Changes In Arterial PO2 Research Articles

Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4-18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.

Exercise facilitates early recognition of cardiac and vascular remodeling in chronic thromboembolic pulmonary hypertension in swine.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients after pulmonary embolism and is accompanied by an impaired exercise tolerance, which is ascribed to the increased right ventricular (RV) afterload in combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present study aimed to investigate changes in arterial Po2 and hemodynamics in response to graded treadmill exercise during development and progression of CTEPH in a novel swine model. Swine were chronically instrumented and received multiple pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2) endothelial dysfunction by administration of the endothelial nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3) combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or 4) served as sham-operated controls (sham). After a 9 wk followup, embolization combined with endothelial dysfunction resulted in CTEPH, as evidenced by mean pulmonary artery pressures of 39.5 ± 5.1 vs. 19.1 ± 1.5 mmHg (Spheres, P < 0.001), 22.7 ± 2.0 mmHg (L-NAME, P < 0.001), and 20.1 ± 1.5 mmHg (sham, P < 0.001), and a decrease in arterial Po2 that was exacerbated during exercise, indicating V/Q mismatch. RV dysfunction was present after 5 wk of embolization, both at rest (trend toward increased RV end-systolic lumen area, P = 0.085, and decreased stroke volume index, P = 0.042) and during exercise (decreased stroke volume index vs. control, P = 0.040). With sustained pulmonary hypertension, RV hypertrophy (Fulton index P = 0.022) improved RV function at rest and during exercise, but this improvement was insufficient in CTEPH swine to result in an exercise-induced increase in cardiac index. In conclusion, embolization in combination with endothelial dysfunction results in CTEPH in swine. Exercise increased RV afterload, exacerbated the V/Q mismatch, and unmasked RV dysfunction. NEW & NOTEWORTHY Here, we present the first double-hit chronic thromboembolic pulmonary hypertension swine model. We show that embolization as well as endothelial dysfunction is required to induce sustained pulmonary hypertension, which is accompanied by altered exercise hemodynamics and an exacerbated ventilation/perfusion mismatch during exercise.

Apnoeic oxygenation in adults under general anaesthesia using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) – a physiological study

BackgroundApnoeic oxygenation during anaesthesia has traditionally been limited by the rapid increase in carbon dioxide and subsequent decrease in pH. Using a Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) technique a slower increase in carbon dioxide than earlier studies was seen. Notably, apnoeic oxygenation using THRIVE has not been systematically evaluated with arterial blood gases or in patients undergoing laryngeal surgery. The primary aim of this study was to characterize changes in arterial PO2, PCO2 and pH during apnoeic oxygenation using THRIVE under general anaesthesia. MethodsAdult patients, (ASA I-II), undergoing shorter laryngeal surgery under general anaesthesia, were oxygenated during apnoea using THRIVE, 100% oxygen, 40–70 litres min−1. A cohort was randomized to hyperventilate during pre-oxygenation. Vital parameters and blood gases were monitored. ResultsThirty-one patients, age 51 (34–76) yr, BMI 25 (4) were included. Mean apnoea time was 22.5 (4.5) min. Patients were well oxygenated, SpO2 was never below 91%. The increase in PaCO2 and end-tidal CO2 during apnoea was 0.24 (0.05) and 0.12 (0.04) kPa min−1, respectively. Hyperventilation during pre-oxygenation generated no difference in PaCO2 at the end of apnoea compared with normoventilation. ConclusionsThis physiological study of apnoeic oxygenation using THRIVE during laryngeal surgery shows that this technique is able to keep patients with mild systemic disease and a BMI <30 well oxygenated for a period of up to 30 min. The THRIVE concept makes it possible to extend the apnoeic window but monitoring of CO2 and/or pH is recommended. Clinical trial registrationNCT02706431.

Polycythemia and high levels of erythropoietin in blood and brain blunt the hypercapnic ventilatory response in adult mice.

