Sildenafil Citrate T herapy in 22 Dogs with Pulmonary Hypertension Background: Pulmonary hypertension (PH) is a disease condition characterized by abnormally increased pulmonary artery pressures and often is associated with a poor prognosis. Sildenafil is a phosphodiesterase inhibitor that causes pulmonaryarterial vasodilation and reduction in pulmonary artery pressures.
Hypothesis: Treatment with sildenafil will improve echocardiographic determinants of PH in dogs, while also improving Animals: Twenty-two dogs with clinical and echocardiographic evidence of pulmonary hypertension.
Methods: A retrospective study evaluating the effects of sildenafil on physical examination, ECG and radiographic findings, blood pressure and echocardiographic findings of PH, clinical score, and outcome was completed. PH was defined as a peaktricuspid regurgitation flow velocity $2.8 m/s or a peak pulmonic insufficiency flow velocity $2.2 m/s.
Results: Sixteen of 22 dogs with PH were elderly females of small body size. Their clinical score was significantly improved (P 5 .0003) with sildenafil treatment, but physical examination findings remained unchanged. Heart rate, respiratory rate,vertebral heart size, ECG heart rate, and systolic blood pressure did not change significantly with sildenafil treatment (P .
.05). Peak tricuspid regurgitation flow velocities did not change significantly with the treatment of sildenafil, but selectedsystolic time intervals were significantly improved. Survival times for all dogs ranged from 8 to .734 days.
Conclusions and Clinical Importance: Sildenafil did not significantly lower the degree of measurable PH in dogs. Clinical improvement and increased quality of life was seen with sildenafil treatment, despite lack of significant change in othervariables.
Key words: Echocardiographic; Heart disease; Pulmonary disease; Systolic time intervals.
Pulmonary hypertension (PH) is a persistent, abnor- vascular concentrations of cyclic guanosine monopho- mal increase in pulmonary systolic or diastolic sphate (cGMP). Increased concentrations of circulating pressure to greater than approximately 30/19 mm Hg.1–5 pulmonary vascular cGMP cause vasodilation by in- PH in dogs can be primary (idiopathic) or secondary to creasing the activity of endogenous nitric oxide.13 Little various diseases, including vascular obliterative diseases has been reported regarding the efficacy of sildenafil such as dirofilariasis and pulmonary thromboembolism; therapy or possible adverse effects in dogs with naturally primary structural pulmonary disease, such as pulmo- occurring PH. The purpose of this study was to describe nary fibrosis, pneumonia, and neoplasia; hyperviscosity; the presenting signs, clinical characteristics, and re- reactive pulmonary arterial vasoconstriction; degenera- sponse to sildenafil therapy in 22 dogs with Doppler- tive mitral valve disease and left-sided congestive heart echocardiographically diagnosed pulmonary hyperten- failure (CHF); or congenital cardiac abnormalities, such as reversed patent ductus arteriosus (rPDA).2–11 Dopplerechocardiography provides a noninvasive and readily available method of diagnosing PH in conscious animalsand is now the method of choice to diagnose naturally Medical records from dogs at the University of Wisconsin Veterinary Medical Teaching Hospital Cardiology Service (2004– occurring PH in veterinary patients.2–5,8 2006) were reviewed to identify dogs who received sildenafil to treat The clinical presentation of dogs with symptomatic echocardiographically identified PH in the years 2004–2006.
PH has been described anecdotally or in case series.2,3,7,12 Thirty-eight dogs who received the drug to treat PH were Echocardiographic and radiographic findings can be identified. Dogs were required to have had at least one follow-up helpful to identify concurrent cardiac disease or echocardiographic examination after at least 7 days of sildenafil pulmonary disease, and Doppler echocardiographic therapy to be included in the study. Twenty-two dogs matching examination allows identification and indirect quantifi- these criteria were identified and studied further.
cation of pulmonary arterial pressure by determination The following information was extracted from the medical of peak tricuspid regurgitation flow velocity (PTRFV), records: signalment, history; presenting complaint; heartworm peak pulmonic insufficiency flow velocity (PPIFV), or status; physical examination findings; and diagnostic test results,including thoracic radiographs, Doppler-echocardiogram, 2-di- both, and subsequent estimation of pulmonary artery mensional (2-D) echocardiogram, systolic blood pressure (SBP) measurement, ECG, CBC count, and serum chemistry evaluation Sildenafil citrate (Viagra)a is a highly selective when available. The final clinical diagnosis was recorded. SBP was phosphodiesterase type V inhibitor that causes pulmo- measured via Doppler sphygmomanometry or oscillometric meth- nary artery vasodilation by increasing pulmonary ods. Dogs who received antihypertensive medication other thanangiotensin converting enzyme inhibitors were excluded from the From the Section of Cardiology, Department of Medical Sciences, SBP analysis. Dogs who received angiotensin-converting enzyme School of Veterinary Medicine, University of Wisconsin, Madison, WI.
