Arterial Blood PCO2 Research Articles

Regulation of ventilation before and after sleep in patients with obstructive sleep apnoea.

The objective was to examine whether abnormal breathing during sleep may affect regulation of ventilation after awakening in patients with obstructive sleep apnoea (OSAS). In 19 patients with OSA and 12 normal subjects we examined ventilatory responses to hypoxia (HVR) and to hypercapnia (HCVR) before and after sleep (BS and AS), and compared the changes in ventilatory responses with respiratory events during sleep. In the OSA group, the values of resting ventilation were significantly smaller in AS than those in BS and end-tidal partial pressure of CO2 in arterial blood (Pco2) (PETCO2) rose significantly from BS to AS. The slopes of the HVR or HCVR did not differ between BS and AS. However, both the response lines shifted downward and minute ventilation (VE)80 (VE at arterial oxygen saturation (Sao2) of 80%) in HVR and VE60 (VE at PETCO2 of 60 mmHg) in HCVR decreased significantly from BS to AS. The percentage changes of VE80 and VE60 were significantly correlated with mean Sao2, total sleep time below Sao2 of 90% and lowest Sao2 during sleep. However, in normal subjects we observed no circadian variation in their ventilatory responses. These data support the hypothesis that repeated episodes of nocturnal hypoxia and hypercapnia may modify the regulation of ventilation after awakening in patients with OSA.

The effects of host carbogen (95% oxygen/5% carbon dioxide) breathing on metabolic characteristics of Morris hepatoma 9618a.

Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% carbon dioxide) breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.

Circulatory response to hyperthermia during acute normovolaemic haemodilution.

Cats anaesthetized with a mixture of chloralose and urethane were exposed to heat stress in two groups. In the first group (n = 10) of control animals, the effect of heat stress on haemodynamic variables was recorded at control haematocrit (HCT) of 42.0 +/- 1.0%. In a second group, the effect of heat stress was studied after induction of acute normovolaemic haemodilution (HCT of 13.0 +/- 1.0%). Haemodilution was induced to a maximum of 60% replacement of blood with dextran (mol.wt. 150,000). Heat stress was induced by surface heating and core body temperature was raised from 37 degrees C to 42 degrees C. The effect of heat stress and haemodilution on various haemodynamic variables, viz. left ventricular pressure (LVP), left ventricular contractility (LVdP/dtmax), heart rate (HR), cardiac output (CO), arterial blood pressure (ABP), right atrial pressure (RAP), and arterial blood PO2, PCO2 and pH was examined. Haemodilution produced significant (P < 0.05) increases in HR and CO but there were no significant (P > 0.05) changes in ABP, RAP, LVdP/dtmax and total peripherial resistance (TPR). Hyperthermia caused a significant fall (P < 0.05) in TPR. However, the percentage fall in TPR was higher in the control group. On exposure to heat stress, there were significant (P < 0.05I increases in HR and CO in both the groups; however, HR and CO values were significantly (P < 0.05) higher in the haemodiluted group compared to the control. The latter findings could be due either to the higher basal values of these variables with the fall in HCT or to inefficient cardiovascular regulatory mechanisms. The lack of efficient regulatory control under such severe stress conditions makes the cardiovascular system of anaemic animals more vulnerable to heat stress. In conclusion, the results of the present study showed deleterious effects of heat stress in both the groups. The higher values of HR and CO in the haemodiluted group may be responsible for circulatory failure at low HCT values, indicating a higher risk in the haemodiluted group as compared to the control group.

