Effect of breathing of a helium-oxygen mixture on the adaptation of the organism to exercise

The reported investigations were carried out on 17 healthy men aged 20-27 years subjected to a 15 minute submaximal exercise on an Elema-Schonander cycle ergometer while breathing ambient air or a helium-oxygen mixture (O2 20% and He 80%). During the exercise test the heart rate was recorded from the ECG tracings, with the respiratory rate and respiratory volume, minute ventilation and arterial blood pressure. The concentrations of lactate (LA), pyruvate (PA) and glucose were determined in the serum of venous blood obtained before and 3 minutes after the exercise. Favourable changes of the reaction of the organism to exercise were observed while the subjects breathed the helium-oxygen mixture. The minute ventilation increased owing to increased respiratory volume, and the exercise caused lower rises in LA, PA and the LA/PA ratio. This may suggest a reduction of respiration cost and a decrease of anaerobic metabolism under these conditions.     

Effects of low-intensity resistance exercise under acute systemic hypoxia on hormonal responses

Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p ≤ 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p ≤ 0.05). The GH significantly increased only after the HR trial (p ≤ 0.05). The NE and testosterone significantly increased after the exercises in both trials (p ≤ 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season.     

Effects of PDH activation by dichloroacetate in human skeletal muscle during exercise in hypoxia

During the onset of exercise in hypoxia, the increased lactate accumulation is associated with a delayed activation of pyruvate dehydrogenase (PDH; Parolin ML, Spreit LL, Hultman E, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Am J Physiol Endocrinol Metab 278: E522-E534, 2000). The present study investigated whether activation of PDH with dichloroacetate (DCA) before exercise would reduce lactate accumulation during exercise in acute hypoxia by increasing oxidative phosphorylation. Six subjects cycled on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake after a saline (control) or DCA infusion while breathing 11% O(2). Muscle biopsies of the vastus lateralis were taken at rest and after 1 and 15 min of exercise. DCA increased PDH activity at rest and at 1 min of exercise, resulting in increased acetyl-CoA concentration and acetylcarnitine concentration at rest and at 1 min. In the first minute of exercise, there was a trend toward a lower phosphocreatine (PCr) breakdown with DCA compared with control. Glycogenolysis was lower with DCA, resulting in reduced lactate concentration ([lactate]), despite similar phosphorylase a mole fractions and posttransformational regulators. During the subsequent 14 min of exercise, PDH activity was similar, whereas PCr breakdown and muscle [lactate] were reduced with DCA. Glycogenolysis was lower with DCA, despite similar mole fractions of phosphorylase a, and was due to reduced posttransformational regulators. The results from the present study support the hypothesis that lactate production is due in part to metabolic inertia and cannot solely be explained by an oxygen limitation, even under conditions of acute hypoxia.     

Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O(2) (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free P(i), in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDH(a)) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [P(i)]. At the end of exercise, PDH(a) was greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.     

Hypoxic initiation of pulmonary hypertension is mediated by serotonin secretion from neuroepithelial bodies in chemodenervated dogs

The purpose of this study was to investigate the stimulatory effect of hypoxia on the secretion of serotonin by neuroepithelial bodies (NEB) as well as to determine the relation between its level and changes in pulmonary arterial pressure (PAP) and also to determinate the effect of serotonin antagonists (pizotifen and methysergide) on the responses of pulmonary and systemic arterial pressures. The experiments were carried out in peripheral chemoreceptor-denervated dogs anesthetized with Na penthabarbital (30 mg/kg i.v.). On the breathing of normoxic and hypoxic (7% O2-93% N2) gas mixtures and on the injection of KCN (80 microg/kg i.v.), PAP, systemic arterial blood pressure (BP), tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) were determined. Also PAP and BP were recorded before and after the injection of pizotifen (0.5 mg/kg i.v.) and methysergide (1 mg/kg i.v.) during normoxic or hypoxic gas mixture breathing. At the end of each experimantal phase, serotonin level, PaO2, PaCO2 and pHa values in blood samples obtained from left ventricle and femoral artery were determined. On the breathing of the hypoxic gas mixture of the chemodenervated dogs, VT, VE and BP significantly decreased (P < 0.001, P < 0.001, P < 0.01). The mean value of PAP and serotonin levels (ventricular and femoral) were found significantly increased when compared with the corresponding normoxic values (P < 0.001, P < 0.05). On the other hand, injection of KCN produced no significant changes in PAP, serotonin levels, BP and respiratory parameters. After the injection of pizotifen, PAP was significantly increased in hypoxia (P < 0.01). After the injection of methysergide, the response of PAP was completely abolished during the breathing of hypoxic gas mixture. The finding of the abolition of response of PAP to hypoxia after the injection of methysergide indicates that serotonin release from NEB may be responsible for the elevation of PAP in hypoxic hypoxia.     

