Metabolism of protein, amino acids, and glucose and their response to insulin in atria and cardiac myocytes of traumatized rats

Soft tissue injury to one hindlimb of rats was used to test the metabolic response of atrial and ventricular muscle to trauma. Effects of insulin on muscle metabolism were also studied. In myocytes and atria from normal animals, insulin increased protein synthesis and decreased protein degradation. For myocytes of rats at one and two days after trauma, this effect of insulin on proteolysis could not be detected. Over the next two days, the inhibitory effect returned to normal. Insulin also did not increase protein synthesis on day 1, but did thereafter. In atria, in contrast to heart cells, the inhibitory effect of insulin on proteolysis was enhanced at two and three days after trauma, and its stimulation of protein synthesis was unaltered. Insulin increased carbohydrate metabolism in both myocytes and atria of normal rats and traumatized rats after 2 days, and trauma did not alter this response. In myocytes, but not atria, trauma led to a faster oxidation of leucine and a significant rise in the production of alanine. Production of glutamine and glutamate was not affected in either tissue. These results show that the metabolic responses to trauma of atrial and ventricular muscle differ considerably.     

Range gated echo-Dopplervelocity and turbulence mapping in patients with valvular aortic stenosis

Flow beyond a stenotic aortic valve (AS) is dynamically complex. Numerous hydraulic studies have demonstrated that at least four well-known major flow areas occur distal to a stenotic valve. These include a jet, an area alongside the jet (the parajet), an area of flow disturbance, and an area in which disturbed flow again becomes laminar downstream. Of these, only the flow disturbance area has markedly turbulent flow, although some turbulence can be at times detected in the area beside the jet. The purpose of this investigation was to test a technique of patient examination that might allow a range-gated pulsed Doppler to detect each of these known areas in the aorta (Ao) of valvular AS patients. A method for mapping flow in the lumen of the Ao root and ascending Ao is detailed. The transverse Ao arch was studied in the standard manner. With this mapping method, 14 patients with AS were studied. We were able to identify the jet in 13 of 14 as a high velocity, narrow-width signal in the Ao root. The parajet area was characterized by no detectable or low flow in 12 of 14, but two patients had late systolic flow disturbance in the parajet area. All patients ahd a strong flow disturbance detected; 3 of 14 were first detected in the Ao root and the remainder were first detected higher in the ascending Ao. The area of relaminarization was not addressed in this study. This investigation demonstrates that a proper interpretation of range-gated pulsed Doppler recordings from areas distal to AS requires knowledge of flow dynamics beyond an obstruction and a methodical range-gated pulsed Doppler examination technique.     

Range gated Doppler ultrasound detection of contrast echographic microbubbles for cardiac and great vessel blood flow patterns

Ultrasonic contrast techniques allow tracking of blood flow in patients with cardiac malformations. One problem often encountered in M-mode contrast is inability to generate adequate microbubbles for recording. Theoretically, echo Doppler should be more sensitive for detection of microbubbles. To test this hypothesis, results of 75 saline injections were studied at catheterization in 16 patients by simultaneously recording contrast M-mode and echo Doppler studies. For this part of the investigation, an ATL 500 system was utilized. The M-mode of this system was found to provide identical information to that of a SmithKline. Records were evaluated without identification of the patient. In all instances (n = 20) in which microbubbles were not expected on the basis of flow pattems, none were detected by Doppler. One error occurred for M-mode. Contrast in the direction of flow was visualized in 50 of 55 injections by echo Doppler. In these, a frequency dispersion was present, but even more striking was a marked rise in the time interval histographic input signal strength indicator. Only 40 of 55 simultaneous M-mode echoes showed a contrast effect (p < 0.05). Doppler microbubble detection was usually represented by a much stronger signal than was M-mode contrast. This investigation demonstrates that range gated Doppler is an effective method for microbubble detection.     

