The Effect of Hydration Status on the ... - Wiley Online Library

J Vet Intern Med 2007;21:1008–1015

The Effect of Hydration Status on the Echocardiographic Measurements of Normal Cats F.E. Campbell and M.D. Kittleson Background: Diagnosis of cardiomyopathy of cats is based on 2-dimensional (2D) echocardiography. However, circulating fluid volume largely determines diastolic cardiac chamber dimensions, and reduced diastolic volume in other species results in what has been called ‘‘pseudohypertrophy of the ventricular myocardium.’’ Hypothesis: Altered hydration produces changes on 2D echocardiography that may confound the diagnosis or severity assessment of cardiomyopathy of cats. Animals: Ten normal colony-sourced mixed breed cats were included. Methods: Cats were examined by echocardiography at baseline and at completion of 3 protocols (volume depletion and maintenance-rate and anesthetic-rate IV fluid administration) applied in randomized crossover design with a 6–7 day washout period. Results: Volume depletion increased diastolic left ventricular interventricular septal (IVSd) and free wall diameter (4.5 6 0.4 to 5.8 6 0.6 mm; P , .001) with wall thickness exceeding 6 mm in 4 cats. Diastolic left ventricular internal diameter (LVIDd) decreased, and reduction in systolic left ventricular internal diameter (LVIDs) produced end-systolic cavity obliteration in 7 cats. Left-atrial-to-aortic-root ratio (LA : Ao, 1.4 6 0.2 to 1.2 6 0.1, P , .05) and left atrial area in diastole (LAAd) decreased with volume depletion. Maintenance-rate IV fluid administration increased LAAd and fractional shortening (FS%). Anesthetic-rate IV fluid administration increased LVIDd, FS%, LAAd, and LA : Ao ratios (to 1.7 6 0.1, P , .01), producing an LA : Ao ratio above normal limits in 6 cats. A systolic heart murmur developed with administration of fluid at maintenance (n 5 1) and anesthetic rates (n 5 6). Conclusions: Altered hydration status produces changes in the echocardiographic examination of normal cats that may lead to an erroneous diagnosis of cardiomyopathy or mask its presence. Hydration status should be considered during echocardiographic examination in cats. Key words: Dehydration; Fluid administration; Heart murmur; Pseudohypertrophy; Volume depletion.

he cardiomyopathies of cats include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy.1–4 The diagnosis of cardiomyopathy of cats usually is made by echocardiography. Echocardiographic diagnosis of HCM is based on the presence of left ventricular (LV) concentric hypertrophy, specifically, LV free wall or interventricular septal thickness that equals or exceeds 6 mm in diastole.2 Other findings on 2dimensional (2D) echocardiography in cats with HCM may include papillary muscle hypertrophy, reduced LV diastolic chamber dimension, end-systolic cavity obliteration, systolic anterior motion of the mitral valve, and left atrial (LA) enlargement. The degree of both LA dilatation and LV concentric hypertrophy are of prognostic importance.2,5 LA dilatation results primarily from LV diastolic dysfunction, and severe LA dilatation reflects increased LV filling pressure that is sufficient to produce congestive failure.6 LA dilation also reduces the velocity of blood flow through the atrium,7 which may

T

From the Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA. Previously presented as an abstract at the European College of Veterinary Internal Medicine annual meeting in Glasgow, Scotland, September 2005. Reprint requests: F.E. Campbell, Veterinary Teaching Hospital, University of Queensland, St Lucia, QLD 4072, Australia; e-mail: [email protected]. Submitted January 11, 2007; Revised March 7, 2007; Accepted April 12, 2007. Copyright E 2007 by the American College of Veterinary Internal Medicine 0891-6640/07/2105-0018/$3.00/0