Effect of breathing an oxygen-helium mixture under positive pressure on biochemical parameters

In 35 subjects the effect of breathing an oxygen-helium mixture or oxygen during 10 minutes under positive pressure of 40 hPa was studied. Immediately before positive-pressure breathing, in the last minute of this breathing, and 30 minutes after its and blood samples were taken for investigations. Positive-pressure breathing caused in both groups a rise-in the haematocrit value, total protein, albumin and glucose levels. The level of lactic acid rose during breathing oxygen by 74% and that of pyruvic acid increased by 44%, while during the use of the oxygen-helium mixture both these compounds failed to rise during positive-pressure breathing and 30 minutes after its completion.     

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.     

Metabolic effects of exposure to hypoxia plus cold at rest and during exercise in humans

To determine effects on metabolic responses, subjects were exposed to four environmental conditions for 90 min at rest followed by 30 min of exercise: breathing room air with an ambient temperature of 25 degrees C (NN); breathing room air with an ambient temperature of 8 degrees C (NC); hypoxia (induced by breathing 12% O2 in N2) with a neutral temperature (HN); and hypoxia in the cold (HC). Hypoxia increased heart rate (HR), systolic blood pressure (SBP), pulmonary ventilation (VE), respiratory exchange ratio (R), blood lactate, and perceived exertion during exercise while depressing rectal temperature (Tre) and O2 uptake (VO2). Cold exposure elevated SBP, diastolic blood pressure (DBP), VE, VO2, blood glucose, and blood glycerol but decreased HR, Tre, and R. Shivering and DBP were higher and Tre was lower in HC compared with NC. HR, SBP, VE, R, and lactate tended to be higher in HC compared with NC, whereas VO2 and blood glycerol tended to be depressed. These results suggest that cold exposure during hypoxia results in an increased reliance on shivering for thermogenesis at rest whereas, during exercise, heat loss is accelerated.     

Slow Breathing and Hypoxic Challenge: Cardiorespiratory Consequences and Their Central Neural Substrates

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O₂) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.     

Pulmonary gas exchange in humans during normobaric hypoxic exercise

Previous studies (J. Appl. Physiol. 58: 978-988 and 989-995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation of the breathing pattern structure in competitive exercises of kettlebell lifters

The goal of the research was to determine the characteristics of the breathing pattern in kettlebell lifters. The following main indicators of external respiration were recorded during exercise performance: respiratory rate (RR, f), tidal volume (TV, V _T ), and respiratory minute volume (RMV, V _E ). The dependence of these parameters on the qualification of athletes and competitive exercise intensity was estimated. An SMP-21/01-“R-D” spirograph was used for qualitative and quantitative assessment of the main indicators of breathing patterns in kettlebell lifters. The characteristic changes in breathing of masters of sports (MS) and candidate masters of sport (CMS) were shown mainly for the three parameters, respiratory rate and tidal volume, as well as in the number of breathing cycles per cycle of exercise. Respiratory rate increases and tidal volume decreases at a high-intensity exercise. In international masters of sports (MSIC), the number of breathing cycles per cycle of competitive exercise and, consequently, respiratory rate remain constant independent of physical load. They show the predominance of only one index, tidal volume, which increases from 0.7 ± 0.1 L to 1.2 ± 0.1 L (p < 0.01) with increasing intensity of exercise. We have found transitional forms of breathing patterns in the competitive exercises of kettlebell lifting. The results lay the basis for the development of a novel concept of training and improvement of breathing technique in kettlebell lifting.     

