Arterial Blood O2 Research Articles

Hypoxia tolerance in elasmobranchs. I. Critical oxygen tension as a measure of blood oxygen transport during hypoxia exposure

The critical O(2) tension of whole-animal O(2) consumption rate (M(O2)), or P(crit), is the water P(O2) (Pw(O(2))) at which an animal transitions from an oxyregulator to an oxyconformer. Although P(crit) is a popular measure of hypoxia tolerance in fishes because it reflects the capacity for O(2) uptake from the environment at low Pw(O(2)), little is known about the interrelationships between P(crit) and blood O(2) transport characteristics and increased use of anaerobic metabolism during hypoxia exposure in fishes, especially elasmobranchs. We addressed this knowledge gap using progressive hypoxia exposures of two elasmobranch species with differing hypoxia tolerance. The P(crit) of the hypoxia-tolerant epaulette shark (Hemiscyllium ocellatum, 5.10±0.37 kPa) was significantly lower than that of the comparatively hypoxia-sensitive shovelnose ray (Aptychotrema rostrata, 7.23±0.40 kPa). Plasma [lactate] was elevated above normoxic values at around P(crit) in epaulette sharks, but increased relative to normoxic values at Pw(O(2)) below P(crit) in shovelnose rays, providing equivocal support for the hypothesis that P(crit) is associated with increased anaerobic metabolism. The M(O2), arterial P(O2) and arterial blood O(2) content (Ca(O(2))) were similar between the two species under normoxia and decreased in both species with progressive hypoxia, but as Pw(O(2)) declined, epaulette sharks had a consistently higher M(O2) and Ca(O(2)) than shovelnose rays, probably due to their significantly greater in vivo haemoglobin (Hb)-O(2) binding affinity (in vivo Hb-O(2) P(50)=4.27±0.57 kPa for epaulette sharks vs 6.35±0.34 kPa for shovelnose rays). However, at Pw(O(2)) values representing the same percentage of each species' P(crit) (up to ∼175% of P(crit)), Hb-O(2) saturation and Ca(O(2)) were similar between species. These data support the hypothesis that Hb-O(2) P(50) is an important determinant of P(crit) and suggest that P(crit) can predict Hb-O(2) saturation and Ca(O(2)) during hypoxia exposure, with a lower P(crit) being associated with greater O(2) supply at a given Pw(O(2)) and consequently better hypoxia tolerance. Thus, P(crit) is a valuable predictor of environmental hypoxia tolerance and hypoxia exposures standardized at a given percentage of P(crit) will yield comparable levels of arterial hypoxaemia, facilitating cross-species comparisons of responses to hypoxia.

Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise

Chronic reductions in tissue O(2) tension (hypoxia) are associated with muscle atrophy and blunted hypertrophic responses to resistance exercise (RE) training. However, the effect of hypoxia on muscle protein synthesis (MPS) at rest and after RE is unknown. In a crossover study, seven healthy men (21.4 ± 0.7 yr) performed unilateral leg RE (6 × 8 repetitions at 70% 1-repetition maximum) under normoxic (20.9% inspired O(2)) and normobaric hypoxic (12% inspired O(2) for 3.5 h) postabsorptive conditions. Immediately after RE the rested leg was biopsied, and a primed continuous infusion of [1,2-(13)C(2)]leucine was maintained for 2.5 h before final biopsies from both legs to measure tracer incorporation and signaling responses (i.e., ribosomal S6 kinase 1). After 3.5 h of hypoxia, MPS was not different from normoxia in the rested leg (normoxia 0.033 ± 0.016 vs. hypoxia 0.043 ± 0.016%/h). MPS increased significantly from baseline 2.5 h after RE in normoxia (0.033 ± 0.016 vs. 0.104 ± 0.038%/h) but not hypoxia (0.043 ± 0.016 vs. 0.060 ± 0.063%/h). A significant linear relationship existed between MPS 2.5 h after RE in hypoxia and mean arterial blood O(2) saturation during hypoxia (r(2) = 0.49, P = 0.04). Phosphorylation of p70S6K(Thr389) remained unchanged in hypoxia at rest but increased after RE in both normoxia and hypoxia (2.6 ± 1.2-fold and 3.4 ± 1.1-fold, respectively). Concentrations of the hypoxia-responsive mTOR inhibitor regulated in development and DNA damage-1 were unaltered by hypoxia or RE. We conclude that normobaric hypoxia does not reduce MPS over 3.5 h at rest but blunts the increased MPS response to acute RE to a degree dependent on extant SpO(2).

