Arterial Blood CO2 Tension Research Articles

Therapeutic hypercapnia reduces blood\u2013brain barrier damage possibly via protein kinase C\u03b5 in rats with lateral fluid percussion injury

BackgroundThis study investigated whether therapeutic hypercapnia (TH) ameliorated blood–brain barrier (BBB) damage and improved the neurologic outcome in a rat model of lateral fluid percussion injury (FPI), and explored the possible underlying mechanism.MethodsRats underwent lateral FPI and received inhalation of 30%O2–70%N2 or 30%O2–N2 plus CO2 to maintain arterial blood CO2 tension (PaCO2) between 80 and 100 mmHg for 3 h. To further explore the possible mechanisms for the protective effects of TH, a PKC inhibitor staurosporine or PKCαβ inhibitor GÖ6976 was administered via intracerebral ventricular injection.ResultsTH significantly improved neurological function 24 h, 48 h, 7 d, and 14 d after FPI. The wet/dry ratio, computed tomography values, Evans blue content, and histological lesion volume were significantly reduced by TH. Moreover, numbers of survived neurons and the expression of tight junction proteins (ZO-1, occludin, and claudin-5) were significantly elevated after TH treatment at 48-h post-FPI. TH significantly increased the expression of protein kinase Cε (PKCε) at 48-h post-FPI, but did not significantly change the expression of PKCα and PKCβII. PKC inhibitor staurosporine (but not the selective PKCαβ inhibitor-GÖ6976) inhibited the protective effect of TH.ConclusionsTherapeutic hypercapnia is a promising candidate that should be further evaluated for clinical treatment. It not only protects the traumatic penumbra from secondary injury and improves histological structure but also maintains the integrity of BBB and reduces neurologic deficits after trauma in a rat model of FPI.

Neuroprotective effects of therapeutic hypercapnia on spatial memory and sensorimotor impairment via anti-apoptotic mechanisms after focal cerebral ischemia/reperfusion

A number of studies have demonstrated that therapeutic hypercapnia ameliorates neurological deficits and attenuates the histological damage of cerebral ischemia-reperfusion injury. However, the effects of therapeutic hypercapnia on impaired spatial memory have not been reported. Here we aimed to investigate the effects and mechanisms of therapeutic hypercapnia on spatial memory in a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Adult male rats were randomly assigned into three experimental groups: sham (sham operation), IR (MCAO/R), and hypercapnia [arterial blood CO2 tension (PaCO2) 80–100mmHg+IR] groups. Sensorimotor deficits and spatial memory testing were evaluated by an 18-point scoring system and an 8-arm radial maze task, respectively. The hippocampal histological damage and the percentage of apoptotic neurons were evaluated by hematoxylin and eosin (HE) staining as well as flow cytometry. Western blotting was used to investigate the changes of the apoptosis-related Bcl-2 and Bax proteins. The results indicated that hypercapnia treatment significantly improved the abilities of impaired sensorimotor and spatial memory after MCAO/R. Moreover, hypercapnia treatment significantly increased the percentage of surviving neurons and decreased the percentage of apoptotic neurons in the hippocampus after MCAO/R damage. The expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax were significantly increased and decreased in the hypercapnia treated rats, respectively. These findings suggest that therapeutic hypercapnia can attenuate neuronal apoptosis and improve impaired spatial memory and sensorimotor after MCAO/R, which may be attributable to its anti-apoptotic effects through modulation of apoptosis-related protein.

