Elevation Of PCO2 Research Articles

Alcohol Poisoning and Venous Hyperoxia

ABSTRACTVenous PCO2 and PO2 in the presence of normal arterial PCO2 and PO2 in patients with alcoholic intoxication have not been previously evaluated. The objective of this study was to compare arterial and venous blood gases in patients with alcoholic intoxication and healthy controls. Sixteen patients with alcoholic intoxication and 20 controls underwent simultaneous blood sampling from a radial artery and an antecubital vein for acid-base analysis. Osmolality and ethanol blood concentration was estimated. Elevated venous pO2 were found in 56% of patients with alcoholic poisoning compared with 15% of controls. A formula was found describing possible arterio-venous shunt accounting for elevated venous pO2 and enabling calculation of the relevant venous carbon dioxide content and CO2 product. The values of the venous pO2 and arterio-venous shunt were more significant in the alcohol group than in controls (p = 0.002, p = 0.001, respectively). Percentage of patients with a-v shunts was significantly higher in the alcohol group (81%) than in controls (25%) (p = 0.002, OR 2.6, 95% CI 0.13–6.52). The relevant venous CO2 and CO2 product had the non-significant trend to be higher in the alcohol group. In conclusion, this study reports ethanol-induced venous pO2 and pCO2 elevation. This may be associated with the effects of tissue perfusion stealing and high oxygen consumption. On the other hand, possible beneficial consequences may occur: acceleration of alcohol elimination and reduction of alcohol-induced tissue damage.

A pilot study to assess the safety and efficacy of carbon dioxide insufflation during colorectal endoscopic submucosal dissection with the patient under conscious sedation

Endoscopic submucosal dissection (ESD) is accepted as one of the treatments for en bloc resection of large superficial colorectal lesions. This procedure is performed by using air insufflation, is time consuming, and is associated with severe abdominal discomfort. The safety and efficacy of carbon dioxide (CO(2)) insufflation during colonoscopy already has been assessed in some trials. To assess the safety and efficacy of CO(2) insufflation instead of air insufflation during colorectal ESD with the patient under conscious sedation. A case-control series with a historical control. A total of 35 consecutive patients were enrolled in this study. Another 35 consecutive patients who previously received colorectal ESDs by using air insufflation were included as a historical control. Arterial partial pressure of CO(2) (pCO(2)) was measured before and after each procedure with the total dose of midazolam used as an index of abdominal discomfort. The mean (standard deviation [SD]) operation time was 90 +/- 57 minutes in the CO(2) group and 100 +/- 80 minutes in the control group (not significant). In the CO(2) group, the mean (SD) dose of midazolam was significantly lower than that of the control group; 5.6 +/- 4.9 mg and 9.7 +/- 5.9 mg, respectively (P = .005). Blood analysis revealed a slight pCO(2) elevation in the CO(2) group; however, only 2 patients complained of mild abdominal discomfort. Abdominal discomfort and pCO(2) were not evaluated in the control group. This study strongly suggests that CO(2) insufflation is safe and effective during lengthy colonic endoscopic procedures, eg, ESD, with the patient under conscious sedation.

Elevated CO2 increases the leaf temperature of two glasshouse-grown C4 grasses.

This study investigates the effect of elevated CO2 partial pressure (pCO2)-induced stomatal closure on leaf temperature and gas exchange of C4 grasses. Two native Australian C4 grasses, Astrebla lappacea (Lindl.) Domin and Bothriochloa bladhii Kuntze, were grown at three different pCO2 (35, 70 and 120 Pa) in three matched, temperature-controlled glasshouse compartments. The difference between leaf and air temperature (ΔT) was monitored diurnally with thermocouples. ΔT increased with both step-increases of ambient pCO2. Average noon leaf temperature increased by 0.4 and 0.3°C for A. lappacea with the 35-70 and 70-120 Pa steps of pCO2 elevation, respectively. For B. bladhii, the increases were 0.5°C for both pCO2 steps. ΔT was strongly dependent on irradiance, pCO2 and air humidity. Leaf gas exchange was measured at constant temperature and high irradiance at the three growth pCO2. Under these conditions, CO2 assimilation saturated at 70 Pa, while stomatal conductance decreased by the same extent (0.58-fold) with both step-increases in pCO2, suggesting that whole-plant water use efficiency of C4 grasses would increase beyond a doubling of ambient pCO2. The ratio of intercellular to ambient pCO2 was not affected by short- or long-term doubling or near-tripling of pCO2, in either C4 species when measured under standard conditions.