Intermittent hypoxia augments acute hypoxic sensing via HIF-mediated ROS

Carotid bodies and neonatal adrenal medullary chromaffin cells (AMC) respond rapidly to acute hypoxia before compromising cellular functions. Responses to acute hypoxia are dynamically altered by chronic perturbations in arterial blood O2 levels resulting from breathing disorders. Sleep disordered breathing with recurrent apneas cause periodic decreases in arterial blood O2 or intermittent hypoxia (IH). Recent studies suggest that reactive oxygen species (ROS) mediate cellular adaptations to prolonged hypoxia. In this article we discuss the evidence for ROS in mediating exaggerated carotid body and AMC responses to acute hypoxia by IH and the underlying cellular and molecular mechanisms. IH increases ROS levels, and anti-oxidants prevent IH-induced augmented responses of the carotid body and AMC to hypoxia. The enhanced hypoxic sensitivity by IH involves ROS-dependent recruitment of transmitters/modulators in the carotid body and Ca2+ signaling mechanisms in AMC. Mechanisms by which IH elevates ROS include activation of NADPH oxidases, inhibition of mitochondrial complex I activity and down-regulation of anti-oxidant enzymes. Transcriptional regulation of pro- and anti-oxidant enzymes by hypoxia-inducible factors 1 and 2 appears to be a major molecular mechanism regulating ROS generation by IH.

The Hematocrit Paradox - How Does Blood Doping Really Work?

The wide-spread assumption that doping with erythropoietin or blood transfusion is only effective by increasing arterial blood O2 content because of rising hematocrit is not self-evident. "Natural blood dopers" (horses, dogs) increase both hematocrit and circulating blood volume during exercise by releasing stored erythrocytes from the spleen. Improvement of aerobic performance by augmenting hemoglobin concentration may be expected until the optimal hematocrit is reached; above this value maximal cardiac output declines due to the steep increase of blood viscosity. Therefore an enlarged blood oxygen content might only be useful if the normal hematocrit of man during exercise is suboptimal. However, recent studies suggest that cardiac power rises after erythropoietin allowing an unchanged cardiac output in spite of increased viscosity. Other factors underlying improved performance after blood doping might be: augmented diffusion capacity for oxygen in lungs and tissues, increased percentage of young red cells with good functional properties (after erythropoietin), increased buffer capacity, increase of blood volume, vasoconstriction, reduced damage by radicals, mood improvement by cerebral effects of erythropoietin. Also the importance of placebo is unknown since double-blind studies are rare. It is suggested that blood doping has multifactorial effects not restricted to the increase in arterial oxygen content.

Complex Therapy for Intraoperative Blood Loss during Pelvic Bone Repair

Objective: to introduce blood saving technologies and to develop algorithms for management of patients with pelvic fractures. Subjects and methods. Sixty patients aged 40.6±2.3 years with pelvic fractures were examined. The banking of packed autoerythrocytes and auto freshly frozen plasma (AutoFFP), intraoperative acute hypervolemic hemodilution (AHH), and instrumental reinfusion of washed autoerythrocytes were made in all the patients. Blood loss volume averaged 32.1±1.7 ml/kg. The parameters of central hemodynamics (CH), blood oxygen-transport function, the blood system (red blood cells, hemoglobin, packed cell volume, and platelets) were studied. AutoFFP was transfused in the most traumatic period of surgery, autoblood was on completion of surgical hemostasis, and washed autoerythrocytes were within 3—4 hours after surgery. Postoperative reductions in hemoglobin to below 80 g/l and packed cell volume below 25% are indications for packed autoerythrocyte transfusion. Results. During preoperative autoblood banking, the parameters of CH and the blood system underwent no changes, all variations in the parameters were within the normal range and compensatory. When AHH and instrumental washed erythrocyte reinfusion were conducted, there was a significant increase in cardiac index (CI), stroke index by 37 and 30%, respectively; reductions in total peripheral vascular resistance index by 38%, mean blood pressure by 18%, moderate hypercoagulation, and significant decreases in hemoglobin, packed cell volume, red blood cells by 17, 15, and 18%, respectively. The values of acid-base condition and homeostasis underwent no considerable changes. Arterial blood O2 content was significantly lowered by 16%; however, global O2 uptake remained unchanged at the baseline levels due to the increase of CI by 30% of the baseline level. Conclusion. The application of blood saving technologies, preoperative autoblood banking in particular, AHH, and instrumental washed autoerythrocyte reinfusion allowed a refusal to use allo-geneic blood components during pelvic repair, by preventing the development of hemotransfusion complications. Key words: blood loss, blood saving, packed autoerythrocytes, auto freshly frozen plasma, acute hypervolemic hemodilution, autohemotransfusion, instrumental washed autoerythrocyte reinfusion, spinal epidural anesthesia.

