Cardiorespiratory interactions during periodic breathing in awake chronic heart failure patients

We applied spectral techniques to the analysis of cardiorespiratory signals [instantaneous lung volume (ILV), instantaneous tidal volume (ITV), arterial O(2) saturation (Sa(O(2))) at the ear, heart rate (HR), systolic (SAP), and diastolic (DAP) arterial pressure] during nonapneic periodic breathing (PB) in 29 awake chronic heart failure (CHF) patients and estimated the timing relationships between respiratory and slow cardiovascular (<0.04 Hz) oscillations. Our aim was 1) to elucidate major mechanisms involved in cardiorespiratory interactions during PB and 2) to test the hypothesis of a central vasomotor origin of PB. All cardiovascular signals were characterized by a dominant (>/=84% of total power) oscillation at the frequency of PB (mean +/- SE: 0.022 +/- 0.0008 Hz), highly coherent (>/=0.89), and delayed with respect to ITV (ITV-HR, 2.4 +/- 0.72 s; ITV-SAP, 6.7 +/- 0.65 s; ITV-DAP, 3.2 +/- 0.61 s; P < 0.01). Sa(O(2)) was highly coherent with (coherence function = 0.96 +/- 0. 009) and almost opposite in phase to ITV. These findings demonstrate the existence of a generalized cardiorespiratory rhythm led by the ventilatory oscillation and suggest that 1) the cyclic increase in inspiratory drive and cardiopulmonary reflexes and 2) mechanical effects of PB-induced changes in intrathoracic pressure are the more likely sources of the HR and blood pressure oscillations, respectively. The timing relationship between ITV and blood pressure signals excludes the possibility that PB represents the effect of a central vasomotor rhythm.     

Postevent ventilation as a function of CO(2) load during respiratory events in obstructive sleep apnea.

Maintenance of eucapnia during sleep in obstructive sleep apnea (OSA) requires a balance between CO(2) loading during apnea and CO(2) elimination. This study examines individual respiratory events and relates magnitude of postevent ventilation to CO(2) load during the preceding respiratory event in 14 patients with OSA (arterial PCO(2) 42-56 Torr). Ventilation and expiratory CO(2) and O(2) fractions were measured on a breath-by-breath basis during daytime sleep. Calculations included CO(2) load during each event (metabolic CO(2) production - exhaled CO(2)) and postevent ventilation in the 10 s after an event. In 12 of 14 patients, a direct relationship existed between postevent ventilation and CO(2) load during the preceding event (P < 0.05); the slope of this relationship varied across subjects. Thus the postevent ventilation is tightly linked to CO(2) loading during each respiratory event and may be an important mechanism that defends against development of acute hypercapnia in OSA. An inverse relationship was noted between this postevent ventilatory response slope and the chronic awake arterial PCO(2) (r = 0.90, P < 0.001), suggesting that this mechanism is impaired in patients with chronic hypercapnia. The link between development of acute hypercapnia during respiratory events asleep and maintenance of chronic awake hypercapnia in OSA remains to be further investigated.     

Relationship between resting ventilatory chemosensitivity and maximal oxygen uptake in moderate hypobaric hypoxia.

This study tested the hypothesis that the extent of the decrement in (.)Vo(2max) and the respiratory response seen during maximal exercise in moderate hypobaric hypoxia (H; simulated 2,500 m) is affected by the hypoxia ventilatory and hypercapnia ventilatory responses (HVR and HCVR, respectively). Twenty men (5 untrained subjects, 7 long distance runners, 8 middle distance runners) performed incremental exhaustive running tests in H and normobaric normoxia (N) condition. During the running test, (.)Vo(2), pulmonary ventilation (Ve) and arterial oxyhemoglobin saturation (Sa(O(2))) were measured, and in two ventilatory response tests performed during N, a rebreathing method was used to evaluate HVR and HCVR. Mean HVR and HCVR were 0.36 +/- 0.04 and 2.11 +/- 0.2 l.min(-1).mmHg(-1), respectively. HVR correlated significantly with the percent decrements in (.)Vo(2max) (%d(.)Vo(2max)), Sa(O(2)) [%dSa(O(2)) = (N-H).N(-1).100], and (.)Ve/(.)Vo(2) seen during H condition. By contrast, HCVR did not correlate with any of the variables tested. The increment in maximal Ve between H and N significantly correlated with %d(.)Vo(2max). Our findings suggest that O(2) chemosensitivity plays a significant role in determining the level of exercise hyperventilation during moderate hypoxia; thus, a higher O(2) chemosensitivity was associated with a smaller drop in (.)Vo(2max) and Sa(O(2)) under those conditions.     

