George R. Noren

Mumps-Virus Infection in Pregnant Women and the Immunologic Response of Their Offspring

Abstract Twelve Eskimo children were evaluated 10 years after intrauterine exposure to mumps virus. The mothers of all 12 gave serologic evidence of having been exposed to mumps virus, as did nine older children born before the epidemic (these nine also had positive mumps skin tests). None of the 12 children conceived during the epidemic had mumps-virus neutralizing antibodies, and 10 of 12 had positive mumpsvirus skin tests. Of 32 children born after the epidemic 31 were negative for mumps-virus neutralizing antibody whereas six had a positive mumps skin test. Exposure of the embryo or fetus to mumps virus therefore seems to have evoked immunologic recognition that persisted into childhood. The immunologic response was primarily cellular and manifested by delayed hypersensitivity.

Anomalous Origin of the Left Coronary Artery from the Pulmonary Trunk with Special Reference to the Occurrence of Mitral Insufficiency

Nine cases of anomalous origin of the left coronary artery from the pulmonary trunk, involving patients ranging in age from 2 months to 7 years, have been reviewed. In six patients, mitral insufficiency was a prominent feature and, in three of these patients, mitral insufficiency presented the major problem, clinically.Of the five patients who died, necropsy was done in four. In each, healed infarction of the posterior papillary muscles of the left ventricle was demonstrated and, in two, the anterior papillary muscles were also involved.The clinical picture was that of an acyanotic patient with nonspecific respiratory complaints and retardation of growth. In five patients, there were symptoms (although a presenting complaint in only one) which are considered classic for this anomaly. These symptoms included episodes of pallor, dyspnea, and perspiration. Eight patients experienced cardiac failure in infancy and response to digitalis was effective in each.In this study, endocardial fibroelastosis, without associated cardiac malformations other than mitral insufficiency, presented difficulty in the differential diagnosis. The vectorcardiogram in the horizontal plane was most helpful in the diagnosis of anomalous origin of the left coronary from the pulmonary trunk. The QRS sÊ loop in the horizontal plane in this anomaly was oriented posteriorly to the left and its direction was clockwise, in contrast to the counterclockwise direction of the loop in endocardial fibroelastosis.Selective ascending aortography or selective right coronary arteriography established the diagnosis in seven cases.

The syndrome of idiopathic hypercalcemia of infancy with associated congenital heart disease

The relationship of idiopathic hyercalcemia of infancy with the syndrome of supravalvular aortic stenosis and/or peripheral pulmonary stenosis, mental retardation, and peculiar facies has been emphasized in the recent literature. There remains, however, a paucity of reported instances in which the hypercalcemia was documented. Two patients are described in whom the diagnosis in infancy was idiopathic hypercalcemia with associated congenital heart disease. Recent revaluation of the cardiac lesions demonstrated isolated supravalvular aortic stenosis in one case and isolated peripheral pulmonary artery stenoses in the other case. There was no maternal history of excessive vitamin intake during pregnancy in either case.

Postoperative Follow-Up of Patients with Ventricular Septal Defect

This study deals with 341 patients who underwent operative correction of ventricular septal defect at the University of Minnesota Hospitals from 1954 to 1960. Seventy-one patients (21%) died during operation or in the immediate postoperative period; another 30 patients (9%) died following discharge from the hospital and as late as 14 years after operation. One hundred-forty patients had postoperative cardiac catheterizations, 28 of whom were catheterized more than five years after operation. Postoperative hemodynamic data were compared with available preoperative data and show no significant change in total pulmonary resistance. Although the majority of our survivors are asymptomatic, we believe that periodic postoperative clinical and laboratory evaluation is important to the continued well-being of the patient.

