Evaluation of Arterial Blood Gases and Arterial Blood Pressures inBrachycephalic Dogs

G.L. Hoareau, G. Jourdan, M. Mellema, and P. Verwaerde

Background: Brachycephalic dogs (BD) are prone to congenital upper airway obstruction (brachycephalic syndrome,

BS). In humans suffering from sleep apnea, upper airway obstruction is known to cause hypertension. There is no informa-

tion regarding the influence of BS in dogs on cardiorespiratory physiology.

Hypothesis: BD are prone to lower PaO2, higher PaCO2, and hypertension compared with meso- or dolicocephalic dogs

(MDD).

Animals: Eleven BD and 11 MDD.

Methods: After a questionnaire was completed by the owner, a physical examination was performed. Height and

thoracic circumferences were measured. Arterial blood gases, electrolyte concentrations, and packed cell volume (PCV)

were measured. Systolic (SAP), mean (MAP), and diastolic (DAP) arterial blood pressure recordings were performed.

Results: A total of 7 French and 4 English bulldogs met the inclusion criteria. The control group consisted in 6 Bea-

gles, 2 mixed breed dogs, 1 Staffordshire Bull Terrier, 1 Parson Russell Terrier, and 1 Australian Cattle Dog. Statistically,

BD had lower PaO2, higher PaCO2, and higher PCV when compared with controls (86.2 ± 15.9 versus

100.2 ± 12.6 mmHg, P = .017; 36.3 ± 4.6 versus 32.7 ± 2.6 mmHg, P = .019; 48.2 ± 3.5 versus 44.2 ± 5.4%, P = .026,

respectively). Also, they had significantly higher SAP (177.6 ± 25.0 versus 153.5 ± 21.7 mmHg, P = .013), MAP

(123.3 ± 17.1 versus 108.3 ± 12.2 mmHg, P = .014), and DAP (95.3 ± 19.2 versus 83.0 ± 11.5 mmHg, P = .042). BD with

a PaCO2 >35 mmHg were significantly older than those with a PaCO2 � 35 mmHg (58 ± 16 and 30 ± 11 months,

P = .004).

Conclusion: Results of this study suggest that some BD are prone to lower PaO2, higher PaCO2, and hypertension when

compared with MDD. Age may be a contributing factor.

Key words: Chronic hypoxemia; Hypertension; Peripheral chemoreflex.

Introduction

Brachycephaly refers to canine breeds with “severeshortening of the muzzle, and therefore the under-

lying bones, and a more modest shortening and widen-ing of the skull”.1 Conformational anomalies inbrachycephalic dogs (BD) often are referred to as thebrachycephalic syndrome (BS).2 The BS is character-ized by increased upper airway resistance because ofnarrowed nostrils (58–85% of BD3,4), an elongatedand thickened soft palate (87–96%3,4), everted laryn-geal saccules (55–58%3,4), and a hypoplastic trachea(46%3–5). Prominent nasopharyngeal turbinates havealso been reported.6

Studies have demonstrated laryngeal and pharyngealdysfunction in BD.7–9 However, little is known aboutthe consequences of upper airway obstruction on thephysiology of lower airways and lung parenchyma.10,11

Although De Lorenzi et al recently showed a highincidence of bronchial collapse in BD that most likelywas because of chronic upper airway obstructionand the associated increase in negative intrathoracicpressures,12 the ability of BD to ventilate andoxygenate has been described clinically only in 5French Bulldogs.13

There is a similar paucity of literature on the effectsof upper airway obstruction in the BS on the cardiovas-cular system. Research on increased upper airway

From the School of Veterinary Medicine, William R. PritchardVeterinaryMedical TeachingHospital (Hoareau), and the Departmentof Surgical and Radiological Sciences (Mellema), University ofCalifornia, Davis, CA; and the Anaesthesia and Critical Care Unit,National Veterinary School of Toulouse, Toulouse, France (Jourdan,Verwaerde). The results of this study were presented at the 10thannual meeting of the European Veterinary Emergency and CriticalCare Society, Utrecht, Holland, June 2011.