运动酸碱失衡恢复过程影响因素的研究

本研究对不同水平运动员在４００ｍ和１５００ｍ跑前及跑后恢复期中进行了摄氧量（ＶＯ２）、心输出量（ＣＯ）、血乳酸浓度（ＬＡ）和血气指标的测定,其目的是探讨影响运动酸碱失衡恢复快慢的主要因素。结果显示：１．不同水平运动员血液缓冲能力及运动后１５ｍｉｎ酸碱失衡恢复无显著差异（Ｐ＞０．０５）,但他们运动后ＬＡ和ｐＨ有显著差异（Ｐ＜０．０５）。这提示ＬＡ和ＰＨ变动的多少不是由血液缓冲能力的强弱所致,ＬＡ上升越少则酸碱失衡恢复过程越短。２．较高水平运动员心肺机能动员快,潜力大,与一般水平运动员有显著差异（Ｐ＜０．０５）。心肺机能的强弱一方面对运动中ＬＡ生成的多少有影响,另一方面与ＬＡ缓冲能否顺利进行有关。因此它对运动酸碱失衡恢复的快慢起着重要的作用。     

Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux during steady-state exercise

The aim of this study was to determine whether the decreased muscle and blood lactate during exercise with hyperoxia (60% inspired O2) vs. room air is due to decreased muscle glycogenolysis, leading to decreased pyruvate and lactate production and efflux. We measured pyruvate oxidation via PDH, muscle pyruvate and lactate accumulation, and lactate and pyruvate efflux to estimate total pyruvate and lactate production during exercise. We hypothesized that 60% O2 would decrease muscle glycogenolysis, resulting in decreased pyruvate and lactate contents, leading to decreased muscle pyruvate and lactate release with no change in PDH activity. Seven active male subjects cycled for 40 min at 70% VO2 peak on two occasions when breathing 21 or 60% O2. Arterial and femoral venous blood samples and blood flow measurements were obtained throughout exercise, and muscle biopsies were taken at rest and after 10, 20, and 40 min of exercise. Hyperoxia had no effect on leg O2 delivery, O2 uptake, or RQ during exercise. Muscle glycogenolysis was reduced by 16% with hyperoxia (267 +/- 19 vs. 317 +/- 21 mmol/kg dry wt), translating into a significant, 15% reduction in total pyruvate production over the 40-min exercise period. Decreased pyruvate production during hyperoxia had no effect on PDH activity (pyruvate oxidation) but significantly decreased lactate accumulation (60%: 22.6 +/- 6.4 vs. 21%: 31.3 +/- 8.7 mmol/kg dry wt), lactate efflux, and total lactate production over 40 min of cycling. Decreased glycogenolysis in hyperoxia was related to an approximately 44% lower epinephrine concentration and an attenuated accumulation of potent phosphorylase activators ADPf and AMPf during exercise. Greater phosphorylation potential during hyperoxia was related to a significantly diminished rate of PCr utilization. The tighter metabolic match between pyruvate production and oxidation resulted in a decrease in total lactate production and efflux over 40 min of exercise during hyperoxia.     

Effects of expiratory threshold loading during steady-state exercise.

Increases in functional residual capacity (FRC) decrease inspiratory muscle efficiency; the present experiments were designed to determine the effect of FRC change on the ventilatory response to exercise. Six well-trained adults were exposed to expiratory threshold loads (ETL) ranging from 5 to 40 cmH2O during steady-state exercise on a bicycle ergometer at 40-95% VO2max. Inspiratory capacity (IC) was measured and changes of IC interpreted as changes of FRC. ETL did not consistently limit exercise performance. At heavy work (greater than 92% VO2max) minute ventilation decreased with increasing ETL; at moderate work (less than 58% VO2max) it did not. Decreases in ventilation were due to decreases in respiratory frequency with prolongation of the duration of expiration being the most consistent change in breathing pattern. At moderate work levels, FRC increased with ETL; at maximum work it did not. Changes in FRC were dictated by constancy of tidal volume and a fixed maximum end-inspiratory volume of 80-90% of the inspiratory capacity. When tidal volume was such that end-inspiratory volume was less than this value, FRC increased with ETL. Mouth pressure measured during the first 0-1 s of inspiratory effort against an occluded airway (P0-1) was increased by ETL equals 30 cmH2O, in spite of the fact that ventilation was decreased. We concluded that changes in FRC due to ETL had no effect on the ventilatory response to exercise and that changes in P0-1 induced by ETL did not reflect changes of inspiratory drive so much as changes of the pattern of inspiration.     