increase the risk of thromboembolism in cats with HCM.8 Diagnosis of other forms of cardiomyopathy in cats likewise is largely dependent on 2D echocardiographic examination. Although the objective criteria by which each of the cardiomyopathies of cats is distinguished are not well defined, atrial dilatation as a nonspecific marker of increased ventricular filling pressures is fundamental in the diagnosis and severity assessment of myocardial disease.9,10 More advanced echocardiographic techniques such as pulsed-wave Doppler transmitral and pulmonary venous flow profiles and pulsedwave and color Doppler tissue imaging have been used to evaluate diastolic function in cats.11–14 However, additional studies are required before the value of these techniques in the routine diagnosis of the cardiomyopathies of cats can be determined. Circulating fluid volume is one of the major determinants of diastolic cardiac chamber dimensions.15 Furthermore, pseudohypertrophy (an increase in the thickness of the LV walls with no change in mass) is documented in other species in association with decreased diastolic volume secondary to hypovolemia16 and cardiac tamponade.17 Studies are lacking in cats, but similar effects of circulating fluid volume on echocardiographic measurements may compromise the accuracy of echocardiographic examination in the diagnosis of cardiomyopathy. The aim of this study was to quantify the effects of mild-to-moderate volume depletion and 2 commonly used IV fluid-administration protocols, by a randomized crossover trial on the echocardiographic measurements of normal cats and to identify changes that may confound the diagnosis or severity assessment of the cardiomyopathies of cats.

Echocardiographic Effects of Altered Hydration

Materials and Methods Animals Ten normal colony-sourced mixed breed cats were studied. Cats were cared for according to the principles outlined in the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and their use was approved by the Institute for Animal Care and Use Committee, University of California, Davis. Cats were identified as healthy and free from cardiovascular disease by physical examination, serum biochemistry, PCV, urinalysis, thoracic radiography, electrocardiography, and echocardiography. To control for any dietary influence on circulating fluid volume,18 we fed cats a sole diet of commercial adult maintenance dry kibblea ad libitum for at least 7 days before beginning the study and throughout the study duration, except on assessment days when food was withheld.

Baseline Assessment Cats were identified as eligible for inclusion in the study if they met the following criteria: (1) Physical examination results were normal, and thoracic auscultation identified a regular heart rhythm and no heart murmur; (2) serum biochemistry, PCV, and urinalysis results were within the reference ranges for normal cats; (3) subjective interpretation of thoracic radiographs indicated normal pulmonary parenchyma, vasculature, and cardiac silhouette; (4) a 6lead ECG identified a sinus rhythm or sinus tachycardia with a mean electrical axis between 210 and +160 degrees; and (5) echocardiography identified LV free wall (LVFWd) and interventricular septal wall (IVSd) dimensions during diastole of ,6 mm, 2D LA to aortic (Ao) ratio (LA : Ao) of # 1.5, no or only trivial insufficiencies of the pulmonic and tricuspid valves, no insufficiency of the aortic and mitral valves, ventricular outflow velocities determined by a pulsed-wave Doppler of ,1.5 m/s, and pulsedwave tissue Doppler velocity of the lateral mitral valve annulus determined from the left apical 4-chamber view of .10 cm/s. After the initial echocardiographic examination, by which cats were identified as eligible for inclusion in the study, acepromazine (0.1 mg/kg) and hydromorphone (0.1 mg/kg) were administered by SC injection and echocardiography was repeated 20–40 minutes later. This repeated echocardiogram then was compared with the initial echocardiogram to identify any effects of sedation, which was subsequently administered to facilitate accurate echocardiographic examination at the completion of each experimental protocol.

Study Protocol In randomized crossover design, 3 protocols were employed and included volume depletion and IV administration of isotonic saline at 2 fluid rates with a 6–7 day washout between protocols. At the start of each protocol, cats were sedated, the urinary bladder was emptied by manual compression, body weight was determined, and an IV catheter was placed in the cephalic vein from which blood was obtained for determination of PCV and total protein (TP) and through which saline or furosemide could subsequently be administered.

Volume-Depletion Protocol b

Furosemide was administered at 2–4 mg/kg IV every 1–2 hours until either a 7–10% reduction in body weight occurred, or if weight reduction was ,7%, a cumulative dose of 14 mg/kg furosemide had been administered over 7 hours. Food and water were withheld from the start of the protocol, and cats were examined and weighed before each furosemide injection to identify

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when the protocol end-point was reached. At the protocol endpoint, a final physical examination including thoracic auscultation was performed. Cats then were sedated, blood samples were collected for determination of PCV and TP, the urinary bladder was manually expressed, and final body weight was determined before repeated echocardiographic examination. Immediately after this protocol was completed, isotonic saline was administered over several hours according to standard fluid therapy guidelines19 until cats were rehydrated and body weight had returned to baseline.

