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RodRussell
16th February 2010, 05:18 PM
An October 2009 video by cardiologist Mark Oyama on MVD in Cavaliers (and an overview of canine heart disorders in general) may be watched at http://ondemand.thecanonhouse.com/CHF/Oyama/oyama.html

This was his presentation to the AKC National Parent Club Canine Health Conference last October. Be patient while watching; he starts out talking about cardiomyopathy in Boxers, but soon enough he turns to MVD in Cavaliers.
--
Rod Russell
Orlando, Florida

Margaret C
26th February 2010, 12:13 AM
I have just caught up with myself a little, so managed to find the time to watch this. Very interesting indeed.
Also the later discussion on survival time versus quality of life.

Thank you Rod for posting this link, and the other one on Simon Platt's talk, which I will watch tomorrow.

EddyAnne
26th February 2010, 05:24 AM
Rod thanks for posting the address. I found it very interesting even though I had read the latest publishings on MVD. Interestingly Mark Oyama mentioned Fibrillin-1 just before he went into mentioning Serotonin, and from a genetical point of view I would be interested in what Genetic Research may reveals regarding MVD and also CM, and note the following part from Clare Rusbridge's webpage at this address.
http://www.veterinary-neurologist.co.uk/research.htm

Finding the gene(s) for Chiari malformation
Investigation of possible candidate gene - Fibrillin 1
Genetic studies in humans with Chiari malformation type 1 have indicated significant areas (high LOD scores) on chromosomes 9 and 15 (for more information click here). On chromosome 15 there is a very large gene called Fibrillin-1 which has already been associated with genetic conditions that involve mis-shapen skulls including Marfan syndrome and Shprintzen-Goldberg syndrome (the defects in this syndrome include CM). Fibrillin has been suggested as a possible positional candidate gene. It is very large gene coding for an amino acid which is a constitutive element of extracellular microfibrils in connective tissues. Fibrillin 1 sequence analysis in affected CKCS, Yorkshire Terrier, Bull Terrier, Boston Terrier, Chihuahua, Brussels Griffon and King Charles breeds is ongoing.
.

Tania
26th February 2010, 10:01 PM
Thank you Rod for posting this. I found the the Serotonin theory really interesting!

EddyAnne
27th February 2010, 12:31 AM
Yes really interesting and Oyama mentioned something about clinical trials on dogs to study the impact of a drug that inhibits the Serotonin.

Meanwhile Genetic Researchers are looking into DNA and I noted Oyama mentioned Fibrillin-1 regarding MVD, and note Clare Rusbridge also mentions Fibrillin-1 regarding CM, and both MVD and CM involve Cavaliers.

Regarding Serotonin the following Abstract is from this address.
http://www.ingentaconnect.com/content/bpl/jvim/2009/00000023/00000006/art00012;jsessionid=5mmnh4jn786oo.alexandra

Serum Serotonin Concentrations in Dogs with Degenerative Mitral Valve Disease
Authors: Arndt, J.W.1; Reynolds, C.A.1; Singletary, G.E.1; Connolly, J.M.2; Levy, R.J.2; Oyama, M.A.1

Source: Journal of Veterinary Internal Medicine, Volume 23, Number 6,
November/December 2009 , pp. 1208-1213(6)
Publisher: Blackwell Publishing

Abstract:

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:
Prospective analysis. Serum 5HT concentration was measured by an ELISA test.

Results:
Median serum 5HT concentration was significantly higher in dogs with DMVD and in dogs predisposed to DMVD as compared with controls (DMVD, 765.5 ng/mL [interquartile range, 561.3-944.4]; predisposed, 774.9 ng/mL [528.3-1,026]; control, 509.8 ng/mL [320.8-708.8]; P= .0001). Subgroup analysis of predisposed dogs indicated significantly higher serum 5HT concentrations in Cavalier King Charles Spaniel (CKCS) dogs than in other breeds (CKCS, 855.0 ng/mL [635.8-1,088]; non-CKCS, 554.2 ng/mL [380.6-648.4]; P= .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.
.

Margaret C
27th February 2010, 02:18 PM
Interesting that serotonin is used as an anti-depressant in human medicine

EddyAnne
27th February 2010, 05:00 PM
Interesting that serotonin is used as an anti-depressant in human medicine
Margaret yes and from me some simple layman thoughts about Serotonin.

