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Biomedical subjects

W F Friedman

Publications and source records attributed to W F Friedman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Cardiac arrhythmias: the role of pharmacologic intervention.

The growing menu of drugs used to treat arrhythmias in children enhances the importance of antiarrhythmic selection based on the application of underlying electrophysiologic and pharmacokinetic principles, as well as a reduction of the side effect to benefit ratio. No attempt has been made in this report to discuss the diagnosis of arrhythmias in children, nor is the list of agents we discuss all-encompassing. Rather, the major thrust has been to promote an understanding of the important relationship between anatomic considerations, basic electrophysiology, and developmental pharmacology in directing therapy. We wish to emphasize that many of the studies quoted in this report are investigational, and that not all of the applications listed in the text and tables are approved for use in pediatric patients in the United States. Nevertheless, the information may serve as a guideline to developing management strategies for the individual child with an arrhythmia. Given the number of new antiarrhythmic agents under development, it would be no surprise if, in a few years, a paper such as this one discussed several new drugs we have not mentioned. We hope that the principles we have outlined will serve as a framework for incorporating these new agents into clinical practice as they become available.

Anti-Arrhythmia Agents↗
PubMed1988

Excitation-contraction coupling in developing mammalian myocardium: evidence from voltage clamp studies.

The single sucrose gap voltage clamp technique was used to study excitation-contraction coupling processes in right ventricular papillary muscles from New Zealand White rabbits at various stages of development. In response to voltage clamp controlled depolarizations, muscles from newborn rabbits were found to exhibit a monotonically increasing tension response reaching a steady state level that was maintained for the duration of depolarization. In contrast, more mature myocardium responded to similar depolarizations by developing an early peak of tension before relaxing to a steady state level. Measurement of the ratio of early peak or phasic tension to steady state or tonic tension revealed a statistically significant increase in the phasic tension component with maturation. In addition, Ca2+ loading of immature myocytes via a conditioning voltage clamp step resulted in enhancement of phasic tension in subsequent test depolarizations. Finally, the voltage dependence of tonic tension was found to be the same in all age groups. In contrast, the voltage dependence of phasic tension, seen only in the more mature myocardium, differed from that of tonic tension. The results of this investigation suggest that tension development in the immature myocardium is supported largely by the influx of Ca2+ across the sarcolemma. As the myocardium matures, intracellular Ca2+ uptake and rerelease by the sarcoplasmic reticulum plays an increasingly important role in tension development. A developmental schema is presented to account for the observed maturational changes in excitation-contraction coupling.

Age Factors↗
PubMed1987

Biochemistry of information storage in the nervous system.

The use of molecular biological approaches has defined new mechanisms that store information in the mammalian nervous system. Environmental stimuli alter steady-state levels of messenger RNA species encoding neurotransmitters, thereby altering synaptic, neuronal, and network function over time. External or internal stimuli alter impulse activity, which alters membrane depolarization and selectively changes the expression of specific transmitter genes. These processes occur in diverse peripheral and central neurons, suggesting that information storage is widespread in the neuraxis. The temporal profile of any particular molecular mnemonic process is determined by specific kinetics of turnover and by the geometry of the neuron resulting in axonal transport of molecules to different synaptic arrays at different times. Generally, transmitters, the agents of millisecond-to-millisecond communication, are subject to relatively long-lasting changes in expression, ensuring that ongoing physiological function is translated into information storage.

Adrenal Medulla↗
PubMed1987

Results of the Senning procedure in infants with simple and complex transposition of the great arteries.

Because of interest in the arterial switch operation, recent experience with the Senning operation in patients with simple and complex transposition of the great arteries (TGA) was examined. Between 1982 and 1985, 35 patients with simple TGA (group I) and 10 patients with complex TGA (group II) underwent a Senning operation. Mean duration of follow-up was 14 months for group I and 24 months for group II. In group I, 1 patient died early and no patient died late; infrequently, right ventricular dysfunction, tricuspid regurgitation, baffle obstruction or arrhythmias occurred. In group II, no patient died early and 3 died late. In addition, many patients required prolonged digoxin therapy. Because the arterial switch operation has a high early mortality risk and an undetermined long-term morbidity and mortality risk, the Senning operation (or other venous switch operations) is considered the preferred surgical approach for simple TGA. In contrast, an arterial switch operation is performed in patients with complex TGA (without subpulmonic obstruction). Comparison of the early and late morbidity and mortality of the arterial vs the venous switch operation may be helpful in selecting the appropriate surgical approach to complex TGA.

