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OBJECTIVE To investigate the relationship between invasively measured stroke volume (SV) and (1) esophageal Doppler-derived indices such as stroke distance (StrokeD), flow time corrected (FTc), stroke distance variation (SDV), and peak velocity variation (PVV); and (2) arterial load (AL) variables during evaluation of fluid responsiveness (FR) in anesthetized dogs undergoing sudden hemodynamic shifts in blood volume. ANIMALS 6 healthy male dogs. PROCEDURES Dogs were anesthetized with isoflurane, ventilated mechanically, and instrumented to undergo sequential, nonrandomized experimental stages. The dogs transitioned from normovolemia (NORMO-BL) to hypovolemia (30% blood loss; HYPO-30), followed by autologous blood transfusion, and then to hypervolemia (colloid bolus). During each stage, SV was quantified using pulmonary artery thermodilution and its relationship with StrokeD, FTc, SDV, and PVV; and AL variables such as effective arterial elastance (Ea), dynamic arterial elastance (Eadyn), and total arterial compliance (Ca) were established. RESULTS As SV decreased significantly during HYPO-30 compared to NORMO-BL, there was a significant (P < .001) decrease in StrokeD, FTc, and Ca, with simultaneous increases in SDV, PVV, Ea, and Eadyn. Upon restoration of blood volume, these values stabilized closer to NORMO-BL. A significant (P < .001) correlation was observed between SV and StrokeD, FTc, Ea, Eadyn, and Ca. CLINICAL RELEVANCE Minimally invasive StrokeD, FTc, SDV, and PVV act as SV surrogates and help assess FR during different blood volume stages in healthy dogs. During hypovolemia-induced hypotension, Ea, Eadyn, and Ca may be able to guide therapeutic decisions favoring improvement in blood pressure and SV.

Development of pulmonary hypertension is an independent predictor of poor outcome in dogs affected by myxomatous valvular degeneration (MMVD). Systolic pulmonary arterial pressure is routinely estimated by Doppler echocardiography applying the simplified Bernoulli equation to the velocity of tricuspid regurgitation (sPAP_D). The accuracy of this estimation is unknown in dogs with MMVD, but experimental studies suggest that the method is imperfect. In order to fill this knowledge gap we prospectively enrolled dogs affected by MMVD and cardiac remodeling - American College of Veterinary Internal Medicine (ACVIM) stages B2 and C MMVD for which treatment had been unchanged for at least one month. A flow-directed thermodilution monitoring catheter was percutaneously placed in the right jugular vein and advanced to the main pulmonary artery. Pulmonary arterial systolic pressure was recorded through this catheter connected to a pressure-transducer and data acquisition-analysis system (sPAP_C). A second operator simultaneously acquired tricuspid regurgitant velocity spectra to calculate sPAP_D. Each operator was blinded to the result of the other technique. Twenty dogs were enrolled. Technical difficulties prevented catheterization in 2 dogs. Eighteen measurement pairs were therefore used for comparison of sPAP_C and sPAP_D through Bland-Altman analysis and linear regression. A statistically significant bias between sPAP_C and sPAP_D (mean difference=0.5mmHg; Confidence interval: -6.5mmHg, +7.5mmHg) was not detected. The limits of agreement between the techniques were wide (-27.3mmHg, +28.2mmHg). Regression analysis failed to identify a significant linear association between the two techniques (r=0.11, p=0.17). In conclusion, sPAP_D poorly agrees with sPAP_C measurement in dogs affected by MMVD in ACVIM stages B2 and C. In these dogs, sPAP_D could under- or over-estimate sPAP_C by more than 20mmHg, and therefore caution should be used when interpreting PASP_D. Master of Science The most common heart disease of dogs is myxomatous mitral valve disease (MMVD). In many affected dogs, this disease can be complicated by the development of high pressure in the vessels of the lungs, a condition called pulmonary hypertension (PH). On average, dogs with MMVD and PH have shorter survival compared to dogs affected solely by MMVD. The pulmonary pressure in dogs is usually estimated using cardiac ultrasound (echocardiography). This technique has the advantage of being "non-invasive" but it is not a direct measurement of pressure, therefore it may not be accurate. In order to evaluate the accuracy of echocardiography in measuring pulmonary pressure, in this study we compared direct measurements of pulmonary pressure obtained through cardiac catheterization to the measurements estimated using echocardiography, in dogs affected by MMVD. We performed this on 18 dogs affected by MMVD, with one person performing the direct measurements and another performing the echocardiographic ones; the two people were not aware of the measurements obtained with the other technique. We found that the echocardiographic estimated pressures can be very different from the real pressures measured with cardiac catheterization. Particularly, echocardiography resulted both in relevant over- and under-estimation of the real pressure, in an unpredictable way. This study therefore suggests that pulmonary pressures estimated by echocardiography should be interpreted cautiously in dogs affected by MMVD.

Myxomatous mitral valve degeneration (MMVD) is the most common canine cardiac disease. In the studies presented in this dissertation, we used advanced echocardiographic techniques to elucidate several aspects of MMVD in dogs. Our hypothesis was that the mitral valve (MV) morphology could have a role in the development of MMVD. First, we tested whether we could use real time three-dimensional transthoracic echocardiography (RT-3DTTE), and an offline software for MV analysis to evaluate canine MV. We described that the technique was feasible and repeatable, we evaluated the morphology of the MV in healthy dogs, and we provided reference values for MV morphologic variables in this species. Then, we used the same technique to compare healthy dogs to dogs affected by MMVD. We found that dogs affected by MMVD have more circular and flatter valve. We then analyzed the MV of healthy Cavalier King Charles Spaniels (CKCSs), given the high predisposition of this breed for MMVD. Our findings indicate that compared to healthy dogs of other breeds, the MV of healthy CKCSs is flatter and has less leaflet tenting, corroborating our hypothesis that an altered MV morphology could represent a predisposing factor for disease development. We also used RT–3DTTE to characterize the area of the regurgitant MV orifice of dogs affected with MMVD, finding that the technique requires further standardization in order to become clinically useful. The elevation of pulmonary venous pressure caused by MMVD can, in some dogs, cause pulmonary arterial hypertension (PH), which is a risk factor associated with worse outcome in dogs with MMVD. Diagnosis of PH in dogs with MMVD is usually made by estimating pulmonary pressure using Doppler echocardiography. We are currently evaluating the accuracy of this technique, compared to invasive measurement of pulmonary pressure. Only preliminary data are presented regarding this study, as the disclosure of the blinding would have infringed the power of the study. Our preliminary results demonstrate that there is only moderate agreement between the two techniques, indicating that caution should be used when deriving the non-invasive estimation of systolic pulmonary pressure in order to make clinical decisions. Ph. D.