The DCO2 Measured by Gastric Tonometry Predicts Survival in Children Receiving Extracorporeal Life Support: Comparison With Other Hemodynamic and Biochemical Information

To assess the role of gastric tonometry in monitoring children receiving extracorporeal life support (ECLS) and to determine if DCO2 or pHi in the weaning phase of ECLS predicts survival. A prospective study of consecutive patients treated with ECLS. A tertiary pediatric ICU that is the ECLS referral center for Australia. Twenty consecutive children receiving ECLS for cardiovascular or respiratory failure. All children were monitored throughout their ECLS course using a tonometer inserted into the stomach via the orogastric route. The PCO2 in the tonometer balloon was measured every 4 to 6 h and the pHi was calculated using the Henderson-Hasselbalch equation. The DCO2, which is the difference between PCO2 in tonometer saline solution and arterial blood, was calculated. We compared the ability of pHi, DCO2, heart rate, mean arterial pressure, arterial pH, base deficit, and blood lactate to predict death or survival during the weaning phase. Measurements were taken on the lowest level of support, which for veno-arterial extracorporeal membrane oxygenation and ventricular assist device was defined as the lowest ECLS pump flows, and on veno-venous extracorporeal membrane oxygenation was defined as the time of lowest ECLS gas flow. Predictive power was assessed using the receivor operating characteristic (ROC) analysis on the data collected at these times. In the weaning phase of ECLS, the pHi was significantly lower in children who died (pHi = 7.21; 95% confidence intervals, 7.14 to 7.28) than in those who survived (pHi = 7.38; 95% confidence intervals, 7.28 to 7.47). The DCO2 was significantly higher in children who died (23.6 mm Hg; 95% confidence intervals, 14.3 to 33.1) compared with survivors (4.7 mm Hg; 95% confidence intervals, -0.78 to 10.1). The area under the ROC curve was 0.95 for DCO2 (and 0.88 for pHi). pHi and DCO2 predicted survival better than base deficit (area under ROC curve, 0.82), blood lactate level (0.29), arterial pH (0.65), heart rate (0.62), and mean arterial pressure (0.74). DCO2 is a clinically meaningful measurement in children receiving ECLS. A high DCO2 was a good predictor of death in this series. Gastric tonometry may provide a useful measure of the adequacy of regional perfusion and oxygenation in this group of patients.

Resuscitation with diaspirin crosslinked hemoglobin increases cerebral and renal blood perfusion in hemorrhaged rats.

Diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare Corp., Round Lake, IL, USA), a hemoglobin-based blood substitute has been found to be an effective resuscitative agent following hemorrhage in animals. The present study was undertaken to determine the effect of DCLHb on microvascular perfusion in the brain and kidney following hemorrhage in anaesthetized, male Sprague Dawley rats using laser Doppler flowmetry. Hemorrhage was induced by withdrawal of arterial blood at a rate of 0.5 to 1.0 ml/min until blood pressure of 35-40 mmHg was achieved. This was maintained for up to 30 min. The arterial blood pH, pO2, pCO2 and total hemoglobin (THb) were monitored. Hemorrhage significantly decreased pH, pCO2 and THb and increased pO. Hemorrhage significantly decreased (26%) brain blood perfusion due to a decrease (17%) in the concentration of moving red blood cells (CMBC). In the kidney there was a greater decrease (65%) in blood perfusion due to a significant decrease in both CMBC (28%) and red blood cell velocity (49%). Resuscitation with vehicle (Ringer's lactate, 4 ml/kg, i.v.) did not produce any improvement in cerebral and renal blood perfusion. Resuscitation with DCLHb (400 mg/kg, i.v.) improved perfusion in the brain (112%) due to an increase in the CMBC (69%) and the velocity of red blood cells (33%). Similarly, in the kidney, DCLHb increased perfusion (178%) by increasing CMBC (55%) and red blood cell velocity (89%) of hemorrhaged rats. The increase in renal blood perfusion was more marked (p < 0.001) than the changes in cerebral blood perfusion following resuscitation with DCLHb in hemorrhaged rats. It is concluded that DCLHb can significantly increase cerebral and renal blood perfusion of hemorrhaged rats and this effect may contribute to its efficacy as a resuscitative solution.

Gastric intramucosal pH: an indicator of weaning outcome from mechanical ventilation in COPD patients.

