Increase In Carbon Dioxide Tension Research Articles

Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis.

Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. The aim of this study was to systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness.PubMed, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible.We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in carbon dioxide tension (0.27 kPa, 95% CI 0.08-0.45 kPa,) and no significant change in oxygen tension and oxygen saturation (both p>0.05). Nonserious respiratory depression (definition variable/not stated) was described in four out of 1064 patients. One cancer patient pretreated with morphine for pain needed temporary respiratory support following nebulised morphine for breathlessness (single case study).We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed.

Cerebral vasomotor reactivity: steady-state versus transient changes in carbon dioxide tension.

New FindingsWhat is the central question of this study?The relationship between changes in cerebral blood flow and arterial carbon dioxide tension is used to assess cerebrovascular function. Hypercapnia is generally evoked by two methods, i.e. steady-state and transient increases in carbon dioxide tension. In some cases, the hypercapnia is immediately preceded by a period of hypocapnia. It is unknown whether the cerebrovascular response differs between these methods and whether a period of hypocapnia blunts the subsequent response to hypercapnia.What is the main finding and its importance?The cerebrovascular response is similar between steady-state and transient hypercapnia. However, hyperventilation-induced hypocapnia attenuates the cerebral vasodilatory responses during a subsequent period of rebreathing-induced hypercapnia.Cerebral vasomotor reactivity (CVMR) to changes in arterial carbon dioxide tension () is assessed during steady-state or transient changes in . This study tested the following two hypotheses: (i) that CVMR during steady-state changes differs from that during transient changes in ; and (ii) that CVMR during rebreathing-induced hypercapnia would be blunted when preceded by a period of hyperventilation. For each hypothesis, end-tidal carbon dioxide tension () middle cerebral artery blood velocity (CBFV), cerebrovascular conductance index (CVCI; CBFV/mean arterial pressure) and CVMR (slope of the linear regression between changes in CBFV and CVCI versus ) were assessed in eight individuals. To address the first hypothesis, measurements were made during the following two conditions (randomized): (i) steady-state increases in of 5 and 10 Torr above baseline; and (ii) rebreathing-induced transient breath-by-breath increases in . The linear regression for CBFV versus (P = 0.65) and CVCI versus (P = 0.44) was similar between methods; however, individual variability in CBFV or CVCI responses existed among subjects. To address the second hypothesis, the same measurements were made during the following two conditions (randomized): (i) immediately following a brief period of hypocapnia induced by hyperventilation for 1 min followed by rebreathing; and (ii) during rebreathing only. The slope of the linear regression for CBFV versus (P < 0.01) and CVCI versus (P < 0.01) was reduced during hyperventilation plus rebreathing relative to rebreathing only. These results indicate that cerebral vasomotor reactivity to changes in is similar regardless of the employed methodology to induce changes in and that hyperventilation-induced hypocapnia attenuates the cerebral vasodilatory responses during a subsequent period of rebreathing-induced hypercapnia.

Instability of the Middle Cerebral Artery Blood Flow in Response to CO2

BackgroundThe middle cerebral artery supplies long end-artery branches to perfuse the deep white matter and shorter peripheral branches to perfuse cortical and subcortical tissues. A generalized vasodilatory stimulus such as carbon dioxide not only results in an increase in flow to these various tissue beds but also redistribution among them. We employed a fast step increase in carbon dioxide to detect the dynamics of the cerebral blood flow response.Methodology/Principal FindingsThe study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. We used transcranial ultrasound to measure the time course of middle cerebral artery blood flow velocity in 28 healthy adults. Normoxic, isoxic step increases in arterial carbon dioxide tension of 10 mmHg from both hypocapnic and normocapnic baselines were produced using a new prospective targeting system that enabled a more rapid step change than has been previously achievable. In most of the 28 subjects the responses at both carbon dioxide ranges were characterised by more complex responses than a single exponential rise. Most responses were characterised by a fast initial response which then declined rapidly to a nadir, followed by a slower secondary response, with some showing oscillations before stabilising.Conclusions/SignificanceA rapid step increase in carbon dioxide tension is capable of inducing instability in the cerebral blood flow control system. These dynamic aspects of the cerebral blood flow responses to rapid changes in carbon dioxide must be taken into account when using transcranial blood flow velocity in a single artery segment to measure cerebrovascular reactivity.

