Decrease In Arterial Oxygen Tension Research Articles

A Rare Cause of Severe Biventricular Dyssynchrony During Venoarterial Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Failure

A Rare Cause of Severe Biventricular Dyssynchrony During Venoarterial Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Failure

Peripheral chemoresponsiveness during exercise in male athletes with exercise‐induced arterial hypoxaemia

What is the central question of this study? Do highly trained male endurance athletes who develop exercise-induced arterial hypoxaemia (EIAH) demonstrate reduced peripheral chemoresponsiveness during exercise? What is the main finding and its importance? Those with the lowest arterial saturation during exercise have a smaller ventilatory response to hypercapnia during exercise. There was no significant relationship between the hyperoxic ventilatory response and EIAH. The findings suggest that peripheral chemoresponsiveness to hypercapnia during exercise could play a role in the development of EIAH. The findings improve our understanding of the mechanisms that contribute to EIAH. Exercise-induced arterial hypoxaemia (EIAH) is characterized by a decrease in arterial oxygen tension and/or saturation during whole-body exercise, which may in part result from inadequate alveolar ventilation. However, the role of peripheral chemoresponsiveness in the development of EIAH is not well established. We hypothesized that those with the most severe EIAH would have an attenuated ventilatory response to hyperoxia and hypercapnia during exercise. To evaluate this, on separate days, we measured ventilatory sensitivity to hyperoxia and separately hypercapnia at rest and during three different exercise intensities (25, 50% of and ventilatory threshold (∼67% of )) in 12 males cyclists ( =66.6±4.7mlkg-1 min-1 ). Subjects were divided into two groups based on their end-exercise arterial oxygen saturation (ear oximetry, ): a normal oxyhaemoglobin saturation group (NOS, =93.4±0.4%,n=5) and a low oxyhaemoglobin saturation group (LOS, =89.9±0.9%, n=7). There was no difference in (66.4±2.9vs.66.8±6.0mlkg-1 min-1 , respectively, P=0.9), peak ventilation during maximal exercise (182±15vs.197±32lmin-1 , respectively, P=0.36) or ventilatory response to hyperoxia (P=0.98) at any exercise intensity between NOS and LOS groups. However, those in the LOS group had a significantly lower ventilatory response to hypercapnia (P=0.004, (η2 =0.18). There was also a significant relationship between the mean hypercapnic response and end-exercise (r=0.75, P=0.009) but not between the mean hyperoxic response and end-exercise (r=0.21, P=0.51). A blunted hypercapnic ventilatory response may contribute to EIAH in highly trained men due to a failure to increase ventilation sufficiently to offset exercise-induced gas exchange impairments.

Exercise-induced arterial hypoxemia; some answers, more questions.

Exercise-induced arterial hypoxemia (EIAH) is characterized by the decrease in arterial oxygen tension and oxyhemoglobin saturation during dynamic aerobic exercise. Since the time of the initial observations, our knowledge and understanding of EIAH has grown, but many unknowns remain. The purpose of this review is to provide an update on recent findings, highlight areas of disagreement, and identify where information is lacking. Specifically, this review will place emphasis on (i) the occurrence of EIAH during submaximal exercise, (ii) whether there are sex differences in the development and severity of EIAH, and (iii) unresolved questions and future directions.

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

BackgroundAspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue.MethodsMale Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion.ResultsLung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4–24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung.ConclusionThese findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

Pulmonary Arterial Hypertension-Specific Drug Therapy in COPD Patients with Severe Pulmonary Hypertension and Mild-to-Moderate Airflow Limitation

Background: Patients with severe pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD) present a poor outcome. Specific PH treatment could improve the clinical and hemodynamic status of these patients but may worsen arterial blood gases. Objectives: Our study retrospectively included 28 patients with severe precapillary PH (mean pulmonary arterial pressure >35 mm Hg) associated with mild-to-moderate COPD [forced expiratory volume in 1 s (FEV₁) >50% predicted]. All patients underwent specific pulmonary arterial hypertension (PAH) treatment as mono-, bi- or triple therapy. Methods: Our single-center study was conducted based on retrospective data of 537 right heart catheterizations (RHCs) performed on patients with COPD from January 2004 to June 2014. An echocardiography, comprehensive blood tests, pulmonary function tests, and a high-resolution computed tomography were performed before the RHCs. All patients underwent RHC with a Swan-Ganz catheter. Results: Compared to baseline, patients treated with specific PAH drugs showed a significant increase in cardiac index at long term (2.5 ± 0.7 liters/min/m² at baseline vs. 3.2 ± 0.6 liters/min/m² at 6/12 months; p = 0.003) as well as a decrease in pulmonary vascular resistance in the long term (8.4 ± 4.2 Wood units at baseline vs. 5 ± 1.7 Wood units at 6/12 months; p = 0.008). There was a slight decrease in arterial oxygen tension (Pa<smlcap>O</smlcap>₂) after 3 months of treatment (-2.4 ± 7.21 mm Hg; p = 0.066). During a median follow-up of 3 years, 12 patients (42.8%) died (including all causes of death). Conclusions: This preliminary report suggests that the use of specific PH therapy in severe PH associated with mild-to-moderate COPD can improve pulmonary hemodynamic parameters, with worsening of Pa<smlcap>O</smlcap>₂, which had no clinical significance and did not lead to specific PAH therapy withdrawal in any patient.

