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Biomedical subjects

J Metcalfe

Publications and source records attributed to J Metcalfe.

At least 55 records · Page 3Linked to original sources

Adrenergic mechanisms in the control of plasma lipids in man.

The effects on plasma lipids of beta-blocking antihypertensive agents with differing degrees of selectivity and intrinsic sympathomimetic activity were studied. The interrelationship between changes in lipid factors, lipoprotein lipase function, the degree of response, and pretreatment characteristics were examined. Beta-adrenergic blockade increased plasma triglycerides but decreased high-density lipoprotein cholesterol. Cardioselective drugs (atenolol and metoprolol) had less effect on triglyceride and very low-density lipoprotein cholesterol than the nonselective beta blockers (propranolol and oxprenolol). Inhibition of lipoprotein lipase was suggested by a reduction of the fractional removal rate of triglyceride in conjunction with increased total and very low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol. Consistent decreases in free fatty acids lend argument against elevated triglyceride synthesis.

Adrenergic beta-Antagonists↗

Stimulation of growth of the chick embryo by acute hyperoxia.

We have previously demonstrated that continuous incubation in elevated concentrations of ambient oxygen leads to accelerated growth of the chick embryo. We now report that a similar growth response is elicited by acute (72 h) exposure beginning on the 16th day of incubation. White Leghorn eggs were paired by initial weight and incubated in air for 15 days in forced-draft incubators. Embryos were sampled on days 11, 13 and 15 (experiments 1, 2, 3) or 13, 14 and 15 (experiment 4), freed of all extra-embryonic membranes and weighed. On day 16 the experimental group was switched to 60% O2. The control group was maintained in air. A portion of the remaining eggs from each group was opened on days 16, 17 and 18 (experiment 4), or alternatively all the remaining eggs were opened at the end of the 18th day of incubation (experiments 1, 2, 3). Linear regression analysis of growth curves obtained by plotting log wet embryo weight (g) vs log incubation age (d) showed a significantly greater rate of growth (slope) for days 15-18 in embryos exposed to 60% O2. These results support the hypothesis that growth of the chick embryo is normally limited by the availability of oxygen.

Animals↗

Capillaries and muscle fibers in the heart of the hyperoxic chick embryo.

Cardiomegaly was induced in chick embryos by incubation in 60% O2. On day 18 sections of heart were taken from these and from controls matched by egg weight before incubation in 21% O2. The ratio of left/right ventricular weight was the same in the two groups and so was the concentration of water in the ventricles. The densities of capillaries and of muscle fibers were determined in seven selected myocardial regions in order to establish (1) the cellular nature of the cardiomegaly, and (2) the effect of elevated O2 on capillary growth. In five of the regions no significant difference in capillary density was seen, but the cross-sectional area of the fibers rose significantly in all seven, especially in the right ventricle. Capillary density increased in the hyperoxic group in two areas immediately adjacent to the lumen of the right ventricle. These results suggest that oxygen causes hypertrophy of cardiac muscle fibers in the chick embryo without altering the capillary supply.

Animals↗

Effect of exercise on uterine blood flow in the pregnant Pygmy goat.

Pygmy goats in the last third of pregnancy were trained to walk on a treadmill at rates up to 2.0 mph and up an inclination of 0-15 degrees. Electromagnetic flowmeters were placed unilaterally on a uterine artery, and measurements were made while the goats were standing quietly on the treadmill and during 5 min of exercise. Blood flow fell during exercise in all five animals studied, and this reduction was proportional to the level of exertion. At the highest level of exercise that these animals would voluntarily perform, uterine artery blood flow fell by 32 +/- 3 (SE) % (P less than 0.001) from control. In four additional animals the radioactive microsphere technique was used to measure uterine blood flow at rest and after 5-7 min of exercise. In these animals, exercise caused total uterine blood flow to fall by 18 +/- 10%; cotyledonary (placental) blood flow fell by 8 +/- 13%, while myoendometrial blood flow decreased by 52 +/- 12% (P less than 0.05). Thus nonplacental portions of the pregnant Pygmy goat uterus suffer major reductions in blood flow during exercise. This vasoconstriction may be due to exercise per se or to concomitant hypocapnia or hyperthermia. Singleton and twin kids born to animals that exercised were of normal birth weight.

