Arterial Blood PCO2 Research Articles

From the editors

From the editors

Retrotrapezoid nucleus: a litmus test for the identification of central chemoreceptors

Central chemoreception is the mechanism by which arterial blood PCO2 is detected by the CNS to regulate breathing. Two main theories have been proposed to account for the phenomenon. The distributed chemosensitivity theory argues that pH sensitivity is a widespread attribute of brainstem neurones and that central chemoreception results from the cumulative effects of pH on countless neurones. The specialized chemoreceptor theory envisions the existence of small and specialized populations of CNS cells (chemoreceptors) that are unique in their ability to detect very small pH fluctuations and, via specific connections, regulate a respiratory network that is itself unresponsive to pH. The recently identified CO2‐sensitive neurones of the retrotrapezoid nucleus (RTN) seem to possess most of the attributes that one would expect of such chemoreceptors. In this review we also suggest that many fewer medullary neurones are intrinsically responsive to CO2 in vivo than might have been anticipated from prior experimentation in vitro. The properties of RTN neurones provide renewed support for the specialized chemoreceptor theory of central chemoreception, proposed in the early 1960s. However, many uncertainties remain, especially as regards the molecular mechanisms of chemoreception, the type of cell that actually detects pH in vivo (neurone, glia or others) and the number and location of bona fide central chemoreceptors.

Frequency of plain film abnormalities and some clinical findings of acute pulmonary embolism – correlation with severity of pulmonary arterial obstruction

Background: The aim of the study was to find out if chest x-ray abnormalities and some clinical signs and findings in patients with acute pulmonary embolism (PE) correlate with the degree of pulmonary arterial obstruction (CT obstruction index – CTOI) determined with scoring system on spiral CT angiograms (SCTA). Material and methods: In 41 pts (16 men, 25 women; age range 20–89 years, mean 65 years) with SCTA proven acute PE, plain chest films were retrospectively reviewed for signs of acute PE. A scoring system based on site and degree of arterial obstruction enabled measurement of severity of obstruction on SCT angiograms. Some clinical signs (sudden onset dispnea, chest pain, syncope), ECG, pH and pCO2 of arterial blood were evaluated and compared between group with major PE (10 pts with CTOI > 40%) and the rest (31 pts with CTOI 40% (60% vs. 22.5%; p value < 0.05). There was no difference in frequency of clinical signs, pH and pCO2 of arterial blood between patients with major and minor PE. Conclusions: In pts with CT proven acute PE, oligemia on chest x-ray and ECG signs of right ventricular strain correlate with severity of pulmonary arterial obstruction. Clinical simptoms, pH and pCO2 of arterial blood show no correlation with degree of pulmonary arterial obstruction.

Time window of fibroblast growth factor-18-mediated neuroprotection after occlusion of the middle cerebral artery in rats.

To assess the time window for fibroblast growth factor-18 (FGF18)-mediated neuroprotection, FGF18 was administered by intravenous infusion at various times after transient occlusion of the middle cerebral artery (MCAO) in rats. Vehicle or FGF18 (100 microg x kg(-1) x h(-1)) was infused at 0.25, 0.5, 1.0, 2.0, 4.0, or 8.0 hours after MCAO with infarct volumes and behavioral deficits measured at 24.0 hours after MCAO. A separate group of animals received the infusions 24 hours after MCAO with endpoints measured at 48 hours after MCAO. Infusion of FGF18 reduced infarct volumes and improved scores in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was most efficacious when infused within 2 hours after MCAO. Significant reductions in infarct volumes and reductions in deficits of reference memory and motor activity were also observed with FGF18 infused 24 hours after MCAO. Measurements taken at infusion times before 2 hours after MCAO showed that regional cerebral blood flow was increased by FGF18. Administration of vehicle or FGF18 had no significant effect on mean arterial blood pressure, heart rate, brain temperature, blood pH, Pco2, or Po2. These results demonstrate that FGF18 is an effective neuroprotective agent when administered early after transient MCAO in rats. Efficacy observed with infusions at later times suggests an expanded time window for FGF18-mediated neuroprotection.

Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolization.

Pregnane steroids have sedative and neuroprotective effects on the brain, due to interactions with the steroid-binding site of the GABAA receptor. In the adult brain, synthesis of the pregnane steroids is increased in response to stress. Therefore, we have used umbilicoplacental embolization to mimic chronic placental insufficiency during late gestation in sheep, to investigate the expression of the steroidogenic enzymes p450scc, 5alpha-reductase type I (5alphaRI), 5alpha-reductase type II (5alphaRII), and allopregnanolone (AP) content in the fetal brain. Umbilicoplacental embolization was induced from 114 d gestation (term approximately 147 d) by daily injection of inert microspheres into the umbilical artery and continued for 17-23 d. Fetal arterial oxygen saturation was reduced to approximately 60% of the preembolization value in each fetus, with a significant reduction in blood arterial Po2, pH, and plasma glucose concentrations (p < 0.05) and a significant increase in blood arterial Pco2 and plasma lactate concentrations (p < 0.05). At postmortem at 131-137 d gestation, embolized fetuses were growth-restricted (2.10 +/- 0.14 kg, n = 5) compared with age-matched controls (4.43 +/- 0.56 kg, n = 7, p < 0.05). Umbilicoplacental embolized fetuses showed increased P450scc expression in the primary motor cortex; 5alphaRI expression was not changed in any of the regions examined, whereas 5alphaRII expression was markedly increased in all brain regions. Brain AP content did not significantly change, whereas plasma concentrations were increased. These findings suggest that the increased expression of p450scc and 5alphaRII may be a response that maintains AP concentration in the fetal brain after compromised placental function and/or intrauterine stress.

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

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

The effect of an L-type calcium channel blocker on the hemodynamics of orbital arteries in dogs.

(1) To determine the effect of the l-type calcium channel blocker amlodipine on color Doppler ultrasound-determined vascular resistance and blood flow velocities in the distal retrobulbar arteries of dogs; (2) to determine any effect of blood pressure and PCO2 rate on such color Doppler-determined circulatory measurements. Color Doppler imaging measurements of the short posterior ciliary artery, long posterior ciliary artery, and ophthalmic artery of normal eyes of 10 dogs were obtained under isofluorane anesthesia before and 1 week after oral amlodipine administration. Mean systemic arterial blood pressure and PCO2 were monitored. The mean resistive index decreased significantly in the short posterior ciliary artery (P = 0.0347), in the long posterior ciliary artery (P = 0.0092), and ophthalmic artery (P = 0.0004) following systemic amlodipine administration. The end diastolic velocity increased significantly in the long posterior ciliary artery (P = 0.0368) and ophthalmic artery (P < 0.0001). The peak systolic velocity increased significantly in the ophthalmic artery (P = 0.0256). Mean systemic arterial blood pressure was significantly negatively associated with resistive index (P < 0.0001) and significantly associated with the log of the end diastolic velocity (P < 0.0001). Systemically administered amlodipine increases color Doppler imaging-determined blood flow velocity and decreases vascular resistive index in the ophthalmic artery, short posterior ciliary artery and long posterior ciliary artery of normal dogs. Changes in systemic arterial blood pressure can significantly affect the measurement of color Doppler imaging parameters.

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage

Objectives: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. Study design: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO2, base excess, oxygen saturation (SatO2), and PO2 were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. Results: Our data showed severe ischemia (CaF: 10 ± 7 mL/min; FMABP: 29 ± 8 mm Hg) and acidemia (pH: 7.0 ± 0.05; base excess: −9.9 ± 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. Conclusion: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion. (Am J Obstet Gynecol 2003;188:413-8.)