inhibitors were only included in the SBP analysis if the dose was Reprint requests: Heidi Kellum, Veterinary Medical Teaching unchanged between examination points. A standard 6-lead ECG Hospital, Madison, WI 53706; e-mail: [email protected].
was recorded with the dog in right lateral recumbency.
Submitted January 10, 2007; Revised March 6, 2007; May 22, Thoracic radiographs were evaluated by a board-certified radiologist at the time of clinical evaluation. At the time of review, the presence and distribution of the pulmonary infiltrate pattern E 2007 by the American College of Veterinary Internal noted were recorded. Enlargement patterns were considered to be right-sided if any combination of main pulmonary artery, right short-axis view). The timing and dose of sildenafil therapy wasrecorded. At follow-up, the dogs’ owners’ perception of clinicalprogress was recorded with the history, physical examination, anddiagnostic test results after sildenafil therapy.
All dogs received a composite clinical score at presentation and at follow-up at least 7 days later, based on (1) the presence of overtclinical signs, including exercise intolerance, respiratory distress,abdominal distension, or cough as assessed by the attendingclinician based on a physical examination; and (2) the owner’sgeneral assessment of the dog’s well being, including occurrence ofsyncopal episodes. Dogs with overt clinical signs significantly Pulmonary artery velocity flow profiles: type I (normal, affecting quality of life received a clinical score of 2, dogs with a dome-like profile with the peak velocity flow occurring in the identifiable clinical signs but moderate or mild impact on quality of middle of systole with symmetric acceleration and deceleration life received a score of 1, and dogs with no clinical signs received phases), type II (the peak velocity flow occurring early in systole a score of 0. The owner’s assessment of general well being was with a steep and rapid acceleration phase and slower deceleration based on owner’s reports of activity levels, attitude, and appetite.
phase), or type III (the same as type II but a notch occurs in the The scores for both categories were added together (maximum score for worst affected dogs 5 4) and recorded at presentation andat the first follow-up evaluation.
atrial, right ventricular, caudal vena cava, or hepatic enlargement Dogs were categorized into 1 of 3 groups based on the were noted. Left-sided enlargement pattern was recorded if left confirmed or presumed etiology of PH. Group 1 (rPDA) included atrial or left ventricular enlargement was noted. Pulmonary venous dogs with echocardiographically confirmed rPDA. Group 2 size was recorded as a separate variable, and other abnormalities (respiratory disease) included dogs with PH that was attributed to respiratory disease and for which increased left atrial pressureswere unlikely based on echocardiographic confirmation of normalleft atrial size. Group 3 (heart disease) included dogs with PH that was attributed to severely increased left atrial pressures, as assessed All echocardiographic examinations were reviewed by a single by a left atrial : aortic ratio that exceeded 2.0 on echocardiographic person (HBK). Full echocardiographic studies were performed at examination. For the dogs in group 3, it was unclear if there were the time of original presentation in all dogs. Echocardiograms were concurrent respiratory contributions to their PH.
repeated at least 7 days after initiation of sildenafil therapy.
The cause and date of death was ascertained by medical record Standard 2-D views14 and Doppler echocardiographic studies were review for dogs who did not survive at the end of the study period.
performed by using a cardiac ultrasound unit.b Doppler evalua- Dogs still alive or euthanized for unrelated reasons were censored tions were performed by using a 2.5- or 3-MHz transducer. The at the time of the end of the study period or date of euthanasia. For right- or left-sided view that allowed for optimal alignment of dogs euthanized for clinical signs related to PH, the date of regurgitant flow (tricuspid regurgitation [TR] and pulmonic euthanasia was considered equivalent to the date of death.
insufficiency [PI]) was used to measure instantaneous pressure The following variables and findings were compared between gradients. Pulmonic stenosis was ruled out by evaluating for presentation and follow-up: physical examination, composite normal valvular anatomy and mobility on 2-D echocardiography clinical score, Doppler and 2-D echocardiographic values, SBP, and identification of laminar pulmonic flow profile via pulsed-wave thoracic radiographs, laboratory results, and ECG findings.
