Heart rate changes evoked by hypoxia in the anaesthetized, artificially ventilated cat.

Reflex changes in heart rate evoked by hypoxia were investigated in cats anesthetized with chloralose and ventilated by positive pressure during administration of vecuronium or gallamine. In five cats receiving vecuronium and with aortic pressure stabilized, systemic hypoxia (arterial O2 pressure (Pa, O2) 34.9 mmHg) reduced heart rate by 55.8 +/- 7.5 beats min-1 (mean +/- S.E.M.). After administration of atropine, hypoxia (Pa, O2 32.1 mmHg) increased heart rate by 28.2 +/- 3.4 beats min-1. After subsequent bilateral ablation of carotid sinus and vagus nerves, hypoxia (Pa, O2 31.9 mmHg) increased heart rate by 7.1 +/- 1.8 beats min-1. The cardiac accelerator response to hypoxia was further examined in groups of cats treated with gallamine and atropine. In four vagotomized cats, local perfusion of both carotid sinuses with hypoxic blood (Pa, O2 37.7 mmHg) increased heart rate by 15.5 +/- 2.3 beats min-1. In the same cats, systemic hypoxia (Pa, O2 38.3 mmHg) increased heart rate by 16.4 +/- 2.3 beats min-1. The heart rate increment in cats which had undergone either bilateral adrenalectomy or cardiac sympathectomy was similar to the increment in unoperated cats. The increment was significantly less in cats which had both adrenal glands and cardiac sympathetic nerves ablated. It is concluded that stimulation of the carotid bodies in the cat excites both parasympathetic and sympathetic cardiac nerves simultaneously.     

During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level.

To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O(2) delivery with O(2) demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 mug (kg body mass)(-1) min(-1)) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 +/- 1.0 versus 7.9 +/- 1.0 l min(-1)) and femoral arterial oxygen delivery (1.2 +/- 0.2 versus 1.3 +/- 0.2 l min(-1); control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 +/- 14.2 versus 83.3 +/- 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 +/- 5.3 to 72.0 +/- 10.2% (P < 0.05), and the corresponding venous O(2) content was increased from 25.5 +/- 10.0 to 46.3 +/- 18.5 ml l(-1) (control and ATP, respectively, P < 0.05). With ATP, leg arterial-venous O(2) difference was decreased (P < 0.05) from 139.3 +/- 9.0 to 116.9 +/- 8.4(-1) and leg .VO(2max) was 20% lower compared to the control trial (1.1 +/- 0.2 versus 0.9 +/- 0.1 l min(-1)) (P = 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O(2) delivery with O(2) demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg .VO(2peak) is not limited by restricted vasodilatation in the altitude-acclimatized human.     

Nitric oxide synthase inhibition speeds oxygen uptake kinetics in horses during moderate domain running

Within the moderate exercise intensity domain, the speed of oxygen uptake (V(O(2))) kinetics at the transition to a higher metabolic rate is thought to be limited by an inertia of the oxidative machinery. Nitric oxide (NO)-induced inhibition of O(2) consumption within the electron transport chain may contribute to this inertia. This investigation tested the hypothesis that a reduction or removal of any such NO effect via infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) would speed V(O(2)) kinetics at the onset of moderate exercise. Five Thoroughbred geldings underwent four transitions to running speeds of 7 m sec(-1) (two control, C, 2 L-NAME [20 mg kg(-1)]) on an equine treadmill during which pulmonary gas exchange was determined using a bias flow system. Consistent with exercise in the moderate intensity domain, in none of the transitions was a V(O(2)) slow component elicited. The L-NAME treatment significantly accelerated V(O(2)) kinetics via a reduction of the primary amplitude time constant (C, 17.3 +/- 1.7; L-NAME, 11.8 +/- 1.5 sec, P < 0.05) concomitant with faster overall dynamics (i.e. T(50) and T(75) both P < 0.05) and a trend toward a decreased O(2) deficit (C, 6.4 +/- 0.7; L-NAME, 4.7 +/- 1.2 L; P = 0.06). These data support the notion that NO contributes prominently to the oxidative enzyme inertia and thus the speed of V(O(2)) kinetics at the onset of moderate intensity exercise in the horse.     