Transient mesenteric ischaemic episodes tracked by continuous jejunal PCO2 monitoring during liquid feeding.

To test the effect of liquid feeds on the responses to splanchnic ischaemia of a continuous rapid response PCO2 sensor inserted in the jejunum. Prospective experimental animal study in a university research laboratory. Adult male Wistar rats. Adult male Wistar rats (285-425 g) were anaesthetised with sodium pentobarbitone 60 mg/kg i.p. and ventilated with 100% oxygen and isoflurane via tracheostomy to a PaCO2 of 30-40 mmHg. A sensor was inserted into the mid-jejunum to record PCO2 every second. Distal aortic pressure was transduced. Four control rats received no feeds whilst in another four rats liquid feed was infused into the proximal jejunum at 3 ml/h. In each rat five episodes of splanchnic ischaemia were induced by 2-min elevations of an aortic sling to a mean distal aortic pressure of 30 mmHg. PCO2 elevations were always detectable, usually less than a minute from the onset of splanchnic ischaemia in both fed and unfed rats, with no difference in mean times to detectable response. In the fed rats there was a small but significant increase in the time to peak sensor response (196+/-16 vs. 180+/-12 s) and a trend towards an elevated mean baseline luminal PCO2 (67+/-9 vs. 55+/-4 mmHg). Brief episodes of splanchnic ischaemia were tracked successfully by a rapid response jejunal continuous PCO2 sensor during the infusion of a proprietary liquid feed preparation despite minor changes in PCO2 response characteristics and a possible elevation in baseline luminal PCO2.

The role of antacids in gastrotonometry: an in vitro study

Objective: To evaluate in vitro the value of antacids as an alternative to H2 blockers to raise gastric juice pH for reliable PCO2 tonometry in the human stomach. Design and setting: Laboratory study in a university hospital. Interventions: A bath was filled with 0.1 M hydrochloric acid at pH 1.3 and CO2 was gassed through the acid to simulate an intragastric environment. Experiments were performed in duplicate. Both the manual saline technique and the new semi-continuous, semi-automated air technique of PCO2 tonometry were used to evaluate the effects of adding i) aluminium oxide/magnesium hydroxide (Antagel ®) and ii) sodium bicarbonate on the PCO2. The latter technique was done to simulate intragastric CO2 production following buffering of gastric acid by bicarbonate in the mucosa, or in the saliva or pancreatic/duodenal juice entering the stomach, an effect that can be prevented in vivo by prior administration of H2 blockers. Endpoints: Changes in tonometrically determined PCO2 after the addition of alkali. A secondary endpoint was the difference between the manual saline and the semi-continuous air tonometry techniques. Measurements and main results: The mean pH increased from 1.3 to 4.0 after adding 40 ml aluminium oxide/magnesium hydroxide. The subsequent addition of sodium bicarbonate, dosed to increase pH above 6.5, caused a steep rise in PCO2 from 34 and 39 mm Hg to 134 and 99 mm Hg, for each experiment respectively, as measured by conventional tonometry, and from 37 and 38 mm Hg to 116 and 115 mmHg, respectively, for the air technique. These changes were transient. Air tonometry detected changes in PCO2 more rapidly than the manual technique. Conclusions: Adding antacids elevates the PCO2 in hydrochloric acid and does not prevent CO2 generation after the addition of sodium bicarbonate, even though the pH is raised from about 1 to 4. The clinical use of antacids instead of H2 blockers to prevent spurious PCO2 elevations following buffering of acid by bicarbonate, and thereby increase the reliability of gastric tonometry, should be discouraged.

Effect of acidosis on contraction, intracellular pH, and calcium in the newborn and adult rabbit aorta.