IV Fluid Protocols c

Isotonic saline was administered by cephalic catheter and automated infusion pump at 2 rates, a standard maintenance rate of 2.5–3 mL/kg per hour19 (maintenance rate) and a rate typically administered during anesthesia and surgery of 10 mL/kg per hour19 (anesthetic rate). Saline was administered at the maintenance rate for 24 hours and at the higher anesthetic rate for 7 hours such that a total volume of 70 mL/kg was administered for each protocol. Water was offered ad libitum. Food was withheld from the start of both protocols until completion. At completion of IV fluid administration, a final physical examination including thoracic auscultation was performed. Cats then were sedated, blood samples were collected for determination of PCV and TP, the urinary bladder was manually expressed, and final body weight was determined before repeated echocardiographic examination.

Echocardiography Echocardiographic examinationd was performed with the cat lightly restrained in lateral recumbency on a purpose-designed table, which allowed placement of the transducere on the dependent side of the thorax. Electrodes attached to the skin overlying the stifles and right elbow allowed the simultaneous recording of a lead II ECG that was displayed on the ultrasound monitor. All examinations were performed by the same experienced echocardiographer (F.E.C), who was not blinded. Dimensional measurements of the LV were made from a right parasternal short-axis view20 at the level of the papillary muscles from 2D images using the leading-edge method21 and included IVSd and LVFWd and the internal diameter of the LV in diastole and systole (LVIDd and LVIDs, respectively). Measurements of the LV chamber area at end-diastole (LVCAd) and systole (LVCAs) were made from 2D echocardiographic images at the same level by tracing around the inner edge of the endocardial border including the papillary muscles. Calipers were positioned at the onset of the QRS complex on the simultaneously recorded ECG for determination of diastolic measurements, and systolic measurements were made from the frame with the smallest chamber dimension immediately preceding ventricular expansion. Using a modification of a previously described technique,22 we determined LA and Ao dimensions from a right parasternal 2D short-axis view at the heart base by directing the calipers in a line along the commissure between the noncoronary and the left coronary aortic valve cusps through the aorta and left atrium. LA area in diastole (LAAd) was determined from the same view by tracing around the endocardial border. All LA and Ao measurements were determined immediately before atrial systole at the onset of the P wave on the ECG. Baseline echocardiographic examination also included colorflow Doppler assessment of all valves and pulsed-wave Doppler assessment of both outflow tracts to identify valvular insufficiencies or outflow obstruction, which then would exclude an individual cat from study entry. Diastolic function was evaluated at baseline by determination of the early diastolic velocity of the lateral mitral annulus from the left parasternal 4-chamber view by

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Campbell and Kittleson

Table 1. Echocardiographic measurements (mean 6 SD) of normal cats (n 5 10) at baseline before and 20–40 minutes after sedation with SC injection of acepromazine (0.1 mg/kg) and hydromorphone (0.1 mg/kg).* Echocardiographic Parameter Heart rate (bpm) IVSd (mm) LVFWd (mm) LVIDd (mm) LVIDs (mm) FS (%) LA (mm) Ao (mm) LA : Ao ratio

Before Sedation 208 4.5 4.4 13.4 6.6 50 12.1 8.5 1.4

6 6 6 6 6 6 6 6 6

17 0.3 0.4 2.3 1.7 9 0.6 0.6 0.1

After Sedation 225 4.5 4.4 13.4 6.4 49 11.7 8.5 1.4

6 6 6 6 6 6 6 6 6

34 0.4 0.3 1.8 1.3 5 1.0 0.7 0.1

Results Animals The 10 normal mixed breed cats consisted of 8 females and 2 males. Median age of the group was 3 years (range, 2–7 years), and body weight was 3.8 6 0.8 kg.

Sedation

IVSd, diastolic interventricular septal diameter; LVFWd, left ventricular free wall diameter; LVIDd, diastolic left ventricular internal diameter; LVIDs, systolic left ventricular internal diameter; FS%, fractional shortening; LA, left atrium; Ao, aorta. * No significant differences were identified.

pulsed-wave tissue Doppler imaging. The gate of the 12-MHz transducer was placed perpendicular to myocardial movement; the Nyquist limit was set at 10–15 cm/s; sweep speed, 100 cm/s; and filter, at 50 MHz. Peak diastolic velocity was measured from early diastolic mitral annular velocity or summated early and late diastolic mitral annular velocity, and values exceeding 10 cm/s were accepted as normal and necessary for study inclusion.13 All measurements were made from 4 to 5 consecutive cardiac cycles and averaged.