Doppler echocardiography with peak pulmonary artery flowvelocities less than 1.5 m/s. The modified Bernoulli equation (the change in pressure equals 4 times the velocity squared) was appliedto the PTRFV and PPIFV to calculate the instantaneous right Data analysis was performed with standard statistical software.c ventricular to right atrial and pulmonary artery to right ventricular Because of small sample sizes, normal distribution could not be pressure gradients, respectively. A PTRFV $2.8 m/s or peak TR assumed and all variables were analyzed with nonparametric flow gradient (PTRFG) $31.4 mm Hg or a PPIFV $2.2 m/s or methods. A Wilcoxian signed rank test was used to compare values a peak PI flow gradient (PPIFG) $19 mm Hg was considered to be at baseline versus posttreatment. A Kruskal-Wallis test was used to abnormally high and indicative of PH.2,4 Right atrial pressures were compare the clinical score before and after sildenafil administration not measured or estimated in these dogs.
among the 3 subgroups. A decrease of $1 point on clinical score Pulmonary velocity flow profiles were subjectively evaluated was classified as improvement at follow-up. P values ,.05 were and classified as either type I, II, or III (Fig 1).2,4 Systolic time considered significant for all tests. Results are given as the median intervals (acceleration time [AT], ejection time [ET], AT : ET, pre- ejection period [PEP]) were measured as previously described byusing a simultaneously recorded ECG.4,15,16 The pulmonic AT was measured from the initial deflection of pulmonary blood flowprofile to the peak flow. Systolic time interval variables were not Of the 22 dogs included in the study, 15 were spayed The right ventricle was evaluated subjectively for evidence of females, 4 were neutered males, 1 was a sexually intact right ventricular hypertrophy and abnormal interventricular septalwall motion. The diameter of the main pulmonary artery (MPA) female, and 2 were sexually intact males. There was 1 was evaluated as a pulmonary artery to aorta diameter ratio. MPA mixed-breed dog, and the remaining 21 dogs were enlargement was noted if the pulmonary artery diameter exceeded purebred, consisting of 3 West Highland White Terriers, the diameter of the aortic root in the same plane (right parasternal 3 Miniature Poodles, 2 Maltese, 2 Yorkshire Terriers, 2 Scottish Terriers, and 1 dog each of the following breeds: paced rhythm at 80 bpm for concurrent persistent atrial Australian Cattle Dog, Japanese Chin, Rat Terrier, standstill. One dog each had single atrial and ventricular Norwich Terrier, Cavalier King Charles Spaniel, Welsh premature complexes. Two dogs (both rPDA dogs) had Terrier, Brittany Spaniel, American Water Spaniel, and a right axis deviation in the frontal plane.
Springer Spaniel. The age of the dogs at the time of Thoracic radiographs were performed in 20 dogs at diagnosis of PH ranged from 0.6 to 15.4 years (median, presentation. The vertebral heart size was recorded in 18 12.5 years). The weight of the dogs at the time of dogs, and not all thoracic radiographs were available for diagnosis ranged from 2.4 to 21 kg (median, 8.0 kg).
review. MPA enlargement was noted in 6 dogs (30%).
Pulmonary infiltrates were noted in 16 dogs (73%).
Thirteen dogs had broncho-interstitial or interstitialpulmonary infiltrates, and broncho-alveolar or intersti- All dogs were examined because of referral for tial-alveolar infiltrates were noted in 3 dogs. Four of the problems suspected to be cardiac or respiratory in 16 dogs had pulmonary infiltrates as the only abnor- origin. The most common presenting complaint was mality noted. Less common abnormal pulmonary cough, reported in 17 dogs (77%). Also common were findings included narrow trachea (n 5 2), atelectasis of respiratory distress, ‘‘raspy’’ breathing, or referral for 1 lung lobe (n 5 1), a pulmonary mass lesion (n 5 1), auscultated pulmonary crackles (n 5 10 [45%]), lethargy bronchiectasis (n 5 1), and rounding of the lung lobes (n (n 5 7 [32%]), syncope or collapse episodes (n 5 7 [32%]), or exercise intolerance (n 5 5 [23%]). Five dogs Seven of 16 dogs with pulmonary infiltrates had had heart murmurs at the time of presentation but only combined left and right heart enlargement patterns, 3 2 were examined for murmur evaluation without other dogs with pulmonary infiltrates had right-sided enlarge- complaints. Both of these dogs had rPDA as a final ment patterns only, and 2 dogs had left-sided enlarge- diagnosis. Two dogs were presented for evaluation of ment patterns only. One dog of 16 with pulmonary abdominal distention, ascites, or both. Most of the dogs infiltrates had pulmonary venous congestion, and this had more than one presenting complaint (n 5 16 [73%]).
dog had severe cardiomegaly and previously diagnosed Sixteen dogs (73%) were given a clinical score of 4 at left-sided CHF. Four dogs had cardiac abnormalities admission, 2 dogs (9%) had a score of 3, 3 dogs (14%) without pulmonary infiltrates. Two of these dogs had had a score of 2, 1 dog (5%) had a score of 1, and no both right- and left-sided enlargement patterns, and 2 had a right-sided enlargement pattern only. The latter 2dogs were diagnosed with rPDA.
