PATET ratio by Doppler echocardiography: noninvasive detection of pediatric pulmonary arterial hypertension.

Pulmonary artery acceleration time (PAT) and PAT: ejection time (PATET) ratio are echocardiographic measurements of pulmonary arterial hypertension (PAH). These noninvasive quantitative measurements are ideal to follow longitudinally through the clinical course of PAH, especially as it relates to the need for and/or response to treatment. This review article focuses on the current literature of PATET measurement for infants and children as it relates to the shortening of the PATET ratio in PAH. At the same time, further development of PATET as an outcome measure for PAH in preclinical models, particularly mice, such that the field can move forward to human clinical studies that are both safe and effective. Here, we present what is known about PATET in infants and children and discuss what is known in preclinical models with particular emphasis on neonatal mouse models. In both animal models and human disease, PATET allows for longitudinal measurements in the same individual, leading to more precise determinations of disease/model progression and/or response to therapy. IMPACT: PATET ratio is a quantitative measurement by a noninvasive technique, Doppler echocardiography, providing clinicians a more precise/accurate, safe, and longitudinal assessment of pediatric PAH. We present a brief history/state of the art of PATET ratio to predict PAH in adults, children, infants, and fetuses, as well as in small animal models of PAH. In a preliminary study, PATET shortened by 18% during acute hypoxic exposure compared to pre-hypoxia. Studies are needed to establish PATET, especially in mouse models of disease, such as bronchopulmonary, as a routine measure of PAH.

Can veterinary medicine improve diversity in post-graduate training programs? Current state of academic veterinary medicine and recommendations on best practices.

The American Association of Veterinary Clinicians (AAVC) convened a Diversity, Equity, and Inclusivity working group in March 2021 to address the limited diversity (including but not limited to ethnic, racial, and cultural diversity) in clinical post-DVM graduate training programs and academic faculty. Concurrent with a working group formation, the AAVC developed a strategic plan. The central mission of the AAVC is to develop, support, and connect academic leaders to fuel the future of the veterinary medical profession. House officers and their training programs are central to all goals outlined in the strategic plan. Amongst other strategic goals, the working group identified best practices for intern and resident recruitment and selection. We report herein from the current health profession literature ways to identify and recruit talented, diverse candidates especially those with non-traditional (atypical) preparation and experience. We also provide recommendations on best practices for intern and resident selection. This document highlights holistic approaches, some of which are incrementally being incorporated into the Veterinary Intern Resident Matching Program application, that emphasize diversity as a selection criteria for intern and resident selection an important step towards building a more resilient and inclusive workforce. These include expanding candidate assessment beyond grades and class rank into a more standardized method for screening candidates that includes consideration of life experiences and talents outside of veterinary medicine.

Safety of transesophageal pacing for 24 hours in a canine model.

BACKGROUND: Temporary epicardial pacing is often necessary following surgical correction of congenital heart disease. Epicardial pacing wires, while generally effective, can, however, become nonfunctional. Transesophageal atrial pacing (TEAP) can be a useful adjunct in this setting. The potential for esophageal damage with sustained TEAP is unknown. We assessed the safety of continuous (24 hours) TEAP by evaluating gross and histological changes to the esophagus in a canine model. METHODS: Thirteen juvenile beagle dogs were fitted with a 4-Fr multipolar catheter placed transnasally into the esophagus to a level to sustain atrial capture. Pacing was established in nine dogs for 24 hours while four control dogs had catheters but no pacing stimulus applied. Paced dogs were divided into two groups: group A (n = 5) that were euthanized immediately and group B (n = 4) that were euthanized 7 days after the pacing period. Nonpaced dogs (group C, n = 4) were treated similar to group A. Gross and histological examination of the esophageal tissue was completed. RESULTS: Gross and histological evidence of mild esophagitis was noted in dogs from groups A and C but not in dogs from group B. There was no evidence of esophageal stricture or fibrosis in any dog from any group. CONCLUSIONS: TEAP did not result in permanent esophageal changes after 24 hours of stimulation. Microscopic lesions of mild erosive esophagitis, seen after 24 hours of TEAP, were absent 7 days postpacing. Mechanical irritation from the catheter cannot be ruled out as a cause of these changes.

Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway.