Female↗
PubMed1987

Coarctation repair without cardiac catheterization in infants.

Of 35 infants who underwent an operation for coarctation of the aorta, 15 did not undergo cardiac catheterization before surgery. The diagnoses in all uncatheterized patients were made by clinical examination, chest radiography, ECG, and two-dimensional echocardiography combined with pulsed Doppler echocardiography. Associated anomalies diagnosed by two-dimensional/Doppler echocardiography included a patent ductus arteriosus in all patients, bicuspid aortic valve in six, small ventricular septal defect in four, and complete common atrioventricular canal in one. In no instance was the diagnosis of coarctation in error. In addition, the clinical significance of the ventricular septal defect was judged correctly by two-dimensional echocardiography, and no patient required an early reoperation because of significant left-to-right shunt. Two significant lesions were missed in one patient each: mitral stenosis and aortic stenosis. These diagnoses were missed in patients who were first seen with either profound congestive heart failure or shock. Coarctation of the aorta and associated lesions can be diagnosed accurately by two-dimensional echocardiography. This permits proper patient management without the added risk of cardiac catheterization. Although mitral and aortic lesions may be missed because of low cardiac output, this does not result in management errors.

Aortic Coarctation↗
PubMed1986

Aortic dilation, dissection, and rupture in patients with Turner syndrome.

We report two patients with Turner syndrome who had aortic dissection and rupture, one with prior repair of coarctation. We also note the high incidence (8.8%) of unrecognized aortic root dilation in a group of 57 patients with Turner syndrome whom we prospectively evaluated by echocardiography. Our analysis and review of previously reported cases suggests that multiple risk factors may exist for aortic dissection, including coarctation, bicuspid aortic valve, and systemic hypertension, but that these need not be present. Aortic root dilation may be an additional finding that suggests the patient with Turner syndrome is also at risk. When it is present, magnetic resonance imaging visualizes the entire aorta and allows quantification of the site and degree of dilation. In patients with dissection, the aorta often exhibits pathologic evidence of cystic medial necrosis similar to the finding in patients with Marfan syndrome. Therapeutic methods to decrease risk, such as those directed toward prevention of bacterial endocarditis, blood pressure control, and perhaps prophylactic beta blockade or surgical reconstruction, may need to be considered. Patients with Turner syndrome, their families, and the physicians who care for them should be aware of the significance of unexplained chest pain, dyspnea, or hypotension as potential manifestations of aortic dissection or rupture.

Adolescent↗
PubMed1985

Treatment of congestive heart failure by altering loading conditions of the heart.

We have not emphasized the traditional approaches to the treatment of congestive heart failure, because there is abundant literature detailing the importance of rest and comfort for the patient, reduction of solute load, and administration of digitalis and diuretics. Instead, we have sought to emphasize the therapeutic interventions that are aimed at changing the mechanical loading conditions of the heart. Treatment expectations must be viewed within an age- or maturity-dependent framework. Thus, when a preterm or full-term newborn infant requires cardiocirculatory support, diminished cardiac reserve limits the benefits derived from diverse treatment methods. This unique fragility of the developing heart and circulation places a premium on the astute manipulation of all of the factors that determine optimum cardiovascular adaptation to stress. Beyond infancy, although cardiovascular reserve increases, it remains imperative to modify therapy by using cardioactive drugs that deal specifically with the separate mechanical and contractile variables to assure optimum survival.

Captopril↗
PubMed1984

New concepts and drugs in the treatment of congestive heart failure.

This article seeks to make clear the basic differences in the treatment of heart failure between therapeutic maneuvers that are aimed at improving the mechanical loading conditions of the heart and those that are aimed at augmenting the fundamental contractile or inotropic state of the myocardium. Emphasis is placed on recognizing that treatment expectations must be viewed within an age- or maturity-dependent framework, since a diminished margin of cardiocirculatory reserve exists in the smallest and youngest patients that limits the extent of benefit that may be derived from diverse treatment approaches.

Cardiotonic Agents↗
PubMed1984

Systemic venous and pulmonary arterial flow patterns after Fontan's procedure for tricuspid atresia or single ventricle.