This study investigated the effect of acidosis on intracellular pH (pHi), intracellular calcium concentration ([Ca]i), and vascular contraction in the aorta of the newborn and adult rabbit. Isometric tension, pHi, and [Ca]i were measured in an isolated ring preparation. After the vascular contraction was induced with 50mM KC1, the effect of respiratory acidosis produced by elevation of PCO2 was studied. Respiratory acidosis caused a transient depression followed by a recovery of contractile tension. The decrease in developed tension was greater in the newborn than in the adult. The decrease in pHi during acidosis was similar in the two age groups. [Ca]i increased during acidosis and the increase was greater in the newborn than in the adult. These data show that the vasorelaxant effect of acidosis in the newborn aorta is greater than that in the adult aorta. The greater vasodilation in the newborn cannot be explained by the difference in pHi or [Ca]i.

The effect of CO2 and apnea on cochlear and middle ear blood flow in guinea pigs

The effect of 10% CO2 (in air) and apnea on cochlear blood flow (CBF) and middle ear blood flow (MEBF), capillary vessel diameters and blood pressure (BP) were investigated in guinea pigs. Intravital microscopic techniques (IVM) using video system, and laser Doppler flowmetry (LD) were used. MEBF was measured in the blood vessels of the middle ear mucosa over the cochlea and CBF was measured in the lateral wall vessels in the second or third cochlear turn. During 10% CO2 respiration for 10 min, the highest vessel diameter dilated about 11% in the middle ear and 5% in the cochlea. During 5 minutes apnea, the highest vessel diameter constricted about 30% in the middle ear and 5% in the cochlea. Elevation of PCO2 dilate blood vessels with constant PO2, but constriction of blood vessels as observed in extremely low PO2 range even if PCO2 was elevated. The ratio of the change in blood flow volume to the change in BP was obtained after the change in blood flow volume was calculated from blood flow velocity and blood vessel diameter. The mean change of ratio in MEBF was a 10% decrease with 10% CO2, 28% decrease with apnea in IVM. The mean change of ratio in CBF was a 44% increase with 10% CO2, 14% increase with apnea in IVM, 67% increase with 10% CO2, 42% increase with apnea, in LD. The change of CBF in LD was about 20% larger than in IVM. Our results showed that CBF belonging to vertebral artery system was more strongly maintained in association with autoregulation even under conditions of low PO2 or high PCO2 compared to MEBF in the external carotid artery system. It was suggested that blood flow behavior was significantly different between the middle ear and inner ear.

A new algorithm for the determination of intramucosal pH and mucosal plasma lactate concentration

The conventional calculation of gastric intramucosal pH (pHi) makes the invalid assumption that mucosal and arterial plasma bicarbonate concentrations are identical. Mucosal bicarbonate concentrations exceed arterial during aerobic O2–CO2 exchange, causing underestimation of intramucosal pH. Conversely, because of locally reduced bicarbonate concentrations, the conventional calculation significantly overestimates intra-mucosal pH in regional mucosal lactic acidosis, as shown by direct intramucosal pH measurement in animal models of splanchnic ischaemia. Accurate pHi calculation is important since mucosal acidosis is the probable cause of loss of barrier function in gut ischaemia. We devised an algorithm eliminating arterial bicarbonate from the calculation by: (i) determining the aerobic and anaerobic components of the arterial-mucosal pCO2 gap using an equation for the Dill nomogram: (ii) introducing a factor quantifying the fall in base excess (BE) which accompanies anaerobic pCO2 elevation (determined in vitro by anaerobic addition of lactic acid to blood): (iii) applying the Siggaard-Andersen algorithm to derive mucosal end-capillary pH from the calculated mucosal BE. The pHi was estimated by the new and conventional algorithms tor mucosal pCO2 values ranging from normal to those associated with severe intramucosal acidosis, assuming [Hb]= 15 g%, SaO2 = 97%, arterial pCO2 = 40 mmHg, BE = 0 meq/l and plasma (lactate) =1.5 mmol/l.

