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Biomedical subjects

E B Clark

Publications and source records attributed to E B Clark.

At least 55 records · Page 3Linked to original sources
PubMed1991

Diastolic filling characteristics in the stage 12 to 27 chick embryo ventricle.

Cardiac output is affected by the diastolic filling characteristics of the ventricle. We hypothesized that the relative contributions of passive and active filling change as the ventricle develops from a smooth-walled tube to a trabeculated four-chamber heart. In stage 12 to 27 white Leghorn chick embryos, we simultaneously measured ventricular pressure with a servo-null micropressure system and dorsal aortic and atrioventricular velocities with a 20-MHz pulsed-Doppler velocity meter. The analog waveforms were sampled at 500 Hz and converted to digital format via an analog/digital board. We partitioned diastole into passive and active components. The passive phase began with the return of the pressure curve to baseline and extended to the onset of the a-wave. The active phase began with the upstroke of the atrial velocity curve and extended to the upstroke of the ventricular pressure curve at end-diastole. Data are presented as mean +/- SEM (n greater than or equal to 6 at each stage) and analyzed by analysis of variance and regression analysis. At similar cycle lengths ranging from 480 to 600 ms (p greater than 0.05), end-diastolic pressure increased from 0.24 +/- 0.02 mm Hg at stage 12 to 0.55 +/- 0.01 mm Hg at stage 27. Passive and active filling volumes were 92 (0.0038 +/- 0.0005 mm3) and 8% (0.0004 +/- 0.0002 mm3), respectively, at stage 12 and changed to 24 (0.23 +/- 0.08 mm3) and 76% (0.62 +/- 0.08 mm3), respectively, at stage 27. The ratio of passive to active filling volume decreased from 7.89 to 0.35.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus.

Most studies on the relationship of maternal diabetes to cardiovascular malformations (CVM) have been prospective investigations of pregnancy outcome and therefore could not identify associations with rare cardiac lesions. The results of a retrospective study shed new light on the risks of specific cardiac defects in diabetic pregnancies. The Baltimore-Washington Infant Study, a population-based case-control investigation of CVM, provides information on maternal diabetes reported in personal interviews. Among 2259 mothers of cases, 35 (1.5%) reported diabetes present before pregnancy (called "overt") and 95 (4.2%) reported diabetes only during pregnancy (called "gestational"). Among 2,801 mothers of controls, 14 (0.5%) had overt diabetes and 83 (3.0%) had gestational diabetes. Malformation-specific risks were expressed as odds ratios (OR) with 99.5% confidence intervals (CI). The strongest associations with overt maternal diabetes were found with double outlet right ventricle (OR 21.33; 99.5% CI 3.34, 136.26), and truncus arteriosus (OR 12.81; 99.5% CI 1.43, 114.64). No significant diagnosis-specific associations were found with gestational diabetes. Non-cardiac malformations were present in 23% of infants with CVM whose mothers had overt diabetes and in 26% of infants with CVM whose mother had gestational diabetes, in 32% of infants with CVM whose mothers did not have diabetes, and in 4% of controls. Double outlet right ventricle and truncus arteriosus are malformations dependent upon neural-crest-cell-derived ectomesenchymal tissues; these are precisely the conotruncal abnormalities that result from experimental ablation of the neural crest in chick embryos. The association with diabetes suggests a further etiologic link between these two lesions.

Case-Control Studies↗
PubMed1990

Correlation of ventricular area, perimeter, and conotruncal diameter with ventricular mass and function in the chick embryo from stages 12 to 24.