Use and limitations of time interval histogram output from echo Doppler to detect mitral regurgitation

The specific objective of this investigation was to assess the reliabllity of time interval histographic (TIH) analysis of the output of the range gated pulsed Doppler for separating children with a variety of causes of mitral regurgitation (MR) from an additional group of 49 children who had various other forms of acyanotic heart disease. Investigators in this study were unaware of all diagnoses. Echo Doppler records were analyzed at a time unrelated to performance of the study to further isolate interpretation from any memory of the examination. The criterion for recognition of MR was a 1 cm or greater systolic TIH frequency dispersion in the left atrium as imaged by precordial and suprasternal M-mode Doppler techniques. No control patients had evidence of MR and 11 of 17 with MR were detected by at least one observer. All those with rheumatic MR were detected by both observers. Two of four patients with mitral valve prolapse were detected by only one observer. Four of six endocardial cushion defect patients with MR through a cleft in the anterior mitral leaflet demonstrated at catheterization were not detected by the echo Doppler. These data indicate that TIH of range gated pulsed Doppler has general clinical utility for detecting MR. However, in the presence of a cleft mitral leaflet, false negative diagnosis was frequent under the conditions of study. Further, MR due to mitral valve prolapse is more difficult to detect than MR due to rheumatic heart disease. The principal difficulties of insensitivity in MR appear related to decreased Doppler maximum velocity sensing with increased distance from the transducer, effect of regurgitant jet length displacing the flow disturbance, and the MR produced by different types of mitral lesions have different directions, magnitudes, and characteristics.     

Response to trauma of protein, amino acid, and carbohydrate metabolism in injured and uninjured rat skeletal muscles

Soft tissue injury to one hindlimb produced trauma in rats without affecting their food intake or weight gain. Histologic examination showed damage to the soleus and gastrocnemius muscles but not to the extensor digitorum longus muscle. The protein content of the injured soleus muscle was lower than that of the contralateral soleus at one day after injury, and was reflected in vitro by a faster rate of protein degradation. The injured soleus also showed greater rates of protein synthesis, glucose uptake, glycolysis, oxidation of glucose, pyruvate, and leucine, and de novo synthesis of alanine. During three days after the injury, urinary nitrogen excretion increased progressively and was paralleled by a faster rate of protein degradation in uninjured muscles incubated with glucose, insulin, and amino acids. In these muscles, the inhibition of protein degradation by insulin diminished, while its stimulation of protein synthesis was unaffected. This insensitivity of proteolysis to insulin in trauma can explain the increased rate of this process. The oxidation of glucose and pyruvate were lower in the diaphragms of traumatized than of normal rats incubated with leucine, while glycolysis and uptake of 2-deoxyglucose did not differ. The degradation of leucine and isoleucine was greater in the diaphragms of traumatized animals and was associated with a faster de novo synthesis of alanine. For the uninjured soleus muscles of the traumatized rats, the slower rates of oxidation of glucose, glycolysis, and uptake of 2-deoxyglucose in the presence of insulin showed an insensitivity of glucose metabolism to this hormone. In contrast, no differences were seen in these various metabolic processes between the extensor digitorum longus muscles of traumatized and normal rats. These data suggest that the response of skeletal muscles to trauma may depend on their physiologic and biochemical characteristics.     

Accuracy of two-dimensional echocardiography in the detection of aneurysms of the ventricular septum

Eight children with angiographically proven aneurysm of the membranous ventricular septum (AVS) assoclated with ventricular septal defect were studied by real-time cross-sectional echocardiography. A curvilinear, sickle (dome-shaped), or irregular echo arising from the interventricular septum and bulging toward the right ventricle in systole was visualized in all patients. This finding was detected in 7 of 8 long axis views, 5 of 8 short axis views, 5 of 7 apex four-chamber views, and 4 of 7 subcostal four-chamber views. In addition, real-time cross-sectional echocardiographic studies were performed in 40 patients with angiographically proven membranous ventricular septal defect without AVS; in only one patient was the abnormal echo suggesting aneurysm of the ventricular septum detected in the long axis and apex four-chamber views. Our echo study suggests that two-dimensional echocardiography has acceptable specificity for the diagnosis of AVS.     