Effect of postoperative xylazine administration on cardiopulmonary function and recovery quality after isoflurane anesthesia in horses

To evaluate equine cardiopulmonary function and recovery quality after administration of 0.25 or 0.50 mg/kg xylazine intravenously (IV) during recovery. Randomized, blinded, prospective, clinical study. Horses (n = 20). During recovery after 3 hours of isoflurane anesthesia for arthroscopic surgery, horses were administered either 0.25 mg/kg (G25, n = 10) or 0.50 mg/kg (G50, n = 10) xylazine intravenously. Vital signs and arterial blood samples were obtained during recovery before sedation (baseline), 5, 10, 20, 30, and 45 minutes after xylazine and 30 minutes after standing. The quality of recovery scores ranged from 10 to 72 (10 = best, 72 = worst). G25 horses recovered faster (mean ± SD, 33 ± 5 min) than G50 horses (50 ± 7 min, P < .0001). Mean maximal decrease in arterial oxygen tension was 55 ± 11 mmHg in G25 (at 10 minutes; P < .05) and 54 ± 7 mmHg in G50 (at 20 minutes; P < .01). G25 group had a total recovery score (23 [range 18-29]) and number of attempts to stand (4 ± 2) greater than the G50 group (18 [10-23] and 1 ± 1, respectively; P < .001). Both doses of xylazine promoted a moderate and transient hypoxemia during recovery; however, the 0.5 mg/kg dose produced a longer and improved quality of recovery from anesthesia.

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension ( ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption ( ) = 49 ± 1, range 28-62 ml kg(-1) min(-1)) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (~85% ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation ( ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg(-1) min(-1)), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min(-1)), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism.

Role of MaxiK-type calcium dependent K+ channels in rat carotid body hypoxia transduction during postnatal development

Carotid body chemoreceptors transduce a decrease in arterial oxygen tension into increased sinus nerve action potential (AP) activity which undergoes a maturational increase in the post-natal period. MaxiK-channels channels are proposed to play a major role in organ function based on their maturation-dependent expression in glomus cells and inhibition by acute hypoxia. To better resolve the role of this channel, single-unit AP activity of rat chemoreceptor neurons was recorded, in vitro, during a progressive decrease in oxygen from normoxia (∼150 Torr) to moderate hypoxia (∼60 Torr). Blockade of MaxiK channels with charybdotoxin (100 nM) in both older (P16-P18) and younger (P2-P3) animals resulted in no significant change in AP activity, but increased nerve conduction speed in the older animals. In dissociated glomus cells, charybdotoxin slightly enhanced the intracellular calcium response to acute hypoxia at both ages. We conclude that MaxiK channels play little or no role in mediating the response to acute, moderate hypoxia, either in the newborn or older animal.

