3rd Min Research Articles

Involvement of Septal Muscarinic Receptors in Cholinergically Mediated Changes in Rat Rearing Activity

We tested the hypothesis that septal muscarinic receptors of the rat are involved in exploratory behavior control, at least as reflected in the measure of rearing activity. At a dose capable of inducing hippocampal theta rhythm, carbachol injection into the septum significantly increased the number of rearings from the 2nd to the 5th min postinjection. The increase was maximal in the 3rd min and gradually declined until the 9th min postinjection, when it was near the control level. This behavioral effect was blocked by prior injection of atropine. These data, when considered with other findings showing a similar motor response caused by the hippocampal injection of the cholinergic agonist, strongly suggest that the cholinoceptive cholinergic components of the septohippocampal system play a role in the release of exploratory behavior. This role might be mediated via muscarinic receptors at the septal level. Moreover, the time course of behavioral action of carbachol injected into the septum is of particular importance for studies on the effect of the drug on performance of the rat in learning and memory tests requiring contribution of exploratory behavior.

Vasoconstriction in active calf persists after discontinuation of combined exercise with high-intensity elbow flexion.

The present study aimed to determine whether vasoconstriction in active calf occurring during combined exercise diminished or persisted when added low- and high-intensity elbow flexion exercise ceased and single leg exercise continued. Six active women (mean age, 21.2 years) participated in this study. During 10-min plantar flexion exercise at 10% of maximum voluntary contraction (MVC), elbow flexion exercise at 10% MVC was added over the 3rd and 4th min. Calf blood flow did not change significantly upon superimposition and cessation of this elbow flexion exercise. However, when elbow flexion exercise at 50% MVC was added during the 7th and 8th min, calf blood flow above the resting value (2.23 +/- 0.23 mL 100 mL-1 min-1) decreased significantly (P < 0.05) from 6.72 +/- 0.87 (6th min) to 5.14 +/- 1.36 mL 100 mL-1 min-1 after 2 min of combined exercise and was accompanied by a similar change in the non-exercising calf blood flow value. The vascular conductance of the exercising calf decreased significantly (P < 0.01) from 6.48 +/- 1.08 (6th min) to 3.11 +/- 1.27 mL 100 mL-1 min-1 mmHg-1 at the end of the 2nd min of combined plantar flexion exercise with elbow flexion exercise at 50% MVC. After elbow flexion exercise at 50% MVC was discontinued and plantar flexion exercise at 10% MVC alone was performed, the vascular conductance in the exercising calf remained significantly low for the next 2 min. These results indicate that the vasoconstriction induced by adding high-intensity arm exercise is persistent, suggesting a major contribution of metabo-receptor-mediated vasoconstriction rather than central command- and mechano-receptor-mediated vasoconstriction.

Plasma metabolites, volume and electrolytes following 30-s high-intensity exercise in boys and men.

It has been shown that boys recover faster than men following brief, high-intensity exercise. Better to understand this difference, plasma metabolite concentration, volume, electrolyte concentration [electrolyte], and hydrogen ion concentration [H+] changes were compared in five prepubescent boys [mean age 9.6 (SD 0.9) years] and 5 men [mean age 24.9 (SD 4.3) years] following 30-s, all-out cycling. Blood was collected prior to, at the end, and at the 1st, 3rd and 10th min following exercise. At the 10th min of recovery, the men's lactate concentration was 14.2 (SD 1.8) mmol.l-1 and [H+] was 66.1 (SD 5.9) nmol.l-1, compared with 5.7 (SD 0.7) mmol.l-1 and 47.5 (SD 1.2) nmol.l-1 respectively, in the boys (P < 0.01 for both). The glycerol concentration was higher in the boys at the end of exercise and until the 3rd min of recovery. Plasma volume (PV) decreased more in the men [16.9 (SD 3.0)%] than in the boys [9.4 (SD 2.8)%]. In both groups, [electrolyte] increased after exercise, tending to be higher in the men. Recovery of plasma [electrolyte] and PV started earlier in the boys (1st min) than in the men (3rd min). These findings would support the notion of a lesser reliance on glycolytic energy pathways in children and may explain the faster recovery of muscle power in boys compared to men.

Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart rate (HR) elicited by 3 min of static handgrip at 30% of the maximum voluntary contraction in 12 healthy volunteers. Before each handgrip trial, subjects were treated with intravenous administration of either saline placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and integrated electromyographic activity of exercising muscles remained fairly constant during each trial. In agreement with our earlier findings, during control handgrip minute ventilation progressively increased (P < 0.01) due to a rise in tidal volume and, to a lesser extent, in respiratory frequency. Mean inspiratory flow, MBP, and HR also increased (P < 0.01). End-tidal PCO2 decreased (P < 0.05) during the late phases of control handgrip bouts. Ketoprofen administration reduced serum thromboxane B2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01) and significantly attenuated mean increases in minute ventilation (40.25 +/- 0.60%), tidal volume (37.78 +/- 7.48%), respiratory frequency (55.94 +/- 17.92%), inspiratory flow (42.66 +/- 5.11%), MBP (22.33 +/- 6.82%), and HR (11.04 +/- 2.75%) during the 3rd min of handgrip. End-tidal PCO2 remained close to normocapnic levels. In agreement with previous animal investigations, the present results show that arachidonic acid metabolites are involved in the regulation of the cardiovascular responses to static efforts in humans, possibly through a stimulatory action on muscle receptors. Furthermore, they provide the first experimental evidence that products of the cyclooxygenase metabolic pathway play a role in the mediation of the respiratory adjustments elicited by this form of exercise.

Independence of ventilation and blood lactate responses during graded exercise.

The effect of power output increment, based on an increase in pedal rate, on blood lactate accumulation during graded exercise is unknown. Therefore, in the present study, we examined the effect of two different rates of power output increments employing two pedal rates on pulmonary ventilation and blood lactate responses during graded cycle ergometry in young men. Males (n = 8) with an mean (SD) peak oxygen uptake of 4.2 (0.1) l.min-1 served as subjects. Each subject performed two graded cycle ergometer tests. The first test, conducted at 60 rev.min-1, employed 4 min of unloaded pedaling followed by a standard power output step increment (SI) of 60 W every 3rd min. The second test, conducted at 90 rev.min-1, employed 4 min of unloaded pedaling followed by a high power output step increment (HI) of 90 W every 3rd min. Venous blood was sampled from a forearm vein after 5 min of seated rest, 4 min of unloaded pedaling, and every 3rd min of graded exercise. Peak exercise values for heart rate, oxygen uptake (VO2), and ventilation (VE) were similar (P > 0.05) for SI and HI exercise, as was the relationship between VE and VO2, and between VE and carbon dioxide production (VCO2). However, the relationship between blood lactate concentration and VO2 was dissimilar between SI and HI exercise with blood lactate accumulation beyond the lowest ventilatory equivalent of oxygen, and peak exercise blood lactate concentration values significantly higher (P < 0.05) for SI [12.8 (2.6) mmol.l-1] compared to HI [8.0 (1.9) mmol.l-1] exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The Magnitude, the Kinetics and the Metabolic Efficiency of First-Phase Insulin Response to Intravenous Glucose are Related

We investigated the relationship between the kinetics, the magnitude and the metabolic efficiency of first-phase insulin response (FPIR) to intravenous glucose. Twenty healthy control subjects and fifty first degree relatives of Type 1 diabetic patients were studied using a standardized protocol for the intravenous glucose tolerance test (IVGTT). The first significant increase in plasma insulin concentrations above baseline appeared as early as the 2nd min (1 min before the end of glucose injection, fast response) in 80% of controls and 70% of relatives, and at the 3rd min or later (delayed response) in the remaining subjects. The greatest delay in insulin release (5th min) was observed in 4 of 6 relatives of Type 1 diabetic patients with impaired FPIR. In the controls and the relatives, the subjects with a fast insulin response had a significantly higher FPIR (controls 215.4 +/- 93.5 vs 59.7 +/- 5.6 microU/ml, p < 0.001 and relatives 143.5 +/- 61.8 vs 55.9 +/- 27.7 microU/ml, p < 0.001) and showed better glucose assimilation (controls 3.05 +/- 1.05 vs 1.64 +/- 0.16%/min, p < 0.05 and relatives 2.6 +/- 0.96 vs 1.6 +/- 0.85%/min, p < 0.01) during IVGTT than the subjects with a delayed response. Moreover, for normal FPIR values in the group of relatives of Type 1 diabetic patients, a fast response was associated with a significantly better glucose assimilation as assessed by the incremental area under the glucose curve (358.6 +/- 64.7 vs 539.2 +/- 67.7 mmol/l per 90 min, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pacing-induced Ventricular Fibrillation Leading to Oxygen Free Radical Formation in Aerobically Perfused Rat Hearts