The aim of this study was to determine whether gastric intramucosal pH (pHim) and/or gastric intramucosal carbon dioxide tension (PCO2,im) measured by tonometry can be used to predict the success of weaning in chronic obstructive pulmonary disease (COPD) patients. Twenty six consecutive COPD patients, undergoing mechanical ventilation for acute respiratory failure and satisfying the criteria of weaning from mechanical ventilation with nasogastric tonometer in place, were studied. Arterial blood gas values and PCO2,im were measured 24 h before (H-24), just before (H0), and after 20 min of a weaning trial on T-piece (H20min). Weaning failure was defined as the development of respiratory distress and/or arterial blood gas impairments during the first 2 h of spontaneous breathing on T-piece, or reintubation within 24 h after extubation. Between the weaning failure (n = 6) and weaning success (n = 20) groups, there were no differences in blood gas analysis readings at H-24 and H0 before the weaning period, age, Simplified Acute Physiology Score (SAPS) on admission, SAPS on the day of weaning trial, and duration of ventilation. Clinical status, tonometric and arterial gasometric data were similar at H-24 and H0 in all patients. During mechanical ventilation, pHim was < or = 7.30 in patients who failed weaning and > 7.30 in patients who were successfully weaned (p < 0.001; 100% sensitivity and specificity). The threshold value for PCO2,im of 8.0 kPa (60 mmHg) represents a clear demarcation with respect to outcome before the weaning trial. PCO2,im values during mechanical ventilation are significantly different (p < 0.001) between patients who were successfully weaned and those who were not (6.9 +/- 0.9 vs 9.9 +/- 1.1 kPa (51.9 +/- 6.7 vs 74.3 +/- 8.0 mmHg, respectively)). At H20min, pHim and PCO2,im were still statistically different between the weaning failure and the weaning success group. We conclude that measurement of gastric intramucosal pH (or gastric intramucosal carbon dioxide tension) represents a simple and accurate index to predict weaning outcome in chronic obstructive pulmonary disease patients before attempting weaning.

Effect of exposure time on the survival of immature pigs in a confined atmosphere.

Our purpose if to develop a survival strategy for man trapped in a confined space. A previous study showed that in the rat there is a critical exposure time beyond which hypoxic survival improves. To evaluate the general applicability of these findings in the rat and the influence of body size, the effect of exposure time on hypoxic survival was studied in immature pigs (26 kg). The pig consumed the oxygen in a sealed chamber until hypoxic collapse. We measured blood pressure, oxygen consumption, inspired O2 and CO2, minute ventilation, ECG, body temperature, and PO2, PCO2 and pH in arterial and venous blood. Five groups of pigs were confined in different initial volumes of air, producing total exposure times of 0.5, 1.3, 2.3, 4.8 and 6.7 h. There was no significant difference between the experimental groups for any of the parameters measured during the exposure. Unlike the rat, in the pig there was no "adjustment time" beyond which the animal could survive to a lower PIO2. Terminal inspired PO2 increased as a function of exposure time. This was related to either hypoventilation or lung edema. There was a correlation between the level of carbon dioxide in the blood at 60-70 torr inspired oxygen and the terminal PO2. Pigs which failed to clear the carbon dioxide succumbed early to hypoxia. In a confined space it is preferable to maintain normoxic conditions for as long as possible.

Effect of alkali therapy with NaHCO3 or THAM on cardiac contractility.

