Myocardial performance and extracellular ionized calcium in a severely failing human heart.
A 16-year old patient had severe end-stage congestive heart failure that was refractory to large doses of beta-agonists. Low serum ionized calcium (Ca2+) levels were corrected by CaCl2 infusions. Myocardial performance correlated directly with serum Ca2+ levels. At the time of transplantation the patient's heart was removed and studied in vitro by both classic and biochemical pharmacologic techniques. Isolated papillary muscles and adenylate cyclase preparations were markedly subsensitive to isoproterenol stimulation, and myocardial membranes were nearly devoid of beta-adrenergic receptors. In contrast, papillary muscles responded normally to calcium, and adenylate cyclase responses to fluoride and histamine were normal. Beta-adrenergic receptor down-regulation may render beta-agonists ineffective, and in such situations the myocardial contractile state may become dependent on extracellular Ca2+.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D002118:Calcium / Q000097:blood*; D002122:Calcium Chloride / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002122:Calcium Chloride; D002118:Calcium