SUMMARY1. Summit metabolism of lambs declined steadily from about 3-51. 02/kg. hr during the first day of life, to about 2-0 1. 02/kg .hr at 2 months of age.2. The contributions of shivering and non-shivering thermogenesis to these changes were estimated by three independent methods; nonshivering thermogenesis was stimulated by catecholamines in a thermoneutral environment, shivering was suppressed by curariform drugs during summit metabolism, and an attempt was made to suppress non-shivering thermogenesis during summit metabolism by use of the sympatholytic drugs phentolamine and propranolol. Drugs were given by intravenous infusion during measurement of oxygen consumption in a closed circuit respiration chamber.3. 'Resting' metabolic rate of lambs during the first day of life was increased two to three-fold, from 11. 02/kg. hr, by either adrenaline or noradrenaline infused at 1-10 ltg/kg. min. The increase declined with increasing age of lamb and was virtually absent by 3 weeks. The response to catecholamines appeared maximal at the dose levels used.4. Muscular paralysis induced by suxamethonium or gallamine reduced summit metabolism by about 2 1. 02/kg . hr in all lambs examined within the first 2 months of life. The residual metabolic rate, and the metabolic response to catecholamines under thermoneutral conditions, declined with age in the same manner, and their magnitudes were similar.5. Summit metabolism in lambs aged up to 2 months was depressed to varying degrees by the sympathetic inhibitors phentolamine, propranolol and hexamethonium. The depression with propranolol was greater, and the decline with age clearer, than with phentolamine. Hexamethonium and phentolamine depressed blood pressure, propranolol decreased heart rate Phy. I98 252 G. ALEXANDER AND THE LATE D. WILLIAMS and phentolamine and propranolol each suppressed shivering in some experiments.6. In 1 day-old lambs estimates of non-shivering thermogenesis, by the various methods, ranged from 0-8 to 1-41. 02/kg.hr (mean 1 1 1. or 31 % of summit metabolism), and the estimates of shivering ranged from 13 to 191. 02/kg.hr (mean 16 1. or 46% of summit metabolism). However, in lambs 1-month old, estimates of non-shivering thermogenesis from sympathetic inhibition (0-6 and 0-8 1. 02/kg.hr) were considerably higher than estimates from muscular paralysis or stimulation by catecholamines (0.2 and 0 011. 02/kg.hr). It is suggested that the depression of summit metabolism by the sympathetic inhibitors is not solely due to specific inhibition of non-shivering thermogenesis, at least in the older lambs. 7. The possession of a non-shivering thermogenic mechanism in addition to shivering is of clear survival value to new-born lambs.

SUIMMARY1. Cardiac output in lambs less than 3 days old was 50-100 % higher during summit metabolism than during exposure to thermoneutral conditions.2. The Fick method, based on oxygen consumption, and the dye dilution method for determination of cardiac output, gave qualitatively similar results, but there were considerable quantitative discrepancies.3. The thermogenic tissues, muscle and brown fat, extracted some 80 % of the oxygen from the blood perfusing them during summit metabolism.4. Significant right to left shunts through the foramen ovale were detected in about half of the lambs during the first few days of life; the size and incidence of shunts decreased with advancing age but were apparently independent of environmental conditions. 5. During exposure to extreme cold, left to right shunts through the ductus arteriosus were detected in a high proportion of lambs, < 12 hr old, with detectable foramen ovale shunts. Pressure measurements in pulmonary and systemic arteries in very young lambs indicated that right to left shunting via the ductus was unlikely to occur; none was detected.6. Summit metabolism was poorly related to oxygen carrying capacity of blood, but significant correlations of summit metabolism with cardiac output (positive) and with oxygen saturation of mixed venous blood (negative) were observed, though not consistently.7. It is concluded that the great variability of summit metabolism between lambs older than 6 hr is not readily explained in terms of cardiovascular phenomena, but that the quantity and efficiency of thermogenic tissues probably play an important role in limiting summit metabolism.

Vagally mediated heart rate variability (vmHRV), a measure of the parasympathetic nervous system’s control over the heart, is often negatively related to maladaptive emotional outcomes. Recent work suggests that quadratic relationships involving these factors may be present; however, research has not investigated gender differences in these nonlinear functions. To address this gap, the current study tested for quadratic relationships between resting vmHRV and depression and positive affect while investigating gender differences in these relationships. Significant quadratic effects were found between resting vmHRV and reports of both depression symptoms and positive affect in women but not men. Specifically, the lowest levels of depression and the highest levels of positive affect were found at moderate vmHRV in women. These results suggest that examinations of vmHRV’s nonlinear associations require the consideration of gender. Our findings are interpreted based on proposed differential neuropsychological mechanisms of vmHRV in men versus women.