Premedication with oral midazolam with or without parental presence

In this study, we aimed to investigate whether the combination of low-dose (0.25 mg kg(-1)) midazolam premedication with parental presence can effectively reduce anxiety at induction as well as provide a smoother emergence. Institutional ethics committee approval and informed consent from one of the parents were obtained prior to the study. Sixty ASA grade I or II children undergoing surgery were enrolled in the study. Children were randomized to receive either 0.5 mg kg(-1) midazolam orally (group M) or 0.25 mg kg(-1) midazolam orally with parental presence (group MP) or parental presence alone (group P). The child's anxiety and sedation scores were evaluated as 1-4 points on the Anxiety Scale and as 0-4 points on the University of Michigan Sedation Scale (UMSS), respectively, at the entrance to the operating room and for tolerance to the face mask. Heart rate, the mean arterial blood pressure and O2 saturation (%) were assessed at repeated intervals before and after induction. At the end of surgery, the child's Anxiety Scale score, UMSS score, Observer's Pain Scale (OPS) score and FLACC score were also assessed. There were no differences between groups in demographic variables and duration of surgery or anaesthesia. Mean blood pressure changes were similar between groups at measured intervals, but the heart rate was higher in group M before and after induction of anaesthesia (P<0.05). UMSS score was greater in both midazolam groups (groups M and MP) in the preoperative period (P<0.05). Anxiety Scale scores for anxiolysis were higher in groups M and MP than in group P (less anxious and more sedated) at 20 min after premedication, at the entrance to the operating room and at mask tolerance time points (P<0.05). During recovery there was no significant difference in sedation, recovery scores or behavioural anxiety assessment between groups, Anxiety Scale score, UMSS score, FLACC score, Visual Analog Scale (VAS) score and Observer's Pain Scale score in groups MP, M and P. Preoperative administration of midazolam 0.5 mg kg(-1) for premedication alone, without parental presence at induction, and that of low-dose midazolam 0.25 mg kg(-1) for premedication with parental presence at induction are both equally effective in reducing separation anxiety and providing a smooth emergence. However, parental presence alone, without midazolam for premedication, is not an adequate approach for this outcome. If the environment for parental presence is convenient, the dose of midazolam may be reduced and induction and emergence conditions may still be of high quality.

A Beat-by-Beat Cardiovascular Index, CARDEAN: A Prospective Randomized Assessment of Its Utility for the Reduction of Movement During Colonoscopy

We sought to determine whether online use of a beat-by-beat cardiovascular index, CARDEAN (Alpha-2, Lyon, France), modifies the incidence of patient movement during colonoscopy under anesthesia. Monitoring included an electrocardiogram, oscillometric and noninvasive beat-by-beat arterial blood pressure, O2 saturation, bispectral index (BIS), and CARDEAN. CARDEAN consists of beat-by-beat Finapres (Ohmeda, Madison, WI) combined with an algorithm that detects hypertension followed by tachycardia and produces an index scaled 0 to 100. The anesthesiologist was denied access to Finapres and CARDEAN. Propofol was adjusted to keep 40<BIS<60. Alfentanil 3.5 microg x kg(-1) was administered according to conventional signs (tachycardia, hypertension, and movement), unless the patient had signs of brady/apnea or Spo(2) <95%. One hundred fifty-nine patients presenting for colonoscopy under propofol anesthesia were prospectively randomized to (i) control: no other intervention, or (ii) CARDEAN: in addition to conventional signs, an observer instructed the anesthesiologist to administer alfentanil when CARDEAN was >60. The primary outcome was the number of observed movements. Data were analyzed in 146 patients (control: 75; CARDEAN: 71). The doses of propofol and alfentanil were similar in both groups. When BIS was <60, movements were less frequent in the CARDEAN group (3.3 movements/100 min [2.3-4.8]) than in the control group (6.7 [5.3-8.5]) (odds ratio: 0.5 [0.32; 0.76], P = 0.001). During the first 10 minutes of the procedure, the incidence of movements was 38% and 59% in the CARDEAN and control groups, respectively (P = 0.04). With BIS <60, CARDEAN-guided opioid administration is associated with a reduction of 51% of clinically unpredictable movements in unparalyzed patients undergoing colonoscopy. More studies are required to refine the role of CARDEAN in surgical settings.

