Calcium and catecholamines: relevance to cardiomyopathies and significance in therapeutic strategies.
There are marked differences between human cardiomyopathies, especially of the hypertrophic variety, and animal models. There is no simple way in which a hyperadrenergic state can explain the contractile abnormalities, although additional effects of calcium overload or marked hypertrophy come somewhat closer to linking animal and human diseases. One of the best links between excess catecholamine stimulation and myocardial damage lies in the enhanced sarcolemmal permeability which is mediated by beta-adrenergic stimulation and calcium ions in an isolated rat heart model. The therapeutic success of beta-adrenergic blockade and especially calcium antagonists in no way provide firm evidence for a hyperadrenergic state nor for intracellular calcium overload. In human hypertrophic cardiomyopathy, these agents may be acting merely by enlarging cavity size. In dilated cardiomyopathy, the use of beta-adrenergic blockers is still highly controversial and calcium antagonists are not well tested. It is the lack of appropriate models for both hypertrophic cardiomyopathy and dilated cardiomyopathy which is holding up research in this important area.
Opie
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Walpoth
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Barsacchi
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D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000323:Adrenochrome / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002147:Calmodulin / Q000502:physiology; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002395:Catecholamines / Q000378:metabolism*; D002415:Cats; D006224:Cricetinae; D000242:Cyclic AMP / Q000502:physiology; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008647:Mesocricetus; D008954:Models, Biological; D011941:Receptors, Adrenergic / Q000378:metabolism; D017983:Receptors, Catecholamine; D012376:Rodent Diseases / Q000235:genetics / Q000503:physiopathology; D012508:Sarcolemma / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D002147:Calmodulin; D002395:Catecholamines; D011941:Receptors, Adrenergic; D017983:Receptors, Catecholamine; D000323:Adrenochrome; D000242:Cyclic AMP; D002118:Calcium