Early alterations in the function of sarcoplasmic reticulum in a naturally occurring model of congestive cardiomyopathy

In a naturally occurring model of congestive cardiomyopathy-round heart disease of turkeys, Ca2+ transport of isolated cardiac sarcoplasmic reticulum was evaluated at 1, 10, 28, and 56 days of age. Ca2+ binding in round heart disease birds was reduced to between 55% and 75% of values measured in age-matched commercial control turkeys (P less than 0.05 to less than 0.01). Similarly, Ca2+ uptake in round heart disease birds was reduced to between 52% and 87% of values measured in age-matched commercial control turkeys (P less than 0.05 and less than 0.01). Ca2+-stimulated ATPase values were similar in 1-, 10-, and 28-day-old round heart disease and commercial control turkeys. However at 56 days of age, when all round heart disease birds showed moderate to marked left ventricular dilatation. Ca2+-stimulated ATPase was reduced to 75% of control values (P less than 0.05). Depression of Ca2+ binding and Ca2+ uptake preceded the appearance of cardiac dilatation and may contribute to the pathogenesis of round heart disease. Depression of Ca2+-stimulated ATPase, present only after cardiac dilatation developed, appears to be secondary to cardiac failure. Sarcoplasmic reticulum function in round heart disease birds immunosuppressed by cyclophosphamide treatment (40 mg . kg-1 . d-1 for the first 4 days of age) was evaluated at 10 days of age. This treatment increased Ca2+ binding by 73% (P less than 0.05), and Ca2+-uptake by 58% (P less than 0.01) over values measured in untreated round heart disease birds. Reversal of the altered Ca2+ transport in sarcoplasmic reticulum by early immunosuppression supports the hypothesis that the immune system plays an integral part in the development of the congestive cardiomyopathy of round heart disease.

Carnitine Alterations in Spontaneous and Drug- Induced Turkey Congestive Cardiomyopathy

ABSTRACT: Carnitine and acylcarnitines were measured in plasma and tissues of control turkeys, turkeys with an inbred spontaneous cardiomyopathy, and turkeys with furazolidone- induced cardiomyopathy. Heart failure was evident in both types of cardiomyopathy from decreased systemic blood pressure and cardiac dilatation compared to controls. Plasma free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine were significantly elevated by 76 to 614% (p < 0.01) in the two cardiomyopathy models compared to control. The highest carnitine levels were found in the most hypotensive turkeys. Liver free carnitine and short-chain acylcarnitine levels were also elevated by 45 to 537% (p < 0.05) in both types of cardiomyopathy. Free carnitine was elevated by 126% in left ventricle and by 54% in skeletal muscle of the furazolidone-treated turkeys (p < 0.05). We speculate that hepatic synthesis of carnitine may be increased in response to hypotension and progressive cardiac dysfunction in cardiomyopathic turkeys. Such an increase may be useful to promote β-oxidation of fatty acids as a cardiac energy source.

An Overview of Primary Endocardial Fibroelastosis and Chronic Viral Cardiomyopathy

Our original observations and speculations concerning primary endocardial fibroelastosis provoked understandable disbelief, and we summarize in this paper the efforts to solve a pathogenetic mystery. Although not so apparent at the outset, our researches represented experimental questions about the fundamental cause of an important, broad spectrum of chronic cardiomyopathic disease of man. Primary endocardial fibroelastosis is characterized by the proliferation of fibrous and elastic tissue beneath the left ventricular endocardium. Internally strictured by a jacket of thick connective tissue, the heart loses the resilient contractile force necessary to sustain sufficient cardiac output. Following the preliminary studies of Noren, Adams, and Anderson [1], we undertook extensive clinical and laboratory investigation of the proposed association of intrauterine mumps virus infection and endocardial fibroelastosis. In a substantial number of clinically documented and necropsy-verified cases of primary endocardial fibroelastosis, we found the almost uniform presence of delayed cutaneous hypersensitivity to mumps virus in the absence of circulating neutralizing antibody [2]. Clinically, these children were assessed by careful cardiovascular physical examination, routine thoracic radiography, electrocardiography, cardiac catheterization and angiography, and, when indicated, skeletal muscle biopsy. We attempted to isolate the diagnosis of a chronic cardiomyopathy, which may be a more suitable pathophysiologic label for primary endocardial fibroelastosis, from the

Arachidonic acid metabolism in thrombocytes and vascular tissues of turkeys.

