Ventilation in intact and glossopharyngeal nerve sectioned anaesthetized rats exposed to oxygen at high pressure.

The cause of the initial hyperventilation, which occurs on exposure to O2 at high pressure (o.h.p.), has been investigated by measuring tidal volume (VT), frequency of breathing (f) and hence ventilation (VE) in thirty-six barbiturate-anaesthetized rats, with or without their glossopharyngeal (IX) nerves sectioned, during 30-60 min of exposure to o.h.p. at 4, 6 or 8 atm absolute. In intact rats the rates of rise of VT, f and VE with time during exposure to o.h.p. were smallest at 4 and greatest at 8 atm absolute. In IX-sectioned rats the rates of rise of VT at 4, 6 and 8 atm absolute and of f at 4 atm absolute were similar to those of intact rats. At 6 atm absolute and even more so at 8 atm absolute, however, f decreased. Hence the slope of VE in IX-sectioned compared with intact rats was similar at 4 atm absolute but smaller at 6 and 8 atm absolute. In fact at 8 atm absolute VE remained constant in IX-sectioned rats. Since the slope of VE versus time in intact rats was steeper the greater the pressure and since the removal of carotid bodies in IX-sectioned rats reduced the VE slope at 6 and 8 atm absolute, the stimulus to the hyperventilation induced by o.h.p. cannot be an accumulation of CO2 in the brain resulting from the lack of O2 desaturation of haemoglobin. This theory would predict that VE should be identical at all pressures above 3.5 atm absolute. The findings in the IX-sectioned rats indicate a major contribution of the carotid bodies to the f increase in o.h.p. They may be stimulated by a histotoxic hypoxia induced by early O2 poisoning. Since the VT increase on exposure to o.h.p. was both large and fairly similar in intact and IX-sectioned rats, it is suggested that a large part of the VT increase was caused by stimulation of the central chemoreceptors by lactic acidosis induced by an o.h.p.-induced histotoxic hypoxia of the brain.

Experimental subdural retrobulbar injection of anesthetic.

Sudden respiratory arrest following retrobulbar block, a complication which has gained increasing attention, is explained by an experimental study in which radiopaque dye was injected into the intraorbital subdural space, as could easily be done in a living patient, and was shown by radiography to diffuse posteriorly along the subdural space to the midbrain surrounding the respiratory center. Clinical implications are discussed.

Scanning electron microscopy of vascular casts in experimental ocular vasoproliferation.

Scanning electron microscopy of vascular casts was used to investigate three experimental models of neovascularization. In each experimental situation, the casts provided a valuable three dimensional representation of the newly formed blood vessels and permitted subclassification of the vessels within normal and proliferating vascular networks. They defined also the predominant origin of new vessels from venules and capillaries, and enabled the evolution of proliferating vessels into arterioles and venules to be documented. Although vascular casts must be interpreted with caution in light of the possibility of incomplete filling and other artifacts, they are a valuable tool in the study of ocular vasoproliferation.

Interaction of hypoxia and hypercapnia on ventilation, tidal volume and respiratory frequency in the anaesthetized rat.