Ventilatory response to consecutive short hypercapnic challenges in children with obstructive sleep apnea

In healthy adults, a ventilatory pattern characterized by progressively increased tidal volume (VT), and decreased respiratory rate (RR) accompany repeated short hypercapnic ventilatory challenges, while minute ventilation (VE) remains constant. We hypothesized that the peculiar ventilatory pattern seen in adults would be blunted in children with obstructive sleep apnea syndrome (OSAS) who undergo comparable intermittent or chronic alveolar PCO2 elevation. We measured ventilatory responses to five challenges of 2-min duration (C1-C5) with 5% CO2 in O2, separated by 5-min room-air breathing intervals (R1-R4), in nine children with OSAS and in eight age-, sex-, and body mass index-matched controls. In all children, CO2 significantly increased VE when compared with baseline conditions (22.3 +/- 2.2 vs. 9.5 +/- 0.9 (SE) l/min; P < 0.001). In control subjects, progressive VT increases from 0.67 +/- 0.10 liter in C1 to 0.92 +/- 0.13 liter in C5 occurred (P < 0.01), whereas RR decreased from 33.9 +/- 5.1 breaths/min in C1 to 27.8 +/- 3.7 breaths/min in C5 (P < 0.02), resulting in VE increases across CO2 challenges (22.3 +/- 4.9 l/min in C1 vs. 25.1 +/- 5.0 l/min in C5; P < 0.005). The RR decrease was primarily related to progressive prolongation of expiratory time (TE) (1.1 +/- 0.1 s in C1 to 1.5 +/- 0.2 s in C5; P < 0.002). In contrast, VT, RR, and TE did not change in a consistent fashion in OSAS patients with repeated CO2 challenges (OSAS vs. control: P < 0.0001). Furthermore, in OSAS, VE was similar with repeated challenges (22.4 +/- 2.2 1/min in C1 vs. 23.9 +/- 1.9 l/min; P = not significant), such that changes in VE over time significantly differed in OSAS and controls (P < 0.001). We conclude that healthy children modify their ventilatory strategy to repeated hypercapnia. We speculate that in OSAS these mechanisms are already fully implemented because of recurrent alveolar hypoventilation accompanying increased upper airway resistance, leading to blunted temporal trends of ventilatory response.

Ventilatory responses to repeated short hypercapnic challenges

In early phases of respiratory disease, patients are more likely to experience intermittent hypercapnia than a continuous increase in PCO2. The effect of intermittent arterial PCO2 elevation on subsequent breathing patterns is unclear. To examine this issue, a series of six ventilatory challenges (CH1-CH6), consisting of 2 min of breathing 5% CO2 in O2, followed by 5 min in room air (RA) were performed in 10 naive healthy subjects (age 12-39 yr). Minute ventilation (VE) increased from 11.9 +/- 1.0 (SE) l/min in RA to 27.6 +/- 3.0 l/min in 5% CO2 (P < 0.0005) in each of the six hypercapnic challenges. Respiratory rate increased from 21.3 +/- 2.6 breaths/min on RA to 29.6 +/- 3.9 breaths/min during CH1 (P < 0.05). However, respiratory rate consistently decreased with successive CO2 challenges (CH6: 21.5 +/- 2.6 breaths/min; P < 0.02). Thus, maintenance of VE was achieved by gradual increases in tidal volume with each of the first four consecutive CO2 challenges (CH1: 1.05 +/- 0.09 liters; CH4: 1.44 +/- 0.13 liters; P < 0.002). Similarly, the ratio of tidal volume to inspiratory time increased from CH1 (1.16 +/- 0.16 l/s) to CH6 (1.57 +/- 0.21 l/s; P < 0.001). These changes in ventilatory strategy were not observed when RA recovery periods were extended to 15 min in five subjects. We conclude that during repeated short hypercapnic challenges similar levels of VE are achieved. However, increased mean inspiratory flows are generated to maintain VE. We speculate that intermittent hypercapnia either modifies central controller gain or induces a long-term modulatory effect to account for the progressive changes in ventilatory components.