Ventricular form and function are interrelated during cardiovascular development. The study of muscle mechanics requires the real-time measurement of length, area, or volume. Because volume measures are not currently possible in the embryonic heart, we tested the hypothesis that end-diastolic (ED) and end-systolic (ES) ventricular perimeter, area, and conotruncal diameter correlate with ventricular mass and function in the stage 12 to stage 24 white Leghorn chick embryo. Video images of the contracting heart were recorded at 60 Hz on 1/2" videotape and studied with a custom image-analysis workstation. ED and ES video fields were selected by maximum and minimum ventricular area and were planimetered for epicardial ventricular perimeter, area, and conotruncal diameter. Data are reported as (mean +/- SEM, n greater than or equal to 8) and were tested by analysis of variance and regression analysis. Heart rate calculated from cycle length increased from 78 +/- 6 beats/min at stage 12 to 162 +/- 5 beats/min at stage 24. ED and ES area increased geometrically versus stage (y = 0.53 - 0.08x + 0.004x2, r = 0.96, p less than 0.001; and y = 0.60 - 0.09x + 0.004x2, r = 0.98, p less than 0.001, respectively). ED and ES perimeter and conotruncal diameter increased linearly versus stage (r = 0.95, p less than 0.001; r = 0.96, p less than 0.001; and r = 0.93, p less than 0.001; r = 0.93, p less than 0.001, respectively). Shortening fraction for each measurement increased from stage 12 to 16 or 18 then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Effect of changes in circulating blood volume on cardiac output and arterial and ventricular blood pressure in the stage 18, 24, and 29 chick embryo.

We studied the hemodynamic effects of changing volume loading in the chick embryo, before autonomic innervation, to test the hypothesis that the Frank-Starling mechanism functions in the embryonic myocardium. Dorsal aortic blood velocity was measured by pulsed Doppler. Heart rate and aortic diameter were also measured to calculate cardiac output and stroke volume index. Vitelline arterial and ventricular pressures were measured with a servo-null micropressure system in stage 24 embryos. Infusing isotonic solution intravenously resulted in linear increases in stroke volume index for stages 18 (y = 388x + 6.89), 24 (y = 466x + 7.86), and 29 (y = 549x + 4.96). The slopes and intercepts were statistically the same for all three stages. Similar volume loading in stage 24 embryos initially increased mean arterial pressure linearly, but at higher loading conditions, the rate of rise lessens. Thus, volume loading resulted in a decrease in vascular resistance. Withdrawing blood from stage 24 embryos resulted in a decrease in ventricular peak systolic and end-diastolic pressures. With reinfusion of the blood, systolic and end-diastolic pressures initially rose above baseline levels and later returned to normal. We conclude that a length-tension relation is present in the preinnervated embryonic heart and that vascular resistance changes inversely with loading conditions. We speculate that these mechanisms are the primary hemodynamic control mechanism in the early chick embryo.

Animals↗
PubMed1989

Patterns of cardiac care in infants with Down syndrome.

To determine if the pattern of cardiac care is affected by the presence of Down syndrome (DS) we analyzed the records of infants enrolled in the Baltimore-Washington Infant Study, a regional case-control study of congenital cardiovascular malformations. The age at cardiac diagnosis, the timing of cardiac surgery, and the one-year outcome were compared in 160 infants with DS and 540 infants with the same cardiac diagnoses but without chromosomal or other extracardiac anomalies (Isolated cardiovascular malformation [ICM] group). Cardiac referral and diagnosis were accomplished by 13 weeks of age in 78% of infants with DS and 67% of those with ICMs. However, by 26 weeks of age, the proportion of infants in both groups was comparable. Cardiac surgery was performed before 1 year of age in 99 of 160 infants with DS and in 141 of 540 infants with ICMs. The surgical outcome was similar in the two groups. We conclude that for defects of comparable severity, the pattern of cardiac care in the Baltimore-Washington, DC, area for infants with DS is timely and comparable to care for infants with ICMs.

Down Syndrome↗
PubMed1989

Cardiac malformations in relatives of infants with hypoplastic left-heart syndrome.

