Diaphragm length and breathing pattern changes during hypoxia and hypercapnia

39

Respiration Physiology (1986) 65, 39-53

Elsevier

D I A P H R A G M L E N G T H AND B R E A T H I N G P A T T E R N C H A N G E S D U R I N G HYPOXIA AND HYPERCAPNIA

J . D . ROAD, S.L. N E W M A N and A. G R A S S I N O Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada

Abstract. In this study diaphragmatic length changes were measured during quiet breathing and during augmentation of breathingwith hypoxiaand hypercapniain supine anesthetized dogs. The breathing pattern and the VT-TI relationship during hypoxia were different than those during hypercapnia. The crnral diaphragm shortened more than the costal diaphragm with both stimuli, and the mount of shortening in relation to the tidal volume impfied that there was considerable distortion of the chest wall during hyperventilation. The velocityof shortening of both parts of the diaphragm at similar levels of ventilation was greater during hypoxia than hypercapnia. The velocities found with hyperventilation suggested that force-velocity considerations did not reduce force generation. Hypoxic stimulation resulted in a reduction in the resting length of both parts of the diaphragm, and was associated with a positive shift in baseline pleural pressure which impliedgas trapping. The large tidal diaphragmaticshorteningfound with augmented breathing and the shorter resting length with hypoxiaindicated that length-foree properties are important in force generation. Breathing pattern Control of breathing

Diaphragm Dog

Hypercapnia Hypoxia

The effect of breathing hypoxic or hypercapnic gas mixtures on the functional residual capacity (FRC) has been reported to be different. Bouverot and Fitzgerald (1969) found an increase in the F R C with hypoxic stimulation. However, Daubenspeck (1972) as well as Bouverot and Fitzgerald (1969) found no increase in the F R C with hypercapnic stimulation. The increased F R C seen during hypoxic breathing has been suggested to be a consequence of increased resting tone in the intercostal muscles (Bouverot and Fitzgerald, 1969). There has been a controversy regarding the breathing pattern in response to hypoxic and hypercapnic stimulation. Some investigators have found that the augmentation in ventilation is associated with a similar increase in tidal volume and frequency regardless of the method of stimulation (Hey et al., 1966; Widdicombe and Winning, 1974). Others Accepted for publication 22 March 1986

0034-5687/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)

40

J.D. ROAD et al.

have found that there is indeed a difference in the breathing patterns depending on the methods of stimulation (hypoxia or hypercapnia) used (Garcia and Cherniack, 1967; Fitzgerald, 1973; Gautier, 1976). Alterations in the FRC or in the breathing pattern will have consequences for respiratory muscle length changes and accordingly for their force generation. Furthermore, the diaphragm has been described as consisting of two parts; costal and crural (Briscoe, 1920; De Troyer et al., 1982). The recruitment of these parts may be different, as the crural diaphragm has recently been shown to be preferentially activated with hypercapnia (Van Lunteren et al., 1984). To address the above controversial findings, we studied the length changes of the costal and crural diaphragm using the technique of sonomicrometry in anesthetized dogs. They were studied under several levels of steady state hypoxia and during hyperoxic CO2 rebreathing.

Methodology The experiments were performed on nine supine dogs (weight 20-25 kg). The dogs were anesthetized with 20 mg per kilogram of sodium pentobarbitone given intravenously. The maintenance dose of pentobarbitone was in the range of 1-1.5 mg/kg per hour or enough to just suppress the corneal reflex. The dogs were intubated with a cuffed # 9 endotracheal tube and the femoral artery and vein were canulated. The temperature was monitored with a rectal thermometer and kept between 37.5-38.5 °C, by an electrical heating pad, throughout the experiment. Two pairs of piezoelectric transducers (2.5 mm in diameter) were placed in the costal and crural parts of the diaphragm by abdominal laparotomy. The transducers were placed 15-20 mm apart parallel with the muscle fibers in both parts of the diaphragm. These piezoelectric transducers were connected to a sonomicrometer (model 120, Triton Technology, San Diego, CA). This technique provided an accurate method of assessing respiratory muscle length changes including the velocity of shortening (Newman et al., 1984). With this technique the distance between the two transducers is continuously sampled (1537 Hz) and thereby the amount of muscle shortening during an inspiration can be recorded. This change in length with respect to time can then be used to determine the velocity of diaphragmatic shortening during inspiration. Tidal diaphragm shortening was def'med as the maximum baseline deflection from the resting length at Functional Residual Capacity LFRc, and was expressed as a percentage of the resting length (~o LFRC). The peak velocity (~o LFRC" sec - 1) was defined as the maximal baseline deflection over a 0.1 sec time interval during inspiratory shortening. The mean velocity of shortening was the tidal shortening (~o LFRC) divided by the in spiratory time (TI). Esophageal (APes) and abdominal (APab) pressure swings were measured by latex balloons. The esophageal balloon was positioned in the middle esophagus and t'filed with 0.5 ml of air; the abdominal balloon was placed under the central tendon and filled with 1.0 ml of air. Transdiaphragmatic pressure swings (APdi) were taken as the

