The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats

The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group ( P  < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP.Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group ( P  < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates ( P  < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.     

Interaction of a Motor Response, and Reaction Time and Time Estimation Tasks, on Heart Rate and Skin Conductance

The influence of motor responding and typical psychophysiological tasks on heart rate was tested by manipulating motor requirements of reaction time (RT) and time estimation (TE) tasks. Thirty-four volunteers were assigned randomly to four groups. Two groups squeezed a hand dynamometer at the start of a trial and the other two groups squeezed at the finish of the trial. The force of the squeeze was also manipulated: either 3 kg (3) or 7 kg (7). The four groups were Start 3, Start 7, Finish 3, and Finish 7. All subjects participated in the TE and RT tasks. The dependent variables were measurements of forearm flexor muscle tension, heart rate and skin conductance. It was found that the manipulations of when and with what force a person squeezed the dynamometer resulted in reliable group differences in muscle tension. The magnitude of acceleratory components of the triphasic (acceleration-deceleration-acceleration) cardiac response was amplified by tension. The magnitude of the deceleratory component seemed to depend on both muscle tension and stimulus processing. Except for the magnitude of the response-bound deceleration, RT and TE produced very similar heart rate responses, and skin conductance did not differ among groups. The data were interpreted as providing evidence that motor response acts as an amplifier for the phasic HR produced by common psychological paradigms.     

Effect of aerobic capacity on sweat rate and fluid intake during outdoor exercise in the heat

We measured the aerobic capacity, sweat rate and fluid intake of trained athletes during outdoor exercise and examined the relationship between aerobic capacity and thermoregulatory responses at high ambient temperatures. The maximal aerobic capacity ( ) of the subjects, nine male baseball players of college age, was determined by maximal exercise tests on a cycle ergometer. The subjects practised baseball regularly without drinking fluids from 1330 to 1530 hours. After 30 min rest, they played a baseball game with free access to a sports drink at 15°C from 1600 to 1830 hours. At a mean ambient temperature of 36.7 (SEM 0.2)°C, the mean percentage of body mass loss (m _b) and increase of oral temperature (T _o) from 1330 to 1530 hours was 3.47 (SEM 0.12)% and 0.81 (SEM 0.14)°C, respectively. The sweat loss from 1330 to 1830 hours was 56.53 (SEM 1.56)ml · kg^–1 of body mass (M _b) while the mean fluid consumption was 44.78 (SEM 2.39)ml · kg^–1 ofm _b, with recovery of 76.08 (SEM 2.81)% of sweat loss. The was significantly inversely correlated withm _b, fluid intake and rehydration amount, but showed no correlation withT _o. These results would suggest that at a given exercise intensity in subjects with a higher aerobic capacity body temperature is maintained with a lower sweating rate than that in subjects with a lower aerobic capacity.     

Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design

Oxygen plays an important role in the cultivation of primary cellsex vivo. In this study, we used hermetically sealed tissue culture well inserts equipped with oxygen electrodes to measure the oxygen utilization of cultured human bone marrow mononuclear cells (BM MNCs). The oxygen uptake rate (OUR) of BM MNCs was determined during a 14-day culture in which both adherent and nonadherent cells were present. Early in the culture, the cells exhibited very low OURs. The specific OURs (uptake rate per cell) were at approximately 0.005 μmol/10⁶ cells/hr shortly after the initiation of culture. The OUR then increased as the cultures developed. After about 8 to 10 days of cultivation the specific OURs had increased to 0.038±0.006 and 0.025±0.005 μmol/10⁶ cells/hr for adherent and nonadherent cells, respectively, after which no further increase was observed. Based on these oxygen uptake rate data, a mathematical model of oxygen diffusion was formulated and use to investigate issues associated with hematopoietic bioreactor design, including initial cell density, medium depth, reactor configuration, and oxygen partial pressure.In situ OUR measurements confirmed predicted oxygen limitations based on the mathematical model and the experimentally determined OURs. High-density hematopoietic cultures present design challenges in terms of sufficient and uniform delivery of oxygen to an active hematopoietic culture. These challenges can be met by using parallelplate bioreactors with thin liquid layers.     

An Attempt to Elk it Cardiac Orienting and Defense Responses in the Newborn to Two Types of Facial Stimulation

Cardiac and behavioral reactivity of the human newborn to facial stimulation eliciting approach and escape responses were compared in order to test the distinction between cardiac orienting and defensive reactions. Each infant received 8 trials each of check stimulation (stroking near the mouth) and ear stimulation (pinch on the ear lobe). HR response to both tactile stimuli were accelerations of different amplitude when motor responses were also present. When no overt behavioral response was observed, stroking on the check elicited cardiac deceleration while ear stimulation again elicited acceleration. Thus, cardiac orienting was demonstrated in newborns when a rooting stimulus was presented that did not elicit overt head turning. The HR response to ear stimulation on trials unaccompanied by observed movements was a larger acceleration than to cheek stimulation when movement was present. This finding suggests that movement itself does not produce the observed HR increase, but rather that central processing of the signal value of the stimulus determines both overt and cardiac responding.     

