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  • A new treatment for hypertrophy?

    Health
    Viagra May Reverse Enlarged-Heart Damage
    By Amanda Gardner
    HealthDay Reporter


    SUNDAY, Jan. 23 (HealthDayNews) --Viagra, the drug most often associated with restoring male sexual powers, may play an entirely different role in treating enlarged hearts.

    In male mice, sildenafil citrate (the generic name for Viagra) successfully treated enlargement and thickening of the heart, not only stopping further growth of the heart muscle, but also actually reversing the growth and damage that had already taken place.

    Trials in humans are slated to get underway later this year.

    "If, indeed, what works in mice works in humans, this will become a standard part of care," said Dr. Richard Stein, a national spokesman for the American Heart Association. "This is very important."

    "By treating mice with Viagra in doses that would be similar to what a person would get, we found that we could block hypertrophy [enlarging and thickening of the heart muscles] and could prevent progression to heart failure," said study co-author Dr. Hunter Champion, an assistant professor of medicine at Johns Hopkins University School of Medicine. "Heart failure is a huge problem in the United States. It is the No. 1 reason for hospitalization through Medicare."

    The findings, which will be published in the February issue of Nature Medicine, represent a "clinical home run," as Stein put it.

    They also represent a scientific breakthrough because they revealed mechanisms involved in heart thickening and the progression to heart failure.

    Approximately 65 million Americans have high blood pressure or hypertension, which can lead to cardiac hypertrophy, a thickening of the heart muscle brought on because the heart has to pump harder to get its job done. At least one fourth of people with high blood pressure have cardiac hypertrophy, which also increases the risk of heart failure or sudden death by a factor of two to three, Champion said.

    In one experiment, Champion and his colleagues divided 10 to 40 male mice into two groups, one that was fed Viagra and one that received a regular diet. They then constricted the main artery in the mice, causing the heart to pump harder and resulting in a condition essentially the same as hypertrophy.

    The mice who got Viagra only developed half the hypertrophy that the other animals did. The Viagra mice also showed 67 percent less muscle fibrosis (stiffening), and also had smaller hearts and improved heart function.

    In another experiment, the researchers gave Viagra to part of a group of male mice that had already developed hypertrophy. After two weeks, fibrosis and muscle growth almost completely disappeared in the mice given Viagra while hearts continued to grow in the control mice.

    Viagra works, both in the heart and the penis, by inhibiting an enzyme called PDE5A.

    In the penis, however, PDE5A relaxes the smooth muscle, allowing the blood to flow and nature to resume its course.

    By contrast, in the heart muscle, rather than producing a direct relaxation response, PDE5A helps break down cyclic GMP, a molecule that acts to curb stresses and overgrowth in the heart.

    "The result is so impressive because it works on more than just one pathway," Champion said. "A boxer with just one jab in his repertoire is going to lose the fight, but if you have a good right jab, left jab and uppercut, you're going to be a much better fighter."

    Experts had not previously known that PDE5A was involved in heart function. They had also suspected that excessive heart muscle growth was an adaptive response to malfunction in the heart. This study, however, indicates that not all hypertrophy is the same and that Viagra might block the "bad" hypertrophy, Champion explained.

    In a way, Viagra is coming full circle. The drug was originally developed to dilate coronary blood vessels in people with angina. It didn't work for angina, but while being tested, was revealed to have the erectile dysfunction effect, for which it is now famous.

    Champion believed that the effect on the heart may actually be seen in the entire class of drugs, not just Viagra. "It could very well be that Levitra or Cialis would do the same thing," he said, referring to Viagra's two competitors in the erectile dysfunction marketplace.

    In general, the researchers are ahead of the game because Viagra is already approved. "The beautiful thing about this drug is we know that there are 20 million prescriptions written for Viagra. We know it to be a very safe drug," Champion said.

    It may be a while, though, before Viagra as heart therapy becomes a possibility: Heart failure drug trials take time to prove measurable results.

    But Champion added, "I will say, if it is half as impressive as we see in the mice, it might not take that long."

    Researchers will also be looking to see if Viagra has any effect on other systems in the body.

    More information

    The American Heart Association has more on cardiac hypertrophy and other forms of cardiomyopathy.
    Daughter of Father with HCM
    Diagnosed with HCM 1999.
    Full term pregnancy - Son born 11/01
    ICD implanted 2/03; generator replaced 2/2005 and 2/2012
    Myectomy 8/11/06 - Joe Dearani - Mayo Clinic.