Corresponding author: Dr G.L. Hoareau, Emergency andCritical Care Service, Veterinary Medical Teaching Hospital, Uni-versity of California, Davis, One Shields Avenue, Davis, CA95616-8747, USA; e-mail: glhoareau@ucdavis.edu.

Submitted August 4, 2011; Revised March 9, 2012;Accepted March 27, 2012.

Copyright © 2012 by the American College of Veterinary InternalMedicine

10.1111/j.1939-1676.2012.00941.x

Abbreviations:

A-a gradient alveolar-arterial oxygen gradient

ABG arterial blood gas

ABP arterial blood pressure

BCS body condition score

BD brachycephalic dog

BS brachycephalic syndrome

CPAP continuous positive airway pressure

DAP diastolic arterial blood pressure

EPO erythropoietin

HR heart rate

MAP mean arterial blood pressure

MDD meso- or dolicocephalic dog

OSA obstructive sleep apnea

PaO2 arterial partial pressure of oxygen

PaCO2 arterial partial pressure of carbon dioxide

PCR peripheral chemoreflex

PCV packed cell volume

RR respiratory rate

SAHS sleep apnea/hypopnea syndrome

SAP systolic arterial blood pressure

TP total protein

J Vet Intern Med 2012

resistance because of conformational anomalies (eg, nar-rowing of the air passage, obesity, prominent tongue,nasal congestion) in humans has indicated that thesepatients have an increased risk for the sleep apnea/hypopnea syndrome (SAHS). The hallmark of SAHS iscomplete upper airway collapse during sleep that canresult in intermittent nocturnal hypoxemia and systemichypertension.14,15 The incidence of hypertension inhumans suffering from sleep apnea is high and SAHS isa known risk factor for development of hypertension.16

The mechanisms are unclear, but increased sympatheticactivity, endothelial damage, decreased nitric oxide pro-duction, and negative intrathoracic pressures may play arole in the development of hypertension.16,17 BecauseEnglish Bulldogs have been used as a spontaneousmodel for human SAHS,18 it would be reasonable topresume that other BD may similarly be at risk for sleepapnea. However, it is currently unknown if BD with BSare also at increased risk for hypertension.

The primary objective of this study was to evaluateventilation and oxygenation in BD. The secondaryobjective was to measure arterial blood pressures(ABP) of BD. We hypothesized that BD would havehigher arterial partial pressure of carbon dioxide(PaCO2), and ABP and lower arterial partial pressureof oxygen (PaO2) when compared to non-BD.

Materials and Methods

Owner consent was obtained. Patients were cared for accord-

ing to institutional guidelines.

BD and Control Dogs

Pugs, Boston Terriers, French and English Bulldogs (Group

B) that presented to our institution between March and May

2008 were included in the study if they were 0.5–8 years old, and

if they were systemically healthy (ie, were brought in for wellness

examination, routine vaccinations, or for the purpose of the

study and had normal physical examination findings apart from

potential BS). The control group (Group C) consisted of healthy

(as evaluated by normal physical examination) meso- or

dolicocephalic dogs (MDD). MDD are dogs with long or med-

ium-sized muzzles.1 This group was comprised of dogs owned by

veterinary students or obtained from laboratories (ie, Beagles not

recently involved in any protocol). MDD were matched in age

and weight with BD. Absence of overt stertor also was confirmed

with the owners of the control dogs. Dogs presenting with evi-

dence of illness, especially upper airway obstruction for MDD

(eg, snoring, reverse sneezing, wheezing), were excluded from the

study. Heights, thoracic circumferences, and 5-point body condi-

tion scores (BCS) were recorded.

Owner Questionnaire

To assess the daily impact of potential BS on BD, owners

were asked about the subjective frequency of syncope, open-

mouth breathing, and snoring experienced by their pets.