In a pilot study of relatives of infants with hypoplastic left-heart syndrome (HLHS), we obtained a medical history, cardiovascular examination, and echocardiogram in 48 first-degree relatives of 11 probands with isolated HLHS and 3 with HLHS and noncardiac malformations. Echocardiography confirmed heart defects in 5 of 41 relatives of patients with isolated HLHS. In four instances, the cardiac abnormality was unrecognized. Among 7 relatives of infants with HLHS and extracardiac anomalies, no heart defects were detected. Cardiac defects occurred in first-degree relatives of probands at a frequency higher than previously predicted by an additive multifactorial model of inheritance. These findings suggest that first-degree relatives of HLHS probands may have an increased risk for subclinical cardiac defects and that genetic factors likely contribute to the cause of left-heart blood-flow lesions.

Family↗
PubMed1989

Abnormalities in position of left ventricular papillary muscles in congenital aortic stenosis.

Subclinical structural abnormalities may accompany some congenital cardiovascular abnormalities. Echocardiographic observations led us to hypothesize that the positions of the left ventricular papillary muscles are abnormal in hearts with aortic valvar stenosis. To test this hypothesis, we examined 6 normal heart specimens and hearts with congenital cardiovascular malformations, including 5 with pulmonary atresia and an intact ventricular septum, 6 with tetralogy of Fallot and 5 with aortic valvar stenosis. We marked the papillary muscles and the mitral commissures, X-rayed the hearts, and measured the angular positions of the papillary muscles using the midpoint of a chord drawn between the mitral commissures as a reference point. The direction from the midpoint to the lateral commissure was designated as 0 degrees. The data (mean +/- SEM) were analyzed using a computer program (ANOVA). In normal hearts, the anterolateral and posteromedial papillary muscles were positioned, respectively, at 43 +/- 19 degrees and 126 +/- 26 degrees. The positions of the papillary muscles were similar to normal in the hearts with pulmonary atresia (62 +/- 38 degrees and 128 +/- 27 degrees) and tetralogy of Fallot (40 +/- 13 degrees and 130 +/- 37 degrees). In aortic stenosis, the locations of the papillary muscles (-76 +/- 42 degrees and 71 +/- 25 degrees) were significantly different from normal (P less than 0.05). The arc between the papillary muscles was 83 +/- 16 degrees in normals and 147 +/- 45 degrees in aortic stenosis (P less than 0.05). The length of the arc was similar to normal in other heart specimens. Thus, the papillary muscles were abnormally positioned in aortic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Stenosis↗
PubMed1989

Effect of increased pressure on ventricular growth in stage 21 chick embryos.

We studied the effect of increased ventricular pressure on heart growth in the stage 21 (3.5-day) chick embryo. Ventricular pressure was increased by constricting the conotruncus with a loop of 10-0 nylon tied in an overhand knot. The embryos were reincubated, and physiology and cellular morphology were evaluated at successive stages of development, stages 21, 24, 27, and 29. Ventricular pressure was measured with a servo-null pressure system, and cardiac output was measured with a 20-MHz pulsed Doppler velocity meter. Ventricular and embryo dry weights were measured on an electronic microbalance, myocyte organelle composition was measured by a point counting technique, and cell growth response was measured by DNA and protein assay. The conotruncal loop increased ventricular pressure in experimental compared with control embryos, i.e., at stage 24, 2.88 +/- 0.13 vs. 1.96 +/- 0.05 (SE) mmHg (P less than 0.05), respectively, without affecting cardiac output. Ventricular dry weight increased in experimental vs. control embryos, i.e., at stage 24, 114 +/- 7 vs. 85 +/- 4 micrograms (P less than 0.05), respectively, whereas embryo weights were similar between the two groups. The difference in ventricular weights was due to myocyte hyperplasia, since organelle proportion of myofibrils and mitochondria, DNA-to-protein ratio, and myocyte area were similar in experimental voice control embryos. Thus the adjustment of myocardial mass to ventricular work occurs even during the earliest stages of embryonic development. Cardiac growth and morphogenesis are parallel but separable processes.

Animals↗
PubMed1989

Aortic impedance and hydraulic power in the chick embryo from stages 18 to 29.