Hyper‐response of OP3 to systemic hyperoxia in the dark‐adapted retina

We have demonstrated that the third wavelet (OP3) of the scotopic flash oscillatory potential (OP) complex shows a hyper-response during experimentally-induced systemic hyperoxia. The objective of the present study was to further evaluate and detail the time course of this enhanced retinal response. Twenty healthy adults volunteered for this study. The OPs were recorded with a DTL-type electrode following pupillary dilation and retinal dark adaptation. Stimuli consisted of white flashes. The OPs were recorded at 8 points in time before, during and after breathing pure oxygen (O2). The arterial blood O2 saturation (SaO2), end-tidal CO2 (EtCO2), respiratory rate (RR), pulse rate (PR) and blood pressure (BP) were monitored throughout the experiment. The amplitude of the OPs did not vary significantly across test conditions except for OP3, which increased with systemic hyperoxia and was still elevated by the end of the experiment. The SaO2 and RR increased, the EtCO2 and PR decreased, whereas the BP was not altered during O2 breathing. This study provides further evidence indicating that the neural generators of OP3 display a unique hyper-reactivity to increased systemic O2 levels in the young healthy adult. Further studies looking at OP3 are still needed to determine if this unique behavior could serve as an index of altered oxygen level and retinal function in health or disease.

ROS Signaling in Systemic and Cellular Responses to Chronic Intermittent Hypoxia

Chronic intermittent hypoxia (CIH) is a common and life-threatening condition that occurs in many different diseases, including sleep-disordered breathing manifested as recurrent apneas. Reactive oxygen species (ROS) have been identified as one of the causative factors in a variety of morbidities. The purpose of this article is to present a brief overview of recent studies implicating a critical role of ROS in evoking phenotypic adverse effects in experimental models of CIH and in patients with recurrent apneas. In experimental models, CIH activates ROS signaling that contributes to several systemic and cellular responses that include (a) altered carotid body function, the primary chemoreceptor for sensing changes in arterial blood O2; (b) elevated blood pressures; (c) enhanced release of transmitters and neurotrophic factors; (d) altered sleep and cognitive behaviors; and (e) activation of second-messenger pathways and transcriptional factors. Considerable evidence indicates elevated ROS levels in patients experiencing CIH as a consequence of recurrent apneas. Antioxidants not only prevent many of the CIH-evoked physiologic and cellular responses in experimental settings, but more important, they also offer protection against certain phenotypic adverse effects in patients with recurrent apneas, suggesting their potential therapeutic value in alleviating certain morbidities associated with recurrent apneas.

Swimming alters responses to hypoxia in the Adriatic sturgeon Acipenser naccarii

When the Adriatic sturgeon Acipenser naccarii was exposed to progressive hypoxia under static conditions, it exhibited a linear decline in O2 uptake, behaving as an ‘oxyconformer’. When, however, it was allowed to swim at a low sustained speed, it could regulate O2 uptake down to a mean ±s.e. critical (Pcrit) of 4·9 ± 0·5 kPa (n= 6). At moderate levels of hypoxia, static fish exhibited significant reductions in arterial blood O2 content, and increases in plasma lactate, which were not observed in swimming animals.

The association between the proximal extension of the clot and the severity of pulmonary embolism (PE): a proposal for a new radiological score for PE

The aim of the study was to investigate the association between the proximal level of the clot and the severity of pulmonary embolism (PE). The cohort consisted of 99 consecutive patients with PE diagnosed by multi-detector computed tomography. A new score was constructed by calculating the mean value of the largest affected vessel [sub-segmental = 1, segmental = 2, lobar = 3, main pulmonary artery (MPA) = 4] in each lung. A significant association was found between the most proximal level of PE and pulmonary artery obstruction index (PAOI) (P < 0.0001), right ventricular (RV)/left ventricular (LV) ratio (P < 0.0001), and PaO(2) (P = 0.004). No significant association was found between systolic blood pressure and the level of PE. Troponin-T was elevated in none of the sub-segmental, 5% of segmental, 20% of lobar, and in 56% of PEs in the MPA (P = 0.001). Significant association was found between the proposed score and PAOI (P < 0.0001), RV/LV ratio (P < 0.0001), PaO(2) (P < 0.008). Troponin-T was elevated in 10% of level 1, 0% of level 2, 43% level of 3, 66% of level 4 PE (P < 0.0001). Cut-off level score 4 yielded a sensitivity of 84% and a specificity of 74% for the detection of elevated troponin-T. In conclusion, the study indicates that both the most proximal level of PE and the proposed score are related to the severity of PE as determined by blood oxygenation, biochemical and radiological parameters and could therefore be of value for rapid risk stratification of PE. However, the prognostic value of these classifications and their clinical significance needs to be evaluated in properly designed studies.