Pulmonary hypertension was diagnosed in 21 dogs Results of cardiac and respiratory auscultations were based on the presence of high PTRFV and in 1 dog recorded in 20 dogs. Murmurs were auscultated in 16 of based on a high PPIFV. Nineteen dogs (86%) had mitral 20 dogs (80%). Three dogs had left-sided systolic regurgitation attributable to chronic valvular disease or murmurs only, 1 dog had a right-sided systolic murmur, mitral valve dysplasia. Of these, 8 (42%) had moderate and 12 dogs had systolic murmurs audible on both sides or severe degrees of mitral regurgitation with associated of the thorax. Three dogs had a normal cardiac moderate-to-severe left atrial enlargement. TR was auscultation, with abnormal respiratory sounds. Split present in 21 dogs (95%). Based on their PTRFG, 7 or abnormally loud second heart sounds were auscul- dogs were categorized as having mild PH (#50 mm Hg), tated in 4 dogs. Respiratory auscultation revealed 7 dogs had moderate PH (51–75 mm Hg), and 7 dogs pulmonary crackles (n 5 14 [70%]), wheezes (n 5 1 had severe PH (.75 mm Hg).2 Subjective right-sided [5%]), and harsh or increased respiratory sounds (n 5 4 chamber dilation (atrial or ventricular) was noted in 14 [20%]). Normal respiratory findings were recorded in 4 dogs, and right ventricular wall thickening was present dogs (20%). All 4 of the dogs with normal respiratory in 10 dogs. Systolic septal flattening was present in 6 findings had heart murmurs noted. One dog was dogs and paradoxic septal motion in 1 dog. PI was cyanotic. No dogs were in clinically evident CHF at documented in 15 dogs. The median PPIFG was 29 mm the time of referral, but 7 (32%) were receiving various Hg (range, 8–97 mm Hg). The single dog who was cardiac medications for previously diagnosed CHF, 6 diagnosed based on PI alone had a PPIFG of 25 mm Hg(normal dogs (27%) were receiving respiratory medications, and 4 dogs were receiving both cardiac and respiratory Pulmonary artery flow profiles were evaluated in 21 medications (18%). Five dogs (23%) were not receiving dogs. Although 7 dogs had a PTRFV thought to medications at the time of referral.
represent mild PH, no dogs had a type 1 (normal) flowprofile. Seven dogs had a type II profile, and 3 of thesedogs had concordant gradients indicative of moderate PH. The remaining 13 dogs had type III flow profiles, Presenting ECG findings were available for 16 dogs.
and 5 of these had severe PH. Main pulmonary artery The most common ECG rhythm diagnoses were sinus dilation was noted in 9 dogs. Systolic time intervals were arrhythmia (n 5 6), normal sinus rhythm (n 5 5), or evaluated in 21 dogs. SBP was recorded in 8 dogs and sinus tachycardia (n 5 4). Atrial fibrillation was present in 1 dog with severe mitral regurgitation and TR Thirteen dogs had serum biochemical analysis. One secondary to endocardiosis. One dog had an artificially dog had normal findings and various other single Comparison of selected physical and diagnostic test results before and after sildenafil therapy.
Peak TR flow gradient (mm Hg) group 1 (rPDA)b Peak TR flow gradient (mm Hg) group 2 (respiratory disease)b Peak TR flow gradient (mm Hg) group 3 (heart disease)b ns, not significant; TR, tricuspid regurgitation; rPDA, reversed patent ductus arteriosus; PA, pulmonary artery; AT, acceleration time; ET, ejection time; PEP, pre-ejection period; PI, pulmonic insufficiency.
a Values are presented as median (range).
b See text for explanation of grouping variables abnormal biochemical values were noted. The PCV was addition of sildenafil, from the time of diagnosis to recorded in 8 dogs (including both dogs with rPDA) and reevaluation, but 7 dogs had medications other than was within expected normal range in all dogs. Heart- sildenafil added before reevaluation, including enalapril, worm status was known in 21 dogs; all were negative.
furosemide, terbutaline, amlodipine, and doxycycline.
