PubMed HealthSearch

Biomedical subjects

J Metcalfe

Publications and source records attributed to J Metcalfe.

At least 19 recordsLinked to original sources

Metabolic consequences of atenolol and propranolol in treatment of essential hypertension.

A six-month study of triglyceride, cholesterol, free fatty acid (FFA), glucose, insulin, growth hormone, and glucagon concentrations was carried out in asymptomatic hypertensive normal-weight men randomly allocated to treatment with atenolol or propranolol. A highly significant increase in the basal plasma triglyceride concentration was observed in propranolol-treated patients after three and six months' treatment, with a smaller but significant increase in atenolol-treated subjects after six months' treatment. The changes in triglyceride concentration could not be ascribed to variations in plasma insulin, growth hormone, or glucagon concentrations. Basal FFA concentrations were reduced during the first three months of treatment in both groups but returned to pretreatment levels after six months. Plasma cholesterol concentrations were unchanged by either agent.

Adult

Hen's eggs with retarded gas exchange. I. Chorioallantoic capillary growth.

The diffusing capacity of the hen's egg for carbon monoxide (D tau co) increases during incubation, reflecting the development of the chorioallantoic circulation. Previous work showed that the increase in D tau co could be diminished by incubating eggs in a 60% oxygen environment. The present work explored the effects of impeding gas exchange on the development of D tau co. Half the shell area was covered during incubation by a removable neoprene membrane which limited D tau co by approximately 20%. No difference could be detected between the D tau co values (measured with the membrane removed) of these eggs and control eggs incubated in the same 21% oxygen environment without a neoprene membrane. We conclude that the development of the chorioallantoic circulation is at its maximum under normal conditions of incubation and cannot be accelerated by restricting gas exchange.

Allantois

Resting hemodynamics and oxygen transport in unanesthetized adult cats.

Characteristics of blood, oxygen transport were determined in seven adult female cats with inlying catheters in the pulmonary artery and a carotid artery. Measurements were made without anesthesia. Cardiac output averaged 167 ml.kg-1.min-1. Blood oxygen capacity averaged 11.6 ml.dl-1. Mean arterial oxygen saturation was 94% and mixed venous oxygen saturation was 49%. Mean oxygen tensions were 97.3% and 36.9 mm Hg in arterial and mixed venous blood, respectively. Mean arteriovenous oxygen concentration difference was 5.1 ml.dl-1, yielding a calculated oxygen consumption of 8.4 ml.kg-1 min-1, 5% higher than the value obtained by spirometric measurements on four of the animals. These data, when compared with previously reported values from species ranging widely in body size, show that the increased oxygen consumption per kg associated with decreasing body size is provided by progressive increases in cardiac output per kg and in arteriovenous oxygen concentration difference. Mixed venous oxygen tension is held within narrow limits in resting, unanesthetized animals.

Animals

Postnatal regulation of oxygen delivery: hematologic parameters of postnatal dogs.

Hematologic parameters influencing tissue oxygen delivery in dogs during the first 4 mo of life have been investigated. The rapid growth and increase in body temperature during this period imply an increased metabolic rate and increased tissue oxygen demand. Hemoglobin concentration and hematocrit decrease during the 1st mo following birth. The total red cell mass does not decrease during this period. The observed hemodilution can be attributed to an increasing plasma volume in the growing animal. The blood oxygen affinity decreases during this same period, resulting in a more effective tissue oxygen delivery. Erythropoiesis, as estimated from the percent circulating reticulocytes, decreases following birth and does not increase until 1 mo of postnatal life. The increase of erythropoietic activity during the 2nd mo of postnatal life coincides with an increase in red cell mass, hematocrit, and hemoglobin concentration.

Animals

Reduction of human blood O2 affinity using dihydroxyacetone, phosphate, and pyruvate.

Human blood oxygen affinity (BOA) was measured after blood from six normal donors was incubated with 4 concentrations of dihydroxyacetone (0.022, 0.044, 0.088, and 0.175 M) plus equimolar disodium phosphate and pyruvate (sodium salt) (0.013, 0.025, 0.05 and 0.1 M) in solutions labeled DDP X 1, DDP X 2, DDP X 4, and DDP X 8, respectively. Blood P50 rose (BOA was reduced) from a control value of 26.0 +/- 0.4 Torr (mean +/- SD) to 29.4 +/- 0.6, 30.6 +/- 0.4, 31.9 +/- 0.15 and 33.3 +/- 1.4 Torr after 2 h of incubation at 37 degrees C with solutions DDP X 1, DDP X 2, DDP X 4, and DDP X 8, respectively. P50 changes at 2 h were 75% complete within 30 min. During these incubations, erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration rose from 0.76 +/- 0.09 mol/mol Hb (control) to 1.09 +/- 0.17, 1.14 +/- 0.10, 1.33 +/- 0.15, and 1.45 +/- 0.25 mol/mol Hb with increasing solution concentration. BOA is decreased by an increase in erythrocyte 2,3-DPG. Reduced BOA may improve oxygen delivery to ischemic tissues.

