Mid-ventricular obstruction: A variant of obstructive cardiomyopathy

In two patients with clinical and catheterization findings of hypertrophic obstructive cardiomyopathy, the level of intraventricular obstruction was found to be in the mid-ventricular area rather than at the junction of the inflow and outflow tracts. One patient died suddenly shortly after unsuccessful outflow tract myectomy. In vivo recognition of this probably rare variant form of obstructive cardiomyopathy rests mainly on the angiographic appearance of the left ventricle and on the recording of pressures in multiple sites of the left ventricular cavity. Surgical relief of the obstruction in these patients is not likely to be obtained by a transaortic left ventricular outflow myectomy but may require either papillary muscle resection by the transatrial or transventricular approach or mid-ventricular septectomy, or both.     

Comparative response of right and left ventricles to volume overload.

The cardiac volume data of 49 normal children were compared with those of 23 with secundum atrial septal defect and 24 with patent ductus arteriosus. Significantly smaller ventricular end-diastolic volumes were observed in the normal infants than in older children (right ventricle 53.9 versus 75.5 cm3/m2; left ventricle 46.7 versus 63.6 cm3/m2). "Distensibility" of the right ventricle (DRV), left ventricle (DLV) and left atrium increased normally with age. DRV and DLV were similar shortly after birth; thereafter, DRV increased more rapidly than DLV (mean DRV 12.7; mean DLV 7.8 cm3/m2 per mm Hg, P less than 0.001). In both atrial septal defect and patent ductus arteriosus, the ipsilateral (involved) ventricles had increased volume, increased output, normal ejection fraction and increased distensibility. The contralateral (left) ventricle in atrial septal defect was smaller than normal (39.6 versus 49.7 cm3, P less than 0.001), and had a smaller ejection fraction (0.63 versus 0.71, P less than 0.01) and output (3.70 versus 4.57 liters/min per m2, P less than 0.005). In contrast, the contralateral (right) ventricle in patent ductus arteriosus remained normal. Left atrial maximal volume was larger than normal in atrial septal defect (46.6 versus 35.9 cm3/m2, P less than 0.001). The left atrial and left ventricular volumes in patent ductus arteriosus were, respectively, 152 and 142 percent of normal, indicating comparable response to the volume load. The left head changes in atrial septal defect may be related both to a functionally restrictive defect and to the difference in distensibility of the ventricles.     

Biventricular dynamics during quantitated anteroseptal infarction in the porcine heart.

The porcine heart has been shown to have close anatomic similarity to the human heart and was used as the experimental model in this study to gain further understanding of the early responses of both ventricles during acute anteroseptal myocardial infarction. High fidelity pressure and flow data were measured and multiple preejection and ejection variables were calculated for both ventricles. Infarct weight and distribution in both ventricles were quantitated. The standard infarction resulted from single stage ligation of the left anterior descending coronary artery just beyond its midpoint and second left ventricular branch. It comprised an average of 15.8 percent of total ventricular myocardium with an infarct/perfused ratio of 0.62 and a periinfarction transition zone of 7.5 mm, and involved significant portions of both ventricles and the interventricular septum. Performance characteristics of both ventricles were altered significantly by anteroseptal infarction and involved all phases of contraction--end-diastole, isovolumic systole and ventricular ejection. Although contractile alterations in the right ventricle were significant, they were somewhat delayed, yielding relatively low correlation coefficients with analogous left ventricular contractile indexes. These correlations became quite distinct during specific ventricular stresses. Comparison of anterolateral and anteroseptal infarction, matched in terms of infarct size, indicated that the right ventricular changes in the latter were related to direct involvement of the right ventricular free wall and septum rather than secondary to left ventricular alterations.     

Protein synthesis and turnover in normal and hypertrophied heart

This review deals with some aspects of the synthesis, assembly and turnover of mitochondrial and myofibrillar proteins in normal and hypertrophied hearts. The dynamic state of the myocardium, in which intracellular proteins and organelles are constantly being destroyed and synthesized, is emphasized. In normal cardiac muscle, mitochondrial inner membrane cytochromes turn over synchronously with half-lives of 5 to 6 days. The various myofibrillar proteins also turn over; the fact that they do so with identical apparent half-lives of 8 to 10 days suggests that these proteins are assembled and degraded synchronously. In cardiac hypertrophy produced by constriction of the ascending aorta in rats, inner mitochondrial membrane cytochromes increase in parallel. Early in hypertrophy (1 day after aortic constriction) cytochrome content per gram of heart weight increases, indicating a disproportionate increase in mitochondrial cytochrome mass. By the third postoperative day there already is a decrease in cytochrome content per gram of heart weight. The increase in mitochondrial cytochrome content observed in the hypertrophied heart appears to be due to a decreased rate of cytochrome destruction as well as to an increased rate of cytochrome synthesis. The data on myosin accumulation are consistent with either decreased destruction of myosin or increased efficiency of reutilization of labeled amino acids.     