Sigmoid capnometry in abdominal aortic aneurysm surgery

A reply EDITOR: We thank Dr Björck for his interest in our work [1] and for giving us the opportunity both to re-emphasize points made in our paper and to correct a reference mistake in the published version. We first apologize to Dr Björck for the reference error in the third paragraph of the discussion part where reference 10 should in fact be reference 19. Furthermore, we share Dr Björck's point of view that sigmoid tonometry monitoring in surgery for aortic aneurysm is best indicated in high-risk patients. In our study, patients included were at high risk with a Parsonnet score ≥4; six of our patients had a combined history of myocardial necrosis and severe chronic obstructive bronchopulmonary disease. The surgical procedure was also particularly difficult as attested by long surgical and clamping times. All these factors explain our high frequency of ischaemic colitis. These patients were selected voluntarily because the main objective of our study was to compare the sigmoid-to-arterial PCO2 gap with the mucosal aspect as assessed by colonoscopy, which is the reference diagnostic tool of ischaemic colitis. It was interesting to observe that patients with the highest PCO2 gap were those who developed the most severe postoperative ischaemic colitis. However, our study was not powerful enough to determine the limits of the PCO2 gap, thus not allowing us to distinguish a normal from an ischaemic intestinal mucosa. In our practice, we do not argue about the sole regional PCO2 but we compare it with arterial PCO2 since tissue PCO2 concentration is dependent on the PCO2 of the perfusing arterial blood. A regional-to-arterial PCO2 gap >4 kPa provides sufficient information suggesting bowel mucosal low flow associated with O2 uptake-to-supply dependency [2], a state known as dysoxia. In this study [1], endoscopically proven ischaemic colitis was shown for PCO2 gaps >6-8 kPa. This leads us to think that a sigmoid PCO2 >15 kPa, an upper technical limit with the Tonocap® as emphasized by Björck [3], is so high, that the intestinal mucosa obviously suffers from dysoxia, preventing any doubt or interpretation. We emphasize furthermore that in our hands PrCO2 rarely goes beyond 10-12 kPa [1]. We would like to point out that trends - rather than absolute PCO2 or pHi - much better reflect any underlying regional PCO2. Therefore, a high PCO2 gap, which persists after aortic declamping without any improvement in the initial postoperative period, will alert the clinicians to perform a colonoscopy. For this reason, automatic measurements of PCO2 are certainly of great help. We agree with Dr Björck that sigmoid capnometry in aortic surgery will be mostly valuable in high-risk patients, whereas further prospective and multicentre studies are required to determine the lower limit of the PCO2 gap associated with colitis dysoxia and the influence of therapeutic correction of a high PCO2 gap on the incidence of bowel injury. G. Lebuffe B. Vallet Department of Anaesthesia and Intensive Care Medicine; University Hospital; Claude Huriez Hospital; Lille, France

Facilitating an understanding of integrative physiology: emphasis on the composition of body fluid compartments.

As a teaching exercise, we used deductive reasoning and a quantitative analysis to convert a number of facts into a series of concepts to facilitate an understanding of integrative physiology and shed light on the composition of the different body fluid compartments. The starting point was the central need to regenerate ATP to perform biologic work. Because a large quantity of O2 must be delivered to cells at a sufficiently high concentration to aid its diffusion into mitochondria, approximately one third of the O2 in inspired air was extracted; this led to a P(CO2) in arterial blood of 40 mmHg (1 mmHg = 133.322 Pa). Blood flow to individual organs must be adjusted precisely to avoid having too low or too high a P(O2) in mitochondria--the latter augments the formation of reactive O2 species. The extracellular fluid (ECF) bicarbonate concentration (E(HCO3)) must be high to minimize H+ buffering by proteins. This high E(HCO3) sets the ECF concentrations of ionized calcium (Ca2+) and inorganic phosphate (HPO4(2-)) because of solubility issues. Three features defined the intracellular fluid (ICF) volume and composition. First, expelling monovalent anions minimized its mass (volume). Second, controlling the tissue P(CO2) ensured a relatively constant net valence on intracellular proteins. Third, the range of ICF Ca2+ concentrations must both induce regulatory signals and avoid Ca3(PO4)2 formation. All the above were incorporated into the integrated response that optimized the capacity for vigorous exercise.