Animals

Influence of progestin upon hemodynamics in castrated male pygmy goats.

Effects of progestin administration for 5 to 6 weeks upon hemodynamics were studied in two separate experiments, using trained, adult castrated male Pygmy goats. Measurements of cardiac output, blood pressure, plasma volume, and oxygen content of arterial and mixed venous blood were made before, during, and after treatment. In experiment 1, four animals were used. Progesterone was implanted subcutaneously in silicone envelopes which released an average of 44 mg of progesterone/day/goat. A 20% decrease in cardiac output occurred by the 5th week of treatment. Blood pressure was maintained by an increased peripheral vascular resistance. The five animals in experiment 2 were given (IM) 6 mg of 17-alpha-hydroxyprogesterone/kg of body weight/day. Cardiac output decreased 17% in the 2nd and 3rd weeks of hormone treatment. 17-alpha-Hydroxyprogesterone caused a transient natriuresis followed by sodium retention. Urinary aldosterone excretion increased after 9 days of treatment, but returned to normal by the 15th day.

Animals

Gas exchange of the fertile hen's egg: components of resistance.

The resistance to diffusion of respiratory gases falls by 50% from day 10 to day 18 in the incubating fertile hen's egg (Temple and Metcalfe, 1970). We have calculated the change in the components of this resistance with respect to incubation age. The egg shell resistance remains unchanged. The chorioallantoic membrane (including capillary endothelium) resistance decreases dramatically from day 10 to day 14 and then remains relatively unchanged. The resistance offered by the blood is unchanged from day 10 to day 12, it decreases by day 14 due to an increase in oxygen capacity and continues to decline at days 16 and 18 because of the combined effects of a continued increase in oxygen capacity and an increase in capillary volume.

Allantois

Physiological effects of lowered blood oxygen affinity in dogs.

Ten adult Labrador retrievers were studied under control conditions and while blood oxygen affinity was lowered by intravenous infusions of glycolytic intermediates. Blood P50 was increased from 32.4 +/- 1.3 mm Hg (mean +/- SD) to 34.3 +/- 1.2 mm Hg, a highly significant increase (P less than 0.001). Blood oxygen capacity, mixed venous oxygen tension and arterial PCO2 were not significantly different in the two conditions. Cardiac output (Q) was lower with the higher P50 (89 +/- 16 ml/kg/min) than in the control state (111 +/- 31 ml/kg/min) but the difference was not statistically significant. The arteriovenous oxygen concentration difference (CaO2 - C-V(O2)) was significantly increased (P less than 0.05) from 4.4 +/- 0.6 vol % to 4.9 +/- 0.8 vol %. Oxygen consumption, the product of Q and (CaO2 - C-V(O2)), was the same in the two conditions: 4.9 +/- 1.3 ml/kg/min (control) versus 4.4 +/- 0.9 ml/kg/min. The animals responded to lowered blood oxygen affinity with increased oxygen extraction by peripheral tissues and a concomitant, although not statistically significant, fall in cardiac output.

Animals

Respiratory characteristics of opossum (Didelphis virginiana) blood during chronic anemia.

In five adult opossums (Didelphis virginiana), blood hemoglobin concentration was lowered from 12.3g% to 6.4g% by daily bleeding. Blood P50 rose significantly (P is less than 0.05) from 44.5 mm Hg to 47.4 mm Hg and the concentration of 2, 3-diphosphoglycerate (DPG) increased from 14.17 mumol/g Hb to 20.90 mumol/g Hb. The observed shift in blood oxygen affinity was of similar magnitude to that recorded in humans with a similar degree of anemia, but the concomitant rise in DPG concentration was greater in opossums than in humans. In the opossum the shift in P50 with anemia can be attributed entirely to the action of DPG as a non diffusible intraerythrocytic anion.

Anemia

Responses to exercise in the pregnant pygmy goat.

Pregnant Pygmy goats were trained to walk on a treadmill up a 10 degree grade at a rate of 1.5 mile/hr for 10 min. Hemodynamic measurements were made in duplicate during late pregnancy and postpartum, at rest and after 3 min of exercise. All kids were weighed within 12 hr of delivery to assess the effect of exercise on fetal growth. Pulse rate, cardiac output and oxygen consumption were higher during pregnancy than postpartum, at rest and also during exercise. Stroke volume increased significantly with exercise. Peripheral vascular resistance (pvr) at rest was lower during pregnancy than postpartum, and decreased significantly during exercise, especially in pregnancy. Exercise was associated with a fall in arterial P(CO2) during pregnancy and postpartum. In goats, as in humans, the increased oxygen demands of pregnancy, during exercise and at rest, are met by an increased cardiac output rather than by increased peripheral oxygen extraction. The individual birth weights of twins, triplets and quadruplets from Pygmy goats who were exercised during late pregnancy were smaller than birth weights of matched newborns from control animals.

Animals

Chemical characteristics of a high molecular weight renin from the renal cortex of the dog.