Thromboxane Receptor Blockade Causes Acidemia in the Ovine Fetus

The placenta produces the vasoactive eicosanoids thromboxane and prostacyclin. We hypothesized that fetal administration of SQ 29,548, a thromboxane receptor blocker, would lack direct cardiorespiratory effects in the ovine fetus. Continuous monitoring of maternal and fetal heart rates, blood pressures, and common umbilical artery blood flow was performed in six chronically catheterized pregnant ewes. Serial maternal and fetal arterial blood gases and serum lactates were obtained. After 120 minutes of infusion, a significant decrease in fetal mean arterial pressure and a significant increase in fetal heart rate was observed. A significant decrease in fetal arterial pH (7.41 ± 0.02 to 7.33 ± 0.02), PO2 (26.8 ± 3.2 to 19.8 ± 3.4), HCO3− (27.2 ± 1.5 to 24.9 ± 2.0), and base excess (2.9 ± 1.6 to 0.2 ± 2.3) with a significant elevation in PCO2 (45.4 ± 2.6 to 50.1 ± 3.3) occurred after 120 minutes of SQ 29,548 infusion. SQ 29,548 infusion caused a significant decrease in common umbilical artery flow, from 249.4...

Sleep-induced respiratory disturbance in children with adenotonsillar hypertrophy: The obstructive sleep dyspnea syndrome

Many children with adenotonsillar hypertrophy or other forms of upper airway narrowing may generate increased respiratory effort in order to overcome upper airway resistance, but do not develop true sleep apnea. This condition is termed obstructive sleep dyspnea syndrome. In this series, 17 infants and children with adenotonsillar hypertrophy underwent complete Polysomnographic evaluations and esophageal pressure monitoring. The majority of these patients were found to have large gradients of negative esophageal pressure during sleep associated with reduction of Po2 and elevation of Pco2, but not true upper airway obstruction. Adenotonsillectomy performed in six of these patients resulted in alleviation of their problem. An explanation of the pathophysiology of this phenomenon is attempted and its possible association with sudden infant death syndrome is discussed.

Fentanyl-induced ventilatory depression: effects of age.

To determine whether infants are more sensitive than older patients to the ventilatory-depressant effects of fentanyl, patients were anesthetized with fentanyl and nitrous oxide (N2O) and ventilatory depression was assessed following elimination of N2O and in the immediate postoperative period. Three groups of patients were studied: infants (1-12 mo old, n = 14), children (1-5 yr old, n = 14), and adults (23-38 yr old, n = 13). Skin-surface PCO2 was measured to determine the peak PCO2 occurring at the end of anesthesia when end-tidal N2O concentration was less than 6%. Naloxone was administered if PCO2 exceeded 70 mmHg. During recovery from anesthesia, ventilatory pattern was recorded using impedance pneumography to determine the longest breath-to-breath interval and the number of episodes of central apnea (defined as breath-to-breath intervals greater than or equal to 10 s in infants and children and greater than or equal to 20 s in adults). Elevation of PCO2 correlated with increasing plasma fentanyl concentrations but did not differ between groups. Four patients (two infants, one child, and one adult) required naloxone. The only subject who had a low plasma fentanyl concentration but required naloxone was a 6-wk-old infant; this was the only subject younger than 3 mo. For each range of fentanyl concentrations, the incidence of apnea increased with age, as did the number of episodes of apnea per subject. Fentanyl-induced ventilatory depression, as assessed by elevation of resting PCO2 during emergence from anesthesia and disruption of ventilatory pattern during recovery from anesthesia, is not greater in infants older than 3 mo than in children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of adrenaline and blood gas conditions on red cell volume and intra-erythrocytic electrolytes in the carp, Cyprinus carpio.