Impact of carbon dioxide and helium insufflation on cardiorespiratory function during prolonged pneumoperitoneum in an experimental rat model.

Experimental studies on laparoscopic surgery are often performed in rats. However, the hemodynamic and respiratory responses related to the pneumoperitoneum have not been studied extensively in rats. Therefore, the aim of this study was to investigate in spontaneously breathing rats the effects of CO2 and helium, insufflation pressure, and duration of pneumoperitoneum on blood pressure, arterial pH, pCO2, pO2, HCO3-, base excess, and respiratory rate. Five groups of 9 Brown Norway rats were anesthetized and underwent CO2 insufflation (6 or 12 mmHg), helium insufflation (6 or 12 mmHg), or abdominal wall lifting (gasless control) for 120 min. Blood pressure was monitored by an indwelling carotid artery catheter. Baseline measurements of mean arterial pressure (MAP), respiratory rate, arterial blood pH, pCO2, pO2, HCO3-, and base excess were recorded. Blood gases were analyzed at 5, 30, 60, 90, and 120 min during pneumoperitoneum, and MAP and respiratory rate were recorded at 5 and 15 min and at 15-min intervals thereafter for 2 h. CO2 insufflation (at both 6 and 12 mmHg) caused a significant decrease in blood pH and increase in arterial pCO2. Respiratory compensation was evident since pCO2 returned to preinsufflation levels during CO2 insufflation at 12 mmHg. There was no significant change in blood pH and pCO2 in rats undergoing either helium insufflation or gasless procedures. Neither insufflation pressure nor the type of insufflation gas had a significant effect on MAP over time. The cardiorespiratory changes during prolonged pneumoperitoneum in spontaneously breathing rats are similar to those seen in clinical practice. Therefore, studies conducted in this animal model can provide valuable physiological data relevant to the study of laparoscopic surgery.

Cutaneous analgesic, respiratory and cardiovascular effects, and beta-endorphin concentration in CSF and plasma of horses after electro-acupuncture

We tested the hypothesis that electro-acupuncture (EAP) can activate the horse's pain modulation system (pituitary or brain stem) to release beta-endorphin in spinal fluid and plasma which provides pain relief in horses. Eight adult healthy mares (510 ± 40 kg) were used in a randomized-crossover design study of 2 hours of EAP (test) and needle placement without electrical stimulation (sham-controls) with at least 3 weeks between experiments. Catheters were aseptically placed in the lumbar subarachnoid space, left carotid artery, and jugular vein of mares, using local anesthesia (2% lidocaine). Cerebrospinal fluid (3 mL) and venous blood (10 mL) were collected for radioimmunoassay of beta-endorphin (Tejwani et al., Life Sci. 1985). Arterial blood pressure, blood pH, PO2, PCO2, PCV, and TS concentrations were determined. Hwato acupuncture needles (28 gauge, 12.5 cm) were inserted at BL 18, 23, 25, and 28 on both sides of the spinal column of mares and were stimulated by an EAP stimulator (ITO IC 4107) using 15 and 30 Hz alternating frequencies, 4 V, 1 mA, and 0.1 ms biphasic square pulses in the test mares. Nociceptive skin pain threshold was measured by skin twitch reflex latency (STRL) and avoidance to radiant heat (48.5 °C cut-off) at the paralumbar fossa. Numerical scores of STRL, sedation, ataxia, respiratory and cardiovascular function, and beta-endorphin concentration in CSF and venous plasma were determined before (time 0), and 30, 60, 90, and 120 minutes after beginning and cessation of EAP and sham-controls. Two-way anova with repeated measures and Dunnett's post test were used. EAP significantly (p < 0.001) increased STRL [12.4 ± 2.1 seconds (mean ± SD) at baseline; 17.3 ± 2.2 seconds at 2 hours after EAP] and concentration of CSF beta-endorphin [17.5 ± 3.9 pg mL−1 (mean ± SD) at baseline; 26.1 ± 6.2 pg mL−1 at 2 hours after EAP], and minimally affected behavior and respiratory and cardiovascular systems of adult mares during and after the 2 hour-testing period.