The objective of this study was to determine whether electrically-induced ventricular fibrillation can elicit oxygen free radical formation, even in the absence of ischemia and reperfusion. Rat hearts ( n = 8 in each group) were perfused aerobically at 37°C and ventricular fibrillation was induced by pacing (20 Hz, 1200 beats/min) for 10 min, during which time no changes in coronary flow rates were observed. In this study, electron spin resonance (ESR) studies using the spin trap 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) demonstrated the formation of oxygen free radicals consisting of 1:2:2:1 quartet with peak concentration at the 3rd min of fibrillation in non-ischemic electrically fibrillating hearts. Since there were no significant changes in coronary flow rates during ventricular fibrillation (22.3 ± 1.3 ml/min in control vs 22.3 ± 0.9 ml/min in pacing-induced fibrillating group), the formation of oxygen free radicals could not be attributed to a pacing-induced ischemic event. In additional studies, hearts were paced by 10 Hz (600 beats/min), to demonstrate whether ventricular tachycardia could elicit free radical formation. In these experiments the genesis of oxygen free radicals was not observable after 1 min, 5 min, and 10 min of tachycardia, but a small amount of OH radicals was detected at the 3rd min of ventricular tachycardia. When DMPO was infused into the heart giving a final perfusate concentration of 2.5 mmoles/litre during the pacing-induced fibrillation period, myocardial function (aortic flow, cardiac outputs, left ventricular developed pressure, first derivative of left ventricular developed pressure,and end-diastolic pressure) was significantly improved after the postfibrillating period. In conclusion, our studies clearly show that electrically-induced ventricular fibrillation is capable of eliciting free radical formation even in the absence of ischemia and reperfusion, and the cardioprotective effect of the spin trap is directly originated from its free radical trapping property and not from the other pharmacological activities of DMPO.

Effect of resistive loads on pattern of respiratory muscle recruitment during exercise

In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no-added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative EEG changes under various conditions of hyperventilation in the sensorimotor cortex of the anaesthetized cat

The effects on the EEG rhythms recorded from the sensorimotor cortex (post-sigmoid gyrus) of anaesthetized cats were studied under 4 conditions of artificial mechanical hyperventilation (HV) before and after cervical bilateral vagotomy. In animals with intact vagus nerves, using visual examination, EEG changes were only observed within the 2nd min during HV produced by increased stroke volume (ΔV) with associated hypocapnia. Quantitative EEG (qEEG) showed that, for the same increase in minute ventilation and the same degree of hypocapnia, ΔV induced a greater and earlier relative decrease (2nd min) in the power density of delta, theta and alpha bands, than increased pump frequency (ΔF). The ΔF tests produced a fall only in the theta band and within the 3rd min. With constant p aCO 2, transient modifications occurred only with ΔV and were limited to the first 30 sec. In bivagotomized cats, moderate EEG responses to ΔV plus associated hypocapnia persisted partly in the alpha band. Finally, no changes appeared with ΔV or ΔF when the vagus nerves were cut and p aCO 2 was maintained constant. The present data suggest strongly that, in anaesthetized cats, peripheral vagal afferents from the respiratory system play a major role in the EEG changes caused by artificial hyperventilation.

