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Biomedical subjects

J C Werner

Publications and source records attributed to J C Werner.

At least 37 records · Page 2Linked to original sources
PubMed1985

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.

Animals↗
PubMed1985

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.

Adolescent↗
PubMed1984

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.

Aorta↗
PubMed1983

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.

Adult↗
PubMed1983

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.

Animals↗
PubMed1983

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.

Animals↗
PubMed1983

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.

Aortic Coarctation↗
PubMed1982

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.

Animals↗
PubMed1981

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.

Administration, Oral↗
PubMed1981

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.

Adenosine Triphosphate↗
PubMed1981

Effects of insulin on ventricular function in diabetic lambs with acidosis.

Diabetes mellitus (DM) was induced in 10 lambs by giving alloxan (150 mg/kg). Two to 4 days later, mean values for glucose were 748 mg/dl, and for arterial pH 7.25 (acute group). Two additional lambs were studied after 3 mo of DM (chronic group). Data were compared with 7 controls (glucose 128 mg/dl, pH 7.36). Left ventricular (LV) performance was assessed from function curves and measurements of LV dP/dtmax. Stroke volume ejected at LV end-diastolic pressure of 5 cmH2O (SV5) was calculated from regression analysis of each curve. SV5 averaged 2.83 +/- 0.34 ml in controls and 2.90 +/- 0.23 ml in the acute diabetics (not significant). Mean values for LV dP/dtmax also did not differ. A significant correlation was found between SV5 and LV weight (P less than 0.001). SV5 was normalized as ml/100 g LV, and average values for the three groups were identical. Insulin (10 U/kg) caused a progressive fall in SV5 in diabetics with severe acidosis (pH 7.00), but not in those with less acidosis (pH 7.28). In nondiabetics given lactic acid (pH 7.01), SV5 fell to 60% of initial values 1 h after insulin. Acidemic animals not given insulin showed no reduction in LV performance in the same time interval. Adrenergic support is necessary to prevent cardiac failure associated with acidosis. The present findings are ascribed to inhibition by insulin of catecholamine inotropic action on myocardium.

Animals↗
PubMed1980

Preservation of left ventricular function by insulin in experimental catecholamine cardiomyopathy.

We have shown previously that insulin reduces myocardial injury associated with norepinephrine (NE) infusion in the rabbit (Am. J. Pathol. 93:399--353, 1978). In the present study, left ventricular function (LVF) was assessed from afterload curves obtained by progressive aortic constriction 2--4 days following NE infusion. The initial slope of the function curves (SFC), maximum dP/dt and left ventricular end-diastolic pressure at 120 mmHg ((LVEDP120) were used for comparison. In 4 controls, SFC averaged 23.8 mmHg/cmH2O. In 10 rabbits given NE, the mean slope was 8.4 (P less than 0.01). However, animals pretreated with insulin before being given NE did not differ from controls (SFC, 19.7 mmHg/cmH2O). These performance data were supported by measurements of LVEDP120, which were 2.8, 12.3 and 3.1 cmH2O, respectively (P less than 0.05 and less than 0.02). In spite of the higher LVEDP, max dP/dt120 was significantly lower in the NE group than in the group given insulin. Histological findings and postmortem measurements of LV volume and mass were consistent with the observed differences in LVF. It is concluded that NE damage reduces LVF and this is largely prevented by pretreatment with insulin.

Animals↗
PubMed1980

Adrenal contribution to cardiac responses elicited by acute hypoxia in piglets.

The adrenal contribution to cardiac responses elicited by acute hypoxia was assessed in 16 piglets, 1-12 wks old, anesthetized with pentobarbital (30 mg/kg). External cardiac work was held constant and parasympathetic blockade was produced in each animal with atropine (1 mg). Hypoxia was produced by addition of N2 to the respirator. In a sham-adrenalectomy group (n = 6) left ventricular (LV) dP/dtmax increased significantly during hypoxia (PaO2 approximately 30 mmHg) to 3,680 +/- 414 mmHg/s from control values of 2,686 +/- 317 mmHg/s (P < 0.01). Heart rate rose from 171 +/- 6 to 186 +/- 7 beats/min (P < 0.02). These responses were not significantly altered by ganglionic blockade with trimethaphan camsylate (0.5 mg x kg-1 x min-1). Equally large increases of LV dP/dtmax appeared when heart rate was held constant by pacing. beta-Adrenoreceptor blockade with practolol (4 mg/kg) sharply reduced but did not eliminate the response. In contrast, no changes in LV dP/dtmax or heart rate were observed during hypoxia in adrenalectomized piglets (n = 6). These findings indicate that the increased cardiac contractility during acute hypoxia in piglets is dependent on the integrity of the adrenal glands and that there is minimal contribution from cardiac sympathetic nerves.

Acute Disease↗
PubMedDate not supplied

Unusual combination of congenital heart defects in an infant with Noonan syndrome.

Congenital heart disease occurs in 35-50% of patients diagnosed with Noonan syndrome. We present an infant with an unusual combination of congenital heart defects not previously reported, including partial atrioventricular septal defect, polyvalvular dysplasia, and progressive hypertrophic cardiomyopathy. We discuss the possible interaction between these lesions that may have led to the patient's rapid demise.

Angiography↗
PubMedDate not supplied

Mitral valve prolapse in persons with Down syndrome.

This study was designed to determine the prevalence of mitral valve prolapse and aortic insufficiency in home-reared, young persons with Down syndrome. Of the 36 individuals (ages 20-32 years) enrolled in this study, 20 had abnormal echocardiographic findings. Thirteen patients had mitral valve prolapse, 3 had both mitral valve prolapse and aortic insufficiency, 2 had only aortic insufficiency, and 2 had other mitral valve disorders. In 14 of the 16 patients with mitral valve prolapse, a midsystolic click was heard. Theories of the pathogenesis and possible complications of mitral valve prolapse and its relationship to exercise and sport activities are discussed.

Adult↗