Skeletal muscle atrophy results from an imbalance in protein degradation and protein synthesis and occurs in response to injury, various disease states, disuse, and normal aging. Current treatments for this debilitating condition are inadequate. More information about mechanisms involved in the onset and progression of muscle atrophy is necessary for development of more effective therapies. Here we show that expression of the mouse ether-a-go-go related gene (Merg1a) K+ channel is up-regulated in skeletal muscle of mice experiencing atrophy as a result of both malignant tumor expression and disuse. Further, ectopic expression of Merg1a in vivo induces atrophy in healthy wt-bearing mice, while expression of a dysfunctional Merg1a mutant suppresses atrophy in hindlimb-suspended mice. Treatment of hindlimb-suspended mice with astemizole, a known Merg1a channel blocker, inhibits atrophy in these animals. Importantly, in vivo expression of Merg1a in mouse skeletal muscle activates the ubiquitin proteasome pathway that is responsible for the majority of protein degradation that causes muscle atrophy, yet expression of a dysfunctional Merg1a mutant decreases levels of ubiquitin-proteasome proteolysis. Thus, expression of Merg1a likely initiates atrophy by activating ubiquitin-proteasome proteolysis. This gene and its product are potential targets for prevention and treatment of muscle atrophy.

Two-dimensional left atrium-to-aorta ratios and left ventricular M-mode transthoracic echocardiographic measurements in clinically normal adult Dachshunds.

OBJECTIVE: To estimate the left atrium-to-aorta ratio (LA:Ao) and establish 95% prediction intervals for left ventricular M-mode transthoracic echocardiographic measurements in clinically normal adult Dachshunds. ANIMALS: 40 healthy Dachshunds. PROCEDURES: For each dog, 3 standard 2-D echocardiographic methods (diameter, circumference, and cross-sectional area) were used to measure the left atrium and aorta and calculate the LA:Ao from right parasternal short axis (RPSA) images obtained at the level of the aortic valve cusps. Left ventricular M-mode measurements were acquired from RPSA images obtained at the chordal level immediately below the mitral valve. Descriptive data were generated, and the 95% prediction intervals were calculated by use of an allometric scaling equation and linear regression and compared with those calculated on the basis of data obtained from dogs of multiple breeds in a previous study. RESULTS: The mean (SD) LA:Ao was 1.40 (0.13), 2.09 (0.17), and 2.85 (0.48) for the diameter, circumference, and cross-sectional area methods, respectively. The 95% prediction intervals for the left ventricular M-mode measurements determined by an allometric scaling equation on the basis of Dachshund-specific data were narrower than those determined on the basis of data obtained from dogs of multiple breeds. For that allometric equation, scaling exponents on the basis of Dachshund-specific data ranged from 0.129 to 0.397 and did not absolutely conform to the presumed index for linear measurements (ie, body weight(0.333)). CONCLUSIONS AND CLINICAL RELEVANCE: The LA:Aos and 95% prediction intervals calculated in this study can be used as preliminary guidelines for echocardiographic measurements of clinically normal Dachshunds.

Transcatheter closure of an atrial septal defect in a dog.

Atrial septal defect, while rare in dogs, can result in severe clinical signs. Surgical correction of atrial septal defect requires open-heart surgery. Transcatheter closure techniques provide minimally invasive surgical alternatives.

Suspected iatrogenic paradoxical embolization in a cat.

A cat was evaluated for a 5-year history of progressive, episodic, exercise-induced cyanosis and panting. Diagnostic testing demonstrated tetralogy of Fallot with predominant right-to-left shunting and right-sided heart failure. Following diagnostic catheterization, the cat developed clinical signs consistent with systemic arterial thromboembolization and was euthanized. Necropsy findings included multiple thrombi within the right atrium and ventricle, and thromboemboli within the terminal aorta and right common carotid artery, a condition most consistent with iatrogenic paradoxical embolization secondary to diagnostic catheterization. Paradoxical embolization and thromboembolic complications of diagnostic catheterization are discussed.

Pulmonary artery dissection in eight dogs with patent ductus arteriosus.