Changes in arterial Po2, Pco2, and pH are the strongest stimuli sensed by peripheral and central chemoreceptors to adjust ventilation to the metabolic demand. Erythropoietin (Epo), the main regulator of red blood cell production, increases the hypoxic ventilatory response, an effect attributed to the presence of Epo receptors in both carotid bodies and key brainstem structures involved in integration of peripheral inputs and control of breathing. However, it is not known whether Epo also has an effect on the hypercapnic chemoreflex. In a first attempt to answer this question, we tested the hypothesis that Epo alters the ventilatory response to increased CO2 levels. Basal ventilation and hypercapnic ventilatory response (HCVR) were recorded from control mice and from two transgenic mouse lines constitutively expressing high levels of human Epo in brain only (Tg21) or in brain and plasma (Tg6), the latter leading to polycythemia. To tease apart the potential effects of polycythemia and levels of plasma Epo in the HCVR, control animals were injected with an Epo analog (Aranesp), and Tg6 mice were treated with the hemolytic agent phenylhydrazine after splenectomy. Ventilatory parameters measured by plethysmography in conscious mice were consistent with data from electrophysiological recordings in anesthetized animals and revealed a blunted HCVR in Tg6 mice. Polycythemia alone and increased levels of plasma Epo blunt the HCVR. In addition, Tg21 mice with an augmented level of cerebral Epo also had a decreased HCVR. We discuss the potential implications of these findings in several physiopathological conditions.

A mathematical model of diffusional shunting of oxygen from arteries to veins in the kidney

To understand how arterial-to-venous (AV) oxygen shunting influences kidney oxygenation, a mathematical model of oxygen transport in the renal cortex was created. The model consists of a multiscale hierarchy of 11 countercurrent systems representing the various branch levels of the cortical vasculature. At each level, equations describing the reactive-advection-diffusion of oxygen are solved. Factors critical in renal oxygen transport incorporated into the model include the parallel geometry of arteries and veins and their respective sizes, variation in blood velocity in each vessel, oxygen transport (along the vessels, between the vessels and between vessel and parenchyma), nonlinear binding of oxygen to hemoglobin, and the consumption of oxygen by renal tissue. The model is calibrated using published measurements of cortical vascular geometry and microvascular Po(2). The model predicts that AV oxygen shunting is quantitatively significant and estimates how much kidney Vo(2) must change, in the face of altered renal blood flow, to maintain cortical tissue Po(2) at a stable level. It is demonstrated that oxygen shunting increases as renal Vo(2) or arterial Po(2) increases. Oxygen shunting also increases as renal blood flow is reduced within the physiological range or during mild hemodilution. In severe ischemia or anemia, or when kidney Vo(2) increases, AV oxygen shunting in proximal vascular elements may reduce the oxygen content of blood destined for the medullary circulation, thereby exacerbating the development of tissue hypoxia. That is, cortical ischemia could cause medullary hypoxia even when medullary perfusion is maintained. Cortical AV oxygen shunting limits the change in oxygen delivery to cortical tissue and stabilizes tissue Po(2) when arterial Po(2) changes, but renders the cortex and perhaps also the medulla susceptible to hypoxia when oxygen delivery falls or consumption increases.

Chest tcpO2 changes during constant-load treadmill walking tests in patients with claudication

Changes in chest transcutaneous-pO2 at rest (ΔtcpO2) mimic absolute changes in arterial-pO2 during moderate exercise, although the absolute starting values may dramatically differ. We retrospectively studied 485 patients (group 1), prospectively studied 292 new patients (group 2) and estimated the intra-test and the test–retest reproducibility of ΔtcpO2 during constant-load treadmill tests: 3.2 km h−1, 10% grade, using the cross correlation technique. Patients were classified into groups according to their best fit to nine pre-defined mathematic models. Respectively, 71% and 76% of patients of groups 1 and 2 fitted with a model showing a ΔtcpO2 increase during and a decrease following exercise. Another 18% and 12% of the patients of groups 1 and 2 respectively fitted with a model that showed an abrupt decrease at exercise onset, a slow increase during walking and an overshoot in the recovery period, referred here as a walking-induced transcutaneous hack (WITH) profile. The mean rmax value for the cross-correlation analysis was 0.919 ± 0.091 and 0.800 ± 0.129 for intra-test and test–retest reproducibility. Most profiles show the expected ΔtcpO2 exercise-induced increase. Future studies are needed to confirm and explain the WITH profiles that we found, and screen for potential-associated diseases.