Animals↗

Left ventricular size, output, and structure during guinea pig pregnancy.

We investigated left ventricular (LV) hemodynamics, pressure-volume relations, and morphometry to determine what cardiac changes characterize pregnancy in the guinea pig. Time-bred virgin guinea pigs were paired by weight with unbred controls. Hemodynamic studies and LV pressure-volume relations were obtained on days 59-68 of the 68-day gestation. Weight of control sows increased from 817 to 902 g (P less than 0.01) and pregnant sows from 810 to 1,251 g (P less than 0.01). LV weights were not different. When indexed for maternal weight minus uterus and contents, pregnancy produced increases in O2 consumption, +48% (P less than 0.01); cardiac output, +32% (P less than 0.05); and stroke volume, +46% (P less than 0.025). Passive LV pressure-volume curves (dP/dV) were shifted to the right (P less than 0.025), but dP/dV at constant pressure was unchanged. Using a thin-walled spherical model, elastic modulus at constant stress was not different. The percent LV inter- and intracellular volumes and myocyte myofibril and organelle volumes were unchanged during pregnancy. In the guinea pig, pregnancy increases LV output, stroke volume, and size without changes in LV mass, morphometry, or elastic modulus.

Animals↗

Organ growth in chick embryos incubated in 40% or 70% oxygen.

Incubation of eggs in 60% oxygen has been shown to enhance growth of the chick embryo. To determine whether oxygen accelerates growth over a range of concentrations, eggs were incubated in 40% or 70% O2. Control eggs, pair-matched by initial weight, were simultaneously incubated in room air (21% O2). Embryo and organ weights from matched pairs of eggs were compared on incubation days 14, 16 and 18 (40% O2) or 10, 12, 14, 16 and 18 (70% O2). Embryos incubated in 40% O2 displayed a pattern of growth enhancement similar to that previously reported for 60% O2. Accelerated embryonic growth was maintained through day 18. The heart showed the greatest percentage increase in weight over control, exceeding that of the whole embryo on days 16 and 18. The brain displayed significant enhancement only on day 16. Weight of the liver was unaffected by hyperoxia. Embryos in 70% O2 exhibited accelerated growth in all of the tissues examined early in incubation. Growth rate of the hyperoxic embryos then declined, so that embryo weight on day 18 did not differ from control. The brain, heart, eye, and proventriculus plus gizzard from 70% O2 embryos weighed significantly less than controls on day 18. Growth inhibition was most striking in the heart; heart/body weight ratio of 70% O2 embryos was significantly less than control throughout the observation period. The results confirm the growth accelerative effect of oxygen and suggest that the degree of growth enhancement is proportional to the ambient oxygen concentration. Accelerated growth cannot be maintained, however, in 70% O2.

Animals↗

Surgical repair of lesions associated with corrected transposition. Late results.

Between 1970 and 1980 19 patients aged 13 months to 47 years (mean 16 years) had surgical repair of lesions associated with corrected transposition. Four had had previous palliative surgery. Operations were performed for ventricular septal defects in 17 (multiple in two), and in addition 10 had relief of pulmonary stenosis, three had atrial septal defects closed, and three had valve replacement for left atrioventricular valve regurgitation. Two patients had annuloplasty for isolated left atrioventricular valve regurgitation. There was a high operative mortality (37%). Twelve survivors left hospital and were followed up for three to eight years. There is concern about the high incidence of left atrioventricular valve regurgitation and progressive postoperative left sided ventricular dysfunction. Heart block after surgical intervention contributes to this, and careful pacemaker policies are necessary as two late deaths were related to this. Only one patient is asymptomatic and without complications 40 months after operation. These disappointing late results are partly related to the onset of heart block, but it seems that independent systemic ventricular function may deteriorate in some patients. Thus surgical treatment of lesions associated with corrected transposition should be recommended only in those with important symptoms or signs of changing systemic ventricular dysfunction.