Arterial Blood Sampling and Analysis

If the dogs showed signs of stress or abnormal breathing on

presentation (eg, tachypnea, hyperpnea), sampling was delayed

and the animal was first given time to calm down, with its

owner, in a quiet and cool room. The owner also was present

in cases where the animal could not be restrained easily with-

out inducing stress. A 1 mL polypropylene syringe was hepa-

rinized by aspirating 0.5 mL of liquid sodium heparin into the

body of the syringe and then drawing the plunger back to the

1 mL mark. All air in the syringe then was expelled, followed

by 10 repetitions of 1 mL of air being drawn into and expelled

from the syringe.19,20 Arterial blood sampling was attempted

from the dorsal pedal artery first. If this was unsuccessful,

femoral arterial sampling then was performed. The skin was

clipped and aseptically prepared. The artery was punctured

with a 25 G needle, and blood was collected into the heparin-

ized syringe. Samples were acquired in < 1 minute. If air was

trapped in the syringe at the time of sampling, bubbles were

immediately expelled from the body of the syringe with the

bevel of the needle facing up. Samples were analyzed within

1–3 minutes of sampling. Temperature-corrected arterial blood

gases (ABG) and hemoglobin concentrations were measured

with commercially available cartridges.a The bicarbonate con-

centration was derived by the machine with the formula

[HCO3�] = 0.0307 9 PaCO2 9 10 (pH–6.129). The remaining

blood was used to measure packed cell volume (PCV) and

total protein concentration (TP) by refractometry. The alveo-

lar-arterial oxygen gradient (A-a gradient) was calculated with

the following formula: A-a gradient = (147 � PaCO2/

0.8) � PaO2.

Blood Pressure Measurements

After a period of rest, 5 oscillometric systolic (SAP), mean

(MAP), and diastolic (DAP) ABP measurements were per-

formed.b The cuff size was approximately 40% of the circumfer-

ence of the leg above the tibiotarsal joint.21 The highest and

lowest readings were rejected, and the average of the 3 remaining

values then was calculated.

Statistical Analysis

All statistical analyses were done by commercial software.c

Intergroup comparisons were performed after verifying homosce-

dasticity and homogeneity of the variances with a unilateral Stu-

dent t-test for unpaired series. For A-a gradient data, 2 MDD

had negative calculated values and were assigned the value zero

for analysis purposes. Normal distribution was confirmed by

Shapiro-Wilk testing. Differences in mean values for A-a gradi-

ents were assessed with a Student t-test. For results with vari-

ances that were not homogenous (ie, F test with P < .1), an

Aspin-Welch or a Mann-Whitney test was used. A P value < .05

was considered significant. Results are presented as mean ± stan-

dard deviation unless otherwise indicated. Stepwise regression

was used to identify factors associated with increased PaCO2

in BD.

Results

Population Description

Eleven BD met the inclusion criteria for Group B: 7French and 4 English Bulldogs. Eleven MDD were inGroup C: 6 Beagles, 2 mixed breed dogs, 1 Stafford-shire Bull Terrier, 1 Parson Russell Terrier, and 1Australian Cattle Dog. For dogs in Group B, age,weight, and BCS were 43 ± 19 months, 18 ± 7 kg, and3.4/5 ± 0.5, respectively. For dogs in Group C, age,

2 Hoareau et al

weight, and BCS were 38 ± 13 months, 15 ± 7 kg, and3/5 ± 0.4, respectively. The difference in BCS betweenthe 2 groups was statistically significant (P = .044). Nostatistical difference between the 2 groups was foundin age and weight.

Questionnaire Results

In Group B, the questionnaire indicated that 3 dogs(27%) had previously experienced syncopal episodes atleast once in their lifetime, and 2 dogs (18%) breathedwith open mouths most of the time. All ownersreported a high frequency of snoring, even when thedogs were awake. One dog (9%) coughed frequently.Six dogs (55%) were diagnosed with the BS, whichwas surgically corrected in 2/6 dogs.

Physical Examination

The temperatures, heart rates (HR), and respiratoryrates (RR) in Group B were 38.5 ± 0.5°C, 118 ± 31beats/min, and 47 ± 38 breaths/min, respectively. InGroup C, they were 38.5 ± 0.3°C, 114 ± 31 beats/min,and 32 ± 16 breaths/min, respectively. There were nosignificant differences between the 2 groups in any ofthese parameters.