Changes in arterial PO2, physiological blood parameters and intracellular antioxidants in free-swimming Atlantic cod (Gadus morhua) exposed to varying levels of hyperoxia

Free-swimming Atlantic cod (Gadus morhua) were exposed to water oxygen pressures (P(w)O₂) ranging from 18.1 to 41.5 kPa and sampled for blood using an indwelling caudal artery cannula. Arterial blood oxygen pressure (P(a)O₂) increased with increasing P(w)O₂, from 12.0 kPa in normoxia (18.1 kPa) to 34.2 kPa in the highest hyperoxic level tested (41.5 kPa). Blood CO₂ pressure and plasma bicarbonate concentration increased with P(w)O₂, indicating reduced ventilation with increased P(w)O₂. Plasma glucose, sodium and potassium were not affected by water oxygen level. Blood oxidative stress biomarkers, reduced glutathione, oxidized glutathione and the oxidative stress index (ratio between oxidized and total glutathione) differed intermittently between normoxia and hyperoxia. The oxidative stress index was higher in the blood of exposed compared to unexposed control cod. Together with elevated P(a)O₂, these findings suggest increased production of reactive oxygen species and increased oxidative stress in Atlantic cod exposed to hyperoxia.

Lack of arterial PO2 downregulation in Atlantic salmon (Salmo salar L.) during long-term normoxia and hyperoxia

Regulation of arterial partial pressure of O2 (PaO2) in Atlantic salmon (Salmo salar) was investigated during resting conditions in normoxic and hyperoxic water. Dorsal aorta cannulated adult Atlantic salmon (1.2-1.6 kg, n=8) were exposed to 2 week sequential periods of normoxia [16.7±1.1 kPa (mean±SD)] and hyperoxia (34.1±4.9 kPa) in individual tanks containing seawater (33.7±0.2 ppt) at stable temperature conditions (8.7±0.7°C) and a light regime of L:D=12:12. Tank design and sampling procedures were optimized to provide suitable shelter and current for the fish, and to allow repeated, undisturbed sampling of blood from free-swimming fish. Fish were sampled regularly through the experimental period. PwO2, PaO2, blood ion composition (Na+, K+, Cl-), acid-base status (pH, PCO2, HCO3-), haematocrit and glucose were measured. The most frequently observed PaO2 values were in the range of 60-80% of PwO2, both during normoxia and hyperoxia, and PaO2 values were significantly lower during normoxia than during hyperoxia. Blood pH, PCO2 and HCO3- were significantly elevated during hyperoxia, while, Na+, Cl- and Hct were significantly lower. K+ and glucose showed no significant differences. This study demonstrates a lack PaO2 regulation in Atlantic salmon to low partial pressures, in contrast to previous reports for many aquatic gill breathing animals. Both during normoxia and hyperoxia, PaO2 reflects PwO2, and alterations in external PO2 consequently result in proportional arterial PO2 changes. Physiological adaptation to hyperoxia, as illustrated by changes in several blood parameters, does not include down-regulation of PaO2 in Atlantic salmon. The lack of PaO2 regulation may make Atlantic salmon vulnerable to the oxidative stress caused by increased free radical formation in hyperoxic conditions.

Rapid intravenous infusion of 20 ml/kg saline does not impair resting pulmonary gas exchange in the healthy human lung

Rapid infusion of intravenous saline, a model of pulmonary interstitial edema, alters the distribution of pulmonary perfusion, raises pulmonary capillary blood volume, and increases bronchial wall thickness in humans. We hypothesized that infusion would disrupt pulmonary gas exchange by increasing ventilation/perfusion ((.)VA/(.)Q) inequality as opposed to a diffusive impairment in O2 exchange. Seven males (26 +/- 3 yr; FEV1: 110 +/- 16% predicted.) performed spirometry and had (.)VA/(.)Q mismatch measured using the multiple inert gas elimination technique, before and after 20 ml/kg iv of normal saline delivered in approximately 30 min. Infusion increased thoracic fluid content from transthoracic impedance by 12% (P < 0.0001) and left FVC unchanged but reduced expiratory flows (FEF(25-75) falling from 5.1 +/- 0.4 to 4.2 +/- 0.4 l/s, P < 0.05). However, (.)VA/(.)Q mismatch as measured by the log standard deviation of the ventilation (LogSD(.)V) and perfusion (LogSD(.)Q) distributions remained unchanged; LogSD(.)V: 0.40 +/- 0.03 pre, 0.38 +/- 0.04 post, NS; LogSD(.)Q: 0.38 +/- 0.03 pre, 0.37 +/- 0.03 post, NS. There was no significant change in arterial PO2 (99 +/- 2 pre, 99 +/- 3 mmHg post, NS) but arterial PCO2 was decreased (38.7 +/- 0.6 pre, 36.8 +/- 1.2 mmHg post, P < 0.05). Thus, infusion compressed small airways and caused a mild degree of hyperventilation. There was no evidence for a diffusive limitation to O2 exchange, with the measured-predicted alveolar-arterial oxygen partial pressure difference being unaltered by infusion at FIO2 = 0.125 (4.3 +/- 1.0 pre, 5.2 +/- 1.0 post, NS). After infusion, the fraction of perfusion going to areas with (.)VA/(.)Q < 1 was increased when a subject breathed a hyperoxic gas mixture [0.72 +/- 0.06 (FIO2 = 0.21), 0.80 +/- 0.06 (FIO2 = 0.30), P < 0.05] with similar effects on ventilation in the face of unchanged (.)VA and (.)Q. These results suggest active control of blood flow to regions of decreased ventilation during air breathing, thus minimizing the gas exchange consequences.