Arterial blood gas and pH analysis: Clinical approach and interpretation

Arterial blood gas and pH analysis are performed during anesthesia or critical care medicine for (1) assessment of acid-base balance, (2) assessment of pulmonary oxygenation of arterial blood, and (3) assessment of alveolar ventilation by measurement of arterial blood PCO2. Total physiologic and alveolar dead spaces are evaluated by comparing the alveolar PCO2 with the mixed expired and mixed alveolar PCO2, respectively. This article provides a clinical approach and interpretation of arterial blood gas and pH analysis.

Vergleich der Effekte von endotrachealem Absaugen und Surfactantapplikation auf Hämodynamik und Oxygenierung Frühgeborener - Eine Nahinfrarotspektroskopie-Studie1

Aim of this study was to assess whether the decrease in heart rate and oxygen saturation occurring acutely after bolus administration of surfactant is different from the effect of endotracheal suctioning and whether there are effects on cerebral haemodynamics and oxygenation. Twelve premature infants, birth weight 720-1560 g (Median 935 g), gestational age 25-30 weeks (Median 28 weeks), were investigated during surfactant administration (Curosurf) as a single bolus and a preceding endotracheal suctioning procedure. Using near infrared spectroscopy changes in cerebral blood volume and cerebral oxygenation index were assessed. Heart rate, arterial oxygen saturation, PCO2, and arterial blood pressure were registered continuously. Data were compared at 30, 60 and 120 seconds after the beginning of suctioning and surfactant administration. Endotracheal suctioning and surfactant administration induced a similar decrease in heart rate (-29/min, SD 25, p < 0.01 and -30/min, SD 23, p < 0.001) during the first 30 seconds and in oxygen saturation at the 30 seconds datapoint (-3%, SD 2, p < 0.01 and -3%, SD 6, p < 0.05). The decrease in oxygen saturation persisted at 60 seconds after the start of suctioning (-4%, SD 5, p < 0.05). In contrast, oxygen saturation was no longer different from baseline levels 60 seconds after surfactant administration (+1%, SD 6, p = 0.5). After suctioning, cerebral oxygenation index had decreased significantly from baseline levels at 30, 60, and 120 seconds. In contrast, after surfactant administration, no significant difference from baseline was noted at 30 and 60 seconds and a significant increase occurred at 120 seconds. Mean arterial blood pressure, PCO2, and cerebral blood volume did not change significantly during endotracheal suctioning and during surfactant administration. Acute decreases in heart rate and oxygen saturation during bolus administration of surfactant are equal to effects occurring during endotracheal suctioning. However, the decrease in oxygen saturation is shorter and more importantly, no decrease in cerebral oxygenation occurs.

A visual aid for teaching ventilation-perfusion relationships.

To help students understand the concept of the ventilation-perfusion ratio (VA/Q) and the effects that VA/Q mismatching has on pulmonary gas exchange, a "sliding rectangles" visual aid was developed to teach VA/Q relationships. Adjacent rectangles representing "ventilation" and "perfusion" are slid past one another so that portions of the ventilation and perfusion rectangles are not touching, illustrating the concepts of dead-space ventilation (VD) and shunt flow (QS). The portion of the ventilation bar representing VD is further subdivided into anatomical and alveolar VD and used to show the effects of alveolar dead space on the PO2 (PAO2) and PCO2 of alveolar air (PACO2); movement away from the "ideal" point). Similarly, the portion of the perfusion bar representing QS is used to define anatomical and physiological shunts and the effect of shunts on the PO2 (PaO2) and PCO2 of arterial blood (PaCO2). The genesis of the PAO2-PaO2 (A-a) PO2 difference as well as the effects of VA/Q mismatching and diffusion abnormalities can all be discussed with this visual aid. This approach has greatly assisted some students in mastering this traditionally difficult area of respiratory physiology.

Plasma immunoreactive endothelin levels in children with cystic fibrosis.