Hypoxemia during surgery: learning from history, science, and current practice

Prevention of hypoxemia remains one of the primary goals related to the safe practice of anesthesia. Development of the pulse oximeter has allowed for the reliable detection and prompt treatment of hypoxemia. As reviewed by Drs. Ehrenfeld et al. in this issue of the Journal, routine intraoperative application of pulse oximetry coupled with parallel increases in patient safety has made a significant impact on the practice of anesthesia. Careful conduct of anesthesia based on real-time knowledge of blood oxygenation (SpO2) stands in stark contrast with anesthesia practice patterns of previous eras in which short-term maintenance of anesthesia with high concentrations of nitrous oxide was regarded as effective and safe in healthy pre-oxygenated patients. With the invention and use of the oxygen electrode, it gradually became apparent that profound decreases in arterial oxygen tension occurred with the former method of anesthetic induction. Nonetheless, several clinical studies were continued wherein high concentrations of nitrous oxide with reciprocally low concentrations of inspired oxygen were explored. This practice led to the frequent occurrence of clinically significant hypoxemia. In their classic article published a half century ago, Heller et al. reported the following with respect to induction of anesthesia: ‘‘It is preferable to start with an 80/20 mixture of N2O and O2 rather than to subject the anxious wakeful patient to a preliminary period of (100%) oxygen breathing.’’ Although such approaches were developed at a time of limited availability of anesthetic agents, this practice – thankfully differs dramatically from our current approach. These days, we often advocate the avoidance of nitrous oxide, and pre-oxygenation is advocated routinely as one means to prevent hypoxemia. The large database of the current study helps us to appreciate further the frequency and risks of perioperative hypoxia, moving us forward from the days of ‘‘black gas anesthesia’’. In their report in this issue of the Journal, Ehrenfeld et al. present the incidence of hypoxemia during surgery using data they derived from a sizeable series of electronic records from two large medical centres. The authors report that hypoxemia (SpO2 90%) is infrequent (6.8%) but perhaps too common for an entity that anesthesiologists always try to avoid. Indeed, severe hypoxemia (SpO2 85%) occurred in 3.5% of patients. They also reported that transient hypoxemia occurred during all phases of anesthesia, especially during induction and emergence and particularly in patients who were American Society of Anesthesiologists (ASA) physical status III or IV. Aside from recognizing that we have not ‘‘conquered’’ intraoperative hypoxemia, what other important lessons can be learned from these data? First, we should reiterate the most obvious positive news. Acceptable levels of SpO2 ([ 90%) were maintained G. M. T. Hare, MD, PhD Department of Anesthesia, Keenan Research Centre in the Li Ka Shing Knowledge Institute and the Cara Phelan Centre for Trauma Research, St. Michael’s Hospital, Toronto, ON, Canada

Nicotinic acetylcholine receptors do not mediate excitatory transmission in young rat carotid body

Carotid body chemoreceptors transduce a decrease in arterial oxygen tension into increased action potential (AP) activity on the sinus nerve, which increases the drive to breathe. The mechanism by which AP activity increases is unresolved, but acetylcholine (ACh), acting through nicotinic receptors, is postulated to be a major contributor to nerve excitation based partly on the demonstration that pharmacological antagonism of nicotinic receptors reduces the afferent nerve response in some studies. However, most previous studies relied on indirect measures of chemoreceptor activity or utilized a recording configuration that is sensitive to AP morphology in addition to AP frequency. In the present study, single-unit AP activity was recorded from the soma of rat chemoreceptor neurons in vitro. The nicotinic blocker mecamylamine (50 microM) ablated the excitatory actions of exogenous ACh and increased, rather than decreased, AP activity during moderate hypoxia. At higher dosage (500 microM) AP height was reduced, conduction velocity slowed, and conduction failure occurred, especially during hypoxia, producing the appearance of a decreased response to hypoxia. Recovery from mecamylamine block was slow (>10 min). In contrast to mecamylamine, suramin, a P2X receptor blocker, reversibly inhibited the response to hypoxia, suggesting relatively free diffusion of drugs to the glomus cell/nerve synaptic site. These results strongly suggest that ACh acting through nicotinic receptors does not mediate excitatory transmission in rat carotid body and that previous results demonstrating such a role may have been partially influenced by changes in AP morphology or conduction failure.

Very Early Extubation after Open-Heart Surgery in Children Does Not Influence Cardiac Function

The objective of our study was to evaluate hemodynamic effects and the cardiac function after very early extubation within the first 6 hours after open-heart surgery in children. During a 12-month period, we performed a retrospective study of 50 children (ages 3 months to 7 years) admitted to the pediatric intensive care unit immediately after minor cardiac surgery. All children were extubated within the first 6 hours after their arrival. Arterial blood and central venous pressure were monitored, and arterial blood gas analysis was performed. Cardiac index, stroke volume index, systemic vascular resistance index, and extravascular lung water index were measured by thermodilution. Early extubation of children after minor open-heart surgery with cardiopulmonary bypass is safe and does not affect cardiac functions. A slight decrease of arterial oxygen tension not resulting in respiratory or metabolic acidosis or reintubation was noted. Very early extubation in children after open-heart surgery does not promote cardiodepressive effects. It is a safe procedure that helps to reduce the unnecessary and prolonged mechanical ventilation of children after cardiopulmonary bypass surgery.

