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Biomedical subjects

E B Clark

Publications and source records attributed to E B Clark.

At least 73 records · Page 4Linked to original sources

Effect of heart rate increase on dorsal aortic flow in the stage 24 chick embryo.

We evaluated the effect of increased heart rate on cardiac output and stroke volume in the stage 24 chick embryo (day 4 of a 21-day incubation). Blood flow was measured with a 20 MHz pulsed-Doppler flowmeter. Heart rate was increased by pacing with square wave stimuli (1 ms duration, less than 4 mA). The sinus venosus was paced from bipolar Teflon-coated silver electrodes in eight embryos and the ventricular apex was paced in three embryos. The pacing rates were at the intrinsic heart rate (P:I); 125% of intrinsic heart rate (P:125%I); and 150% of intrinsic heart rate (P:150%I). Physiologic measurements during pacing were compared to those obtained at the control intrinsic rate (I). We also evaluated the velocity profile of atrioventricular inflow and conotruncal outflow at intrinsic rate and during sinus venosus and ventricular pacing. With sinus venosus pacing, mean dorsal aortic blood flow was similar at control (1.07 +/- 0.05 mm3/s) and P:I (1.06 +/- 0.06 mm3/s) (mean +/- SEM). However, at P:125%I and P:150%I, mean dorsal aortic blood flow decreased significantly (P:125%I, 0.88 +/- 0.05 mm3/s; P:150%I, 0.67 +/- 0.07 mm3/s) (p less than 0.05). Stroke volume per beat also decreased with increasing heart rates (I, 0.41 +/- 0.02 mm3; P:I, 0.39 +/- 0.02 mm3; P:125%I, 0.28 +/- 0.02 mm3; P:150%I, 0.18 +/- 0.02 mm3) (p less than 0.05). With rapid sinus venosus pacing, the atrioventricular blood flow velocity profile showed a rate-dependent decrease in passive ventricular filling while active filling remained the same or increased slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cerebral infarction complicating Fontan surgery for cyanotic congenital heart disease.

We report on four children who had cerebral vascular events in the first three months after the Fontan procedure for complex cyanotic congenital heart disease. Potential risk factors in these children included congestive heart failure, postoperative thrombocytosis, and cardiac arrhythmias. These cases suggest that children who undergo Fontan surgery may be at increased risk for cerebral infarction.

Adolescent↗

Morphologic characteristics of aortic atresia: implications for fetal hemodynamics.

We studied hearts with aortic atresia to determine the relationship between cardiac morphology and fetal cardiac blood flow. We compared measurements of aortic, pulmonary, and tricuspid valve circumference and right ventricular wall thickness among 37 hearts with aortic atresia and mitral hypoplasia, 14 hearts with aortic atresia together with mitral atresia and 24 normal hearts. Right ventricular free wall thickness and tricuspid and pulmonary valve annular circumferences were greater and aortic circumferences were smaller in hearts with aortic atresia than in normal hearts (P less than 0.05). Between the subgroups of aortic atresia, the aortic circumference was 5 +/- 1 mm in those with mitral atresia compared to 7 +/- 2 mm in association with mitral hypoplasia (P less than 0.05). The morphologic differences between the subgroups of aortic atresia are consistent with differences in fetal blood flow. Left heart blood flow was likely to be greater during development in those hearts with aortic atresia and mitral hypoplasia than in those with the combination of aortic and mitral atresia.

Aorta↗

Ventricular function and morphology in chick embryo from stages 18 to 29.

We evaluated wet and dry ventricular and embryo weights, hemodynamic parameters of ventricular function, and myocardial myocyte organelle composition in the developing chick embryo. Phasic and dP/dt ventricular pressure were measured with a servo null pressure system, and phasic, mean, and dV/dt dorsal aortic velocities were measured with a 20-MHz pulsed-Doppler meter. Ventricular and embryo weight increased geometrically with development, but at different rates, so that the ventricle-to-embryo weight ratio decreased from 0.02 to 0.001 just prior to hatching. Ventricular systolic and end-diastolic pressure increased from 1.31 +/- 0.05/0.33 +/- 0.03 mmHg at stage 18 to 3.45 +/- 0.10/0.82 +/- 0.03 mmHg at stage 29, while dP/dt increased from 23.04 +/- 1.32 to 79.55 +/- 3.69 mmHg/s over the same period. Dorsal aortic dV/dt increased from 878 +/- 17 to 2.076 +/- 65 mm/s2 from stage 18 to 29. Myocyte percent volume of myofibrils increased from 16.7 +/- 0.9% at stage 18 to 23.6 +/- 1.1% at stage 27 and diminished to 18.4 +/- 0.8% at stage 29. Mitochondrial percent myocyte volume remained constant at about 11%. These data define the parameters of normal ventricular function and morphology during embryonic development in the chick.