Plasma immunoreactive endothelin levels were determined in 31 children and adolescents with cystic fibrosis and it was examined whether these levels correlated with the severity of the disease. The study comprised 16 cystic fibrosis patients (mean (SD) age 13.0 (4.9) y) with impaired lung function (Group A), 15 cystic fibrosis patients (11.2 (5.5) y) with unimpaired lung function (Group B) and 28 healthy controls (10.6 (4.3) y) (Group C). The selection and classification of patients into groups was based on criteria including the grade of finger-clubbing, the Brasfield chest radiograph score and spirometric and arterial blood gas values. In all subjects, plasma immunoreactive endothelin, atrial natriuretic peptide, renin, serum aldosterone levels and serum and urine electrolytes were measured. Plasma endothelin levels were significantly higher in Group A (range 2.5-8.4 pg/ml, median 3.2 pg/ml) than those in Group B (1.3-3.8 pg/ml, median 2.0 pg/ml, p < 0.001) and Group C (1.5-3.5 pg/ml, median 2.5 pg/ml, p < 0.001), whereas they did not differ between groups B and C. They correlated positively with the severity of finger-clubbing, heart rate, arterial blood PCO2, plasma atrial natriuretic peptide levels and serum aldosterone levels and negatively with the arterial blood PO2, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and the Brasfield chest radiograph score. In multivariate regression analysis PO2 was the only independent factor found to significantly affect plasma endothelin levels. In conclusion, plasma immunoreactive endothelin levels are increased in cystic fibrosis patients with impaired pulmonary function and are related to the severity of the disease.

Aminophylline influences cerebral hyperperfusion after severe birth hypoxia.

Doppler sonographic investigations have presented cerebral hyperperfusion in neonates after severe asphyxia. Neonates with disturbed cerebral blood flow velocity (CBFV) tend to have poor outcomes. The purpose of this clinical study was to examine the influence of aminophylline on cerebral hyperperfusion. An intravenous bolus of 4 mg/kg aminophylline was given to nine neonates with Doppler sonographic signs of cerebral hyperperfusion. CBFV was determined before, 5 min, 60 min and 120 min after aminophylline administration and on the following day. After aminophylline the mean systolic (56.5 vs. 41.6 cm/s) and end diastolic (21.0 vs. 12.3 cm/s) blood flow velocity decreased and the mean pulsatility index (0.83 vs. 1.1) increased significantly. Repeated measurements showed a decrease in blood flow velocities and an increase in pulsatility index on the following days. Heart rate, mean arterial blood pressure and pCO2 were not significantly changed. We conclude that aminophylline influences cerebral hyperperfusion in neonates with disturbed autoregulation.

Plasma immunoreactive endothelin levels in children with cystic fibrosis

Plasma immunoreactive endothelin levels were determined in 31 children and adolescents with cystic fibrosis and it was examined whether these levels correlated with the severity of the disease. The study comprised 16 cystic fibrosis patients (mean (SD) age 13.0 (4.9) y) with impaired lung function (Group A), 15 cystic fibrosis patients (11.2 (5.5) y) with unimpaired lung function (Group B) and 28 healthy controls (10.6 (4.3) y) (Group C). The selection and classification of patients into groups was based on criteria including the grade of finger‐clubbing, the Brasfield chest radiograph score and spirometric and arterial blood gas values. In all subjects, plasma immunoreactive endothelin, atrial natriuretic peptide, renin, serum aldosterone levels and serum and urine electrolytes were measured.Conclusions: Plasma endothelin levels were significantly higher in Group A (range 2.5‐8.4 pg/ml, median 3.2 pg/ml) than those in Group B (1.3‐3.8 pg/ml, median 2.0 pg/ml, p &lt;0.001) and Group C (1.5‐3.5 pg/ml, median 2.5 pg/ml, p &lt;0.001), whereas they did not differ between groups B and C. They correlated positively with the severity of finger‐clubbing, heart rate, arterial blood PCO2, plasma atrial natriuretic peptide levels and serum aldosterone levels and negatively with the arterial blood PO2, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and the Brasfield chest radiograph score. In multivariate regression analysis PO2 was the only independent factor found to significantly affect plasma endothelin levels. In conclusion, plasma immunoreactive endothelin levels are increased in cystic fibrosis patients with impaired pulmonary function and are related to the severity of the disease.