Prolonged spiking in the Emfit sensor in patients with sleep-disordered breathing is characterized by increase in transcutaneous carbon dioxide

A phenomenon of prolonged spiking in movement sensors, such as static-charge-sensitive bed or Emfit (electromechanical film) sensors, has been connected to an increase in carbon dioxide tension in wakefulness. Spiking is also a common finding in sleep studies. This made us hypothesize that carbon dioxide changes might also happen in sleep during prolonged spiking episodes in Emfit sheet. We examined four different kinds of breathing pattern episodes: normal breathing, episodes of repetitive apnea, episodes of repetitive hypopnea and episodes with prolonged spiking lasting at least 3 min. One hundred and fifteen episodes from 19 polysomnograms were finally admitted to the study according to the protocol. The changes in the transcutaneous carbon dioxide tension (TcCO2) were defined for different breathing patterns. During prolonged spiking episodes the TcCO2 increased significantly and differed statistically from the TcCO2 changes of normal breathing and periodic breathing patterns (episodes of apnea and hypopnea). The rise in TcCO2 during prolonged spiking episodes might suggest that prolonged spiking is representing another type of breathing disturbance during sleep differing from periodic breathing patterns. The Emfit sensor as a small, flexible and non-invasive sensor might provide useful additional information about breathing during sleep.

Effect of hypobaric hypoxia on blood gases in patients with restrictive lung disease.

Several publications have reported effects of hypobaric conditions in patients with chronic obstructive pulmonary disease. To the current authors' knowledge, similar studies concerning patients with restrictive lung disease have not been published. The effect of simulated air travel in a hypobaric chamber on arterial blood gases, blood pressure, and cardiac frequency during rest and 20 W exercise, and the response to supplementary oxygen in 17 patients with chronic restrictive ventilatory impairment has been investigated. Resting oxygen tension in arterial blood (Pa,O2) decreased from 10.4+/-1.6 kPa at sea level to 6.5+/-1.1 kPa at 2,438 m simulated altitude, and decreased further during light exercise in all patients (5.1+/-0.9 kPa). Pa,O2 at this altitude correlated positively with sea-level Pa,O2 and transfer factor of the lung for carbon monoxide (TL,CO), and negatively with carbon dioxide tension in arterial blood (Pa,CO2). Pa,O2 increased to acceptable levels with an O2 supply of 2 L x min(-1) at rest and 4 L x min(-1) during 20 W exercise. In conclusion, most of the patients with restrictive ventilatory impairment developed hypoxaemia below the recommended levels of in-flight oxygen tension in arterial blood during simulated air travel. Light exercise aggravated the hypoxaemia. Acceptable levels of oxygen tension in arterial blood, with only a minor increase in carbon dioxide tension in arterial blood, were obtained by supplementary oxygen.

Role of the splanchnic circulation in acid-base balance during cardiopulmonary bypass.