DIAPHRAGM LENGTH AND BREATHING PATTERN CHANGES

41

algebraic sum of APab and APes, measured at the time of peak APes. The balloons were connected to pressure transducers (Sandborn 267, B.C.) by 50 cm of PE200 tubing. The flow was measured by a pneumotachygraph (Fleisch No. 2) connected to the endotracheal tube. The flow signal was electrically integrated to give tidal volume (VT). TI and TE were derived from points of zero flow on the flow tracing. All parameters were recorded on a strip chart recorder (Hewlett Packard Model 7700). Arterial blood gases were analysed by a Coming pH blood gas analyser (Model 165-2 Coming Medical, Medfield, MA). Control measurements were performed during quiet tidal breathing before the application of each different gas mixture. The system used for delivering the hypoxic gases was a Douglas bag connected to a one way Hans-Rudolph valve. The gas mixtures included room air (21~ oxygen), 13~ oxygen-balance nitrogen (13~ oxygen), 10~o oxygen-balance nitrogen (10 ~ oxygen) and 7 ~o oxygen-balance nitrogen (7 ~o oxygen). The animals were allowed five minutes to equilibrate on each gas mixture. Control parameters were then repeated. A mean of eight consecutive breaths was determined for each parameter when ventilation was found to be stable. Comparisons were made by paired t-test unless otherwise stated. CO2 rebreathing was accomplished through the same system; however, the expiration end of the Hans-Rudolph valve was connected to the Douglas bag to allow rebreathing. Initially the rebreathing gas was 100~o oxygen. The CO2 rebreathing and hypoxic breathing protocols were applied in random order to avoid systematic errors.

Results

When breathing was stimulated dttdng hypoxia, ventilation predictably increased. The mean tidal volume increased from 254 + 24 ml on 21% oxygen to 408 + 22 ral ( + SE) with 7 % oxygen. The respiratory frequency increased from 23 + 3 to 54 + 6 (breaths per minute + SE) while overall minute ventilation increased from 5.8 + 1.3 to 23 + 9 (litres per minute + SE) with 7% oxygen. The mean data are shown in fig. 1. The mean Pao2 (ram Hg + SE)with 21~o oxygen was 73 + 5, with 13% oxygen 40 + 2, with 10~/o oxygen 29 + 3 and with 7 ~o oxygen 22 + 3. With hypercapnic stimulation the data was analysed during the control period, at the midpoint of the CO2 rebreathing run (raid CO2) and at the end of the CO2 run (end CO2). The tidal volume increased from 260 + 21 ml at the beginning to 464 + 35 ml (_ SE) at the end of the CO2 rebreathing. In this case the respiratory frequency increased from 23 + 3 breaths per minute to 32 + 5 breaths per minute, accordingly minute ventilation increased from 6.1 +_ 1 to 15 + 3.8 (liters per minute + SE) at the end of the run (fig. 1). Analysis of the phases of the breathing cycle for hypoxia and hypercapnia are shown in fig. 2. The mean TI decreased from 0.77 + 0.06 on room air to 0.48 + 0.03 (sec+ SE) with 7Y/o oxygen while the mean TE decreased from 1.8 + 0.37 to 0.64 + 0.11 (sec + SE). During CO2 rebreathing the mean TI decreased from 0.76 + 0.04 to 0.69 + 0.05

42

J.D. ROAD

et al.