Despite increasing use of Fontan or modified Fontan repairs, the comparative hemodynamic efficacy of different types of connections are unresolved. Accordingly, we undertook a prospective study designed to determine postoperative flow patterns after Fontan's operation. Seven subjects had tricuspid atresia and eight had single ventricle. Ages ranged from 5 to 38 years (mean 16.4). Ten subjects had nonvalved right atrial-to-pulmonary arterial connection, and four had nonvalved right atrial-to-right ventricular communication. A valved conduit established continuity between the right atrium and right ventricle in one subject. Doppler flow profiles were recorded in the pulmonary artery and in the superior and inferior venae cavae of each. A reference electrocardiogram was used for timing purposes. In 14 patients, forward flow in the pulmonary artery was biphasic. Flow began at the end of the T wave (early ventricular diastole), peaked at or before the P wave (atrial systole), and returned to baseline by the peak of the R wave. Forward flow recommenced at the peak of the R wave (ventricular systole) and returned to baseline at the end of the T wave. Flow in the superior vena cava varied, and could not be recorded in three subjects. Between the end of the P wave and peak of the R wave (atrial systole) flow was reversed in eight, absent in three, and forward in one patient. Forward flow occurred between the peak of the R wave and the end of the T wave and was either continuous or biphasic. Fourteen patients had adequate studies of inferior vena cava flow; reversed flow during atrial systole occurred in 10 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Inotropic effects of prostaglandin D2 and E1 on the newborn rabbit heart.

This study determines the inotropic effects of prostaglandin D2 (PGD2) and prostaglandin E1 (PGE1) in the isolated, arterial perfused newborn (NB) and adult (A) rabbit heart. Significant positive inotropism of PGD2 was observed at all concentrations studied (1 X 10(-17) to 1 X 10(-7) M) in the two age groups; the effect in the NB was significantly greater (p less than 0.05) than that in the A at PGD2 concentrations higher than 1 X 10(-17) M. Significant positive inotropism of PGE1 was observed at PGE1 concentrations higher than 1 X 10(-8) M in the NB, and only at 1 X 10(-6) M in the A. In the NB, the relaxation parameters [1/2 RT and the ratio of +dT/dt (max) to -dT/dt (max)] decreased to 80% of control after PGE1 infusion, but not after PGD2 infusion. In contrast, relaxation parameters in the A were not different from control. Propranolol (1 X 10(-6) M) did not alter the positive inotropic action of PGD2 and PGE1 in the NB. These data indicate that: 1) the positive inotropic effects of PGD2 and PGE1 in NB are greater than that in the A, 2) PGE1 and not PGD2, enhances myocardial relaxation only in the NB, 3) the contractile effects of PGD2 and PGE1 are not mediated by beta-receptors.

Alprostadil↗
PubMed1984

Studies of pulmonary prostaglandin biosynthetic and catabolic enzymes as factors in ductus arteriosus patency and closure. Evidence for a shift in products with gestational age.

The mechanisms underlying patency of the ductus arteriosus in utero and closure shortly after birth should permit optimal regulation of this important physiologic process. Although many studies indicate that vasodilatory prostaglandins contribute to patency, the contribution of the prostaglandin or prostanoid pathways to the closure mechanism has been less evident. The present studies tested a hypothesis which relates products of the cyclooxygenase pathway to modulation of ductal caliber. We began by defining the prostaglandin biosynthetic and catabolic activities of isolated fetal and neonatal lung as a function of gestational age. Inasmuch as biosynthetic enzymes compete for the same substrate, namely PGH2, the competitiveness of the enzymes was explored by varying endoperoxide concentration. The results indicate that the types and quantities of products formed by lung tissue are dependent markedly on both gestational age and substrate concentration. Cyclooxygenase activity was relatively constant through term, but increased sharply in neonatal lung tissue Although PHG2-PGE2 isomerase activity was high throughout gestation, prostacyclin synthase activity was only moderate and age-invariant after 130 d gestation. Lung thromboxane synthase activity increased markedly at 144 d gestation and in the neonatal lung. Catabolic activity (represented by 15-hydroxyprostaglandin dehydrogenase) was relatively high up to 130 d, became sharply minimal at term but increased in activity rapidly in the neonatal lung. These findings support the concept of a "balance" between dilatory and constrictor products of the cyclooxygenase pathway as one determinant of both patency of the ductus arteriosus and closure at birth or after administration of prostaglandin synthetase inhibitors.

Animals↗
PubMed1984

Prostaglandin biosynthetic activities of isolated fetal lamb ductus arteriosus, other blood vessels, and lung tissue.