We examined the impact of alkali therapy on myocardial contractility in a model of myocardial ischemia in dogs using direct measurements of myocardial contractile function. Myocardial ischemia in the left anterior descending (LAD) artery territory was induced using a perfusion circuit from the internal carotid artery to the LAD artery. Myocardial contractile function was assessed using sonomicrometry for measurement of percent systolic shortening (%SS), preload recruitable stroke work (PRSW) slope, and end-systolic pressure-length relationship (ESPLR) area. Because the blood flow in LAD artery was diminished by approximately 70%, there was a significant decrease in O2 delivery and uptake by the ischemic myocardium. Ischemia led to a significant fall in LAD regional contractile function with %SS decreasing from 15 +/- 2 to 7 +/- 2%, PRSW slope from 82 +/- 10 to 37 +/- 5 mmHg, and ESPLR area from 121 +/- 2 to 48 +/- 14 mmHg.mm (P < 0.05). In six dogs, the intracoronary administration of NaHCO(3) resulted in a significant increase in pH in LAD arterial and venous blood. There was, however, no significant increase in %SS (6 +/- 2), PRSW slope (43 +/- 10 mmHg), or ESPLR area (60 +/- 13 mmHg.mm). Since administration of NaHCO(3) resulted in a significant increase in PCO2 in LAD arterial and venous blood, similar experiments were carried out in five dogs, but with the intracoronary infusion of the amine buffer THAM [tris(hydroxymethyl)aminomethane (Tris) buffer; 2-amino-2-hydroxyl-1,3-propandiol] instead of NaHCO3. Although administration of THAM resulted in a significant increase in pH and a significant decrease in PCO2, in both LAD arterial and venous blood, there was no significant improvement in any of the parameters used to assess myocardial contractile function. In conclusion, administration of alkali (NaHCO3 or THAM) does not enhance the contractile function of the ischemic myocardium.

Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hypercapnia

To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia. Prospective, controlled study. Research laboratory. Female Marino ewes. Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n = 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n = 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation). Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 +/- 0.03 at normocapnia to 7.14 +/- 0.01 (p < .01 vs. normocapnia) as blood PCO2 increased to 81.2 +/- 1.8 torr (10.8 +/- 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 +/- 0.02 at normocapnia and was maintained at 7.37 +/- 0.01 while PaCO2 was increased to 80.3 +/- 0.9 torr (10.7 +/- 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 +/- 0.6 L/min at normocapnia vs. 6.8 +/- 1.0 L/min at 1 hr [p < .05]; pH-corrected group: 4.1 +/- 0.4 at normocapnia vs. 5.7 +/- 0.4 L/min at 1 hr [p < .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p < .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p < .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 +/- 1.5 mm Hg at normocapnia vs. 26.8 +/- 5.1 at 1 hr, p < .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 +/- 1.6 mm Hg at normocapnia to 7.7 +/- 4.2 at 1 hr). Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.

Stragegies to reduce surface area requirements for carbon dioxide removal for an intravenacaval gas exchange device.

Experimental and clinical use of the intravascular oxygenator (IVOX), an intravenacaval gas exchange device, in acute respiratory failure yielded a CO2 transfer of 40-70 ml/min (approximately 30% of adult CO2 production) at normocapnia. Although significant, this rate of CO2 removal is not clinically useful. To maximize CO2 transfer, given the same gas exchange properties and structure design of the IVOX, the authors analyzed the effects of permissive hypercapnia (stepwise increase in arterial blood pCO2 up to 100 mmHg) and active blood mixing (with an intraaortic balloon pump) on different sizes of IVOX (sizes 7, 8, and 9 mm, surface area 0.21, 0.32, and 0.41 m2, respectively) using a previously established ex vivo circuit to model the human vena cava. The CO2 net transfer coefficient (KCO2) was averaged for all sizes and applied to extrapolate the surface area requirements under different pCO2 and with active blood mixing. Results showed that KCO2 increased in a linear relationship with blood flow. Increases in blood flow and blood pCO2 further increase CO2 removal and decrease surface area requirements. For blood flow at 4.0 L/min, the membrane surface area required for 150 ml/min CO2 removal at blood pCO2 of 40 mmHg is 1.76 m2, but can be decreased to 0.47 m2 at blood pCO2 of 80 mmHg, and further to 0.42 m2 with additional active blood mixing. A 0.42 m2 surface area is associated with an O2 transfer of 80 ml/min without and 107 ml/min with active blood mixing. It is concluded that CO2 removal by IVOX alone is limited by insufficient surface area and the resistance in the blood-surface boundary layer. The combination of permissive hypercapnia, adequate blood flow, and active blood mixing can substantially improve CO2 removal and can therefore achieve clinically significant CO2 removal by intravenacaval gas exchange devices during severe respiratory failure.