Response of cerebral blood flow to changes in PCO2 in fetal, newborn, and adult sheep

Developmental effects on the response of cerebral blood flow (Qc) and cerebral O2 consumption (CMRO2) to changes in CO2 tension were assessed in unanesthetized fetal, newborn, and adult sheep. Blood flow was measured using the radioactive microsphere technique. CMRO2 was calculated as the product of Qc and the difference in O2 content between arterial and sagittal sinus blood (CaO2 -- CVO2). The response of Qc to changes in arterial CO2 tension increased from fetus [3.53 +/- 0.56 ml.100 g-1.min-1.mmHg PaCO2(-1) (SE)] to newborn (5.16 +/- 0.59) to adult (6.20 +/- 0.63). Only the fetal-adult difference was significant (P less than 0.05). It has been suggested that developmental differences in CO2 responsiveness of cerebral blood flow are the result of differences in CMRO2. We corrected for differences in CMRO2 by looking at the response to CO2 of the variable 1/(CaO2--CVO2). According to the Fick principle 1/(CaO2--CVO2) = Qc/CMRO2, i.e., blood flow per unit O2 consumption. The fetal response was not significantly different from the newborn, but the adult was significantly different from both (P less than 0.05). Thus the difference in CO2 response of cerebral blood flow between fetus and adult cannot be explained by differences in CMRO2.     

Bloodless testing for microporous membrane oxygenator failure: a preliminary study

The use of a bloodless solution and high pressure to accelerate microporous membrane oxygenator (MMO) failure was investigated. It was hypothesized that albumin acts as a wetting agent, contributing to plasma leakage through the membrane, and that high MMO outlet pressure accelerates the process. Three MMO, B-Bentley BCM-40 (n = 7), M-Medtronic Maxima (n = 4), and S-Sarns 16310 (n = 7) were tested at 37 +/- 2 degrees C using three identical closed recirculating circuits and four conditions: 1) Lactated Ringer solution (LR) with MMO outlet pressure (Pmo) 750 mmHg; 2) LR + albumin (4 g/100 ml), Pmo 150 mmHg; 3) LR + albumin, Pmo 300 mmHg; and 4) LR + albumin, Pmo 750 mmHg. "Blood" flow and gas flow were maintained at 2 l/min. Failure was indicated when Na+ was detected in the effluent of the MMO exhaust gas. There were no failures without albumin in the solution. B and M showed no signs of failure under any of the test conditions at 78 hours. S failed at (mean +/- SEM) 4.9 +/- 1.0, 12.1 +/- 0.2, and 19 hours for conditions 4, 3, and 2 respectively. Preceding failure, inlet gas pressure increased more than eightfold (27 +/- 1 to 224 +/- 34 mmH2O). These preliminary results are similar to previous findings with blood and suggest that high MMO outlet pressure and the presence of albumin may promote plasma breakthrough for S. The combination may provide a basis for an accelerated bloodless test for MMO compatibility with long-term respiratory support.     

Seasonal changes in blood oxygen transport and acid-base status in the tegu lizard, Tupinambis merianae

Oxygen-binding properties, blood gases, and acid-base parameters were studied in tegu lizards, Tupinambis merianae, at different seasons and temperatures. Independent of temperature and pH, blood oxygen affinity was higher in dormant lizards than in those active during the summer. Haematocrit (Hct) and hemoglobin content ([Hb]) were greater in active lizards resulting in a higher oxygen-carrying capacity. Nucleoside triphosphate content ([NTP]) was reduced during dormancy, but the ratio between [NTP] and [Hb] remained unchanged. Dormancy was accompanied by an increase in plasma bicarbonate ([HCO-(3)]pl) and an elevation of arterial CO2 partial pressure (PaCO2) and CO2 content in the plasma (CplCO2). These changes in acid-base parameters persist over a broad range of body temperatures. In vivo, arterial O2 partial pressure (PaO2) and O2 content (CaO2) were not affected by season and tended to increase with temperature. Arterial pH (pHa) of dormant animals is reduced compared to active lizards at body temperatures below 15 degrees C, while no significant difference was noticed at higher temperatures.     

