular filling pressure was noted over the next 24 hr, after which all hemodynamic variables remained stable. The magnitude of these hemodynamic changes resembled the effects of many established vasodilator drugs and was further enhanced after meals. These data indicate that hemodynamic improvement may be observed without any therapeutic intervention during the course of invasive studies in patients with severe chronic heart failure; such changes may lead investigators to attribute efficacy to ineffective drug therapy. To minimize the occurrence of such responses, we recommend that intravascular catheters be inserted the day before drug evaluation and that hemodynamic measurements be made with patients in a postprandial state.

Adult↗
PubMed1985

Long-term oral administration of amrinone for congestive heart failure: lack of efficacy in a multicenter controlled trial.

A number of uncontrolled studies have indicated that oral administration of amrinone, a phosphodiesterase inhibitor with potent positive inotropic effects in experimental preparations, may be beneficial in patients with chronic congestive heart failure. The present multicenter trial was designed to prospectively evaluate clinical response and change in exercise tolerance during 12 weeks of amrinone therapy in a double-blind, placebo-controlled protocol. Ninety-nine patients with NYHA functional class 3 or 4 congestive heart failure on digitalis and diuretics, of whom 31 were also receiving captopril, were enrolled. After baseline clinical assessment and determination of exercise tolerance, radionuclide left ventricular ejection fraction, and roentgenographic cardiothoracic ratio, patients were randomly assigned to receive amrinone or placebo, beginning at 1.5 mg/kg tid and increasing to a maximum dosage of 200 mg tid. After 12 weeks of therapy or at the last blinded evaluation in patients who did not complete this protocol, there were no significant differences from baseline values between treatment with amrinone or placebo with regard to symptoms, NYHA functional class, left ventricular ejection fraction, cardiothoracic ratio, frequency and severity of ventricular ectopy, or mortality. Exercise tolerance improved significantly from baseline by 37 +/- 10% (mean 163 sec) in patients on amrinone and 35 +/- 11% (mean 149 sec) in patients on placebo, but there was no significant difference between treatments. Adverse reactions were significantly more frequent and more severe on amrinone, occurring in 83% of patients and necessitating withdrawal in 34%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Vasodilator therapy for primary pulmonary hypertension. Limitations and hazards.

Vasodilator drugs were initially administered to patients with primary pulmonary hypertension based on the unproven hypothesis that pulmonary vasoconstriction played an important role in the pathogenesis of the disease. There were early reports of hemodynamic and clinical improvement after treatment with various vasodilating agents, but subsequent experience did not confirm these uncontrolled observations, and emphasized the limitations and hazards of this approach. Vasodilator therapy generally fails to reduce pulmonary vascular resistance selectively during long-term administration and frequently leads to systemic hypotension, exacerbation of the pulmonary hypertensive state, worsening of right ventricular failure, and systemic arterial desaturation. Beneficial hemodynamic responses are seen in only 15% to 25% of patients. Vasodilator therapy should not be considered an established treatment of patients with primary pulmonary hypertension.

Adrenergic alpha-Antagonists↗
PubMed1985

Does pulmonary vasoconstriction play an important role in patients with primary pulmonary hypertension? A skeptic's view of vasodilator therapy.

Despite isolated reports of dramatic hemodynamic and clinical improvement over the past 30 years, most patients with primary pulmonary hypertension fail to benefit from treatment with vasodilator drugs and many develop serious adverse reactions. The failure of this approach strongly suggests that pulmonary vasoconstriction does not play an important role in the pathogenesis of this disorder.

Humans↗
PubMed1984

Efficacy of captopril in low-renin congestive heart failure: importance of sustained reactive hyperreninemia in distinguishing responders from nonresponders.