Action potential and contraction of heart muscle

Current concepts of the mechanisms responsible for the cardiac action potential are reviewed, as are the relations between the electrical activity and cardiac contraction. The development of techniques allowing direct control of the membrane voltage of cardiac cells has led to a rapid increase in our understanding of the cellular basis of cardiac electrophysiology. There appear to be 8 separately identifiable ionic channels that interact to produce the distinctive cardiac action potential. These “voltage clamp” methods also provide a new approach to the study of excitation-contraction coupling in heart muscle. The application of these methods has led to several new ideas about the relation between membrane voltage and contraction. In addition to triggering contraction, the cardiac action potential plays an important role in the control of contraction, and the nature of this electrical control is examined.     

Acute aortic arch dissection: reevaluation of the indications for medical and surgical therapy.

Of 42 patients with dissection of the aorta, 4 had important arch involvement. Results were good in 2 patients treated medically. In two other patients wrapping the arch with a Dacron graft successfully prevented fatal hemorrhage. This technique avoids the need for arch replacement in selected cases. From this experience and a review of others a flow sheet was developed to guide decision-making in the surgical and medical management of patients with aortic dissection.     

Cell proliferation during cardiac growth

During the embryonic development of the myocardium both undifferentiated cells and cells containing muscle-specific proteins divide. As the heart grows and approaches maturity, its muscle cells progressively lose their mitotic activity; myocardial cell enlargement then becomes the principal process by which the heart as a whole enlarges. Mitotic figures in nuclei of heart muscle cells are frequent in the neonatal rat but become very rare at about the third month of postnatal life. Both in the developing and adult animal the work load is one of the determinants of cardiac size. The cytologic features of cardiac enlargement depend on the stage of development of the heart at the time when the stimulus to growth occurs. A work load imposed on embryonic or early neonatal hearts results in enlargement characterized by an increase in both the number and size of myocardial cells. The adult heart enlarges only by enlargement of its component muscle cells. Division of ventricular muscle cells in mammals is not activated after cardiac injury. The inability of ventricular myocardial cells to regenerate stands in sharp contrast to skeletal muscle, which is capable of considerable tissue repair, involving both regeneration of individual fibers and reconstitution of the whole muscle.     

Quantitative electron microscopic description of heart muscle cells. Application to normal, hypertrophied and thyroxin-stimulated hearts

Mathematical techniques can be used to extract quantitative information from tissue electron micrographs of heart muscle. With these methods it has been possible to measure the fractions of myocardial cell volume made up of myofibrils, mitochondria, sarcotubules, T system and sarcoplasm, as well as the membrane areas per unit of cell volume of plasma membrane, sarcotubular membrane and mitochondrial cristae. The techniques have been used to quantitate the changes in the ultrastructure of myocardial cells in experimental left ventricular hypertrophy and in experimentally induced hypothyroidism before and after treatment with thyroxin. These measurements have demonstrated striking and physiologically significant changes in the ultrastructural composition of the cells. The pattern of ultrastructural change in ventricular hypertrophy differs in characteristic ways from the pattern during thyroxin-stimulated cardiac cellular growth. These observations have suggested certain generalizations about the constraints to which growing myocardial cells are subject.New and simple microchemical methods have been developed to determine the cardiac contents of myofibrils and mitochondrial cristae. The methods are applicable to samples of heart muscle obtained at autopsy, surgery or biopsy, as well as to experimental material. Application of these techniques to the study of experimental left ventricular hypertrophy and thyroxin-stimulated growth of myocardial cells has confirmed and extended the results of quantitative measurements on electron micrographs. It is suggested that the approaches described can form the basis of a quantitative electron microscopic and microchemical pathology of heart muscle.     

Time-related changes in the Q-T interval in acute myocardial infarction: possible relation to local hypocalcemia

In 63 patients with either acute transmural or nontransmural myocardial infarction, the Q-T interval was prolonged beyond normal limits on at least 1 of the 5 days after infarction in 27 patients (8 with transmural and 19 with nontransmural infarction). The time-related changes in the corrected Q-T (Q-Tc) interval were defined for the entire sample and showed significant expansion, maximal on day 2, from a preinfarction control value. By day 5, the Q-Tc interval was no longer significantly prolonged and was not expanded beyond normal limits in any patient. Various possible causes of Q-T prolongation in myocardial infarction are local hypothermia, local conduction delay, neurogenic effect and local hypocalcemia. Collateral evidence suggests that the letter may contribute significantly to prolongation.     