Continuous Intra-Arterial Blood Gas Monitoring

Arterial blood gas analysis is necessary for the optimal management and treatment of many critically ill patients. Currently, arterial blood gases (ABG) are measured intermittently. Continuous measurement of PO2, PCO2, and pH in arterial blood would be a major medical advance for the intensivist. Certain patient populations in the intensive care unit (ICU) would clearly benefit from continuous intra-arterial blood gas monitoring (CIABGM). CIABGM would not be expected to totally replace intermittent ABG sampling and periodic calibration of a CIABGM device may also be necessary.

Ventilation and carbon dioxide exchange in exercising horses: effect of inspired oxygen fraction.

Thoroughbred horses (TB) have no ventilatory response to added CO2 during near-maximal exercise. To see whether that reflects mechanical limits to ventilation or the control of breathing, we examined the effects of varying inspired O2 fraction (0.16, 0.21, or 0.30) in five normal TB standing quietly and galloping at 10 and 14 m/s on a level treadmill. We measured gas exchange (O2 consumption and CO2 production) and ventilation with a flow-through mask system. We also measured PO2, PCO2, and O2 contents in arterial and mixed venous blood and calculated cardiac output by using the Fick equation. Low inspired O2 fraction (0.16 vs. 0.21) had significant effects in TB galloping at 14 m/s. Arterial PO2 then was 38 Torr compared with 56 Torr for horses on air. Tidal volume and minute ventilation were 20% greater than their corresponding values on air, which were 12 liters and 1,475 l/min, respectively, whereas respiratory frequency did not change. O2 consumption and CO2 production were unchanged, but alveolar ventilation was 6% greater, despite increased alveolar and physiological dead spaces, so arterial PCO2 was lower (45 vs. 50 Torr on air). Thus, hypoxia was an effective stimulus to breathing, and minute ventilation was not mechanically limited in TB breathing air at the speeds studied.

Renal acid-base transport: The regulatory role of the inner medullary collecting duct

A 36-year-old white woman was referred to Boston City Hospital for evaluation of occasional periods of generalized muscle weakness and shortness of breath for approximately 2 years. Five years previously she had had her first episode of nephrolithiasis and since that time has passed 1 to 2 stones per year. Analysis of three stones indicated that they consisted of calcium phosphate and calcium oxalate. Her serum calcium, 5.1 mEq/liter, and iPTH level, 50 1.dEqIml, were within normal limits. However, her 24-hour urinary excretion of calcium, 550 mg, was elevated. Her renal function has been stable, with plasma creatinine values between 0.7 and 0.9 mg/dl. The only other significant abnormality noted in prior evaluations for these complaints was the finding of mild hyperchioremic metabolic acidosis. The arterial plasma pH was 7.37; serum HC03, between 18—20 mEq/liter; and serum K, 3.1 mEq/liter. During the current evaluation, physical examination was entirely normal. No demonstrable muscle weakness could be elicited. All reflexes were present and equal symmetrically. Electrocardiogram was within normal limits. Laboratory evaluation included: BUN, 16 mg/dl; creatinine, 0.9 mg/dl; calcium, 5.2 mEq/liter; phosphate, 3.8 mg/dl; sodium, 137 mEq/ liter; potassium, 2.6 mEq/liter; chloride, 111 mEq/liter; bicarbonate, 16 mEq/liter; arterial blood pH, 7.36; and arterial blood PCO2, 29 mm Hg. Urinalysis revealed 5—6 red blood cells and 5—10 white blood cells/highpower field; the pH was 6.5. Net acid excretion, 37 mEq/day, was inappropriately low for a systemic acidosis, and potassium excretion was 75 mEq/day despite hypokalemia. An intravenous pyelogram and renal sonograni documented bilateral papillary tubular ectasia and nephrocalcinosis of the papillary collecting duct and were consistent with medullary sponge kidney.