  • #2
    VIAGRA is good now???

    I am very very surprised by this news. We were told (male HCMers) avoid it for a very good reason, a normally weak HCM heart may have difficultly to deal with too much pumping of the blood (specially during sex) which is common sense. I guess before some us jump on this news and to take the V and have S need to read between the lines. Behrang

    Comment


    • #3
      I would urge caution and skepticism for now. Especially since this is 180 degrees opposite from what we have been told.
      • This is just one study, and its just mice.
      • There are many conditions that are cardiac hyperthrophic. HCM is just one of them and may not be appropriate for this research (now if it had only been a study on cats).
      • I’m sure Lisa will we weighing in on this soon.
      Fx

      Comment


      • #4
        But lets all cross our fingers. A cure for HCM whose only side effect is..(well, you know).
        Jall

        Diagnosed with unobstructed HCM in 2004 after a bad experience playing tennis
        Graduated to obstructed HCM by Dec, 2008.

        Life outside of HCM: Law, Photography, Tennis, Music, raising kids and camping

        Comment


        • #5
          Hey everyone,

          Just to clarify why I posted this originally.....I wanted to share an interesting article that I read. In no way do I suggest that anyone with HCM should run out and get some Viagra. This is obviously research at the very early stages which is of interest to HCM'er. That's all. Its just interesting and maybe a little humorous.

          Have a nice day.

          Cynthia
          Daughter of Father with HCM
          Diagnosed with HCM 1999.
          Full term pregnancy - Son born 11/01
          ICD implanted 2/03; generator replaced 2/2005 and 2/2012
          Myectomy 8/11/06 - Joe Dearani - Mayo Clinic.

          Comment


          • #6
            Cynthia, thanks for posting this article.
            Regardless as to whether this turns out to be helpful or not in the treatment of HCM/HOCM, researchers are now wiser than they were before the study.
            Another door has opened, who knows where this discovery will take us.

            Experts had not previously known that PDE5A was involved in heart function

            Pam
            It's not what you gather, but what you scatter that tells what kind of life you have lived.

            Dx in Feb/99. Obstructed. No ICD, no surgeries, no family history. 2 sons ages 14 and 6.

            Comment


            • #7
              Hypertrophy development

              Hi

              I hate to rain on any possible parades, but I doubt that this will help HCM. The Forbes article I read (http://www.forbes.com/lifestyle/heal...out523571.html

              explains that the Viagra is acting on the blood vessels and the smooth heart muscle. Well, HCMers don't have smooth heart muscle. We have disorganized muscle full of pockets of glycogen or collagen.

              THey only looked at hypertrophy (as far as I can tell) caused by high blood pressure, which is not the same as hypertrophy caused by HCM. So, I'm not holding my breath on this one.

              However, if it really pans out, it would save millions of lives and for that, I am grateful.

              S

              Comment


              • #8
                Re: Hypertrophy development

                Originally posted by Sarah
                The Forbes article I read
                explains that the Viagra is acting on the blood vessels and the smooth heart muscle. Well, HCMers don't have smooth heart muscle. We have disorganized muscle full of pockets of glycogen or collagen.
                You missed the next paragraph:
                "By contrast, in the heart muscle, rather than producing a direct relaxation response, PDE5A helps break down cyclic GMP, a molecule that acts to curb stresses and overgrowth in the heart."

                Comment


                • #9
                  I don't mind being a guinea pig, or mouse in this case. he he

                  Comment


                  • #10
                    Well, HCMers don't have smooth heart muscle. We have disorganized muscle full of pockets of glycogen or collagen.
                    Actually, what is meant by "smooth muscle" is not in respect to what you would expect. Smooth muscle is called smooth because of a small molecule that "studs" the muscle called sarcomeres. This is a connection point for muscle fibers. In skeletal muscle (like arm or leg muscles) there are many thousands (maybe 100,000 per cell) of the sarcomeres that join together the individual muscle cells. In tissues such as cardiac muscle or veins and arteries even, the muscle tissue has none of the sarcomeres. If you look at it under a microscope it looks smooth -as compared to- skeletal muscle, which has a striated appearance because of the sarcomeres. So this kind of muscle came to be called smooth muscle. It is also a muscle that contracts involuntarily, as opposed to muscles of the bicep for example where you decide when to contract it.

                    True, our cardiac muscle does grow in disarray, but it is still by definition smooth muscle. The disarray is actually the individual muscle cells that are in disarray.