Surgical correction of truncus arteriosus in infancy

An 8 week old infant with severe heart failure from type 1 truncus arteriosus underwent successful corrective surgery employing the Rastelli procedure with use of deep hypothermia and total circulatory arrest. Postoperative hemodynamic studies showed complete closure of the septal defect, disappearance of truncal stenosis, but presence of mild porcine valve stenosis. This procedure is possible even in very small subjects and is preferable to palliative pulmonary arterial banding.     

Unstable angina pectoris: National cooperative study group to compare surgical and medical therapy: III. Results in patients with S-T segment elevation during pain

A prospective randomized study comparing intensive medical therapy with urgent coronary bypass surgery for the acute management of patients with unstable angina pectoris was carried out by nine cooperating medical centers under the auspices of the National Heart, Lung, and Blood Institute. Between 1972 and 1976, a total of 288 patients were entered into the study; 79 of these (27 percent of the total study group) with 70 percent or more fixed obstruction in one or more coronary arteries had episodes of pain at rest associated with transient S-T segment elevation. Forty-two were randomized to medical and 37 to surgical therapy. The hospital mortality rate was 4.8 percent for the medical and 5.4 percent for the surgical group (difference not significant). The rate Of in-hospital myocardial infarction was 12 percent in the medical and 14 percent in the surgical group (difference not significant).During the 1st and 2nd years of follow-up, 25 percent in the medical and 15 percent in the surgical group complained of New York Heart Association class III or IV angina (difference not significant). During an average follow-up period of 42 months 45 percent of the medically treated patients later underwent surgery to relieve unacceptable angina. In the medical group 65 percent were working full- or part-time at the end of 1 year and 61 percent at the end of 2 years of follow-up; comparable figures for the surgically treated group were 63 and 68 percent.The results indicate that patients with unstable angina pectoris with transient S-T segment elevation during pain at rest with fixed obstruction of 70 percent or more in one or more coronary arteries do not differ significantly from patients with pain at rest associated with transient S-T segment depression or T wave inversion. The condition of such patients can be stabilized, and they can be managed with a maximal medical program including propranolol and long-acting nitrates in pharmacologic doses with good control of pain in most and no increase in rate of early mortality or myocardial infarction. Later, elective surgery can be performed with a lower risk and good clinical results if the patient's angina fails to respond to intensive medical therapy.     

Thyroid abnormalities in children of parents who have Graves' disease: Possible Pre-Graves' disease

We have studied possible premonitory features of Graves' disease among offspring of parents who had this condition. One-hundred-fifty-three children of parents with Graves' disease were examined, as were 129 control children selected on the basis of a negative history for Graves' disease among first-degree relatives. Examination consisted of a physical examination, brief medical history, and determination of a variety of thyroid function and autoimmunity tests. Thirty-six percent of children of parents with Graves' disease had one or more abnormality, as compared to 24% of the control children. The incidence of abnormalities increased with age and were more common in females. The abnormalities in both groups were similar in variety and intensity, and differed mainly quantitatively in frequency. Half of the minor abnormalities detected in the thyroid, including firmness, enlargement, or lobulations, were accompanied by chemical abnormalities such as a high or low T₄ level, abnormal thyroglobulin or triiodothyronine (T₃) level, or the presence of antithyroid antibodies. One quarter of children having some minor abnormality in the thyroid had definite evidence of Hashimoto's thyroiditis. Bioassays for long-acting thyroid stimulator (LATS) were positive in 2 of 95 children of parents with Graves' disease, and in 1 of 49 control children. Assays for thyroid stimulatory immunoglobulins, cell-mediated immunity to thyroid antigens, and thyroglobulin immune complexes were negative. There was a clustering of abnormalities in certain families, suggesting that these families may be prone to develop subsequent clinical illness. During follow-up examination extending over 3 yr, a significant fraction of children lost or modified the original abnormality or developed a new abnormality. During observation, one child developed asymptomatic thyrotoxicosis, one developed exophthalmos, one developed vitiligo, and one had the onset of Hashimoto's thyroiditis. The data suggest that there is a progressive evolution of abnormalities in thyroid function, and that these are especially common within certain families. It may be possible to determine from sequential examinations which children are at risk, with a high degree of probability of developing thyrotoxicosis. The abnormalities found in these children change from year to year and do not represent a necessarily progressive process. The data indicate the presence of a condition that may be called “Pre-Graves' Disease”, a dynamic state of disordered antithyroid immunity, which may lead to overt thyrotoxicosis in some children.     