Lidocaine pretreatment attenuates inflammatory response of acute lung injury induced by Endotoxin in rabbits

Objective To evaluate the effect on inflammatory response and dose-response relationship of lidocaine pretreatment in Endotoxin-induced acute lung injury rabbit model.Methods Thirty anesthetized rabbits were randomly divided into six groups(n = 5 each).Lung injury was induced in rabbits by intravenous infusion of Escbericbia coli endotoxin(100 μg/kg over a 60 min period).10 min before infusion of endotoxin, one group was assigned to receive intravenous infusion of saline(as control);while others received intravenous infusion of lidocaine at different concentrations. Homodynamics, arterial oxygen tension and cytokines concentrations in plasma were recorded. The lung wet-to-dry-weight ratio was analyzed as an index of pulmonary edema. Light microscopic findings (lung injury score) were compared in the six groups. Results Endotoxin caused marked decrease in arterial oxygen tension, and increase in the lung wet-to dry-weight ratio, interleukin-6,interleukin-10 and tumor necrosis factor-α in plasma. Lidocaine pretreatment attenuated these changes significantly (P0.05). Endotoxin increased lung injury score. These changes were attenuated by lidocaine significantly in relation with its doses(P0.05). Conclusion Results suggest that intravenous lidocaine pretreatment might attenuates inflammatory response in relation with its doses in endotoxin-induced acute lung injury rabbit model.

Open and Closed-circuit Endotracheal Suctioning in Acute Lung Injury

Closed-circuit endotracheal suctioning (CES) is advocated for preventing hypoxemia caused by the loss of lung volume resulting from open endotracheal suctioning (OES). However, the efficiency of CES and OES on tracheal secretion removal has never been compared in patients with acute lung injury. The authors designed a two-part study aimed at comparing gas exchange and efficiency between OES and CES performed at two levels of negative pressure. Among 18 patients with acute lung injury, 9 underwent CES and OES at 3-h intervals in a random order using a negative pressure of -200 mmHg. Nine other patients underwent CES twice using two levels of negative pressure (-200 and -400 mmHg) applied in a random order. After each CES, a recruitment maneuver was performed using 20 consecutive hyperinflations. Tracheal aspirates were weighed after each suctioning procedure. Arterial blood gases were continuously recorded using an intravascular sensor. Open endotracheal suctioning induced a significant 18% decrease in arterial oxygen tension (Pa(O2)) (range, +13 to -71%) and an 8% increase in arterial carbon dioxide tension (Pa(CO2)) (range, -2 to +16%) that persisted 15 min after the end of the procedure. CES using -200 cm H2O did not change Pa(O2), but tracheal aspirate mass was lower compared with OES (0.6 +/- 1.0 vs. 3.2 +/- 5.1 g; P = 0.03). Increasing negative pressure to -400 cm H2O during CES did not change Pa(O2) but increased the tracheal aspirate mass (1.7 +/- 1.6 vs. 1.0 +/- 1.3 g; P = 0.02). Closed-circuit endotracheal suctioning followed by a recruitment maneuver prevents hypoxemia resulting from OES but decreases secretion removal. Increasing suctioning pressure enhances suctioning efficiency without impairing gas exchange.

Mitochondrial Function and Carotid Body Transduction

Carotid body chemoreceptors respond to a decrease in arterial oxygen tension by increasing spiking activity on the sinus nerve. Our understanding of the oxygen-transducing ability of the organ arose from studies in the 1930s intended to understand how metabolic poisons stimulated breathing. Since that time, an intimate link between energy state and hypoxia sensing has been assumed and forms the basis of the metabolic hypothesis of oxygen sensing. This hypothesis is supported by studies demonstrating a loss of mitochondrial potential in carotid body cells at oxygen tensions that cause no change in cells from other tissues. Although the nature of the coupling between mitochondrial function and nerve excitation remains unresolved, experimental evidence supports roles for (1) release of mitochondrial calcium stores, (2) modulation of membrane channels that are linked to mitochondrial complexes I and IV, and (3) generation of signaling intermediates, such as reactive oxygen species (ROS) from complex I and III of the electron transport chain. If the mitochondrion is the oxygen-sensing site for peripheral chemoreceptors, then there exists the potential ability to manipulate, perhaps pharmacologically, the sensing function by alterations in expression of uncoupler proteins or chemicals that can alter the affinity of cytochrome oxidase for oxygen. Such manipulation may be useful for the treatment of hypoventilation syndromes or high altitude accommodation.