Adolescent↗

Adrenergic mechanisms in control of plasma lipid concentrations.

The mechanisms of the changes in plasma lipids concentrations observed after beta-blockade were examined in 53 patients with hypertension receiving treatment with atenolol, metoprolol, propranolol, and oxprenolol in a randomised cross-over trial. Significant increases in mean plasma total and very-low-density lipoprotein (VLDL) triglyceride and reductions in high-density lipoprotein (HDL) cholesterol and free fatty acids concentrations wer observed with all four drugs, the increase in plasma triglyceride concentration being greatest after propranolol and oxprenolol. No significant changes were observed in total of LDL cholesterol concentrations, but HDL:LDL ratios and HDL cholesterol as a proportion of total cholesterol fell significantly. Thus plasma lipid concentrations should be monitored after three to six months of long-term treatment. Changes in triglyceride, HDL cholesterol and free fatty acid concentrations were associated with a highly significant reduction in clearance of soya oil (Intralipid) in 25 patients studied but were unrelated to changes in blood pressure. The fall in HDL cholesterol and rise in free fatty acid concentrations were significantly less in those with initially reduced HDL cholesterol or raised free fatty acid concentrations respectively. It is proposed that unopposed alpha stimulation inhibits lipoprotein lipase with a subsequent rise in plasma triglyceride and fall in HDL cholesterol concentration. Analysis of the relation between pretreatment concentrations and subsequent changes suggests that excessive alpha stimulation may impair production of HDL cholesterol in those with low HDL cholesterol concentrations before treatment. Subtle catecholamine-mediated changes in plasma lipid concentrations might provide a mechanism for the relation between stress and the development of cardiovascular events.

Adrenergic beta-Antagonists↗

Organ growth in hyperoxic and hypoxic chick embryos.

Chick embryos and their organs were weighed in order to compare retarded growth with accelerated growth. Growth was quickened by incubating eggs in 60% O2/40% N2 and slowed by covering part of the shell of eggs incubated in air. A control group was incubated in air without any covering. At two-day intervals from the twelfth to the eighteenth days inclusive, eggs were opened and the embryos dissected and weighed. An organ was 'spared' if it differed from its control weight proportionately less than did the whole embryo. Covered eggs were opened only on the eighteenth day and showed sparing of brain and heart and hepatic stunting in excess of body stunting. Hyperoxic eggs spared brain and liver during the period in question, but the heart grew proportionately more than the other tissues between days 16 and 18. These data show that the availability of oxygen alters the rate of embryonic growth, and induces differential growth among individual organs.

Animals↗

Comparative studies of the respiratory functions of mammalian blood. XII. Black galago (Galago crassicaudatus argentatus) and brown galago (Galago crassicaudatus crassicaudatus).

Respiratory characteristics of blood from sixteen adult male galagos were studied (8 brown and 8 black). The average body weight of the black galagos was significantly higher than that of the brown(1.512 +/- 0.162 vs. 0.988 +/- 0.099 kg, respectively). The blood oxygen capacities for black and brown galagos were 20.6 +/- 1.9 and 21.5 +/- 1.8 vol percent, respectively. The Bohr factor for blood from the black galago was -0550 +/- 0.039 (n = 9) and for brown galago blood was -0.523 +/- 0.050 (n = 6). There was no significant (P greater than 0.05) difference in P50 values of blood from the two subspecies of galagos, 36.7 +/- 1.1 vs. 37.7 +/- 0.9 mm Hg for the black and brown, respectively. The Haldane effect for black galago blood was higher than that for brown (7.5 vs. 65 vol percent, respectively). The concentrations of 2.3-DPG were similar in black and brown galago blood, 16.16 +/- 1.52 vs. 16.37 +/- 0.76 mumol/g Hb, respectively. Starch gel electrophoresis showed three major components of hemoglobin from both subspecies. There is a trend toward decreasing blood oxygen affinity as one ascends the primate evolutionary scale, which may be secondary to the trend toward a greater adult body weight.

