About

Mark A Oyama, DVM, MSCE, DACVIM, is a Professor of Cardiology at the University of Pennsylvania School of Veterinary Medicine. He holds the Charlotte Newton Sheppard Endowed Chair of Medicine and serves as Chair of the Department of Clinical Sciences & Advanced Medicine. His research expertise includes cardiac biomarkers such as troponin and natriuretic peptides (BNP, ANP), diuretic resistance, clinical trials, serotonin signaling, and myxomatous valve disease. His work involves animal models of heart disease and heart failure, as well as epidemiology and biostatistics. Dr. Oyama's clinical expertise encompasses canine and feline models of heart disease and the molecular mechanisms underlying myxomatous mitral valve disease. He has contributed to understanding the pathophysiology of heart conditions in veterinary patients and has published extensively on these topics.

Research topics

• Computer Science
• Cardiology
• Medicine
• Internal medicine

Selected publications

• Effect of the sodium glucose transporter-2 inhibitor dapagliflozin on urine and blood biomarkers in dogs with heart disease

  Journal of Veterinary Internal Medicine · 2026-03-01

  articleOpen accessSenior author

  BACKGROUND: Sodium-glucose transport 2 inhibitors (SGLT2i) decrease morbidity and mortality in human patients with heart failure through a variety of proposed mechanisms, including natriuresis and glucosuria. The effects of SGLT2i on urine sodium (uNa) and urine glucose (uGlu) concentrations in dogs with heart disease have not been evaluated. HYPOTHESIS/OBJECTIVES: Administration of the SGLT2i dapagliflozin to dogs with heart disease will be well-tolerated and increase uNa and uGlu concentrations. Laboratory results and biomarker assays will provide insight into potential mechanisms of action. ANIMALS: Ten client-owned dogs with heart disease with or without congestive heart failure. METHODS: Prospective multicenter open-label uncontrolled study. Blood and urine biochemistry and oxidative and inflammatory biomarkers were evaluated at baseline and 5-7 days after 0.45-1 mg/kg/day PO dapagliflozin. RESULTS: A treatment effect was observed for uGlu (baseline, 14 mg/dL; IQR, 2-19 mg/dL; treatment effect +3102 mg/dL; IQR, 2390-4387 mg/dL; P = .002) but not for uNa (baseline, 75 mmol/L; IQR, 28-129 mmol/L; treatment effect, -41 mmol/L; IQR, -96-21 mmol/L; P = .12). Serum total thiol concentration increased (baseline, 145 μmol/L; SD, 32 μmol/L; treatment effect, +7 μmol/L; SD, 9 μmol/L; P = .04), suggesting an antioxidative effect. Serious adverse effects, including hypoglycemia or ketoacidosis, were not observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Short-term PO dapagliflozin was well-tolerated and associated with glucosuria but not natriuresis. Clinical benefit of SGLT2i in dogs with heart disease might include non-natriuretic mechanisms, such as anti-inflammatory, antioxidative, or metabolic effects.

  PublisherOA PDFDOI

• Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptor

  Frontiers in Cardiovascular Medicine · 2026-02-12

  articleOpen access

  Background Aortic Stenosis (AS) is a highly prevalent disease involving physiological and structural remodeling of aortic valve, yet lacks effective medical therapy to halt its progression. Serotonin (5HT) signaling has been implicated in valvular disease. We hypothesized that AS is associated with impaired 5HT clearance due to reduced serotonin receptor (SERT) expression and increased 5HT receptor (HTR) activity. Methods Sixty-six patients with severe AS undergoing aortic valve (AV) replacement were enrolled in the study, and samples from their explanted AV were harvested. Anatomically normal control AVs were obtained from transplant donors. Explanted AVs were collected for gene expression analysis and 5-HTTLPR genotyping. Gene expression was assessed by RT2-profiler gene array. In vivo , 8-week-old mice received 28-day Angiotensin-II (AngII) infusions ± HTR2B antagonist (LY272015) through subcutaneous Alzet osmotic-pump implants. AV structure and function were assessed via echocardiography, histology, and RNA sequencing. Human aortic valve interstitial cells (AVICs) were treated with AngII ± SERT siRNAs to assess 5HT signaling and profibrotic/procalcific markers. Results AS patients exhibited reduced SERT and increased HTR signaling. AngII ± SERT siRNA promoted VIC osteogenic marker expression. In mice, AngII caused AV thickening, increased velocities and gradients, and activation of fibrosis and mildly calcification-related gene sets, including serotonin, TGF β , Wnt/ β -catenin, PI3K/Akt, and Notch pathways. Pharmacological inhibition of HTR2B preserved AV structure, normalized transvalvular velocities and pressure gradients, and reversed AngII-induced transcriptional changes. Conclusions In human and mouse AVs, reduced SERT expression and increased HTR2B signaling contribute to early-onset fibro-calcific remodeling. HTR2B inhibition by LY272015 reverses these effects, suggesting it as a potential therapeutic strategy for fibrotic remodeling in AS.