Reply from Bruno Grassi, Michael C. Hogan and L. Bruce Gladden

Reply from Bruno Grassi, Michael C. Hogan and L. Bruce Gladden

Chemoreceptor and pulmonary stretch receptor interactions within amphibian respiratory control systems

The hypercapnic drive to breathe in amphibians is generally greater than hypoxic ventilatory drive and a variety of interdependent control systems function to regulate both the hypoxic and hypercapnic ventilatory responses. During exposure to hypercapnic conditions, breathing increases in response to input from central chemoreceptors (sensitive to CSF pH/CO(2) levels) and peripheral chemoreceptors (sensitive to arterial blood O(2) and CO(2)). On the other hand, olfactory CO(2) receptors in the nasal epithelium inhibit breathing during exposure to acute hypercapnia. Further complexity arises from the CO(2)-sensitive nature of the pulmonary stretch receptors (PSR) which provide both tonic (stimulates lung inflation at low lung volumes; deflation at higher volumes) and phasic (generally excitatory) feedback. This review focuses on interactions between the various populations of chemoreceptors and interactions between chemoreceptors and PSR. Differences between various levels of experimental reduction (i.e., in vitro; in situ; in vivo) are highlighted as are the effects of chronic respiratory challenges on acute hypoxic and hypercapnic chemoreflexes.

The Addition of O2 to the CO2 Does Not Prevent the Systemic Effects of the CO2 Pneumoperitoneum in a Rabbit Model

CO2 pneumoperitoneum used in endoscopic surgery induces systemic effects by CO2 absorption. It was claimed that a reduction in CO2 pneumoperitoneum-induced metabolic hypoxemia was achieved by the addition of small amounts of O2 to the CO2 in a rabbit ventilated model. We reevaluated the effects of the addition of O2 to the CO2 pneumoperitoneum upon CO2 absorption in a rabbit model. The effects of a pneumoperitoneum using 100% CO2, 90% CO2 + 10% O2, 95% CO2 + 5% O2, or 100% O2 on arterial blood gases, acid base and O2 homeostasis were evaluated in nonintubated rabbits. A pneumoperitoneum pressure of 10 cm H2O (approximately 7.35 mm Hg) was used. CO2 pneumoperitoneum of 120 minutes affected blood gases and acid base homeostasis. Whereas partial pressure of CO2 and HCO3 increased (P < 0.001) during pneumoperitoneum, pH and partial pressure of O2 decreased (P < 0.001). Similar results were obtained in O2-CO2 pneumoperitoneum (P > 0.05). CO2 pneumoperitoneum profoundly affected blood gases and acid base homeostasis, resulting in metabolic hypoxemia. The addition of O2 to the CO2 did not prevent the systemic effects of CO2 pneumoperitoneum in nonintubated animals.

Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

Patients with chronic bronchial asthma show a depressed ventilatory response to hypoxia (DVH), but the underlying mechanism remains unclear. We tested whether DVH existed in ovalbumin (Ova)-treated guinea pigs, an established animal model of asthma. Twelve guinea pigs were exposed to Ova (1% in saline) or saline aerosol (control) for 5 min, 5 days/wk, for 2 wk. After completing aerosol exposure, the animals were anesthetized and exposed to systemic hypoxia. Ova treatment had no effects on animal body weight, baseline cardiorespiratory variables, or arterial blood O2 and CO2 tensions, but it attenuated the ventilatory response to hypoxia (10 breaths of pure N2) by 65% (P < 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 microg) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% (P < 0.05) and 74% (P < 0.05), respectively. In contrast, Ova exposure failed to affect the ventilatory response to CO2 (7% CO2-21% O2-balance N2 for 5 min; P > 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C fibers (PCFs) with right atrial injection of capsaicin (5 microg) was markedly increased in the Ova-sensitized group (5.02 +/- 1.56 s), compared with the control group (1.82 +/- 0.45 s; P < 0.05). These results suggest that Ova sensitization induces a DVH in guinea pigs, which probably results from an attenuation of the carotid chemoreceptor-mediated ventilatory excitation and an enhancement of the PCF-mediated ventilatory inhibition.