Does an acute COPD crisis modify the cardiorespiratory and ventilatory adjustments to exercise in horses?

The present study was conducted to understandbetter the mechanisms leading to the decrease in exercise capacityobserved in horses suffering from chronic obstructive pulmonary disease (COPD). Five COPD horses were submitted to a standardized submaximal treadmill exercise test while they were in clinical remission or inacute crisis. Respiratory airflow,O₂ andCO₂ fractions in the respired gas,pleural pressure changes and heart rate were recorded, and arterial andmixed venous blood were analyzed for gas tensions, hemoglobin, andplasma lactate concentrations. O₂ consumption, CO₂ production,expired minute ventilation, tidal volume, alveolar ventilation, cardiacoutput, total pulmonary resistance, and mechanical work of breathingwere calculated. The results showed that, whensubmaximally exercised, COPD horses in crisis were significantly morehypoxemic and hypercapnic and that their total pulmonary resistance andmechanical work of breathing were significantly higher and theirexpired minute ventilation significantly lower than when they were inremission. However, their O₂consumption remained unchanged, which was probably due to theoccurrence of compensatory mechanisms, i.e., higher heart rate, cardiacoutput, and hemoglobin concentration. Last, their net anaerobicmetabolism seemed to be more important.

     

Changes in HIF-1α protein, pyruvate dehydrogenase phosphorylation, and activity with exercise in acute and chronic hypoxia

Exercise under acute hypoxia elicits a large increase in blood lactate concentration ([La](b)) compared with normoxic exercise. However, several studies in humans show that with the transition to chronic hypoxia, exercise [La](b) returns to normoxic levels. Although extensively examined over the last decades, the muscle-specific mechanisms responsible for this phenomenon remain unknown. To assess the changes in skeletal muscle associated with a transition from acute to chronic hypoxia, CD-1 mice were exposed for 24 h (24H), 1 wk (1WH), or 4 wk (4WH) to hypobaric hypoxia (equivalent to 4,300 m), exercised under 12% O(2), and compared with normoxic mice (N) at 21% O(2). Since the enzyme pyruvate dehydrogenase (PDH) plays a major role in the metabolic fate of pyruvate (oxidation vs. lactate production), we assessed the changes in its activity and regulation. Here we report that when run under hypoxia, 24H mice exhibited the highest blood and intramuscular lactate of all groups, while the 1WH group approached N group values. Concomitantly, the 24H group exhibited the lowest PDH activity, associated with a higher phosphorylation (inactive) state of the Ser(232) residue of PDH, a site specific to PDH kinase-1 (PDK1). Furthermore, protein levels of PDK1 and its regulator, the hypoxia inducible factor-1α (HIF-1α), were both elevated in the 24H group compared with N and 1WH groups. Overall, our results point to a novel mechanism in muscle where the HIF-1α pathway is desensitized in the transition from acute to chronic hypoxia, leading to a reestablishment of PDH activity and a reduction in lactate production by the exercising muscles.     

Ventilation and metabolism of the Djungarian hamster (Phodopus sungorus) and the albino mouse

Metabolic rates (O2 consumption and CO2 production) were similar in the Djungarian hamster and the white mice. The Djungarian hamster had a decreased tidal volume, an increased frequency of breathing (due to a lengthened expiratory time) and a decreased minute ventilation compared to that of the mouse. Although the relative ventilatory increase in response to hypercapnia or hypoxia was similar in the hamster and the mouse, the breathing patterns during exposures differed.     

Short-term potentiation of breathing in humans.