Little is known about the hemodynamic properties of the rapidly expanding arterial bed during embryonic development. Using a servo-null pressure system and 20-MHz pulsed Doppler velocity meter, we recorded simultaneous dorsal aortic pressure and velocity waveforms. The waveforms were digitized at 3-msec intervals and subjected to Fourier analysis. We calculated hydraulic energy and the impedance spectrum to 10 Hz. From stages 18 to 29, heart rate (148 +/- 3 to 193 +/- 9 beats/min), systolic pressure (1.14 +/- 0.12 to 3.04 +/- 0.10 mm Hg), and mean dorsal aortic blood flow (21 +/- 2 to 214 +/- 19 mm3/min) increased. Peripheral vascular resistance (Z0: 30.4 +/- 4.8 to 6.4 +/- 0.7 dyne x sec/mm5), and the impedance moduli (Z1: 6.5 +/- 1.0 to 1.7 +/- 0.2 dyne x sec/mm5; Z2: 6.1 +/- 1.2 to 1.7 +/- 0.1 dyne x sec/mm5; Z3: 7.3 +/- 1.1 to 1.7 +/- 0.2 dyne x sec/mm5) decreased. Total hydraulic power increased from 48 +/- 7 to 2,606 +/- 96 nW, while the proportion of oscillatory energy increased from 29 +/- 2% to 65 +/- 4%. With development hydraulic load decreases, total external work increases and the dorsal aorta and embryonic vascular bed becomes more compliant. A greater proportion of total energy is expanded in pulsatile blood flow, suggesting that ventricular-arterial coupling is less efficient later in development.

Animals↗
PubMed1989

Hemodynamics of the stage 12 to stage 29 chick embryo.

The heart is the first functioning organ in the embryo and provides blood flow during cardiac morphogenesis from a muscle-wrapped tube a few cells thick to the four-chambered pump. We described the hemodynamics of the chick embryo from stage 12 (50 hours of a 21-day incubation) to stage 29 (6 days), during which the embryo weight increased 120-fold. We measured ventricular, embryo and extraembryonic vascular bed wet weights, dorsal aortic blood flow with a directional pulsed-Doppler velocity meter, and ventricular and vitelline arterial blood pressures with a servo-null micropressure system. The data are reported as mean +/- SEM. With rapid development and morphogenesis, dorsal aortic blood flow increased from 0.015 +/- 0.004 to 2.40 +/- 0.20 mm3/sec parallel to the geometric increase of wet embryo weight from 2.22 +/- 0.10 to 267.5 +/- 9.7 mg. Dorsal aortic blood flow normalized for embryo and extraembryonic weight remained relatively constant (Y = 2.13 + 0.02X, r = 0.23, SEE = 0.03). Stroke volume increased from 0.01 +/- 0.003 to 0.69 +/- 0.03 mm3, and heart rate doubled from 103 +/- 2 to 208 +/- 5 beats/min. Systolic, diastolic, and mean vitelline arterial pressure increased linearly from 0.32 +/- 0.01, 0.23 +/- 0.01, and 0.28 +/- 0.01 mm Hg at stage 12 to 2.00 +/- 0.06, 1.22 +/- 0.03, and 1.51 +/- 0.04 mm Hg, respectively, at stage 29. Ventricular peak systolic and end-diastolic pressure increased from 0.95 +/- 0.04 and 0.24 +/- 0.02 at stage 12 to 3.45 +/- 0.10 and 0.82 +/- 0.03 at stage 29, respectively. The hemodynamic waveforms were similar to those found in the four-chamber heart of the mature animal. These data are integral to understanding the interrelation of function and form during cardiac development.

Animals↗
PubMed1989

Effect of heart rate increase on dorsal aortic flow before and after volume loading in the stage 24 chick embryo.

