Mechanisms of differential growth of heart ventricles in newborn pigs.

The left ventricular free wall (LVFW) grew approximately three times faster than the right ventricular free wall (RVFW) during the first 10 days of life in neonatal pigs. Faster growth was associated with proportional increases in total RNA and messenger RNA. These findings indicated that greater capacity for protein synthesis was a major factor in accelerated growth. Despite faster growth, heart content of ribosomal subunits was higher in piglets than in 60-day-old pigs or adult rats, suggesting a relatively slower rate of peptide chain initiation than elongation. When hearts from 5-day-old pigs were perfused in vitro, protein synthesis was more rapid in the LVFW than in the RVFW. In the absence of added insulin, the higher rate was due to both greater efficiency and greater capacity for protein synthesis. In the presence of the hormone, greater capacity was responsible for the increased rate of protein synthesis in the LVFW as compared with the RVFW.

Atrial automatic ectopic tachycardia due to an atrial tumor.

A dilated cardiomyopathy picture has been produced by rapid atrial and ventricular rates sustained for a long period of time in some patients. The ventricular tachycardias have in some instances been associated with ventricular tumors as the cause of the tachycardia. Once the tumor is removed, the tachycardia stops and the heart function improves. Atrial ectopic tachycardias also produce a similar picture, but have not been associated with atrial tumors. Such a case is presented with an atrial rhabdomyoma producing atrial ectopic tachycardia and a dilated, poorly contracting myocardium. The tumor was resected and the tachycardia was immediately abolished. Cardiac function quickly returned to normal.

Acute myocardial effects of chloramphenicol in newborn pigs: a possible insight into the gray baby syndrome.

Mechanical function and mitochondrial respiration were observed in newborn pig hearts in the presence of chloramphenicol. Isolated perfused hearts exposed to chloramphenicol (25, 50, or 100 micrograms/ml) demonstrated acute reductions in pressure development and cardiac output accompanied by elevated left atrial filling pressure. The effects of chloramphenicol and chloramphenicol succinate (25, 50, 100, or 200 micrograms/ml) on oxidative activity of isolated mitochondria were also investigated. With unesterified chloramphenicol, inhibition of state 3 respiration was most apparent when glutamate and palmitylcarnitine were supplied as substrates. Inhibition of mitochondrial oxidation of succinate or glutamate was only detectable at 200 micrograms/ml. Inhibition of alpha-ketoglutarate oxidation was not seen at any concentration of antibiotic studied. Chloramphenicol succinate most strongly inhibited state 3 oxidation of succinate and alpha-ketoglutarate and had relatively mild effects on oxidation of glutamate and palmitylcarnitine. Succinate oxidation by submitochondrial particles was unaffected by chloramphenicol succinate, a result suggesting interference with succinate transport.

Ductus arteriosus aneurysm presenting as pulmonary artery obstruction: diagnosis and management.

The occurrence of pulmonary artery obstruction in an 8 day old infant as a complication of an aneurysm of a nonpatent ductus arteriosus is reported, together with the echocardiographic and angiographic findings. To relieve the obstruction, the aneurysm and an intrapulmonary thrombus were successfully removed with the use of cardiopulmonary bypass when the infant was 3 months old.

Aerobic capacity, obesity, and atherosclerotic risk factors in male adolescents.

Correlations between aerobic capacity, obesity, and atherosclerotic risk factors were evaluated in adolescents with low-to-moderate levels of physical fitness. Subjects with higher levels of fitness had a more favorable risk profile with decreased body mass index, lower systolic and diastolic blood pressure and plasma triglyceride levels, and higher plasma high-density lipoprotein-cholesterol levels. Simple linear regression analysis revealed an association between body mass index and blood pressure, plasma triglyceride and plasma high-density lipoprotein-cholesterol. The level of aerobic fitness as determined by exercise duration was also associated with the same atherosclerotic risk factors. However, multiple linear regression analysis demonstrated that body mass index provided the largest explanation, by those variables examined, of the interindividual variance in blood pressure, plasma triglyceride, and high-density lipoprotein-cholesterol. Aerobic fitness contributed only minimally to the variation in these risk factors. These findings suggest that if aerobic conditioning is used to modify atherosclerotic risk factors, it should be accompanied by a reduction in weight in adolescents with low-to-moderate levels of physical fitness.