Animals↗

Postpericardiotomy syndrome.

Postpericardiotomy syndrome, a frequent complication of open-heart surgery, is characterized by fever, chest pain, and pericardial and pleural effusions. These signs may develop 1 to 12 weeks after intracardiac surgery in approximately 30 percent of patients. Although the etiology of the syndrome is unknown, evidence points to a viral and/or autoimmune cause. Postpericardiotomy syndrome is diagnosed after excluding other conditions such as endocarditis and pneumonia. In many cases, the syndrome is self-limiting and occurs only once, but in other cases the symptoms have recurred as many as eight times. When the symptoms recur, management is more difficult because optimal pharmacologic treatment is not known. Antiinflammatory agents, such as salicylates and steroids, represent the drugs most commonly used. Although analgesics with codeine or oxycodone are important for the patients' symptomatic relief, early recognition of the syndrome is the key to limiting the discomfort and possible complications associated with this condition.

Analgesics↗

Hemodynamic effects of environmental hyperthermia in stage 18, 21, and 24 chick embryos.

Environmental hyperthermia is a hazard to the poikilothermic chick embryo. We studied effects of hyperthermia on mean vitelline arterial blood pressure and mean dorsal aortic blood flow in stage 18, 21, and 24 chick embryos. The pressure was measured with a servo-null micropressure system, and the blood flow was measured with a 20 MHz pulsed Doppler flowmeter. Temperature was monitored with a needle thermoprobe positioned adjacent to the embryo. Data were obtained at 37 degrees C, after warming to 40 degrees C, and then after cooling to 37 degrees C. At stage 21, the pressure increased from 0.96 +/- 0.05 (+/- SE) to 1.04 +/- 0.06 mm Hg on warming and returned from 1.05 +/- 0.04 to 0.87 +/- 0.04 mm Hg on cooling. Pressure measurements during warming and cooling were performed in two separate groups of embryos because of technical problems. The blood flow, studied using different groups of the embryo from the pressure study, also increased from 0.65 +/- 0.06 to 0.75 +/- 0.06 mm3/s on warming and returned to 0.56 +/- 0.05 mm3/s. The heart rate increased from 173 +/- 2 to 211 +/- 3 at 40 degrees C and returned to 170 +/- 3 at 37 degrees C. Stroke volume (flow/heart rate) did not change during the temperature variation. Vascular resistance, the quotient of pressure to blood flow obtained by a ratio analysis, changed from 1.53 +/- 0.33 (median +/- 95% confidence interval) to 1.42 +/- 0.29 mm Hg/mm3/s on warming and changed to 1.60 +/- 0.32 mm Hg/mm3/s on cooling. Similar results were obtained at stages 18 and 24.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of isoproterenol on cardiovascular function in the stage 24 chick embryo.

The developing cardiovascular system of the chick embryo is susceptible to teratogenic effects of catecholamines. Yet the mechanism for the teratogenetic action is unclear. Since catecholamines affect cardiovascular physiology, we studied the acute effect of the beta-agonist isoproterenol on mean atrial pressure, heart rate, mean dorsal aortic blood flow, mean arterial pressure and vascular resistance in stage 24 chick embryos. Dorsal aortic blood velocity was measured with a 20-MHz pulsed-Doppler velocity meter and intravascular pressure was measured with a servo-null pressure system. Isoproterenol in doses of 2 X 10(-4) micrograms (2.5 micrograms/kg), 8 X 10(-4) micrograms (10 micrograms/kg), and 1.2 X 10(-3) micrograms (15 micrograms/kg) was injected intravenously in 5-microliters aliquots of chick Ringer's solution. Additional groups of embryos were treated with the beta-antagonist propranolol, and isoproterenol plus propranolol. Control embryos received 5 microliters chick Ringer's solution to assess the hemodynamic effects of a volume injection. We found that isoproterenol caused no change in mean atrial pressure, heart rate, or mean arterial pressure. However, isoproterenol caused a dose-related decrease in dorsal aortic blood flow and a 2.5-fold increase in vascular resistance. The effects of isoproterenol were blocked by propranolol, which suggested that the increase in vascular resistance was mediated by beta-receptor stimulation.

