Background: Increased serotonin (5HT) signaling has been implicated in valvular disease of humans and animals, including canine degenerative mitral valve disease (DMVD). High circulating 5HT concentration is a potential source of increased signaling, and serum 5HT concentrations have not been previously reported in dogs with DMVD.Hypothesis: Dogs with DMVD and small breed dogs predisposed to DMVD have higher serum 5HT concentrations than large breed controls.Animals: Fifty dogs affected with DMVD, 34 dogs predisposed to DMVD but without cardiac murmur or echocardiographic evidence of DMVD, and 36 healthy large breed control dogs.Methods [380.6-648.4]; P 5 .0023). Age, platelet count, and platelet morphology were not correlated with 5HT concentration in any group.Conclusions and Clinical Importance: Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD. Additional investigation into a possible role of 5HT in the pathogenesis of DMVD is warranted.

Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated in the mdx mouse, restoration of cardiac dystrophin expression in large animal models of Duchenne muscular dystrophy (DMD) has proven to be a challenge. In large animals, investigators have focused on using intravenous injection of antisense oligonucleotides (AO) to mediate exon skipping. In this study, we sought to optimize restoration of cardiac dystrophin expression in the golden retriever muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA) carrying antisense sequence to target the exon splicing enhancers of exons 6 and 8 and correct the disrupted reading frame. We demonstrate restoration of cardiac dystrophin expression at 13 months confirmed by reverse transcription-PCR (RT-PCR) and immunoblot as well as membrane localization by immunohistochemistry. This was accompanied by improved cardiac function as assessed by cardiac magnetic resonance imaging (MRI). Percutaneous transendocardial delivery of rAAV6 expressing a modified U7 exon skipping construct is a safe, effective method for restoration of dystrophin expression and improvement of cardiac function in the GRMD canine and may be easily translatable to human DMD patients.

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These results indicated that QoL is more important to owners of cats with heart disease than longevity. The various priorities and concerns of cat owners should be taken into account in order to provide optimal care.

Hypothesis/ObjectivesAltered serotonin (5‐hydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantified [5HT] in platelet‐rich plasma (PRP), platelet‐poor plasma (PPP), mitral valve leaflets (MV), and left ventricular myocardium (LV).AnimalsForty‐five dogs comprised 4 plasma groups of Cavalier King Charles Spaniels (CKCS) or non‐CKCS, either healthy (CON) or MMVD affected: CKCS CON (n = 12); non‐CKCS CON (n = 8); CKCS MMVD (n = 14); non‐CKCS MMVD (n = 11). Twenty‐four dogs comprised 3 tissue groups: MMVD (n = 8); other‐HD (heart disease) (n = 7); non‐HD, extracardiac disease (n = 9).MethodsHigh‐performance liquid chromatography measured PRP, PPP, MV, and LV [5HT].ResultsPlatelet‐rich plasma platelet [5HT] was greater in CKCS CON (1.83 femtograms/platelet [fg/plt]; range, 0.20–4.76; P = .002), CKCS MMVD (1.58 fg/plt; range, 0.70–4.03; P = .005), and non‐CKCS MMVD (1.72 fg/plt; range, 0.85–4.44; P = .003) versus non‐CKCS CON (0.92 fg/plt; range, 0.63–1.30). There was no group difference in PPP [5HT]. MV [5HT] was significantly higher in MMVD (32.4 ng/mg; range, 8.4–106.7) versus non‐HD (3.6 ng/mg; range, 0–28.3; P = .01) and LV [5HT] was significantly higher in MMVD (11.9 ng/mg; range, 4.0–104.8) versus other‐HD (0.9 ng/mg; range, 0–10.1; P = .011) and non‐HD (2.5 ng/mg; range, 0–6.9; P = .001).Conclusions and Clinical ImportancePlatelet [5HT] was highest in healthy CKCS and both MMVD groups, but plasma [5HT] showed no group differences. Tissue [5HT] was highest in MV and LV of MMVD‐affected dogs, suggesting altered 5HT signaling as a potential feature of MMVD. Interactions of platelet, valvular, and myocardial 5HT signaling warrant further investigation.