Hypoxic ventilatory responsiveness in Tibetan compared with Han residents of 3,658 m

Lifelong high-altitude residents of North and South America acquire blunted hypoxic ventilatory responses and exhibit decreased ventilation compared with acclimatized newcomers. The ventilatory characteristics of Himalayan high-altitude residents are of interest in the light of their reportedly lower hemoglobin levels and legendary exercise performance. Until recently, Sherpas have been the only Himalayan population available for study. To determine whether Tibetans exhibited levels of ventilation and hypoxic ventilatory drives that were as great as acclimatized newcomers, we compared 27 lifelong Tibetan residents of Lhasa, Tibet, China (3,658 m) with 30 acclimatized Han ("Chinese") newcomers matched for age, body size, and extent of exercise training. During room air breathing, minute ventilation was greater in the Tibetan than in the Han young men because of an increased respiratory frequency, but arterial O2 saturation and end-tidal PCO2 did not differ, indicating similar levels of effective alveolar ventilation. The Tibetan subjects had higher hypoxic ventilatory response shape parameter A values and hypercapnic ventilatory responsiveness than the Han subjects. Among the Han subjects, duration of high-altitude residence correlated with the degree of blunting of the hypoxic ventilatory drive. Paradoxically, hyperoxia (inspired O2 fraction 0.70) increased minute ventilation and decreased end-tidal PCO2 in the Tibetan but not in the Han men. We concluded that lifelong Tibetan residents of high altitude neither hypoventilated nor exhibited blunted hypoxic ventilatory responses compared with acclimatized Han newcomers, suggesting that the effects of lifelong high-altitude residence on ventilation and ventilatory response to hypoxia differ in Tibetan compared with other high-altitude populations.     

Influences of morphine on the ventilatory response to isocapnic hypoxia

BACKGROUND: The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. METHODS: The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). RESULTS: At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). CONCLUSIONS: Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.     

Effects of cardiac output on blood and tissue pH during general anesthesia with constant ventilation

We investigated the effects of cardiac output on blood and tissue pH in 106 adult patients undergoing cardiac or non-cardiac surgery under general anesthesia. After anesthetic induction, the minute ventilation volume was kept constant at 10 ml.kg-1 x 10 cycles.min-1. A pulmonary artery catheter and a nasogastric tube incorporating a tonometer were inserted. During surgery, cardiac index (CI), pH, Pco2, BE, So2 and Hb of arterial and mixed venous blood as well as gastric intramucosal pH (pHi) were measured simultaneously. Oxygen uptake index (Vo2I) and blood CO2 contents were calculated. The measurements were repeated every 10 to 20 minutes during surgery or during the prebypass period. Two patients with preoperative cardiogenic shock were excluded from data analysis because of development of severe acidosis and 624 sets of data from 104 patients were analyzed. Arterial and mixed venous pH correlated negatively with CI. Blood Pco2 and base excess (BE) correlated positively and negatively, respectively, with CI. Blood lactate concentration measured 142 times in the last 30 patients correlated positively with CI. Vo2I correlated positively with CI and Paco2 correlated positively with Vo2I. Veno-arterial differences in Pco2 and Cco2 correlated negatively with CI. Due to the difference, Caco2 correlated positively with CI, while Cvco2 did not correlate with CI. pHi correlated negatively with CI but only marginally. By multiple regression analysis, pHi was not affected significantly by CI, while it showed positive correlation with pHa, Hb, Sao2 and negative correlation with blood temperature. When cardiac output increased, blood pH decreased due to increased Pco2 and decreased BE. An increase in Paco2 might result from both an increase in Vo2 or Vco2 and decreased ventilation-to-perfusion ratio. A decrease in BE might result from increased washout of acids (e.g. lactate) from the tissue to the central circulation. In contrast to blood pH, pHi or tissue pH was not affected significantly by cardiac output unless patients were in cardiogenic shock.     