Therapeutic effect of tirilazad mesylate (U-74006F), mannitol, and their combination on experimental ischemia.

The effect of tirilazad mesylate (U-74006F), mannitol, and their combination was investigated on focal cerebral ischemia induced by permanent middle cerebral artery (MCA) occlusion in rabbits. Rabbits were divided into four groups receiving vehicle, U-74006F, mannitol, and U-74006F plus mannitol. Hematocrit (hct), glucose, mean arterial blood pressure (MABP), pH, PCO2, and PO2 were measured both before and after occlusion. Seventy-two hours following the permanent MCA occlusion, the neurological outcome was assessed and a quantitative neuropathologic examination was performed in all rabbits. The neurological outcome was better in the rabbits treated with U-74006F plus mannitol than in the other groups. The size of infarction of the affected hemisphere following MCA occlusion was 49.7% in the control group, 30.6% in the U-74006F group, 47.6% in the mannitol group, and 24.1% in the U-74006F plus mannitol group. There was a statistically significant reduction in infarct size in the U-74006F plus mannitol group compared with the other groups (P < 0.05). The ratio of ischemic neurons to total neurons in the cortex was smaller in the U-74006F plus mannitol group than in the other groups. The ratio of ischemic neurons to total neurons in the subcortex was significantly lower in the U-74006F plus mannitol group than in the other groups (P < 0.05). Our data provide evidence for the beneficial effects of both U-74006F and U-74006F plus mannitol in promoting neurological recovery and preservation of the ischemic area.

Frusemide and weight carriage alter the acid:base responses of horses to incremental and to brief intense exertion.

We speculated that frusemide would attenuate the acidosis associated with intense exertion, and that weight carriage would mitigate this effect. Therefore, in each of 2 experiments we measured pulmonary artery and systemic arterial blood pH, PCO2, PO2 and pulmonary artery temperature in 9 horses during exertion on a treadmill after each of 3 treatments. The treatments were: 1) injection of saline solution (C), 2) injection of frusemide (1 mg/kg bwt, i.v. 4 h before running) (FU) and 3) injection of frusemide (F) as for FU and the horses carried weight equal to that lost in the 4 h after frusemide administration (FL). In Experiment 1 the horses performed an incremental exercise test of 90 s at each of 4, 7 and 9 m/s (4 degrees incline). In Experiment 2, the horses ran on a treadmill inclined at 4 degrees for 3 min at 3 m/s, at approximately 120% VO2max for 2 min, and 3 m/s for 5 min. Blood samples for measurement of blood pH, PCO2 and PO2 were collected into heparinised glass syringes. Values were adjusted for changes in pulmonary artery blood temperature. Data were analysed using a 2 way repeated measures ANOVA. There was a consistent pattern in both experiments characterised by a mild alkalosis or mitigated acidosis, compared to C, at rest and during exercise and recovery after FU (P < 0.05). Weight carriage blunted or inhibited the effect of frusemide during exercise and recovery. In experiment 2, at the end of the sprint, FU treatment resulted in a less severe acidosis than did C or FI: mixed venous pH for C, FU, and FL at the end of the sprint were 6.93, 6.98 and 6.93, respectively (P interaction = 0.038), mixed venous base excess was -12.4, -9.91, and -11.8 mmol/l, respectively, and arterial base excess of -1.44, -12.7 and -14.1 mmol/l (P interaction = 0.006) respectively. These effects persisted into recovery. A similar pattern of responses occurred during the incremental exercise test, with weight carriage offsetting the alkalinizing effect of frusemide. We conclude that frusemide attenuates the acidosis of intense exertion and that carriage of weight prevents this effect.