经微流口鼻罩呼气末二氧化碳监测的准确度研究

目的观察经微流口鼻罩呼气末CO2分压[PET(CO2)]监测的准确度,以及吸氧对PET(CO2)监测的影响。方法选择美国麻醉医师协会(ASA)分级Ⅰ～Ⅲ级,意识清醒、拟在局部麻醉下行数字减影脑血管造影术的患者42例,其中男性24例,女性18例;年龄18～65岁,平均年龄46岁。随机分为两组,吸氧组和不吸氧组。吸氧组患者用微流口鼻罩吸氧(氧流速5 L/min),并同时监测经微流口鼻罩PET(CO2);不吸氧组患者只监测经微流口鼻罩PET(CO2),不吸氧。两组患者均持续监测心率(HR)、收缩压/舒张压(SBP/DBP)、脉搏氧饱和度(SpO2)、PET(CO2),在PET(CO2)稳定并持续5 min情况下抽取股动脉血,测定动脉血二氧化碳分压[Pa(CO2)],并同时记录PET(CO2)。结果两组患者的年龄、性别、术中血流动力学变化相比差异无统计学意义。两组患者经微流口鼻罩PET(CO2)与Pa(CO2)相关性较好,吸氧(氧流速5L/min)情况下PET(CO2)与Pa(CO2)相关系数r=0.815,不吸氧时PET(CO2)与Pa(CO2)相关系数r=0.694。两组患者Bland-Altman一致性分析结果相似,吸氧组Pa(CO2)与PET(CO2)的差值[Pa-ET(CO2)]为(0.41±0.34)kPa[(3.10±2.56)mmHg],95%一致性界限为-0.256～1.080 kPa(-1.92～8.12 mmHg),不吸氧组Pa-ET(CO2)为(0.25±0.33)kPa[(1.90±2.49)mmHg],95%一致性界限为-0.396~0.902 kPa(-2.98～6.78 mmHg)。两组Pa-ET(CO2)相比差异无统计学意义(P>0.05)。结论经微流口鼻罩监测的PET(CO2)与Pa(CO2)有强相关性和较好的一致性,经微流口鼻罩PET(CO2)可以准确反映Pa(CO2)。氧流速5 L/min对经微流口鼻罩PET(CO2)监测的准确度没有影响。     

Cerebral blood flow sensitivity to CO2 measured with steady-state and Read's rebreathing methods

The ventilatory response to carbon dioxide (CO2) measured by the steady-state method is lower than that measured by Read's rebreathing method. A change in end-tidal P CO2 (PET CO2) results in a lower increment change in brain tissue P CO2 (Pt CO2) in the steady-state than with rebreathing: since Pt(CO2) determines the ventilatory response to CO2, the response is lower in the steady-state. If cerebral blood flow (CBF) responds to Pt CO2, the CBF-CO2 response should be lower in the steady-state than with rebreathing. Six subjects undertook two protocols, (a) steady-state: PET CO2 was held at 1.5 mmHg above normal (isocapnia) for 10 min, then raised to three levels of hypercapnia, (8 min each; 6.5, 11.5 and 16.5 mmHg above normal, separated by 4 min isocapnia). End-tidal P O2 was held at 300 mmHg; (b) rebreathing: subjects rebreathed via a 6 L bag filled with 6.5% CO2 in O2. Transcranial Doppler-derived CBF yielded a higher CBF-CO2 sensitivity in the steady-state than with rebreathing, suggesting that CBF does not respond to Pt CO2.     