The dogs’ heights and thoracic circumferences were38.8 ± 8.1 cm and 60.6 ± 13 cm for Group B, and40.5 ± 7.8 cm and 56.8 ± 9.1 cm for Group C, respec-tively. There was no statistical difference between the 2groups.

Arterial Blood Gas Results

The findings are presented in Table 1. Arterial pHwas not statistically different between the 2 groups(P = .34). Bicarbonate concentrations and PaCO2

were both significantly higher in Group B than inGroup C (P = .021 and .019, respectively). The PaO2

and anion gap were significantly lower in Group Bthan in Group C (P = .017 and .012, respectively).No significant difference was found between the 2groups for the A-a gradient (P = .07). Hemoglobinconcentration was significantly higher in BD than incontrols (P = .018). No statistically significant differ-ence was found for the hemoglobin saturation value(P = .06).

Packed Cell Volume and Total ProteinConcentration

The PCV was significantly higher in Group B thanGroup C (48 ± 4% versus 44 ± 5%, P = .026). No sta-tistical difference was found between the 2 groups forTP (62 ± 8 g/L in Group B and 58 ± 5 g/L in GroupC, P = .063).

Arterial Blood Pressure Measurements

Results are presented in Table 2. The SAP, MAP,and DAP were significantly higher in BD comparedwith controls (P = .013, .014, and .042, respectively).

Subgrouping Results

To investigate potential factors associated with highPaCO2, dogs in Group B were divided according towhether their PaCO2 was above or below the medianPaCO2: BD with PaCO2 > 35 mmHg were assigned tothe higher PaCO2 group (n = 5; range: 36–44 mmHg),where BD with PaCO2 � 35 mmHg were assigned tothe lower PaCO2 group (n = 6; range: 29–35 mmHg).All previous parameters were compared between thesubgroups, and between each individual subgroup andthe MDD group. Values are reported only whenP < .05.

Animals in the higher PaCO2 group were significantlyolder than both the lower PaCO2 (P = .004) and controlgroups (P = .03). Mean age within the higher PaCO2

group was 58 ± 16 months, whereas for the lowerPaCO2 and control groups ages were 30 ± 11 monthsand 38 ± 13 months, respectively. Moreover, stepwiseregression showed that age, pH, and [HCO3

�] wereassociated with PaCO2 results in BD (P = .04, <.0001,

Table 1. Arterial blood gas measurement results in brachycephalic dogs (group B, n = 11) compared to control,meso- or dolicocephalic dogs (group C, n = 11) (fraction of inspired oxygen 21%).

pHa

PaCO2

(mmHg)

[HCO3�]

(mmol/L)

PaO2

(mmHg)

A-a gradient

(mmHg)

SaO2

(%)

tHb

(mg/dL)

Anion Gap

(mmol/L)

Group B 7.40 ± 0.02 36.3 ± 4.6* 20.5 ± 2.3* 86.2 ± 15.9* 15 ± 12 95.2 ± 3.7 16.7 ± 1.3* 22.2 ± 6.3*

Group C 7.40 ± 0.04 32.7 ± 2.6 18.4 ± 2.2 100.2 ± 12.6 6 ± 11 97.1 ± 0.9 15.2 ± 1.9 27.3 ± 2.1

pHa, arterial pH; PaCO2, carbon dioxide arterial partial pressure; [HCO3�], arterial bicarbonate ion concentration; PaO2, oxygen arte-

rial partial pressure; A-a gradient, alveolar-arterial oxygen gradient [(147 � PaCO2/0.8) � PaO2]; SaO2, arterial hemoglobin saturation;

tHb, arterial hemoglobin concentration. Reference range: PaCO2 36–44 mmHg, PaO2 90–100 mmHg.

*P < .05.

Table 2. Mean systolic (SAP), mean (MAP), diastolic(DAP) arterial blood pressures in brachycephalic dogs(group B, n = 11) compared to control, meso- ordolicocephalic dogs (group C, n = 11).

