Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma

Vascular endothelial growth factor (VEGF) is a dimeric glycosylated polypeptide growth factor with potent angiogenic, mitogenic, and vascular permeability-enhancing properties specific for endothelial cells. In humans, VEGF seems to play a major role in tumor growth, and plasma concentrations correlate with tumor burden, response to therapy, and disease progression. This study compared plasma VEGF concentrations in healthy client-owned dogs (n = 17) to dogs with hemangiosarcoma (HSA; n 16). Dogs with HSA were significantly more likely to have detectable concentrations of plasma VEGF (13/17) compared to healthy dogs (1/17; P < .001). The median plasma VEGF concentration for dogs with HSA was 17.2 pg/mL (range, < 1.0-66.7 pg/mL). Plasma VEGF concentrations in dogs with HSA did not correlate with stage of disease or tumor burden, but 1 dog had undetectable VEGF during chemotherapy that subsequently increased with disease progression.     

Cardiac troponins I and T in dogs with pericardial effusion

Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are sensitive and specific markers for myocardial ischemia and necrosis. Dogs with pericardial effusion frequently have myocardial ischemia and necrosis, and these changes are more severe in dogs with hemangiosarcoma (HSA). We investigated the utility of using serum cTnI and cTnT concentrations to identify the idiopathic pericardial effusion from that associated with HSA. Blood samples for measurement of cTnI and cTnT concentrations were collected before pericardiocentesis in 37 dogs with pericardial effusion. Eighteen dogs had a mass consistent with HSA, 6 dogs had idiopathic pericardial effusion, 1 dog had mesothelioma, and 1 dog had a heart base tumor. No final diagnosis was achieved for 11 dogs. Dogs with pericardial effusion had significantly higher serum concentrations of cTnI (P < .001) but not cTnT (P = .16) than did normal dogs. Dogs with HSA had significantly higher concentrations of cTnI (2.77 ng/dL; range: 0.09-47.18 ng/dL) than did dogs with idiopathic pericardial effusion (0.05 ng/dL; range: 0.03-0.09 ng/dL) (P < .001). There was no difference in the concentration of cTnT between dogs with HSA and those with idiopathic pericardial effusion (P = .08). Measurement of cTnI may be useful in helping to distinguish between idiopathic pericardial effusion and pericardial effusion caused by HSA.     

Serum and Plasma Vascular Endothelial Growth Factor Levels in Various Cat Populations

Introduction:  Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. Elevated levels within tumors, and in serum, plasma, and tumor effusion have been correlated with the development of metastatic disease, recurrence, and poor prognosis in many tumors in humans. Canine VEGF has been sequenced as homologous with the human form, and elevated serum and plasma VEGF have been found in dogs with hemangiosarcoma. Feline VEGF has also been sequenced, and shares homology with the human and canine forms.
Materials and Methods:  Stored serum and plasma samples from normal cats, cats with various neoplasms, and cats with non‐neoplastic disease were evaluated with a commercial ELISA kit (R&D Systems, Minneapolis MN). Samples were run in duplicate, and a standard curve was performed for each plate. The data were analyzed for differences between populations, and between serum and plasma levels in the same patient to determine the optimal sample for evaluating VEGF in cats.
Results:  In seven apparently healthy cats mean plasma VEGF was 95.6 pg/mL. In non‐neoplastic disease (7 cases), mean plasma VEGF was 117.3 pg/mL and mean serum VEGF level was 219.7 pg/mL. In ten tumor‐bearing patients mean plasma VEGF was 247.1 pg/mL, and mean serum VEGF was 322.3 pg/mL. Statistical analysis showed no significant difference between mean serum and plasma VEGF concentrations within each group or between groups (p > 0.05).
Discussion:  Serum and plasma VEGF levels could not be used to distinguish between healthy cats and cats with neoplastic or non‐neoplastic disease.     

Fibronectin Concentrations in Pleural and Abdominal Effusions in Dogs and Cats

A commercial nephelometric test kit for human fibronectin (FN) was found suitable for the estimation if fibronectin concentration in body effusions of cats and dogs. The FN measurements were set in relation to the FN concentration of plasma pools in cats and dogs. A discrimination line of 31.5% completely separated malignant from cardiogenic pleural effusions in cats. For the diagnosis of a malignant pleural effusion, sensitivity was 100% and specificity was 57%. Pleuritis also resulted in high FN concentrations. The FN concentration in malignant pleural effusions in dogs differed significantly ( P < .02) from that in cardiogenic effusions. There were no clinically useful differences in the FN concentration in peritoneal effusions in cats and dogs. The FN/albumin ratio was significantly higher ( P < .02) in dogs with neoplastic abdominal effusion than in those with congestive heart failure.     