Group 1 (rPDA) included 2 dogs, group 2 (re- Adverse effects, which included lethargy, somnolence, spiratory disease) included 11 dogs, and group 3 (heart clear nasal discharge, and erect ears, presumed to be the result of sildenafil therapy, were reported in 4 of 22 dogs(18%). No dog had sildenafil therapy discontinuedbecause of clinical adverse effects.
Clinical History/Response to Medication. The median Diagnostic Test Results. SBP did not differ signifi- number of days elapsed until first follow-up examination cantly compared with presentation measurements (n 5 in all dogs was 31 (range, 7–521 days). The sildenafil 5) at follow-up. Thoracic radiographs were performed in dosages ranged from 2.08 to 5.56 mg/kg per day 9 dogs at follow-up. The vertebral heart size at follow-up (median, 3.13 mg/kg). The appropriate sildenafil dose (median, 11.8 vertebral lengths), did not differ from that was reformulated and placed into capsules by the at initial examination median value (Table 1). Pulmo- Veterinary Medical Teaching Hospital pharmacy for nary infiltrates were present in 5 of 9 dogs at follow-up (56%), and the degree and description of the infiltrateswere unchanged between presentation and follow-up.
Physical Examination at Follow-up. Neither heart rate Echocardiographic examinations were recorded in 22 nor respiratory rate changed significantly with sildenafil dogs after sildenafil treatment (selected findings Table 1).
treatment (Table 1). Results of cardiac and respiratory TR was present in 21 dogs after sildenafil treatment. The auscultations were recorded in 20 dogs, and no dogs had median PTRFG (55 mm Hg; range, 30–179 mm Hg) was clinically significant changes in their murmurs or unchanged from presentation measurements. No sub- groups had detectable changes in median PTRFGcompared with presentation. Septal flattening was no Clinical Score at Follow-up. There was a statistically longer present in 4 of 6 affected dogs (Fig 2). The median significant difference in composite clinical scores at PPIFG did not change after therapy (n 5 10). Eight dogs presentation and at follow-up (P 5 .0003). Total clinical had no categorical change in the flow profile category score decreased by $2 in 14 dogs (64%), and 8 dogs had after therapy, 4 dogs improved by one category and one a clinical score of 0 after treatment. Clinical improve- dog’s profile worsened by one category. There was no ment was evident as increased activity, increased exercise difference in the median PTRFG change when dogs with ability, increased ease of breathing, improved demeanor, an improved profile category were compared with dogs decreased ascites in affected animals, improved cough, with worsening or no change in profile category (P 5 .38).
and cessation or reduced frequency of syncopal or Right ventricular systolic time intervals were evaluated in collapse episodes. There were no significant differences 14 dogs. There was a statistically significant increase (P 5 in change in the median clinical score among the 3 .006) in the median pulmonary AT after sildenafil therapy disease-based subgroups (P 5 .17). Most dogs (n 5 15 (Table 1). The AT : ET ratio was significantly increased [68%]) had no changes in medications, other than the (n 5 14, P 5 .017), and the PEP was significantly Kaplan-Meier curve of clinical outcome of 22 dogs with PH treated with sildenafil. Vertical ticks mark point of dog datacensoring.
improvement in dogs who received sildenafil for PH.
Improvement in clinical signs appeared to be the mostreliable indicator of success of therapy. Other echocar-diographic findings may support changes in pulmonaryartery pressures, but the variability in Doppler gradientmeasurements may make PTRFV or PPIFV an unreli-able indicator of success in a clinical population.
The majority of the dogs in this study of natural occurring PH were elderly females of small body size.
Forty-five percent of the dogs in the study were terrier Echocardiographic views of a dog with pulmonary breeds. Chronic pulmonary diseases that predispose to hypertension. (A) and (B) were obtained from the right parasternal PH are reported to be more common in terrier breeds,12 short-axis view and are of the left and right ventricles at the level of but the predominance of female dogs in this study has the papillary muscles. Both images depict end-diastole. (A) Shows severe septal flattening at the time of diagnosis of PH. (B) Shows In this study, the most common presenting signs were resolution of septal flattening after sildenafil therapy.