We found an acid extract of normal dog kidneys to contain two distinct molecular weight forms of renin-like activity. Gel filtration chromatography showed peaks of activity as estimated molecular weights of 65,000 and 41,000. The high molecular weight fraction (HMW) comprised only 1% of the total activity of the extract. Both HMW and low molecular weight (LMW) fractions were inhibited by anti-human renin antibody and had similar broad pH-dependent activity optima between pH 6.0 and 7.5 in homologous substrate. The Michaelis constant (Km) of HMW was 3.6 times the Km of LMW. Both renins bound reversibly to concanavalin A-Sepharose with comparable affinities. HMW and LMW eluted from DEAE-Sephadex at similar salt concentrations without conversion of HMW to LMW. Transient acidification effected partial conversion of HMW to LMW without changing the total activity. Preincubation of HMW with trypsin increased the activity 40% and effected complete conversion of HMW to LMW. The apparent molecular weight difference between HMW and LMW is probably due to a covalently bound fragment(s) and not to a noncovalently bound moiety such as has been described in the rabbit and the hog. Both HMW and LMW are glycoproteins whose terminal sugar constituents possibly are similar. HMW dog renin is a new molecular form of renin that is convertible to a more active lower molecular weight renin with tryptic proteolysis.

Animals

Postnatal changes in blood respiratory characteristics in an American opossum (Didelphis virginiana).

The oxygen affinity of opossum blood changes in the postnatal period. The youngest opossums studied were 53 days of age (dated from the day of transit from vagina to pouch) and still confined to the maternal pouch: they had a blood P50 of 32.6 +/- 2.9 mm Hg. The blood P50 value then increased significantly, in two steps. First, while the young were still in the pouch, blood P50 rose secondary to a rise in the concentration of 2,3-diphosphoglycerate (DPG). Blood P50 and DPG concentration then remained stable until the animals left the maternal pouch, when DPG rose again, causing a further increment in the blood P50 which peaked at 48.7 +/- 4.5 mm Hg in animals 148 days old. Blood P50 subsequently decreased significantly, reaching the adult value (42.0 +/- 1.9 mm Hg) at about 250 days.

Animals

Kinetic differences between uterine and renal renins in the dog.

It has previously been reported that in the dog the Michaelis constant (Km) of renal renin with respect to homologous plasma substrate is the same as that for the angiotensin-generating enzyme extractable from the myometrium during pregnancy. We have reexamined the kinetics with a different methodology. Enzyme preparations from dog kidneys, the uterus of a nonnephrectomized pregnant bitch, and the uterus of a nephrectomized pregnant bitch were used. The substrate, prepared by diluting plasma from a nephrectomized, hysterectomized pregnant bitch, had a maximum endogenous substrate concentration of 1,750 ng/ml angiotensin I equivalents. Lineweaver-Burk kinetic analysis was used to calculate the Michaelis constants at pH 6.2. The Km of the renal enzyme was 720 ng/ml, of the enzyme prepared from the nonnephrectomized uterus 1,570 ng/ml, and of the nephrectomized dog uterus 1,500 ng/ml. The uterine enzyme was not activated by transient acid treatment, in contrast to renins reported from other sources. The data support the concept of biochemical heterogeneity of the two enzymes in the dog.

Angiotensinogen

Serum biochemistry values in normal pygmy goats.

Blood serum of pygmy goats (both sexes, and castrated males) was analyzed to establish biochemical reference values. Influence of age on reference values was also studied. Serum biochemical analyses were made for urea nitrogen, creatinin, bilirubin, lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase, glucose, uric acid, and total lipids. These serum values for pygmy goats were similar to those reported for man, except as follows: Aspartate aminotransferase activities were slightly higher than those reported for man. Glucose concentrations in pygmy goats were slightly lower than in human beings, and uric acid levels were significantly lower than the values for man. Female and castrated male goats had lower total lipid concentrations than did human beings, whereas intact males had higher concentrations. Thus, of the 9 measured variables for pygmy goats, 5 were comparable to human values. This, together with other attributes, including the small size which conduces to economics of maintenance and enhances the desirability of using pygmy goats in research.

Alkaline Phosphatase

Hematologic values in normal pygmy goats.

Pygmy goat blood was analyzed to determine hematologic base-line values. Male, female, and castrated male goats were used in this investigation. Influence of age on these variables was also studied. Most of the hematologic values of pygmy goats were similar to the reference values reported for several other ruminant species and for man. Values significantly different from reference values in man were as follows: Erythrocyte counts were slightly higher than for human beings. The relative lymphocyte count was comparable to that in infants, but significantly greater than values in adult human beings. Also, although not of statistical significance, hemoglobin levels in goats were slightly lower than in both infants and adult human beings, and the leukocyte count was just slightly higher than the usual values for infants and adult human beings. Thus, of 9 hematologic variables, only 1 was significantly different from those in man, and 2 were slightly different. The fact that pygmy goats have hematologic responses similar to those of man, and the similarity of hematologic values to reference values in man, further enhances the pygmy goat for use as an experimental animal.

Animals