  PublisherOA PDFDOI

• Plasma Cardiac Troponin-I Concentration in Normal Horses and in Horses with Cardiac Abnormalities

  Animals · 2025-01-03 · 1 citations

  articleOpen access

  Cardiac troponin-I (cTnI) is a highly sensitive and specific marker of myocardial injury detectable in plasma by immunoassay techniques. Inclusion criteria over a 3-year period required a diagnosis of cardiac disease accompanied by electrocardiographic (ECG) and cardiac ultrasound examinations (n = 23) in adult horses (≥2 years of age). A second group of normal adult ponies (n = 12) was studied as a reference group. Heparinized jugular venous blood samples were collected and centrifuged within 30 min, and the plasma was separated and frozen at −70 °C for subsequent batched cTnI analysis. The lower limit of detection was 0.01 ng/mL, and the upper limit was 100 ng/mL of plasma. Normal equine plasma cTnI concentrations ranged from 0.01 to 0.03 ng/mL (n = 12). Horses with non-arrhythmogenic murmurs (n = 4) included tricuspid (0.05 ng/mL cTnI), mitral (0.07), and aortic insufficiencies (0.01, 0.02). Horses with benign atrial fibrillation (n = 8) had a cTnI range of <0.01–0.09 ng/mL, with four horses having cTnI concentrations falling slightly outside the reference range (0.04, 0.05, 0.06, and 0.09). Horses with ventricular arrhythmias (ventricular premature contractions or ventricular tachycardia) and documentable myocardial toxicities or immunological reactions (n = 5) had cTnI concentrations of 0.05, 0.21, 0.31, 15.18, and >100 ng/mL. Horses with ventricular arrhythmias but no documentation of myocardial toxicity (n = 3) had cTnI concentrations of 0.34, 0.46, and 80.42 ng/mL. When grouped by arrhythmia type and compared using the Mann–Whitney Rank Sum Test, the median ventricular arrhythmia cTnI (0.40 ng/mL) was significantly higher than the median atrial fibrillation cTnI (0.04 ng/mL, p < 0.001). It was concluded that horses with myocardial toxicities and ventricular arrhythmias often had severe elevations in plasma cTnI.

  PublisherOA PDFDOI

• Pathophysiology and Anesthetic Management of Patients with Cardiovascular Disease

  2024-06-21 · 3 citations

  otherSenior author

  In animals with suspected cardiac disease, care must be taken both prior to and during anesthesia to assess the heart's ability to (1) provide adequate cardiac output and tissue perfusion, (2) maintain low venous pressures and prevent congestion, and (3) avoid arrhythmias. This chapter outlines preanesthetic evaluation of dogs and cats with cardiac disease and presents anesthetic considerations for patients with specific types of cardiac disease, including mitral valve regurgitation, dilated cardiomyopathy, shunting congenital defects (ventricular septal defect, patent ductus arteriosus [PDA], Tetralogy of Fallot, and reverse PDA), subaortic and pulmonic stenoses, hypertrophic and restrictive cardiomyopathy, and pericardial effusion. An overview of hypotension and shock is also provided.

  PublisherDOI

• Observed and expected reliability of echocardiographic volumetric methods and critical change values for quantification of mitral regurgitant fraction in dogs

  Journal of Veterinary Internal Medicine · 2024-09-27 · 5 citations

  articleOpen accessSenior authorCorresponding

  Abstract Background Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability. Hypothesis Observed intra- and interobserver accuracy and variability in healthy dogs help model CCV for RFMR. Animals Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs. Methods Accuracy, variability, and CCV of 2 observers using geometric and flow-based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort. Results Accuracy of methods to determine RFMR in descending order was 4-chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413. Conclusions and Clinical Importance Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV.