In the stage 24 chick embryo, a paced increase in heart rate reduces stroke volume, presumably by rate-dependent decrease in passive filling. We hypothesized that rate-dependent stroke volume reduction could be abolished by volume loading. Dorsal aortic blood velocity was measured with a 20 mHz pulsed-Doppler meter from a 0.75-mm piezoelectric crystal (eight embryos), and atri-oventricular velocity was simultaneously measured from the ventricular apex (six embryos). Sinus venosus pacing (stimuli of 1 ms duration and less than 4 mA) was performed at intrinsic rate (P:I) and at 150% of intrinsic rate (P:150%I). Volume loading was performed during P:150%I by intravenous injection of 7.5 microL of chick Ringer's solution. Using atrioventricular velocity profile, stroke volume was divided into the proportion due to passive (E-phase) and active (A-phase) filling. Stroke volume was compared during P:I, P:150%I, immediately (P:150%I') and 30 s after (P:150%I") volume loading. Data (mean +/- SEM) were compared by ANOVA. During pacing, stroke volume (mm2/cycle) decreased but increased after volume loading (I, 0.43 +/- 0.03; P:I, 0.37 +/- 0.03; P:150%I, 0.19 +/- 0.03; P:150%I', 0.24 +/- 0.05; P:150%I", 0.28 +/- 0.04 (p less than 0.005). During P:150%I, E-phase filing disappeared and was not restored by volume loading, whereas, A-phase filling diminished but was restored by volume loading. In stage 24 chick embryos, rate-dependent stroke volume decrease is reversed by volume loading that restores stroke volume due to an increase in active filling but not passive filling. Thus, even at rapid heart rate, the embryonic ventricle responds to volume loading, indicating that the Frank-Starling relationship functions during tachycardia in the embryonic heart.

Animals↗
PubMed1988

Prenatal detection of cardiovascular malformations by echocardiography: an indication for cytogenetic evaluation.

Prenatal diagnosis of congenital cardiovascular malformations by echocardiography may signal associated chromosome abnormalities. The exact proportion of these associations is not known but is expected to be higher than that with live-birth. To estimate the risk that a fetus with an echocardiographically detected heart defect has an autosomal trisomy or Turner syndrome, we adjusted the known frequency of aneuploidy in live-born infants with congenital cardiovascular malformations by the reported rate of spontaneous abortion, with data from a population-based case-control study of congenital cardiovascular malformations in which 268 cases (12.7%) had both congenital cardiovascular malformations and a chromosome abnormality. Included in the present analysis were 188 aneuploid infants with congenital cardiovascular malformations that would have been detectable by fetal echo. When data are adjusted for the high spontaneous abortion rate of aneuploid fetuses, we estimate that there would have been more than a threefold increase in aneuploidy over the 13% seen at live-birth. Thus cytogenetic analysis is appropriate in a fetus with echo-diagnosed congenital cardiovascular malformations.

Aneuploidy↗
PubMed1988

Cognitive development in transposition of the great vessels.

Ten children who had had transposition of the great vessels (TGV) repaired, deep hypothermia, and cardiac arrest were examined. Seven children with acyanotic heart disease and 12 unaffected siblings were tested for comparison. Their intelligence, academic achievement, and behaviour was studied. The group with TGV had lower performance subscores on the intelligence test, an increase in somatic complaints, and aggressive behaviour.

Achievement↗
PubMed1987

Familial risks of congenital heart defect assessed in a population-based epidemiologic study.

Congenital heart defects (CHD) represent a heterogeneous group of disorders caused by chromosome abnormalities, mendelian disorders, teratogenic exposures, and unknown etiologic mechanisms. A large group of various isolated defects is presumably multifactorial in origin. Previous studies of familial risks for specific anatomic defects obtained from clinical series may include significant biases and obscured pathogenic relationships. In this population-based study we analyzed all cases of CHD in infants and a control birth cohort in the Baltimore-Washington area. The rates of CHD were defined for first-degree relatives of cases with isolated defects, grouped by a pathogenic classification scheme. Precurrence risks were found to vary among the groups, and risks for flow lesions were higher than previously reported. The sibling precurrence risk for hypoplastic left heart syndrome (13.5%) was not significantly different from that expected for an autosomal recessive mechanism; the risks for different types of ventricular septal defects (VSD) varied among mechanistic groups. The results indicate that the additive multifactorial model does not adequately account for the risks in all forms of isolated CHD of unknown etiology.

District of Columbia↗