Tracheobronchial perfusion during exercise in ponies

Tracheobronchial circulation during exercise has previously not been examined. Therefore blood flow to the trachea and bronchi (up to 7th generation of branching) was studied in seven healthy adult ponies at rest and during the 3rd and 10th min of exercise performed at a treadmill speed setting of 25 km/h. The ambient air temperature varied from 19 to 20 degrees C and humidity from 35 to 45%. To determine blood flow radionuclide-labeled 15-microns-diameter microspheres were injected into the left ventricle via a catheter advanced from the left carotid artery (exposed using local anesthesia), and a reference sample was obtained from the aorta. Adequate mixing of microspheres with blood was demonstrated by similar perfusion values for left and right kidneys. Exercise increased heart rate (194 +/- 9 and 200 +/- 7 beats/min) and mean aortic pressure (169 +/- 8 and 156 +/- 4 mmHg) of ponies at 3rd and 10th min. Tracheal blood flow (6.7 +/- 0.5 ml.min-1 x 100 g-1) of resting ponies was only one-third of the bronchial blood flow (21.6 +/- 4.9 ml.min-1 x 100 g-1) Significant changes in tracheal perfusion did not occur at 3rd or 10th min of exercise. Although bronchial perfusion also did not change at the 3rd min of exercise, it rose dramatically to 202.8 +/- 30.3 ml.min-1 x 100 g-1 during the 10th min. Concomitantly, renal blood flow decreased at 10th min of exertion. The large increase in bronchial blood flow at 10th min of exertion may have been necessitated by the need to help dissipate body heat.

Relationship Between Numbers of α2- and β2-Adrenoceptors in Teat Tissue and Blood Cells and Milkability of Primiparous Cows

Milking characteristics were measured on 14 cows at morning milkings. After collection of blood, cows were slaughtered and teats were removed. β2-Adrenoceptors on teat tissue and lymphocyte membranes were identified by binding of [3H]dihydroalprenolol. For the determination of α2-adrenoceptors on teat tissue and blood platelet membranes, [3H]rauwolscine was used. In teat tissue and blood cells, except for the amount of milk collected during the 3rd min, all other milking parameters were highly correlated with the ratio of β2-adrenoceptors to α2-adrenoceptors. Good milkability appears to be associated with low ratio of β2-adrenoceptors to α2-adrenoceptors densities in teat tissue, and a high ratio of β2- to α2-adrenoceptors densities in blood cells.We postulated earlier that a low ratio of β2 to α2-adrenoceptors in teat tissue of fast milking cows probably reflects changes of mainly prejunctional adrenoceptors. From our results on blood cells, we are now hypothesizing that in teat tissue prejunctional and extra junctional α2- and β2-adrenoceptors might have been identified together, whereas α2- and β2-adrenoceptors identified on blood platelets and lymphocytes, respectively, are reflecting by preference extra junctional adrenoceptors. Extra junctional adrenoceptors are activated primarily by circulating epinephrine. The high ratio of β2- to α2-adrenoceptors observed in blood cells of fast milking cows might indicate a decreased vasomotor tone in the teat and an increased dilatation of the teat sphincter in these animals.

Nonadrenergic bronchodilation in adult and young guinea pigs

The contribution of the nonadrenergic inhibitory system to airway responses to infusion of 5-hydroxytryptamine (5-HT) was evaluated in anesthetized, tracheotomized, and paralyzed young (13 days) and adult (82 days) guinea pigs. Animals were mechanically ventilated by a constant flow ventilator. Compliance (C) and conductance (G) of the respiratory system were continuously monitored. Three series of experiments were performed involving intravenous pretreatment with 1) atropine (3 mg/kg) and propranolol (1 mg/kg); 2) atropine (3 mg/kg), propranolol (1 mg/kg), and phentolamine (2 mg/kg); and 3) atropine (3 mg/kg) and hexamethonium (2 mg/kg). 5-HT was then intravenously infused for 5 min at a rate of 40 ng.kg-1.s-1 in adults and 60 ng.kg-1.s-1 in young guinea pigs to obtain the same degree of bronchoconstriction in both groups. At the 3rd min of the infusion, bilateral cervical vagotomy was performed and C and G were measured at the maximal response, 1-2 min thereafter. Vagotomy increased bronchoconstriction (P less than 0.01) in both young animals and adults. Phentolamine did not modify this increase, but hexamethonium completely inhibited it. These results indicate that, in adult and young guinea pigs, 5-HT infusion induces reflex activation of the nonadrenergic inhibitory system, which in turn modulates the bronchoconstrictor responses to 5-HT. This neural modulation is not mediated by an alpha-adrenergic pathway.

