Effects of Treatment with Thromboxane A2 Synthase Inhibitor on Pulmonary Hypertension: A Pilot Study
27th ECVIM-CA Congress, 2017
J. Lee1; W. Kim2; W. Yoon3; H. Kim1
1VIP Animal Medical Center, Seoul, South-Korea; 2Columbia University, New York, NY, USA; 3Guardian Angel Veterinary Hospital, Anyang, South-Korea

Thromboxane A2 (TXA2) is an important multifactorial mediator in the pathogenesis of pulmonary hypertension. Although endothelium-derived TXA2 causes excessive pulmonary vascular resistance by acting as a potent vasoconstrictor, mitogen of vascular smooth muscle cells and promoter of platelet aggregation, there is no current therapeutic strategy for pulmonary hypertension, targeting TXA2 formation. The aim of this study is to assess possible beneficial effects of inhibiting TXA2 synthesis in patients with pulmonary hypertension.

Sixteen client-owned dogs with proven moderate-to-severe pulmonary hypertension were randomly assigned to the treatment (n=8; ozagrel hydrochloride, 5 mg/kg bid PO) or control group (n=8; sildenafil citrate, 1 mg/kg BID PO). All patients have already been treated with standard protocol including sildenafil (1.8±0.6 mg/kg, BID). Pulmonary hypertension associated with left-side heart failure (LA/Ao >1.6 and LVIDDn >1.7) was excluded in the population. Several clinical indices, which relate to hypoxia (lactate, SpO2, base excess), thrombosis (d-dimer), azotemia (BUN, creatinine), congestion (NT-proBNP) and echocardiographic indices (peak velocity of tricuspid regurgitation, Ao/MPA), were tracked down for four weeks.

The treatment led to significant and gradual decreases in lactate and d-dimer (p<0.01; from 5.6±1.9 mmol/L to 1.8±1.0 and from 7.4±6.8 to 1.2±1.1 μg/ml, respectively) but significantly increased SpO2 and base excess (p<0.01; from 87±5.3 to 95±1.8% and from -8.4±3.2 to -3.1±1.9 mmol/L, respectively) in the patients. Compared to controls, the treatment group exhibited statistically significant changes in only lactate level (p=0.02) and SpO2 (p=0.016). However, treatment of TXA2 synthase inhibitor showed the tendency to improve the other variables, such as NT-proBNP and tricuspid regurgitant flow, implicating the potential role of TXA2 synthase inhibitor in pulmonary vascular impedance. Abnormal behavior such as licking footpads and joints has been reported to be a putative side effect of the treatment in one case.

These results suggest that TXA2 synthase inhibitor may contribute to the improvement of pulmonary hemodynamics in pulmonary hypertension by alleviating pulmonary vasoconstriction and preventing thrombosis.

Disclosures

No disclosures to report.

  

Speaker Information
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J. Lee
VIP Animal Medical Center
Seoul, South Korea


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