The role of the splanchnic circulation in the development of the metabolic acidosis of cardiopulmonary bypass (CPB) is not fully understood. New quantitative methods of acid-base balance now offer the ability to define this phenomenon more accurately. Accordingly, we studied acid-base changes across the splanchnic circulation during CPB and defined and quantified the factors that contributed to acid-base balance. Prospective cohort study. Tertiary institution. Ten patients undergoing CPB for coronary artery bypass surgery. Sampling of arterial and hepatic venous blood at four time intervals: postinduction, on CPB during cooling and rewarming, and at skin closure. Measurement of serum Na+, K+, Mg++, Ca++, Cl-, HCO3-, and phosphate concentrations, arterial and hepatic venous blood gases and serum albumin, and lactate and pyruvate concentrations at each collection point. Analysis of findings according to quantitative physicochemical principles. All patients developed a mild metabolic acidosis with a decrease in median serum bicarbonate concentration from 24.97 mEq/L after induction to 22.29 mEq/L at cooling and 22.23 mEq/L at rewarming (p < .05). Before CPB, the pH decreased by 0.0275 (p < .05) across the splanchnic circulation, representing an increase of 2.26 nmol/L of hydrogen ions. Nevertheless, the splanchnic circulation induced a metabolic alkalosis, with a median transsplanchnic increase in the base excess of 1.50 mEq/L (p < .05). This change was largely due to a decrease in serum chloride and lactate concentration across the splanchnic circulation (p < .05). The acidifying effect of the splanchnic circulation was therefore the result of cell respiration with a median increase in carbon dioxide tension of 5.75 mm Hg (p < .05), causing the strong ion difference effective to increase by 1.94 mEq/L (p < .05). There were no other anions or acids added to the circulation by splanchnic organs (no change in strong ion gap). During and after CPB the splanchnic metabolic alkalinizing effect continued and the respiratory acidifying effect was reduced. This caused the splanchnic circulation to be pH neutral at these times. Using quantitative biophysical methods it can be demonstrated that the splanchnic circulation does not contribute to the metabolic acidosis of CPB, and that it continues to have a metabolic alkalinizing effect involving significant lactate extraction. However, its respiratory acidifying effect continues, although at a reduced rate.

Changes in blood-gas tensions during apnoeic oxygenation in paediatric patients

We report changes in arterial blood-gas tensions for up to 5 min of apnoeic oxygenation in 26 anaesthetized paediatric patients (21 children, five infants). Changes in oxygen and carbon dioxide tension were greatest in the first minute of apnoeic oxygenation. In subsequent minutes, rates of change in gas tension were approximately constant. The rate of decline in oxygen tension (31 (95% confidence interval (CI) 20.1-42.2) mm Hg min-1) was more than three times that reported in studies in adults. The rate of increase in carbon dioxide tension (4.2 (95% CI 3.7-4.7) mm Hg min-1) was similar to that reported in adults. After successful preoxygenation, oxygen tension remained greater than 290 mm Hg in all children (age > 1 yr) throughout the study. This was not the case in infants. We found no correlation between changes in blood-gas tensions and age or weight of patients. The small number of infants studied showed rapid decreases in oxygen tension which if sustained would be expected to limit the safe duration of apnoeic oxygenation, unlike adults where apnoeic oxygenation is limited by hypercapnia. Extrapolation of our results suggests that when preoxygenation has been successful, apnoeic oxygenation could continue safely in children for at least 10 min. Infants may become hypoxic after only 2 min.

Hereditarily elongated carotid sinus nerve in a rat colony

A specific colony of Wistar rats was found in which the common carotid artery bifurcates at an unusually caudal position, thereby the carotid sinus nerve that originates from the bifurcation is elongated. The present study was done to determine whether this elongated nerve carries baro- and chemosensations in the same manner as the carotid sinus nerve of conventional rats or of other species. In chloralose-urethane anesthetized rats of this specific colony, the afferent discharges were recorded from the elongated carotid sinus nerve in response to a phenylephrine-induced rise in blood pressure and a fall in oxygen tension, as well as an increase in carbon dioxide tension in the respiratory gas. Reflex effects of electrical stimulation of the nerve were also examined. In nerve recording, the afferent discharges of the elongated carotid sinus nerve were increased by any of the perturbations, hypertensive, hypoxic or hypercapnic. Electrical stimulation of the elongated carotid sinus nerve caused an initial rise and a subsequent fall in blood pressure, bradycardia, and an increase of respiratory volume and rate. These results confirmed that the elongated carotid sinus nerve of rats in this colony contains both baroreceptor and chemoreceptor afferent fibers. It seems that this colony of rats proffers a beneficial material which will facilitate the studies to analyze the features and reflex functions of carotid body chemoreceptors and/or carotid sinus baroreceptors.

Effects of exaggerated lithotomy position on ventilation and hemodynamics during radical perineal prostatectomy.