Biochemical analysis of pericardial fluid and whole blood in dogs with pericardial effusion

Studies evaluating pericardial fluid analysis in dogs to determine the etiology of pericardial effusions have yielded conflicting results. The purpose of this prospective study was to compare acid-base status, electrolyte concentrations, glucose, and lactate of pericardial fluid to peripheral blood from dogs with pericardial effusion and to compare these variables between dogs with neoplastic and nonneoplastic pericardial effusion. Acid-base status, electrolyte concentrations, glucose, hematocrit, urea nitrogen, and lactate concentrations were evaluated in peripheral blood samples and in pericardial effusion samples of 41 client-owned dogs with pericardial effusion. Common abnormal findings in the peripheral blood of dogs with pericardial effusion included hyperlactatemia (n = 38 [of 41]; 93%), hyponatremia (n = 25/41; 61%), hyperglycemia (n = 13/41; 32%), and hypermagnesemia (n = 13/41; 32%). Bicarbonate, sodium, ionized calcium, glucose, and hematocrit were all significantly lower in the pericardial fluid compared with peripheral blood, whereas lactate, chloride, and PCO2 were significantly higher in the pericardial fluid. When comparing the concentrations of variables in the pericardial fluid of dogs with neoplasia (n = 28) to those without neoplasia (n = 13), pH, bicarbonate, and chloride were significantly lower in dogs with neoplasia, whereas lactate, hematocrit, and urea nitrogen were significantly higher in the pericardial fluid of dogs with neoplasia. The difference between peripheral and pericardial glucose concentrations was significantly larger in dogs with neoplasia than in dogs without neoplasia. Although differences between variables in dogs with neoplastic and nonneoplastic pericardial effusion were documented, clinical relevance is likely limited by the degree of overlap between the 2 groups.     

Thoracoscopic partial pericardiectomy in 13 dogs

Thirteen dogs with cardiac tamponade resulting from pericardial effusion were prospectively evaluated to determine feasibility and outcome of thoracoscopic partial pericardiectomy. A lateral thoracoscopic approach allowed adequate exposure to remove a 4- to 5-cm-diameter section of pericardium in all dogs. Complete resolution of cardiac tamponade occurred in all dogs for which there was follow-up (11 dogs). Ten of 13 dogs (76.9%) had neoplastic pericardial effusion. One of these dogs remains alive at 220 days postoperatively and is asymptomatic. The mean survival of the remaining 9 patents with neoplastic effusion was 128 days (range, 14-544 days; median, 38 days). Three of 13 patients (23.1%) had idiopathic pericardial effusion. Two of these dogs remain alive at 585 and 1,250 days postoperatively. One dog with idiopathic pericardial effusion developed cardiomyopathy and was euthanized 18 days after the procedure. Results indicate that the procedure was technically successful in all dogs. No anesthetic complications occurred. Procedural complications included phrenic nerve transection (1 dog), lung laceration (1 dog), and moderate intraoperative bleeding (1 dog). No adverse clinical manifestations of the complications were apparent. We conclude that thoracoscopic partial pericardiectomy is technically feasible and offers several advantages over conventional open thoracic surgical pericardiectomy.     

Validation of an adenosine deaminase assay and its use in the evaluation of body fluids in dogs

Adenosine deaminase activity (ADA) (EC 3.5.4.4) was determined according to the method of Slaats and associates in the autoanalyzer Hitachi 705.(1) The analytical quality was controlled. Accuracy was tested by supplementing a sample with an ADA solution. The measured difference of ADA was close to the calculated one. The within-run and between-run precision of the method was sufficient. The detection limit was 1 U/l. ADA measurements were set in relation to a canine plasma pool and expressed as a percent to achieve reproducibility due to the lack of a commercial ADA standard. Body cavity effusions of 156 dogs were examined. The ADA of neoplastic effusions and the ADA of cardiac congestive effusions differed highly significantly (p < 0.001) in pleural and in peritoneal effusions. A discrimination value of 60% for pleural and a discrimination value of 100% ADA for peritoneal effusions separated neoplastic from cardiac congestive effusions. ADA determination in the serum of dogs did not contribute to the etiological differentiation of effusions. The elevation of ADA seemed to originate from the effusion, because the ratio of ADA (effusion/serum) was relatively high in cases of canine neoplasia. In this analysis the ADA in body cavity effusions of dogs was determined for the first time.     