OBJECTIVES: To describe a series of dogs with pulmonary artery dissection and patent ductus arteriosus (PDA). ANIMALS: Eight dogs. METHODS: Retrospective case series. RESULTS: Pulmonary artery dissection was diagnosed in 8 dogs, 3 were Weimaraners. Four dogs presented in left-sided congestive heart failure, 4 presented for murmur evaluation and without clinical signs, and 1 presented in right-sided congestive heart failure. In 7 dogs the dissection was first documented concurrent with a diagnosis of uncorrected PDA. In the other dog, with pulmonary valve stenosis and PDA, the dissection was observed on autopsy examination 17 months after balloon pulmonary valvuloplasty and ductal closure. Median age at presentation for the 7 dogs with antemortem diagnosis of pulmonary artery dissection was 3.5 years (range, 1.5-4 years). Three dogs had the PDA surgically ligated, 2 dogs did not undergo PDA closure, 1 dog failed transcatheter occlusion of the PDA with subsequent surgical ligation, 1 dog underwent successful transcatheter device occlusion of the PDA, and 1 dog had the PDA closed by transcatheter coil delivery 17 months prior to the diagnosis of pulmonary artery dissection. The 2 dogs that did not have the PDA closed died 1 and 3 years after diagnosis due to heart failure. CONCLUSIONS: Pulmonary artery dissection is a potential complication of PDA in dogs, the Weimaraner breed may be at increased risk, presentation is often in mature dogs, and closure of the PDA can be performed and appears to improve outcome.

Transarterial coil embolization of patent ductus arteriosus in small dogs with 0.025-inch vascular occlusion coils: 10 cases.

Patent ductus arteriosus (PDA) is the most common congenital cardiac disease in the dog and generally leads to severe clinical signs, including left-sided congestive heart failure. Historically, definitive treatment consisted of surgical ligation; however, the use of vascular occlusion devices by minimally invasive techniques has gained popularity in veterinary medicine during the past decade. Adequate vascular access is a major limiting factor for these minimally invasive techniques, precluding their use in very small dogs. The clinical management of PDA with 0.025-in vascular occlusion coils in a minimally invasive transarterial technique in 10 dogs is described. The dogs were small (1.38 +/- 0.22 kg), were generally young (6.70 +/- 5.74 months), and had small minimal ductal diameters (1.72 +/- 0.81 mm from angiography). Vascular access was achieved, and coil deployment was attempted in all dogs with a 3F catheter uncontrolled release system. Successful occlusion, defined as no angiographic residual flow, was accomplished in 8 of 10 (80%) dogs. Successful occlusion was not achieved in 2 dogs (20%), and both dogs experienced embolization of coils into the pulmonary arterial tree. One of these dogs died during the procedure, whereas the other dog underwent a successful surgical correction. We conclude that transarterial PDA occlusion in very small dogs is possible with 0.025-in vascular occlusion coils by means of a 3F catheter system and that it represents a viable alternative to surgical ligation. The risk of pulmonary arterial embolization is higher with this uncontrolled release system, but this risk may decrease with experience.

Evaluation of antiplatelet effects of ticlopidine in cats.

OBJECTIVE: To determine whether ticlopidine exerts an antiplatelet effect, estimate the pharmacodynamics of ticlopidine, and evaluate any acute adverse effects associated with administration of ticlopidine in cats. ANIMALS: 8 domestic purpose-bred sexually intact male cats. PROCEDURE: Ticlopidine was administered orally (50 mg, q 24 h; 100 mg, q 24 h; 200 mg, q 24 h; and 250 mg, q 12 h). Each treatment period consisted of 10 days of drug administration. Platelet aggregation studies with adenosine diphosphate (ADP) and collagen and evaluation of oral mucosal bleeding times (OMBTs) were performed on days 3, 7, and 10 during each drug administration. Serotonin was measured to evaluate secretion at baseline and on day 10 for cats that received the 250-mg dosage. RESULTS: A significant reduction in platelet aggregation was detected in response to ADP on days 7 and 10 at 100 mg, on day 3 at 200 mg, and on days 3, 7, and 10 at 250 mg. A significant increase in the OMBT and decrease in serotonin release on day 10 at 250 mg was also detected; however, the cats had anorexia and vomiting at the 250-mg dosage. CONCLUSIONS AND CLINICAL RELEVANCE: Although there was a consistent antiplatelet effect at the 250-mg dosage, there was dose-dependent anorexia and vomiting that we conclude precludes the clinical usefulness of this drug in cats.

Antiplatelet effects and pharmacodynamics of clopidogrel in cats.