similar to previous reports and included cough, lethargy,syncope, and exercise intolerance.1,3,5,10,17 However, 2 dogs decreased (n 5 12, P 5 .002). Twelve dogs had were diagnosed after referral for evaluation of heart biochemical analysis at follow-up. No clinically impor- murmur alone. Both of these were young dogs diagnosed as having a rPDA and severe PH. In dogs withEisenmenger’s complex, severe PH is a result of pulmo- Outcome. Survival times ranged from 8 to .734 days nary vascular obstructive disease rather than occurring in (Fig 3). The median survival time for all dogs could not the presence of airway or pulmonary parenchymal be calculated, because more than 50% of the dogs were disease.18 This can account for the lack of the respiratory alive at the end of the study period. The median follow- signs in the dogs with rPDA even though these signs were up of censored dogs was 247 days (range, 8–698 days).
common in other dogs with PH. Signs of pulmonary Ten dogs (45%) were euthanized or died by the end of vascular obstructive disease, such as cyanosis, exercise the study period. Five of these dogs died of witnessed intolerance, and syncope, were not originally reported by respiratory distress or were euthanized in extreme the owners, but both dogs were noted by the owners to respiratory distress and were considered to have died have increased activity levels while receiving sildenafil.
or been euthanized because of their PH. Based on this A review of these and previously reported findings series of 22 dogs with PH treated with sildenafil, if dogs suggests that there are no pathognomonic clinical signs survived the first week of therapy, the probability of or physical findings that can be used to diagnose PH survival to 3 months after initiation of therapy was 95%.
with certainty. Populations at risk for PH often include There was an 84% probability of survival at 6 months dogs at risk for more common diseases with similar and a 73% probability of survival at 1 year after signs, including mitral insufficiency with CHF and chronic obstructive pulmonary diseases. More specificclinical history or findings suggestive of PH, including a history of syncope, the presence of TR murmurs,tachypnea, split or loud second heart sound, or Sildenafil was well tolerated in the dogs studied here, cyanosis,2,3,5,12 were recorded variably and often in the and both owners and veterinarians reported clinical presence of more generic cardiorespiratory abnormali- ties. Small-breed dogs with clinical signs and physical the ability of the dog to tolerate the examination. The findings of cardiorespiratory disease might benefit from addition of the right atrial pressure (if known) to the TR screening for PH, especially if syncope was reported.
gradient theoretically provides the most accurate pre- Results of this study suggested that successful treatment diction of pulmonary systolic pressure,4,23 but right atrial with sildenafil does not alter physical examination pressure is not routinely measured in dogs. Because of findings in dogs with PH and that a lack of change in the innate error in estimations of right atrial pressure physical findings did not predict a lack of clinical and because only one dog was diagnosed as having right response to sildenafil. Abnormal physical examination heart failure based on clinical signs, the PTRFG alone findings in these dogs could have at least partially represented underlying cardiorespiratory abnormalities Pulmonary artery pressures assessed by TR and PI and might not be expected to change with sildenafil did not change significantly after sildenafil treatment as a whole or by disease subgroup. This differs from the Clinical scores at initial examination represented findings in a recent study3 and studies performed in a range of severity of clinical signs. All dogs had some humans,19–22 which have a significant reduction of indication of impairment of daily activity. After pulmonary artery pressure when treated with sildenafil.
treatment, the median clinical score improved signifi- In conscious dogs who were dyspneic, difficulty in cantly, and 8 dogs had a clinical score of 0 (no clinical obtaining repeatable, precise measurements of PTRFV signs) after therapy. These findings might reflect the jets could limit documentation of response to therapy, improved pulmonary hemodynamics and functional and other clinical findings should be taken into account capacity with regression of right ventricular hypertro- when evaluating the response to sildenafil treatment.
phy19 and is in agreement with previous studies of dogs3 Pulmonary artery flow profiles have been used in and people.19–22 The possibility that PH could have been dogs and humans to estimate the severity of the associated with an acute, potentially transient event, PH.2,4,6,15–17,24 In this study, the pulmonary artery flow such as pulmonary thromboembolism might explain an profile categorizations did not always correctly associate apparent treatment effect. Group 3 dogs could have with the severity of the calculated gradient at pre- improved because of the instigation of furosemide sentation. Nonetheless, the lack of normal pulmonary therapy and subsequent resolution of pulmonary edema.
artery flow profiles recorded at presentation suggested The clinical scoring system used in this study was meant that identification of an abnormal flow profile may be to reflect owner-assessed changes, as well as clinical potentially valuable in supporting a diagnosis of PH, but changes recorded by the attending clinician. Though the usefulness of this variable to monitor the effects crude, the score was able to reflect the significant therapy was not apparent in this study.