Ventilation and haemodynamics were studied in nine anaesthetized male patients undergoing perineal prostatectomy in the exaggerated lithotomy position (flexed, head-down position). In the flexed head-down position, as compared to the supine position, there was a significant decrease in arterial oxygen tension (13.1 +/- 2.1 to 11.2 +/- 1.1 kPa, p < 0.001), a significant increase in carbon dioxide tension (4.6 +/- 5.7 to 5.7 +/- 0.2 kPa, p < 0.001) and shunt fraction (7.8 +/- 2.3 to 14.0 +/- 3.0%, p < 0.01). There were also increases in pulmonary wedge pressures (11.3 +/- 2.9 to 17.9 +/- 2.9 mmHg, p < 0.01), mean pulmonary artery pressures (17.6 +/- 3.8 to 25.2 +/- 3.5 mmHg, p < 0.001) and central venous pressures (11.9 +/- 2.1 to 14.7 +/- 2.8, p < 0.05). Mean arterial pressure fell from 92 +/- 14 to 75 +/- 10 mmHg (p < 0.05). Heart rate and cardiac output were unchanged. All these changes had already been seen but to a lesser extent when the patients were positioned in the flexed supine position. When the patients were returned to the supine position following surgery, arterial oxygen tension was returned to baseline values. Mean pulmonary artery, pulmonary capillary wedge and central venous pressures also fell significantly. It is concluded that the extreme exaggerated lithotomy used during surgery results in impaired oxygenation and increased cardiac filling pressures but to acceptable levels in healthy anaesthetized patients. All values returned to normal when patient position was normalized after surgery.

Metabolic and hormonal responses to adrenoceptor antagonists in exercising rats

alpha- and beta-adrenoceptors play a key role in the regulation of nutrient supply to working muscles during exercise. To assess their influence in the regulation of substrate utilization, rats were studied during alpha- or beta-adrenoceptor blockade. Energy metabolism was studied by means of indirect calorimetry before, during, and after moderate swimming exercise. Blood samples were taken for the determination of nutrient and hormone concentrations. In addition, central venous blood samples were withdrawn for determination of blood gases, pH, and total hemoglobin concentration (c/Hb). alpha- and beta-adrenoceptor blockade decreased the rates of energy expenditure (EE) and fat oxidation (fat-ox) during and after swimming in comparison to swimming without adrenoceptor blockade. The oxidation of carbohydrates (CHO-ox) was increased in both cases. alpha-Blockade prevented the exercise-induced increase in blood glucose, plasma free fatty acids (FFA) were not affected, and plasma insulin, norepinephrine (NOR), epinephrine (EPI), and lactate were markedly increased. beta-adrenoceptor blockade prevented the exercise-induced increases in blood glucose and FFA. EPI increased slightly more than and NOR less than in the control experiment. The exercise-induced decrease in insulin was more pronounced after beta-blockade. alpha-Blockade caused a less pronounced decrease in venous oxygen saturation (SO2) and tension (PO2) than in the control experiment. The exercise-induced increase in carbon dioxide tension (PCO2) was almost absent. After beta-blockade, venous SO2 and PO2 decreased more and PCO2 increased more than in the control experiment. It is concluded that both alpha and beta-blockade restrict the rate of EE during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise cardiorespiratory function before and one year after operation for pectus excavatum

In 35 patients with pectus excavatum (aged 17.9 +/- 5.6 years) pulmonary function and maximal exercise test results were compared before and at 1 year after operation. The lower posteroanterior chest diameter on the lateral x-ray film was significantly smaller than normal (p < 0.0001) and increased significantly after operation (p < 0.0001). Preoperatively, total lung capacity (86.0% +/- 14.4%; p = 0.0001) and inspiratory vital capacity (79.7% +/- 16.2; p = 0.0001) were significantly smaller than predicted and further decreased after operation (-9.2% +/- 9.2%; p = 0.0001 and -6.6% +/- 10.7%; p = 0.0012, respectively). Arterial blood gas values displayed normal patterns with increasing exercise both before and after operation. Only the arterial pH decreased more after operation than before (p = 0.0026). After operation there was a significant increase in maximal oxygen uptake (oxygen uptake; p = 0.0002 and oxygen uptake per kilogram; p = 0.0025) and oxygen pulse (oxygen uptake/heart rate approximates an indirect parameter for stroke volume; p = 0.0333) during exercise, whereas the maximal work performed was unchanged. Efficiency of breathing (ratio of tidal volume/inspiratory vital capacity) at maximal exercise improved significantly after operation (p = 0.0005). Ventilatory limitation of exercise (defined by an increase in carbon dioxide tension during exercise) was found in 43.9% of the patients before operation. A tendency of improvement was noted (not significant) after operation (difference in carbon dioxide tension 0.6 +/- 0.4 kPa before versus 0.3 +/- 0.5 kPa after operation). However, the group with normal preoperative carbon dioxide elimination had a ventilatory limitation of exercise after operation (difference in carbon dioxide tension -0.4 +/- 0.3 kPa before versus -0.1 +/- 0.3 kPa after operation; p = 0.0128) with a significant increase in oxygen consumption (p = 0.0007). In conclusion the subjective physical improvement after operation is not explained by changes in cardiorespiratory function at exercise. The data suggest a higher work of breathing after operation.

