PubMed Health⌕ Search

Biomedical subjects

Lip-Bun Tan

Publications and source records attributed to Lip-Bun Tan.

22 records · Page 2Linked to original sources
PubMed2003

Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.

Excessive levels of catecholamines have long been known to be cardiotoxic, but less well known are their toxic effects on skeletal muscle. By using an antimyosin monoclonal antibody and quantitative methods to measure the extent of myocyte necrosis, and by employing modulators of adrenoceptors (ARs), including clenbuterol, bupranolol, propranolol, bisoprolol, atenolol, ICI-118551, phenoxybenzamine, prazosin, and yohimbine, the involvement of ARs in isoproterenol-induced myotoxicity was characterized. In the myocardium, the toxic effects were predominantly mediated via the beta(1)-ARs. In the soleus muscle, it was almost solely via the beta(2)-ARs. Myotoxicity was also observed in the myocardium when challenged with the beta(2)-AR agonist clenbuterol. This was found to be mediated via sympathetic presynaptic beta(2)-ARs, leading to enhanced release of norepinephrine. This effect was abolished by prior treatment with reserpine. The skeletal muscle was found to be more sensitive to the myotoxic effects than cardiac muscle at lower doses of beta-AR agonists. These experiments introduce a new way of assaying beta-AR antagonists by classifying them according to their ability to prevent catecholamine-induced myotoxicity. Further research along these lines may deepen understanding of which beta-blockers work best in heart failure therapy.

Adrenergic beta-Antagonists↗
PubMed2003

Cardiomyocyte death and the ageing and failing heart.

Mammalian cardiomyocytes have limited regenerative capacity, such that cell death can result in a net loss of viable contractile elements and a decrease in cardiac functional reserve, both during normal ageing and after insults to the myocardium leading to heart failure. At least four types of cell death have been described, with apoptosis and necrosis being the most extreme phenotypes and most extensively studied. Many of the classical morphological and biochemical features associated with these forms of cell death have been derived from studies conducted in vitro and these may not always faithfully reflect events occurring in vivo. Before therapeutic interventions can be realistically developed, more studies need to be undertaken in vivo to simultaneously investigate these different death pathways, their control mechanisms and their relative contributions in depleting the pool of viable cardiomyocytes. We recently demonstrated immunohistochemically that a single injection of either a natural or synthetic catecholamine induces both cardiomyocyte apoptosis (identified by an anti-caspase 3 antibody) and necrosis (identified by an anti-myosin antibody) in the rat heart in vivo. After optimising the experimental conditions for hormone dose and temporal and spatial peaks of damage, the incidence of necrosis was 4-10 times greater than the incidence of apoptosis. Myocytes in the soleus muscle were also severely (7-10 %) damaged, involving both apoptosis and necrosis. In both striated muscles high levels of myocyte co-localisation for apoptosis and necrosis were observed, suggesting that secondary necrosis had occurred in most of the apoptotic myocytes in vivo. The ability of the catecholamines to cause myocyte death suggests that they might play an aetiological role in the progression of heart failure where over-activation of the sympathetic system results in sustained pathophysiological levels of these catecholamines.

Aging↗
PubMed2002

Myotoxic effects of clenbuterol in the rat heart and soleus muscle.

Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. Clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.

Adrenergic beta-Agonists↗