25

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w (0 Fig. 1. Minute ventilation (VE)is plotted against tidal volume (VT)for room air breathing (•), 13% oxygen, (O), 10% oxygen (A), 7% oxygen (A), mid CO: ( I ) and for end CO2 ([S]). Bars indicate SE (n = 9). 0.5 0.4 0.3 ~, 0.2 0.1 0 TIME

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Fig. 2. Tidal volume ( V T ) is shown in relation to time for hypoxia (upper panel) and hypercapnia (lower panel). The symbols are identical to those in fig. 1. Bars indicate SE.

DIAPHRAGM LENGTH AND BREATHING PATTERN CHANGES

43

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Fig. 3. Tidal volume (VT) is plotted against inspiratory time (TI) in the upper graph and expiratory time (TE) in the lower graph for the 3 levels of hypoxia (O), and the CO 2 rebrcathing (O). Bars indicate SE.

(sec +_SE P < 0.05) at the end of the run and the TE decreased from 1.8 + 0.31 to 1.2 + 0.26 ( s e c _ SE P < 0.05). The increase in frequency with hypoxia was accomplished by a reduction in both TI and TE. Both were significantly reduced (P < 0.01 when compared to the control) with each hypoxic gas mixture (fig. 3). With 13 % oxygen there was a predominant reduction in TE; subsequently both TI and TE decreased with 10 % and 7 % oxygen (fig. 3). Minute ventilation (VE) during hypercapnia was increased primarily by increases in tidal volume (fig. 1). Accordingly, TE did not change to the same degree as during hypoxia and TI was reduced only at the highest level of ventilation with CO2 rebreathing (fig. 3). In fig. 4 the ratio ofinspiratory and expiratory duration is shown during hypoxia and hypercapnia. This ratio did not change significantly compared to control with hypercapnia at any level of ~tE; however, with hypoxia there was a significant increase. Furthermore, when this ratio is compared at similar levels of ventilation (isoventilation) 13% oxygen and mid CO2 there was a difference (P < 0.05). The mean VE with 13% oxygen, 10.7 + 2.2 and mid CO 2 VE 11 + 3.8 (L/min +_SE) were not different. Similarly VE with 10% oxygen 15.8 + 3 and end CO2, 15 +_ 3.8 (L/min, SE) were also not different. This facilitated comparison of breathing pattern and muscle length changes at isoventilation. At both levels ofisoventilation tidal volume was significantly increased (P < 0.05) during hypercapnia compared to hypoxia. TI was

J.D. ROAD et al.

44 25 20 •

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Diaphragm length changes. As we have previously reported (Newman et al., 1984), these dogs demonstrated during quiet breathing in the supine position more crural than ~/E (L-rain"1) costal

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Fig. 5. The relationship between minute ventilation ('¢E) and tidal diaphragmatic shortening (~oLyRe) for hypercapnia on the left and hypoxia on the right. Bars indicate SE. Crural shortening was greater (P < 0.05) than costal shortening at all levels of "VE as depicted by the asterisks.

45

D I A P H R A G M LENGTH AND B R E A T H I N G PATTERN C H A N G E S

costal diaphragmatic shortening 10.3 + 2.6 and 5.6 + 1.3 (%LFKc + SE), respectively. With increases in ~rE the shortening of the crural diaphragm remained significantly higher than the costal diaphragm (fig. 5). In fig. 5 the maximum diaphragmatic shortening in both parts was seen with 7 ~o oxygen. With 7 ~o oxygen for the crural and costal parts respectively, the shortening was 20.4 + 4.5 and 15.1 + 3.8 (~oLFRc + SE). Note in fig. 5 that at points of isoventilation (10~o oxygen and end CO2; 13~ oxygen and mid CO2), diaphragmatic shortening was similar in the two conditions.

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Fig. 6. In the upper graph is the relationship between minute ventilation (~'E) and peak velocity of shortening ( ~ LFR c • see - ~) for hypercapnia on the lett and hypoxia on the fight. Crural velocity was greater than costal velocity but not at all levels of ~'E (* P < 0.05). In the lower graph is the relationship between tidal volume (VT) and peak velocity of shortening (%LrRc" see- 1). Asterisks indicate greater crural than costal velocity of contraction (* P < 0.05), Bars indicate SE.