Pulmonary gas exchange following rapid intravenous saline infusion

Rapid infusion of i.v. saline, a model of pulmonary interstitial edema, alters the distribution of pulmonary perfusion, raises pulmonary capillary blood volume, and increases bronchial wall thickness in humans. We hypothesized infusion would disrupt pulmonary gas exchange by altering VA/Q matching. Seven males (26±3 years, FEV1 110±16% pred.) performed spirometry and had the distribution of VA/Q measured using MIGET, before and after 20ml/kg i.v. of normal saline delivered in ~30 minutes. Infusion increased thoracic fluid content by 12% (P &lt; 0.0001), left FVC unchanged, but reduced expiratory flows (e.g. FEF25–75 fell from 5.1±0.4 to 4.1±0.4 l/sec, P &lt; 0.05). However, infusion left the distribution of VA/Q unchanged; log SDV 0.40±0.03 pre, 0.38±0.04 post, NS; logSDQ, 0.38±0.03 pre, 0.37±0.03 post, NS. There was no significant change in arterial PO2 (99.2±2.5 pre, 99.5±2.9 mmHg post, NS) but arterial PCO2 was decreased (38.7±0.6 pre, 37.1±1.1 mmHg post, P&lt;0.05). Thus, infusion compressed small airways, and caused a mild degree of hyperventilation, but the matching of ventilation to perfusion was maintained, suggesting active control of blood flow to minimize the gas exchange consequences.

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury

LETTERS TO THE EDITORMaintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injuryE. Costa, and M. AmatoE. Costa, and M. AmatoPublished Online:01 Jun 2007https://doi.org/10.1152/japplphysiol.00154.2007MoreSectionsPDF (27 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat To the Editor: In the intriguing report by Syring et al. (3), the authors concluded that comparable reductions in tidal recruitment were obtained by either applying external positive end-expiratory pressure (PEEP) or by increasing respiratory rate. This latter conclusion deserves scrutiny, but their data seem not to support it. First, the reported time constant (0.47 s) of the oxygen probe used (1) is too long. By considering the short equilibrium time available in the high-rate group (inspiratory time = 1.66 s/expiratory time = 0.83 s), one could predict that this catheter measured only 82.5% of the actual arterial Po2 oscillations in these animals. In the best scenario, part of the decrease in arterial Po2 oscillations in the high-rate group should be ascribed to insufficient temporal resolution of the catheter. The same group, however, had previously shown that arterial Po2 changes following massive alveoli recruitment or derecruitment required 10–20 s to stabilize (1). By considering such longer time constants, the perceived swings in arterial Po2 would be just 13% of those in equilibrium. Therefore, respiratory rate should have a profound impact on the measured amplitude of arterial Po2 irrespective of the amount of tidal recruitment. Another important methodological limitation was the high plateau pressure used (28 cmH2O). Under low-PEEP conditions, such high inspiratory pressure in rabbits commonly exceeds the reopening pressure and results in tidal recruitment (2), which increases lung capillary Po2 each inspiration, resulting in a higher average arterial Po2 especially when inspiration is long (inspiratory time = 1.66 s). In this context, a high average arterial Po2 in the high-rate group was not enough to guarantee a permanently open-lung status. To prove that, the authors should demonstrate a high average arterial Po2 even after decreasing plateau pressures substantially.REFERENCES1 Baumgardner JE, Markstaller K, Pfeiffer B, Doebrich M, Otto CM. Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on PaO2 oscillations after saline lavage. Am J Respir Crit Care Med 166: 1556–1562, 2002.Crossref | ISI | Google Scholar2 Rotta AT, Gunnarsson B, Fuhrman BP, Hernan LJ, Steinhorn DM. Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury. Crit Care Med 29: 2176–2184, 2001.Crossref | PubMed | ISI | Google Scholar3 Syring RS, Otto CM, Spivack RE, Markstaller K, Baumgardner JE. Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury. J Appl Physiol 102: 331–339, 2007.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: M. Amato, 455 Dr. Arnaldo Ave., Rm. 2206, Sao Paulo SP 01246903, Brazil (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByA fibre optic oxygen sensor that detects rapid PO2 changes under simulated conditions of cyclical atelectasis in vitroRespiratory Physiology & Neurobiology, Vol. 191A Numerical Model of the Respiratory Modulation of Pulmonary Shunt and PaO2 Oscillations for Acute Lung Injury12 December 2009 | Annals of Biomedical Engineering, Vol. 38, No. 3Reply to Costa and AmatoJames E. Baumgardner, and Rebecca S. Syring1 June 2007 | Journal of Applied Physiology, Vol. 102, No. 6 More from this issue > Volume 102Issue 6June 2007Pages 2414-2414 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00154.2007PubMed17551113History Published online 1 June 2007 Published in print 1 June 2007 Metrics