changes in quality of life experienced by many of these Right ventricular systolic time intervals have been dogs. Although there were too few dogs in group 1 to used to support the diagnosis of PH in dogs4,16 and assess, disease groups 2 and 3 did not differ in their people.15,25 Here, right ventricular AT, AT : ET, and PEP response to sildenafil in terms of clinical score. This were reduced compared with normal at presentation, might indicate that the etiology of PH is not necessarily consistent with PH.4,15,16,25 Values of #0.31 for the a predictor of response to sildenafil therapy or could AT : ET and an AT value of #0.058 seconds were reflect the difficulty of separating dogs with primary predictive of PH,4 and these values might be useful to pulmonary disease and those with both cardiac and diagnose PH in animals without insufficiency jets.
pulmonary disease. A clinical score improvement was Although the median AT : ET of 0.30 and AT of 0.050 fairly consistent, despite a lack of a significant change in seconds falls within the range consistent with PH by PTRFG and PPRFG in response to therapy, possibly these diagnostic cutoff values, 43% of AT : ET ratios reflecting the variability in Doppler echocardiographic were .0.31 and 38% of AT were .0.058 seconds, measurements based on Doppler interrogation beam demonstrating the variability of this parameter when used in dogs with Doppler-demonstrated PH of various Thoracic radiographs did not significantly change etiologies. Although the change in systolic time intervals with sildenafil treatment. Cardiomegaly and pulmonary for the group was statistically significant, the reduction infiltrates were common and nonspecific findings, and in PEP and the increase in AT was small (0.01 seconds).
most dogs with PH did not have enlarged pulmonary These changes may not impart clinical significance, and arteries noted. Although thoracic radiographic assess- the range precludes its application in assessing response ment of PH is frequently complicated by changes associated with concurrent cardiopulmonary disease Etiologic categorization of group 1 and 2 dogs was processes, the presence of pulmonary infiltrates without relatively straightforward, but the third group was more pulmonary venous enlargement was a consistent finding ambiguous. Three of the category 3 dogs had moderate- and may lead the clinician to consider PH as a differen- to-severe mitral regurgitation, pronounced pulmonary tial diagnosis in a dog who is dyspneic.
crackles on physical examination, and pulmonary Peak flow velocity and associated gradients of TR or infiltrates on thoracic radiographs, but no evidence of PI were used to diagnose PH in this study. This method pulmonary venous enlargement. These animals were allows rapid, noninvasive estimation of pulmonary suspected to have concurrent cardiac and pulmonary pressures in dogs, but accuracy of predicted pressure disease as the cause of PH, but there was no gradients depends on operator skill and experience and histopathologic confirmation. Pulmonary artery pres- sures .40 mm Hg were suspected to represent more associated with dead worms in canine heartworm disease. J Vet than left heart failure alone (n 5 19), but pulmonary artery pressures in excess of left atrial pressures may 8. Serres FJ, Chetboul V, Tissier R, et al. Doppler echocardi- occur in dogs with PH secondary to left heart failure if ography-derived evidence of pulmonary arterial hypertension indogs with degenerative mitral valve disease: 86 cases (2001–2005).
reactive PH because of hypoxia is present.11,26 J Am Vet Med Assoc 2006;229:1772–1778.
Clinically apparent adverse effects of sildenafil were 9. Zabka TS, Campbell FE, Wilson DW. Pulmonary arterio- uncommon in this population and did not necessitate pathy and idiopathic pulmonary arterial hypertension in six dogs.
drug discontinuation in any dog, but dogs were often receiving multiple medications at the time of appearance 10. Glaus TM, Soldati G, Maurer R, Ehrensperger F. Clinical of clinical signs, making it difficult to attribute adverse and pathological characterisation of primary pulmonary hyperten- effects to sildenafil alone. No biochemical abnormalities sion in a dog. Vet Rec 2004;154:786–789.
could be directly correlated with sildenafil therapy.
11. Glaus TM, Hassig M, Baumgartner C, Reusch CE.
There were a number of limitations of this study. A Pulmonary hypertension induced in dogs by hypoxia at different small number of dogs were available for review, high-altitude levels. Vet Res Commun 2003;27:661–670.
12. Corcoran BM, Cobb M, Martin MW, et al. Chronic especially when subgroups were studied. There was no pulmonary disease in West Highland White Terriers. Vet Rec 1999; standard diagnostic workup for these dogs, which resulted in incomplete diagnostic testing and results.