Maternal placental vascular compliance in rabbits

We studied compliance on the maternal side of the placenta of 20 New Zealand white rabbits, using 51Cr and 125I labels to determine erythrocyte, plasma, and whole-blood volumes per gram of placental tissue under varying maternal pressure conditions. At normal maternal arterial (Pa) and venous (Pv) pressures of 71.8 and 5.5 mmHg, placental blood volume (mean +/- SE) was 0.447 +/- 0.051 ml/g placental tissue. When venous pressure was raised (Pa = 45.5, Pv = 12.2) by occluding the inferior vena cava, blood volume increased to 0.729 +/- 0.068 ml/g, a significant 63% rise. However, when arterial pressure was lowered by occluding the aorta in two steps, dropping to Pa = 33.8, Pv = 7.0, and Pa = 13.5, Pv = 5.4, volume did not decrease significantly. We estimated intervillous space pressure (Pivs) from arterial and venous pressures assuming a ratio of venous to total resistance of 0.02. Compliance calculated from the slope of Pivs vs. volume was 0.0471 ml/mmHg per g. Maternal placental hematocrit averaged 27%, appreciably less than the circulating hematocrit of 38%. Overall, the results suggest that placental volume would be maintained during hypotension and would increase when venous pressure is elevated.     

The cerebellar fastigial nucleus contributes to CO2-H+ ventilatory sensitivity in awake goats

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO(2)-H(+) sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N=9) for injection (0.5-10 microl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO(2)-H(+) sensitivity did not differ significantly (P>0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic Pa(CO2) (P>0.10). The coefficient of variation of eupneic Pa(CO2) was 4.0+/-0.6 and 3.7+/-0.4% over the 2 weeks before and after the lesion, respectively. CO(2)-H(+) sensitivity expressed as inspired ventilation/Pa(CO2) decreased from 2.15+/-0.17 pre-lesion to 1.58+/-0.26 l/(min mmHg) 3-6 days post-lesion (P<0.02, -27%). There was no significant (P>0.10) recovery of sensitivity between 7 and 10 days post-lesion. The lesion also increased (P<0.05) the day-to-day variability of this index by nearly 100%. When CO(2) sensitivity was expressed as elevated inspired CO(2)/room air V (I), values at 7%, but not 3 and 5% inspired CO(2), were reduced and more variable (P<0.05) after the ibotenic acid injections. We conclude that during wakefulness, the CFN contributes relatively more to overall ventilatory drive at high relative to low levels of hypercapnia.     

Oxygen kinetics and debt during recovery from expiratory flow-limited exercise in healthy humans

In healthy subjects expiratory flow limitation (EFL) during exercise can lower O(2) delivery to the working muscles. We hypothesized that if this affects exercise performance it should influence O(2) kinetics at the end of exercise when the O(2) debt is repaid. We performed an incremental exercise test on six healthy males with a Starling resistor in the expiratory line limiting expiratory flow to approximately 1 l s(-1) to determine maximal EFL exercise workload (W (max)). In two more square-wave exercise runs subjects exercised with and without EFL at W (max) for 6 min, while measuring arterial O(2) saturation (% SaO(2)), end-tidal pressure of CO(2) (P (ET)CO(2)) and breath-by-breath O(2) consumption VO2 taking into account changes in O(2) stored in the lungs. Over the last minute of EFL exercise, mean P (ET)CO(2) (54.7 +/- 9.9 mmHg) was significantly higher (P < 0.05) compared to control (41.4 +/- 3.9 mmHg). At the end of EFL exercise %SaO(2) fell significantly by 4 +/- 3%. When exercise stopped, EFL was removed, and we continued to measure VO2. During recovery, there was an immediate step increase in [Formula: see text] so that repayment of EFL O(2) debt started at a higher VO2 than control. Recovery VO2 kinetics after EFL exercise was best characterized by a double-exponential function with fundamental and slow time constants of 27 +/- 11 and 1,020 +/- 305 s, compared to control values of 41 +/- 10 and 1,358 +/- 320 s, respectively. EFL O(2) debt was 52 +/- 22% greater than control (2.19 +/- 0.58 vs. 1.49 +/- 0.38 l). We conclude that EFL exercise increases the O(2) debt and leads to hypoxemia in part due to hypercapnia.     