46

J.D. ROAD et al.

The peak velocities of shortening in the crural and costal parts of the diaphragm were different at rest: 23.5 + 5.7 and 13.6 + 3.1 (%LFR c" s e c - ~ + SE), respectively. With 13 % oxygen they were also different, however; with 10 % oxygen and 7 ~o oxygen there was no difference between the costal and crural peak velocity of shortening (fig. 6). During hypercapnia the velocities were different at control and at end CO 2. A consequence of the greater reduction in T1 during hypoxia as opposed to hypercapnia was increased peak velocity of shortening at isoventilation and equal tidal volumes (fig. 6). Although not present at moderate levels of stimulation these differences became apparent with 10% oxygen. Peak costal velocity was 46.7 + 11 with 10~/o oxygen compared to 25.8 + 3.6 (%LFR c" s e c - ~, P < 0.05 + SE) at end CO 2 points of isoventilation. Similarly peak crural velocity was 60.2 + 12 with 10% oxygen and 43 + 7 (%LFRc" sec - ~, P < 0.05 + SE) at end CO 2. Where the tidal volume was equal (10% and mid CO2) the peak velocities were also greater (P < 0.05) during hypoxia (fig. 6, lower graph). The mean velocity of shortening, tidal shortening divided by inspiratory time, was different for the crural and costal diaphragms at most levels of VE during both hypercapnia and hypoxia (fig. 7). At isoventilation (10% oxygen vs end CO2) costal mean velocity was greater with hypoxia than hypercapnia 24.3 + 5.8 and 15.5 + 2.7 (~oLFR C " s e c - ], P < 0.05 + SE). Crural mean velocity was not quite significant.

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Fig. 7. The relationship between minute ventilation (~/E) and the mean velocity of shortening (~/oLFRc" sec- ') for hypercapnia on the left and hypoxia on the right. Bars indicate SE. The crural mean velocity was greater than the costal at most levels of %'E(* P < 0.05).

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Fig. 8. Identity plots showing the relative change in costal vs crural velocity (upper graph) and costal v s crural tidal shortening(lower graph). The conditions are symbolized as above; room air breathing (O), 13% oxygen (O), 10% oxygen (&), 7% oxygen (A), mid CO2 ( 1 ) and end CO2 (1"1). Bars indicate SE,

T o determine whether one part o f the diaphragm was recruited more than the other with hypercapnia or hypoxia the relative tidal shortenings were calculated. Fig. 8 depicts an identity plot with the relative change in tidal shortening and in peak tidal velocities for the costal and crural diaphragms. There was a trend towards more costal than crural

48

J.D. R O A D et al. 8

u. J ~P

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Fig. 9. The changein restinglengthat FRC (%ALFac)is plottedfor the costal( I ) and the crural part (A) against arterial Pao2 (mm Hg). Bars indicateSE. recruitment in both shortening, and velocity of shortening but this did not reach significance.

Resting muscle length.

We did not measure the FRC or changes in the FRC, however, we noted changes in the resting baseline length at FRC (ALFRc) of both the costal and crural diaphragm with hypoxic stimulation but not with hypercapnic stimulation. Crural baseline resting length shortened more than the costal, shortening to 6.1 + 1.6~o ALFRc with 7 ~ oxygen. The costal diaphragm baseline resting length shortened to 2.7 + 1.5 To ALFRc with 7 ~ oxygen. The amount of shortening was related to the degree of hypoxia (fig. 9). Interestingly, these changes in resting length were seen only with hypoxia and were associated with increases in the baseline esophageal pressure. The increases in baseline esophageal pressure were in turn related to the degree of hypoxia: 1.0 + 0.3, 2.0 + 1.0 and 2.5 + 1.0 (cm HzO + SE) for 13, 10, and 7~/o oxygen, respectively.