OBJECTIVE: To evaluate antiplatelet effects and pharmacodynamics of clopidogrel in cats. DESIGN: Original study. ANIMALS: 5 purpose-bred domestic cats. PROCEDURE: Clopidogrel was administered at dosages of 75 mg, p.o., every 24 hours for 10 days; 37.5 mg, p.o., every 24 hours for 10 days; and 18.75 mg, p.o., every 24 hours for 7 days. In all cats, treatments were administered in this order, with at least 2 weeks between treatments. Platelet aggregation in response to ADP and collagen and oral mucosal bleeding times (OMBTs) were measured before and 3, 7, and 10 days (75 and 37.5 mg) or 7 days (18.75 mg) after initiation of drug administration. Serotonin concentration in plasma following stimulation of platelets with ADP or collagen was measured before and on the last day of drug administration. Platelet aggregation, OMBT, and serotonin concentration were evaluated at various times after drug administration was discontinued to determine when drug effects were lost. RESULTS: For all 3 dosages, platelet aggregation in response to ADP platelet aggregation in response to collagen, and serotonin concentration were significantly reduced and OMBT was significantly increased at all measurement times during drug administration periods. All values returned to baseline values by 7 days after drug administration was discontinued. No significant differences were identified between doses. None of the cats developed adverse effects associated with drug administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of clopidogrel at dosages ranging from 18.75 to 75 mg, p.o., every 24 hours, results in significant antiplatelet effects in cats.

In vitro effect of pimobendan on platelet aggregation in dogs.

OBJECTIVE: To determine whether pimobendan has in vitro antithrombotic properties through inhibition of platelets in canine blood samples. ANIMALS: 10 healthy adult dogs. PROCEDURES: Blood samples were collected from each dog into tubes containing hirudin or sodium citrate. Pimobendan was added to blood samples (final concentration, 0.0, 0.01, 0.1, 1.0, or 10.0µM) containing hirudin prior to undergoing collagen- and ADP-induced whole blood impedance aggregometry. Plasma thromboxane concentrations were measured after platelet aggregation. Pimobendan was also added to blood samples (0.0, 0.01, or 10.0µM) containing sodium citrate prior to thromboelastographic evaluation. RESULTS: Compared with findings for 0.0µM pimobendan, composite platelet aggregation (area under the curve [AUC]) and maximal platelet aggregation (aggregation units [AUs]) at 10.0µM pimobendan were significantly decreased for collagen-induced aggregation (AUC, 349.7 ± 58.4 vs 285.1 ± 72.2; maximal platelet aggregation, 196.2 ± 25.8 AUs vs 161.5 ± 38.0 AUs), and the AUC and velocity of aggregation at 10.0µM pimobendan were significantly decreased for ADP-induced aggregation (AUC, 268.5 ± 35.1 vs 213.4 ± 77.2; velocity of aggregation, 15.7 ± 2.9 AUs/min vs 11.8 ± 3.5 AUs/min). Pimobendan had no significant effect on plasma thromboxane concentration or thromboelastographic variables, regardless of concentration. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro, pimobendan had an antiplatelet effect in canine blood samples at a concentration 1,000-fold higher than that clinically achievable. These antiplatelet properties do not appear to contribute to the positive clinical profile of the drug in dogs. Pimobendan administration would not appear to confer a risk for bleeding and does not have to be avoided in dogs with thrombocytopenia or those concurrently receiving antiplatelet drugs.

Dose determination of fondaparinux in healthy cats.