Cerebral blood flow and oxygen consumption in the newborn dog

Cerebral blood flow (CBF), CBF responses to changes in arterial CO2 tension, and cerebral metabolic rate for oxygen (CMRO2) were measured in newborn dogs, by means of a modification of the Kety and Schmidt technique employing 133Xe. Mongrel dogs of 1-7 days of age were paralyzed and passively ventilated with 70% N2O and 30% O2. CBF was derived by analysis of paired serial 20-microliter samples of arterial and of cerebral venous blood from the superior sagittal sinus. At an arterial PCO2 of 36.9 +/- 3.7 Torr and a mean arterial blood pressure of 62 +/- 10 Torr, CBF was 23 +/- 8 ml/min per 100 g. The arteriovenous oxygen content difference averaged 5.6 vol%, and CMRO2 was 1.13 +/- 0.30 ml O2/min per 100 g. CBF increased or decreased by 0.58 ml/min/100 g per Torr change in PCO2. Our results suggest that in the newborn, basal CBF and CBF responses to CO2 are considerably lower than in the adult and parallel the lower metabolic needs of the newborn brain.     

Estimating the effect of lung collapse and pulmonary shunt on gas exchange during breath-hold diving: the Scholander and Kooyman legacy

We developed a mathematical model to investigate the effect of lung compression and collapse (pulmonary shunt) on the uptake and removal of O(2), CO(2) and N(2) in blood and tissue of breath-hold diving mammals. We investigated the consequences of pressure (diving depth) and respiratory volume on pulmonary shunt and gas exchange as pressure compressed the alveoli. The model showed good agreement with previous studies of measured arterial O(2) tensions (Pa(O)(2)) from freely diving Weddell seals and measured arterial and venous N(2) tensions from captive elephant seals compressed in a hyperbaric chamber. Pulmonary compression resulted in a rapid spike in Pa(O)(2) and arterial CO(2) tension, followed by cyclical variation with a periodicity determined by Q(tot). The model showed that changes in diving lung volume are an efficient behavioural means to adjust the extent of gas exchange with depth. Differing models of lung compression and collapse depth caused major differences in blood and tissue N(2) estimates. Our integrated modelling approach contradicted predictions from simple models, and emphasised the complex nature of physiological interactions between circulation, lung compression and gas exchange. Overall, our work suggests the need for caution in interpretation of previous model results based on assumed collapse depths and all-or-nothing lung collapse models.     

Blood pressure control in arterial- and cardiopulmonary receptor denervated dogs.

The mechanisms influencing arterial blood pressure and heart rate were studied in conscious foxhounds after chronic sino-aortic and cardiopulmonary denervation (N = 6). In previous investigations it was shown, that this denervation produces hypertension and tachycardia, which is confirmed by the present study: Mean arterial blood pressure increased from 101 +/- 3 to 123 +/- 6 mmHg (P less than 0.05), and heart rate rose from 85 +/- 6 to 124 +/- 5 beats min-1 (P less than 0.001). The variability of mean arterial blood pressure, but not that of heart rate increased (from 6 +/- 1 to 22 +/- 2 mmHg (P less than 0.001). The administration of the alpha-adrenergic blocker prazosin reduced both mean arterial blood pressure (-33 +/- 8 mmHg, P less than 0.01) and its variability (-12 +/- 1 mmHg, P less than 0.01), thus suggesting an alpha-adrenergic mediated hypertension. beta-blockade by propranolol blunted the heart rate increase (-24 +/- 5 beats min-1, P less than 0.05). Although plasma renin activity increased in the denervated dogs, converting enzyme inhibition had little effect on mean arterial blood pressure and heart rate. In conclusion, chronic sino-aortic and cardiopulmonary denervation enhances the alpha and beta-adrenergic component of cardiovascular control in a different fashion. While the alpha-adrenergic component induces fluctuations around an elevated arterial blood pressure level, the beta-adrenergic tone to the heart increases without any significant increase in variability.     

Carbon dioxide and liver blood flow.