SAP (mmHg) MAP (mmHg) DAP (mmHg)

Group B 178 ± 25* 123 ± 17* 95 ± 19*

Group C 154 ± 22 108 ± 12 83 ± 11

*P < .05.

Arterial Blood Gases in Brachycephalic Dogs 3

and <.0001, respectively). The BCS also was higher inthe higher PaCO2 group than in Group C (3.6 ± 0.5/5versus 3 ± 0.4/5 in Group C, P = .018). When com-pared with Group C, the lower PaCO2 group had signifi-cantly higher SAP, DAP, and MAP (P = .031, .020, and.023, respectively), whereas the higher PaCO2 grouponly had higher SAP and MAP (P = .034 and .044,respectively; see Table 3). No statistical difference wasfound between the 2 subgroups of BD for ABP.

The comparison between the 2 subgroups of GroupB also indicated no significant difference in RR(72 ± 45 breaths/min versus 27 ± 9 breaths/min,respectively, P = .126). The HR was lower in the dogswith higher PaCO2 (93 ± 24 beats/min versus 138 ± 20beats/min, respectively, P = .004).

Arterial blood gas results are summarized inTable 4. No statistical difference was found betweendogs with lower PaCO2 and MDD. The higher PaCO2

group had significantly higher [HCO3�] (P = .002) and

lower PaO2 and anion gap (P = .004 and .03, respec-tively) when compared with the lower PaCO2 group.Compared with controls, the higher PaCO2 group hadsignificantly higher [HCO3

�] and hemoglobinconcentration (P = .001 and .041, respectively),and lower PaO2 and anion gap (P = .003 and .001,respectively).

Discussion

The main findings of this study were that our popu-lation of BD had significantly lower PaO2, higherPCV, PaCO2, and ABP when compared with MDD.

Upper airway obstruction in certain BD is a com-plex mechanism. The pathogenesis of upper airwaydysfunction in BD may be similar to that seen inhumans suffering from SAHS. Also known as obstruc-tive sleep apnea (OSA) in its end stages, SAHS is acommon disease in human patients.22,23 It has beencorrelated with a chronic hypoxemia and stimulationof the peripheral chemoreflex (PCR) because of com-plete upper airway obstruction during sleep. Hypox-emia, and to a much lesser extent, hypercapnia are themain stimuli for activation of peripheral chemorecep-tors in the carotid body and aortic arch.24,25 Uponactivation, peripheral chemoreceptors initiate the PCR,in which cranial nerves X (vagus nerve) and XI (acces-sory nerve) conduct impulses to the higher respiratorycenter in the medulla oblongata of the brainstem.There, the information is primarily integrated in thenucleus tractus solitarius, which in turn functions tocoordinate input from other reflexes also governingcardiac and respiratory functions (ie, the baropulmo-nary stretch and central chemoreflex). Once this infor-mation has been processed in the brainstem, a cardio-respiratory response is elaborated: in the presence ofhypoxemia and hypercapnia, the PCR will stimulatean increase in minute ventilation, sympathoexcitatoryvascular tone, and vagal tone to the heart, signalingbradycardia and increased blood pressure. At the sametime, the increased minute ventilation (tachypnea andhyperpnea26) will stimulate the baropulmonary stretchreceptors, resulting in a HR higher than normal.24,25

In vivo, changes in HR also are governed by othermechanisms and therefore may not be dictated only bythe PCR.25 The English Bulldog has been well-estab-lished as a spontaneous model for SAHS.18 Predispos-ing factors identified in humans include narrowing ofthe air passage, obesity, and nasal congestion, andsimilar conformational abnormalities have beendescribed in English Bulldogs. Studies have furtherdemonstrated that the airway dilator muscles of Eng-lish Bulldogs can suffer from decreased tone that willprogressively permit closure of the upper airway. Thishas been documented on histology and magnetic reso-nance imaging.8,9 Muscle fibers are progressively con-verted from type a to type b (the latter constrictingmore strongly, but also more transiently, than the for-mer). Once hypoxemia is sensed and the PCR is trig-gered, the animal abruptly awakens and the muscles

Table 3. Comparison of mean systolic (SAP), mean(MAP), and diastolic (DAP) blood pressures betweenbrachycephalic dogs with higher PaCO2

(PaCO2 > 35 mmHg, n = 5), lower PaCO2

(PaCO2 � 35 mmHg, n = 6), and control, meso- ordolicocephalic dogs (n = 11).