Effect of a subanesthetic minimum alveolar concentration of isoflurane on two tests of the hypoxic ventilatory response

BACKGROUND: These experiments were designed to study the effect of 0.1 minimum alveolar concentration isoflurane on the hypoxic ventilatory response as measured by two common methods of hypoxic testing: when normocapnic hypoxia was induced abruptly and when it was induced gradually. We hypothesized that any disparity in results would be due to an isoflurane effect that was manifested differently in the two tests. METHODS: After 20 min for uptake and equilibration of 0.1 minimum alveolar concentration end-tidal isoflurane or carrier gas in hyperoxia, isocapnic hypoxia was induced either abruptly over 60-80 s ("step" test) or gradually over 10 min ("ramp" test), followed by 20 min of isocapnic hypoxia at 45 mmHg end-tidal oxygen. Control of the hypoxic and isocapnic stimuli was accomplished accurately by a computer-controlled dynamic end-tidal forcing system. Eight subjects performed each test in the presence and absence of isoflurane. RESULTS: For both step tests and ramp tests, 0.1 minimum alveolar concentration isoflurane had no effect on minute ventilation during the defined periods of hypoxia. With isoflurane, delta VE45, the acute change in ventilation from hyperoxia to hypoxia, was 97 +/- 20% (mean +/- SEM) of the control response for step tests and 100 +/- 25% of the control response for ramp tests. The step tests produced significantly larger acute hypoxic responses than did the ramp tests, but by the end of 20 min of hypoxia, ventilation was similar for both tests. CONCLUSIONS: Neither method of hypoxic testing demonstrated the level of isoflurane effect reported by others. A comparison of the two methods of hypoxic testing suggests that ramp tests, as commonly performed, do not allow adequate time for full expression of the acute hypoxic ventilatory response. Step tests also better separated the opposing hypoxic effects of carotid body stimulation and central ventilatory depression.     

Intraoperative end-tidal carbon dioxide values and derived calculations correlated with outcome: prognosis and capnography

OBJECTIVE: To determine how much information concerning resuscitation and outcome is provided by the end-tidal CO2 and derived variables obtained during surgery. DESIGN: Retrospective chart review. SETTING: Emergency hospital operating room. PATIENTS: One hundred critically ill or injured patients requiring major surgery and having a mortality rate of 41%. INTERVENTIONS: Standard intraoperative monitoring, including continuous capnography, plus arterial blood gas analyses every 1 to 1.5 hrs during surgery. MEASUREMENTS AND MAIN RESULTS: There was only a fair correlation between the PaCO2 and end-tidal CO2 (r2 = .14). The mortality rates in these patients were highest in those patients who had the lowest end-tidal CO2 values, the highest arterial to end-tidal CO2 differences, and the highest estimated alveolar deadspace fraction. A persistent end-tidal CO2 of < or = 28 torr (< or = 3.8 kPa) was associated with a mortality rate of 55% (vs. 17% in those patients with a higher end-tidal CO2). The mortality rate was also increased in patients with a persistent arterial to end-tidal CO2 difference of > or = 8 torr (> or = 1.1 kPa) (58% vs. 23%). CONCLUSIONS: End-tidal CO2 and derived values should be monitored closely in critically ill or injured patients. Efforts should be made--by increasing cardiac output and core temperature and by adjusting ventilation as needed--to maintain the end-tidal CO2 at > or = 29 torr (> or = 3.9 kPa) and the arterial to end-tidal CO2 difference at < or = 7 torr (< or = 1.0 kPa).     