To determine the efficacy of converting-enzyme inhibition in patients with low-renin congestive heart failure (CHF), the long-term hemodynamic and clinical responses to captopril were evaluated in 26 consecutive patients with severe, chronic CHF whose pretreatment plasma renin activity (PRA) was less than 2 ng/ml/hour. After 2 to 8 weeks of continuous treatment with captopril, 14 patients (54%) showed long-term hemodynamic benefits, of whom 13 (50%) improved clinically by at least 1 New York Heart Association functional class. To distinguish responders from nonresponders, patients were grouped based on the presence or absence of sustained reactive hyperreninemia (PRA during chronic therapy greater than 4 ng/ml/hour). After 2 to 8 weeks of therapy with captopril, 14 patients had sustained reactive hyperreninemia. Their cardiac index increased by 0.33 liters/min/m2 (p less than 0.01), left ventricular filling pressure decreased by 12.6 mm Hg (p less than 0.001), mean right atrial pressure decreased by 4.9 mm Hg (p less than 0.001) and systemic vascular resistance decreased by 529 dyne s cm-5 (p less than 0.001). Twelve of these 14 patients improved clinically. Twelve other patients had no reactive increase in PRA, and these patients showed no significant improvement in any hemodynamic variable after 2 to 8 weeks of treatment with captopril; only 1 of the 12 patients improved clinically (p less than 0.001 between groups). The 2 groups were otherwise similar with regard to pretreatment demographic, hemodynamic and hormonal variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Vasodilator and inotropic therapy for severe chronic heart failure: passion and skepticism.

Although substantial progress has been made in the last 5 years in the development of vasodilator and inotropic drugs for the management of patients with severe chronic heart failure, much of the enthusiasm that surrounded the introduction of many of these agents has subsequently been tempered by reports of drug failure or adverse reactions. In this review and analysis, currently available vasodilator and inotropic agents are critically and comparatively evaluated to assess their respective advantages and limitations. It is apparent that the ability of most of these drugs to produce substantial clinical benefits in patients with severe heart failure has probably been overstated. Therapy fails to achieve the desired clinical results all too frequently, possibly as the result of: the choice of an ineffective drug; the administration of an effective drug in subtherapeutic doses; the administration of an effective drug to improperly selected patients; the failure of initial hemodynamic benefits to be sustained; the occurrence of severe or serious adverse reactions; and the failure to alter concomitant therapy appropriately. The present analysis indicates that there is no uniformly effective or safe vasodilator or inotropic drug for patients with severe heart failure; all agents have important limitations. Of the available therapeutic choices, however, long-term converting enzyme inhibition appears to produce more consistent hemodynamic and clinical benefits with an acceptable degree of adverse reactions than other pharmacologic approaches for the management of these severely ill patients.

Administration, Oral↗
PubMed1982

Selection of vasodilator drugs for patients with severe chronic heart failure: an approach based on a new classification.

Although vasodilator drugs are of proven worth in the management of patients with severe heart failure, a useful system of classification of vasodilator drugs has not yet been devised. The traditional system of classification based on the dominant arterial and/or venous sites of action as determined by limb plethysmography has major conceptual and practical limitations. This article discusses the merits of a new classification format based on pharmacological mechanisms of action. According to this new system, vasodilator drugs can be divided into two groups: (1) direct-acting agonists (hydralazine, minoxidil, nitrates and nitroprusside) which demonstrate dose-dependent responses and generalised vasodilator effects, and thus require invasive monitoring for dose titration; and (2) neurohumoral antagonists (prazosin, trimazosin, phentolamine, captopril and teprotide), whose effects are qualitatively and quantitatively independent of the dose administered, show marked regional heterogeneity and have characteristic temporal patterns of response. This new classification system permits the rational formulation of clinical recommendations concerning the choice of a vasodilator drug for patients with severe chronic heart failure. However, widespread application of this new classification system awaits the development of reliable means of identifying patients with neurohumoral-dependent vasoconstriction without the necessity of a therapeutic trial.

Heart Failure↗
PubMed1979

Rebound hemodynamic events after the abrupt withdrawal of nitroprusside in patients with severe chronic heart failure.

We studied the hemodynamic events that followed abrupt withdrawal of nitroprusside in 20 patients with severe chronic heart failure. With nitroprusside, cardiac index increased from 1.96 to 2.87 liters per minute per square meter of body-surface area, but it decreased to 1.66 (P less than 0.001) after withdrawal of nitroprusside. Left ventricular filling pressure and systemic vascular resistance decreased from 23.9 to 15.3 mm Hg and from 1642 to 921 dyn.sec.cm-5, respectively, with nitroprusside, but increased to 30.4 mm Hg and 2109 dyn.sec.cm-5 (both P less than 0.001) upon its discontinuation. These rebound changes were maximal 10 to 30 minutes after nitroprusside withdrawal and returned to control levels one to three hours later. Although in 17 of 20 patients, these rebound changes caused no or minimal exacerbation of symptoms, pulmonary edema, which resolved in three patients. Activation of reflex vasoconstrictive forces during vasodilator therapy may explain these effects of withdrawal.