Should elective repair of coarctation of the aorta be done in infancy?

Our experience with the subclavian flap repair for coarctation of the aorta over the past 10 years includes 53 patients under 1 year of age. Of this group, 35 were newborn infants. All but two had an associated patent ductus arteriosus and 23 (66%) had associated intracardiac anomalies. All neonates had severe congestive heart failure and operation was carried out promptly after they were stabilized with diuretics and inotropic agents. Prostaglandin infusions have been essential to the care of many of these patients. Operative mortality was two of 53 patients (4%). No patient more than 4 days old operation has died, and concomitant pulmonary artery banding was performed in five infants with no deaths. Running nonabsorbable suture was used in 21 patients, interrupted nonabsorbable suture in 23, and continuous monofilament absorbable suture in the last nine. Mean follow-up time has been 46 months. Invasive follow-up studies, performed in 11 patients, have revealed residual systolic gradients of 5, 15, and 20 mm Hg in three and 0 mm Hg in one in whom continuous suture technique was used. The other seven had interrupted suture technique, and no gradient was present. Initial follow-up information for the group with absorbable suture repair suggests no residual gradients. No patient had significant upper extremity or hand morbidity. Eight patients had normal blood pressure and normal arm-to-leg gradients after exercise. When absorbable vascular suture is unavailable, an interrupted suture technique is superior to a continuous running repair. In view of the low operative mortality, the excellent growth of the repaired area, yet the likelihood of late development of cardiovascular disease (especially hypertension) if the repair is effected in childhood or adolescence, we favor prompt subclavian flap repair of coarctation of the aorta in all infants with or without symptoms. Concomitant pulmonary artery banding is seldom indicated.

Pulsed Doppler and two-dimensional echocardiographic findings in aortico-left ventricular tunnel.

Two-dimensional echocardiography was used to make the anatomic diagnosis of aortico-left ventricular tunnel in a 1 day old infant. Pulsed Doppler echocardiography allowed directional flow to be determined within the tunnel. The findings were confirmed by cardiac catheterization and by direct visualization at the time of surgical repair. Aortic valve insufficiency was excluded before and after surgery using pulsed Doppler echocardiography. The anatomy and physiology of aortico-left ventricular tunnel can thus be documented using noninvasive techniques.

Evaluation of the pediatric surgical patient with congenital heart disease.

Children with cardiac disease who undergo noncardiac surgical procedures may encounter risks beyond those usually associated with surgical procedures. In this article, several complicating factors seen in children with heart disease are discussed, including arrhythmias, cyanosis, congestive heart failure, pulmonary hypertension, and subacute bacterial endocarditis.

Coarctation in Taussig-Bing malformation of the heart. Surgical significance.