Neurally adjusted ventilatory assist (NAVA) in pediatric intensive care—A randomized controlled trial

Neurally adjusted ventilatory assist (NAVA) has been shown to improve patient-ventilator synchrony during invasive ventilation. The aim of this trial was to study NAVA as a primary ventilation mode in pediatric intensive care and to compare it with current standard ventilation modes. One hundred seventy pediatric intensive care patients were randomized to conventional ventilation or NAVA. The primary endpoints were time on the ventilator and the amount of sedation needed. To enable comparison between sedative agents, a "sedative unit" was defined for each drug. The median time on the ventilator was 3.3 hr in the NAVA group and 6.6 hr in the control group (P = 0.17), and the length of stay in the PICU 49.5 hr in the NAVA group and 72.8 hr in the control group (P = 0.10, per protocol P = 0.03). The amount of sedation needed in the total patient population did not differ between the groups (P = 0.20), but when postoperative patients were excluded (19 vs. 20 patients), the amount was significantly lower in the NAVA group (0.80 vs. 2.23 units/hr, P = 0.03). Lower peak inspiratory pressure and a lower inspired oxygen fraction were found in the NAVA group (P = 0.001 for both). Arterial blood CO2 tensions were slightly higher in the NAVA group up to 32 hr of treatment (P = 0.008). There were no significant differences in the other ventilatory or vital parameters, arterial blood gas values or complications. We found NAVA to be a safe and feasible primary ventilation mode for use with children. It outscored standard ventilation in some aspects, as it was able to enhance oxygenation even at lower airway pressures and led to reduced use of sedatives during longer periods of treatment.

Therapeutic hypercapnia improves functional recovery and attenuates injury via antiapoptotic mechanisms in a rat focal cerebral ischemia/reperfusion model

Recent studies have demonstrated neuroprotective effects of therapeutic hypercapnia for different forms of brain injury. However, few studies have assessed the neuroprotective and neurobehavioral effects of hypercapnia in focal cerebral ischemia, and the underlying mechanisms are still unclear. Here, we investigated the effects of therapeutic hypercapnia in focal cerebral ischemia in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Adult male Sprague Dawley rats were subjected to 90min of MCAO/R and subsequently exposed to increased carbon dioxide (CO2) levels to maintain arterial blood CO2 tension (PaCO2) between 80 and 100mmHg for 2h. Neurological deficits were evaluated with the corner test at days 1, 7, 14, and 28. Infarction volume and apoptotic changes were assessed by 2, 3, 7-triphenyltetrazolium chloride (TTC) staining, and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining at 24h after reperfusion. Apoptosis-related proteins (Bcl-2, Bax, cytochrome c, and caspase-3) were investigated by western blotting. The results of this study showed that therapeutic hypercapnia significantly reduced infarct volume and improved neurological scores after MCAO/R. Moreover, hypercapnia treatment increased the survival rate at 28 days after reperfusion. The TUNEL-positive neurons in the ipsilateral cortex were significantly decreased in the hypercapnia group. Mitochondrial Bcl-2 and Bax cortical expression levels were significantly higher and lower, respectively, in hypercapnia-treated rats. In addition, hypercapnia treatment decreased cytosolic cytochrome c and cleaved caspase-3 expression and increased cytosolic Bax expression. These findings indicate that therapeutic hypercapnia preserves brain tissue and promotes functional neurological recovery through antiapoptotic mechanisms.

Hyperhydration prior to a simulated second day of the 3-day moderate intensity equestrian competition does not cause arterial hypoxemia in Thoroughbred horses