  PublisherOA PDFDOI

• Utility of focused cardiac ultrasonography training in veterinary students to differentiate stages of subclinical myxomatous mitral valve disease in dogs

  Journal of Veterinary Internal Medicine · 2024-03-27 · 6 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND: Differentiation of the subclinical phases of myxomatous mitral valve disease (MMVD) in dogs relies heavily on echocardiography. Focused cardiac ultrasonography (FCU) is a point-of-care technique that can assess heart size. HYPOTHESIS/OBJECTIVES: Veterinary students trained in FCU can differentiate dogs with subclinical MMVD based on left ventricular (LV) and left atrial (LA) dimensions. ANIMALS: Forty-eight dogs with subclinical MMVD. METHODS: Veterinary students were trained to measure LV dimension and LA-to-aortic root dimension ratio (LA : Ao) using FCU. Dogs were categorized into 2 cohorts based on whether or not the LV normalized internal diastolic dimension was ≥1.7 and LA : Ao was ≥1.6. Agreement between FCU and echocardiographic studies performed by cardiologists was evaluated. RESULTS: One-hundred and forty-six FCU examinations were performed by 58 veterinary students on 48 dogs. Overall agreement between students and cardiologists was moderate (Fleiss' kappa, 0.54; 95% confidence interval [CI], 0.39-0.69; P < .001). Percentage accuracy in observations with heart dimensions less than the cutoffs (86/89, 97%) was significantly higher than in observations in with larger hearts (31/57, 54%; P < .001). Agreement increased from moderate to good as heart sizes became more extreme. Degree of confidence by students in performing FCU was significantly higher at the end vs start of the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Categorization of dogs with subclinical MMVD by veterinary students using FCU was associated with moderate to good agreement with echocardiography. Focused cardiac ultrasonography is a point-of-care method that can help assess clinical stage in dogs with subclinical MMVD.

  PublisherOA PDFDOI

• Sodium glucose transporter 2 inhibitors: Will these drugs benefit non‐diabetic veterinary patients with cardiac and kidney diseases?

  Journal of Veterinary Pharmacology and Therapeutics · 2024-07-13 · 5 citations

  reviewOpen accessSenior author

  Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked. The primary mechanism(s) by which SGLT2 inhibitors are cardio- and nephroprotective remain to be fully characterized. This paper reviews these suggested mechanisms in the context of the pathophysiology of progressive cardiovascular and kidney diseases in dogs and cats with the goal of predicting which categories of non-diabetic veterinary patients these drugs might be of most benefit.

  PublisherOA PDFDOI

• Longitudinal analysis of echocardiographic and cardiac biomarker variables in dogs with atrial fibrillation: The optimal rate control in dogs with atrial fibrillation II study

  Journal of Veterinary Internal Medicine · 2024-06-15 · 5 citations

  articleOpen access

  BACKGROUND: ≤ 125 bpm) increases survival in dogs with atrial fibrillation (AF). The mechanisms remain unclear. HYPOTHESIS/OBJECTIVES: Investigate echocardiographic and biomarker differences between RC and non-RC (NRC) dogs. Determine if changes post-anti-arrhythmic drugs (AAD) predict successful RC in subsequent Holter monitoring. Evaluate if early vs late RC affects survival. ANIMALS: Fifty-two dogs with AF. METHODS: Holter-derived mean heart rate, echocardiographic and biomarker variables from dogs receiving AAD were analyzed prospectively at each re-evaluation and grouped into RC or NRC. The primary endpoint was successful RC. Between group comparisons of absolute values, magnitude of change from admission to re-evaluations and end of study were performed using Mann-Whitney tests or unpaired t-tests. Logistic regression explored variables associated with inability to achieve RC at subsequent visits. Kaplan-Meier survival analysis was used to compare survival time of early vs late RC. RESULTS: At visit 2, 11/52 dogs were RC; at visit 3, 14/52 were RC; and at visit 4, 4/52 were RC. At the end of study, 25/52 remained NRC. At visit 2, both groups had increased cardiac dimensions, but NRC dogs had larger dimensions; biomarkers did not differ. At the end of study, RC showed decreased cardiac dimensions and end-terminal pro-brain natriuretic peptide (NT-proBNP) compared with NRC. No variables were useful at predicting RC success in subsequent visits. Survival analysis found no differences between early vs late RC. CONCLUSIONS AND CLINICAL IMPORTANCE: The RC dogs had decreased cardiac dimensions and NT-proBNP, suggesting HR-mediated reverse-remodeling might benefit survival, even with delayed RC achievement. Pursuit of RC is crucial despite initial failures.