Discussion

Ventilatory response. Anesthesia has previously been shown to depress the ventilatory response to hypercapnia and hypoxia (Gautier, 1976). The response with isocapnic hypoxia, as opposed to hypocapnic hypoxia, was also greater in awake dogs (Jennings and Macklin, 1972) and in anesthetized cats (Gautier, 1976). In the former study the mean minute ventilation in similar sized (19-29 kg) awake dogs was 30 L/min with 10~ oxygen (hypocapnic hypoxia), approximately twice the anesthetized response we obtained. The intra-dog variability in breathing patterns however was considerably greater in the awake state (Jennings and Macklin, 1972). Nevertheless, in the awake state the velocities and amounts of diaphragmatic shortening may be even greater than those seen in this study.

DIAPHRAGM LENGTH AND BREATHINGPATTERN CHANGES

49

Breathing pattern. We found a clear difference in the pattern of breathing when ventilation was stimulated by hypercapnia as opposed to hypoxia. The plot shown in fig. 1 indicates a predominant increase in breathing frequency during hypoxia as compared to hypercapnia. These findings are similar to those of Garcia and Cherniack (1967) and Fitzgerald (1973) in pentobarbital anesthetized dogs. In the former study isocapnic hypoxia produced a similar predominant increase in frequency when compared to hypercapnia. In awake dogs the results were conflicting. Anrep and Hammouda (1932) found a similar, primarily frequency response during hypoxia, whereas Jennings and Maeklin (1972) found no difference. The results in conscious man were also different (Haldane et al., 1919; Hey et al., 1966). The differences in the phases of the breathing cycle between each condition were also similar to the findings of Gautier (1976). In fig. 4 the relationship between TI and TE is not strictly linear for the two conditions: TI decreased proportionately to TE with hypercapnia but with increasing ventilation TE decreased more than TI with hypoxia. Accordingly the ratio TI/TE increased markedly with hypoxia. A difference in the relationship TI-TE between the two conditions was seen even at low levels of ventilation, but comparisons at higher levels were not possible due to the attenuated hypercapnic ventilatory response. This supports the concept that other factors in addition to TI determine the duration of TE. TI was not uniquely related to VT in the two conditions (fig. 3). These data suggest that the Brener-Hering reflex alone cannot account for the duration of TI in the anesthetized dog, and are again similar to the t'mdings of Gautier (1976) in the awake cat. This divergence could have been due to the different effects of the two stimuli on the medullary neurons in this anesthetized preparation. If central inspiratory activity acts in parallel with a nonvagal mechanism that increases the off-switch excitability as suggested by Bradley et aL (1975), then these different stimuli may have had variable effects through this pathway with hypoxia increasing the off-switch excitability. Peripheral inputs from pulmonary stretch receptors (PSR) could have influenced the off-switch; however, this does not seem to explain the different VT-TI relationship that we found between the two conditions. The LFa c of the diaphragm shortened and presumably the FRC increased with hypoxia, it can therefore be argued that afferent PSR activity is different in the two conditions. If peripheral PSR activity resulted in the dissimilar breathing patterns then vagotomy should abolish these differences. However, Cherniack et al. (1973) found that these different patterns persisted after vagotomy. Although they did not measure TI and TE, they found that after vagotomy the more rapid, shallow breathing pattern ofhypoxia persisted. Therefore these different breathing patterns may be mediated centrally or through nonvagal peripheral afferent activity. Regional diaphragmatic length changes. Diaphragmatic tidal shortening was greater in the crural than the costal part of the diaphragm at all levels of ventilation studied. Several factors may explain this difference. In the dog model of De Troyer et al. (1983) the crural diaphragm is shown to displace the abdomen alone, whereas the costal diaphragm displaces the abdomen and the fib cage. The abdominal hydrostatic pressure

50

J.D. ROAD et al.

