Cardiomyopathy (Heart Failure) and Taurine

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Cardiomyopathy (Heart Failure) and Taurine

Bericht door Willy » di aug 26, 2003 10:49 am

<h4>Taurine: a conditionally essential amino acid in humans? An overview in health and disease</h4><I>
Lourenco R, Camilo ME. Servicos Farmaceuticos do Hospital de Santa Maria, Lisbon, Portugal. r.lourenco@fm.ul.pt</I><BR>
Taurine, a sulphur containing amino acid, is the most abundant intracellular amino acid in humans, and is implicated in numerous biological and physiological functions. This comprehensive overview explores areas, from its characterisation to its potential clinical benefit as a conditionally essential amino acid and a pharmaconutrient. In healthy individuals the diet is the usual source of taurine; although in the presence of vitamin B6 it is also synthesised from methionine and cysteine. Taurine has a unique chemical structure that implies important physiological functions: bile acid conjugation and cholestasis prevention, antiarrhythmic/inotropic/chronotropic effects, central nervous system neuromodulation, retinal development and function, endocrine/metabolic effects and antioxidant/antiinflammatory properties. Taurine is an essential amino acid for preterm neonates and is assured by breast milk. Specific groups of individuals are at risk for taurine deficiency and may benefit from supplementation, e.g. patients requiring long-term parenteral nutrition (including premature and newborn infants); those with chronic hepatic, heart or renal failure. Further studies are required to determine the benefits of replenishing taurine pools as well as the need to include taurine routinely in parenteral nutrition regimens.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>Conditioned nutritional requirements: therapeutic relevance to heart failure</h4><I>
Sole MJ, Jeejeebhoy KN. University of Toronto, Toronto, Canada. michael.sole@uhn.on.ca</I><BR>
BACKGROUND: The advent of disease, genetic predisposition or certain drug therapies may significantly alter the nutritional demands of specific organs. Several specific metabolic deficiencies have been found in the failing myocardium: (1) a reduction in L-carnitine, coenzyme Q10, creatine, and thiamine--nutrient cofactors important for myocardial energy production; (2) a relative deficiency of taurine, an amino acid integral to intracellular calcium homeostasis; (3) increased myocardial oxidative stress and a reduction of antioxidant defenses. Deficiencies of carnitine or taurine alone are well documented to result in dilated cardiomyopathy in animals and humans. Each of these deficiencies is amenable to restoration through dietary supplementation. A variety of nutrients have been investigated as single therapeutic agents in pharmacologic fashion, but there has been no broad-based approach to nutritional supplementation in congestive heart failure to correct this complex of metabolic abnormalities. METHOD AND RESULTS: We have demonstrated deficiencies in carnitine, taurine and coenzyme Q10 in cardiomyopathic hamster hearts during the late stage of the cardiomyopathy. In another study, we randomized placebo diet against a supplement containing taurine, coenzyme Q10, carnitine, thiamine, creatine, vitamin E, vitamin C, and selenium to cardiomyopathic hamsters during the late stages of the disease. Supplementation for 3 months markedly improved myocyte sarcomeric structure, developed pressure, +dp/dt, and -dp/dt. We also documented carnitine, taurine and coenzyme Q10 in biopsies taken from human failing hearts, the levels correlating with ventricular function. A double-blind, randomized, placebo-controlled trial of a supplement containing these nutrients, given for 30 days, restored myocardial levels and resulted in a significant decrease in left ventricular end-diastolic volume.
CONCLUSION: These experiments suggest that a comprehensive restoration of adequate myocyte nutrition may be important to any therapeutic strategy designed to benefit patients suffering from congestie heart failure. Future studies in this area are of clinical importance.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction</h4><I>
Jeejeebhoy F, Keith M, Freeman M, Barr A, McCall M, Kurian R, Mazer D, Errett L. Division of Cardiovascular Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.</I><BR>
BACKGROUND: Congestive heart failure depletes the myocardium of carnitine, coenzyme Q10 (CoQ10), and taurine--substances known to influence mitochondrial function and cell calcium. We hypothesized that feeding patients a nutritional supplement that contained carnitine, CoQ10, and taurine would result in higher myocardial levels of these nutrients and improve left ventricular function. METHODS: Forty-one patients who underwent aortocoronary artery bypass with an ejection fraction < or =40% at referral were randomly assigned to a double-blind trial of supplement or placebo. Radionuclide ventriculography was performed at randomization and before surgery. Surgical myocardial biopsies, adjusted for protein content, were analyzed for carnitine, CoQ10, and taurine levels. RESULTS: The groups were well matched. Minor exceptions were supplement group versus placebo group for digoxin use (7 vs 0, respectively; P =.009) and age (62 +/- 11 years vs 69 +/- 5 years, respectively; P =.04). There were significantly higher levels in the treated group compared with the placebo group for myocardial levels of CoQ10 (138.17 +/- 39.87 nmol/g wet weight and 56.67 +/- 23.08 nmol/g wet weight; P =.0006), taurine (13.12 +/- 4.00 micromol/g wet weight and 7.91 +/- 2.81 micromol/g wet weight; P =.003), and carnitine (1735.4 +/- 798.5 nmol/g wet weight and 1237.6 +/- 343.1 nmol/g wet weight; P =.06). The left ventricular end-diastolic volume fell by -7.5 +/- 21.7 mL in the supplement group and increased by 10.0 +/- 19.8 mL in the placebo group (P =.037).