Reductions in cardiac output in hypoxic young pigs: systemic and regional perfusion and oxygen metabolism

We tested the hypotheses that, in hypoxic young pigs, reductions in cardiac output restrict systemic oxygen transport to a greater extent than does hypoxia alone and that compensatory responses to this restriction are more effective in higher than in lower priority vasculatures. To study this, 10- to 14-day-old instrumented awake hypoxic (arterial oxygen tension = 39 Torr) pigs were exposed to reduced venous return by inflation of a right atrial balloon-tipped catheter. Blood flow was measured with radionuclide-labeled microspheres, and oxygen metabolism was determined with arterial and venous oxygen contents from appropriate vessels. Hypoxia resulted in a reduction in oxygen tension; increases in cardiac output and perfusion to brain (72% over baseline), heart, adrenal glands, and liver without reductions to other organs except for the spleen; reductions in systemic and intestinal oxygen delivery; and increases in systemic and intestinal oxygen extraction without changes in systemic, cerebral, or intestinal oxygen uptake. During hypoxia, decreasing venous return was associated with increases in arterial lactic acid concentration and central venous pressure; attenuation of the hypoxia-related increase in cardiac output; sustained increases in brain (72% over baseline) and heart perfusion; reductions in lung (bronchial artery), pancreatic, renal, splenic, and intestinal (-50% below baseline) perfusion; decreases in systemic and gastrointestinal oxygen delivery; sustained increases in systemic and intestinal oxygen extraction; and decreases in intestinal oxygen uptake, without changes in cerebral oxygen metabolism. We conclude that when venous return to the heart is reduced in hypoxic young pigs, the hypoxia-related increase in cardiac output was attenuated and the relative reduction in cardiac output was associated with preserved cerebral oxygen uptake and compromised intestinal oxygen uptake. Regional responses to hypoxia combined with relative reductions in cardiac output differ from that of hypoxia alone, with the greatest effects on lower priority organs such as the gastrointestinal tract.     

Pyridoxalated hemoglobin polyoxyethylene conjugate does not restore hypoxic pulmonary vasoconstriction in ovine sepsis

OBJECTIVES: Hypoxic pulmonary vasoconstriction, a protective mechanism, minimizes perfusion of underventilated lung areas to reduce ventilation-perfusion mismatching. We studied the effects of sepsis on hypoxic pulmonary vasoconstriction and attempted to determine whether hypoxic pulmonary vasoconstriction is influenced by pyridoxalated hemoglobin polyoxyethylene conjugate, a nitric oxide scavenger. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational intensive care unit at a university medical center. SUBJECTS: Nineteen female merino sheep, divided into three groups: group 1, controls (n = 5); group 2, sheep with sepsis (n = 6); and group 3, septic sheep treated with pyridoxalated hemoglobin polyoxyethylene conjugate (n = 8). INTERVENTIONS: All sheep were instrumented for chronic study. An ultrasonic flow probe was placed around the left pulmonary artery. After a 5-day recovery, a tracheostomy was performed and a double-lumen endotracheal tube was placed. Animals in groups 2 and 3 received a 48-hr infusion of live Pseudomonas aeruginosa (6 x 10(4) colony-forming units/kg/hr). After 24 hrs, sheep in group 3 received pyridoxalated hemoglobin polyoxyethylene conjugate (20 mg/kg/hr) for 16 hrs; sheep in groups 1 and 2 received only the vehicle. Hypoxic pulmonary vasoconstriction was repeatedly tested by unilateral hypoxia of the left lung with 100% nitrogen. Hypoxic pulmonary vasoconstriction was assessed as the change in left pulmonary blood flow. MEASUREMENTS AND MAIN RESULTS: In the animals in group 1, left pulmonary blood flow decreased by 62 +/- 8 (SEM)% during left lung hypoxia and remained stable during repeated hypoxic challenges throughout the study period. After 24 hrs of sepsis, left pulmonary blood flow decreased from 56 +/- 10% to 26 +/- 2% (group 2) and from 50 +/- 8% to 23 +/- 6% (group 3). In the sheep in group 2, there was no adaptation over time. Pulmonary shunt fraction increased. Pyridoxalated hemoglobin polyoxyethylene conjugate had no effect on hypoxic pulmonary vasoconstriction or pulmonary shunt. The animals receiving the bacterial infusion developed a hyperdynamic circulatory state with hypotension, decreased systemic vascular resistance, and increased cardiac output. Pyridoxalated hemoglobin polyoxyethylene conjugate increased mean arterial pressure and systemic vascular resistance but did not influence cardiac index. Pulmonary arterial pressure was increased during sepsis and increased even further after pyridoxalated hemoglobin polyoxyethylene conjugate administration. Oxygenation and oxygen delivery and uptake were not affected by pyridoxalated hemoglobin polyoxyethylene conjugate. CONCLUSIONS: Hypoxic pulmonary vasoconstriction is blunted during sepsis and there is no adaptation over time. It is not influenced by pyridoxalated hemoglobin polyoxyethylene conjugate. Pyridoxalated hemoglobin polyoxyethylene conjugate reversed hypotension and, with the exception of an increase in pulmonary arterial pressure, had no adverse effects on hemodynamics or oxygenation.     

Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs

We have studied the effects of i.v. bolus doses of magnesium sulphate (MgSO4) 60, 90 and 120 mg kg-1 on haemodynamic state, the coronary circulation and myocardial metabolism in nine dogs anaesthetized with pentobarbitone and fentanyl. MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI) and an increase in the time constant of left ventricular isovolumic relaxation. Stroke volume increased, systemic vascular resistance decreased and cardiac output did not change significantly. MgSO4 produced decreases in coronary perfusion pressure, coronary vascular resistance and myocardial oxygen consumption (MVO2). Coronary sinus blood flow, lactate extraction ratio and the ratio of LVMWI to myocardial MVO2, that is an index of cardiac efficiency, did not change significantly. This study indicated that the depressant effect of MgSO4 on cardiac function was offset by lowering of peripheral vascular resistance, so that cardiac pump function remained effective, and the almost constant coronary sinus blood flow resulted from the decrease in coronary vascular resistance even at higher doses.     

Decreased ventilation response to hypoxia in children with asthma

We measured the ventilation and inspiratory muscle activity responses to hypoxia and hypercapnia in 18 children with asthma. Ventilation was less efficient in the asthmatic children in that more inspiratory muscle activity per liter of ventilation was required than in normal children. Asthmatic and healthy children had similar ventilation responses to hypercapnia; at all levels of end-tidal Pco2, the inspiratory muscle activity was greater in those with asthma. However, during progressive isocapnic hypoxia, asthmatic patients did not increase their inspiratory muscle activity at a rate greater than normal. Thus, because of inefficient ventilation, they had significantly decreased ventilatory responses to hypoxia. Neither ventilation nor inspiratory muscle activity response to hypoxia was correlated with duration of illness or with the degree of airways obstruction present. These results demonstrate that children with chronic asthma have decreased hypoxic responsiveness and suggest that neither long-term airways obstruction nor intermittent hypoxia associated with asthma is necessary to diminish hypoxic response in asthmatic patients. An asthmatic child with depressed hypoxic responsiveness may be at increased risk of hypoxic complications or respiratory failure during acute asthma.     

Age alters regional distribution of blood flow during moderate-intensity exercise