Measurement of plasma atrial natriuretic peptide as an indicator of prognosis in dogs with cardiac disease

Twenty-three dogs with heart failure were evaluated in a 12-month study by measuring baseline plasma atrial natriuretic peptide (ANP) concentrations. Ten dogs were classified as having mild to moderate cardiac disease (group 1) and 13 dogs were classified as having severe cardiac disease (group 2). The mean plasma ANP concentration for the group 1 dogs was 64 +/- 45 pg/mL and for the group 2 dogs, 328 +/- 122 pg/mL. The median survival time (1,095 d) for group 1 dogs was significantly greater (P < 0.05) than for group 2 dogs (58 d). A significantly (P < 0.05) greater median survival was noted for dogs with plasma ANP < 95 pg/mL (1095 d) compared with those with ANP > 95 pg/mL (58 d). Plasma ANP concentrations are a potential noninvasive predictor of survival in dogs with heart failure.     

Evaluation of the presence of selected viral and bacterial nucleic acids in pericardial samples from dogs with or without idiopathic pericardial effusion

Many viruses have been identified in pericardial fluid and in tissue samples from humans with pericarditis by means of molecular diagnostics. In canine idiopathic pericardial effusion there is as yet no conclusive evidence to support the involvement of an infectious agent. This study was designed to investigate a possible relationship between idiopathic pericardial effusion in dogs and viruses most commonly encountered in humans affected with viral pericarditis. Coxsackievirus B3 RNA, influenza virus type A RNA, human adenovirus type 2 DNA, human cytomegalovirus DNA, and parvovirus B19 DNA were investigated using PCR on pericardial effusion samples and pericardial tissue specimens collected from 14 dogs with idiopathic pericardial effusion. PCR was also used to test for two bacteria, Borrelia burgdorferi and Chlamydia pneumoniae. The same microorganisms were also looked for in pericardial effusions or pericardial washes from 10 dogs with neoplastic pericardial effusion, and in samples collected from 10 dogs which died of a non-cardiac disease. One pericardial effusion sample from a dog with the idiopathic form of the disease tested positive for influenza virus type A and sequencing of the amplicon confirmed the PCR result. In another dog from the same group a cytomegalovirus was detected by PCR in the effusion, but sequencing showed this to be a false-positive result. The genomes of the microorganisms investigated were not detected in neoplastic effusions or pericardial washes. The results indicate that viral and bacterial DNA/RNA of relevance for human pericarditis is rare in pericardial samples from dogs with idiopathic pericardial effusion. The finding of influenza type A viral RNA in pericardial fluid from one dog with the idiopathic form of the disease warrants further investigation.     

Endostatin concentrations in healthy dogs and dogs with selected neoplasms

Endostatin prevents angiogenesis and tumor growth by inhibiting endothelial cell proliferation and migration. The purpose of this study was to determine serum endostatin concentrations in 53 healthy dogs and in 38 dogs with confirmed malignant neoplasms. Endostatin concentration was determined with a competitive enzymatic immunoassay (EIA) with rabbit polyclonal antibody generated against a recombinant canine endostatin protein. Both the presence of cancer and increasing age were associated with increased serum concentration of endostatin. Endostatin concentration in healthy dogs was 87.7 +/- 3.5 ng/mL. Upper and lower limits of the reference range for serum endostatin concentration in healthy dogs were 60 and 113 ng/mL. Dogs with lymphoma (LSA) and hemangiosarcoma (HSA) had endostatin concentrations of 107 +/- 9.3 ng/mL. In conclusion, this study demonstrates that endostatin can be quantified in dogs and that endostatin concentrations are high in dogs with HSA and LSA.     