                    Not sure if that helps or confuses things, but I just wanted to add that in.

                    Doug
                    NEMC's (Boston) First Myectomy 7-22-2003

                    Comment


                    • #11
                      I'm skeptical about the use of viagra in HCM. The hypertrophy they're talking about is the type you get from overuse of the muscle, like when you have high blood pressure and the heart has to pump harder to make the blood move. Viagra works by dilating blood vessels, which isn't a good thing for HCM'ers. Many HCM'ers don't have high blood pressure to start with and when you dilate the vessels, the pressure will drop even more, leaving you will less blood to fill the chambers. We'll have to see how this pans out. That's not to say this drug may have its place in treating those with hypertrophy from high blood pressure, though. We'll just have to wait and see.

                      Reenie
                      Reenie

                      ****************
                      Husband has HCM.
                      3 kids - ages 23, 21, & 19. All presently clear of HCM.

                      Comment


                      • #12
                        thanks, Doug. Good explanation, but I couldn't type that much. Linda

                        Comment


                        • #13
                          Thanks Linda.

                          I also meant to add my skepticism on the use of Viagra for HCM types of hypertrophy. I agree with you Reenie.
                          NEMC's (Boston) First Myectomy 7-22-2003

                          Comment


                          • #14
                            Hi Doug-
                            You are correct about heart muscle being known as “smooth muscle” and heart muscle is different than skeletal muscle when examined by microscope. However it isn’t because heart muscle lacks sarcomeres. In fact- HCM is now described as a disease of the sarcomere. Sarcomeres are a basic component of all muscle fibers, and specifically the major component responsible for muscle contraction. Sarcomeres in cardiac muscle are unique in a biochemical sense and perhaps this is what you were referring to.

                            I was given several information sheets regarding the genetic test done by the Laboratory for Molecular Medicine. The lead in statement:
                            “Genetic studies have defined HCM as a disease of the sarcomere – caused by mutations in any of 11 genes that encode different elements of the contractile apparatus in cardiac myocytes.”

                            Aren’t I a nit-picker??
                            • 1995: Brigham & Women’s Hospital - diagnosed with Atrial Fibrillation
                            • 2004: Falkner Hospital – diagnosed with Congestive Heart Failure
                            • 2004: Tufts NEMC– diagnosed with “End Stage” Hypertrophic Cardiomyopathy
                            • 2005: Genetic Test – Laboratory for Molecular Medicine. HCM confirmed – missense mutation detected in TNNT2 gene
                            • 2009: Brigham & Women’s - Third cardioversion begin Amiodarone for AFib
                            • 2011: Brigham & Women’s - Medtronic ICD implant

                            Comment


                            • #15
                              Hey Boz,

                              HAH! Nit picking is good. Keeps one on his toes. I was trying actually to not be too technical and in doing so I did mis-state it a little. And, (trying again not to get too technical) in fact there are 3 types of muscle. In truth, there is skeletal, smooth AND cardiac muscle. The fact is, Cardiac muscle is actually somewhere in between skeletal muscle and smooth muscle, structurally. It does contain sarcomeres but much different are how the cells actually connect. They connect end to end at a point called an intercalated disc. So cardiac muscle cells are more like smooth muscle cells in that they contain only one large, central nucleus, are capable of involuntary contraction, and in appearance they look more like smooth muscle but they are striated like skeletal muscle cells, and the sarcomeres are there, but don't give the same appearance as skeletal muscle. Early on it was thought cardiac muscle was the same as smooth muscle because of the appearance, but with newer technology and electron microscopy it was shown that it was a whole different type of muscle altogether, so it was reclassified.

                              So I think I may be getting too technical but I know for me it was good to understand structurally what exactly was this disease doing in my heart and how come it manifested in this way.

                              Boz, you actually are right on target and stated it better than I. The sarcomere is why our muscle cells are in disarray (cardiac muscle cells only). It really gets very complicated as I think of it so maybe I should just shut up at this point. But offline it is a fun discussion I think...at least for a science geek like me. I have a link to a web site that explains it in gory detail for anyone who might care. Drop me a PM I will send it to you.


                              Sorry for getting off the subject here regarding the Viagra. So, it does seem hard to believe that a drug like Viagra can do anything to fix a disease that is just so inherently structural in nature.

                              Doug
                              NEMC's (Boston) First Myectomy 7-22-2003

                              Comment

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