This study was designed to determine blood flow to the liver during hypercapnia and combined hypercapnia-hypoxia with the portal vein and hepatic artery intact except for placement of an electromagnetic flow probe around these vessels. Twenty mongrel dogs weighing 30-45 kg were anesthetized with pentobarbital and flow probes and occluders were surgically implanted. Ten of these dogs were subjected to hypercapnia alone. During inspiration of 6% CO2 in room air, portal vein flow increased from 588 +/- 73 ml/min to 731 +/- 113 ml/min (p less than .05), while hepatic artery flow did not change significantly from its control mean of 221 +/- 38 ml/min. In the remaining dogs, inhalation of 6% O2 resulted in a reduction of portal blood flow within 30 min from 527 +/- 55 ml/min to 381 +/- 41 ml/min (p less than .01). Again, mean hepatic artery flow did not increase significantly above its control of 273 +/- 43 ml/min. Subsequent inhalation of 6% CO2 plus 6% O2 (combined hypercapniahypoxia) for 30 min in these same animals resulted in a significant increase of portal vein blood flow from 514 +/- 46 ml/min to 716 +/- 116 ml/min (p less than .05). Thus, hypercapnia alone increases total liver blood flow, primarily by an increase in portal vein flow. Hypoxia results in a decrease in portal vein flow. The superimposition of hypercapnia on hypoxia restores blood flow to a level close to that found with hypercapnia alone. Hypercapnia in the range of 63 +/- 4 mmHg PCO2 overwhelms the tendency toward a reduction of portal vein blood flow induced by an arterial PO2 of 42 +/- 5 mmHg in the presence of mild hypocapnia (PCO2 : 30.2 +/- 1 mmHg).     

Influence of elevated renin substrate on angiotensin II and arterial blood pressure in conscious mice

The present experiments were performed to determine the influence of intravenous administration of renin substrate on plasma angiotensin II levels and mean arterial blood pressure in conscious C57BL/6J mice. Mice with chronic indwelling femoral arterial and venous catheters were acutely or chronically administered intravenous doses of a synthetic peptide corresponding to the 14 amino acids on the N-terminal of angiotensinogen. A dose-dependent increase in arterial blood pressure was observed as the intravenous bolus dose of the renin substrate was increased from 0.18 to 180 nmol kg(-1) with a maximal increase in pressure of 40 +/- 3 mmHg achieved following administration of the 18 nmol kg(-1) bolus (n = 11). Additional experiments demonstrated that a sustained intravenous infusion of the renin substrate led to a long-term increase in arterial blood pressure. The continuous infusion of renin substrate at 0.05 nmol kg(-1) min(-1) for 3 days did not alter arterial blood pressure from the control level of 119 +/- 5 mmHg (n = 5); however, arterial blood pressure significantly increased to 129 +/- 6 mmHg with an infusion rate of 0.5 nmol kg(-1) min(-1) and further increased to 141 +/- 3 mmHg when the renin substrate infusion was increased to 5.0 nmol kg(-1) min(-1). Finally, the infusion of renin substrate at 5.0 nmol kg(-1) min(-1) resulted in a significant increase in plasma angiotensin II concentration from 34 +/- 6 pg ml(-1) in vehicle-infused mice to 288 +/- 109 pg ml(-1). These results demonstrate that modulation of the circulating level of angiotensinogen can alter the plasma angiotensin II level and arterial blood pressure in normal animals.     

The Contribution of Chemoreflex Drives to Resting Breathing in Man

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as "wakefulness", has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a P(ET,O2) (end-tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to P(ET,CO2) (end-tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold P(ET,CO2) was exceeded, ventilation increased linearly with P(ET,CO2). We considered the sub-threshold ventilation to be an estimate of the behavioural drives to breathe (mean +/- S.E.M. = 3.1 +/- 0.5 l min(-1)), and compared it to ventilation at rest (mean +/- S.E.M. = 9.1 +/- 0.7 l min(-1)). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold P(CO2) observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean +/- S.E.M. = 42.0 +/- 0.5 mmHg). However, P(ET,CO2) during rebreathing estimates mixed venous or tissue P(CO2), whereas the resting P(ET,CO2) during resting breathing estimates P(a,CO2) (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in P(ET,CO2) at rest and at the start of rebreathing (the plateau estimates the mixed venous P(CO2) at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean +/- S.E.M. = 26.0 +/- 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting P(ET,CO2) values (mean +/- S.E.M. = 34.3 +/- 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation. Experimental Physiology (2001) 86.1, 109-116.     