SAP (mmHg) MAP (mmHg) DAP (mmHg)

Lower PaCO2

group

175.7 ± 21.7* 126.0 ± 21.7* 100.5 ± 20.9*

Higher PaCO2

group

180.0 ± 31.1* 120.0 ± 10.9* 89.0 ± 17.0

*Statistical difference with control group, P < .05.

Table 4. Comparison of arterial blood gas results between brachycephalic dogs with higher PaCO2

(PaCO2 > 35 mmHg, n = 5), lower PaCO2 (PaCO2 � 35 mmHg, n = 6), and control, meso- or dolicocephalic dogs(n = 11) (fraction of inspired oxygen 21%).

pHa

PaCO2

(mmHg)

[HCO3�]

(mmol/L)

PaO2

(mmHg) SaO2 (%)

tHb

(mg/dL)

Anion Gap

(mmol/L)

Lower PaCO2 group 7.41 ± 0.03 33.0 ± 2.1† 18.9 ± 1.5 94.0 ± 12.6† 96.8 ± 1.2 16.5 ± 1.1 25.4 ± 3.9†

Higher PaCO2 group 7.40 ± 0.02 40.2 ± 3.3* 22.4 ± 1.3*† 76.8 ± 15.2* 93.2 ± 4.8 17.0 ± 1.6* 18.4 ± 6.7*

*Statistical difference with control group.†Statistical difference between the higher and lower PaCO2 groups

pHa, arterial pH; PaCO2, carbon dioxide arterial partial pressure; [HCO3�], arterial bicarbonate ion concentration; PaO2, oxygen

arterial partial pressure; SaO2, arterial hemoglobin saturation; tHb, arterial hemoglobin concentration.

4 Hoareau et al

involved in upper airway opening rapidly and stronglycontract. Chronically, this abrupt change in musculartone leads to inflammation, edema, and fibrosis.8,9

This further diminishes the ability of the muscles tomaintain upper airway patency, leading to laryngealcollapse. Thus, with time BD are at risk for worseningupper airway obstruction.7–9

Only a few studies have addressed the link betweenupper airway obstruction and alveolar gasexchange.10,11 The absence of a statistically significantdifference in A-a gradient between the 2 groups iscontradictory with the significantly lower PaO2 in BD.Concluding that A-a gradient was not differentbetween the 2 groups should be done cautiouslybecause the small sample size increases risk of Type IIerror. The difference in PaO2 between the 2 groupswith no difference in A-a gradient also could be evi-dence that hypoventilation is driving lower PaO2 inour BD population. Evidence of chronic mild subnor-mal PaO2 in BD previously has been reported: a cau-sality between chronic hypoxemia and hyperplasiafollowed by neoplastic transformation of the chemore-ceptors in dogs27 and cattle28 have been postulated.Correspondingly, BD (especially Boxers and BostonTerriers) are known to be prone to chemodectomas.29

We therefore suggest that the lower PaO2 might beassociated with the upper airway obstruction observedin the BS. A recent study in humans showed thatupper airway and bronchial inflammation, as well asendothelial dysfunction, was correlated with the sever-ity of the upper airway obstruction.30 Although pleuralpressures of BD have never been reported, a study31

showed that BD suffering from airway obstruction hadsignificantly shorter expiratory-to-inspiratory timesratio compared with a historical control group, furthersupporting the hypothesis of high resistance to flow oninspiration. As supported by previous reports of bron-chial collapse in BD,12 it can therefore be postulatedthat the lower airways of BD are exposed to recurrentand highly negative pressures because of the effort toovercome upper airway resistance (up to �65 mmHgin human patients with SAHS32). Recurrent barotrau-ma has the potential to lead to inflammation, edemaformation, and potentially fibrosis of the lower airwaysand pulmonary parenchyma. This may contribute tothe lower PaO2 observed in our BD. To verify thishypothesis, trans esophageal pressure measurementswould be needed to assess the transmural pressuregradient.