Animals↗

Effects of restriction of maternal uterine blood supply on postnatal conditioning of heart rate and behavioral development in dogs.

An examination was made of the heart rate responses during aversive classical conditioning of 5- to 6-week-old Labrador puppies exposed to restricted maternal uterine blood supply during gestation. The direction of the heart rate responses of the treated puppies was consistently decelerative, whereas nontreated controls showed both decelerations and accelerations. The absence of accelerative heart rate changes, combined with the observed depression of base level heart rate and attenuated emotional behavior in the experimental animals relative to controls suggests that uterine blood supply insufficiency may have impaired normal autonomic development in utero.

Animals↗

Accelerated respiratory response to moderate exercise in late pregnancy.

We studied the rates of change of expired ventilation (VE, BTPS), O2 consumption (VO2, STPD) and CO2 production (VCO2, STPD) at the start and stop of 6 min of 50-W bicycle exercise, comparing 20 healthy young women at 38 weeks of pregnancy (G) and 3 months postpartum (NG). VO2, VCO2 and VE were significantly greater at rest for G than for NG. The absolute increases of VO2 and VCO2 from steady-state rest (SSR) to steady-state exercise (SSE) were the same for G and NG. The absolute increase of VE from SSR to SSE was significantly greater for G than NG. VCO2 and VE increased more rapidly in G than NG, but only during the first 90 sec of exercise. Recovery rates after exercise were equal for G and NG. We believe that lower extremity muscles of G contract on more distended veins at the onset of exercise, forcing increased volumes of venous blood through the lungs, increasing VO2 and VCO2. VE follows VCO2 closely.

Adult↗

Oxygen availability and growth of the chick embryo.

Two experiments were performed using White Leghorn eggs incubated in 50% humidity, at 38 degrees centigrade, and an average barometric pressure of 747 Torr. In one experiment, eggs in the experimental group were each half covered with a neoprene membrane, reducing the diffusing capacity by approximately 20%, and incubated in 21% O2. In the second experiment, the experimental eggs were incubated (uncovered) in 60% O2. Control eggs were incubated (uncovered in 21% O2 simultaneously with the experimental eggs in each study. A relationship between egg surface area (calculated from weight of the freshly laid egg) and embryo weight at 18 days was confirmed for all three groups. When comparisons were made among the groups, there was significant retardation of embryonic growth in the half-covered eggs; in contrast, embryos from eggs incubated in 60% O2 were significantly heavier at 18 days that control eggs incubated in air. The fact that embryo growth can be accelerated by incubation of the egg in 60% O2 suggests that the oxygen tension in blood leaving the chorioallantoic capillaries normally limits the rate of embryonic growth for the first 18 days of incubation in this species.

Animals↗

Postnatal regulation of oxygen delivery: control of erythropoiesis following birth in dogs.

Blood hemoglobin concentration decreases during the first postnatal month of canine life. Red cell production, as indicated by reticulocyte levels, decreases following birth and does not increase until the second postnatal month. Bleeding and transfusion studies were performed to determine if the canine erythropoietic system is defective during this early neonatal period or is operating at a less than maximal rate due to adequate oxygen delivery to those tissues which regulate erythropoiesis. There is no fundamental defect in the erythropoietic system since bleeding stimulated reticulocyte formation during the first postnatal month. Conversely, the reticulocytosis that normally occurs during the second postnatal month was suppressed when oxygen delivery was increased by a red cell transfusion. We conclude that adequate oxygen delivery following birth causes a reduction in red cell production and results in postnatal anemia. Due to increasing metabolic oxygen requirements of continued growth, the blood oxygen delivery becomes inadequate by the second postnatal month and red cell production is stimulated.

2,3-Diphosphoglycerate↗