Novel roles of a local angiotensin‐generating system in the carotid body

The carotid body is a highly vascularized network of chemoreceptor cells, which are located at the bifurcation of the internal and external carotid arteries arising from the common carotid artery. Carotid body chemoreceptors, called glomus (type 1, catechol-secreting) cells release dopamine in response to rapid changes in arterial PO2, PCO2 and pH, thus increasing carotid body sinus nerve activity and provoking centrally mediated cardiopulmonary responses (Gonzalez et al. 1994). The endocrine (circulating) renin–angiotensin system (RAS) plays a role in regulating the blood pressure, electrolyte and fluid homeostasis. The aspartyl protease renin cleaves the precursor of the system, angiotensinogen, to yield angiotensin I, which is subsequently cleaved by angiotensin converting enzyme (ACE) to yield the physiologically active octapeptide angiotensin II (Ang II). Pressor responses to Ang II are largely mediated through activation of the type 1 receptor (AT1R). It is now recognized that the RAS exists in diverse mammalian cells and organs, where it plays diverse roles in their respective tissues and organs. Apart from the haemodynamic function, they include, but are not limited to, cell proliferation, apoptosis, oxidative stress and inflammatory as well as fibrotic actions. This so-called local RAS which adds to and/or differs from the circulating RAS, frequently operated in a paracrine and/or autocrine manner (Lavoie & Sigmund, 2003). Newly discovered functions of locally generated Ang II in tissues and organs are of particular interest in the physiological and pathophysiological aspects. Such a system has recently been proposed to exist in the carotid body: here, key RAS components (including angiotensinogen, ACE, AT1R and AT2R) are expressed in the absence of renin, suggesting the existence of a renin-independent biosynthetic pathway for Ang II or an intrinsic angiotensin-generating system in the carotid body (Lam & Leung, 2002). This system may play a key role in modulating the carotid body response to hypoxia. Ang II itself increases carotid body efferent activity, presumably via AT1R activation (Allen, 1998). Meanwhile, chronic hypoxia up-regulates several key RAS components in the carotid body, including a time-course-dependent activity of ACE (Lam & Leung, 2003; Lam et al. 2004). Specifically, expression of the AT1R on glomus cells is enhanced, consistent with increased expression of the AT1R at gene and protein level (Leung et al. 2000). Chronic hypoxia thus enhances AT1R-mediated efferent activity (Leung et al. 2000). In addition, AT1R activation increases intracellular calcium levels in dissociated glomus cells, an effect which is enhanced three-fold by chronic hypoxaemia (Fung et al. 2002). Taken together, all data suggest that chronic hypoxia is a major factor that increases AT1R expression and function in the carotid chemoreceptor, with likely changes in cardiopulmonary function. Thus the excitatory action of Ang II on the glomus cells may increase the chemosensitivity of the carotid body and may counteract the blunting effect of chronic hypoxia. Notwithstanding this involvement of a local angiotensin-generating system in the carotid body, details of the molecular and cellular mechanisms underlying the modulation require extensive study. A paper by Li & Schultz (2006) in this issue of The Journal of Physiology adds valuable data to this story. Using a rabbit model of congestive heart failure (CHF), the authors demonstrate a role for local glomus Ang II/AT1R signalling in increasing the sensitivity of Kv channels to hypoxia. High concentrations of Ang II (> 1 nm) directly inhibit Kv currents (Ik) while changes in Kv channel protein expression may contribute to the suppression of Ik and enhanced sensitivity of Ik to hypoxia in the CHF state. This study has two significant implications: Ang II can enhance the oxygen sensitivity of Kv channels via the mediation of AT1R and the cellular Ang II–AT1R pathway is functional in carotid glomus cells of CHF but not normal animals. In spite of this solid evidence, the precise mechanism by which CHF up-regulates the Ang II–AT1R and its function in the carotid body have yet to be resolved. In this regard, chronically impaired cardiac output resulting from CHF might be sufficient to render a prolonged deprivation of oxygen delivery to carotid glomus cells, a state akin to chronic hypoxia, thus leading to activation of its cellular RAS pathway. These data indicate a paracrine/autocrine role of Ang II in the modulation of enhanced carotid chemoreceptor sensitivity to chronic hypoxia characterized in chronic heart failure. In summary, the carotid body is the major organ central to the physiological responses to various forms of hypoxic stress: acute, chronic and intermittent hypoxia. Thus, activation of the RAS by hypoxia might be commonly associated with chronic cardiopulmonary diseases and sleep apnoea. Of great interest in this context is the emerging data of evidence for the existence of a local carotid angiotensin-generating system, which is up-regulated by chronic hypoxia to alter carotid chemoreceptor sensitivity. The data of Li and Schultz thus support this concept.