Dehydration and the associated impairment of cardiovascular and thermoregulatory function comprise major veterinary problems in horses performing prolonged exercise, particularly under hot and humid conditions. For these reasons, there is considerable interest in using pre-exercise hyperhydration to help maintain blood volume in the face of the excessive fluid loss associated with sweat production during prolonged exertion. However, recently it was reported that pre-exercise hyperhydration causes arterial hypoxemia in horses performing moderate intensity exercise simulating the second day of an equestrian 3-day event competition (E3DEC) which may adversely affect performance (Sosa Leon et al. in Equine Vet J Suppl 34:425-429, 2002). These findings are contrary to data from horses performing short-term maximal exertion, wherein hyperhydration did not affect arterial O2 tension/saturation. Thus, our objective in the present study was to examine the impact of pre-exercise hyperhydration on arterial oxygenation of Thoroughbred horses performing an exercise test simulating the second day of an E3DEC. Control and hyperhydration studies were carried out on seven healthy Thoroughbred horses in random order, 7 days apart. In the control study, horses received no medications. In the hyperhydration experiments, nasogastric administration of NaCl (0.425 g/kg) 5 h pre-exercise induced a plasma volume expansion of 10.9% at the initiation of exercise. This methodology for inducing hypervolemia was different from that of Sosa Leon et al. (2002). Blood-gas tensions/pH as well as plasma protein, hemoglobin and blood lactate concentrations were measured pre-exercise and during the exercise test. Our data revealed that pre-exercise hyperhydration neither adversely affected arterial O2 tension nor hemoglobin-O2 saturation at any time during the exercise test simulating the second day of an E3DEC. Further, it was observed that arterial blood CO2 tension, pH, and blood lactate concentrations also were not affected by pre-exercise hyperhydration. However, hemodilution in hyperhydrated horses caused an attenuation of the expansion in the arterial to mixed-venous blood O2 content gradient during phases B and D of the exercise protocol, which was likely offset by an increase in cardiac output. It is concluded that pre-exercise hyperhydration of horses induced in the manner described above is not detrimental to arterial oxygenation of horses performing an exercise test simulating the second day of an E3DEC.

Clinical evaluation of an instrument to measure carbon dioxide tension at the oxygenator gas outlet in cardiopulmonary bypass

This paper presents the clinical testing of a new capnograph designed to measure the carbon dioxide tension at the oxygenator exhaust outlet in cardiopulmonary bypass (CPB). During CPB, there is a need for reliable, accurate and instant estimates of the arterial blood CO2 tension (PaCO2) in the patient. Currently, the standard practice for measuring PaCO2 involves the manual collection of intermittent blood samples, followed by a separate analysis performed by a blood gas analyser. Probes for inline blood gas measurement exist, but they are expensive and, thus, unsuitable for routine use. A well-known method is to measure PexCO2, ie, the partial pressure of CO2 in the exhaust gas output from the oxygenator and use this as an indirect estimate for PaCO2. Based on a commercially available CO2 sensor circuit board, a laminar flow capnograph was developed. A standard sample line with integrated water trap was connected to the oxygenator exhaust port. Fifty patients were divided into six different groups with respect to oxygenator type and temperature range. Both arterial and venous blood gas samples were drawn from the CPB circuit at various temperatures. Alfa-stat corrected pCO2 values were obtained by running a linear regression for each group based on the arterial temperature and then correcting the PexCO2 accordingly. The accuracy of the six groups was found to be (+/- SD): +/- 4.3, +/- 4.8, +/- 5.7, +/- 1.0, +/- 3.7 and +/- 2.1%. These results suggest that oxygenator exhaust capnography is a simple, inexpensive and reliable method of estimating the PaCO2 in both adult and pediatric patients at all relevant-temperatures.

Pre-and post-branchial blood respiratory status during acute hypercapnia or hypoxia in rainbow trout,Oncorhynchus mykiss

