Unexpected cell shape change raises possibility of novel therapeutic approach; Further animal study urged before human testing
BETHESDA, Md. (May 12, 2005) – Not only is low thyroid function very common in congestive heart failure, it also indicates a reduced likelihood of recovery, and an increased chance of death.
But based on earlier work showing that whatever leads to heart failure it is always preceded by changes in the heart cells, a new study demonstrates that a moderate dose of thyroid hormones (TH) over 30 days "normalizes" the shape of the cardiac cells (myocytes) and reduces stress on the heart's wall nearly 40%.
"As patients move toward heart failure, the myocytes become longer and flatter, and the wall stress worsens," according to the head of the laboratory where the research was performed. "But moderate TH therapy selectively targeted myocyte cross-sectional shape and modified it in a positive way.
This is the first clue on what might be a novel therapeutic approach to heart failure because of the return to a more normal heart cell shape," according to A. Martin Gerdes, director of the Cardiovascular Research Institute, University of South Dakota.
The study, entitled "Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure," appears in the May issue of the American Journal of Physiology-Heart and Circulatory Physiology, published by the American Physiological Society. The research was conducted by Tracy A. Thomas, James A. Kuzman, Brent E. Anderson, Susan M. K. Andersen, Evelyn H. Schlenker, Maurice S. Holder and A. Martin Gerdes.
More animal testing needed before move to humans
Based on positive preliminary findings, the University of South Dakota-Florida A&M University research paper reports that moderate TH positively affected heart remodeling and reduced wall stress in ways warranting further study. However the authors warn that since the mechanism of thyroid hormone influence on diseased hearts isn't known, continuous TH therapy could endanger heart failure patients, particularly in accidental overdose.
In the U.S. alone, heart failure contributes to or causes about 300,000 deaths each year, according to the National Heart, Lung, and Blood Institute. The unit of the National Institutes of Health estimates that about 5 million people in the U. S. have heart failure and the number is growing. Each year, 550,000 people are diagnosed for the first time.
Unique cardiac cell re-shaping reduced heart wall stress 38%
"This is the first study to look at the implications of thyroid hormone therapy on hypertensive heart failure," Gerdes said. There is "an abundance of evidence that thyroid dysfunction contributes to heart failure," Gerdes noted, "but this study showed that a moderate TH dosage reduced wall stress 38% without affecting blood pressure."
The paper said the effect came about because the TH "produced a unique, never-before-observed pattern of myocyte remodeling." This is particularly important, Gerdes said, because no matter what the underlying cause of heart failure in humans, the last phase in heart failure – progression to dilatation – is always accompanied by elongation of heart muscle cells (myocytes), without concomitant cell widening.
The paper notes that "it isn't clear at this time whether the critical defect in myocyte remodeling in progression to congestive heart failure is due solely to excessive myocyte lengthening or to impaired transverse growth. It is possible that myocytes are responding normally to increased preload by adding new series sarcomeres, whereas the normal check on this system -- balanced myocyte transverse growth -- is where the true dysfunction lies."
However Gerdes warned since "this is the first study to disclose these positive effects with TH, we don't yet have enough information to do this intelligently in humans. Care should be taken in administering TH to humans for heart disease since there is so little information available from animal studies."
The current study said that the "most interesting effects were on the left ventricular myocyte shape…and these changes correlated beautifully with echocardiogram-derived measurements of chamber diameter and wall thickness. Additionally, the anatomical changes led to a surprising reduction in left ventricular systolic wall stress despite the presence of sustained hypertension."
- Since there appears to be such a strong link between low thyroid function and heart failure, more animal studies need to focus on this entire subject. "There is a strong likelihood that improvements in human patient outcome may occur if we have the proper scientific basis on which to proceed in an intelligent manner," Gerdes said.
- Future animal studies also should try to demonstrate that TH treatment can actually reduce mortality in heart failure, since this is the most important question from a clinical standpoint, Gerdes said.
- An area where additional work is merited, the paper says, is to uncover the signaling mechanisms by which the THs alter myocyte shape, which aren't known. If the impaired thickening of myocytes in progression to chamber dilatation and failure is related to thyroid dysfunction, which is common in heart failure patients, it is possible that treatment may help arrest progressive chamber dilatation.
- Interestingly, there was no change in myocyte shape with the low-dose TH despite reversal of the myosin-isoform abnormality, which is a marker of fetal-gene program (FGP) reactivation, the paper notes. "This suggests that signaling related to myocyte growth could be independent of changes in the FGP" -- another potential area for follow up.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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He who has never failed somewhere, that man can not be great.
~ Herman Melville