Serotonin medications have been around for many years, and humans and dogs manufacture their own Serotonin where there are "normal levels". High levels of Serotonin over a period of time at the heart valves could cause medical induced or driven MVD, and where this might occur then doctors and vets may want to periodically listen to the heart with their Stethoscope. But I think that in most cases Serotonin medication is given where for one reason or another the levels of Serotonin have dropped below "normal levels" and they want to restore it back to "normal levels".

In relation to medications to reduce high levels of Serotonin at the heart valves. Well that might require a special medication that targets and does NOT reduce the levels of Serotonin elsewhere within the body as a reduction elsewhere may lead to various problems.

With Cavaliers the question is what is causing the high levels of Serotonin at the heart valves. Well we do know a lot of Cavaliers have Heritable MVD and why Researchers are looking into DNA for the cause. Maybe think of high levels of Serotonin at the heart valves as "secondary" where the actual cause comes from the genes, avoid breeding those genes that do this then there may be NO need for special Serotonin medications.
.

Tania
27th February 2010, 05:41 PM
Over the years I have met a few people who have taken Serotonin to lift their spirits! Dr. Oyama mentioned out of all the dogs The Cavaliers are the Happiest Dogs in the World! probably because of the high levels of Serotonin. In laymans language, does this mean when MVD was not around, would the temperament of the Cavalier been different? Are the high levels of Serotonin relatively new. I will have a transcript of this around Wednesday if anyone would like a copy.

Kate H
27th February 2010, 11:22 PM
Tania, I would really appreciate a copy of your transcript - my speakers are on the blink and my lip-reading skills aren't great! I'll PM you my own email address if that's OK.

Kate, Oliver and Aled

amanda L
24th March 2010, 04:32 PM
Thanks for posting Rod, very interesting presentation and results, just wondering if you or anyone else knows what is the serotonin-blocking agent (drug K, used in western blot analysis expts), Mark Oyama is investigating? Ok, just reviewed a publication, think maybe its 5HT-R2A ketanserin?

RodRussell
24th March 2010, 05:40 PM
...Ok, just reviewed a publication, think maybe its 5HT-R2A ketanserin?

I'm not sure, since Dr. Oyama was circumspect about it in his talk, but as you have found elsewhere, he is researching use of ketanserin, a 5HT-R2A receptor blocker, and GR55562, a 5HT-R1B receptor blocker, and he also commented in his most recent article* that:

"...Marfan syndrome may represent a human condition similar to canine 5HT/TGF-b1–mediated disease, and treatments that are effective in humans with Marfan syndrome may have application in dogs."

*See: http://cavalierhealth.org/mitral_valve_disease.htm#Insights_into_Serotonin

EddyAnne
24th March 2010, 11:54 PM
"...Marfan syndrome may represent a human condition similar to canine 5HT/TGF-b1–mediated disease, and treatments that are effective in humans with Marfan syndrome may have application in dogs."

Note also mis-shapen skulls including Marfan syndrome which I just bolded below and here is a copy of my previous post.

I found it very interesting even though I had read the latest publishings on MVD. Interestingly Mark Oyama mentioned Fibrillin-1 just before he went into mentioning Serotonin, and from a genetical point of view I would be interested in what Genetic Research may reveals regarding MVD and also CM, and note the following part from Clare Rusbridge's webpage at this address.
http://www.veterinary-neurologist.co.uk/research.htm

Finding the gene(s) for Chiari malformation
Investigation of possible candidate gene - Fibrillin 1
Genetic studies in humans with Chiari malformation type 1 have indicated significant areas (high LOD scores) on chromosomes 9 and 15 (for more information click here). On chromosome 15 there is a very large gene called Fibrillin-1 which has already been associated with genetic conditions that involve mis-shapen skulls including Marfan syndrome and Shprintzen-Goldberg syndrome (the defects in this syndrome include CM). Fibrillin has been suggested as a possible positional candidate gene. It is very large gene coding for an amino acid which is a constitutive element of extracellular microfibrils in connective tissues. Fibrillin 1 sequence analysis in affected CKCS, Yorkshire Terrier, Bull Terrier, Boston Terrier, Chihuahua, Brussels Griffon and King Charles breeds is ongoing.
.

RodRussell
25th March 2010, 02:14 AM
Amazing! MVD, CM/SM, and even oversized platelets (a possible source of the excess seratonin), could all be linked together in the CKCS!