Interestingly, we showed that BD in our populationhad lower PaO2 but also higher hemoglobin concentra-tions and PCV than controls. This might be a compen-satory mechanism to maintain normal arterial contentof oxygen. The PaO2 is a minor component of the arte-rial content of oxygen but is a major regulated factorin the body.33,34 Chronic hypoxia is a strong stimulusfor red cell production. Obstructive sleep apnea mighthave been present in some of our subjects and thosedogs might experience episodes of hypoxemia at night,which might be sufficient to stimulate erythropoietin(EPO) production as discussed in human medicine.35

Serum concentration of EPO also has been shown todecrease with treatment of sleep apnea with continu-ous positive airway pressure (CPAP).36 Also, therenin-angiotensin-aldosterone system has been shownto be activated in humans with the SAHS, and renincan enhance red blood cell production.37–41 In ourstudy, young dogs did not show a significant differencewhen compared with controls, whereas older dogs hadsignificantly higher hemoglobin concentrations.This could represent a worsening in their gas exchangedisorder as they age.

We also found that BD had higher PaCO2 comparedwith MDD. This could be explained by probableupper airway obstruction. Increased PaCO2 also maytrigger the central chemoreflex, which should haveincreased minute ventilation. Several hypotheses couldaccount for the persistence of slightly higher PaCO2.First, PaCO2 may not have been high enough to trig-ger the central chemoreceptors and induce an increasein respiratory rate or tidal volume high enough todecrease PaCO2. Second, dogs in our study may haveundergone habituation, and the PaCO2 threshold mayhave been reset to a higher value. Finally, respiratorymuscles fatigue in conjunction with increased workload(eg, increased upper airway resistance, decreased pul-monary compliance), which also might be an explana-tion for this finding.

The increase in bicarbonate concentration may be ametabolic compensatory mechanism that allows BD tomaintain normal arterial pH. Age appeared to be animportant factor in the evaluation of ABG in thestudy population. Older dogs were more prone tohigher PaCO2 with no significant difference in RR sug-gesting tidal volume reductions because of age-relatedchanges such as decreased compliance or increasedresistance, although other factors also may playa role.42

Subgrouping results suggest that age could be amajor contributor to the effect of BS on ABG. TheBD with higher PaCO2 were significantly older thanthose with lower PaCO2. Older BD also had signifi-cantly lower PaO2 than MDD and younger BD. Nodifference was found between young BD and theMDD. This could represent progression of dysfunctionof the pulmonary parenchyma in the older BD. Over-all, BD in the present study did not show a significantincrease in HR or RR in face of subnormal PaO2, butdid demonstrate an increase in ABP. The sensitivity ofthe PCR to PaO2 is referred to as peripheral chemo-sensitivity. Most of the literature regarding peripheralchemosensitivity is based on observations made eitherfrom humans living at high altitude or from animalmodels (sheep,43,44 goats,45,46 and cats43,47–49). Areview of the literature showed that short exposure tohypoxemia would provoke an increased response ofthe PCR. In chronic hypoxemic situations, the organ-ism can undergo a phenomenon called “habituation”or “desensitization to hypoxemia”. After chronic expo-sure to hypoxemia, the peripheral chemoreceptordevelops decreased sensitivity and response to lowPaO2.

50,51 It is controversial whether or not changes in

Arterial Blood Gases in Brachycephalic Dogs 5

PaO2 or PaCO2 are the main stimuli for breathing.Both PaO2 and PaCO2 are implicated in the control ofbreathing52 and the level of one can alter the body’sresponse to changes in level of the other.53 Although,changes in PaCO2 are the most significant driving forcefor ventilatory changes in air breathers,54 a decreasedPaO2 can trigger a ventilatory response as well.