Diagnostic value of pericardial fluid analysis in the dog

The physical, chemical, and cytologic characteristics of 50 pericardial effusions were reviewed to determine their value to the clinician for distinguishing a variety of pericardial disorders in the dog. Pericardial fluid analysis allowed identification of chylous and bacterial pericardial effusions. Overlap in the ranges of RBC counts, nucleated cell counts, and protein concentrations between dogs with neoplastic and nonneoplastic disorders precluded identification of the cause of the effusion. Of 19 neoplastic effusions, 74% were not detected on the basis of cytologic findings and 13% of 31 nonneoplastic effusates were falsely reported as positive or suspect for a neoplasm. It was concluded that pericardial fluid analysis, including cytologic examination, did not reliably distinguish neoplastic from nonneoplastic disorders.     

Can malignant and inflammatory pleural effusions in dogs be distinguished using computed tomography?

Computed tomography (CT) is the primary imaging modality used to investigate human patients with suspected malignant or inflammatory pleural effusion, but there is a lack of information about the clinical use of this test in dogs. To identify CT signs that could be used to distinguish pleural malignant neoplasia from pleuritis, a retrospective case‐control study was done based on dogs that had pleural effusion, pre‐ and postcontrast thoracic CT images, and cytological or histopathological diagnosis of malignant or inflammatory pleural effusion. There were 20 dogs with malignant pleural effusion (13 mesothelioma, 6 carcinoma; 1 lymphoma), and 32 dogs with pleuritis (18 pyothorax; 14 chylothorax). Compared to dogs with pleuritis, dogs with malignant pleural effusions were significantly older (median 8.5 years vs. 4.9 years, P = 0.001), more frequently had CT signs of pleural thickening (65% vs.34%, P = 0.05), tended to have thickening of the parietal pleura only (45% vs. 3%, P = 0.002) and had more marked pleural thickening (median 3 mm vs. 0 mm, P = 0.03). Computed tomography signs of thoracic wall invasion were observed only in dogs with malignant pleural effusions (P = 0.05). There were no significant differences in pleural fluid volume, distribution or attenuation, degree of pleural contrast accumulation, amount of pannus, or prevalence of mediastinal adenopathy. Although there was considerable overlap in findings in dogs with malignant pleural effusion and pleuritis, marked thickening affecting the parietal pleural alone and signs of thoracic wall invasion on CT support diagnosis of pleural malignant neoplasia, and may help prioritize further diagnostic testing.     

Evaluation of cholesterol and triglyceride concentrations in differentiating chylous and nonchylous pleural effusions in dogs and cats

Serum and pleural fluid cholesterol and triglyceride concentrations and cholesterol/triglyceride ratios were determined in 9 dogs and 9 cats with pleural effusion (8 nonchylous, 10 chylous). The pleural fluid triglyceride concentrations were significantly higher (P less than 0.05) and the pleural cholesterol/triglyceride ratios were significantly lower (P less than 0.05) in chylous effusions than in nonchylous effusions in all animals. There were no differences in serum cholesterol and triglyceride concentrations and serum cholesterol/triglyceride ratios for chylous and nonchylous effusions in either species. There also were no differences in pleural fluid cholesterol concentrations between the 2 groups in the dog or cat. It was concluded that determinations of cholesterol/triglyceride ratios may be an accurate method for helping distinguish chylous from nonchylous effusions in dogs and cats.     

Analysis of Factors Affecting Survival in Dogs With Aortic Body Tumors

OBJECTIVE: To evaluate the effect of perioperative and operative variables on survival time in dogs with aortic body tumors. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Twenty-four client-owned dogs with histologically confirmed aortic body tumor. METHODS: Seventy-eight patient records of dogs seen at the University of Illinois Veterinary Teaching Hospital between 1989 and 1999 with a diagnosis of a heart-base mass were reviewed. Dogs without histologic conformation of an aortic body tumor were excluded. Age; sex; breed; the presence of pleural effusion, pericardial effusion, or abdominal effusion; evidence of cardiac arrhythmias; evidence of distant metastasis; treatment with pericardectomy; treatment with chemotherapy; and time from diagnosis until euthanasia or death were recorded on a spreadsheet. Cox proportional-hazard ratios were used to calculate the relationship of risk variables to survival time. Median survival time was determined using life-table analysis. RESULTS: Twenty-four dogs met the criteria for inclusion in the study. The median age of dogs with aortic body tumors was 9 years. All dogs had a surgical biopsy performed. Fourteen dogs had a pericardectomy at the time of the biopsy procedure. Of all factors analyzed, only treatment with pericardectomy had a significant influence on survival (P =.0029). Dogs that had pericardectomy survived longer (median survival, 730 days; range, 1-1,621 days) compared with dogs that did not have pericardectomy (median survival, 42 days; range, 1-180 days). This finding was independent of the presence or absence of pericardial effusion at the time of surgery. CLINICAL RELEVANCE: Dogs that are diagnosed with aortic body tumors may benefit from a pericardectomy at the time of surgical biopsy.     