1. Carp, when subjected to air stress in vivo, developed a hypoxaemia associated with an acidosis due to elevation of PCO2 and arterial lactate content. Adrenaline and noradrenaline levels rose markedly, and the mean corpuscular haemoglobin concentration (MCHC in mmol Hb l-1 red blood cells) decreased, indicating swelling of the erythrocytes. 2. No effect of adrenaline could be observed in vitro after equilibration at normal pH and oxygenation level. 3. Simulation of air stress in vitro, by using hypercapnic hypoxia together with adrenaline, caused appreciable swelling of the red cells. The effect of adrenaline could be blocked by propranolol and was reversible when the blood gases were readjusted to normal values. Swelling due to hypercapnic hypoxia was not affected by propranolol. 4. At normal PO2, lowering pH by increasing PCO2 or adding HCl to the blood at PCO2 = 3.5 mmHg (1 mmHg = 133.3 Pa) both led to swelling of red cells; further swelling occurred when adrenaline was added. 5. At normal or even elevated intracellular pH, hypoxia led to red cell swelling; further swelling occurred when adrenaline was added. 6. The swelling of red cells under hypoxic and/or acidotic conditions (induced by either added HCl or increased PCO2) was associated with an increase in the intracellular K+, Na+ and Cl- levels, together with an increase in the Donnan distribution ratio of Cl-, rCl. delta K+:delta Na+ was 4:1. The swelling associated with the addition of adrenaline was also accompanied by an increase in K+, Na+, Cl- and rCl. In this case the ratio delta K+:delta Na+ was 1:2.4. 7. There was a correlation between the Donnan ratio, rCl, and the change in MCHC, even in those cases where extracellular and intracellular pH were above normal. In addition to pH and oxygen saturation, rCl should therefore be considered as a possible triggering factor for the action of adrenaline. 8. In addition to the increased catecholamine levels, stress during sampling may be inferred if low values of MCHC and high values of intraerythrocytic chloride and a high chloride distribution ratio, rCl, are found in whole blood.

Elevation of tissue PO2 with improvement of tissue perfusion by topically applied CO2.

Local absorption of CO2 was examined, by tissue gas analysis with medical mass spectrometry, in rabbits placed in a bath. The results obtained clearly showed that (1) Elevation of subcutaneous tissue PO2 was followed by elevation of PCO2 in the subcutaneous tissue. (2) Local absorption of CO2 through skin was confirmed by elevation of the levels of subcutaneous PO2 and PCO2 at the site exposed to CO2. (3) Tissue perfusion during the CO2 bath was moderately higher than that observed with tap water bathing. The mechanism of oxygen release into the tissue by CO2 bathing is thought to involve increased [H+] and PCO2 in the red blood cells, which shifts the hemoglobin dissociation curve to the right, thus facilitating oxygen release at the tissue level. There is, therefore a good possibility, that the improved tissue perfusion together with the increased oxygen in the tissue will favourably affect wound healing and chronic degenerative disorders, thus facilitating rehabilitation.

Relationship between luminal Na+/H+ exchange and luminal K+ conductance in diluting segment of frog kidney.

Experiments were performed in the isolated perfused kidney of K+ adapted Rana pipiens to investigate the relationship between luminal K+ conductance and H+ transport in cells of the diluting segment. Inhibition of luminal Na+/H+ exchange by amiloride or by omission of luminal Na+ blocked luminal K+ conductance. Acidification of the kidney perfusate by elevation of pCO2 also reduced luminal K+ conductance. This effect could be prevented by furosemide. Since the steepest transcellular Na+ potential difference, directed from the lumen into the cell, is found when luminal Na+/Cl-/K+ cotransport is inhibited by furosemide, we conclude that luminal Na+/H+ exchange is most efficient at these conditions and thus could attenuate intracellular acidification.

Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary PCO2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHCO3. Proximal tubular bicarbonate reabsorption and PCO2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A group of nine age-matched control animals, fed the same diet but not given furosemide, was studied for comparison. In a third group of controls, the filtered load of bicarbonate was varied over the same range as in the CMA rats by plasma infusion and aortic constriction. The CMA rats had significant alkalemia and hypokalemia (4-7 d: pH 7.58, HCO3 38.3 meq/liter, K+ 2.1 meq/liter; 11-14 d: pH 7.54, HCO3 38.1 meq/liter, K+ 2.5 meq/liter). Nonetheless, proximal bicarbonate reabsorption was not significantly different from that seen in control rats at any given load of filtered bicarbonate (from 250 to 1,300 pmol/min). In both control and CMA rats, 83-85% of the filtered bicarbonate was reabsorbed by the end of the accessible proximal tubule. These observations indicate that proximal bicarbonate reabsorption is determined primarily by the filtered load in chronic metabolic alkalosis. When single nephron glomerular filtration rate (SNGFR) is reduced by volume depletion in the early postfurosemide period, the filtered load and the rate of proximal bicarbonate reabsorption remain at or below control levels, maintaining metabolic alkalosis. In the late postfurosemide period, however, SNGFR returned to control levels in some instances. In these animals, both the filtered load and rate of proximal reabsorption were increased above the highest levels seen in control animals. The PCO2 gradient between the peritubular capillaries and arterial blood (Pc-Art) was significantly higher in CMA than in control, even though the rate of proximal bicarbonate reabsorption did not differ. Thus, proximal bicarbonate reabsorption did not appear to be the primary determinant of Pc-Art PCO2. PCO2 in the early proximal (EP) tubule was significantly higher than in either the late proximal (LP) tubule or peritubular capillaries in both control and CMA rats. The EP-LP PCO2 gradient correlated directly with proximal bicarbonate reabsorption (P less than 0.05). The small elevation in PCO2 in EP may be related to CO2 generated at this site in the process of bicarbonate reabsorption.

