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)

Neural crest ablation versus sham surgical effects in a chick embryo model of defective cardiovascular development.

In chick embryos, ablation of premigratory neural crest destined for the third, fourth, and sixth pharyngeal arches results in persistent truncus arteriosus and interrupted aortic arch. Studies of cardiogenesis in these embryos have shown decreased ejection fraction and ventricular dilation with normal cardiac output. The experimental embryos that survive to d 11 of incubation have a higher cardiac output than nonsurvivors at the same earlier stage of development. We hypothesize that this survival is due to a surgically induced decrease in vascular resistance of the embryonic and vitelline vessels. Embryos from 15 opened eggs, eight sham-operated embryos, and 13 neural crest-ablated embryos were examined at stage 18. The sham-operated embryos were treated identically with the experimental embryos except that neural crest was not ablated. Ejection fraction and cardiac output were determined by cinephotography. Mean dorsal aortic and diastolic ventricular (approximates mean atrial) pressures were determined by a servo-null pressure technique and used to calculate vascular resistance. The experimental embryos had a significantly decreased ejection fraction in comparison with either sham-operated embryos or embryos from eggs that remained unopened until just before cinephotography. The experimental and sham-operated embryos had a higher cardiac output than embryos from unopened eggs. The calculated vascular resistance was also significantly lower in both the experimental and sham-operated embryos than in the embryos from unopened eggs. Neural crest ablation appears to cause a decreased ejection fraction. Sham surgery is associated with a higher cardiac output and lower vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Hemodynamic changes and compensatory mechanisms during early cardiogenesis after neural crest ablation in chick embryos.

Microcinephotography was used to study early heart development in chick embryos with ablations of the neural crest known to result in persistent truncus arteriosus with associated aortic arch anomalies. The premigratory neural crest destined for the 3rd and 4th pharyngeal arches and the aorticopulmonary septum were ablated. When the embryos reached the looped cardiac tube stage (stage 18), 15 experimental and 15 control embryos were filmed at 100 frames/s under controlled environmental conditions. End-diastolic and end-systolic dimensions were determined for the conotruncus and presumptive right ventricle that together compose the bulbus cordis. The results showed that the shortening fractions and ejection fractions were significantly depressed in the experimental embryos. The experimental embryos exhibited dilation and decreased emptying of the ventricle. There was no difference in heart rate or stroke volume between the control and experimental embryos. Thus, the calculated cardiac output was the same in the control and experimental groups. It appeared that the experimental embryos compensated for decreased contractility by ventricular dilation. These functional compensations in very early cardiac development may play an etiologic role in the subsequent development of structural heart defects.

Relation of early hemodynamic changes to final cardiac phenotype and survival after neural crest ablation in chick embryos.

BACKGROUND: Microcinephotography was used to study a model of persistent truncus arteriosus created in chick embryos by ablation of premigratory neural crest destined for the third and fourth aortic arch arteries as well as the septum of the cardiac outflow tract. METHODS AND RESULTS: Twenty-five control embryos and 105 of 202 experimental embryos were filmed on day 3 of incubation and then reincubated. The remaining 97 experimental embryos were not filmed because of twisting of the embryos, but they were reincubated. There was no difference in either the survival rate (p greater than 0.23) from day 3 to day 11 of incubation or the incidence of persistent truncus arteriosus (p greater than 0.08) between the filmed and the nonfilmed embryos. Incomplete looping of the cardiac tube observed in experimental embryos during early cardiogenesis correlated with a right ventricular origin of the outflow vessels in the definitive heart. Hemodynamic measurements indicated that there was no difference in heart rate, ejection fraction, systolic and diastolic areas, stroke volume, and cardiac output between controls and the experimental group as a whole. However, embryos that did not survive to day 11 had decreased stroke volume (p less than 0.001) and cardiac output (p less than 0.001), whereas embryos that survived to day 11 with cardiac malformations had increased stroke volume and cardiac output in early embryogenesis. CONCLUSIONS: Increased stroke volume and cardiac output may be necessary factors for survival in embryos with cardiac dysmorphogenesis and probably are associated with dilation of the ventricular portion of the cardiac tube, which leads to malalignment of the outflow vessel or vessels.

A national survey on the pediatric cardiologist's clinical approach for patients with Kawasaki disease.

In 1994, the American Heart Association (AHA) published the most recent guidelines for long-term cardiovascular management of Kawasaki disease. Since then, recent publications have shed new light on different diagnostic, prognostic, and management issues. We sought the opinion of pediatric cardiologists practicing in U.S. fellowship programs on the subject by means of a multiple-choice survey. Two questions addressed therapy in the acute phase, each preceded by a statement from related literature. Ten duplicate questions addressed the long-term cardiovascular management in five sets of paired questions; each question was first given in reminiscence of a clinical situation and then preceded by a statement from particular publications representative of new information that has become available since the publication of the 1994 AHA guidelines. All questions were provided in the same mailing. Replies were received from 97 participants practicing at 29 institutions. For the acute illness, 21% of respondents do not use high-dose aspirin, and 50% support reassessment of current guidelines. Universal intravenous immune globulin (IVIG) administration is followed by 97%, among whom 20% agree that evaluation of selection criteria is needed. For long-term management, 60-75% advocate regular follow-up of risk level I patients, and 80% favor periodic follow-up, with stress imaging (34-40%), for risk level II. For risk level IV more respondents favor stress echocardiography as opposed to nuclear imaging, in consonance with recent literature. For risk levels III and IV, 36-40% perform coronary angiography on a regular basis, whereas 60% do so when coronary symptoms are present or when stress imaging suggests myocardial ischemia. Finally, 19-25% of respondents do not routinely advise healthy lifestyle to patients free of coronary artery lesions. In conclusion, the guidelines for conventional therapy in the acute phase and long-term cardiovascular management need to be revised.

Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen unterminally coupled to the diphtheria protein CRM197.

Vaccines consisting of oligosaccharide (OS) derived from Haemophilus influenzae type b capsular polysaccharide and conjugated to carrier proteins had been shown capable of eliciting memory-type capsular polysaccharide of H. influenza type b antibody responses in human infants, but the structural variables governing immunogenicity were not defined. Here a series of conjugates were made with the diphtheria protein CRM197 and with uniterminally coupled OS haptens that varied in chain length, exposed terminal residue, or multiplicity of loading as defined by ribose/protein ratio. Adults were given a single injection, 1-yr-old infants were given a two-injection sequence, and capsular polysaccharide of H. influenzae type b antibody responses were assessed by radioantigen binding. Vaccines C-4r, C-6r, and C-12r, in which ribitol-ended OS of mean length 4, 6, or 12 repeat units were coupled at low hapten loading, were about equally immunogenic (geometric means 2 to 5 micrograms/ml in infants, 5 to 9 micrograms/ml in adults). Vaccine C7p was made with a higher loading of OS having mean length 7 repeat units and having mainly phosphate monoester at the exposed termini Vaccine C-7R was made from a portion of C-7p by enzymatic removal of most of the terminal phosphates. Compared to the C-4r, C-6r, and C-12r series, vaccines C-7p and C-7R induced geometric means about 10-fold higher in adults and 20-fold higher in infants. Thus OS chain length (in the range studied) and exposed terminus are less critical variables in this system than the extent of hapten loading.