Serum concentrations of monocyte chemoattractant protein‐1 in healthy and critically ill dogs

Background: The chemokine monocyte chemoattractant protein‐1 (MCP‐1) is a primary regulator of monocyte mobilization from bone marrow, and increased concentrations of MCP‐1 have been associated with sepsis and other inflammatory disorders in critically ill people. The relationship between MCP‐1 and disease in dogs has not been evaluated previously. Objective: The purpose of this study was to assess serum concentrations of MCP‐1 in healthy dogs, dogs in the postoperative period, and critically ill dogs. We hypothesized that MCP‐1 concentrations would be significantly increased in critically ill dogs compared with postoperative or healthy dogs. Methods: Serum concentrations of MCP‐1 were measured in 26 healthy control dogs, 35 postoperative dogs, and 26 critically ill dogs. Critically ill dogs were further subgrouped into dogs with sepsis, parvovirus gastroenteritis, immune‐mediated hemolytic anemia, and severe trauma (n=26). MCP‐1 concentrations were determined using a commercial canine MCP‐1 ELISA. Associations between MCP‐1 concentrations and disease status were evaluated statistically. Results: MCP‐1 concentration was significantly higher in critically ill dogs (median 578 pg/mL, range 144.7–1723 pg/mL) compared with healthy dogs (median 144 pg/mL, range 4.2–266.8 pg/mL) and postoperative dogs (median 160 pg/mL, range 12.6–560.4 pg/mL) (P<.001). All subgroups of critically ill dogs had increased MCP‐1 concentrations with the highest concentrations occurring in dogs with sepsis. However, differences among the 4 subgroups were not statistically significant. Conclusion: Critically ill dogs had markedly increased serum concentrations of MCP‐1 compared with postoperative and healthy dogs. These results indicate that surgery alone is not sufficient to increase MCP‐1 concentrations; thus, measurement of MCP‐1 may be useful in assessing disease severity in critically ill dogs.     

Plasma Taurine Concentrations in Normal Dogs and in Dogs With Heart Disease

Plasma taurine concentrations were determined in 76 dogs with dilated cardiomyopathy (DCM), 28 dogs with acquired valvular disease (AVD), and 47 normal (control) dogs. The data were collected at 2 referral centers. The Animal Medical Center, New York, NY (AMC), and the University of California, Davis (UCD), and the studies were conducted independently. Different anticoagulants (sodium citrate at AMC and lithium heparin at UCD) were used to collect the plasma samples. Paired analysis of samples showed a significant difference in plasma taurine concentrations, depending on the anticoagulant used. Consequently, results from each clinic were analyzed separately. Plasma taurine concentrations were significantly higher in dogs with AVD (median, 133 nmol/mL; range, 25 to 229 nmol/mL) than in control dogs (median, 63 nmol/mL; range 44 to 224 nmol/mL) and dogs with DCM (median, 72 nmol/mL; range, 1 to 247 nmol/mL) at AMC (P= .001). The number of dogs with AVD at UCD was too small to draw meaningful conclusions. At UCD, the median plasma taurine concentration was 98 nmol/mL (range, 28–169 nmol/mL) in dogs with AVD, 75 nmol/mL (range, 0.1–184 nmol/mL) in dogs with DCM, and 88 nmol/mL (range 52–180 nmol/mL) in control dogs. There were no significant differences in plasma taurine concentrations between dogs with DCM and the control dogs at either hospital. Congestive heart failure and administration of cardiac medication had no significant effect on plasma taurine concentrations. Plasma taurine concentration was low (<25 nmol/mL) in 17% (13/76) of the dogs with DCM. Seven of the 13 dogs with low plasma taurine concentrations were Cocker Spaniels or Golden Retrievers. It was concluded that most dogs with DCM do not have low plasma taurine concentrations. However, certain breeds or individual dogs may have low plasma taurine concentrations in association with DCM. Whether this association is causal or not is unknown. The significance of the high plasma taurine concentrations in dogs with AVD is also unknown.     