Adult↗
PubMed1979

Prognostic value of echocardiographic evaluation of septal function in acute anteroseptal myocardial infarction.

To determine the clinical usefulness of echocardiography in patients with anteroseptal myocardial infarction, echocardiograms were performed within 24 hours of admission on 40 patients with acute transmural anteroseptal myocardial infarction. Twenty-one patients had normal septal motion and septal systolic thickening, and 19 patients had abnormalities of one or both of these measurements. Of the 21 patients who had normal septal motion and thickening, only five developed congestive heart failure, none developed bundle branch block, and none died. Of the 19 patients with abnormal septal motion and/or thickening, 17 developed congestive heart failure (p less than .001), seven developed bundle branch block (p less than .001), and six died (p less than .001). Therefore, (1) electrocardiographic evidence of septal infarction does not correlate with abnormalities of the portion of septum seen on echocardiogram, and (2) patients with anteroseptal myocardial infarction and abnormalities of the septum on echocardiogram have more complications and a higher in-hospital mortality rate. These patients may have more extensive myocardial infarction predisposing to pump failure and possibly involving the conduction system.

Aged↗
PubMed1979

Differences in hemodynamic effects of nitroprusside and prazosin in severe chronic congestive heart failure: evidence for a direct negative chronotropic effect of prazosin.

To compare the hemodynamic effects of prazosin and nitroprusside in patients with severe congestive heart failure, nine patients with heart failure refractory to conventional therapy received oral prazosin and intravenous nitroprusside administered so as to produce a similar decrease in left ventricular filling pressure in each patient. By this comparison, both drugs produced similar decreases in mean right atrial pressure, mean pulmonary arterial pressure and systemic and pulmonary vascular resistance. However, with nitroprusside, cardiac index increased more (+0.97 versus +0.73 liters/min per m2, P less than 0.01) and mean arterial pressure decreased less (-13.7 versus -18.3 mm Hg, P less than 0.05) than with prazosin. Both drugs produced similar changes in stroke volume index (+11.7 cc/beat per m2 with nitroprusside and +12.5 with prazosin) and stroke work index (+8.1 g-m/m2 with nitroprusside and +6.6 with prazosin). Therefore, the differences in the hemodynamic responses observed with the two agents were due to the significantly greater decrease in heart rate with prazosin (-8 beats/min) than with nitroprusside (-2 beats/min, P less than 0.05). These clinical data support experimental evidence suggesting that there is a significant negative chronotropic action of prazosin independent of its peripheral vascular effects.

Administration, Oral↗
PubMed1979

The effects of maternally administered pethidine or epidural bupivacaine on the fetus and newborn.

The continuous fetal heart rate rate pattern, condition of the baby at birth and its subsequent behaviour were compared in three groups of infants whose mothers received during labour either no drugs, intramuscular pethidine or epidural bupivacaine. The blood levels of pethidine and bupivacaine were measured at delivery in a maternal vein, and umbilical artery and vein, and in the newborn during the first 48 hours of life. The only significant changes in the fetal heart rate pattern occurred in association with maternal hypotension or uterine hyperstimulation. The Apgar scores at one minutes were 7 or less in more infants in the intramuscular pethidine and epidural bupivacaine groups as compared with the controls. There were no differences in the Apgar scores at five minutes. Neonatal behaviour during the first six weeks of life was not significantly affected by pethidine or epidural bupivacaine when compared with the control group. Pethidine and bupivacaine were shown to cross the placenta freely. The half-life of these drugs in the newborn was longer than in the adult.

Anesthesia, Epidural↗
PubMedDate not supplied

Ophthalmology's botanical heritage.

Many of today's important ophthalmic pharmaceuticals have a rich ethnobotanical history. Solanaceous plants, the source of atropine, have contributed to medical therapy since the beginning of Western civilization. The botanical source of physostigmine played a pivotal role as an ordeal poison in the culture of Old Calabar, West Africa. Native peoples of Amazonia treasured plants containing pilocarpine as panaceas because of their impressive diaphoretic effect. Nineteenth century scientists examining these plants because of their folkloric reputations discovered their active compounds and documented their physiological effects. Ophthalmologists such as Argyll Robertson, Laqueur, and Weber built upon this research to bring these pharmaceuticals into therapeutic use. The ongoing loss of the world's tropical rain forests threatens to destroy a vast storehouse of untested biological compounds.

Glaucoma↗