Evaluation of novel diagnostic and therapeutic modalities for treatment of canine pulmonary hypertension

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Pimobendan, a phosphodiesterase III inhibitor and calcium channel sensitizing agent, was hypothesized to decrease the severity of pulmonary hypertension (PHT) in a prospective short-term, double-blinded, crossover design, with a long-term, open-label component. Ten dogs with a peak tricuspid regurgitant pressure gradient (TRPG) [greater than or equal to] 50 mmHg on echocardiogram were enrolled. PHT was secondary to myxomatous valve disease in 8 of the dogs, and chronic pulmonary disease in 2. Dogs were examined on days 0, 14, 21, 35, and 91. In the 35-day short-term phase, dogs were randomly allocated to receive either placebo or pimobendan (0.18-0.3 mg/kg, PO q12h) for 14 days. Following a 1 week washout, the dogs received the alternative treatment for 14 days. All dogs then received pimobendan for 8 weeks. Data was analyzed using a two-period crossover design. Short-term comparison of pimobendan vs. placebo: All dogs had a decreased peak TRPG on pimobendan therapy in comparison to placebo (p=0.0061), with a mean decrease of 16.37 ± 12.89 mmHg. All dogs demonstrated a significant decrease in NT-proBNP levels while receiving pimobendan (p=0.0023), with a mean difference of 708.8 ± 508.6 pmol/L. A significant improvement in the summed QOL score was noted in 9/10 dogs (p=0.016). Long-term comparison of day 0 vs. 91: 9/10 dogs showed a decreased peak TRPG (p=0.03), with a mean decrease of 14.0 ± 15.6 mmHg. No significant changes in NT-proBNP levels (p=0.34) or the summed QOL scores (p=0.41) were seen. Failure to show improvement may be secondary to progressive disease or the small sample size.