Donald O. Nutter

Cardiac abnormalities in cachectic patients before and during nutritional repletion

Abstract The effect of PCU and HA on heart dimensions and function was examined with non-invasive methods in 10 patients with severe undernutrition of diverse etiology. Control subjects were 10 normal men and women matched to their cachectic counterparts by height and sex. The study was conducted in two phases. In phase A, baseline studies of heart dimensions and function were completed. Phase B consisted of cardiovascular and metabolic monitoring during 4 to 6 weeks of enteral or parenteral HA. Phase A was characterized by a reduced radiographic total heart volume, echo EdV, LV mass, and CO. These reductions, however, were only one half to one eighth as great as the losses in BW. The patients therefore entered HA with an elevated LV mass index and cardiac index. Ejection phase indices of LV function (EF and Vcf) were normal or enhanced. Phase B studies in five subjects showed that decreased cardiac size and output were correctible by HA, but at differing rates. Ventricular volume and CO corrected more rapidly than LV mass under the conditions of rapid repletion where the daily sodium intake was 2 to 4 grams, and values for cardiac index reached 250 per cent of normal. Resting metabolic rate also increased during phase B. The combination of an elevated output, excessive sodium retention, and increased metabolic rate while LV mass was still reduced appeared to be responsible for cardiac decompensation in two of five repleted patients. To prevent cardiac decompensation during the HA of undernourished subjects, we propose the use of low salt regimens, a slower rate of HA and serial monitoring of cardiac dimensions and function by clinical examination and echo.

In Vivo Analysis of Adrenergic Receptor Activity of Dobutamine

Studies were performed in anesthetized dogs to evaluate the cardiac and systemic effects of intravenously administered dobutamine and to determine its direct effects on the renal and femoral vascular beds. The results demonstrated that dobutamine possessed an inotropic efficacy similar to that of isoproterenol and norepinephrine; its chronotropic effect was similar to or greater than that of norepinephrine. In contrast to norepinephrine, dobutamine increased cardiac output and reduced total peripheral resistance with minimal effects on mean aortic pressure. Studies on the denervated hind limb demonstrated that dobutamine stimulated both alpha and beta receptors. The dose of dobutamine which produced a 50% increase in femoral blood flow was 180 times the required dose of isoproterenol and the dose which produced a 50% increase in contractile force was 43 times the required dose of isoproterenol. Studies on the renal vasculature demonstrated that dobutamine caused no dopamine-like renal vasodilator activity and only minor vasodilation mediated by beta receptors. We concluded that dobutamine is more cardioselective than is isoproterenol. The dobutamine-induced decrease in peripheral resistance observed in the whole dog was presumably due to increased myocardial contractility coupled with a greater net effect of beta-adrenergic vasodilation than alpha-adrenergic vasoconstriction. Studies with reserpine-treated dogs showed that all dobutamine-induced effects were due to a direct action on receptors.

Echocardiographic study of cardiac dimensions and function in the endurance-trained athlete

Adaptive cardiac responses to isotonic training were studied with echocardiographic measurement of cardiac dimensions and function in 20 endurance runners whose maximal aerobic capacity on the treadmill was 4.88 +/- 0.13 (mean standard error of mean) liters of oxygen/min. They were compared with 26 young sedentary control subjects whose capacity was 3.34 +/- 0.11 liters of oxygen/min (P less than 0.001). A modest degree of right and left ventricular chamber enlargement and left ventricular hypertrophy was observed in endurance runners (left ventricular mass index 140 +/- 6 g/m2 compared with 107 +/- 4 g/m2 in sedentary control subjects, (P less than 0.001). Resting heart rate was slower in endurance runners (51 +/- 2 versus 62 +/- 2 beats/min, P less than 0.001) and resting left ventricular function as evaluated with ejection fraction and maximal posterior wall shortening velocity and mean circumferential shortening velocity (VCF) was comparable or slightly depressed in endurance runners (0.98 +/- 0.03 versus 1.02 +/- 0.05 circumferences/sec [difference not significant]). This study suggests that isotonic training results in adaptive changes in ventricular volume and mass, slower heart rates that may be associated with more efficient pumping function (that is, increasing stroke volume) and insignificant alterations in resting ejection phase indexes of left ventricular function.

Reversible Severe Congestive Cardiomyopathy in Three Cases of Hypophosphatemia

Three patients presented with severe congestive cardiomyopathy of unknown cause. All three had a profound depression of serum phosphorus levels resulting from the chronic ingestion of large quantities of a phosphorus-binding antacid. Results of physical examination and echocardiograms were consistent with cardiomegaly and severe myocardial dysfunction, and chest films showed enlargement of the cardiac silhouette with interstitial pulmonary edema. Serum phosphorus was restored to normal levels, and within 2 to 5 weeks the results of physical examination and echocardiogram of each patient returned to normal. We conclude that these patients had reversible hypophosphatemic cardiomyopathy and show the importance of inorganic phosphorus in myocardial metabolism and function. Serum phosphorus measurements should be a part of the routine evaluation of patients with congestive cardiomyopathy because, at least in some patients, hypophosphatemia appears to be a reversible cause of this disorder.