Effects of spontaneously chosen crank rate variations on electromyographic responses in sub-maximal arm exercise in inexperienced subjects

The aim of the present study was to compare electromyographic responses during arm exercises with a crank rate chosen spontaneously (T_S) or set at 20% below or above (T_–20, T₊₂₀) the spontaneously chosen crank rate (SCCR). Ten male physical education students performed arm exercises with intensities ranging from 20% to 80% of maximal power. Muscular activity levels were analysed for the biceps brachii and the triceps brachii muscles using integrated rectified surface electromyography (iEMG). All values were presented as the mean and standard deviation. During T_S, the sum of iEMG for the two muscles studied was significantly (P<0.05) lower than during T₊₂₀ for each power output. No significant differences were observed in iEMG values between T_S and T_–20. The hypothesis that SCCR relates to a minimisation of muscle activation during an upper body exercise was not confirmed. Variations superior or inferior to a 20% increase of the iEMG responses do not influence it. Moreover, the selection of crank rates depends on the power output and the SCCR increased significantly (P<0.05) with increasing power output.     

Heart Rate Reactivity and Type A Behavior as Modifiers of Physiological Response to Active and Passive Coping

We examined the long term predictivity of heart rate reactivity (HRR) and its relation to cardiovascular and biochemical activity during rest and during tasks requiring active and passive coping. HRR was determined in 28 young men by measuring peak heart rate change to cold pressor one year after performing tasks eliciting active and passive coping. Heart rate change to cold pressor was significantly correlated with change to active coping (r= .65, p<.01) and to passive coping (r= .53, p<.01). Responses to the tasks were equivalent for Type A and B subjects. On the other hand, high HRRs were significantly more reactive than low HRRs with the effect being most apparent during active coping. HRR appeared to be a trait stable over one year which predicted enhanced cardiac, neuroendocrine, and neuromuscular response.     

Delayed pressure urticaria

Delayed pressure urticaria (DPU) is a poorly understood syndrome. We describe 17 patients with DPU. Chronic urticaria was present in 94%. All had negative challenges for immediate demographism and cold urticaria. DPU was induced with a pressure challenge on the shoulder of 15 pounds for 15 min. Average onset of pressure lesions after challenge was 6.5. Lesions were painful, not pruritic, peaked at 9 hr, and disappeared by 24 to 48 hr. Fever, chills, and/or arthralgias occurred in 78%. Positive laboratory abnormalities included leukocytosis in 20% and elevated erythrocyte sedimentation rate in 37.5%. Skin biopsies of lesions showed perivascular round cell infiltrates and negative immunofluorescence. Urticaria responded to antihistamines, but not aspirin, in 100% of patients, while pressure lesions improved with nonsteroidal anti-inflammatory drugs (NSAID), but not antihistamines, in 80% of patients. Both urticaria and DPU were controlled with prednisone, which was necessary in 87.5% of patients. A severe nonremitting course was noted in 7%, 40% had a moderate remitting course requiring intermittent prednisone, and 53% had a mild remitting disease requiring no medication or antihistamines and/or NSAID only. We conclude that DPU is more common than previously appreciated and likely involves mediators other than histamine, possibly the prostaglandin system.     

Radiographic quantification of alveolar bone level changes

The "random burst" theory has recently been proposed as an explanation of the pattern of periodontal disease progression. The theory predicts that the progression of bone loss at individual sites is not dependent upon previous bone loss and age. A longitudinal radiographic study was designed to test this hypothesis, and to describe the changes in bone level over 2 years in a group of 180 subjects (18-68 years of age) who were not under systematic periodontal treatment. The results indicated that 94% of the sites did not show significant changes in the alveolar bone level during the observation period. The mean annual bone loss for the total population was 0.11 mm. By regressing longitudinal bone loss upon age, it was shown that the rate of bone loss increased rapidly between 33 and 56 years of age while a different pattern was shown for the age intervals 18-32 and 57-68 years. Also, the rate of bone loss increased with increasing initial bone loss. This was less evident in the oldest age group. It was concluded that the progression of bone loss in the present material is consistent with a "burst" theory. However, the progression did not occur randomly with regard to previous loss of alveolar bone and time.     

Dopamine in the conscious dog with chronic heart-block

Summary The chronotropic effects of dopamine were studied in the conscious dog with chronic A-V block. Dopamine at 12.5–200 g/kg and 12.5–50 g/kg/min lowered atrial rate independently of dose. After blockade of muscarine receptors or alpha-adrenoceptors, it raised atrial rate. After blockade of dopamine receptors, dopamine still lowered atrial rate, and did so dose-relatedly after blockade of beta-adrenoceptors. It raised ventricular rate, and at high doses also induced ventricular rhythm disorders. Blockade of muscarine receptors enhanced the ventricular cardioaccelerator effect of dopamine (P<0.025) at 100 g/kg, while blockade of alpha-adrenoceptors reduced it (P<0.05). Blockade of dopamine receptors did not modify this effect, but blockade of beta-adrenoceptors reversed it. Dopamine at 25–200 g/kg raised mean blood pressure. This effect was enhanced by blockade of muscarine receptors, reversed by blockade of alpha-adrenoceptors, and was unaffected by blockade of beta-adrenoceptors or dopamine receptors. These results show that the atrial cardiomoderator effect of dopamine is a vagal reflex response to its hypertensive action, and that it is limited by its direct beta-adrenergic stimulating action. They also show that the ventricular cardioaccelerator effect of dopamine is attenuated by a reflex vagal depressor effect consequent to the induced hypertension. No evidence was found for the existence of positive chronotropic dopamine receptors in either atria or ventricles.A preliminary report of these findings was presented at the Symposium on Peripheral Dopaminergic Receptors, July 1978, in Strasbourg, France (Boucher et al. 1979b)