1. Ventilation ( V(E)), tidal volume (V(T)), respiratory frequency (f) and arterial and end-tidal gas tensions were measured in seventy-one tracheostomized New Zealand white rats ( approximately 405 g) anaesthetized with an initial dose of pentobarbitone followed by repeated small doses to ensure that a weak limb-withdrawal reflex remained.2. O(2) consumption (1.2 ml (s.t.p.d.) min(-1) 100 g(-1)), CO(2) production (1.0 ml (s.t.p.d.) min(-1) 100 g(-1)), heart rate (357 min(-1)), V(E) (43 ml min(-1) 100 g(-1)), P(a,CO2) (34 mmHg) and P(a,O2) (84 mmHg) in the control periods did not change significantly during the course of the experiment.3. Inspirates of 21% O(2) with 2-10% CO(2), 15, 10 or 7.5% O(2) with either no or sufficient CO(2) to maintain normocapnia and 15 or 10% O(2) with 4, 6 or 8% CO(2) were tested. Steady-state responses were measured after 2 min of exposure.4. Hypoxic-hypercapnic interaction on V(E), V(T) and f determined by a three-inspirate test ((i) hypoxia alone, (ii) hypercapnia and (iii) these hypoxic and hypercapnic levels combined) yielded various conclusions depending on the level of asphyxia examined. Essentially, the milder the asphyxia the more the interaction appeared additive or even multiplicative and the stronger the asphyxia the more the interaction appeared occlusive. However, this test is unsuitable for accurately showing interactions because the P(a,O2) achieved in asphyxia was higher than in hypoxia and the asphyxial P(a,CO2) was lower than in hypercapnia.5. For isoxic conditions (P(a,O2) = 97, 77 and 51 mmHg), V(E) and V(T) were related linearly to P(a,CO2) whilst f was related hyperbolically with convexity upwards (P(a,O2) 97 mmHg) or downwards (P(a,O2) 77 and 51 mmHg).6. For isocapnic conditions (P(a,CO2) = 33, 40 and 48 mmHg), V(E) and V(T) were inversely related to P(a,O2) with a hyperbolic curve (convexity downwards) whilst f was inversely and linearly related (P(a,CO2) 33 mmHg) or constant (P(a,CO2) 40 and 48 mmHg).7. Multivariate analyses showed that the hypoxic-hypercapnic interaction was additive for V(T) but occlusive for V(E) and f and the occlusion was more severe in the latter. This was illustrated graphically for the variable plotted against P(a,CO2) or P(a,O2) as parallel shifts in regression lines for V(T), flatter regression lines for V(E) during asphyxia and a virtually constant f during asphyxia.8. V(E) responses and sensitivities to hypoxia and hypercapnia, the shape of V(E), V(T) and f regression lines against P(a,O2) and P(a,CO2) and the type of hypoxic-hypercapnic interaction on each variable in the rat were compared with other species.9. Possible causes of the occlusive hypoxic-hypercapnic interaction in the rat were considered.

The short-latency respiratory response to sudden withdrawal of hypercapnia and hypoxia in man.

Five healthy young male subjects were maintained in a state of mild asphyxia (PA, CO2 approximately 45 torr, 6.0 kPa, PA, O2 approximately 50 torr, 6.6 kPa), i.e. with moderately strong drives from both arterial and intracranial chemoreceptors VT, TT and TI were recorded and V and TE derived breath by breath. The arterial chemoreceptor component was briefly and abruptly reduced, perhaps silenced, by two separate procedures, each repeated twenty-four times on each subject: B, removal of hypercapnia (two breaths hypoxia with PI, CO2 = 0 through a separate inspiratory line) and C, removal of asphyxia (two breaths O2). In control tests, A, the maintenance mixture was replaced by an identical mixture, using an identical manipulation. For each subject means of B and C were compared with means of A and with each other. Quick reflex changes (first three breaths) in V, VT and TE in tests B were not appreciably different from those in tests C in any subject; changes in TI were minimal in all. Thus removal of only the hypercapnic component of the arterial chemoreflex drive appears to be as efficient as the removal of both components simultaneously.

Inspiratory-expiratory responses to alternate-breath oscillation of PACO2 and PAO2.

Breath-by-breath respiratory responses of three healthy adults to imposed alternate-breath oscillation of end-tidal PCO2 (between +5 and +15 torr above the eupnoeic level) and/or PO2 (between 80 and 45 torr) were studied at rest and during mild cycle ergometer exercise. There was often alternation in inspiratory and expiratory tidal volumes and mean flows, and in expiratory duration, but not in inspiratory duration. The latency of responses, estimated by cross-correlation, corresponded closely to the lung-ear transport delay (measured by oximetry). There were two general patterns of response: in-phase, with inspiratory responses leading expiratory, and, more often, out-of-phase, with expiratory responses leading inspiratory. These patterns were associated with arrival of the onset of the alternating signal at the ear in inspiration and expiration, respectively. It is concluded that the timing of alternating humoral signals at the carotid bodies in relation to the phase of respiration determines the pattern of inspiratory-expiratory response, and that expiratory events can be independent of the previous inspiration.