Cerebrospinal fluid pH and PCO2 rapidly follow arterial blood pH and PCO2 with changes in ventilation

Cerebrospinal fluid pH and PCO2 rapidly follow arterial blood pH and PCO2 with changes in ventilation

Effect of orally administered cadmium on in situ pH, PCO2, and bicarbonate concentration in rat testis and epididymis.

Acute injections of high doses of cadmium (Cd) induce marked testicular necrosis. However, the effects of low-dose oral Cd exposure, on a chronic basis, are not well documented. The present investigation was designed to examine the effects of such exposure on in situ pH, PCO2, and bicarbonate concentration ([HCO3-]) in the rat testis and epididymis, plasma testosterone levels, and testis and epididymis weights. Male Sprague-Dawley rats were exposed to 50 or 100 ppm Cd for 40 d. Oral administration of 50 or 100 ppm Cd was associated with significant alkalinization of luminal fluid in seminiferous tubules (ST) but did not alter in situ pH values in proximal caput (PCP), middle caput (MCP), or proximal cauda epididymidis (PCD). The in situ PCO2 values in ST, PCP, MCP, and PCD of control animals were indistinguishable from each other and from values after Cd exposure, and all values were significantly higher than system arterial blood (SAB) PCO2. Oral Cd exposure at 50 or 100 ppm did not change the values for bicarbonate in SAB, PCP, or MCP but increased markedly the value in ST. Plasma testosterone levels and testis and epididymis weights were not altered after oral cadmium administration. These findings suggest that, at the doses employed in this study, Cd exposure may result in subtle alterations in the blood-testis barrier and subsequent impairment of acid-base pathways. Furthermore, the traditional view of Cd-related testicular insult based on acute injection protocols needs to be reevaluated in terms of environmental relevance.

Cerebrospinal fluid pH and PCO2 rapidly follow arterial blood pH and PCO2 with changes in ventilation.

Changes in ventilatory rate affect arterial blood pH and PCO2 within seconds to minutes, but the corresponding acute changes for cerebrospinal fluid (CSF) pH and PCO2 have been as well documented. Using our previously-described swine model of brain retraction ischemia, we examined changes in arterial and CSF pH and PCO2 with acute changes in ventilation in four animals. Newly developed fluorescent dye technology permitted near-instantaneous recording of CSF pH and PCO2 during acute hyperventilation (end-tidal PCO2 of 20 mm Hg) and acute hypoventilation (end-tidal PCO2 of 50 mm Hg). The Puritan-Bennett 3300 Intra-Arterial Blood Gas Monitor (PB3300) was used with the sensor placed in the CSF in the interhemispheric fissure posterior to the corpus callosum. The following data were gathered at 5, 15, 30, and 60 minutes after the ventilatory change: arterial pH and PCO2, end-tidal CO2, laser-Doppler cerebral blood flow, and CSF pH and PCO2. The baseline (normoventilation) values for arterial and CSF pH and PCO2 in swine were comparable to those in humans: arterial pH 7.44 and PCO2 43 mm Hg; CSF pH 7.31 and PCO2 55 mm Hg. Changes in pH and PCO2 with hyperventilation and hypoventilation occurred rapidly in both arterial blood and CSF. Steady-state values were reached within 15 minutes for hypoventilation, and 30 minutes for hyperventilation. The correlation between arterial and CSF values for both pH and PCO2 at 5, 15, 30, and 60 minutes were all very highly significant (P < 0.001) except for arterial and CSF PCO2 at 5 minutes (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal Fluid pH and PCO2 Rapidly Follow Arterial Blood pH and PCO2 with Changes in Ventilation

Cerebrospinal Fluid pH and PCO2 Rapidly Follow Arterial Blood pH and PCO2 with Changes in Ventilation

Simultaneous influence of blood pressure, PCO2, and PO2 on cerebral blood flow velocity in preterm infants of less than 33 weeks' gestation.