gradient in the supine position dictates that the abdominal load applied to the crural diaphragm is greater than for the costal diaphragm. However the costal diaphragm has in addition the elastance of the rib cage to overcome. Furthermore, the crural diaphragm is more compliant than the costal part at supine FRC (Road et al., 1986). This implies that the series and/or the parallel elastic components of the crural diaphragm are more compliant accordingly greater shortening could be anticipated on this basis as well. The length-force relationship for the two parts of the diaphragm (Road et aL, 1986) does not explain the difference during quiet tidal breathing as both parts are contracting near their optimal range at supine resting length. Finally, activation of the crural diaphragm may be greater as the two parts have been shown to have separate segmental innervation, Sant'Ambrogio et ai. (1963). Clearly, additional studies are needed to determine which mechanism predominates and the functional significance of this difference. When breathing was stimulated the crural diaphragm continued to shorten more. However, as is evident from fig. 8, the relative increases in shortening were similar and there was a trend towards more costal recruitment. Van Lunteren et al. (1984), have shown by electromyography that with augmentation of breathing during hypercapnia there is greater crural than costal recruitment. On this basis a relatively greater increase in crural than costal shortening might be predicted during hyperventilation. The amount of excitation therefore does not explain the similar increase in costal shortening. Although crural activation may be higher initially these relative changes suggest another mechanism to explain the similar relative increase in costal shortening with increases in ventilation. Assuming there is no change in the abdominal load, these findings may be explained by length-force considerations. The increased shortening found during hypoxia and hypercapnia and the increase in the FRC found during hypoxia would both tend to disadvantage the costal and crural diaphragms in terms of length-force properties. However, since the costal diaphragm is stretched beyond its optimal length at supine LFRc (Road et al., 1986) the decrease in baseline resting length would improve the costal length-force relationship and a tidal shortening of 15 ~o would not result in a significant loss of force generating capacity. It is assumed that this capacity in turn would produce more shortening. The crural diaphragm however is shorter than its optimal length at supine LFR¢ and therefore could, with shortening of the baseline resting length and 20~o tidal shortening, be disadvantaged. Accordingly the crural diaphragm would become less effective as a pressure generator and hence shorten less. The large tidal shortenings found in this study are surprising, Hill (1970) postulated that length-tension considerations should play a negligible role in skeletal muscle contraction. This was thought to be due to the muscles' fixed attachments which were presumed to prevent shortening beyond the optimal range of less than ten percent. However, the diaphragm may be different in this regard as the central tendon is quite mobile. The degree of shortening we found during hypoxia and hypercapnia would indicate length-tension characteristics are important. Furthermore, the reduced ventilatory response we found in this anesthetized preparation would indicate that still larger shortening can be anticipated with higher levels of ventilation in the awake state. The consequence of the breathing pattern in hypoxia was increased velocity of

DIAPHRAGM LENGTH AND BREATHINGPATTERN CHANGES

51

shortening. Both the peak velocity and the mean velocity of the two parts of the diaphragm increased markedly. The peak velocity with 7Yo oxygen was 58yo LFRc" see- 1 and 68 ~ LFRc" see - 1 for the costal and crural diaphragms respectively. The maximum velocity of shortening found by Newman et al. (1984) was 5.0 and 4.7 LFRc" Sec- I for the costal and crural parts. Those values were obtained by bilateral supramaximal stimulation of the phrenic nerve with the abdominal cavity open. During hypoxia in this study, peak velocities during spontaneous breathing were therefore 12 and 15~ of the maximum velocity for the costal and crural parts respectively. The optimum velocity reported for skeletal muscles is 30~ of maximum (Hill, 1938), and is determined by the force-velocity rdationship. Compared to 4Y/o of maximum during quiet tidal breathing the velocities with hypoxia approach the optimal velocity and hence presumably improved efficiency. This supports the findings of Siafakas et al. ( 1981) who found negligible force-velocity effects during stimulated breathing in cats. It is probable that in their cats stimulated breathing led to a more optimal velocity of diaphragmatic shortening rather than higher than optimal velocities. Other factors contribute to the efficient transfer of muscle contraction and shortening to changes in lung volume. The diaphragm's contribution to tidal volume can be estimated, assuming that the diaphragm contracts as a piston and that there is no change in the circumference of the upper area of the zone of apposition. Based on these assumptions a contribution of 41 ~ of the tidal volume was determined for the canine diaphragm, (Newman etal., 1984). This figure was derived using 6Yo tidal diaphragmatic shortening and a tidal volume of 440 ml. This calculated contribution to tidal breathing was somewhat less than that estimated in humans (Agostoni et aL, 1965), and may have been due to the degree of rib cage breathing in this preparation (Newman et al., 1984). During hypoxia with a tidal volume of 400 ml, diaphragmatic shortening was 15 and 22~ for the costal and crural parts respectively. Using the same assumptions as above, the diaphragmatic contribution would be three times or 123Yo of tidal volume. If the assumptions are true, then a significant amount of diaphragmatic shortening is not transmitted directly into tidal volume and must be absorbed in distortion of the chest wall during inspiration. This suggests that parts of the rib cage are moving paradoxically or that the series elastic component is being stretched. However, our study did not include rib cage volume measurements. Distortion of the chest wall may therefore impede the transfer of muscle contraction to ventilation. A further implication of these findings is that surface measurements of the rib cage and abdominal compartments may markedly underestimate the relative shortening of the diaphragm at high levels of ventilation. The two stimuli which we used, hypoxia and hypercapnia, are both known to affect respiratory muscle endurance. We made the measurements after a brief adaptation to hypoxia, and the CO 2 measurements with rebreathing were also of short duration. However, there is a possibility that some of the transformation of neural drive to ventilation was impeded by reduced muscle contraction as a result of reduced energy supplies. Presumably this would be compensated for by further increases in neural activation; however we cannot elaborate further without data on the level of activation.