Ventilatory control during exercise in children with mild or moderate asthma

The aim of this study was to specify whether during exercise the neural response to increased resistive load in asthmatic children corresponds to a modification of the neuromuscular inspiratory drive, to a modification of the breathing pattern, or to both. Thus, nine children with mild or moderate asthma (aged 10-15 yr) and nine normal children (aged 11-16 yr) were studied during an incremental load exercise with a cyclic ergometer, the load of which was increased by steps of 30 W.3 min-1. During the 3rd min of each workload, we measured the following parameters: O2 consumption (VO2), CO2 production (VCO2), ventilation (VE), tidal volume (VT), respiratory frequency (f), ratio of inspiratory to total time of respiratory cycle (T1/TTOT), mean inspiratory flow (VT/T1) as well as mouth occlusion pressure measured at 100 ms (P0.1), and inspiratory power for breathing (W). At maximum level, the two groups showed identical values for heart rate, ventilation divided by weight (VEBW), T1/TTOT), VT/T1, P0.1, and W. However, asthmatic children had lower maximal power (P less than 0.02), higher tidal volume divided by weight (VTBW) (P less than 0.05), and lower f (P less than 0.01). At a same level of exercise (60, 90, or 120 W), in both groups, we found identical values for P0.1, VEBW, VO2, T1/TTOT, and VTBW/T1. However, asthmatic patients exhibited higher VTBW and lower f(limit of significance). This resulted from higher inspiratory and total time durations. Furthermore, they showed a higher inspiratory power for breathing. It was the same for f and VTBW if the results were expressed in relation to the VO2 in ml.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Wheelchair racing

Effects of different hand rim diameters in wheelchair racing were studied with respect to physiological and technique parameters at five speed levels (N = 8 wheelchair sportsmen). In each of five subsequent 15-min exercise tests on a treadmill, a different sized hand rim was mounted to the rear wheels (0.3, 0.35, 0.38, 0.47, 0.56 m). In each test, speed increased with 0.83 m.s-1 every 3 min, starting at 0.83 m.s-1 and ranging up to 4.17 m.s-1 (slope: 0.5 degrees). Cardiorespiratory responses (ventilation, oxygen cost, heart rate, respiratory exchange ratio, mechanical efficiency) and timing data (cycle time, push time, recovery time, push angle, and work per cycle) were obtained every 3rd min, together with the movement pattern of trunk and arm segments. Clear effects of rim diameter and speed were seen for the physiological parameters (P less than 0.05). In physiological terms, D5 appeared the least beneficial, followed by D4. Moreover, increasing rim diameter had a significant effect on movement pattern of the upper arm in the sagittal as well the frontal plane of motion. However, no timing effects were seen with changing rim diameter. On the other hand, timing parameters varied markedly with speed, whereas the segmental excursions of the upper limb did not show a "speed-effect". In general, small hand rims show lower cardiorespiratory responses. This may be related to the decreased segmental excursions of the upper limb and the lower linear hand velocity. Together with a low rolling and air drag, heart rate, and oxygen cost, these are important prerequisites in racing events.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular response during upright isometric dead lift in young, older, and elderly healthy men.

Isometric exercises raise the mean arterial blood pressure and impose serious stress on left ventricular function. It may be more dangerous for older than for younger people. The effect of aging on blood pressure response was studied in 75 subjects, 25 normal young men aged 25 +/- 4 years, 25 older men aged 51 +/- 3.2 years, and 25 elderly men aged 68 +/- 4 years, during upright isometric dead lift at 30% maximal voluntary effort for 3 min. The heart rate, systolic blood pressure, and diastolic blood pressure were measured during the 3rd min of dead lift contraction. Tension exerted was significantly lower in the older group (33 +/- 4 kg) and lowest in the elderly group (26.9 +/- 6 kg) compared with the young group (43 +/- 8 kg). All groups showed similar and significant increases in heart rate, systolic and diastolic blood pressure during dead lift (p less than 0.01). These data indicate a similar pattern of blood pressure response to acute pressure overload in young, older, and elderly normal men.