Determinants of blood oxygenation during pregnancy in Andean and European residents of high altitude

High altitude decreases birth weight, but this effect is diminished in long vs. short-resident, high-altitude populations. We asked whether women from long vs. short-resident, high-altitude populations had higher arterial oxygenation levels by comparing 42 Andean and 26 European residents of La Paz, Bolivia (3,600 m), serially during pregnancy (weeks 20, 30, and 36) and again 4 mo postpartum. Pregnancy raised hypoxic ventilatory sensitivity threefold, resting ventilation (.Ve), and arterial O(2) saturation (Sa(O2)) in both groups. Ancestry, as identified using 81 genetic markers, correlated with respiratory pattern, such that greater Andean ancestry was associated with higher respiratory frequency and lower tidal volume. Pregnancy increased total blood and plasma volume approximately 40% in both groups without changing red blood cell mass relative to body weight; hence, hemoglobin fell. The hemoglobin decline was compensated for by the rise in .Ve and Sa(O2) with the result that arterial O2 content (Ca(O2)) was maintained near nonpregnant levels in both groups. Birth weights were similar for all Andean and European babies, but after adjusting for variation in gestational age, maternal height and parity, Andeans weighed 209 g more than Europeans. Babies with heavier birth weights and greater ponderal indices were born to Andean women with higher Ve during pregnancy. We concluded that while maternal .Ve and arterial oxygenation were important, some factor other than higher Ca(O2) was responsible for protecting Andeans from altitude-associated reductions in fetal growth.     

Intermittent hypoxia increases ventilation and Sa(O2) during hypoxic exercise and hypoxic chemosensitivity.

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (Sa(O2)) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and Sa(O2) during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (VO2), expired minute ventilation (VE), and Sa(O2) were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2 (VE/VO2) and Sa(O2) during submaximal exercise. There were significant correlations among the changes in HVR at rest and in VE/VO2 and Sa(O2) during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.     

Role of the altitude level on cerebral autoregulation in residents at high altitude.

Cerebral autoregulation is impaired in Himalayan high-altitude residents who live above 4,200 m. This study was undertaken to determine the altitude at which this impairment of autoregulation occurs. A second aim of the study was to test the hypothesis that administration of oxygen can reverse this impairment in autoregulation at high altitudes. In four groups of 10 Himalayan high-altitude dwellers residing at 1,330, 2,650, 3,440, and 4,243 m, arterial oxygen saturation (Sa(O(2))), blood pressure, and middle cerebral artery blood velocity were monitored during infusion of phenylephrine to determine static cerebral autoregulation. On the basis of these measurements, the cerebral autoregulation index (AI) was calculated. Normally, AI is between zero and 1. AI of 0 implies absent autoregulation, and AI of 1 implies intact autoregulation. At 1,330 m (Sa(O(2)) = 97%), 2,650 m (Sa(O(2)) = 96%), and 3,440 m (Sa(O(2)) = 93%), AI values (mean +/- SD) were, respectively, 0.63 +/- 0.27, 0.57 +/- 0.22, and 0.57 +/- 0.15. At 4,243 m (Sa(O(2)) = 88%), AI was 0.22 +/- 0.18 (P < 0.0005, compared with AI at the lower altitudes) and increased to 0.49 +/- 0.23 (P = 0.008, paired t-test) when oxygen was administered (Sa(O(2)) = 98%). In conclusion, high-altitude residents living at 4,243 m have almost total loss of cerebral autoregulation, which improved during oxygen administration. Those people living at 3,440 m and lower have still functioning cerebral autoregulation. This study showed that the altitude region between 3,440 and 4,243 m, marked by Sa(O(2)) in the high-altitude dwellers of 93% and 88%, is a transitional zone, above which cerebral autoregulation becomes critically impaired.     