Predictors of nocturnal oxyhemoglobin desaturation in COPD

It would be useful to detect predictors of marked nocturnal oxyhemoglobin desaturation (NOD) among COPD patients, who do not have respiratory failure when awake and sleep apnea (SA). Stable COPD patients with awake Pa(O2) ≥ 60 mmHg and Pa(CO2) ≤ 45 mmHg underwent cardio-respiratory polysomnography to exclude SA and to assess NOD. The patients that spent more than 30% of night time with Sp(O2) < 90%, were defined desaturators (D), and the others non desaturators (ND). Pulmonary function testing was performed to determine lung volumes, maximal flow rates, lung diffusion capacity for carbon monoxide and maximal inspiratory and expiratory pressure (P(Imax) and P(Emax)). Negative expiratory pressure test was performed to assess tidal expiratory flow limitation. Supine pharyngometry was performed to determine upper airway size, shuttle walking test to assess exercise desaturation. Twenty-one patients were included in the study (18 male, age 66.0±7.2 years, Body Mass Index 25.9±4.4 kg/m(2), FEV(1) 47.2±16.4% pred., Pa(O2) 74.7±6.9 mmHg, Pa(CO2) 40.3±3.4 mmHg): 10 were D and 11 ND. Significant differences between the two groups were found in diurnal Pa(CO2) (D: 42.4±3.0 vs. ND: 38.3±2.6mmHg; p<0.01), diurnal Sp(O2) (D: 94.0±1.5 vs. ND: 95.9±0.9%; p<0.01), inspiratory capacity (IC) (D: 69.6±11.9 vs. ND: 87.0±17.7% pred.; p<0.05), and oro-pharyngeal junction area (OPJ) (D: 0.8±0.2 vs. ND: 1.2±0.3 cm(2); p<0.01). Among parameters related to marked NOD at the univariate analysis, [Formula: see text] and OPJ remained as independent predictors after stepwise multiple regression analysis. These findings indicate that previously unrecognized factors such as smaller upper airway caliber and lung dynamic hyperinflation are associated with marked NOD in stable COPD patients without daytime respiratory failure and SA.     

Early morning impairment in cerebral autoregulation and cerebrovascular CO2 reactivity in healthy humans: relation to endothelial function

The reduction in cerebrovascular reactivity to CO(2) and/or endothelial function that occurs in the early hours after waking are potential causes for the increased risk for cardiovascular events at this time point. It is unknown whether cerebral autoregulation is reduced in the morning. We tested the hypothesis that early morning reduction in endothelium-dependent vascular reactivity would be linked to changes in cerebrovascular reactivity to CO(2) and cerebral autoregulation (CA). Overnight changes in a dynamic cerebral autoregulation index (ARI) were determined from continuous recordings of blood flow velocity in the middle cerebral artery (MCAv) and arterial blood pressure (BP) during transiently induced hypotension in 20 individuals. Frontal cortical oxygenation (near infrared spectroscopy) and cerebral haemodynamics were also monitored during hypercapnia and before and during 3 min of active standing. Brachial artery flow-mediated endothelium-dependent vasodilatation (FMD) and endothelium-independent dilatation (NFMD) were also monitored. From evening to morning, there was a significant lowering in ARI (5.3 +/- 0.5 versus 4.7 +/- 0.6 a.u.; P < 0.05), cerebrovascular reactivity to CO(2) (5.3 +/- 0.6 versus 4.6 +/- 1.1% mmHg(-1); P < 0.05) and FMD (7.6 +/- 0.9 versus 6.0 +/- 1.4%; P < 0.05). The lowered FMD was related to the decrease in cerebrovascular reactivity to CO(2) (r = 0.76; P < 0.05). Transient reductions in morning MCAv and cortical oxyhaemoglobin concentrations were observed upon resuming a supine-to-upright position (P < 0.05 versus evening). The early morning reduction in cerebral autoregulation may facilitate the onset of cerebrovascular accidents; this may be of particular relevance to at-risk groups, especially upon resuming the upright position.