OBJECTIVE: To establish practical doses and administration frequencies of fondaparinux for cats that would approximate human therapeutic peak and trough plasma anti-factor Xa activities for thromboprophylaxis (TP) and thrombosis treatment (TT) protocols. ANIMALS: 6 healthy adult purpose-bred cats. PROCEDURES: Dosage protocols for TP and TT were selected on the basis of a single compartment pharmacokinetic model incorporating data from humans but modified to account for the higher body weight-normalized cardiac output of cats. Fondaparinux was administered at 0.06 mg/kg, SC, every 12 hours (TP) for 7 days in one session, and 0.20 mg/kg, SC, every 12 hours (TT) for 7 days in another, with a minimum of 1 week separating the sessions. Plasma anti-factor Xa activity was measured before fondaparinux administration (day 1) and at 2 (peak) and 12 (trough) hours after drug administration on days 1 and 7. Platelet aggregation and thromobelastographic (TEG) parameters were also measured 2 hours after drug administration on day 7. RESULTS: Peak plasma anti-factor Xa activities on day 7 for TP (median, 0.59 mg/L; range, 0.36 to 0.77 mg/L) and TT (median, 1.66 mg/L; range, 1.52 to 2.00 mg/L) protocols were within therapeutic ranges for humans. However, only the TP protocol achieved trough anti-factor Xa activity considered therapeutic in humans (median, 0.19 mg/L; range, 0.00 to 0.37 mg/L) on day 7. There were significant changes in the TEG parameters at peak for the TT protocol, suggesting a hypocoagulable state. No significant changes in platelet aggregation were evident for either protocol. CONCLUSIONS AND CLINICAL RELEVANCE: A fondaparinux dosage of 0.06 or 0.20 mg/kg, SC, every 12 hours, was sufficient to achieve a peak plasma anti-factor Xa activity in cats that has been deemed therapeutic in humans. This study provided preliminary data necessary to perform fondaparinux dose-determination and clinical efficacy studies.

Use of transesophageal atrial pacing to provide temporary chronotropic support in a dog undergoing permanent pacemaker implantation.

A 14.5-kg, 13-year-old female spayed Cocker spaniel was evaluated because of episodic hind limb weakness. Results of examination were consistent with sick sinus syndrome with intermittent second-degree atrioventricular block. Transesophageal atrial pacing was successful in providing chronotropic support during permanent pacemaker implantation. Transesophageal atrial pacing appears to be a viable option for temporary atrial pacing in dogs with hemodynamically marked bradycardia without significant atrioventricular blockade.

Efficacy of transesophageal and transgastric cardiac pacing in the dog.

OBJECTIVES: Determine if temporary artificial cardiac pacing can be accomplished from transesophageal or transgastric pacing sites. ANIMALS, MATERIALS AND METHODS: Nine purpose bred Beagle dogs had a multipolar electrophysiology pacing catheter inserted transnasally and advanced into the distal esophagus or stomach under general anesthesia. Artificial atrial pacing was attempted using a bipolar configuration from the distal esophagus with the dogs in left lateral recumbency. Artificial ventricular pacing was attempted from the distal esophagus and stomach using unipolar and bipolar configurations with the dogs in multiple positions. RESULTS: Transesophageal atrial pacing was accomplished in all dogs with a mean threshold of 10.5 mA (+ or - 3.9) and a 15 mm polar separation with no skeletal muscle stimulation. All attempts at transgastric and transesophageal ventricular pacing were unsuccessful. CONCLUSIONS: Transesophageal atrial pacing using standard cardiac pacing equipment is simple to perform and is a viable alternative to temporary transvenous or transthoracic pacing for supraventricular bradyarrhythmias without atrioventricular conduction disturbances. Transesophageal and transgastric ventricular pacing does not appear possible using the pacing configurations in this study.

Cranial vena caval syndrome secondary to transvenous pacemaker implantation in two dogs.

Superior vena caval syndrome is a rare, but reported complication of transvenous pacemaker implantation in humans. This syndrome can occur secondary to fibrotic and/or thrombotic obstruction of venous blood flow into the right atrium. The therapeutic approach depends on the suspicion of the presence of an active thrombus and may include antithrombotics, angioplasty and/or surgical venoplasty. We describe two dogs that developed severe pleural effusion secondary to stricture formation in the cranial vena cava 4 years after dual chamber transvenous pacemaker implantation. The stenosis was most likely due to fibrosis secondary to the transvenous pacemaker leads. Balloon angioplasty of the lesion resulted in resolution of the pleural effusion in both patients. Balloon angioplasty appears to be a viable therapeutic approach in dogs with cranial vena caval syndrome caused by focal stenotic lesions.

Transcatheter closure of patent ductus arteriosus in a dog with a peripheral vascular occlusion device.

A 4-month-old, intact female mixed-breed dog presented to the Purdue University Veterinary Teaching Hospital for evaluation of a cardiac murmur. A large left-to-right patent ductus arteriosus (PDA) was diagnosed and interventional correction was achieved with a commercially available peripheral vascular occlusion device (VOD). The VOD is composed of a nitinol wire mesh and is similar in composition and shape to a commercially available human PDA occluder, however, it can be deployed through smaller delivery catheters and is much less expensive. The product and procedural details of the device are described.