The development of newer, load-independent indices of contractility has not substantially reduced general clinical reliance on ejection fraction and shortening fraction to detect abnormalities of contractility, in spite of common understanding of the preload and afterload dependence of percent fiber shortening. The more widespread application of sensitive indices of contractility has been impeded in part by complex methods of acquisition and analysis of data as well as uncertainty concerning the clinical importance of the additional derived information. Substantial recent experience with analysis of stress-shortening and stress-velocity, nonetheless, demonstrates that physiologically meaningful indices of afterload, preload, and contractility can be obtained noninvasively without hemodynamic interventions. There is extensive theoretical and experimental basis for these methods, and the limitations are similar to other global indices of myocardial mechanics. The superiority of methods which allow distinction between contractile abnormalities and abnormal load are particularly important when altered ventricular loading conditions are a prominent feature of the disease state. Several clinical situations have been identified for which analysis of stress-shortening and stress-velocity demonstrates that assessment by fiber shortening alone has resulted in misrepresentation of myocardial status. The clinical utility of assessment of ventricular function is considerably enhanced when the relative contribution of load and contractile performance is determined.

To study the interaction between hemodynamics and morphology in abnormal development of the heart, it is essential to have an animal model with specific and reproducible cardiac malformations. A standardized method was developed for inducing such an anomaly in the chick embryo. For this purpose, all-trans retinoic acid, dissolved in 2% dimethylsulphoxide, was applied on the vitelline membrane of the embryo in concentrations of 1.0 μgm and 0.3 μgm. A total of 207 embryos, staged according to Hamburger and Hamilton, were treated at stages 10 (33 hours of incubation) and 15 (50–55 hours of incubation). Three control groups consisted of embryos solely treated with dimethylsulphoxide, sham operated chicks, and untreated embryos, respectively. The embryos were sacrificed on the 9th, 10th and 11th days of incubation and hearts were examined by microdissection. Additional histologic studies were undertaken in 110 cases. Embryos treated with retinoic acid at both stages of development showed a high percentage of lesions falling within the general spectrum of double outlet right ventricle. The abnormality varied from merely a rightward shift of the aorta to cases with an additional subaortic ventricular septal defect, which, in combination with the rightward positioned aorta, was classified as a double outlet right ventricle. Histologic examination showed the presence of muscular tissue between the leaflets of the aortic and mitral valves. No other types of cardiac malformations were seen. Our results, with respect to timing, resemble data from studies made of hearts after surgical ablation of neural crest at comparable stages. Both method and timing of treatment with retinoic acid are important factors for the induction of specific and reproducible cardiac anomalies. This chick model allows for further detailed study of development of double outlet right ventricle, as well as the assessment of early detectable hemodynamic changes.

The effect of enalapril, an inhibitor of angiotensin converting enzyme, was studied in 35 infants and children with congestive heart failure associated either with residual mitral or aortic regurgitation following intracardiac repair (24 patients) or with dilated cardiomyopathy (11 patients). Enalapril, at an average dose of 0.24 ±0.10 mg/kg, reduced the concentration of angiotensin II in the serum from 115 ± 67 pg/ml to 60 + 30 pg/ml and increased plasma renin activity from 25 + 24 ng/ml/hr to 45 ± 37 ng/ml/hr. There was a significant decrease in hepatomegaly, cardiothoracic ratio, heart rate and blood pressure in both groups of patients. Left ventricular end-diastolic dimension as evaluated by cross-sectional echocardiography, also decreased, whereas fractional shortening and systolic time intervals improved in both groups of patients. Adverse effects were noted in only one infant with postoperative mitral regurgitation who developed renal failure with oliguria, increase of blood urea nitrogen and serum creatinine. Renal function improved dramatically after discontinuation of enalapril. Hyperkalemia (>5mEq/ 1) was observed in four patients, three of whom were receiving spironolactone. Our results showed that enalapril is effective in improving hemodynamics in the relatively short-term treatment of infants and children with congestive heart failure due to postoperative volume overload or dilated cardiomyopathy. These conditions are poorly controlled with conventional medical therapy.