Statistical Analysis All calculations were performed using statistical software.f Data were analyzed using one-way repeated measures analysis of variance. All values including those obtained at baseline before and after sedation and at the completion of each protocol after sedation were compared using Bonferroni post hoc tests. Identification of similar values at baseline before and after sedation validated the use of sedation for all subsequent echocardiographic examinations, which are reported relative to the baseline echocardiogram obtained under sedation. Values are given as the median and range when non-normally distributed or as the mean 6 standard deviation when normally distributed. A P value , .05 was accepted as significant.

Measurements obtained from the initial echocardiogram, for which cats were not sedated and from which eligibility for inclusion in the study was determined, were similar to those taken from the baseline echocardiogram, which was repeated after sedation (Table 1). This design excluded any effects of sedation itself and validated comparison of subsequent echocardiograms performed on sedated cats at the completion of each protocol with the baseline echocardiogram.

Volume-Depletion Protocol Thoracic auscultation of cats at completion of this protocol was normal, and heart rate was similar to that at baseline. Volume depletion produced a mean reduction in body weight of 5% (P , .001) and mean increases in both PCV and TP of 24% (P , .001, Table 2). Significant changes in echocardiographic measurements included increases in both IVSd and LVFWd (Table 3). The LV diastolic wall dimension exceeded 6 mm in 4 cats (Fig 1). Reduction in both LVIDd and LVIDs occurred and resulted in unchanged FS%. Similarly, both LVCAd and LVCAs were decreased, and in 6 cats, end-systolic cavity obliteration was observed. A reduction in LA size was reflected by significant reductions in LA : Ao ratio and LAAd (Fig 2).

Maintenance-Rate IV Fluid Protocol At completion of this protocol, a grade II/VI sternal systolic heart murmur was auscultated in 1 cat, whereas heart rate remained unchanged. Body weight was not altered, but significant reductions in both PCV and TP occurred (Table 2). No change was identified in the thickness of the LV walls or LV chamber dimensions in diastole (LVIDd or LVCAd), but a significant reduction in LVIDs occurred resulting in an increase in calculated

Table 2. Body weight, PCV, and TP (mean 6 SD) of cats (n 5 10) at baseline and at completion of each of 3 protocols.

Body weight (kg) PCV (%) TP (g/dL)

Baseline

Volume Depletion

3.8 6 0.8 37 6 3 7.6 6 0.5

3.6 6 0.8* 46 6 5* 9.4 6 0.4*

TP, total protein. * P , .001 compared with baseline. ** P , .05 compared with baseline.

Maintenance-Rate IV Fluid Anesthetic-Rate IV Fluid Protocol Protocol 3.8 6 0.8 32 6 3** 6.6 6 0.5*

3.9 6 0.9 29 6 6* 6.3 6 0.4*


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Table 3. Echocardiographic measurements (mean 6 SD) from cats (n 5 10) at baseline and at completion of each of 3 protocols. Echocardiographic Parameter

Baseline

Heart rate (bpm) IVSd (mm) LVFWd (mm) LVIDd (mm) LVIDs (mm) FS (%) LVCAd (cm2) LVCAs (cm2) LA (mm) Ao (mm) LA : Ao ratio LAAd (cm2)

225 4.5 4.4 13.4 6.4 49 1.4 0.2 11.7 8.5 1.4 1.4

6 6 6 6 6 6 6 6 6 6 6 6

Volume Depletion

34 0.4 0.3 1.8 1.3 5 0.4 0.1 1.0 0.7 0.1 0.1

230 5.8 5.6 9.4 4.4 50 0.7 0.05 9.7 7.9 1.2 1.0

6 6 6 6 6 6 6 6 6 6 6 6

21 0.6* 0.6* 1.7* 1.2* 13 0.3* 0.06** 1.2* 0.6 0.1{ 0.2{

Maintenance-Rate IV Fluid Protocol 226 4.5 4.5 13.0 4.9 62 1.3 0.1 12.0 8.4 1.4 1.8