Carbon dioxide retention and oxygen desaturation during gastrointestinal endoscopy

Background: Pulse oximetry measures arterial oxygen saturation (Spo2), not hypoventilation, which is directly reflected by increases in carbon dioxide tension. Methods: In the present study, transcutaneous carbon dioxide tension (Ptcco2) and Spo2 were measured during 101 endoscopic procedures selected for long duration or comorbid illnesses, and relationships between hypercapnia and hypoxemia were evaluated. Nasal oxygen was administered only for sustained desaturation (Spo2 < 90%). Results: Mean peak increase in Ptcco2 was significantly higher in patients requiring oxygen for sustained desaturation (16.3 mm Hg; range, 4–52) than in patients breathing room air who had transient or no desaturation (10.2 mm Hg [range, 3–19] and 5.1 mm Hg [range, 0–15]). If nasal oxygen corrected desaturation, even transient recurrence of desaturation indicated worsening CO2 retention, which preceded respiratory arrest in one patient. Independent predictors of hypercapnia were fentanyl and midazolam doses, oxygen requirement, and dementia. Conclusions: Severe hypoventilation may occur during endoscopy, undetected by clinical observation or pulse oximetry, but only in sedated patients who require supplemental oxygen to maintain Spo2 above 90%. After oxygen supplementation corrects desaturation, recurrence of desaturation implies severe hypoventilation and warrants limitation of further sedation.

Exclusion of the placenta during fetal cardiac bypass augments systemic flow and provides important information about the mechanism of placental injury

The in utero correction of congenital cardiac malformations requires the availability of fetal cardiac bypass. One difficulty with fetal cardiac bypass is that very high flow rates are necessary when the placenta is left in the bypass circuit; the placenta requires about 40% of fetal cardiac output, which results in a normal cardiac output of 400 ml/kg per minute. Previous attempts to perform fetal cardiac bypass failed to consistently achieve these high flow rates because of cannula size limitations. On the basis of previous work done in our laboratory with an isolated-placenta model, which demonstrated that at normothermia the placenta would tolerate at least 30 minutes of cessation of umbilical blood flow, we hypothesized that exclusion of the placenta from the fetal cardiac bypass circuit would reduce fetal cardiac output by one half and allow us to obtain better systemic perfusion without compromising placental function. Cardiac bypass was performed in 20 late-gestation fetal lambs. In 10 lambs, no drugs were given; 5 served as controls in which the placenta was perfused; in the last 5, the placenta was excluded by clamping the umbilical cord during bypass. The latter 10 lambs were treated with indomethacin, which is known to improve placental blood flow after fetal cardiac bypass. We measured blood gases and determined regional blood flow with radiolabeled microspheres to assess placental function after bypass. The 5 control fetuses experienced rapid hypercapnea and hypoxemia after bypass, in association with minimal placental blood flow; when the placenta was excluded, arterial carbon dioxide tension rose somewhat more slowly, and placental blood flow after bypass was significantly better. When indomethacin was given, arterial blood gases in both groups showed a mild increase in carbon dioxide tension and similar placental blood flows (about 30% of baseline) after bypass. Indomethacin is known to block the vasoconstrictive response of the placenta to fetal cardiac bypass, implicating the release of vasoactive cyclooxygenase products as the cause of the adverse effects. In this study, placental perfusion on bypass without indomethacin caused much more severe placental dysfunction than did bypass with the placenta excluded from the circuit. The use of indomethacin improved postbypass placental function in both groups, but this effect was much more dramatic in the placenta-perfused group.(ABSTRACT TRUNCATED AT 400 WORDS)