13. Humbert M, Sitbon O, Simonneau G. Treatment of The number of blood pressures measurements per- pulmonary arterial hypertension. N Engl J Med 2004;351:1425– formed was small, which made it difficult to evaluate the systemic effects of a medication with the potential to 14. Thomas WP, Gaber CE, Jacobs GJ, et al. Recommenda- cause hypotension. A variable echocardiographic tech- tions for standards in transthoracic two-dimensional echocardiog- nique made echocardiographic results potentially less raphy in the dog and cat. Echocardiography Committee of the consistent over time. Lastly, dogs who did not appear Specialty of Cardiology, American College of Veterinary Internal for reevaluation after therapy were excluded from the Medicine. J Vet Intern Med 1993;7:247–252.
15. Martin-Duran R, Larman M, Trugeda A, et al. Comparison study. This action could have excluded dogs who are of Doppler-determined elevated pulmonary arterial pressure with severely ill and poor responders, but also could have pressure measured at cardiac catheterization. Am J Cardiol included dogs who responded very well and continued to 16. Uehara Y. An attempt to estimate the pulmonary artery pressure in dogs by means of pulsed Doppler echocardiography.
J Vet Med Sci 1993;55:307–312.
17. Johnson L. Diagnosis of pulmonary hypertension. Clin Tech Small Anim Pract 1999;14:231–236.
18. Haworth SG. Pulmonary hypertension. In: Moller JH, a Viagra, Pfizer U.S. Pharmaceuticals, New York, NY Hoffman JI, eds. Pediatric Cardiovascular Medicine. Philadelphia, b Vivid 5 and Vivid 7, General Electric Medical System, Waukesha, PA: Churchill Livingstone; 2000:709–713.
19. Michelakis ED, Tymchak W, Noga M, et al. Long-term c Prism 4.0a for Macintosh, Graphpad Software Inc, San Diego, CA treatment with oral sildenafil is safe and improves functionalcapacity and hemodynamics in patients with pulmonary arterialhypertension. Circulation 2003;108:2066–2069.
20. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 1. Fleming E, Ettinger S. Pulmonary hypertension. Compend Contin Educ Pract Vet 2006;28:720–730.
21. Humpl T, Reyes JT, Holtby H, Stephens D, et al. Beneficial 2. Johnson L, Boon J, Orton EC. Clinical characteristics of 53 effect of oral sildenafil therapy on childhood pulmonary arterial dogs with Doppler-derived evidence of pulmonary hypertension: hypertension: Twelve-month clinical trial of a single-drug, open- 1992–1996. J Vet Intern Med 1999;13:440–447.
label, pilot study. Circulation 2005;111:3274–3280.
3. Bach JF, Rozanski EA, MacGregor J, et al. Retrospective 22. Ghofrani HA, Wiedemann R, Rose F, et al. Sildenafil for evaluation of sildenafil citrate as a therapy for pulmonary treatment of lung fibrosis and pulmonary hypertension: A hypertension in dogs. J Vet Intern Med 2006;20:1132–1135.
randomised controlled trial. Lancet 2002;360:895–900.
4. Schober KE, Baade H. Doppler echocardiographic prediction 23. Yock PG, Popp RL. Noninvasive estimation of right of pulmonary hypertension in West Highland White Terriers with ventricular systolic pressure by Doppler ultrasound in patients chronic pulmonary disease. J Vet Intern Med 2006;20:912–920.
with tricuspid regurgitation. Circulation 1984;70:657–662.
5. Pyle RL, Abbott J, MacLean H. Pulmonary hypertension 24. Jardin F, Dubourg O, Bourdarias JP. Echocardiographic and cardiovascular sequelae in 54 dogs. Int J Appl Res Vet Med pattern of acute cor pulmonale. Chest 1997;111:209–217.
25. Kosturakis D, Goldberg SJ, Allen HD, Loeber C. Doppler 6. Johnson LR, Hamlin RL. Recognition and treatment of echocardiographic prediction of pulmonary arterial hypertension pulmonary hypertension. In: Bonagura K, ed. Current Veterinary in congenital heart disease. Am J Cardiol 1984;53:1110–1115.
Therapy, XII ed. Philadelphia, PA: WB Saunders; 1995:887–891.
26. Grover RF, Johnson RL Jr, McCullough RG, et al.
7. Hirano Y, Kitagawa H, Sasaki Y. Relationship between Pulmonary hypertension and pulmonary vascular reactivity in pulmonary arterial pressure and pulmonary thromboembolism beagles at high altitude. J Appl Physiol 1988;65:2632–2640.



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