Arterial chemoreceptors, ventilation and heart rate in man.

1. Transient changes of heart rate (HR) and ventilation were recorded following step changes in alveolar gas composition in three healthy subjects. From a steady state of normo- or slightly hypercapnic hypoxia (PA,CO2 38-46 torr, PA,O2 50-60 torr) arterial chemoreceptor stimulation was transiently relieved by breathing a CO2-free mixture for two breaths, either pur O2 (causing a fall in PA,CO2 and a rise in PA,O2; O2 test) or a low O2 mixture (causing a fall in PA,CO2 without any change in PA, O2; CO2 test). For both test types ventilation was either allowed to change freely ('free-breathing' tests) or was consciously maintained at the pre-test level by the subjects ('controlled-breathing tests). The circulatory delay from the lungs to the ear was measured with a sensitive ear oximeter. 2. In all 'free-breathing' tests ventilation decreased significantly after a mean latency of 5.2 sec; the average lung-ear circulation time was 4.9 sec. HR increased slightly above pre-test levels in eighty-one of one hundred and four tests of all types, the changes being significant after a latency identical to that of the ventilatory changes. Except in the 'controlled-breathing' CO2 tests this early tachycardia was followed by a decrease in HR within the following 5-6 sec. 3. These findings indicate that the primary effect of withdrawal of arterial chemoreceptor stimulation in conscious man as in the anesthetized animal is tachycardia. The secondary development of bradycardia in 'free-breathing' CO2 tests is probably due to the operation of a lung reflex sensing changes in ventilation. The absence of bradycardia in 'controlled-breathing' CO2 tests and its presence in 'controlled-breathing' O2 tests, finally, suggest that relief of systemic hypoxia causes a slowing of the heart not due to lung reflexes but to some other mechanism which operates with a latency nearly twice as long as the arterial chemoreflex.

Very small, very short-latency changes in human breathing induced by step changes of alveolar gas composition.

1. Three healthy young males were maintained for sessions of about 1 hr in a state of mild asphyxia (PA,O2 approximately 55, PA,CO2 approximately 45 torr), i.e. with moderately strong drives from both arterial and intracranial chemoreceptors. Tidal volume (VT), breath duration (TT) and duration of inspiration (TI) were recorded, and ventilation (VE) and duration of expiration (TE) were derived breath by breath. 2. The arterial chemoreceptor component of the drive was briefly and abruptly reduced, perhaps silenced, by three separate procedures: the inspiratory pathway was connected for two breaths to a second gas supply line containing, B, hypoxia with Pi,CO2 zero (removal of hypercapnia with maintained hypoxia); C, pure oxygen (removal of asphyxia); and D, oxygen with 40 torr added PCO2 (removal of hypoxia with maintained hypercapnia). In controls, A, the second inspiratory line contained the maintenance mixture so that the switch involved no change of inspiratory gas composition. Each type of test was repeated twenty-four times on each subject. 3. Responses attributable to silencing of arterial chemoreceptors (i.e. with 1 1/2--3 breath latencies about equal to the lung-to-ear circulation time) are reported elsewhere. 4. Very small responses, occurring only half a respiratory cycle after first inhalation of the test mixture, were detected by pooling all responses of each kind from all subjects. When hypoxia was withdrawn, with (C) or without (D) simultaneous withdrawal of hypercapnia, VT and VE were reduced by 3 and 2% respectively, probably because gas mixtures containing high oxygen concentrations are appreciably more viscous than hypoxic mixtures and so require more effort to breathe in and out. When hypercapnia was withdrawn with (C) or without (B) simultaneous withdrawal of hypoxia, TE was significantly lengthened (mean, + 65 +/- 18 msec), 5. The change of TE was discussed in relation to known effects of CO2 on airway receptors in the dog.

Unsafe without a hole: a dangerous cryoextractor.

Due to the absence of an exhaust hole for the expanding gas, a disposable cryoextractor shot its activator button like a bullet out of its top against the ceiling--barely missing the head of the assisting surgeon.