6 6 6 6 6 6 6 6 6 6 6 6

26 0.3 0.3 1.5 1.3{ 10** 0.2 0.1 1.2 0.5 0.1 0.5{

Anesthetic-Rate IV Fluid Protocol 241 4.3 4.5 14.4 5.9 59 1.6 0.2 13.8 8.3 1.7 2.3

6 6 6 6 6 6 6 6 6 6 6 6

22 0.4 0.5 2.0{ 1.2 7{ 0.3{ 0.1 0.8* 0.6 0.1* 0.6*

IVSd, diastolic interventricular septal diameter; LVFWd, diastolic left ventricular free wall diameter; LVIDd, diastolic left ventricular internal diameter; LVIDs, systolic left ventricular internal diameter; FS%, fractional shortening; LA, left atrium; Ao, aorta; LVCAd, left ventricular chamber area at end-diastole; LVCAs, left ventricular chamber area at systole; LAAd, left atrial area in diastole. * P , .001 compared with baseline. ** P , .01 compared with baseline. { P , .05 compared with baseline.

FS%. Both the LA diameter and LA : Ao ratio were unchanged; however, LAAd was significantly increased.

Anesthetic-Rate IV Fluid Protocol Administration of saline at the higher rate did not alter heart rate, but 6 cats developed a grade II-III/VI sternal systolic heart murmur. Both PCV and TP were significantly reduced at completion of this protocol (Table 2). Changes identified by echocardiography included increased LVIDd and LVCAd, which, without concurrent alteration in systolic LV chamber dimensions, produced an increase in FS%. The size of the LA was increased as reflected by an increase in the LA diameter, LA : Ao ratio, and LAAd. In 6 cats, the LA : Ao ratio exceeded the upper limit of normal of 1.5 (Fig 2).

Discussion This study determined that echocardiographic measurements of normal cats are significantly altered by changes in circulating fluid volume. Furthermore, the echocardiographic changes produced by volume depletion and IV fluid administration may be sufficient to confound the diagnosis or severity assessment of cardiomyopathy in cats. Comparison of the LA to the Ao root is a widely accepted technique that facilitates assessment of LA size independent of body size. Numerous studies describe methods of indexing the LA to the Ao via M-mode4,23–25 and 2D echocardiography,26,27 and although some variation exists, a ratio of # 1.5 is expected in normal cats. An increase in LA size and an LA : Ao . 1.5 occurs in response to increased LV diastolic filling pressure arising from any form of myocardial disease, and in cats with HCM, LA dilatation is a negative prognostic indicator.2,5

In this investigation, LA size was altered by all 3 protocols. Volume depletion produced a significant reduction in LAAd and LA : Ao ratio. If similar reductions occur in cats with cardiomyopathy that are dehydrated, these changes may result in underestimation of disease severity. Furthermore, treatment with furosemide for suspected cardiogenic edema or pleural effusion may reduce LA size. This reduction in LA size then suggests lower ventricular filling pressures and may preclude identification of myocardial disease sufficient to account for pulmonary edema. Administration of saline at the maintenance rate did not alter LA : Ao ratio but did alter LAAd, a measurement that includes the left auricle. If LA : Ao had been assessed by M-mode echocardiography with the measurement calipers transecting the left auricle rather than the body of the left atrium, the LA : Ao measurement also may have been increased.26 Administration of saline at the higher anesthetic rate produced increases in both LA : Ao and LAAd, and in the majority of cats, the LA : Ao ratio exceeded 1.5, a value accepted as indicative of the increased LV diastolic and LA pressures that develop in cardiomyopathies of cats. Variation in atrial size with changes in blood volume similarly is documented in humans. Increased LA size occurs with rapid IV fluid administration28,29 and is identified before ultrafiltration in chronically hemodialysed patients30 and in patients with long-standing fluid retention associated with hepatic cirrhosis.31 LV internal dimensions were altered by both the volume depletion and anesthetic-rate IV fluid protocols. Volume depletion produced reductions in both diastolic and systolic chamber dimensions such that FS% was unchanged. Studies of human patients treated with furosemide,32,33 hemodialysis,34 or dehydrated by exercise35 demonstrated reduced diastolic LV chamber dimension without concomitant effects on systolic

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Fig 1. Two-dimensional echocardiographic images obtained from the right parasternal short-axis view at the level of the papillary muscles at end-diastole in an individual cat at baseline (A) and at completion of the volume-depletion protocol (B), demonstrating the increase in interventricular septal and LV free wall diameter and reduction in diastolic LV internal diameter.