Animals↗

Pulmonary stenosis in infants and young children.

Twenty-four patients less than 3 years old underwent operation for pulmonary stenosis. Pulmonary dysplasia was diagnosed preoperatively in only 4 patients; in 20 patients the lesion was categorized simply as pulmonary stenosis. At operation, more severe valve deformities were often present in patients less than 2 years of age. Preoperative evaluation did not reveal the extent of the deformity in 7 additional patients. The deformities included not only valvular dysplasia (thickened redundant valve cusps) but also supravalvular and annular abnormalities. Relief of obstruction was obtained only when all components of the obstructive abnormality were relieved. Patch angioplasty of the right ventricular outflow tract was necessary in 13 patients with complex morphology. Valvotomy was effective only for pulmonary stenosis due to pure commissural fusion. A spectrum of the morphology of pulmonary stenosis is recognized, with more complex lesions than simple commissural fusion identified in younger children. The more complex lesions may require more extensive operations (outflow tract patch) to completely relieve the obstructive pathological condition in the outflow tract.

Cardiac Catheterization↗

Pacemaker management for acute onset of heart block in childhood.

Four children aged 2 to 15 years are described who had Stokes-Adams syndrome as the primary cardiac manifestation of complete heart block. All had mild, nonspecific antecedent symptoms without signs of congestive heart failure. Viral neutralizing antibody titers (coxsackievirus B1 and B2) rose significantly in two patients. Electrocardiography demonstrated complete heart block associated with one or more of the following: right bundle branch block, left anterior hemiblock, left bundle branch block, intraventricular conduction delay, and ventricular standstill. In addition, second-degree heart block was seen during the initial or resolving phases of illness. To prevent further life-threatening episodes of Stokes-Adams syndrome, temporary transvenous pacemakers were placed. Two patients with persisting complete heart block required permanent pacemakers. At last examination, the remaining two patients had sinus rhythm and normal conduction. Nonsurgical acquired complete heart block is unusual in childhood, and may be the only manifestation of myocarditis. Extreme bradycardia, which causes syncope, requires immediate temporary cardiac pacing; if the bradycardia persists, a permanent pacemaker should be implanted.

Acute Disease↗

Effect of environmental hypothermia on vitelline artery blood pressure and vascular resistance in the stage 18, 21, and 24 chick embryo.

We studied the effect of environmental hypothermia on arterial blood pressure, dorsal aortic blood flow, and vascular resistance in stage 18, 21, and 24 chick embryos. The arterial pressure was measured with a servonull micropressure system. Mean dorsal aortic blood flow was calculated from pulsed-Doppler measurement of mean dorsal aortic blood velocity and dorsal aortic diameter. Vascular resistance was calculated by dividing mean vitelline arterial blood pressure by dorsal aortic blood flow. Sequential data were obtained at temperatures of 34.7, 31.1, and 34.1 degrees C. At stage 21, the vitelline arterial blood pressure decreased from 0.82 +/- 0.03 (means +/- SEM) to 0.72 +/- 0.03 mm Hg on cooling and increased from 0.66 +/- 0.05 to 0.87 +/- 0.06 mm Hg on rewarming (p less than 0.05). At stage 21, mean dorsal aortic blood flow decreased from 0.49 +/- 0.02 to 0.33 +/- 0.02 mm3/s with cooling and increased from 0.34 +/- 0.02 to 0.47 +/- 0.02 mm3/s with rewarming. The vascular resistance in stage 21 embryos increased after cooling from 1.68 +/- 0.19 to 2.23 +/- 0.39 mm Hg/mm3/s (means +/- 95% confidence interval). The changes were similar in stage 18 and 24 embryos. We conclude that the reduction of vitelline artery blood pressure resulted from a decrease in cardiac output. In addition, we noted that the vitelline arterial vascular bed can constrict in response to hypothermia prior to autonomic innervation. These changes in hemodynamics may be a teratogenic mechanism for hypothermia-induced cardiac defects in the chick embryo.