During dynamic exercise in warm environments, requisite increases in skin and active muscle blood flows are supported by increasing cardiac output (Qc) and redistributing flow away from splanchnic and renal circulations. To examine the effect of age on these responses, six young (Y; 26 +/- 2 yr) and six older (O; 64 +/- 2 yr) men performed upright cycle exercise at 35 and 60% of peak O2 consumption (VO2peak) in 22 and 36 degrees C environments. To further isolate age, the two age groups were closely matched for VO2peak, weight, surface area, and body composition. Measurements included heart rate, Qc (CO2 rebreathing), skin blood flow (from increases in forearm blood flow (venous occlusion plethysmography), splanchnic blood flow (indocyanine green dilution), renal blood flow (p-amino-hippurate clearance), and plasma norepinephrine concentration. There were no significant age differences in Qc; however, in both environments the O group maintained Qc at a higher stroke volume and lower heart rate. At 60% VO2peak, forearm blood flow was significantly lower in the O subjects in each environment. Splanchnic blood flow fell (by 12-14% in both groups) at the lower intensity, then decreased to a greater extent at 60% VO2peak in Y than in O subjects (e.g., -45 +/- 2 vs. -33 +/- 3% for the hot environment, P < 0.01). Renal blood flow was lower at rest in the O group, remained relatively constant at 35% VO2peak, then decreased by 20-25% in both groups at 60% VO2peak. At 60% VO2peak, 27 and 37% more total blood flow was redistributed away from these two circulations in the Y than in the O group at 22 and 36 degrees, respectively. It was concluded that the greater increase in skin blood flow in Y subjects is partially supported by a greater redistribution of blood flow away from splanchnic and renal vascular beds.     

The effect of hypoxia on the regional distribution of cardiac output in the dog

Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.     

Artifical ventilation and spontaneous respiration under CO2-control (author's transl)

In patients undergoing anaesthesia with controlled respiration the respiratory minutevolume required is not predictable! A "Compact-Respiratory-Monitor" enables the anaesthesiologist to observe simultaneously alveolar respiratory minute volume and end-tidal CO2-concentration as well. During anaesthetics with controlled respiration both values should be kept in parallel, while the end-tidal CO2-concentration has to be stabilized around 4vol% by adjusting the respiratory minute-volume to an adaequate level. Spontaneous changes of these parameters indicate disturbances due to ventilation/perfusion-relationship. This instrument was created for use in daily routine work. Over- and underventilation can be avoided by the use of this instrument.     

Changes in cytosol Ca(2+)-, Mg(2+)-, H(+)-, N(+)-, and K(+)-concentrations in cultivated hepatocytes in hypoxic conditions

AIM: It is assumed that disturbances of cellular ion homeostasis, especially an increase in the cytosolic Ca2+ concentration, are of decisive importance for hypoxic cell injury. The aim of this study is the determination of alterations in the cytosolic Ca2+, Mg2+, H+, Na+ and K+ concentration in cultured hepatocytes during hypoxia. METHODS: The alterations of ion homeostasis under hypoxic conditions were studied in primary cultures of isolated rat hepatocytes by using fluorescence microscopy. RESULTS: The measurements of cytosolic Ca2+ concentration showed no alterations during the first 3-4 h of hypoxia. About 1-2 h before cell injury became evident Ca2+ increased from 147 +/- 28 to 385 +/- 31 nM. Similarly the cytosolic Mg2+ concentration increased from 0.63 +/- 0.05 to 1.42 +/- 0.11 mM in a late stage of hypoxia. In contrast, the cytosolic Na+ concentration increased continuously from 16 +/- 2 mM at start to 76 +/- 9 mM after 5 h of hypoxic conditions. The cytosolic K+ concentration remained constant for 2 h (129 +/- 7 mM) but then decreased down to 31 +/- 18 mM. The intracellular H+ concentration increased slightly under hypoxic conditions, the pH decreased from 7.35 +/- 0.02 to 7.19 +/- 0.04. CONCLUSION: The results indicate that cytosolic Ca2+ plays only a minor role in the pathomechanism of hypoxic hepatocellular injury but suggest an important role of the cytosolic Na+ concentration in this process.     