SUMMARY1. Exposure of lambs at sea level to air containing more than 33 % oxygen resulted in a small increase in summit metabolism (maximum oxygen consumption on severe cold exposure) in some lambs, and in an improvement in the ability to maintain summit metabolism in others; there was a concomitant improvement in the maintenance of cardiac output, but no change in the degree of right to left shunting.2. Hypoxia (12-13 % oxygen in inspired air) reduced summit metabolism of new-born lambs by 25 %; but there was no effect in lambs 6-11 days old.Hypoxia neither reduced cardiac output, nor affected the degree of right to left shunting.3. The results suggest that in very young lambs there is some limitation of summit metabolism imposed by the supply of either oxygen or substrate to thermogenic tissues.

Background: A paradoxical profile of greater elevated sympathetic vasoconstriction (increased total peripheral resistance, TPR) and increased vagally-mediated heart rate variability (HRV) -the so-called Cardiovascular Conundrum- has been reported in African Americans (AAs) both at rest and in response to orthostasis. Whereas some authors have attributed this pattern to genetic factors, others have pointed to the potential role of coping with repeated racial discrimination.Objective: To disentangle between these alternative explanations, we have examined the hemodynamic profile of another population that is likely to be exposed to episodes of discrimination, i.e., sexual minorities.Methods: The first study was conducted on a sample of AAs and European Americans (EAs) with the aim of replicating previous results on the Cardiovascular Conundrum. In the second study, lesbian, gay, and bisexual (LGB) people, matched by age and sex with heterosexual participants, underwent a hemodynamic and autonomic assessment at rest and during an emotional (in the experimental group, both LGB-related and non LGB related), and a cognitive stressor.Results: The first study confirmed a pattern of higher resting HRV, paired with higher TPR, in AAs compared to EAs. In the second study, compared to heterosexuals, the LGB group showed the Cardiovascular Conundrum pattern, characterized by greater HRV and higher TPR at baseline and a more vascular hemodynamic profile and prominent compensation deficit in response to both tasks, and particularly during the LGB-related emotional task. However, in LGB only, the vascular response was negatively correlated with perceived discrimination.Conclusion: Present preliminary results are discussed in terms of maladaptive physiological consequences of exposure to chronic stress and the chronic use of dysfunctional emotion regulation strategies such as suppression.

A new hematopoietic growth factor (Steel factor) has been identified which stimulates erythroid proliferation both in vitro and in vivo. We evaluated the influence of recombinant Steel factor on hemoglobin synthesis in peripheral blood (PB) BFU-E-derived cells from normal donors by radioimmunoassay (RIA) and compared it with stimulation with GM-CSF and interleukin-3 (IL-3). Only Steel factor stimulated a significant increase in BFU-E-derived colony size and a significant increase in fetal hemoglobin (HbF) in BFU-E-derived erythroblasts from 0.49% +/- 0.27% to 6.33% +/- 1.11% in serum-deprived media and from 1.88% +/- 0.24% to 11.17% +/- 0.91% in serum. To determine whether this influence on hemoglobinization also occurred in sickle cell disease, we studied 13 patients with sickle cell disease. In serum-deprived conditions, there was a significant increase in the number and size of BFU-E-derived colonies with Steel factor that was dose-dependent. In addition, the proportion of HbF in progenitor-derived cells increased by 66% from 4.1% +/- 0.6% to 6.8% +/- 1.2% with Steel factor. In serum- containing conditions studied in 12 patients, the increase in percentage of HbF was even greater, from 10.7% +/- 0.9% in control cultures to 22.5% +/- 2.6% with Steel factor. These increases in percentage of HbF were significant and dose-dependent. An increase in percentage of HbF was observed in erythroblasts harvested on day 11, 14, and 18 of culture. A decrease in mean picograms of total Hb per cell after coculture with Steel factor was noted, suggesting that growth kinetics influenced complete hemoglobinization. In serum- deprived conditions, picograms of HbF per cell was not affected by Steel factor, and in serum-containing conditions that augment in vitro HbF production it was enhanced. Thus, Steel factor stimulated a significant increase in percentage of HbF in erythroid cells from normal donors and patients with SCA in vitro.

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