In extremely preterm infants, the protective capacity for cerebral blood flow (CBF) autoregulation may be impaired or absent, which increases the risk for developing cerebral lesions. The purpose of this study was to quantify the simultaneous influence of several vital parameters, such as mean arterial blood pressure (MABP), PCO2, and PO2, on cerebral blood flow velocity (CBFv), which is used as a measure for CBF. In 16 mechanically ventilated infants of < 33 wk gestation, the CBFv in the internal carotid artery was measured every minute for 1 h by a computer-controlled pulsed Doppler device. MABP and transcutaneous PCO2 and PO2 were recorded as well. A multiple linear regression analysis was performed in each patient to determine the individual MABP, PCO2, and PO2 reactivities as a measure for CBF autoregulation. The medians (and ranges) of the whole group were an MABP reactivity of 7.5% (-12.5 to 20.1%) rise in CBFv/1 kPa rise in MABP, a PCO2 reactivity of 32.7% (-8.1 to 79.5%) rise in CBFv/1 kPa rise in PCO2, and a PO2 reactivity of -3.1% (-14.2 to 7.9%) fall in CBFv/1 kPa rise in PO2. In preterm infants, the individual's capacity for MABP-, PCO2-, and PO2-dependent CBF autoregulation can be estimated by means of the present method, even if the vital parameters change simultaneously.

Cerebral metabolic studies in vivo by combined 1H/31P and 1H/13C NMR spectroscopic methods.

Intracellular pH and ammonium ion concentration are potent modulators of cerebral amino acid metabolism. Furthermore, intracellular acidosis and hyperammonemia accompany conditions such as ischemic encephalopathy and seizures and may contribute to the pathological sequelae observed. In vivo NMR spectroscopy permits multiple, non-destructive measurements of important cerebral metabolic intermediates in the same animal. We describe here the use of 1H, and 31P NMR spectroscopy to investigate the effects of acute changes in intracellular pH and ammonium ions on cerebral glutamate, glutamine, and lactate levels in vivo. We then show how 1H NMR can be used to indirectly follow the flow of 13C label from [1-13C] glucose into the cerebral glutamate pool, allowing us to measure cerebral TCA activity in normal and chronically hyperammonemic rats. Male Sprague-Dawley rats (160-210 gm), fasted 24-hours, were tracheotomized, paralyzed and ventilated on 30% O2/70% N2O. NMR spectroscopy was performed at a field strength of 8.4 Tesla using a Bruker AM-360 wide bore spectrometer. An elliptical surface-coil (8 x 12 mm) was double-tuned to either the 1H and 31P or 1H and 13C frequencies. After retraction of extracranial tissues, the coil was positioned over the skull 2 mm posterior to the bregma. Tail arteries and veins were cannulated allowing periodic measurements of PO2, pCO2, pH and glucose in arterial blood and intravenous infusions. Respiratory acidosis was induced in rats by the addition of CO2 to the ventilation gas mixture. Arterial pCO2 increased within 5 min from a pre-hypercarbic value of 36.4 +/- 6.1 mm Hg to 200-220 mm Hg and was maintained at this level for over 1 hour. Hypercarbia led to rapid cerebral acidification. Intracellular pH decreased from 7.18 +/- 0.08 (pre-hypercarbic period) to 6.68 +/- 0.06 (n = 4) at 10 min and remained stable throughout the NMR observation period. Glutamate decreased to 53 +/- 4% of control after 60 min of hypercarbia, while glutamine increased to 126 +/- 7% of control. Acute hyperammonemia was produced by a programmed intravenous infusion of 250 mM ammonium acetate, which rapidly raised and maintained the concentration of ammonium ions in the blood at approximately 500 microM. Shortly after the start of the infusion (10-20 min), the levels of glutamine and lactate rose continuously throughout the experiment, reaching levels of 170 +/- 25% and 260 +/- 60% of control, respectively (n = 12) after 50 min. Glutamate decreased during the same time interval to 80 +/- 4% of control (n = 12).(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Effects on Cerebral Blood Flow in the Baboon Model - Acetazolamide and Nimodipine

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.