In a review of 126 heart specimens of simple complete transposition of the great arteries with ventricular septal defect (VSD), coarctation was noted in eight (6%). In 105 Taussig-Bing heart specimens, coarctation and/or aortic outflow tract obstruction was noted in 56 (53%) (p less than 10(-10). This was similar to our surgical experience in 26 patients with transposition and VSD or Taussig-Bing heart. Six of nine patients with Taussig-Bing heart also had coarctation of the aorta, whereas all 17 patients with transposition and VSD had a normal aorta. Four patients with Taussig-Bing heart underwent coarctation repair and pulmonary artery banding at 2 to 7 days of age. The remaining two patients with Taussig-Bing heart did not have a hemodynamically significant coarctation. Five of the six patients with Taussig-Bing heart and coarctation underwent a Senning procedure between the ages of 7 weeks and 3 1/2 years. In four (all less than 4 months of age) the VSD could not be closed through the tricuspid valve. A right ventriculotomy was done in two and contributed to their deaths. In the other two patients the VSD was left alone and the pulmonary artery banded. Both remain well. The fifth child, aged 3 1/2 years, had the VSD closed through the tricuspid valve but died in the postoperative period of renal failure. The sixth patient is awaiting further operation following coarctation repair and pulmonary artery banding. We conclude that the presence of coarctation strongly suggests that Taussig-Bing heart malformation exists rather than transposition and VSD. Pulmonary artery banding and coarctation repair are the initial procedures of choice in the management of these critically ill newborn infants. Increasing cyanosis and failure to thrive will necessitate further operation. Closure of the VSD through the tricuspid valve in these infants is difficult. Pulmonary artery banding in association with a Senning procedure is preferable to a right ventriculotomy. Closure of the VSD is then planned at a later stage.

Fatty acid and glucose utilization in isolated, working fetal pig hearts.

Fatty acid uptake and the effects of long- and short-chain fatty acids on glucose utilization were assessed in isolated perfused fetal pig hearts (0.9 gestation) in which oxygenated nutrient buffer was pumped from both ventricles at controlled pressure (55 mmHg, mean arterial pressure) and heart rate (180 beats/min). When either 1.5 mM palmitate or 1.0 mM octanoate was added to buffer containing 10 mM glucose and insulin (100 microU/ml), glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed when compared with glucose uptake in the absence of fatty acid. Increased tissue concentrations of glucose 6-phosphate, fructose 6-phosphate, and citrate in hearts perfused with buffer containing octanoate indicated active beta-oxidation and inhibition of phosphofructokinase activity when compared with hearts perfused with glucose alone. In contrast, hearts perfused with buffer containing palmitate showed no increases in these metabolic intermediates. These results suggest that suppression of glucose uptake in the presence of long-chain fatty acid was not the result of phosphofructokinase inhibition but may result from inhibition of glucose transport by palmitate. Determinations of tissue concentrations of free carnitine and carnitine derivatives indicated that, although palmitate underwent esterification to long-chain acyl carnitine in the fetal heart, it failed to undergo extensive beta-oxidation.

Blood pressure response to exercise in children following the subclavian flap procedure for coarctation of the aorta.

Eight patients who underwent repair of coarctation of the aorta as infants (mean age 4.6 months) by the subclavian flap procedure were evaluated by dynamic exercise. Their mean age at the time of exercise testing was 4.6 years. Resting upper to lower limb systolic blood pressure gradients were similar in the patients and control subjects (mean 17 +/- 12 and 2 +/- 14 mm Hg) (p greater than 0.05). Mean resting systolic blood pressures in the upper limb were 121 +/- 10 mm Hg in the patients and 107 +/- 14 mm Hg in the volunteers (p greater than 0.05). The mean gradient between the upper and lower limbs was 13 +/- 19 mm Hg in the patients on dynamic exercise testing. No patient became pathologically hypertensive in the upper limbs during dynamic exercise. These results indicate that the subclavian flap procedure is an effective form of treatment for the symptomatic infant with coarctation of the aorta and can be expected to result in a low incidence of subclinical residual obstruction or restenosis.

Anomalous mitral arcade: echocardiographic and angiographic recognition.

A patient with sudden onset of hemiplegia was noted to have an anomalous mitral arcade at cardiac surgery. Echocardiographic and angiographic data are correlated with the anatomic findings. The clinical significance of this anomaly is discussed.

Fatty acid and glucose utilization in isolated, working newborn pig hearts.