Effect of H+ and elevated PCO2 on membrane electrical properties of rat cerebral arteries.

Some membrane electrical properties of muscle cells from the middle cerebral artery of the rat were recorded with intracellular microelectrodes. The resting membrane potential (Em) of this preparation was -63 mV. Reduction of extracellular pH to 7.0 in the face of a constant PCO2 of 40 mm Hg had no significant effect on Em. Similarly the slope of the steady-state voltage/current curves was not different at pH 7.0 compared to control at pH 7.4. In marked contrast, when PCO2 was elevated to around 60 to 70 mm Hg there was a rapid hyperpolarization and reduction in the slope of the voltage current curve suggesting an increased conductance for one or more ionic species. In addition elevation of PCO2 increased the slope of the Em vs. log[K]0 curve from 46 mV/decade to 59 mV/decade which is in good agreement with a Nernstian potential for a K+ selective membrane. These data suggest that while the smooth muscle cells of rat cerebral arteries are relatively insensitive to a small reduction in extracellular pH; reduction of intracellular pH by elevating PCO2 induces hyperpolarization by increasing K+ conductance (gk). However, it is not clear from these experiments if the PCO2 effects are mediated entirely by changes in pH or if there is a direct membrane action of CO2.

Prognostic factors in fresh water immersion

The records of 63 consecutive fresh water immersion patients seen from 1969 to 1978 were examined retrospectively to evaluate those factors most relevant to the patients' eventual outcome. Nineteen patients had hematuria on admission, all 19 had complicated courses or died as a result of their immersion. Nine of the 63 patients had plasma hemoglobin concentrations of 30 mg/dl or above. Five of the nine died as a result of their immersion. The remaining four developed Adult Respiratory Distress Syndrome but survived. All other parameters measured seemed to have little effect on the prognosis. An elevation of PCO2 on admission seemed difficult to evaluate but might in certain circumstances suggest an ominous prognosis.

Intracranial hemorrhage following administration of sodium bicarbonate in rabbits

Studies on the correlation between hyperosmolality and brain damage, especially intracranial hemorrhage, were carried out on young and newborn rabbits following infusion with 7% sodium bicarbonate. 1) All the young rabbits injected with 7% sodium bicarbonate died of hyperosmolality at over 380 mOsm/L (the mean was 462 mOsm/L) after drip infusion at the rate of 20-60 ml/kg/hr. Young rabbits under a 10% hypoxic environment died even at the 350 mOsm/L level (the mean was 392 mOsm/L) during infusion of 7% sodium bicarbonate. Half of the case of newborn rabbits injected with 7% sodium bicarbonate at 10 ml/kg, intraperitoneally, had intracranial hemorrhage at 335 mOsm/L. When the hyperosmolality reached 392 mOsm/L (50 ml/kg), intracranial hemorrhage was observed in all cases. 2) The main cause of death in young and newborn rabbits was subdural hemorrhage in the subtentorial region. Intraventricular hemorrhage was observed in about 40% of the cases of young and newborn rabbits. 3) The blood pH was elevated by the drip infusion, but when the hyperosmolality reached about 400 mOsm/L, the blood pH began to fall. At the same osmolality, pCO2 showed a marked elevation. It is likely that the decrease of the blood pH was caused by the elevation of pCO2 and the outflow of H+ from intracellular compartments resulting from the hyperosmolality. These results apparently indicate that fatal intracranial hemorrhage was induced by hyperosmolality and was enhanced by the combination of hypoxia and immaturity.