Arterial and Mixed Venous Blood Acid-Base Balance During Hypoperfusion With Incremental Positive End-Expiratory Pressure in the Pig

The authors sought to determine how hypoperfusion influences acid-base balance in arterial and mixed venous blood. In anesthetized, ventilated pigs (n = 12), we determined hemodynamics, O2 uptake, CO2 output, dead-space ventilation, arterial and mixed venous blood acid-base balances, and lactate concentrations during graded reductions in cardiac output by incremental positive end-expiratory pressure (PEEP, 0-20 cm H2O). Cardiac output decreased from 3.2 +/- 0.2 (mean +/- SEM) to 1.2 +/- 0.1 L/min at 20 cm H2O PEEP. Oxygen delivery declined more than O2 uptake did by 60% +/- 2% and 27% +/- 2%, respectively. The decrease in CO2 output (by 21% +/- 2%) was less than that in O2 uptake. Fractional dead-space ventilation increased. At a slight increase in carbon dioxide tension (PCO2) of 4 +/- 1 mm Hg, pH decreased in arterial blood from 7.54 +/- 0.01 to 7.47 +/- 0.02 mmol/L, and standard bicarbonate decreased from 30.3 +/- 0.5 to 27.5 +/- 0.6 mmol/L. The decrease in standard bicarbonate exceeded the increase in blood lactate concentrations. At a similar decrease in standard bicarbonate, the decrease in pH was larger (P less than 0.005) in mixed venous blood than in arterial blood owing to a larger increase in PCO2 (from 40 +/- 2 to 50 +/- 2 mm Hg, P less than 0.005). The changes were reversed after discontinuing PEEP. The authors conclude that ischemia after incremental PEEP results in tissue metabolic acidosis with superimposed respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Capnography for detection of endobronchial migration of an endotracheal tube

A patient is described in whom migration of an endotracheal tube into the right main bronchus was suspected when end-tidal carbon dioxide suddenly decreased from 28 to 22 mm Hg. Acute changes with migration of the endotracheal tube into the main bronchus were also studied in an animal experimental model. End-tidal carbon dioxide decreased and tracheal (inflation) pressure increased, with no change in tidal volume. Arterial blood gases showed time-dependent decreases in pH and oxygen tension and an increase in carbon dioxide tension.

Fetal acidosis in prolonged pregnancy cannot be attributed to cord compression alone

Fetal heart rate abnormalities associated with prolonged pregnancy have been attributed to umbilical cord vulnerability rather than placental insufficiency. Although intrapartum fetal heart rate patterns indicative of umbilical cord compression are common beyond 41 weeks' gestation, fetal intolerance to labor develops only in a subset of such patients. To test the hypothesis that suboptimal placental function contributes to reduced amniotic fluid volume and, ultimately, to fetal intolerance to labor, we prospectively collected biochemical and clinical data on 112 prolonged pregnancies. Data analysis was blinded to outcome and included cord blood acid-base measurements and intrapartum fetal heart rate interpretation. We observed a high incidence of umbilical cord compression (46.4%), but this finding was not predictive of emergent delivery in 32 of 52 cases (61.5%). Fetal acidosis (arterial pH less than 7.20) occurred more often in patients with cord compression, but the anticipated increase in carbon dioxide tension was not observed. Instead, a primary metabolic or combined acidosis was encountered in those fetuses delivered emergently. The additional findings of lower amniotic fluid volume and diminished birth weight in those patients delivered for fetal intolerance to labor suggest a direct role for suboptimal placental function in selected patients with prolonged pregnancy.