Changes in sleep quality of athletes under normobaric hypoxia equivalent to 2,000-m altitude: a polysomnographic study.

This study evaluated the sleep quality of athletes in normobaric hypoxia at a simulated altitude of 2,000 m. Eight male athletes slept in normoxic condition (NC) and hypoxic conditions equivalent to those at 2,000-m altitude (HC). Polysomnographic recordings of sleep included the electroencephalogram (EEG), electrooculogram, chin surface electromyogram, and electrocardiogram. Thoracic and abdominal motion, nasal and oral airflow, and arterial blood oxygen saturation (Sa(O(2))) were also recorded. Standard visual sleep stage scoring and fast Fourier transformation analyses of the EEG were performed on 30-s epochs. Subjective sleepiness and urinary catecholamines were also monitored. Mean Sa(O(2)) decreased and respiratory disturbances increased with HC. The increase in respiratory disturbances was significant, but the increase was small and subclinical. The duration of slow-wave sleep (stage 3 and 4) and total delta power (<3 Hz) of the all-night non-rapid eye movement sleep EEG decreased for HC compared with NC. Subjective sleepiness and amounts of urinary catecholamines did not differ between the conditions. These results indicate that acute exposure to normobaric hypoxia equivalent to that at 2,000-m altitude decreased slow-wave sleep in athletes, but it did not change subjective sleepiness or amounts of urinary catecholamines.     

Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia.

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations (Sa(O(2))) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% Sa(O(2)): OSA patients, 9 +/- 11 mmHg; controls, 12 +/- 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change -37 +/- 19% at Sa(O(2)) 80%) but not in patients (mean change -4 +/- 16% at 80% Sa(O(2))). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline -85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.     

Influence of inhaled nitric oxide on gas exchange during normoxic and hypoxic exercise in highly trained cyclists.

This study tested the effects of inhaled nitric oxide [NO; 20 parts per million (ppm)] during normoxic and hypoxic (fraction of inspired O(2) = 14%) exercise on gas exchange in athletes with exercise-induced hypoxemia. Trained male cyclists (n = 7) performed two cycle tests to exhaustion to determine maximal O(2) consumption (VO(2 max)) and arterial oxyhemoglobin saturation (Sa(O(2)), Ohmeda Biox ear oximeter) under normoxic (VO(2 max) = 4.88 +/- 0.43 l/min and Sa(O(2)) = 90.2 +/- 0.9, means +/- SD) and hypoxic (VO(2 max) = 4.24 +/- 0.49 l/min and Sa(O(2)) = 75.5 +/- 4.5) conditions. On a third occasion, subjects performed four 5-min cycle tests, each separated by 1 h at their respective VO(2 max), under randomly assigned conditions: normoxia (N), normoxia + NO (N/NO), hypoxia (H), and hypoxia + NO (H/NO). Gas exchange, heart rate, and metabolic parameters were determined during each condition. Arterial blood was drawn at rest and at each minute of the 5-min test. Arterial PO(2) (Pa(O(2))), arterial PCO(2), and Sa(O(2)) were determined, and the alveolar-arterial difference for PO(2) (A-aDO(2)) was calculated. Measurements of Pa(O(2)) and Sa(O(2)) were significantly lower and A-aDO(2) was widened during exercise compared with rest for all conditions (P < 0.05). No significant differences were detected between N and N/NO or between H and H/NO for Pa(O(2)), Sa(O(2)) and A-aDO(2) (P > 0.05). We conclude that inhalation of 20 ppm NO during normoxic and hypoxic exercise has no effect on gas exchange in highly trained cyclists.     

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (VO2 peak) = 56.4 +/- 2.8 ml x kg(-1) x min(-1); mean +/- SE]. Subjects exercised on a cycle ergometer at >or=90% VO2 peak) to exhaustion (13.2 +/- 0.8 min), during which time arterial O2 saturation (Sa(O2)) fell from 97.7 +/- 0.1% at rest to 91.9 +/- 0.9% (range 84-94%) at end exercise, primarily because of changes in blood pH (7.183 +/- 0.017) and body temperature (38.9 +/- 0.2 degrees C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (Fi(O2)) = 0.25-0.31] that prevented EIAH (Sa(O2) = 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at Fi(O2) 0.21, the mean force response across 1-100 Hz decreased 33 +/- 5% compared with only 15 +/- 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at Fi(O2) 0.21 (Sa(O2) = 95.3 +/- 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via Fi(O2) 0.17 (Sa(O2) = 87.8 +/- 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (-6 +/- 1% DeltaSa(O2) from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism.     