Our purpose was to study serially, measurements which relate to right ventricular events, using echocardiography and Doppler in full term neonates for the first three weeks after birth. Echocardiographic and pulsed Doppler studies were performed for 21 newborns during the first 36 hours of life, and subsequent serial studies were performed in the second (n=21) and third (n=14) weeks of life. Evaluation included measurement of right isovolumic relaxation time and peak E and A velocities across the tricuspid valve. Pulmonary velocities were studied for evidence of patency of the arterial duct, and to determine acceleration in the pulmonary trunk. Mean right isovolumic relaxation time decreased significantly from 68±9 ms to 39 ± 14 ms (p<0.001) between the first and second week. Mean tricuspid peak E increased significantly between the second (48 ± 7 cm/s) and the third week of life (62 ± 8 cm/s; p<0.001). Mean peak A wave velocity did not change significantly during the time of study. The pulmonary arterial acceleration time increased from the initial measurement (68 ± 10 ms) to the second week (85 ± 9 ms; p<0.001). Changes in right isovolumic relaxation time were significantly related to the changes in the pulmonary arterial acceleration time (r=0.63, p=0.0001), suggesting a significant influence of afterload on diastolic events. These data demonstrate the normal progression of some measures of early right ventricular diastolic function.

We have investigated the spatial distribution of the α and β isoforms of myosin heavy chain in the force-producing ventricular myocardium, the ventricular conduction system and the atrioventricular junctional region of five neonatal human hearts–three born prior to and two at term. The results can be summarized as follows: 1) the force-producing myocardium: in each heart, the β isoform was found to be the predominating isoform, β-negative cells never being observed. Considerable amounts of the α isoform were observed only in those hearts that were obtained from patients dying within the first two weeks of postnatal life. This transient expression is probably correlated with the postnatal increase in levels of circulating thyroid hormone. 2) the ventricular conduction system: in addition to the expression of the β isoform, a strong expression of the α isoform was detected in all the components of the ventricular conduction system in the two full-term hearts. In the preterm hearts, however, this strong expression was mainly restricted to the atrioventricular node and the penetrating atrioventricular bundle. The level of expression of the α isoform in the conduction system of the neonatal hearts, therefore, might reflect the state of maturity of this system at the time of birth. 3) the atrioventricular junctional region: in each heart examined, structures were detected that resembled immunohistochemically and morphologically the atrioventricular node. Although the expression of the isoforms of myosin heavy chain in the conduction system, and in these comparable structures, cannot, as yet, be interpreted with regard to function, these resemblances, coupled with the same developmental background for these structures (they all develop from the so-called “primary ring”) suggest functional affinities during this stage of cardiac development.

We have conducted, in two stages, a descriptive and comparative analysis of the diagnostic and evolutionary clinical aspects of rheumatic fever. The descriptive analysis was based on a sample of 226 patients seen between 1976–1986. The forms and frequency of the manifestations of rheumatic fever were studied, as well as the difficulties encountered in diagnosing mild cases and the risk of making a hasty diagnosis due to the high prevalence of the disease. Subsequent to the establishment of an outpatient clinic for referral of patients with rheumatic fever, as part of a study and control program for the disease, 98 patients were seen in the period 1988–1991. In order to compare the profile of the manifestations in the acute phase with evolutionary aspects over the course of the disease, a subgroup of 61 children, treated in the period 1983–986 was selected to obtain equivalence in size of sample and time of follow-up (p = 0.08). The comparative analysis revealed that no modifications have occurred over the period of study in the profile of the manifestations during the acute phase, and no statistically significant differences have occurred in age at first attack, severity ofcarditis, or in the type ofvalvar and articular involvement. Evolutionary data after rigid control of primary and secondary prevention, however, showed a marked reduction in the incidence of recurrence (p = 0.036), the frequency of hospital admission (p = 0.001) and deaths (p = 0.024). The main factors modifying the evolution of the disease were analyzed. The action of the health team had a fundamental importance in the control of recurrence. This fact is especially important for developing countries, where a reduction of the prevalence of the disease can only be achieved through major structural socioeconomic changes in the community.