The purpose of this study was to determine if the increase in ventilation induced by hypoxic stimulation of the carotid bodies (CB) persists after cessation of the stimulus in humans. I reasoned that a short-term potentiation (STP) of breathing, sometimes called an "afterdischarge," could be unmasked by combining hypoxia with exercise, because ventilation increases synergistically under these conditions. Seven young healthy men performed mild bicycle exercise (30% peak power) while breathing O2 for 1.5 min ("control" state), and their CB were then stimulated by 1.5 min of hypoxic exercise (10% O2--balance N2). CB stimulation was then terminated by changing the inspirate back to O2 as exercise continued. Inspiratory and expiratory duration (TI and TE) and inspiratory flow and its time integral [tidal volume (VT)] were measured with a pneumotachometer. Inspired minute ventilation (VI) and mean inspiratory flow (VT/TI) declined exponentially after the cessation of CB stimulation, with first-order time constants of 28.6 +/- 6.7 and 24.6 +/- 1.6 (SD) s, respectively. The slow decay of VI was due primarily to potentiation of both TI and TE, although the effect on the latter predominated. Additional experiments in six subjects showed that brief intense CB stimulation with four to five breaths of N2 during mild exercise induced STP of similar magnitude to that observed in the hypoxic exercise experiments. Finally, the imposition of hyperoxia during air breathing exercise at a level of respiratory drive similar to that induced by the hypoxic exercise did not change VI significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breathing and lung mechanics in hamsters: effect of pentobarbital anesthesia

An adaptation of the method reported by Skornik, Heimann, and Jaeger (Toxicol. Appl. Pharmacol. 59: 314-323, 1981) was used to evaluate pulmonary mechanics in intact awake hamsters. Lung volume changes were measured with a pressure plethysmograph, and pleural pressure was estimated by the use of a saline-filled esophageal catheter. We report data for normal awake hamsters studied at 18, 20, 22, 32, and 98 wk of age. Age-related differences were observed in tidal volume, dynamic compliance, and pulmonary resistance. To determine to what extent pulmonary mechanics are changed by anesthesia, hamsters were measured during spontaneous breathing while awake and while anesthetized. We found that anesthesia had a marked effect on the breathing pattern of normal hamsters. Twenty-five minutes after injection of pentobarbital sodium (70 mg/kg ip), tidal volume, dynamic compliance, pulmonary resistance, breathing frequency, and minute ventilation were 66, 40, 375, 60, and 41% of the corresponding awake values. Anesthesia always provoked a significant and dose-related decrease in tidal volume and an increase in respiratory period, together resulting in a profound decrease in minute ventilation. These significant differences from the awake values call into question the value of measurements in anesthetized animals. The methods described here yield reasonable and repeatable measurements and, because no anesthesia or surgery is required, they can be used in longitudinal studies when repeated measurements in the same animal over long periods of time can help define pathological changes or the effectiveness of various interventions.     

Effect of verapamil on ventilation and chemical control of breathing in anesthetized rats

The calcium channel blocker, verapamil (0.1-1.0 mg/kg, i.v.) was administered to anesthetized rats to determine its effects on ventilation and on ventilatory responses to hypoxia and CO2. Verapamil produced a dose-dependent increase in tidal volume (VT) and a decrease in respiration rate (f). The bradypnea due to verapamil was characterized by an increase in expiratory duration (TE) and no change of inspiratory duration (TI). Verapamil produced similar changes in VT and f in vagotomized rats. The increase in respiration rate and minute volume due to hypoxia were inhibited by verapamil (0.5 and 1.0 mg/kg) but the increase in tidal volume due to hypoxia was depressed only with the 1.0 mg/kg dose. On the other hand, the increase in VT due to breathing CO2 was not changed by verapamil (0.1-1.0 mg/kg), but depression of the respiratory frequency response to CO2 occurred with 1.0 mg/kg of verapamil. These results indicate that verapamil produced slow, deep breathing and these responses were not mediated by vagal mechanisms. Ventilatory responses to hypoxia were depressed by verapamil. However, since the calcium blocker demonstrated no effect on the VT-CO2 relationship, verapamil did not change ventilatory chemosensitivity to CO2. The data also suggest that mechanisms governing the control of respiratory frequency are more sensitive to verapamil than tidal volume responses.