ABUSING THE FICK PRINCIPLE

Dear Editor-in-Chief: We wish to take umbrage with the data, analysis, and conclusions regarding the interrelationships among cardiac output 𝑄̇, V̇O2max, and O2 extraction presented in the recent paper by LePretre and colleagues (7). The authors utilized the eponymous Fick principle, which is based on simple mass balance considerations and states that can be calculated from simultaneous measurement of V̇O2, and the arterial (CaO2) and mixed venous (CV̇vO2) blood O2 contents (i.e., O2 extraction): Following the landmark publication in 1870, Adolf Fick’s principle has formed a fundamental cornerstone of cardiovascular physiology and medicine (2). For example, in the late 1800s it was used to measure 𝑄̇ in dogs (4) and horses (13), and following the first successful heart catheterization by Werner Forssman in 1929, in man (3,6). Today, with multiple invasive and noninvasive techniques to measure 𝑄̇, the Fick principle is often used to determine O2 extraction: and it is using this form that LePretre et al. supposedly derived their O2 extraction data depicted in Figure 5 and Table 3 of their publication. As evident from equations 1 and 2 above, it is impossible for O2 extraction (CaO2 − CV̄O2) to be changing while both 𝑄̇ and V̇O2 are constant. However, their Figure 5 demonstrates an approximately 30% decrease in CaO2 − CV̄2 at constant rates of 𝑄̇ and V̄O2 (see their Fig. 4) during heavy/severe exercise. Moreover, the mean values for O2max and 𝑄̇max presented in their Table 3 are not consistent with the maximal O2 extraction data in that table. Specifically, the values presented are 13.2, 13.1, and 13.3 mL O2·100 mL−1 blood, whereas those calculated from their data are 20–40% higher (i.e., 15.7, 17.9, and 16.9 mL O2·100 mL−1 blood, respectively). In conclusion, the data presented by LePretre et al. (7) appear to be inconsistent with basic principles of mass balance as delineated by the Fick principle. Moreover, investigations that have measured O2 extraction directly either across the body or exercising limbs at heavy/severe exercise intensities (1,5,9–11) do not demonstrate either a temporal or intensity-related reduction in O2 extraction as depicted by LePretre et al. Indeed, from the relationship established between 𝑄̇ and O2 for dynamic exercise, O2 extraction must increase as a hyperbolic function of muscle(s) and pulmonary O2 (8,12). Thus, it may be appropriate to hold in question the fidelity of the data presented by LePretre et al. and their conclusions based upon that data. Danielle J. Padilla Timothy I. Musch David C. Poole Departments of Anatomy and Physiology and Kinesiology, Kansas State University, Manhattan, KS

Hypoxia Suppresses Symptom Perception in Asthma

Any factor that inhibits the ability of an individual with asthma to recognize their symptoms appropriately may contribute to treatment delay, "near miss" events, and death during acute severe asthma. The purpose of this study was to investigate the effects of two common features of acute severe asthma--hypoxia and hypercapnia--on respiratory sensation. Sixteen individuals with stable asthma were exposed to three gas conditions (34 minutes each): isocapnic hypoxia (arterial blood O2 saturation of approximately 80%), hypercapnia (increase in end-tidal CO2 of approximately 5-10 Torr), or isocapnic normoxia on 3 separate days. The perceived magnitude of externally applied resistive loads, measured during each gas condition, was reduced throughout hypoxia compared with normoxia, and there was a trend for a progressive decline during hypercapnia. Within the 15-minutes postgas inhalation period, methacholine-induced symptoms of difficult breathing, chest tightness, and breathlessness, measured using modified Borg scales, were 25-30% lower after hypoxia compared with normoxia but were not reduced after hypercapnia. We conclude that 30 minutes of sustained hypoxia and possibly hypercapnia impair sensations of respiratory load and that the effects of hypoxia persist for at least 10 minutes after returning to normoxia.

Systemic responses to prolonged hemorrhagic hypotension.