Long-term survival of 23 dogs with pericardial effusions

Twenty-three dogs with pericardial effusions were identified from case records made between 1992 and 2000. Fourteen of the 23 were diagnosed with idiopathic pericardial effusions, and three of these were treated successfully by one pericardiocentesis. In the remaining 11 cases the pericardial effusion recurred; six cases were managed long-term by either two (three cases), three (two cases), or 11 repeated pericardiocenteses, and the remaining five were treated by pericardiectomy. The median survival time of the six dogs treated by repeated pericardiocentesis was five years and nine days.     

Endostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases

To evaluate the relationship between endostatin and vascular endothelial growth factor (VEGF) in cancers of dogs, circulating concentrations of these 2 tumor-associated markers were measured prospectively in healthy dogs (n = 44), dogs with tumors (n = 54), and dogs with nonneoplastic diseases (n = 42 for endostatin; n = 16 for VEGF). A canine-directed enzyme-linked immunosorbent assay kit was used for determination of endostatin, and a human-directed kit was validated for detection of canine VEGF. Concentrations of endostatin for all dogs were 28-408 ng/mL. Increasing serum endostatin concentration was associated with increasing age (P = .0396). Concentrations of endostatin were not different among groups of dogs (P = .1989) when adjusted for age. Mean endostatin concentrations for all dogs were higher in dogs (P = .0124) with detectable VEGF concentrations. Endostatin concentrations, when corrected for age, were related to decreasing PCV (P = .032) but not white blood cell count (P = .225) or platelet count (P = .1990). Measurable VEGF (> or = 2.5 pg/mL) was detected in 3 (7.0%) of 43 healthy dogs. Dogs with tumors had detectable VEGF in 24 (44%) of 54 dogs, with concentrations ranging from 2.5-274 pg/mL; only 1 dog with a nonneoplastic disease process had detectable VEGF. VEGF concentrations for all dogs after correcting for age, endostatin, and disease categories were associated with increased white blood cell count (P = .0032) and platelet counts (P = .0064) and decreased PCV (P = .0017). Linkage between increased endostatin and VEGF concentrations suggests that similar factors may influence concentrations of these markers. Further evaluation of endostatin and VEGF associations in dogs with tumors may provide information on the extent and progression of the disease.     

Pleural effusions

The key to effective evaluation of pleural effusions lies in an understanding of the dynamic nature of its formation and alteration. Trying to fit a specimen neatly into a distinct diagnostic category will not only lead to frustration, but is often unnecessary or incorrect. Combined etiologies are common, and although the possibilities are infinite, certain patterns often present themselves: inflammation frequently complicates congestive failure and neoplasms, hemorrhage is common in neoplastic and chylous effusions, neoplastic effusions may cause transudation from venous obstruction or pericardial stricture, and sepsis is frequently secondary to traumatic effusions. In the presence of atypical findings and the establishment of one cause of pleural effusion, one cannot rule out other operative conditions.     

Activation of the Renin-Angiotensin System in Dogs With Asymptomatic and Mildly Symptomatic Mitral Valvular Insufficiency

The renin-angiotensin system has important pathophysiologic implications in the development of congestive heart failure. The activity of the renin-angiotensin system early in the course of heart disease and heart failure in dogs was evaluated by measuring the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in 18 Cavalier King Charles Spaniels with asymptomatic or mildly symptomatic mitral valvular insufficiency, and in 18 healthy Cavalier King Charles Spaniels. All dogs were unmedicated and had no other diseases. The PRA was high in the dogs with mitral valvular insufficiency (median 3.44 ng/mL/h, interquartile interval 2.59 to 8.66 ng/mL/h) compared with the controls (median 2.51 ng/mL/h, interquartile interval 1.44 to 3.58 ng/mL/h). The PAC was also higher in the dogs with mitral insufficiency (median 53 pg/mL, interquartile interval 33 to 138 pg/mL) than in the control group (median 27 pg/mL, interquartile interval 11.5 to 54 pg/mL). However, there was considerable overlap between the 2 groups in both PRA and PAC. It was concluded from these data that there is early activation of the renin-angiotensin system in some Cavalier King Charles Spaniels with mitral valvular insufficiency. Further prospective studies are needed to determine if early intervention with angiotensin-converting enzyme inhibitors will be valuable in this group of patients.