Cardiac Features of an Unusual X-Linked Humeroperoneal Neuromuscular Disease

To characterize an unusual, sex-linked recessive neuromuscular disease, we studied two families with 37 males who had involvement of distal leg and proximal arm muscle groups. Electromyography and muscle biopsy in five subjects showed features of both neuropathy and myopathy. Bradycardia and syncope in 15 involved subjects were associated with early death (before the age of 50 years). Electrocardiograms in 15 others showed a spectrum of atrial abnormalities that ranged from abnormal P waves to permanent atrial paralysis and from first-degree atrioventricular block to complete heart block. No patient exhibited clinical muscle disease without electrocardiographic atrial disease. Dilated, hypertrophied left ventricles with normal indexes of function were found in three cases with permanent atrial paralysis and chronic junctional bradycardia. Cardiomegaly and cardiac failure were not present in the other cases. We conclude that permanent ventricular pacing (instituted four patients) is indicated in many of these patients to prevent serious sequelae.

Assessment of Left Ventricular Dimensions and Function by Echocardiography

Abstract Left ventricular dimensions and function indexes were measured in 40 patients with cardiac disease by both angiocardiographic and echocardiographic techniques. Good correlation was obtained between echocardiographic and angiographic values in 18 patients with technically excellent studies obtained by both techniques. The left ventricular echogram appears to be an effective technique for the noninvasive determination of left ventricular dimensions and volume. Echocardiographic indexes of ventricular function, including percent shortening of internal diameter, mean shortening velocity of internal diameter, ejection fraction, percent thickening of posterior wall and mean posterior wall velocity, distinguished between groups of patients with normal and abnormal left ventricular function. However, a single echocardiographic or angiographie measurement does not appear to provide selective data for the accurate functional classification of most individual patients.

Permanent paralysis of the atrium in a patient with facioscapulohumeral muscular dystrophy

Abstract A 32 year old man with the facioscapulohumeral (Landouzy-Dejerine) type of muscular dystrophy was evaluated because of a slow pulse rate. Hemodynamic studies were performed at rest and during ventricular pacing. The patients atria were found to be electrically and mechanically silent. This unusual disorder of permanent atrial paralysis (standstill) is reviewed. There seems to be more than a casual relation between permanent atrial paralysis and this form of muscular dystrophy.

Use of isometric handgrip for the indirect assessment of left ventricular function in patients with coronary atherosclerotic heart disease

Abstract The hemodynamic effects of maximal isometric handgrip exercise were determined in 6 normal subjects, 27 patients with coronary atherosclerotic heart disease and 6 patients with idiopathic congestive cardiomyopathy. The hemodynamic responses to isometric handgrip exercise and to dynamic treadmill exercise were compared in normal subjects and patients with atherosclerotic heart disease. In normal subjects, isometric handgrip did not alter heart sounds or precordial apex pulsations, but in patients with atherosclerotic heart disease it either accentuated or evoked atrial or ventricular gallop sounds in 59 and 44 percent, respectively. In patients with atherosclerotic heart disease and those with cardiomyopathy, apical diastolic pulsations markedly increased in amplitude during isometric handgrip. In both normal subjects and patients isometric exercise produced similar responses in systolic time intervals. Isometric handgrip evoked rapid and significant increases in systolic and diastolic blood pressure and heart rate in all normal subjects and patients. The product of systolic blood pressure and heart rate/100 (modified tension-time index) was used as an index of myocardial oxygen demand. Treadmill exercise increased mean modified tension-time index in normal subjects and in patients with atherosclerotic heart disease by 215 (+244 percent) and 147 units (+150 percent), respectively. Handgrip increased mean modified tensiontime index by 52 units in both normal subjects and patients with atherosclerotic heart disease patients (+60 and +49 percent, respectively) and by 38 units (+39 percent) in patients with cardiomyopathy. Isometric handgrip exercise is a simple cardiovascular stress test, applicable at the bedside for provoking abnormal physical signs associated with decreased left ventricular compliance or dysfunction in patients with atherosclerotic heart disease or cardiomyopathy.

Hypertrophic cardiomyopathy and human leukocyte antigen linkage: differentiation of two forms of hypertrophic cardiomyopathy.

To determine whether hypertrophic cardiomyopathy is associated with a human leukocyte antigen (HLA) phenotype, we tissue-typed 70 unrelated afflicted patients and 86 of their asymptomatic family members (from nine separate kindreds). Forty-five per cent of the white patients had B-12 antigen as compared to 23 per cent in matched control subjects; 69 per cent of black patients had a B-5-complex antigen as compared to 33 per cent in matched controls. Patients with a B-12 or B-5-complex antigen were nonhypertensive and had family members with the disease. Patients without these antigens were severely hypertensive and had no affected family members. Linkage analysis of six families revealed a lod score of 7.7 for asymmetric septal hypertrophy and the HLA region of chromosome 6. We conclude that there is a heritable, nonhypertensive form of hypertrophic cardiomyopathy linked to the HLA loci on chromosome 6 and that a sporadic form is associated with severe, systemic hypertension.

Anomalous origin of the right coronary artery from the pulmonary artery

Abstract Two patients with an anomalous right coronary artery arising from the pulmonary artery are presented. The first patient was asymptomatic and had a continuous murmur. The correct diagnosis was established by cardiac catheterization and selective angiography. There was a moderate sized shunt from the dilated left anterior descending coronary artery to the right coronary artery, which arose from the main pulmonary artery. The second patient was also asymptomatic but died several days after a sudden cardiorespiratory arrest. On postmortem examination she was demonstrated to have anomalous origin of the right coronary artery from the pulmonary artery. The left coronary artery was completely occluded at the orifice by a thrombus, and microscopic examination demonstrated evidence of both acute and chronic left ventricular ischemia and infarction. The pathophysiologic alterations and potential danger to patients with this anomaly are discussed.