In vitro verification of Doppler prediction of transvalve pressure gradient and orifice area in stenosis

This study was designed to analyze the validity of application of the modified Bernoulli equation (pressure gradient = 4.0 X velocity2) for estimating the pressure drop and valve orifice area from the jet velocity measured by Doppler ultrasound. We used an in vitro model which permitted interchangeable orifices, accurate measurement of the valve area and pressure drop across the valve. An in-line Doppler ultrasound transducer measured jet velocity (VEL D) at various water flow rates at an incident angle of 180 degrees beyond the various tested orifices. Jet velocity was also determined independently by application of a modified Bernoulli equation using the experimentally measured pressure drop (VEL P) and by a standard continuity equation (VEL Q). VEL P correlated very closely with VEL D (r = 0.981, standard error of the estimate [SEE] = 17.0 and slope of the regression = 0.988). VEL Q, corrected for vena contracta effects, correlated with VEL P (r = 0.986, SEE = 21.6), but had a slope of 0.673. To experimentally determine the exponent of velocity in the Bernoulli equation, we plotted pressure drop against VEL D and found a value of 2.11; theory predicts 2.0. Experimental coefficient of velocity was 3.36 torr/m (standard deviation = 0.52), whereas theory predicts 3.75 for water. Orifice area, calculated using VEL D and the continuity equation, was consistently overestimated by 3 to 12% for flows that produced laminar jets. The pressure gradient and orifice areas calculated from Doppler-derived data accurately predict actual pressure gradients and orifice areas.     

Two-dimensional echocardiography for evaluation of metastatic cardiac tumors in pediatric patients

We have studied five patients with metastatic cancer in whom two-dimensional echocardiography (2DE) demonstrated cardiac or pericardial involvement. Echo studies may guide the clinician in instituting and/or modifying cardiac and cancer therapy in such patients.     

Effect of quinidine on the heart rate and blood pressure response to treadmill exercise

The effect of quinidine on the heart rate and blood pressure response to treadmill exercise was evaluated in 17 normal subjects. Quinidine significantly increased the heart rate at rest and at low levels of exercise. Quinidine had no significant effect on the systolic blood pressure response to any work load. However, quinidine significantly decreased the systolic blood pressure at all exercising heart rates, compared to control, in 15 of the 17 subjects. The magnitude of the decrease in systolic pressure ranged from 1 to 22 mm Hg, with a mean of 10 mm Hg.     

Evaluation of pulmonary and systemic blood flow by 2-dimensional Doppler echocardiography using fast fourier transform spectral analysis

This study was designed to assess the accuracy and problems of noninvasively measuring right and left cardiac output by range-gated pulsed Doppler echocardiography. Sixteen children with cardiac disease, aged 3 months to 17 years, served as the subjects; 2-dimensional range-gated pulsed Doppler echocardiographic data were unobtainable in 2 children, leaving 14 for study. Diagnoses included shunt lesions, valvular abnormalities, coarctation, repaired defects, and Kawasaki's disease. The equipment for this study included a 2-dimensional echocardiographic Doppler sample volume locator. The Doppler frequency shift was analyzed by fast Fourier transform. Twenty 2-dimensional range-gated pulsed Doppler echocardiographic measurements (10 pulmonary and 10 aortic) were made simultaneously with indicator dilution outputs or angiographic outputs. In 4 subjects, 2-dimensional range-gated pulsed Doppler echocardiographic aortic outputs were not possible. For this study, vessel diameter was determined by both echocardiography and angiography, Doppler intercept angle by 2-dimensional echocardiography, and velocity by 2-dimensional range-gated pulsed Doppler echocardiography. Comparison of cardiac output measurements obtained by invasive methods and by 2-dimensional range-gated pulsed Doppler echocardiography (angiographic vessel measurement) showed a correlation of +0.94 (standard error of the estimate [SEE] = 0.53) with a slope of y = 0.83 × + 0.61, indicating that the slope and line of identity were almost equal and the offset from 0 was small. For 2-dimensional range-gated pulsed Doppler echocardiography (echocardiographic vessel measurement), the correlation was +0.94 for aortic flow but only +0.72 for pulmonary flow. Problems encountered in some patients included turbulence, which made velocity measurements unreliable, difficulty in obtaining aortic flow by Doppler echocardiography due to transducer configuration, and measurement of pulmonary diameter by echocardiography. The results indicate that 2-dimensional range-gated pulsed Doppler echocardiographic outputs are accurate under conditions of nonturbulent or minimally turbulent flow and adequate imaging, but only when vessel diameter can be accurately measured.     