Patterns of Changes in Arterial Po2 During One-Lung Ventilation

Survey of Anesthesiology: August 2006 - Volume 50 - Issue 4 - p 209 doi: 10.1097/01.sa.0000228086.66231.fb

Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies

Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. To study pharmacokinetics and cardiopulmonary effects of i.v. DEX. Pharmacokinetics of 3.5 microg/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 45 and 60 mins after administration of DEX 3.5 microg/kg bwt i.v. Data were analysed using ANOVA for repeated measures, and where appropriate Dunnett's t test was used to detect differences from resting values (P < 0.05). Within 2 h after DEX administration, plasma levels were beyond limits of quantification (0.05 ng/ml). Mean values for kinetic parameters for mature and old ponies were: Cmax (ng/ml) 4.6 and 3.8, t 1/2 (min) 19.8 and 28.9 and AUC (ng.min/ml) 34.5 and 44.3, respectively. Heart rate, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure did not change significantly compared to presedation values throughout the 60 min observation period. Compared to presedation values, stroke volume and mixed venous PO2 were reduced for the first 5 mins, paralleled by an increase in systemic and pulmonary vascular resistance. Cardiac index was reduced for the first 10 mins, arterial blood pressures at 20, 30 and 45 mins and respiratory rate throughout the 60 min observation period, but no change in arterial PO2 or PCO2 occurred. DEX administration i.v. causes similar cardiopulmonary changes to those caused by other alpha-2 adrenoceptor agonists, but of very short duration. DEX is redistributed particularly rapidly. DEX might be safer for sedation of horses because of its very short-lasting cardiopulmonary side effects. For long duration sedation, its kinetics favour its use as a continuous infusion.

ATP is a key mediator of central and peripheral chemosensory transduction.

Recent evidence suggests that ATP is a mediator of central (within the ventral surface of the medulla) and peripheral (within the carotid body) chemosensory transduction. This short review discusses the data obtained in experiments in vivo and in vitro supporting this hypothesis. P2 receptors for ATP are expressed within the ventrolateral medulla as well as by the peripheral chemosensory afferent neurones. Blockade of P2 receptors in the ventrolateral medulla attenuates the CO2-induced increase in respiration while blockade of purinergic signalling impairs carotid body function and diminishes the ventilatory response to hypoxia. Furthermore, ATP is released from the ventral surface of the medulla during hypercapnia and from the carotid body during hypoxia. Finally, exogenous ATP applied on the ventral surface of the medulla evokes rapid increase in phrenic nerve activity, while ATP applied to the carotid body evokes marked excitation of the carotid sinus nerve afferents. We suggest that in the ventrolateral medulla ATP is produced following CO2/H(+)-induced activation of central chemosensory elements (neuronal and/or glial) and acts within the respiratory network to produce physiologically relevant changes in ventilation. In the carotid body, ATP contributes in a significant manner to the transmission of the sensitivity of the carotid body to changes in arterial PO2 and may be considered as a key transmitter released by chemoreceptor cells to activate endings of the sinus nerve afferent fibres.