52

J.D. ROAD et al.

Changes in resting length. An increase in the FRC with hypoxia has been previously reported (Bouverot and Fitzgerald, 1969). The decreased resting length we found corresponds to this increase in the FRC. The 5 ~ shortening of the crural diaphragm with 10~o oxygen represents a 330cc passive increase in lung volume as reported by Newman et al. (1984), if one assumes that rib cage muscle activity is absent at FRC. This predicted increase in lung volume is similar to the 20 ~ increase in FRC found by Bouverot and Fitzgerald (1969). However, we found an increase in baseline pleural pressure. This would suggest that tonic intercostal muscle activity is not the main cause of the increase in FRC. The short time constant for the dog lung of 0.045-0.062 sec reported by Crossf'ill and Widdicombe (1961) suggests gas trapping should not be a problem. However, both hypoxia and hypocapnia cause bronchoconstriction (Green and Widdicombe, 1966). Gas trapping would explain the positive baseline pleural pressure while hypoxic and hypocapnic bronchoconstriction would explain the delayed emptying of the lung by increasing the time constant. Therefore the greater increase in breathing frequency with hypoxia and the hypothesized bronchoconstriction may combine to increase lung volume by trapping gas. The abolition of the increased lung volume with removal of the carotid bodies, (Bouverot and Fitzgerald, 1969), would further suggest bronchoconstriction is involved, as carotid denervation is known to prevent hypoxic bronchoconstriction (Nadel and Widdicombe, 1963). These results imply a smaller role for delayed relaxation ofinspiratory muscles with hypoxia as a cause for the increase in FRC. We have shown that hypoxia causes a different ventilatory response and pattern of regional diaphragmatic contraction than hypercapnia in anesthetized dogs. There was an associated increase in lung volume which was probably related to gas trapping. The consequence of rapid shallow breathing during hypoxia is a more efficient velocity of shortening of the diaphragm, but chest wall distortion may decrease this advantage. The increased shortening and increased FRC seen with hypoxia and the increased shortening seen with hypercapnia imply length-force considerations decrease the force generating capacity of the diaphragm, more for the crural than the costal part. Additional studies are needed to determine the exact mechanism or mechanisms responsible for the dissimilar patterns of breathing during hypoxia compared to hypercapnia.

Acknowledgements. The authors wish to thank Lucille Forseille and Kathie Road for their help in the preparation ofthis manuscript.Thisresearchwas supportedby the Canadian LungAssociation,the Medical Research Council of Canada and the American Lung Association.

References Agostoni, E., P. Mognoni, G. Torri and F. Saracino (1965). Relation between changes of rib cage circumferenceand lung volume.J. Appl. Physiol. 21:1179-1186. Anrep, G.V. and M. Hammouda (1932). Observations on panting. J. Physiol. (London) 77: 16-34. Bouverot, P. and R. S. Fitzgerald(1969). Role of the arterial chemoreceptorsin controllinglung volumein the dog. Respir. Physiol. 7: 203-215.

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