Effects of prolonged epinephrine infusion on blood respiratory and acid-base states in the rainbow trout: Alpha and beta effects

Rainbow trout were infused continuously for 12h with epinephrine in the presence or absence of alpha-and/or beta-adrenergic blockade to characterize the specific adrenergic mechanisms involved in the control of blood acid-base status and oxygen transport capacity. Infusion of epinephrine, alone, produced a transient respiratory acidosis, as indicated by an increase in carbon dioxide tension and a decrease in whole blood pH, yet arterial oxygen tension was elevated. Red blood cell pH increased by approximately 0.2 pH units during epinephrine infusion and this increase as well as the increase in oxygen tension were prevented by pretreatment with propranolol (a beta-adrenergic antagonist). Epinephrine infusion during alpha-adrenergic blockade caused a prolonged elevation of blood carbon dioxide tension and abolished the increases in hematocrit and hemoglobin concentrations observed during epinephrine infusion alone. Infusion of the alpha-adrenergic agonists phenylephrine (an alpha1 agonist) or clonidine (an alpha2 agonist) caused respiratory acidosis (decreased pH, increased CO2 tension) and a reduction in oxygen tension. Infusion of isoprenaline (a non-specific beta agonist) caused delayed increases in carbon dioxide and oxygen tensions. We speculate that the increased carbon dioxide tension observed during epinephrine infusion is a result of beta-adrenoceptor mediated inhibition of red blood cell bicarbonate dehydration and not branchial convective or diffusive adjustments. The effects of epinephrine on blood O2 tension, content and carrying capacity are discussed with reference to the participation of alpha- and beta-adrenergic mechanisms at the gill, spleen and red blood cell.

The effect of changes in arterial CO2 tension on plasma lidocaine concentration.

The authors studied the effect of changes in arterial carbon dioxide tension on plasma lidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO2 of 41.4 +/- 0.9 mmHg (mean +/- SE), total plasma lidocaine concentrations were 3.97 +/- 0.20 microgram X ml-1. There was no significant change associated with hypercarbia (PaCO2 = 55.7 +/- 1.5 mmHg, lidocaine = 3.93 +/- 0.18 microgram X ml-1) or hypocarbia (PaCO2 = 19.5 +/- 1.4 mmHg, lidocaine = 4.29 +/- 0.25 microgram X ml-1), despite the known effects of changes in CO2 tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO2 tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 micrograms X ml-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension.

Effects of aluminium in hard, acid water on metabolic rate, blood gas tensions and ionic status in the rainbow trout

Rainbow trout, Salmo gairdneri, cannulated in the dorsal aorta, were exposed to 2 mgl−1 aluminium (added as Al2(SO4)3, 18H2O) at pH = 5.0 in hard water of very high calcium concentrations (3.3 mmol 1−1). No changes were observed in the concentration of the major plasma ions. The fish, however, became hypoxic, as seen from a fall in the dorsal aortic oxygen tension from around 100 mmHg to 30–40 mmHg, and a simultaneous increase in carbon dioxide tension. Moreover, exposure resulted in a 15% increase in standard oxygen uptake. The ventilation frequency doubled and swelling of the erythrocytes was observed. The results are discussed in the light of some earlier data on the effects of acid/aluminium exposure in water of low calcium concentration, and reveal an important role for calcium in the physiological responses to low pH and aluminium.

FAILURE TO INDUCE MALIGNANT HYPERTHERMIA IN MYOTONIC GOATS

Six goats with myotonia congenita were exposed for 1 h to 1% halothane and a single injection of suxamethonium i.v. in an attempt to induce malignant hyperthermia. No evidence of malignant hyperthermia occurred. Suxamethonium did produce a myotonic response in each goat, lasting 10-20s, which was accompanied by a transient increase in aerobic metabolism as indicated by a decrease in PvO2 from 6.6 to 5.7 kPa, an increase in PaCO2 from 5.1 to 6.1 kPa and an increase in PVCO2 from 5.5 to 6.3 kPa. There was no evidence of any metabolic acidosis since the transient changes in pH and buffer base were consistent with the increase in carbon dioxide tension. It is concluded that in goats myotonia congenita does not predispose to susceptibility to malignant hyperthermia.