The cardiopulmonary effects of severe blood loss in anesthetized horses

ObjectiveTo characterize the acute cardiopulmonary effects of severe hemorrhage in anesthetized horses. Study designProspective experimental study. AnimalsThree geldings and six mares, aged 14.4 ± 2.7 years, weighing 486 ± 41 kg (range: 425-550 kg). MethodsHorses were anesthetized using xylazine, guaifenesin, ketamine and halothane or isoflurane. Cardiovascular variables, hematocrit, total solids, capillary refill time (CRT) and color of mucous membranes were measured as blood was collected from the carotid artery into sterile plastic bags. Arterial blood gas analysis was also performed. ResultsThe average amount of blood collected from these horses was (mean ± SD) 53 ± 4.8 mL kg−1 bodyweight (range: 23-32 kg) over 39 ± 4 minutes. Hematocrit decreased from 38 ± 3 to 32 ± 2% after induction of anesthesia and did not change significantly over the period of blood loss. Total solids decreased significantly after induction of anesthesia, and over the period of blood loss. Systolic, mean, diastolic and pulse pressures decreased as blood was lost. Heart rate did not change significantly. Capillary refill time increased from 1.6 ± 0.4 seconds to 4.8 ± 1.3 seconds as blood loss increased. Mucous membrane color deteriorated progressively. Arterial PO2 decreased significantly over the period of blood loss. ConclusionsHematocrit and heart rate do not change significantly during acute severe hemorrhage in the anesthetized horse. Arterial blood pressure, pulse pressure and PaO2 decrease as blood loss increases. Changes in mucous membrane color and CRT also occur as blood loss increases. Clinical relevanceDuring severe hemorrhage in the inhalant-anesthetized horse, both heart rate and hematocrit remain unchanged. Blood pressure decreases and changes in arterial PO2 correlate most strongly with volume of blood lost.

Fetal umbilical cord oxygen values and birth to placental weight ratio in relation to size at birth

Objective: Our purpose was to examine regulatory linkages between fetal oxygenation and fetal and placental growth. We determined umbilical cord PO2 and oxygen saturation, fractional oxygen extraction, and birth to placental weight ratio values in relation to size at birth for a large tertiary hospital population delivering at term. Study Design: The computerized perinatal database of St Joseph’s Health Care London, London, Ontario, was used to obtain the umbilical cord gases, pH, birth weight, placental weight, and other selected information for all term, singleton, liveborn infants between January 1990 and December 1999 (N = 27,043). Oxygen saturation values were calculated from the umbilical cord PO2 and pH data with a previously derived empirical equation; fractional oxygen extraction values were calculated from the umbilical cord oxygen saturation data. Size at birth was divided into the following 5 birth weight categories using neonatal growth standards: fetal growth restriction, <3%; borderline fetal growth restriction, ≥3% and <10%; appropriate for gestational age, ≥10% and ≤90%; borderline large for gestational age, >90% and ≤97%; large for gestational age, >97%. Results: Infants in the borderline fetal growth restriction and fetal growth restriction groups had umbilical vein and artery PO2 and oxygen saturation values that were stepwise lower than respective values for infants in the appropriate for gestational age group. Conversely, infants in the borderline large for gestational age and large for gestational age groups had umbilical vein PO2 and oxygen saturation values that were stepwise higher than respective appropriate for gestational age group values; infants in these groups showed no change in arterial PO2 and oxygen saturation values. Therefore infants in the borderline fetal growth restriction and fetal growth restriction groups had fractional oxygen extraction values that were stepwise higher than the appropriate for gestational age group value, whereas values for infants in the borderline large for gestational age and large for gestational age groups remained unchanged. Birth weight was disproportional to placental weight for infants in the borderline fetal growth restriction and fetal growth restriction groups when compared with that of the infants in the appropriate for gestational age group, with the birth to placental weight ratio values stepwise decreased. Conversely, birth weight was proportional to placental weight for infants in the borderline large for gestational age and large for gestational age groups with the birth to placental weight ratio values thus unchanged when compared with that of the infants in the appropriate for gestational age group. Conclusion: We conclude that fetal oxygenation is related to size at birth across the entire range of birth weights as studied at term from macrosomic to growth-restricted infants; this conclusion supports oxygen as a primary determinant of fetal growth. However, there are differences in the linkage between fetal oxygenation and metabolic rate or growth for these cohort groups that may relate to underlying etiologic processes. (Am J Obstet Gynecol 2001;185:674-82.)