Preservation of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane anesthesia compared to the conscious state in chronically instrumented dogs

BACKGROUND: The authors' objective was to assess the extent to which sevoflurane and desflurane anesthesia alter the magnitude of hypoxic pulmonary vasoconstriction compared with the response measured in the same animal in the conscious state. METHODS: Left pulmonary vascular pressure-flow plots were generated in seven chronically instrumented dogs by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. Pressure-flow plots were generated during normoxia and hypoxia on separate days in the conscious state, during sevoflurane (approximately 3.5% end-tidal), and during desflurane (approximately 10.5% end-tidal) anesthesia. Values are mean+/-SEM. RESULTS: In the conscious state, administration of the hypoxic gas mixture by conical face mask decreased (P < 0.01) systemic arterial PO2 from 94+/-2 mmHg to 50+/-1 mmHg and caused a leftward shift (P < 0.01) in the pressure-flow relationship, indicating pulmonary vasoconstriction. The magnitude of hypoxic pulmonary vasoconstriction in the conscious state was flow-dependent (P < 0.01). Neither anesthetic had an effect on the baseline pressure-flow relationship during normoxia. The magnitude of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane was also flow-dependent (P < 0.01). Moreover, at any given value of flow the magnitude of hypoxic pulmonary vasoconstriction was similar during sevoflurane and desflurane compared with the conscious state. CONCLUSION: These results indicate that hypoxic pulmonary vasoconstriction is preserved during sevoflurane and desflurane anesthesia compared with the conscious state. Thus, inhibition of hypoxic pulmonary vasoconstriction is not a general characteristic of inhalational anesthetics. The flow-dependent nature of the response should be considered when assessing the effects of physiologic or pharmacologic interventions on the magnitude of hypoxic pulmonary vasoconstriction.     

Human ventilatory response to CO2 after 8 h of isocapnic or poikilocapnic hypoxia

During ventilatory acclimatization to hypoxia (VAH), the relationship between ventilation (VE) and end-tidal PCO2 (PETCO2) changes. This study was designed to determine 1) whether these changes can be seen early in VAH and 2) if these changes are present, whether the responses differ between isocapnic and poikilocapnic exposures. Ten healthy volunteers were studied by using three 8-h exposures: 1) isocapnic hypoxia (IH), end-tidal PO2 (PETO2) = 55 Torr and PETCO2 held at the subject's normal prehypoxic value; 2) poikilocapnic hypoxia (PH), PETO2 = 55 Torr; and 3) control (C), air breathing. The VE-PETCO2 relationship was determined in hyperoxia (PETO2 = 200 Torr) before and after the exposures. We found a significant increase in the slopes of VE-PETCO2 relationship after both hypoxic exposures compared with control (IH vs. C, P < 0.01; PH vs. C, P < 0.001; analysis of covariance with pairwise comparisons). This increase was not significantly different between protocols IH and PH. No significant changes in the intercept were detected. We conclude that 8 h of hypoxia, whether isocapnic or poikilocapnic, increases the sensitivity of the hyperoxic chemoreflex response to CO2.     

Effect of pulmonary microembolism on arteriovenous shunt flow

The effects of acute pulmonary hypertension on the fraction of cardiac output shunted through pulmonary arteriovenous communications have been studied in dogs as a possible cause of hypoxia following pulmonary embolization. Pulmonary artery pressure was increased twofold and then fourfold above control values by embolization of the pulmonary vascular bed with polystyrene microspheres. Quantitative measurements of arteriovenous shunt were determined from the fraction of 50 mu radioactively labeled microspheres injected into the inferior vena cava which passed through the pulmonary circulation into systemic vascular beds. There was no increase in the fraction of pulmonary blood flow passing through pulmonary arteriovenous connections, 50 mu in diameter or greater, with pulmonary microembolism when FIo2 was 1. There was a small increase in arteriovenous shunt fraction when pulmonary artery pressure was increased with an FIo2 of 0.21. Physiological shunt measured by the oxygen technique did not increase with pulmonary embolism, but total venous admixture rose significantly. Postmortem gravimetric measurements of lung water indicated pulmonary edema. We conclude that anatomic arteriovenous shunt channels have little physiological significance after pulmonary microembolism in the dog lung. The major cause of hypoxia immediately after pulmonary microembolism is ventilation/perfusion imbalance, probably caused by pulmonary edema.     