The effects of exogenous fatty acids on glucose uptake were assessed in isolated, working newborn pig hearts in which great vessel pressures were controlled (mean 55 mmHg) and oxygenated nutrient buffer was recirculated through the heart for 30 or 60 min. When palmitate (1.5 mM) or octanoate (1.0 mM) were added to buffer containing 10 mM glucose and 100 mU insulin/ml, glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed to less than one-half that observed when glucose alone was present. Increased tissue levels of glucose 6-phosphate, fructose 6-phosphate, and citrate following perfusion in the presence of exogenous fatty acids were consistent with decreased glycolytic activity due to inhibition of phosphofructokinase. Measurements of carnitine in perfused and unperfused hearts indicated that total carnitine levels in neonatal hearts are similar to those of adult pigs. Increased tissue levels of long-chain acyl carnitine, acetyl carnitine, and citrate in hearts perfused with palmitate and glucose in combination with extensive fatty acid uptake and marked suppression of glycolysis indicated that the newborn pig heart is capable of utilizing fatty acids as a primary energy source.

Perinatal changes in mitochondrial respiration of the rabbit heart.

Oxidative metabolism and citrate synthase activity during the perinatal period were assessed in isolated rabbit heart mitochondria at 27 days' gestation (27 dpc), 1 day postpartum (1 dpp) and 10 dpp. Oxygen consumption was measured during state 3 and state 4 respiration using the following substrates: glutamate, alpha-ketoglutarate, pyruvate/malate, succinate/rotenone, acetate, palmitylcarnitine, and palmityl CoA/carnitine. Results obtained from fetal and neonatal animals were compared to values obtained from adult left and right ventricles. Rates of state 3 oxygen consumption per milligram mitochondrial protein using tricarboxylic acid cycle intermediates or palmitylcarnitine were higher in both 1 and 10 dpp animals than in either left or right ventricles. Respiratory activity per milligram mitochondrial protein using these substrates was similar in 27 dpc fetuses and adult left ventricles. The rate of oxidation of palmityl CoA was lower in fetal mitochondria than in adult left ventricle, indicating that the capacity for conversion of long-chain fatty acyl CoA to acylcarnitine necessary for transport of fatty substrates into the mitochondria is decreased in fetal hearts. Increases in myocardial citrate synthase corresponded to increases in mitochondrial mass reported by other investigators.

Carbohydrate metabolism in isolated, working newborn pig heart.

Metabolic activity of the newborn pig heart was observed by means of a preparation that allowed isolated hearts to perform a physiologic work load. A 10-min period of retrograde aortic perfusion was followed by 60 min of recirculating perfusion in which bicarbonate buffer was infused into the right atrium and ejected from both ventricles at measured pressures and flow rates. The buffer was supplemented with either glucose (10 mM), lactate (20 mM), or pyruvate (20 mM), or was unsupplemented. Pressure development and ventricular outputs were stable through 60 min of perfusion with glucose, pyruvate, or lactate supplementation. Myocardial high-energy phosphate and glycogen contents were also stable. In hearts perfused without substrate supplementation, mechanical performance deteriorated after 30 min. Rates of substrate uptake and oxygen consumption indicated that either glucose, lactate, or pyruvate could serve as a primary source of metabolic energy. Minimal lactate production was observed when either glucose or pyruvate were present. These findings indicate that, despite recent emergence from the relatively hypoxic intrauterine environment, the well-oxygenated newborn pig heart did not depend on anaerobic metabolism of glucose for energy production at physiologic work loads.

Oral hydralazine in patients with pulmonary vascular disease secondary to congenital heart disease.

Two patients with pulmonary vascular obstructive disease secondary to congenital heart disease were evaluated hemodynamically before and during oral hydralazine therapy. Both patients were assessed postoperatively and had no significant residual shunts. Pulmonary vascular resistance failed to decrease, and an increase in pulmonary arterial pressure occurred because of increased cardiac output secondary to systemic arteriolar dilatation. These responses were sufficiently consistent to warrant a warning against the use of oral hydralazine except under controlled conditions in patients with secondary pulmonary vascular obstructive disease.