  PublisherOA PDFDOI

• Effect of sodium-glucose cotransporter 2 inhibitor canagliflozin on interstitial glucose concentration in insulin-treated diabetic dogs

  Journal of Veterinary Internal Medicine · 2024-03-26 · 7 citations

  articleOpen access

  Abstract Background The utility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin-treated diabetic dogs. Hypothesis Canagliflozin, a PO-administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin-treated diabetic dogs. Animals Five insulin-treated diabetic dogs. Methods Uncontrolled open label longitudinal study. Canagliflozin (2-4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG &amp;lt;60 mg/dL. Results Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40-500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41-500 mg/dL; P &amp;lt; .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%-2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%-1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P &amp;lt; .001). Conclusions and Clinical Importance Canagliflozin may have a role in improving glycemic control in insulin-treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment.

  PublisherOA PDFDOI

• Metabolic Abnormalities and Reprogramming in Cats with Naturally Occurring Hypertrophic Cardiomyopathy

  ESC Heart Failure · 2024-11-05 · 4 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND AND AIMS: The heart is a metabolic organ rich in mitochondria. The failing heart reprograms to utilize different energy substrates, which increase its oxygen consumption. These adaptive changes contribute to increased oxidative stress. Hypertrophic cardiomyopathy (HCM) is a common heart condition, affecting approximately 15% of the general cat population. Feline HCM shares phenotypical and genotypical similarities with human HCM, but the disease mechanisms for both species are incompletely understood. Our goal was to characterize global changes in metabolome between healthy control cats and cats with different stages of HCM. METHODS: Serum samples from 83 cats, the majority (70/83) of which were domestic shorthair and included 23 healthy control cats, 31 and 12 preclinical cats with American College of Veterinary Internal Medicine (ACVIM) stages B1 and B2, respectively, and 17 cats with history of clinical heart failure or arterial thromboembolism (ACVIM stage C), were collected for untargeted metabolomic analysis. Multiple linear regression adjusted for age, sex and body weight was applied to compare between control and across HCM groups. RESULTS: Our study identified 1253 metabolites, of which 983 metabolites had known identities. Statistical analysis identified 167 metabolites that were significantly different among groups (adjusted P < 0.1). About half of the differentially identified metabolites were lipids, including glycerophospholipids, sphingolipids and cholesterol. Serum concentrations of free fatty acids, 3-hydroxy fatty acids and acylcarnitines were increased in HCM groups compared with control group. The levels of creatine phosphate and multiple Krebs cycle intermediates, including succinate, aconitate and α-ketoglutarate, also accumulated in the circulation of HCM cats. In addition, serum levels of nicotinamide and tryptophan, precursors for de novo NAD+ biosynthesis, were reduced in HCM groups versus control group. Glutathione metabolism was altered. Serum levels of cystine, the oxidized form of cysteine and cysteine-glutathione disulfide, were elevated in the HCM groups, indicative of heightened oxidative stress. Further, the level of ophthalmate, an endogenous glutathione analog and competitive inhibitor, was increased by more than twofold in HCM groups versus control group. Finally, several uremic toxins, including guanidino compounds and protein bound putrescine, accumulated in the circulation of HCM cats. CONCLUSIONS: Our study provided evidence of deranged energy metabolism, altered glutathione homeostasis and impaired renal uremic toxin excretion. Altered lipid metabolism suggested perturbed structure and function of cardiac sarcolemma membrane and lipid signalling.

  PublisherDOI

Frequent coauthors

• John E. Rush

  Tufts University

  113 shared

• Kristin A. MacDonald

  97 shared

• Barret J. Bulmer

  Surgical Specialties (United States)

  94 shared

• D. David Sisson

  Oregon State University

  82 shared

• Dennis J. Trafny

  The Schwarzman Animal Medical Center

  73 shared

• Lisa M. Freeman

  Tufts University

  67 shared

• Suzanne M. Cunningham

  Tufts University

  67 shared

• John M. MacGregor

  67 shared

Labs

• Perelman School of Medicine - Department of Clinical Sciences & Advanced Medicine, University of PennsylvaniaPI

Education

• Cardiology Specialty Training

  University of California Davis

  1997

• DVM

  University of Illinois System

  1994