Sinus nodal echoes. Clinical case report and canine studies

Sinus nodal echoes are illustrated in (1) a case report, and (2) a study of the effects of atrial premature beats after atrial drive in dogs. When atrial premature beats confront the sinus node while it is still refractory, 3 types of response may be seen: (1) Complete interpolation—the subsequent sinus beat (or escape) comes precisely at the expected time; (2) incomplete interpolation—the subsequent sinus beat is delayed; and (3) sinus echoes—the sinus beat appears earlier than expected. In all 3 instances the node is entered, but the pacemaker fails to be reset. Although the echo has the form of a sinus beat, it is followed by a pause, presumably as a result of repenetration of the sinus node through pathways unused during exit. The curves characterizing the expansion by vagal stimulation of the nodal refractory period and total echo circuit time are defined, together with the latency of cholinergic effect on nodal refractoriness, sinus automaticity and exit conduction of the echo. The secondary concealment zone of a completely interpolated atrial premature beat is established. Atrial preexcitation (before the echo) sometimes evokes a second echo. The limiting factor on sustained sinoatrial reciprocation thus appears to be total echo circuit time rather than refractoriness of atrium or echo entrance pathways. The repetitive echoes seen in this study may be the basis for some clinical cases of sinus or atrial tachycardia.     

Biosynthesis of thyroid hormone: basic and clinical aspects.

Thyroid hormone formation requires the coincident presence of peroxidase, H2O2, iodide, and acceptor protein at one anatomic locus in the cell. The peroxidase enzyme appears to be a protoporphyrin lX containing heme protein, with binding sites for both iodide and tyrosine. It is probable that both iodide and tyrosine are oxidized to free radical forms which unite to form iodotyrosine. The peroxidase is also involved through an uncertain mechanism in iodotyrosine coupling and probably in oxidation of sulfhydryl bonds in thyroglobulin. H2O2 may be supplied by microsomal NADPH-cytochrome c reductase or NADH-cytochrome b5 reductase. Other possible intracellular H2OI generating systems include monoamine oxidase and xanthine oxidase. The usual acceptor for iodide is thyroglobulin, which is currently believed to be iodinated within apical secretory vesicles at the cell border just prior to liberation into the colloid, or possibly after liberation into the colloid. Other soluble an insoluble proteins are also iodinated within the gland. The peroxidase is present in numerous cellular structures, but iodination activity occurs primarily, if not only, at the apical cell border. The controls of iodination are imperfectly known. Thyrotrophin modulation of iodide uptake, H2O2 generation, thyroglobulin synthesis, and peroxidase enzyme level obviously are the main regulations. Many of these actions are thought to involve mediation of adenyl cyclase and subsequent activation of intracellular phosphokinases. Antithyroid drugs of the thiocarbamide group are competitive inhibitors of iodination under some circumstances, but if much iodide is present, they react with the oxidized iodine intermediate and are irreversibly inactivated themselves. Clinical problems involving defective peroxidase function are among the most frequent hereditary defects of thyroid hormone formation. Recognized abnormalities include deficient peroxidase, abnormality in binding of the peroxidase apoprotein to its prosthetic group, and other less well-identified abnormalities in peroxidase structure and function. Peroxidase is typically elevated in thyroid tissue from patients with hyperthyroidism sometimes deficient in cold thyroid nodules, and frequently diminished in tissue from patients with Hashimoto's thyroiditis.     

Estimation of circumferential fiber shortening velocity by echocardiography

The M-mode and two-dimensional echocardiograms of 40 young patients were analyzed to compare the mean circumferential fiber shortening velocity (Vcf) of the left ventricle calculated separately by two methods. The mean circumferential fiber shortening velocity was derived from the M-mode echocardiogram as minor axis shortening/ejection time and derived from the two-dimensional echocardiogram as actual circumference change/ejection time. With computer assistance, circumference was determined from the short-axis two-dimensional echocardiographic images during end-diastole and end-systole. Good correlations were obtained between the left ventricular diameter derived by M-mode echocardiography and the vertical axis during end-diastole (r = 0.79) and end-systole (r = 0.88) derived by two-dimensional echocardiography. Likewise, high correlations were noted between diameter and circumference in end-diastole (r = 0.89) and end-systole (r = 0.88). However, comparison of Vcf obtained by M-mode echocardiography with that obtained by two-dimensional echocardiography showed only fair correlation (r = 0.68). Moreover, the diameter/circumference ratio determined in end-diastole and end-systole differed significantly (p less than 0.001), possibly owing to the change in geometry of the ventricular sector image during systole. Although Vcf derived by M-mode echocardiography is a useful index of left ventricular performance, it does not truly reflect the circumference change during systole.