Cyclic AMP and the pathogenesis of myocardial injury.
Rabbits were given N6, O2, dibutyryl 3', 5' - cyclic AMP DB-cAMP), 2.5 micrograms/kg/min, i.v. for 90 min. to determine if activation of the cyclic neucleotide system is a potential cause of myocardial injury. They were sacrificed 7 or 14 days after infusion and the hearts examined by light and electron microscopy. Cardiac lesions were uniformly present in all hearts. They were primarily those of myofribrillar degeneration and characterized by hypercontracted muscle fibers with transverse band formation, but no inflammatory response. Additional ultrastructural alterations included foci of myofiber lysis, mitochondrial translocation, and deep scalloping of sarcolemma. The SR and T system showed varying degrees of dilatation. These changes were equally intense 2 weeks after giving DB-cAMP. Similar findings have been reported in catecholamine cardiomyopathy and numerous pathological states. It is suggested that excessive stimulation of the cyclase system can serve as a common mechanism in the pathogensis of myocardial damage by a broad spectrum stimuli.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003994:Bucladesine / Q000633:toxicity*; D000242:Cyclic AMP / Q000502:physiology*; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D010210:Papillary Muscles / Q000473:pathology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects
D003994:Bucladesine; D000242:Cyclic AMP