Periodic breathing in the mouse.

The hypothesis was that unstable breathing might be triggered by a brief hypoxia challenge in C57BL/6J (B6) mice, which in contrast to A/J mice are known not to exhibit short-term potentiation; as a consequence, instability of ventilatory behavior could be inherited through genetic mechanisms. Recordings of ventilatory behavior by the plethsmography method were made when unanesthetized B6 or A/J animals were reoxygenated with 100% O(2) or air after exposure to 8% O(2) or 3% CO(2)-10% O(2) gas mixtures. Second, we examined the ventilatory behavior after termination of poikilocapnic hypoxia stimuli in recombinant inbred strains derived from B6 and A/J animals. Periodic breathing (PB) was defined as clustered breathing with either waxing and waning of ventilation or recurrent end-expiratory pauses (apnea) of > or = 2 average breath durations, each pattern being repeated with a cycle number > or = 3. With the abrupt return to room air from 8% O(2), 100% of the 10 B6 mice exhibited PB. Among them, five showed breathing oscillations with apnea, but none of the 10 A/J mice exhibited cyclic oscillations of breathing. When the animals were reoxygenated after 3% CO(2)-10% O(2) challenge, no PB was observed in A/J mice, whereas conditions still induced PB in B6 mice. (During 100% O(2) reoxygenation, all 10 B6 mice had PB with apnea.) Expression of PB occurred in some but not all recombinant mice and was not associated with the pattern of breathing at rest. We conclude that differences in expression of PB between these strains indicate that genetic influences strongly affect the stability of ventilation in the mouse.     

Lung and chest wall mechanics in rabbits during high-frequency body-surface oscillation

In eight anesthetized and tracheotomized rabbits, we studied the transfer impedances of the respiratory system during normocapnic ventilation by high-frequency body-surface oscillation from 3 to 15 Hz. The total respiratory impedance was partitioned into pulmonary and chest wall impedances to characterize the oscillatory mechanical properties of each component. The pulmonary and chest wall resistances were not frequency dependent in the 3- to 15-Hz range. The mean pulmonary resistance was 13.8 +/- 3.2 (SD) cmH2O.l-1.s, although the mean chest wall resistance was 8.6 +/- 2.0 cmH2O.l-1.s. The pulmonary elastance and inertance were 0.247 +/- 0.095 cmH2O/ml and 0.103 +/- 0.033 cmH2O.l-1.s2, respectively. The chest wall elastance and inertance were 0.533 +/- 0.136 cmH2O/ml and 0.041 +/- 0.063 cmH2O.l-1.s2, respectively. With a linear mechanical behavior, the transpulmonary pressure oscillations required to ventilate these tracheotomized animals were at their minimal value at 3 Hz. As the ventilatory frequency was increased beyond 6-9 Hz, both the minute ventilation necessary to maintain normocapnia and the pulmonary impedance increased. These data suggest that ventilation by body-surface oscillation is better suited for relatively moderate frequencies in rabbits with normal lungs.     

Validity of inspiratory and expiratory methods of measuring gas exchange with a computerized system.

The accuracy of a computerized metabolic system, using inspiratory and expiratory methods of measuring ventilation, was assessed in eight male subjects. Gas exchange was measured at rest and during five stages on a cycle ergometer. Pneumotachometers were placed on the inspired and expired side to measure inspired (VI) and expired ventilation (VE). The devices were connected to two systems sampling expired O(2) and CO(2) from a single mixing chamber. Simultaneously, the criterion (Douglas bag, or DB) method assessed VE and fractions of O(2) and CO(2) in expired gas (FE(O(2)) and FE(CO(2))) for subsequent calculation of O(2) uptake (VO(2)), CO(2) production (VCO(2)), and respiratory exchange ratio. Both systems accurately measured metabolic variables over a wide range of intensities. Though differences were found between the DB and computerized systems for FE(O(2)) (both inspired and expired systems), FE(CO(2)) (expired system only), and VO(2) (inspired system only), the differences were extremely small (FE(O(2)) = 0.0004, FE(CO(2)) = -0.0003, VO(2) = -0.018 l/min). Thus a computerized system, using inspiratory or expiratory configurations, permits extremely precise measurements to be made in a less time-consuming manner than the DB technique.     

Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans

Our aim was to isolate the independent effects of 1) inspiratory muscle work (W(b)) and 2) arterial hypoxemia during heavy-intensity exercise in acute hypoxia on locomotor muscle fatigue. Eight cyclists exercised to exhaustion in hypoxia [inspired O(2) fraction (Fi(O(2))) = 0.15, arterial hemoglobin saturation (Sa(O(2))) = 81 +/- 1%; 8.6 +/- 0.5 min, 273 +/- 6 W; Hypoxia-control (Ctrl)] and at the same work rate and duration in normoxia (Sa(O(2)) = 95 +/- 1%; Normoxia-Ctrl). These trials were repeated, but with a 35-80% reduction in W(b) achieved via proportional assist ventilation (PAV). Quadriceps twitch force was assessed via magnetic femoral nerve stimulation before and 2 min after exercise. The isolated effects of W(b) in hypoxia on quadriceps fatigue, independent of reductions in Sa(O(2)), were revealed by comparing Hypoxia-Ctrl and Hypoxia-PAV at equal levels of Sa(O(2)) (P = 0.10). Immediately after hypoxic exercise potentiated twitch force of the quadriceps (Q(tw,pot)) decreased by 30 +/- 3% below preexercise baseline, and this reduction was attenuated by about one-third after PAV exercise (21 +/- 4%; P = 0.0007). This effect of W(b) on quadriceps fatigue occurred at exercise work rates during which, in normoxia, reducing W(b) had no significant effect on fatigue. The isolated effects of reduced Sa(O(2)) on quadriceps fatigue, independent of changes in W(b), were revealed by comparing Hypoxia-PAV and Normoxia-PAV at equal levels of W(b). Q(tw,pot) decreased by 15 +/- 2% below preexercise baseline after Normoxia-PAV, and this reduction was exacerbated by about one-third after Hypoxia-PAV (-22 +/- 3%; P = 0.034). We conclude that both arterial hypoxemia and W(b) contribute significantly to the rate of development of locomotor muscle fatigue during exercise in acute hypoxia; this occurs at work rates during which, in normoxia, W(b) has no effect on peripheral fatigue.     

Respiratory system stability and abnormal carbon dioxide homeostasis.

We have tested the hypothesis that interactions among eight parameters of the respiratory and cardiovascular systems that determine the loop gain (LG) of the respiratory CO2 feedback control system might account for the degree of stability or instability of breathing patterns in healthy sleeping volunteers as well as in familial dysautonomia (FD) and congenital central hypoventilation syndrome (CCHS) patients. The predictability of cycle duration was tested as well. We measured the values of CO2 sensitivity, CO2 delivery capacity in the circulation, circulation delay, mean lung volume for CO2, and mixed venous PCO2 in 8 FD patients, 2 CCHS patients, and 19 healthy controls. The values of these parameters were used in a mathematical model to compute the LG of the respiratory control system during sleep for each epoch of respiration analyzed. The strength of the ventilatory oscillations (R) was quantified using power density spectra of the ventilation time series. All subjects were studied at inspiratory O2 concentrations (FIO2) of 0.21 and 0.15; CCHS patients and controls were also studied at 0.12 FIO2 to examine the effect of steady-state hypoxia on respiratory system stability. In 2 FD patients, LG was elevated at both levels of FIO2 and periodic breathing was observed; the values of R were elevated. Elevated mixed venous PCO2 and reduced CO2 delivery capacity were chiefly responsible for the abnormally high LG observed. In three healthy volunteers, high LG and unstable patterns were associated with high chemosensitivity. The CCHS patients, however, remained stable even at 0.12 FIO2 because LG remained equivalent to zero due to a lack of chemosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological evaluation of a new quantitative SPECT method measuring regional ventilation and perfusion.