Hypoxaemia in chronic obstructive pulmonary disease patients during a commercial flight

The aim of the study was to investigate hypoxaemia in chronic obstructive pulmonary disease patients during a commercial flight. The effect of a commercial flight, lasting 5 h 40 min, on arterial blood gas levels and symptoms in 18 chronic obstructive pulmonary disease patients with a pre-flight percutaneous oxygen saturation of 94% and self-reported ability to walk 50 m without severe dyspnoea was studied. The arterial oxygen tension (Pa,O2) decreased from sea level to cruising altitude (10.3+/-1.2 versus 8.6+/-0.8 kPa), but, thereafter, except for one patient, remained stable throughout the flight. During light exercise, however, there was further desaturation (percutaneous oxygen saturation 90+/-4 versus 87+/-4%). After 4 h, a decrease in arterial carbon dioxide tension (5.0+/-0.4 versus 4.8+/-0.4 kPa) and an increase in cardiac frequency (87+/-13 versus 95+/-13 beats x min(-1)) were observed. A pre-flight Pa,O2 of >9.3 kPa did not secure an acceptable in-flight Pa,O2. Aerobic capacity showed the strongest correlation with in-flight Pa,O2. In conclusion, following an initial decrease in arterial oxygen tension, chronic obstructive pulmonary disease patients in a stable state of their disease seem to maintain a stable arterial oxygen tension throughout a flight of intermediate duration, except when walking along the aisle. However, a decrease in arterial carbon dioxide tension, indicating compensatory hyperventilation, could imply a risk of respiratory fatigue during longer flights.

A noninvasive partial carbon dioxide rebreathing technique for measurement of pulmonary capillary blood flow is also a useful oxygenation monitor during one-lung ventilation

Study objectives To test the hypothesis that effective pulmonary capillary blood flow can be a useful indicator for estimating appropriate oxygenation and ventilation during one-lung ventilation in lung surgery. Design Prospective data analysis. Setting A 770-bed general teaching hospital. Patients 15 ASA physical status II and III patients undergoing elective lung surgery. Interventions Patients received general and thoracic epidural anesthesia and underwent lung operation with one-lung ventilation. Measurements We measured effective pulmonary capillary blood flow by a partial CO 2 rebreathing method and oxygenation parameters during two-lung ventilation before surgery, during one-lung ventilation, and during two-lung ventilation after lung surgery. Main results The effective pulmonary capillary blood flow index significantly decreased by 31.6%, which was associated with a significant decrease in arterial oxygen tension (PaO 2). The pulmonary shunt fraction increased to 46.3% during one-lung ventilation. During two-lung ventilation, after chest closure, effective pulmonary capillary blood flow index divided by heart rate (i.e., effective pulmonary blood stroke flow index) was still significantly lower than that seen during two-lung ventilation before thoracotomy. There were significant correlations between effective pulmonary capillary blood flow, pulmonary blood stroke flow index, and PaO 2. Conclusions Effective pulmonary capillary blood flow index and effective pulmonary blood stroke flow index are useful indicators for determining appropriate oxygenation therapy during one-lung ventilation.

Effects of antenatal steroids on ischemic brain injury in near-term ovine fetuses

Background: Hypoxia/ischemia in utero can result in brain damage to the fetus and newborn. Antenatal steroids are a routine part of the management of women who develop premature labor. Pretreatment of young postnatal rats with dexamethasone before hypoxic/ischemic insults has been reported to attenuate brain injury. However, the effects of antenatal steroids on ischemic brain injury in fetuses have not been investigated. Objective: We examined the effects of maternally administered antenatal corticosteroids on ischemic brain injury in near-term ovine fetuses. Methods: Chronically instrumented fetuses at 122 days of gestation were studied 12 h after the last of four 4 mg dexamethasone, or placebo injections were given over 48 h to the ewes. Groups were dexamethasone/ischemic, placebo/ischemic and sham-treated control. Fetuses were exposed to 30 min of carotid occlusion (ischemia) or no occlusion (control) and 72 h of reperfusion. Whole brain coronal sections stained with Luxol fast blue-hematoxylin-eosin were scored for white matter and cerebral cortical lesions. Both areas received pathological scores of 0 to 5 reflecting the degree of injury (0=0%, 1=1–10%, 2=11–50%, 3=51–90%, 4=91–99% and 5=100%). Bilateral carotid blood flow also was measured before, during and after brain ischemia in the dexamethasone/ischemic and placebo/ischemic groups. Results: White matter (WM) and cerebral cortical scores did not differ between the dexamethasone/ischemic and placebo/ischemic (WM: 3.0±1.9 and 2.9±1.7; cortex: 3.1±1.7 and 2.6±1.8, mean±S.D.) groups. White matter and cerebral cortical scores were higher in the dexamethasone/ischemic (WM: 3.0±1.9, P<0.02; cortex: 3.1±1.7, P<0.005) and placebo/ischemic (WM: 2.9±1.7, P<0.006; cortex: 2.6±1.8, P<0.007) than control (WM: 0.2±0.4; cortex: 0.2±0.4) group. Carotid blood flow was relatively higher ( P<0.05) after 24, 48 and 72 h of reperfusion in the dexamethasone/ischemic than placebo/ischemic group. Conclusions: We conclude that maternal pretreatment with antenatal dexamethasone did not attenuate ischemic brain injury in the fetus, and that carotid blood flow was higher during reperfusion in fetuses of dexamethasone than placebo-treated ewes, most likely secondary to decreases in arterial oxygen tension.