Animals↗

Congenital aortic stenosis with hypoplasia of the left sinus of Valsalva. Anatomic reconstruction of the aortic root.

Evaluation of the aortic root in 13 patients with congenital aortic stenosis aged 2.5 to 24 years (mean 8.3 years) has revealed morphologic characteristics of asymmetry of the aortic root caused by a small (hypoplastic) left sinus of Valsalva associated with a supravalvular ridge above the left coronary ostium and dysplasia of the aortic valve. The asymmetry resulted in folding and buckling of the left aortic cusp. The aortic valve was classified as bicuspid in 11 of the 13 patients. Preoperative aortography was characteristic and revealed the diagnosis in all patients. The average left ventricle-aorta systolic pressure gradient was 81 mm Hg. Operative repair consisted of an oblique aortotomy extended in a spiral fashion to the right and posteriorly into the left sinus of Valsalva. Seven patients had further mobilization of the posterior commissure with a second incision to the right of the commissure into the noncoronary sinus. Slightly fused valve commissures were opened in 12 patients. Aortic root reconstruction was accomplished with a spiral Dacron patch and posterior commissural repositioning. Follow-up catheterization at 9 to 35 months (mean 24 months) in five patients demonstrated an average outflow tract systolic gradient of 28 mm Hg and a more symmetrical appearance of the aortic root.

Adolescent↗

Effect of conotruncal constriction on aortic-mitral valve continuity in the stage 18, 21 and 24 chick embryo.

The effect of conotruncal constriction on the development of aortic-mitral valve continuity in stage 18, 21 and 24 chick embryos was studied. A 10-0 nylon suture was tied around the conotruncus, constricting the outflow tract of the heart. The loop was removed after 4 or 24 hours or left permanently in place in 3 subgroups of the 236 experimental embryos. The embryo hearts were harvested at stages after completion of cardiac morphogenesis, fixed in end-diastole and microdissected. The distance between the mitral and aortic anuli was measured from the base of the heart with a calibrated filar micrometer eyepiece. This measurement was compared with the mitral-aortic separation in 72 normal and 132 control embryos. The mitral-aortic separation was similar among normal, control and 4- and 24-hour experimental embryo hearts. However, the mitral-aortic separation increased from 0.34 +/- 0.02 mm in normal hearts to 0.82 +/- 0.25 mm in stage 18, 1.11 +/- 0.36 mm in stage 21 and 0.75 +/- 0.33 mm in stage 24 permanent loop experimental hearts (p less than 0.01). In embryo hearts with an increased mitral-aortic separation, both great vessels arose from the right ventricle, the semilunar valves were at the same level and the ventricular septal defect was present beneath the aortic anulus. We conclude that conotruncal constriction modifies the relation of the aortic and the mitral valve. We speculate that conotruncal constriction alters the migration of mesenchymal tissue into the heart.

Animals↗

Neck web and congenital heart defects: a pathogenic association in 45 X-O Turner syndrome?

This study explores the association between neck web and congenital heart disease in patients with Turner syndrome. Of 193 cases with documented 45 X-O karyotype, 106 (55%) had a web neck and 87 (45%) had a normal neck. The incidence of congenital heart disease was significantly different between these two groups, occurring in 30% of those with web neck and 9% of those with normal neck (x2 = 12.82, P less than .0005). The difference was most striking in coarctation of the aorta for which the prevalence was 25% with web neck and 3% with normal neck (X2 = 17.65, P less than .0001). The association between web neck and congenital heart disease suggests a pathogenic relationship exists between the two. The following hypothesis is proposed to explain the association. Increased lymphatic pressure associated with jugular lymphatic sac obstruction distends the thoracic ducts, which compress the ascending aorta altering intracardiac blood flow. Redirection of intracardiac blood flow produces coarctation of the aorta and other defects in the spectrum of left heart obstruction. This proposed mechanism is an example of a teratogenic event remote from the heart, which alters cardiovascular morphology.

Abnormalities, Multiple↗

The effect of chick embryo hyperflexion on tracheoesophageal development.