Delayed appearance of blood lactate with reduced frequency breathing during exercise.

The purpose of the present study was to investigate the blood lactate (LA-) responses to hypoventilation induced by reduced frequency breathing (RFB) during recovery from exercise. Five male subject performed 16 4 min cycling bouts alternating with 16 min rest periods. Exercise intensities were chosen at power outputs corresponding to 30% VO2max at 2 mMLA-, VO2 at 4 mMLA-, and 90% VO2max in each subject. Breathing frequency was voluntarily controlled starting 10 s before each 3rd min of exercise and maintained throughout the rest of the exercise period. Four different breathing patterns at each exercise intensity were used: normal breathing (NB), breathing every 4 s, breathing every 8 s, and maximal RFB. Except for the NB trials, subjects held their breath at functional residual capacity during each breathing interval. The concentration difference of LA- between the 3rd min sample and the 4th min sample was defined as the lactate change during exercise (delta LA-ex), and that between the 4th min sample and the sample at the 3rd min after the end of the exercise as the lactate change during recovery (delta LA-rec). An ANOVA showed significant (p less than 0.05) differences in breathing procedures only in delta LA-rec. delta LA-rec seemed to increase as compared to NB only at VO2 at 4 mMLA- and 90% VO2max, while delta LA-ex remained unchanged as compared to NB in spite of reduced VA. These results might indicate that RFB inhibited lactate removal from working muscles during exercise.

Toxicité cardiaque de la bupivacaïne et diazépam. Etude expérimentale chez le chien anesthésié

The use of diazepam has been suggested for the treatment of convulsions resulting from accidental high plasma levels of local anaesthetics. However, it has been reported that this drug may increase the cardiac effects of bupivacaine in dogs. The present study aimed to assess the effects of diazepam on the electrophysiological signs of a high-dose intravenous bolus of bupivacaine in fourteen dogs, divided into two groups, and anaesthetized with thiopentone and ventilated. All the animals were given a bolus dose of 4 mg · kg −1 bupivacaine. Immediately afterwards, group I (n = 7) received 0.8 ml · kg −1 normal saline solution and group II (n = 7) was given 4 mg · kg −1 diazepam over 1 min. The parameters measured on lead II of the electrocardiogram were : cycle length (R-R interval), QRS length (QRS) and QT interval corrected for heart rate (cQT). Intranodal (AH) and His-Purkinje (HV) conduction times were measured with recording bipolar stimulation electrodes (USCI 6F). Mean aortic pressure (P̄ao) was measured via a femoral arterial line. In the two groups, the parameters were recorded before and 2, 5, 10 and 15 min after the bupivacaine bolus. Arterial blood samples for measurement of bupivacaine and diazepam serum levels were obtained before and 3, 15 and 30 min after the bupivacaine bolus. There was no significant difference between the two groups in the electrophysiological or haemodynamic parameters at any time. However, the increase in HV and QRS length was a little higher in group I than in group II. The administration of diazepam after bupivacaine resulted in lower serum levels of local anaesthetic : 5.1 ± 0,5 vs 7.6 ± 1.4 μg · ml −1 (p < 0.01) at the 3rd min, and 2.14 ± 0.03 vs 3.0 ± 0.4 μg · ml −1 (p < 0.02) at the 5th min. No pharmacokinetic explanation could be found to explain these results that do not confirm previous studies. It was concluded that high doses of diazepam did not increase cardiac electrophysiological or haemodynamic effects of high plasma levels of bupivacaine.

Effects of hypoxia on lung mechanics in the newborn cat.