CONCLUSIONS: Supplementation results in higher myocardial CoQ10, taurine, and carnitine levels and is associated with a reduction in left ventricular end-diastolic volume in patients with left ventricular dysfunction before revascularization. Because the risk of death for surgical revascularization is related to preoperative left ventricular end-diastolic volume, supplementation could improve outcomes.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>Conditioned nutritional requirements and the pathogenesis and treatment of myocardial failure</h4><I>
Sole MJ, Jeejeebhoy KN. Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.</I><BR>
The majority of symptomatic patients with congestive heart failure have been shown to be significantly malnourished. Myocardial and skeletal muscle energy reserves are also diminished. Total daily energy expenditure in these patients is less than that in control individuals, and high protein-calorie feeds do not reverse the abnormalities; thus, the wasting that occurs in patients with congestive heart failure is metabolic rather than because of negative protein-calorie balance. Several specific deficiencies have been found in the failing myocardium: a reduction in the content of L-carnitine, coenzyme Q10, creatine and thiamine, nutrient cofactors that are important for myocardial energy production; a relative deficiency of taurine, an amino acid that is integral to the modulation of intracellular calcium levels; and an increase in myocardial oxidative stress, and a reduction of both endogenous and exogenous antioxidant defences. In addition, these processes may influence skeletal muscle metabolism and function. Cellular nutritional requirements conditioned by metabolic abnormalities in heart failure are important considerations in the pathogenesis of the skeletal and cardiac muscle dysfunction. A comprehensive restoration of adequate myocyte nutrition would seem to be essential to any therapeutic strategy designed to benefit patients suffering from this disease.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>Cardiac actions of taurine as a modulator of the ion channels</h4><I>
Satoh H. Department of Pharmacology, Nara Medical University, Japan.</I><BR>
During ischemia, hypoxia and cardiac failure, the heart undergoes several adverse changes, including a reduction in taurine (2-aminoethanesulfonic acid). Oral administration of taurine under these disease conditions would be expected to act like a mild cardiac glycoside. Taurine would exert improvement in the accumulation of [Na]i and the loss of alpha-amino acids. Nonetheless, when intracellular taurine content is raised, there would be the benefit of increased Ca2+ release from the sarcoplasmic reticulum and increased Ca2+ sensitivity of the contractile proteins, as well as possible changes in the action potential associated with the actions of taurine on ion channels. In fact, intracellular application of taurine produces the opposite actions to extracellularly administration of the amino acid. From our previous experiments, the electrophysiological actions of taurine on cardiac muscle cells include the following. (a) Prolongation of action potential duration (APD) at high [Ca]i and shortening of APD at low [Ca]i. In multicellular preparations, however, taurine did not always prevent [Ca]o-induced effects. (b) Stimulation of spontaneous activity at low intracellular and extracellular Ca2+ concentrations ([Ca]i and [Ca]o), and vice versa. (c) Inhibition of the L-type Ca2+ current (ICa(L)) at high [Ca]i, and vice versa. (d) Enhancement of the T-type Ca2+ current (ICa(T)). (e) Inhibition of fast Na+ current (INa). (f) Enhancement of TTX-insensitive slow Na+ current. (g) Inhibition of delayed rectifier K+ current (IKrec) at high [Ca]i, and vice versa. (h) Enhancement of the transient outward current (Ito). (i) Inhibition of the ATP-sensitive K+ current (IK(ATP)). Since taurine acts on so many ion channels and transporters, it is clearly non-specific. Although it is very difficult to understand the diversity of taurine's actions, it is possible that taurine can exert its potent cardioprotective actions under the conditions of low [Ca]i, as well as Ca2+ overload. Thus, although taurine-induced modulation of ion channels located on the cardiac cell membrane is complex, the multiple effects may combine to yield useful therapeutic results.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>The role of taurine in the pathogenesis of the cardiomyopathy of insulin-dependent diabetes mellitus</h4><I>
Militante JD, Lombardini JB, Schaffer SW. Department of Pharmacology, Texas Tech University, Health Sciences Center, Lubbock 79430, USA.</I><BR>