Simultaneous venous (pre-branchial) and arterial (post-branchial) extracorporeal blood circulations were utilized to monitor continuously the rapid and progressive effects of acute environmental hypercapnia (water partial pressure of CO2 4.8±0.2 torr) or hypoxia (water partial pressure of O2 25±2 torr) on oxygen and carbon dioxide tensions and pH in the blood of rainbow trout (Oncorhynchus mykiss). During hypercapnia, the CO2 tension in the arterial blood increased from 1.7±0.1 to 6.2±0.2 torr within 20 min and this was associated with a decrease of arterial extracellular pH from 7.95±0.03 to 7.38±0.03; the acid-base status of the mixed venous blood changed in a similar fashion. The decrease in blood pH in vivo was greater than in blood equilibrated in vitro with a similar CO2 tension indicating a significant metabolic component to the acidosis in vivo. Under normocapnic conditions, venous blood CO2 tension was slightly higher than arterial blood CO2 tension difference was abolished or reversed during the initial 25 min of hypercapnia indicating that CO2 was absorbed from the water during this period. Arterial O2 tension remained constant during hypercapnia; however, venous blood O2 tension decreased significantly (from 22.0±2.6 to 9.0±1.0 torr) during the initial 10 min. Hypercapnia elicited the release of catecholamines (adrenaline and noradrenaline) into the blood. The adrenaline concentration increased from 6±3 to 418±141 nmol · l-1 within 25 min; noradrenaline concentration increased from 3±0.5 to 50±21 nmol · l-1 within 15 min. During hypoxia arterial blood O2 tension declined progressively from 108.4±9.9 to 12.8±1.7 torr within 30 min. Venous blood O2 tension initially was stable but then decreased abruptly as catecholamines were released into the circulation. The release of catecholamines occurred concomitantly with a sudden metabolic acidosis in both blood compartments and a rise in CO2 tension in the mixed venous blood only.

Regional cerebral blood flow in pigs estimated by microspheres

Regional cerebral blood flow in anaesthetized pigs is determined with the microsphere method. Five regions of cortical grey matter and three white subcortical areas in each hemisphere are examined together with anatomically classic structures. The validity of the biopsies was confirmed by freeze drying of the tissue. Three flow measurements in a group of six animals showed large interindividual variations whereas regions with the same structure in the particular animal showed a high degree of uniformity. Symmetrical regions in the two hemispheres were similar with a coefficient of variation between sides of less than 5%. The coefficient of variation of the particular flow measurements were 15%. The different brain structures have four discernible flow levels. White subcortical matter has three different flow values and forms together with medulla oblongata and hippocampus the low flow area. Flow in grey cortical matter is of the same magnitude as in unanaesthetized animals and constitutes together with thalamus, mesencephalon, pons and cerebellar hemispheres the intermediate flow level. The high flow areas are nucleus caudatus and lentiformis together with the cerebellar vermis. The choroid plexus, pituitary gland and pineal gland all have very high flow values and seem, in contrast to the rest of the brain, insensitive to the CO2-tension in arterial blood and global cerebral metabolism. Microsphere estimation of regional blood flow seems to be an appropriate technique for evaluating regional cerebral blood with a high degree of spatial resolution in repeated flow measurements.

Ventilatory response in patients with acute lactic acidosis.

The ventilatory response in acute lactic acidosis was assessed in 39 patients. In 18 patients, the acidosis was associated with phenformin ingestion and in 21, with other causes such as shock and sepsis, but not pulmonary edema. Arterial blood CO2 tensions and plasma bicarbonate concentrations were compared to those previously found in patients with uncomplicated diabetic ketoacidosis. In most of the lactic acidosis patients, arterial blood CO2 fell within the 95% confidence band calculated from the data in the ketoacidotic patients. Only 1 lactic acidotic patient had a triflingly lower CO2 tension. Shock was present in 8 of the 9 lactic acidotic patients whose CO2 tensions were more than 2 torr above the 95% confidence band.

Cerebral blood flow and oxygen consumption in the rat brain during extreme hypercarbia.

The effects of hypercapnia (PaCO2 80, 160 and 300 torr) on cerebral metabolic rate for oxygen (CMRO2) and blood flow (CBF) were evaluated in paralyzed, mechanically ventilated rats by use of a 133Xe modification of the Kety-Schmidt inert-gas technique. Hypercapnic rats (PaCO, 80 torr) maintained on N2O, 70 per cent, had a sixfold increase in CBF and a 25 per cent increase in CMRO2, which were not prevented by adrenalectomy or decreases in tissue O2 tensions to near-normal values. Further increases in arterial blood CO2 tensions were associated with decreases in CMRO2 to normal (PaCO2 160 torr) or subnormal values (PaCO2 300 torr). In the last situation there was only a threefold increase in CBF. In rats with PaCO2 about 80 torr that were given propranolol, 2.5 mgċkg-1, during N2O anesthesia, there was only a threefold increase in CBF, while CMRO2 decreased to below normocapnic control values. Rats with PaCO2 80 torr given sedative or anesthetic doses of diazepam (ventilated with O2, 30 per cent, in N2) also had decreased CMRO2 values and had a twofold increase in CBF. It is concluded that hypercapnia activates catecholaminergic neurons in the brain, and that this activation increases oxygen consumption. The increase in flow that occurs with hypercapnia is markedly influenced by activity in catecholaminergic neurons.