Effects of phenobarbital on cerebral blood flow during hypoxia

Phenobarbital (PB), at anticonvulsant dosages, has been used in an attempt to reduce hypoxic brain injury in asphyxiated newborn infants. The effects of PB pretreatment on the cerebral blood flow (CBF) response in hypoxia were studied in 15 curarized and mechanically ventilated piglets: 7 animals were pretreated with 20 mg/kg of PB (group 1) and 8 served as untreated controls (group 2). Successive aliquots (25 ml) of carbon monoxide were introduced into a closed ventilator circuit and CBF (measured with radiolabelled microspheres), arterial blood pressure, blood gases, arterial pH and PaO2 were subsequently determined at different levels of hypoxia. The amount of hemoglobin available for oxygen transport (i.e. total Hb-HbCO) was used to express hypoxic aggression and decreased from grade I (> 2 mmol/l) to grade II (1-2 mmol/l) to grade III (< 1 mmol/l). In the control group, CBF increased during grade-I hypoxia and continuously remained above baseline values during grade-II and grade-III hypoxia. In pretreated animals, however, only grade-II hypoxia was associated with a significant increase in CBF above baseline. In addition during grade-III hypoxia, CBF decreased to the prehypoxic values despite a fall in cerebral oxygen delivery and cardiac index. These data suggest that PB should be used with caution to prevent brain damage in the asphyxiated newborn infants.     

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.     

Steady-state PVECP is superior to transient PVECP in the diagnosis of optic neuritis

The isoflurane-saving and CO2-retaining effects of a charcoal filter were compared with a Siemens standard heat and moisture (HME) exchanger and an emptied specimen (dummy). Isoflurane was delivered during the inspiratory phase and consumption investigated at 10, 15 and 25 cycles min-1. The investigation was performed by ventilation with humidified air with a constant end-tidal CO2 and temperature. For a comparison, isoflurane was delivered in a conventional manner via the ventilator. The arrangement with a charcoal filter reduced the isoflurane consumption by a factor of 2.0-2.6, depending on ventilatory rate. Most of the saving was a result of the method of isoflurane delivery (factor 1.4-2.0), while adding the reflector gave a further reduction (factor 1.3-1.5). One circumstance that reduced the net efficiency of the charcoal filter was that it also reflected CO2; consequently, total minute ventilation had to be increased to maintain constant end-tidal CO2.     

Effects of long-term, high-altitude hypoxemia on ovine fetal cardiac output and blood flow distribution

OBJECTIVE: We sought to determine the effects of long-term hypoxemia on fetal cardiac output and flow distribution. STUDY DESIGN: We exposed six pregnant sheep to high altitude (3820 m) hypoxia from 30 to 135 days' gestation (term 146 days). Ten to 14 days after surgery we determined fetal cardiac output and organ blood flows by means of the radiolabeled microsphere technique during a baseline period and also during an additional 30-minute period of more severe added acute hypoxemia. RESULTS: Baseline maternal arterial PO2 was 60.7 +/- 1.7 torr and fell to 35.1 +/- 3.0 torr during the added acute hypoxemia. Fetal arterial PO2 decreased from 18.5 +/- 1.1 to 11.4 +/- 1.5 torr during added acute hypoxemia. Baseline fetal cardiac output was 351 +/- 55 ml/min/kg, which was significantly lower than previously reported values in low-altitude fetuses. Blood flow to critical organs such as the heart and brain was maintained at levels found in low-altitude fetuses, but flow to the carcass was significantly lower (-49%) than the mean value reported in the literature for low-altitude fetuses. Oxygen delivery was also maintained at normal levels to the brain and heart but was reduced in the kidneys (-31%), gastrointestinal tract (51%), and carcass (-58%). During added acute hypoxemia cardiac output did not change significantly; however, blood flow to the brain, heart, and adrenal glands increased 112%, 135%, and 156% (p < 0.05), respectively. CONCLUSION: We conclude that during long-term hypoxemia redistribution of fetal cardiac output is maintained favoring the brain and heart.