Prenatal ultrasound diagnosis of hypoplastic left heart syndrome in utero associated with hydrops fetalis

Ultrasound is widely used in obstetrics as a screening technique for fetal size and maturity, placental structure and function, and for detection of fetal congenital malformations in complicated pregnancies.^1–3 Our own work on qualitative and quantitative fetal echocardiography^4,5 and the work of others⁶ has suggested that high resolution ultrasound can be used to assess fetal heart rhythm and function, and can detect congenital heart malformations before birth. In this report, we delineate prenatal diagnosis of hypoplastic left heart syndrome in a fetus with signs of hydrops fetalis, who was found after cesarean section to have associated trisomy 13. Additionally, we diagnosed the ususual occurrence of an intraventricular thrombus within the hypoplastic left ventricular cavity. The fetal ultrasound evaluation was of major importance in the perinatal management of both mother and unborn child.     

Two-dimensional echocardiographic study of right ventricular outflow and great artery anatomy in pulmonary atresia with ventricular septal defects and in truncus arteriosus

In this study, we reviewed M-mode and two-dimensional (2DE) echocardiographic observations in 13 patients with pulmonary atresia with ventricular septal defect and in six patients with truncus arteriosus in order to attempt to identify echocardiographic features distinguishing these two abnormalities in which no anatomic connection exists between the right ventricle and the pulmonary artery. M-mode features compatible with the diagnosis of pulmonary atresia with a ventricular septal defect (VSD) were a small but identifiable space anterior to the aorta and/or immobile pulmonic valve echoes appearing to open during diastole rather than systole. By 2DE, the proximal and distal segments of the right ventricular outflow tract could be imaged and the length of the atretic segment estimated. In truncus arteriosus, no outflow tract of the right ventricle could be identified by 2DE or M-mode echocardiography, and the origin of the pulmonary artery from the truncus could be imaged directly in four patients with type I and in one patient with type II truncus. Abnormalities of the truncal valve were also present and were imaged by 2DE in three of our five patients. Our study identified specific echocardiographic criteria for diagnosing truncus arteriosus and pulmonary atresia with VSD and for differentiation between them.     

Two-dimensional echocardiographic evaluation of dilated cardiomyopathy in children

This study examines and quantitates left ventricular (LV) short-axis 2-dimensional (2-D) echocardiograms of 16 normal control subjects and 19 patients who presented with clinical features suggestive of myocarditis leading to severe myocardiopathy. Of the 19 patients, 8 died or had cardiac transplantation: 9 were studied in the chronic phase and 10 in the acute phase. The endocardial surface of the LV short-axis image was digitized at chordal level at end-diastole and end-systole. Digitized traces in systole and diastole were superimposed. The cavity area of systole and diastole was determined and expressed as the percent systolic area reduction ratio. In the control subjects, the left ventricles were round in systole and diastole, contracted concentrically, and had a mean percent systolic area reduction of 53% (range 43 to 67). The left ventricle was not round in systole in the patients with myocarditis, and in 15, only the ventricular septum contracted significantly. Three patients had nonconcentric contraction, and regional contraction was more difficult to judge. The systolic area reduction ratio for the patients was 11 % (range 1 to 33), with no overlap with control subjects (p <0.001). Our results suggest that myocarditis more severely affects the LV free wall than the septum. In chronic patients, LV contraction remained markedly impaired. Quantitative evaluation of short-axis 2-D echocardiograms is a useful and sensitive technique for assessing damage due to presumed myocarditis.     

Role of M mode echocardiography in congenital aortic stenosis

M mode ultrasonic recognition of a bicuspid aortic valve or congenttally stenotic aortic valve rests on detection of the following criteria: eccentricity index, increased leaflet thickness, multiple diastolic cusp lines and presence of a central systolic line. In this investigation, M mode ultrasonic tracings from 118 children were interpreted by evaluators who did not know the diagnosis. Twenty-eight records from children with aortic valve stenosis (25 with a bicuspid valve and 3 with a tricuspid valve), were intermixed with records of 90 children with a catheterization-proved normal aortic valve to determine how many criteria were present in each tracing. Additionally, tracings were reviewed for overall visual appearance of the criteria, without measurement, to attempt to identtty those with an abnormal aortic valve. Finally, all echoes were viewed simultaneously and ranked from the most normal in appearance to the most abnormal aortic valve image. Rankings were then compared with measured pressure gradients across the aortic valve.