Chick embryos were hyperflexed by placement of a ligature at two critical stages in the development of the foregut, in order to test the theory that esophageal atresia and tracheoesophageal fistula result from embryonic hyperflexion. Only one "H-type" tracheoesophageal fistula was found. There were no significant disturbances of either tracheal or esophageal growth.

Animals↗

Effect of caffeine on cardiovascular function in the stage 24 chick embryo.

Caffeine is consumed by an estimated 95% of pregnant women. Yet, it is not known if caffeine alters embryonic cardiovascular function. We measured the effect of caffeine on mean and phasic dorsal aortic blood flow and mean vitelline artery pressure with a 20-MHz pulse Doppler velocity meter and a servo-null pressure system, respectively. We calculated vascular resistance, stroke volume index, and heart rate. We injected 5-microliters aliquots of anhydrous caffeine dissolved in chick Ringer's lactate into a vitelline vein in doses from 1.2 X 10(-5) mg (0.15 mg/kg) to 1.2 X 10(-2) mg (150 mg/kg). Control embryos received 5 microliters chick Ringer's lactate. The hemodynamic measurements were continuously recorded from 1 min prior through 5 min after injection. 9 stage 24 chick embryos were studied at each dose. The data were analyzed by one-way analysis of variance and Tukey's HSD test. Caffeine had no effect on heart rate, but a direct dose-related effect on mean dorsal aortic blood flow, stroke volume index, mean pressure, and vascular resistance. The effect of caffeine on stroke volume index at 5 min was a linear log-dose relationship [y = 0.155 + 0.02 1n (dose), p less than 0.001]. In the chick, caffeine acutely affects cardiovascular function by increasing myocardial contractility and dilating resistance vessels. We speculate this action is mediated through direct cellular effects: increase in free Ca++ and cyclic adenosine monophosphate.

Animals↗

Is the onset of actin histidine methylation under development control in the chick embryo.

It had previously been reported (B. Krzysik, J. P. Vergnes, and I. R. McManus (1971) Arch. Biochem. Biophys. 146, 34-45) that prior to day 11 of embryonic life chick skeletal muscle actin contained little or no 3-methylhistidine, and that between Day 11 and 18, the degree of actin histidine methylation increased until it leveled off at 1 mol of 3-methylhistidine/mol actin. This is the value seen in adult muscle and nonmuscle actins so far analyzed. To determine whether this delayed onset of actin methylation occurred simultaneously throughout the organism or differed from tissue to tissue, the 3-methylhistidine content of cardiac muscle actin from Day 2 of embryonic life to hatching and of brain actin at Days 9, 11, and 14 were analyzed. These results, obtained by analyzing unlabeled actin samples as well as samples labeled in vivo with [3H]histidine, showed that at all stages, 1 mol of 3-methylhistidine was present per mol of actin. When skeletal muscle samples obtained from Day 11 to 18 embryos were analyzed 1 mol of 3-methylhistidine/mol of actin was observed. Thus, in the chick embryo, contrary to those reports published earlier, it was found that actin histidine methylation is not under developmental control.

Actins↗

Total anomalous pulmonary venous connection.

Total anomalous pulmonary venous connection (TAPVC) was repaired by operation in 20 infants during a 101/2-year period (1972 to 1983). Five patients died following operation. Factors that most affected mortality were the condition of the patient prior to repair, the year of operation, and the technique used for repair. Operative mortality before 1976 was significantly different from that after 1976 (57% [4/7] versus 8% [1/13], respectively; p less than 0.04). Prior to 1976, the several techniques used for anastomosis of the left atrium to the common pulmonary vein involved displacement of the heart from its anatomical position. After 1976, a standard approach using a right atriotomy for access was adopted for all such repairs. Intracardiac type of TAPVC was repaired by pericardial patch to direct blood flow through the atrial septal defect to the left atrium. Supracardiac and infracardiac types were repaired by enlarging the atrial septal defect so that a transverse incision through the back of the left atrium was exactly overlying the pulmonary vein posteriorly. A large anastomosis of the left atrium and common pulmonary vein was made with the heart in its natural anatomical position, which eliminates the possibility of distortion of the anastomosis. A pericardial patch was used to close the atrial septal defect. This experience suggests that the right transatrial approach of creating an anatomically correct anastomosis of the left atrium to the common pulmonary vein is an important factor in reducing operative mortality in patients with TAPVC.

Cardiac Catheterization↗