The present study was designed to investigate the effects of hypoxia on lung mechanics in the newborn cat and to determine if vagal efferent innervation to the airways is involved in the response. We studied 11 animals, aged 2-7 days, anesthetized with a mixture of chloralose-urethane administered intraperitoneally. A tracheal cannula was inserted just below the larynx and following paralysis (pancuronium bromide), mechanical ventilation was initiated. A pneumothorax was created by a midline thoracotomy and an end-expiratory load was applied to maintain functional residual capacity. Animals were placed in a flow plethysmograph from which measurements of transpulmonary pressure, flow, and volume, mean inspiratory resistance, and dynamic compliance of the lung were calculated. The experimental protocol consisted of a series of 8-min trials, each preceded by a controlled volume history. The hypoxia challenge was composed of 1 min of ventilation with 40% O2, followed by 5 min exposure to 10% O2 and 2 min of recovery. In the majority of animals (7 out of 11), hypoxia had no effect on lung mechanics compared with control trials. Four animals responded to hypoxia with an increase in resistance and a decrease in compliance. Resistance remained elevated throughout the hypoxia with an average maximal increase of 47.2 +/- 22.2% (SD). Dynamic compliance was significantly decreased at the 2nd, 3rd, and 4th min only of hypoxia. Bilateral vagotomy abolished the response in the four animals and hypoxia had no effect on mechanics postvagotomy. Our data suggest that in most cases changes in lung mechanics do not play a causal role in the biphasic ventilatory response to hypoxia seen in the newborn.

Insulin and C-peptide secretory responses to glucagon in man: studies on the dose-response relationships.

The present study investigated the insulin and C-peptide secretory responses to glucagon in non-diabetic humans. Glucagon induced a transient increase in plasma insulin and C-peptide concentrations. At the dose level of 0.5 mg, glucagon elicited more efficient responses than at the dose level of 0.25 mg (p less than 0.05). However, the responses were not further potentiated by glucagon at 1.0 mg. Plasma glucose levels did not change during the first 2 min after glucagon injection, when already a marked increase in plasma insulin and C-peptide levels were observed. Thereafter, however, plasma glucose levels increased, to be maximal at 20 min after glucagon injection. Calculations of the minute-to-minute increase of plasma insulin and C-peptide levels revealed that plasma insulin levels increased by 32 +/- 7% of the increase in plasma C-peptide levels during the first 2 min, and by 36 +/- 6% of the increase in plasma C-peptide levels during the 3rd and 4th min after injection; the difference being the liver extraction of insulin. We conclude from this study in man that glucagon stimulates insulin secretion through both direct and indirect effects, that following glucagon injection, approximately 65% of the secreted insulin is extracted by the liver, and that the dose level of 0.5 mg glucagon is the optimal dose level for the stimulation of insulin secretion.

Relationship Between Milkability and Adrenoceptor Concentrations in Teat Tissue in Primiparous Cows

Milking characteristics were measured on 19 primiparous cows of the Red Pied breed at morning milkings. Measurements included maximum and average rate of flow, yield of milk through the 1st, 2nd, and 3rd min, amount of milk through the first 2 and first 3min of milking, and milking time. Subsequently cows were slaughtered and teats immediately removed. Adrenoceptors on membranes isolated from teat tissue were identified by radiolabeled antagonists: [3H]dihydroalprenolol for β2 -adrenoceptors, [3H] rauwolscine for α2 -adrenoceptors, and [3 H] prazosin for α2 -adrenoceptors.Measurements of milking characteristics were highly repeatable within cow. Cows showed five distinct and significantly different milk flow patterns, which were characteristic for fast (type I, II), relatively fast (type III), and slow (type IV, V) milking cows. Covariance analysis for the five different types revealed an average regression between α2 -adrenoceptor density and milking rate 1st min as well as between β2 :α2-adrenoceptor ratios and milking rate 2nd min and milking time.A hypothesis is presented to explain these observations. During milking, tone of efferent sympathetic nerves in the teat is low. This phenomenon is more pronounced in fast milking cows. The typical presynaptic adrenoceptor pattern in the teat of fast milkers (low β2 :α2-adrenoceptor ratio) results in a decline of norepinephrine release by feedback mechanisms.