This study also demonstrated that ABP was signifi-cantly higher in BD than MDD. Mechanisms such asactivation of the renin-angiotensin-aldosterone sys-tem,55 arterial wall stiffening,56,57 oxidative damage,endothelial dysfunction,30 and systemic inflammationhave been shown to contribute to hypertension inSAHS patients.57 Reportedly, because of chronic expo-sure to catecholamines, SAHS patients are prone tosystemic and pulmonary hypertension14 that could, ifpresent in affected BD, contribute to oxygenationimpairment as well.58

The BD had slightly higher BCS than controls. Inhumans, obesity is a major risk factor for OSA andeven has been associated with the obesity hypoventila-tion syndrome, which encompasses many perturbationsin ventilatory drive.59 The effect of BCS has been men-tioned as a potential aggravating factor for the BS,60

but no direct correlation could be made between theBCS and the severity of upper airway obstruction.60,61

Torrez et al60 suggested the potential benefit of weightloss for non-upper airway related reasons, which alsohas been discussed in human medicine.59

This study provides pilot data about potential pul-monary and cardiovascular consequences of the BS.Advanced experimental procedures, such as pulmonaryfunction testing, endoscopy, or histological evaluationof lung biopsies, would be necessary in the future toconfirm the presence and quantify the severity of theBS in experimental subjects and also to furtherdescribe mechanisms of disease.

This study has several limitations. First, only 2breeds of BD were represented, and the results maynot directly be extrapolated to all other BD. Second,the study population was heterogeneous in terms ofage, severity, and history of previous surgical correc-tion of the BS. There are no data to address the effectof those factors on the parameters studied here. Itmust be noted, however, that this heterogeneity actu-ally may provide an accurate representation of the het-erogeneous general BD population. Also, we used a 5-point BCS, which was the standard of practice at ourinstitution. The 9-point BCS is more commonly usedin North America and has been shown to correlatebest with actual body fat mass.62

Also, it was unexpected to have negative values forA-a gradients. Nonetheless, negative values of A-a gra-dient previously have been reported.63–65 This mightbe because of summations of errors inherent to the A-a gradient formula (variations in respiratory quotient,barometric pressure, water vapor pressure, pulmonarycapillary temperature) or to measurement variation inpatients with low A-a gradient. The results of the sub-group analysis must be interpreted with cautionbecause the small sample size increases the risk for a

type II error. Finally, other causes of venous admix-ture (eg, pneumonia or right-to-left shunting) wereruled out solely based on an unremarkable medicalhistory and physical examination. Although it is unli-kely that such conditions would have been presentwithout associated clinical signs, these conditions can-not be definitively ruled out without further diagnosticevaluation.

For the first time, our study examined ABG in BDand provided evidence that BD have lower PaO2,higher PaCO2, and higher ABP when compared withMDD. Similar to the pathophysiology of exercise-induced pulmonary hemorrhage in horses and post-obstructive pulmonary edema, oxygenation impair-ment may be because of recurrent barotrauma to over-come upper airway resistance to airflow, which maylead to alveolar tearing, capillary damage, endothelialdysfunction, and interstitium damage.66–68 We alsofound that BD had higher PCV when compared withMDD, potentially in response to their mild chroniclower PaO2. The results of this study may be useful inthe clinical management of BD and patients sufferingfrom the BS, because PaO2 results lower than the stan-dard reference range may be within the referencerange for individual BD. Additional studies will benecessary to determine the effect of breed, age, andBCS on variations in ABG among individual BD, andto assess the effect of surgical correction of the BS onABG and ABP. Surgery has been shown to improvegastrointestinal signs induced by the BS69, and it alsomay affect ABG and ABP. Because increased upperairway resistance may influence lower airway physiol-ogy and lung parenchyma, future studies may provideinsight into the efficacy of surgery in older patientswith the BS.

Footnotes

a Vetstat analyzer, Idexx, Eragny-sur-Oise, Franceb StatMAP 7200, Ramsey Medical Inc, Tampa, FLc Sigma Stat, version 3.1, Systat Software Inc, Chicago, IL

Acknowledgments

The authors thank Ms. Severine Dumond for hertechnical assistance.

This protocol was not supported by any grant.

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