chamber dimension. However, phlebotomized infants36 and pigs16,37 develop reductions in both LV diastolic and systolic dimensions. The reduction in the LVIDs and LVCAs that occurred in volume-depleted cats in this study was sufficient to produce end-systolic cavity obliteration in 7 of the 10 cats. Cats with HCM also are frequently found to have reduced systolic chamber dimensions and end-systolic cavity obliteration2 because increased LV wall thickness may reduce diastolic luminal dimension and also confer a reduction in systolic wall stress (afterload).38 Administration of saline at the maintenance rate did not significantly alter diastolic LV dimensions. This finding was expected because administration of maintenance fluid requirements should be sufficient to meet ongoing metabolic fluid losses and maintain constant circulating fluid volume and preload. However, the significant reduction in LVIDs and subsequent increase in FS% were unexpected because afterload and intrinsic myocardial systolic function should remain unchanged.

Fig 2. Two-dimensional echocardiographic images obtained from the right parasternal short-axis view at the base of the heart demonstrating the left atrial area in diastole (square centimeters) determined in an individual cat by tracing around the endocardial surface of the left atrium at baseline (A) and at completion of the volume-depletion protocol (B) and anesthetic-rate IV fluidadministration protocol (C).

Administration of saline at the higher anesthetic rate increased LVIDd and, likewise, increased calculated FS%. Several studies report similar echocardiographic changes associated with increased circulating blood


volume. Isotonic saline given rapidly at high volumes to healthy dogs39 and humans40 significantly increases LV diastolic dimensions. Similarly, chronically increased blood volume increases LV diastolic dimensions in healthy human subjects fed an excessively high-sodium diet.18,41 An increase in LVFWd and IVSd occurred at completion of the volume-depletion protocol, and, in 4 cats, wall thicknesses exceeded 6 mm. It is widely accepted that LV diastolic wall thickness $ 6 mm is indicative of concentric hypertrophy.2,6,42 The exclusion of outflow obstruction, systemic hypertension, hyperthyroidism, and acromegaly then facilitates the diagnosis of HCM.6 Accordingly, 4 cats in the present study would have been falsely diagnosed with HCM as a result of pseudohypertrophy; consequently, volume depletion and dehydration should be included as exclusion criteria before a definitive diagnosis of HCM can be made in cats with increased LV wall thickness. The reason for the development of a heart murmur in 1 cat at completion of the maintenance-rate IV fluid protocol and in 6 cats at completion of the anestheticrate IV fluid protocol is unknown. Dynamic rightventricular outflow tract obstruction is a common cause of systolic heart murmurs in cats when the right ventricular outflow tract narrows during systole, as the free wall apposes the interventricular septum.43 It is reported to occur most commonly in cats that have concurrent comorbidities that confer a high cardiac output state or in cats that are dehydrated, because both conditions facilitate reduced ventricular systolic dimensions and favor obstructive apposition of the outflow tract walls. The right ventricular outflow tract was not evaluated by either 2D or color-flow Doppler echocardiography in cats in the present study except at baseline, but if the murmur was due to dynamic obstruction of the right-ventricular outflow tract, no murmur was evident at completion of the volume-depletion protocol when reduced chamber dimensions may have been most favorable for murmur development. Alternatively, a systolic murmur may have developed in cats after IV fluid administration due to an increase in the Reynolds number sufficient to cause turbulence of blood flow in the ventricular outflow tracts and great vessels. A reduction in blood viscosity may be expected to accompany the reduction in PCV of cats in this study,44 but modest reductions in PCV alone are unlikely to produce an increase in the Reynolds number sufficient to result in turbulent flow and murmur development.45 However, the increased stroke volume, reflected by increased LVIDd and unchanged LVIDs, through the outflow tracts and great vessels of constant diameter, imparts an increased velocity of blood flow, an increase in Reynolds number, and a propensity for turbulent flow. Pulsed-wave Doppler aortic or pulmonic flow profiles were not obtained in this study; however, studies in human subjects report similar changes in LVIDd in response to volume-loading, and an increase in peak outflow velocities has been documented.29 Cats that developed murmurs may have had increased aortic