An eccentricity index value greater than 1.5, thought to be indicative of a bicuspid aortic valve, was found in 29 percent of patients with aortic stenosis and 20 percent of normal children. Mean eccentricity index values for the two groups were statistically similar. Increased leaflet thickness was not detected in any tracing. Multiple diastolic cusp lines were present in 64 percent of patients with aortic stenosis and 60 percent of normal children. None of these criteria were sensitive or selective for dlagnosing aortic stenosis from an M mode tracing of a given patiënt. On the basis of subjective visual appearance, 39 percent of tracings of patients with aortic stenosis were identified correctly. No useful correlation existed between the ranking an M mode tracing received for degree of valve normality or abnormality and the aortic pressure gradient. This investigation shows that M mode echocardiography of the aortic valve, despite prior recommendations to the contrary, has limited usefulness in diagnosing congenital aortic stenosis.     

Doppler echocardiographic prediction of pulmonary arterial hypertension in congenital heart disease

This study determines the accuracy of Doppler echocardiography (echo) for predicting the presence of pulmonary artery (PA) hypertension from Doppler PA velocity traces. The patient group included 17 patients with congenital cardiac disease who had undergone catheterization. The control group was composed of 15 normal subjects. Doppler traces were analyzed qualitatively and quantitatively. Qualitative assessment included evaluation for a negative presystolic velocity that was the equivalent of the pulmonary a wave detected by M-mode echo. Quantitative assessment included measurement of the following time intervals and ratio of intervals: preejection period (PEP), time to peak velocity (TPV), right ventricular ejection time (RVET), PEP/RVET and TPV/RVET ratios. In the patient group, systolic PA pressure ranged from 22 to 90 mm Hg (mean 50 +/- 23), and mean PA pressure ranged from 12 to 60 mm Hg (mean 32 +/- 17). Five patients had systolic PA pressures of less than or equal to 30 mm Hg and 12 had systolic PA pressures greater than 30 mm Hg. Of 15 control subjects, 14 had a negative presystolic a wave. Of 5 patients with PA pressure less than or equal to 30 mm Hg, 4 had a presystolic negative velocity, and all with higher pressures had no presystolic negative velocity. One patient with pressure less than 30 mm Hg and 2 with PA pressure greater than 30 mm Hg had indeterminate status of presystolic velocity pattern because of turbulence or baseline blanking. The best quantitative indexes for separating patients with normal PA pressure from those with elevated PA pressure were TPV and TPV/RVET, which respectively correlated negatively with systolic PA pressure (r = -0.82, standard error of the estimate [SEE] = 0.02; and r = -0.70, SEE = 0.05). These measurements also correlated negatively with mean PA pressure (r = -0.75, SEE = 0.02; and r = -0.76, SEE = 0.05). Other intervals and ratios had enough individual variability to make them less useful as predictors of PA hypertension.     

Comparison of a QRS scoring system for estimating acute infarct size with radionuclide left ventriculography

A QRS scoring system was compared with left ventricular ejection fraction (LVEF) in 40 patients enrolled in the Multicenter Post Infarction Program. A poor correlation was found between these two parameters. Possible reasons for these findings include the fact that the radionuclide studies were performed at several institutions or that there was a mean interval of 6 days between the time of the ECG and the radionuclide studies. It was determined that the ECGs could be scored by inexperienced scorers. The utility and limitation of the QRS scoring system for prediction of LVEF need further evaluation, particularly if it is to be applied to a multicenter study.     

Mechanisms of hemodynamic actions of furosemide: Differentiation of vascular and renal effects on blood pressure in functionally anephric hypertensive patients

To differentiate diuretic and direct cardiocirculatory properties of furosemide for elucidation of the vasodepressor mechanisms of action of the agent in the acute treatment of hypertension, the peripheral vascular effects of intravenous furosemide (3 mg/kg) on supine blood pressure (BP) and forearm hemodynamics in 11 functionally anephric hypertensive patients (creatinine clearance < 2 ml/min) were studied. BP was recorded by sphygmomanometer and forearm hemodynamics were measured by strain gauge plethysmography. While diastolic BP decreased only 2.7 mm Hg at 30 minutes, forearm blood flow increased 55% (p < 0.01) mediated by decreased peripheral vascular resistance of 30% (p < 0.01) at 15 minutes which dissipated by 30 minutes. Systolic BP, indices of venous capacity, weight, hematocrit, serum electrolytes, and plasma renin activity were unchanged. No diuresis occurred. It is concluded that the early hypotensive effect of furosemide depends upon diuresis.