Characterization and developmental changes of Na+ currents of petrosal neurons with projections to the carotid body.

Carotid body chemoreceptors transduce a decrease in arterial oxygen tension into an increase in spiking activity on the sinus nerve, and this response increases with postnatal age over the first week or two of life. Previous work from our laboratory has suggested a major role of axonal Na(+) channels in the initiation of afferent spiking activity. Using RT-PCR of the petrosal ganglia we identified Na(+) channel TTX-S isoforms Na(v)1.1, Na(v)1.6, and Na(v)1.7 and the TTX-resistant (TTX-R) isoforms Na(v)1.8 and Na(v)1.9 at high levels. Electrophysiologic recordings (at 3 ages: 3 days, 9 days, 18-20 days) of neurons that project to the carotid body exhibited predominantly fast-inactivating sodium currents, with a bimodal recovery from inactivation at -80 mV (fast component approximately 8 ms; slow component approximately 90 ms). Developmental age had little effect with no change in peak current density (approximately 1.4 nA/pF) and was associated with a slight, but significant increase in the speed of recovery from inactivation at -140 and -120 mV but not at other potentials. Assuming that the same Na(+) channel complement is present at the nerve terminal as at the soma, the association of a sensory modality (chemoreception) with a relatively uniform Na(+) channel profile suggests that the rapid kinetics of TTX-S channels may be essential for some aspects of chemoreceptor function beyond mediating simple axonal conduction.

Proinflammatory Cytokines Are Not Released in the Circulation Following Acute Pulmonary Thromboembolism in Pigs

Histological examination of acute lung injury associated with sepsis often revealed thromboembolic lesions in the pulmonary microcirculation. Several inflammatory mediators such as platelet activating factor, thromboxane, and endothelins have also been implicated in the pathogenesis of acute pulmonary thromboembolism (APTE). In the present study we examined the roles of three proinflammatory cytokines, tumor necrosis factor- f (TNF- f ), interleukin 1 g (IL-1 g ), and IL-8, in the early phase of APTE. APTE was induced in 13 anesthetized piglets (22 - 4 kg) by injecting thrombin-induced blood clots directly into the left lower lobar pulmonary artery. Five animals that received only warm sterile saline served as controls. Arterial plasma samples were collected regularly over 8 h so that cytokine levels could be measured later by enzyme-linked immunosorbent assay (ELISA). Administration of clots doubled the mean pulmonary arterial pressure (from 13 - 5 to 26 - 7 mm Hg) and caused significant decrease in arterial oxygen tension (PaO 2 from 390 - 85 to 256 - 89 mm Hg while the FiO 2 was maintained at 1.0). Mean arterial blood pressure and cardiac output remained comparable throughout the experiments after initial fluid resuscitation. Plasma levels of TNF- f , IL-1 g , and IL-8 were not significantly increased in the APTE group when compared with their baseline values or the control group. Our results thus show that APTE is associated with pulmonary hypertension and deterioration of gas exchange but not with the systemic release of TNF- f , IL-1 g , or IL-8. We conclude that these cytokines have minimal impact on the systemic circulation during APTE.

Methylprednisolone attenuates the interleukin-6 response, but exacerbates porcine pulmonary dysfunction induced by infrarenal aortic ischaemia-reperfusion

The authors have demonstrated that MP significantly attenuates the pro-inflammatory response in this model. However, MP has a detrimental effect on pulmonary function as measured by a significant decrease in arterial oxygen tension. Although MP has been shown to be renal protective in the perioperative setting, its negative impact on intraoperative pulmonary function requires further elucidation.