Responses of single-unit carotid body chemoreceptors in adult rats.

1. Our goal was to describe the in situ responses in rats of single-unit carotid body chemoreceptors to changes in arterial PO2 and PCO2. We identified single-unit carotid chemoreceptor activity in male, adult Sprague-Dawley rats by their rapid responses to i.v. NaCN (20 microg) and transient (10 s) asphyxia. 2. Single-unit chemoreceptor responses to isocapnic changes in oxygenation within the arterial oxygen pressure range 34-114 mmHg were described by the power function: f(dis) = 74010(Pa,O2)-2.5; (r2 = 0.6), where f(dis) is the discharge frequency (spikes s-1), P(a,O2) is the arterial oxygen partial pressure (mmHg) and r2 is the correlation coefficient. 3. The responses to iso-oxic changes in CO2, assumed to be linear, had a slope of 0.089 spikes s-1 (mmHg Pa,CO2)-1 (r2 = 0.7). 4. We conclude that carotid body chemoreceptors in adult rats have responses to changes in Pa,O2 and Pa,CO2 similar to those of other species.

Actions of hypoxia on catecholamine synthetic enzyme mRNA expression before and after development of adrenal innervation in the sheep fetus.

We have investigated adrenal mRNA expression of the catecholamine synthetic enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) following acute hypoxia in fetal sheep before (< 105 days gestation, n = 20) and after (> 125 days gestation, n = 20) the development of adrenal innervation and following pretreatment with the nicotinic receptor anatgonist hexamethonium (n = 12). Total RNA was extracted from fetal adrenal glands collected at specific time points at 3-20 h after the onset of either hypoxia ( approximately 50% reduction in fetal arterial oxygen saturation (SO2) for 30 min), or normoxia. Before 105 days, there was a decrease in adrenal TH mRNA expression at 20 h after hypoxia and adrenal TH mRNA expression was directly related to the changes in arterial PO2 measured during normoxia and hypoxia. After 125 days, adrenal TH mRNA levels were suppressed for up to 12 h following hypoxia. In both age groups, adrenal PNMT mRNA expression increased at 3-5 h after hypoxia and was inversely related to the changes in fetal arterial PO2 during normoxia or hypoxia. After 125 days, the administration of hexamethonium (25 mg kg(-1), I.V.) reduced TH mRNA but not PNMT mRNA expression after normoxia. After hexamethonium pretreatment, there was no significant change in either adrenal TH or PNMT mRNA expression following hypoxia. We conclude that acute hypoxia differentially regulates adrenal TH and PNMT mRNA expression in the fetal sheep both before and after the development of adrenal innervation. After the development of adrenal innervation, however, the effect of acute hypoxia upon adrenal TH and PNMT mRNA expression is dependent upon neurogenic input acting via nicotinic receptors.

Cardiorespiratory responses of white sturgeon to environmental hypercapnia.

Cardioventilatory variables and blood-gas, acid-base status were measured in cannulated white sturgeon (Acipenser transmontanus) maintained at 19 degrees C during normocapnic and hypercapnic (Pw(CO(2)) approximately 20 Torr) water conditions and after the injection of adrenergic analogs. Hypercapnia produced significant increases in arterial PCO(2), ventilatory frequency, and plasma concentration of cortisol and epinephrine, and it produced significant decreases in arterial pH and plasma concentration of glucose but no change in arterial PO(2), hematocrit, and concentration of lactate or norepinephrine. Hypercapnia significantly increased cardiac output (Q) by 22%, mean arterial pressure (MAP) by 8%, and heart rate (HR) by 8%. However, gut blood flow (GBF) remained constant. In normocapnic fish, phenylephrine significantly constricted the splanchnic circulation, whereas isoproterenol significantly increased Q and produced a systemic vasodilation. During hypercapnia, propranolol significantly decreased Q, GBF, MAP, and HR, whereas phentolamine significantly decreased MAP and increased GBF. These changes suggest that cardiovascular function in the white sturgeon is sensitive to both alpha- and beta-adrenergic modulation. We found microspheres to be unreliable in predicting GBF on the basis of our comparisons with simultaneous direct measurements of GBF. Overall, our results demonstrate that environmental hypercapnia (e.g., as is experienced in high-intensity culture situations) elicits stress responses in white sturgeon that significantly elevate steady-state cardiovascular and ventilatory activity levels.