The cellular and molecular physiology and pathology of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly studied and understood through the use of animal models. Fundamental differences between the IDDM and NIDDM animal models may help to explain the etiology behind diabetic cardiomyopathy, one of the most severe complications of IDDM. Experimental rat models of IDDM exhibit a characteristic increase in tissue levels of taurine in the heart, a change that is not seen in NIDDM rats. This article deals with the causes and possible consequences of this observation which may contribute to the development of diabetic cardiomyopathy. Modulation of pyruvate dehydrogenase (lipoamide) (PDH; EC 1.2.4.1) activity was found to be a possible mode for taurine involvement. PDH is a mitochondrial protein and is the rate-limiting step in the generation of acetyl CoA from glycolysis. In IDDM, PDH activity is decreased through a mechanism that includes the stimulation of the de novo synthesis of a kinase activator protein (KAP) which phosphorylates PDH and inactivates the enzyme. This lesion does not occur in NIDDM rat hearts. Taurine is known to inhibit the phosphorylation of PDH in vitro, and in taurine-depleted rats PDH phosphorylation is known to increase. Thus, the increased levels of taurine in the diabetic heart may be inhibiting this phosphorylation which in turn may be stimulating the synthesis of KAP through a negative feedback process. The main argument for this theory would be the lack of change in both the taurine levels and the activity of PDH in the NIDDM rat model.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>Possible Cause of Taurine-deficient Cardiomyopathy: Potentiation of Angiotensin II Action</h4><I>
Schaffer S, Solodushko V, Pastukh V, Ricci C, Azuma J. University of South Alabama College of Medicine, Department of Pharmacology, Mobile, Alabama, USA; and *Osaka University, Department of Clinical Evaluation of Medicines and Therapeutics, Osaka, Japan.</I><BR>
Taurine, an amino acid that exhibits anti-angiotensin II and osmoregulatory activity, is found in very high concentration in the heart. When the intracellular content of taurine is dramatically reduced, the heart develops contractile defects and undergoes an eccentric form of hypertrophy. The development of myocyte hypertrophy has been largely attributed to angiotensin II, whose growth properties are antagonized by taurine. Overt heart failure is usually associated with myocyte death, including death due to angiotensin II-induced apoptosis. However, the effect of taurine deficiency on angiotensin II-induced apoptosis has not been examined. To investigate this effect, taurine-deficient cells, produced by incubating rat neonatal cardiomyocytes with medium containing the taurine transport inhibitor, beta-alanine, were exposed to angiotensin II. The peptide increased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase 9 activation more in the taurine-deficient than the normal cell. Angiotensin II also promoted the translocation of protein kinase C (PKC)epsilon and PKCdelta, the expression of Bax, and the activation of c-Jun N-terminal kinase (JNK), effects that were greater in the taurine-deficient cell. However, the data ruled out a role for extracellular signal-related kinase (ERK), Bad, and p38 mitogen-activated protein kinase in the beta-alanine-angiotensin II interaction. Because PKC and JNK affect the expression and phosphorylation state of certain Bcl-2 family members, they appear to contribute to the potentiation of angiotensin II-induced apoptosis by taurine deficiency.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
<h4>Observation on collaborative treatment of dilated cardiomyopathy</h4><I>
Yang YZ, Chen RZ, Zhang JN. Zhongshan Hospital, Medical School of Fudan University, Shanghai 200032. </I><BR>
OBJECTIVE: To observe the therapeutic effect of integrated traditional Chinese and western medicine (TCM-WM) in treating dilated cardiomyopathy (DCM). METHODS: Patients of DCM were randomly divided into two groups, the 164 patients in the TCM-WM group were treated with combination therapy of traditional Chinese and western medicine, consisting of conventional western medicine, such as cardiac diuretic, vasodilative agents, taurine, coenzyme Q10, antiarrhythmics, beta blockers and Chinese herbal preparations such as Astragalus membranaceus and Shengmai injection; while the 156 cases in the control group were treated with conventional western medicine alone, including polarized liquid therapy, etc.
RESULTS: The improvement of clinical symptoms and heart function in the TCM-WM group was significantly better than that in the control group. Although the total number of deceased cases in the two groups were similar, the dead number in 3-6 months in the TCM-WM group was less than that in the control group. Moreover, 1 year later, the deceased number of patients insisted with TCM-WM treatment for over 1 year was significantly less than in those treated for only 3-6 months (1 case vs 11 cases).
CONCLUSION: Under the condition that there is no specific effective drugs, TCM-WM therapy can yet be regarded as an acceptable therapy for treatment of dilated cardiomyopathy.
Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

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