The ventilatory response in uncomplicated diabetic ketoacidosis.

The ventilatory response to uncomplicated sub-acute metabolic acidosis was studied by measuring arterial blood CO2 tension (PaCO2) and pH in 27 episodes of diabetic ketoacidosis without coexisting lactic acidosis. From those data, regression equations and 95% confidence bands were calculated for the relations between PaCO2 and pH. These relations were very similar to those previously described by others in patients with chronic uremic acidosis.

Arterial blood gas tensions and airways obstruction in normal subjects and patients with obstructive lung disease before and during adaptation to altitude (author's transl)

In 49 patients with obstructive airways disease and 15 normal subjects O2 and CO2 tension in arterial blood, vital capacity, maximal midexpiratory flow rate and forced expiratory

Studies of the carbon dioxide and oxygen tensions of urine during application of the stop-flow technique.

Studies by the stop–flow technique were carried out in dogs in which diuresis had been induced with water, with and without the addition of bicarbonate. Urine samples from the collecting duct had greater maximal CO2 tension than was recorded simultaneously in arterial blood, and this peak occurred during infusion of carbonic anhydrase as well as during its inhibition by acetazolamide. With the former procedure, curves of CO2 tension were almost identical with those in standard control experiments. After administration of acetazolamide the values were greater, even when CO2 tension in arterial blood was > 60 mm Hg; otherwise, the curves were of similar shape. Lowest values for O2 tension in urine were recorded from the collecting duct region, and they persisted when urine flow was increased by the administration of acetazolamide or when the dog breathed 100% oxygen. The curves were of similar shape but values were slightly greater during oxygen breathing. The results obtained reflect the operation of hemodynamic mechanisms in the renal medulla, during application of the stop–flow technique.

Cerebrospinal fluid acidbase balance during a changing ventilatory state in man.

Comparison of the rate and magnitude of changes in pH, CO2 tension, and bicarbonate concentration in arterial blood, cisternal spinal fluid, and lumbar spinal fluid was made in man during hyperventilation and recovery. CO2 tension changes in cisternal fluid were rapid and significant, although less in magnitude than those in arterial blood, whereas changes in lumbar fluid CO2 tension were minimal and slow, lagging behind cisternal changes by 10–20 min. The different rates of change following altered ventilation explain some of the reported reversals of the normal lumbar spinal fluid to arterial blood CO2 tension gradients. It also suggests that the choroid plexus is one site of removal of CO2 from spinal fluid. Submitted on December 13, 1962

Effect of salicylates on ventilatory response to inhaled carbon dioxide in normal subjects.

The basic purpose of this investigation was to determine whether salicylates increase the sensitivity of the respiratory center to inhaled CO2. The problem was approached by noting the effect of salicylates upon ventilation and arterial blood Co2 tension and pH during inhalation of compressed air and 3% and 5% Co2 in air. These studies were performed in 30 subjects, 15 of whom ingested 2.1 gm salicylate; the other 15 ingested 3.6 gm. The results demonstrate that the ventilatory response to CO2 was increased only by the larger dose of salicylate. Variations in dead-space volume secondary to increments in tidal volume were observed. Dead-space volume increased in approximately linear fashion with increase in tidal volume. Submitted on October 28, 1959