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velocity, spectral dispersion of the pulsed-wave Doppler aortic flow profile, or both. A systolic murmur may have developed in cats in this study as a result of atrioventricular valvular insufficiency secondary to annular dilatation with increased cardiac chamber dimensions. Color Doppler echocardiographic interrogation of the mitral and tricuspid valves was not performed after baseline assessment in these cats, but significant valvular insufficiencies that resolve after dialysis have been documented in hypervolemic human patients.46 Each of the 3 protocols employed in this study was designed for relevance to commonly encountered clinical situations, but there are several factors that preclude the validity of direct comparisons. First, the echocardiographic changes identified in volume-depleted cats with a mean reduction in body weight of 5% may differ from those of cats with similar weight reductions produced by dehydration because of different effects on intravascular volume. Pharmacologic volume depletion by IV administration of furosemide is produced by drug inhibition of the sodium-potassium-chloride cotransporter in the thick ascending loop of Henle47 and loss of sodium and water. This natriuresis results primarily in a reduction of extracellular fluid of which intravascular volume is a component.48 Alternatively, dehydration, which is initially characterized by an extracellular water deficit due to excessive water loss, reduced water intake, or both is not accompanied by similar sodium loss. The resulting hypernatremia and hypertonicity of the extracellular fluid subsequently produces a relatively greater depletion of intracellular volume when fluid shifts from this larger fluid compartment to equilibrate osmolarity.48 Specifically, during dehydration, the majority of water loss is interstitial and intracellular, while intravascular volume is relatively preserved to maintain circulatory perfusion pressures.49 In addition, furosemide has a direct effect when given IV, which increases venous capacitance and may have contributed to decreased cardiac preload, independent of any alteration in body weight.50 The second factor precluding quantitative comparison of echocardiographic measurements of volumedepleted cats in the current study with cats clinically judged to be similarly dehydrated arises from limitations in clinical assessment of the degree of dehydration. Decreased skin turgor, dry tacky mucous membranes, and sunken globes were observed in volume-depleted cats (results not shown), signs by which dehydration would typically be estimated to be .8%,51 substantially greater than the measured 5% reduction in weight. Some studies in humans suggest that the clinical criteria by which hydration status is assessed overestimate the degree of dehydration by .3%,52,53 and 1 study in veterinary patients similarly demonstrated the inaccuracy of fluid-deficit estimation by physical examination.54 As such, cats evaluated to be 5% dehydrated by accepted clinical criteria are unlikely to demonstrate echocardiographic alterations as substantial as those demonstrated in this investigation.

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Fluid administration during anesthesia is designed to offset some of the vasodilatation and hypotension induced by anesthetic agents, provide metabolic fluid requirements, and compensate for insensible fluid losses including drying of surgically exposed tissues and loss of moisture through the respiratory tract.19 In the present study, administration of fluid IV to conscious cats not subjected to the fluid losses associated with surgery or hemodynamic alterations of anesthesia may be expected to exceed fluid necessary to maintain euvolemia, and identical echocardiographic alterations in anesthetized cats receiving similar fluid protocols may not be expected. One technical limitation of this study was that the echocardiographer was not blinded to the protocol each cat had received at the time of examination, and this may have biased the evaluation. In addition, betweenday intraobserver variability was not evaluated. However, previous studies in cats have reported low variability in echocardiography performed by similarly qualified investigators.27 In conclusion, this study showed that altered hydration status in normal cats produced changes in the echocardiographic measurements of the LV and LA. Pseudohypertrophy and end-systolic cavity obliteration developed with volume depletion, and LA size was reduced. Administration of IV fluids increased LV and LA diastolic dimensions, and several cats developed systolic heart murmurs. These changes may lead to an erroneous diagnosis of myocardial disease, confound the assessment of disease severity, or mask its presence. Hydration status should be considered during echocardiographic examination in cats.

Footnotes a

Purina Adult Feline Maintenance kibble Purina, St. Louis, MO Furosemide 5%, Phoenix Scientific Inc, St Joseph, MO c 0.9% NaCl 500 mL, Baxter, Deerfield, IL d HP Sonos 5500, Hewlett Packard, Andover, MA e 12 MHz f GraphPad Prism, GraphPad Software Inc, San Diego, CA b

Acknowledgments This study was performed at the Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, and was funded by the Center of Companion Animal Health, University of California, Davis.

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