Turkeys are hypertensive compared to mammals of similar size. In vitro synthesis of thrombocyte thromboxane B2 (TxB2), 12L-hydroxy-5,8,10 heptadecatrienoic acid (HHT), 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) and aortic prostaglandin (PG) production was studied in one to ten month old domestic white turkeys. Compared to normal human platelets, TxB2 production was increased (55.4 vs. 31.4%) and HETE production was markedly reduced (6.5 vs. 34.6%) in control thrombocytes. Similar to human platelets in which cyclooxygenase inhibition with aspirin results in an increase in HETE production, block of the thrombocyte enzyme with aspirin doubled the production of HETE. In vitro conversion of radiolabeled arachidonic acid (AA) showed that the primary PG produced by turkey aorta was PGE2. A 6-keto immunoreactive PG was present which comigrated with authentic 6-keto PGF1 alpha, but failure of the aortic supernatant to inhibit adenosine diphosphate or AA induced platelet aggregation suggested that PGI2 was not produced. The vasodepressor potency of PGE1, PGE2 and PGI2 was altered in awake turkeys with PGE1 and PGE2 having five times the hypotensive effect as PGI2. In addition, conversion of AA to PGE2 by aorta in one month turkeys was greater (17.3 vs. 9.2%) than in ten month old turkeys. Systemic arterial pressure was increased in the ten month old turkeys (188 mmHg) compared to one month old turkeys (143 mmHg). Thus, both vascular AA metabolism and the vasodepressor potencies of PGE2 and PGI2 are altered and the activity of the lipoxygenase pathway in thrombocytes is limited in the turkey.

299 MYOCARDIAL ENERGY IMBALANCE IN NEWBORN CARDIO MYOPATHIC TURKEYS

Turkeys (TK) inbred for congestive cardiomyopathy(CCM) have reduced hatchability and a mortality approaching 30% by 10 days of age; cardiac dilation begins at this time. We examined the possibility that an imbalance in cardiac high energy phosphate (HEP) compounds may contribute to these abnormalities. Ventricular ATP, ADP, AMP and CP were compared in control(Con) and CCM TK, 1-31 days old. There was no significant age-related difference in myocardial HEP compounds or in the energy charge [EC=(ATP+ 0.5 ADP)/(ATP+ADP+AMP)] in Con TK (Table). In contrast, ATP and EC in CCM hearts at 1-2 days were reduced compared to 19-31 day TK, and ATP content in CCM hearts at 1-2 days was lower compared to age-matched Con tissue. When cardiac dilation was present in CCM TK (ie 10-31 days), ATP and EC were similar in Con and CCM hearts. CP content in Con and CCM TK hearts was similar at all ages indicating adequate energy formation.These results suggest that energy imbalance in hearts of newborn CCM TK may, in part, contribute to the reduced hatchability or high early mortality; dilation of myopathic hearts is not associated with HEP imbalance.

Catecholamines in turkeys with inbred cardiomyopathy

Abstract Patients with heart failure often have increased adrenergic nervous system activity. However, since the role of catecholamines in the development of inherited dilated cardiomyopathy is not totally clear, this study was designed to examine catecholamines in turkeys with inbred dilated cardiomyopathy (DCM). Plasma and tissue (heart, aorta, and kidney) catecholamines were measured in DCM and normal turkeys at ages 1, 10, 30, and 60 days, with echocardiograms and intra-arterial pressure obtained at 60 days. DCM turkeys weighed less than controls at all ages. At 60 days, cardiac dysfunction was evident by hypotension, cardiac dilatation, and decreased shortening fraction. Unlike other models of heart failure, cardiac norepinephrine was not depleted in DCM birds, and in fact was higher than controls at ages 10 and 30 days. Kidney norepinephrine was also equal to or greater than control birds, and both cardiac and kidney dopamine were present in normally low concentrations. In 60 day old DCM birds, reduced shortening fraction correlated with lower mean arterial pressure ( r = 0.77, P