William G. Troyer

Electrophysiologic Effects of Isoproterenol and Beta Blocking Agents in Awake Dogs

In awake, unrestrained animals beta adrenergic stimulation by isoproterenol increased heart rate and enhanced A-V conduction with no change of conduction in Purkinje tissue or ventricular activation time. The chronotropic and dromotropic responses to isoproterenol were abolished completely by the adrenergic antagonists, propranolol (0.2 mg/ kg) and pronethalol (2 mg/kg). Beta adrenergic blockade with propranolol produced no significant change of heart rate, A-V conduction, conduction velocity in Purkinje tissue, or ventricular activation time. In contrast to the above, pronethalol produced tachycardia, enhanced A-V conduction and prolonged ventricular activation slightly. The tachycardia which followed pronethalol was largely a consequence of vagal inhibition since it could be nearly abolished by prior administration of atropine. Propranolol produced no changes in the refractory period or excitability of atrial muscle. Pronethalol did not alter the excitability of atrial muscle but did prolong the atrial refractory period. Barbiturate anesthesia was found to prolong ventricular activation time, and in anesthetized animals both propranolol and pronethalol caused further depression of conduction. These data support the view that cardiac adrenergic activity has little or no influence on conduction in the ventricle, and suggest that the intensity of sympathetic activity in awake, unrestrained dogs is minimal. The differences in the responses of unanesthetized animals to propranolol and to pronethalol indicate that the latter agent has significant anticholinergic properties as well as certain extra-adrenergic actions on conduction. Failure of blocking doses of both the above agents to alter diastolic thresholds indicates that their anti-arrhythmic properties are not related to an effect on excitability. Beta adrenergic blocking agents appear to exert qualitatively as well as quantitatively different effects in awake and anesthetized preparations, an observation which should be taken into consideration when evaluating the pharmacologic properties of these compounds.

Experimental stress and fat mobilization in lean and obese subjects

Abstract Analysis of free fatty acid values derived from 2 experimental stress situations involving volunteer young adult men reveals lower initial levels and diminished variability in obese subjects. In an exercise situation variability is significantly positively correlated with the initial level of FFA. These findings are discussed in relation to the possibility that insulin activity or adrenergic nervous system activity may be altered in obesity.

LIPID MOBILIZATION IN LEAN AND OBESE SUBJECTS

The history of medical concepts of obesity shows a tendency to view this biological state as a simple and direct result of a disturbance in metabolic processes.’ Such a disturbance has not yet been found at the adipose tissue level in humans despite the recent advances in knowledge of intracellular mechanisms of lipid synthesis and mobilization.’ This lack of success may reflect the inadequacy of a “single cause concept” of obesity. It also suggests that study of the integrated responses of the individual’s lipid and adipose system to stress may be necessary in order to demonstrate a metabolic disturbance in obesity. The discovery of the free fatty acids (FFA) identified a reliable indicator of lipid metabolism with which to study o b e ~ i t y . ~ The demonstration that this fraction of plasma lipids is sensitive to neurohumoral as well as other hormonal factors has provided a link between central nervous system activity and states of fat deposition and m~bil izat ion.~ The first observations of FFA levels in relation to obesity were reported by Dole in 1956.5 He noted venous FFA levels to be higher in obese male subjects than in nonobese controls following an overnight fast of 12 hours. His data also suggested a direct correlation between the extent of obesity and the resting fasting FFA concentration. These findings were later confirmed by Gordon in studies of hospitalized extremely obese patients.6 Orth and Williams found that obese and nonobese women responded in a quantitatively similar manner to infusions of epinephrine, suggesting that no impairment of lipid mobilization existed in o b e ~ i t y . ~ However, Gordon drew attention to a relative failure of plasma FFA to rise with continued fasting beyond the overnight period in obese men patients.6 This observation was confirmed by Opie and Walfish in their study of obese and lean women subjects.’ They noted that while the 12 or 13 hour fasting levels were higher in the obese, when fasting time reached 18-21 hours, FFA levels were lower in the obese subjects than in normal controls. These findings provided the first evidence of impaired FFA mobilization in obesity.

Racial environment, cohesion, conformity and stress

Abstract : The reactions of subjects to the planned and intrinsic events in a standard conformity experiment were obtained by measuring physiological arousal (plasma free fatty acid level). In a 2 X 2 X 2 design, Negroes and whites were compared under the following conditions: (1) subjects recruited either in groups of friends or strangers; (2) subjects did or did not have a group meeting prior to the experiment. The subjects having previous meetings were the least aroused at all points in the experiment. The Negroes, especially those who had no previous meeting failed to relax during a period of inactivity. High conformity rates among Negroes suggest that group ties protected subjects from the stress of specific events, but not from the stress of being in an experiment. (Author)