We have developed a new quantitative single-photon-emission computed tomography (SPECT) method that uses (113m)In-labeled albumin macroaggregates and Technegas ((99m)Tc) to estimate the distributions of regional ventilation and perfusion for the whole lung. The multiple inert-gas elimination technique (MIGET) and whole lung respiratory gas exchange were used as physiological evaluations of the SPECT method. Regional ventilation and perfusion were estimated by SPECT in nine healthy volunteers during awake, spontaneous breathing. Radiotracers were administered with subjects sitting upright, and SPECT images were acquired with subjects supine. Whole lung gas exchange of MIGET gases and arterial Po(2) and Pco(2) gases was predicted from estimates of regional ventilation and perfusion. We found a good agreement between measured and SPECT-predicted exchange of MIGET and respiratory gases. Correlations (r(2)) between SPECT-predicted and measured inert-gas excretions and retentions were 0.99. The method offers a new tool for measuring regional ventilation and perfusion in humans.     

Case study analysis and the remediation of misconceptions about respiratory physiology

Most students enter the physiology classroom with one or more fundamental misconceptions about respiratory physiology. This study examined the prevalence of four respiratory misconceptions and determined the role of case analysis in the remediation of one of them. A case study was used to help students learn about oxygen transport in the blood and a conceptual diagnostic test was used to assess student understanding of the relation between Po(2) and hemoglobin saturation by probing for the corresponding (Sa/Po(2)) misconception. A 36% remediation of the Sa/Po(2) misconception was found to be associated with case analysis. This repair was selective since the frequency of three other respiratory misconceptions was found to be unchanged after classroom instruction about respiratory physiology in lectures and laboratories. Remediation of the Sa/Po(2) misconception before an instructor-led, in-class case review was superficial and temporary. Explanations provided by students who correctly answered the Sa/Po(2) conceptual diagnostic test showed improved conceptual understanding following case analysis. These results suggest that a learning strategy where students actively confront their faulty notions about respiratory physiology is useful in helping them overcome their misconceptions.     

Ventilation and metabolic rate in the platypus: insights into the evolution of the mammalian breathing pattern

The platypus (Ornithorhyncus anatinus) is characterized by a rate of oxygen consumption (V(O2))that is higher than that reported for other similar sized monotremes, similar to marsupials and somewhat lower than eutherians. The platypus is also characterized by a breathing pattern, more typical of a diving mammal, with a high 'inspiratory drive' and a post-inspiratory pause. Further, the platypus reveals an attenuated hyperventilatory response to hypoxia and a reduced hyperpnoea to hypercapnia; such a response to these chemical stimuli is commonly observed in semi-fossorial and diving mammals. Nevertheless, under conditions of normoxia, ventilation (V(E))is matched to (V(O(2)) such that the convection requirement (V(E)/V(O2)) is similar to that reported for other mammals (approx. 37). The apparent consistency of the convection requirement in mammals suggests the blueprint for the design of the mammalian respiratory system has remained an interspecies constant in the three divergent extant sub-classes of mammals.     

Selective reflex activation of the genioglossus in humans

In anesthetized or decerebrate animals, negative pressure applied to the upper airway selectively activates the hypoglossal nerve compared with the phrenic nerve. Conversely, positive pressure reduces hypoglossal nerve activity out of proportion to any change in the phrenic neurogram. We have tested the hypothesis that analogous pressure changes applied to awake humans would selectively inhibit or activate genioglossal electromyographic (EMGge) activity relative to diaphragmatic electromyographic activity (EMGdi). We studied seven normal subjects in a head-out body plethysmograph. Pressure at the mouth was either atmospheric, +10 cmH2O, or -10 cmH2O, and lung volume was held constant by applying an identical pressure to the body surface. Thus the transmural pressure distorting the respiratory system was applied only to the upper airway. Subjects breathed CO2-enriched (2-3%) room air to stimulate phasic respiratory EMGge activity. We found that -10 cmH2O pressure applied selectively to the upper airway resulted in a 49% enhancement of peak-integrated EMGge activity, but EMGdi activity remained at control levels. Positive pressure did not result in any changes in EMGge or EMGdi activity. Neither pressure resulted in significant changes in the magnitude or pattern of ventilation. We conclude that reflex mechanisms maintaining upper airway patency are demonstrable in awake humans and probably have an important role in moment-to-moment modulation of upper airway muscle activity in normal awake humans.