Experimental evidence from many laboratories implicates products of arachidonic acid metabolism in perinatal homeostasis of the circulation of the ductus arteriosus. Studies were conducted to define the potential prostaglandin and prostanoid biosynthetic capabilities of the isolated fetal lamb ductus arteriosus, other fetal blood vessels, and isolated fetal and neonatal lung tissue as possible humoral sources of vasoactive products. Because the biosynthetic pathway is a sequential cascade of enzyme reactions, both radiolabeled synthetic endoperoxide (PGH2) and arachidonic acid were used as substrates. Prostacyclin (PGI2) synthase was the primary enzymatic pathway for metabolism of exogenous PGH2 by the isolated ductus arteriosus; no conclusive evidence was found for enzymatic formation of PGE2 or thromboxane A2 (TXA2). The PGI2 synthase activity of the ductus arteriosus was intermediate between arterial tissues (high) and veins (low). A relatively high cyclooxygenase activity was apparent in isolated lung tissue exhibited enzymatic activity for the formation of PGI2, PGE2, and TXA2 from synthetic PGH2. Lung thromboxane synthase activity was markedly elevated late in term due to an apparent increase in Vmax without change in Km, indicative of increased enzyme concentration. Although exogenous PGE2 has been shown to be a more potent relaxant of the ductus arteriosus than PGI2, our study could not positively identify an enzymatic pathway for the total intramural biosynthesis of PGE2. Similarly, no evidence was found for a locally generated constrictor prostanoid, e.g., TXA2. Our results suggest that humoral sources of vasodilator (PGE2 and PGI2) and vasoconstrictor (TXA2) products may be more important than local production in control of the ductus arteriosus and point to the importance of the fetal and neonatal lung in cardiovascular adaptations and homeostasis.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Two-dimensional echocardiographic assessment of left atrial size in children.

The ability of 2-dimensional echocardiography (2-D echo) to estimate end-systolic left atrial (LA) size and volume was assessed in 140 infants and children. These subjects were divided into 2 groups. Group A included 91 patients with normal LA volume and Group B included 49 patients with LA volume overload. Five echocardiographic views (left parasternal long-axis, left parasternal short-axis, apical 4-chamber, apical 2-chamber and subcostal 4-chamber) were used. From these views, the LA long-axis and minor-axis lengths were measured and the area was planimetered. These echocardiographically derived measurements were compared with angiographically calculated LA volume. Although all echocardiographic measurements correlated well with angiographic LA volume measurements, the echocardiographic area tracked better than length measurements. Echo LA volume was calculated using 5 single-plane and 3 biplane area-length methods. LA volume calculated from either single- or biplane methods correlated well with angiographically determined LA volume. The degree of correlation depended on the method used. Echocardiographic area and estimated LA volume measured from the parasternal long-axis and apical 2-chamber views best separated patients with LA volume overload from normal. Two-dimensional echo using these views accurately segregated all patients with a LA volume greater than 180% of normal and 15 of 21 patients (71%) with an LA volume between 138% and 179% of normal. Thus, 2-D echo is useful in the evaluation of LA size and volume in infants and children.

Adolescent↗
PubMed1983

Mitral valve E point to ventricular septal separation in infants and children.

This investigation establishes heretofore unavailable norms that permit clinical application of mitral valve E point to ventricular septal separation (EPSS) as an ejection phase index in infants and children. The study consisted of 105 normal subjects (1 day through 15 years of age, mean 7.4 years) and 67 patients of comparable age. Fifty-seven patients had increased left ventricular (LV) volume with normal function (ventricular septal defect or patent ductus arteriosus) and 10 patients had increased LV volume with depressed function (dilated cardiomyopathy). In normal subjects, EPSS was 2.5 +/- 1.7 mm and "normalized" EPSS, that is, the ratio of EPSS to end-diastolic dimension (EPSS/EDD), was 0.08 +/- 0.06 (mean +/- standard deviation); there was no correlation between either of these indexes and age, body surface area, height or weight. In patients with ventricular septal defect or patent ductus arteriosus, or both, the EPSS and EPSS/EDD were similar to those of normal subjects (3.2 +/- 2.3 mm and 0.09 +/- 0.06 mm, respectively). In patients with dilated cardiomyopathy, these indexes were significantly increased (p greater than 0.05) (EPSS 16.5 +/- 5.1 mm; EPSS/EDD 0.39 +/- 0.09). The data provide normal values for EPSS and EPSS/EDD in infants and children and show that these indexes are independent of age, body surface area, height or weight. Mitral valve EPSS and EPSS/EDD can now be used in pediatric echocardiography as a simple, practical and accurate means of separating normal from abnormal LV function.

Adolescent↗