Studies are needed to provide a rigorous examination of the relevance of monitored variables during prolonged hemorrhagic hypotension (HH). This study was designed to investigate the parameters that describe biochemical and O2 transport patterns in animals subjected to HH. Systemic parameters that could differentiate survivors from nonsurvivors were identified. An aortic flow probe was implanted in rats (n = 21) for continuous measurement of cardiac output. Experiments were performed 6-9 days after surgery. Rats were bled to a mean arterial pressure of 40 mmHg and kept at that level using Ringer-lactate solution. Arterial and venous blood pressures, gases, acid-base status, glucose, lactate, electrolytes, hemoglobin, O2 saturation, heart and respiratory rates, total peripheral resistance, and O2 delivery and consumption were measured before hemorrhage, soon after 40 mmHg was reached, and 0.5, 1, 2, 3, and 4 h later. Fifty-three percent of rats survived > or =3 h (survivors); others were considered nonsurvivors. Nonsurvivors showed a significantly greater degree of metabolic acidosis than survivors. Arterial PO2, respiratory rate, O2 saturation, O2 content, glucose, and pH were significantly higher in survivors. The rate of Ringer-lactate infusion, arterial K+, and PCO2 were lower in survivors. Arterial K+ and respiratory rate were the only parameters significantly different between survivors and nonsurvivors at all time points during HH. Arterial levels of K+ showed the clearest distinction between survivors and nonsurvivors and may explain the sudden death experienced by animals during HH. The data suggest that early respiratory and metabolic compensations are essential for survival of prolonged HH.

NaHCO(3) does not affect arterial O(2) tension but attenuates desaturation of hemoglobin in maximally exercising Thoroughbreds.

The objective of the present study was to examine the effects of preexercise NaHCO(3) administration to induce metabolic alkalosis on the arterial oxygenation in racehorses performing maximal exercise. Two sets of experiments, intravenous physiological saline and NaHCO(3) (250 mg/kg i.v.), were carried out on 13 healthy, sound Thoroughbred horses in random order, 7 days apart. Blood-gas variables were examined at rest and during incremental exercise, leading to 120 s of galloping at 14 m/s on a 3.5% uphill grade, which elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. NaHCO(3) administration caused alkalosis and hemodilution in standing horses, but arterial O(2) tension and hemoglobin-O(2) saturation were unaffected. Thus NaHCO(3) administration caused a reduction in arterial O(2) content at rest, although the arterial-to-mixed venous blood O(2) content gradient was unaffected. During maximal exercise in both treatments, arterial hypoxemia, desaturation, hypercapnia, acidosis, hyperthermia, and hemoconcentration developed. Although the extent of exercise-induced arterial hypoxemia was similar, there was an attenuation of the desaturation of arterial hemoglobin in the NaHCO(3)-treated horses, which had higher arterial pH. Despite these observations, the arterial blood O(2) content of exercising horses was less in the NaHCO(3) experiments because of the hemodilution, and an attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O(2) content gradient was observed. It was concluded that preexercise NaHCO(3) administration does not affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing short-term, high-intensity exercise.

CO2 induced acute respiratory acidosis and brain tissue intracellular pH: a 31P NMR study in swine.

High concentration carbon dioxide (CO(2)) is used to promote pre-slaughter anaesthesia in swine and poultry, as well as short-lasting surgical anaesthesia and euthanasia in laboratory animals. Questions related to animal welfare have been raised, as CO(2) anaesthesia does not set in momentarily. Carbon dioxide promotes anaesthesia by lowering the intracellular pH in the brain cells, but the dynamics of the changes in response to a high concentration of CO(2) is not known. Based on (31)P NMR spectroscopy, we describe CO(2)-induced changes in intracellular pH in the brains of five pigs inhaling 90% CO(2) in ambient air for a period of 60 s, and compare the results to changes in arterial blood pH, P(CO2), O(2) saturation and HCO(3)(-) concentration. The intracellular pH paralleled the arterial pH and P(CO2) during inhalation of CO(2); and it is suggested that the acute reaction to CO(2) inhalation mainly reflects respiratory acidosis, and not metabolic regulation as for example transmembrane fluxes of H(+)/HCO(3)(-). The intracellular pH decreased to approximately 6.7 within the 60 s inhalation period, and the situation was metabolically reversible after the end of CO(2) inhalation. The fast decrease in intracellular pH supports the conclusion that high concentration CO(2) leads to anaesthesia soon after the start of inhalation.