Effect of endogenous catecholamine on myocardial stunning in a simulated ischemia model.
During ischemia, large amounts of catecholamine are released to the myocardium from the sympathetic nerve endings in the heart. It has not been clearly shown whether the released catecholamine has detrimental or beneficial effects on postischemic myocardial contractile function. The aim of the present study was to investigate the effect of endogenous catecholamine released during ischemia on myocardial contractile function, using ferret papillary muscles in a stimulated ischemia model. Papillary muscles were excised and mounted in organ baths containing oxygenated physiological salt solution at 37 degrees C. In order to eliminate the effect of endogenous catecholamine, a subset of animals was reserpinized for 2 days prior to the experiments. Muscles were stabilized for 1 h, and stretched to the length at which maximal isometric tension developed. Ischemia was simulated by changing the solution to liquid fluorocarbon bubbled with 95% N2 and 5% CO2. After 20 min of ischemia, the bathing medium was replaced with oxygenated physiological salt solution and developed tension was measured for 60 min. Pharmacologic agents with specific effects on myocardial autonomic pathways were used to investigate the cellular mechanisms of the observed effects. Tension recovery of reserpinized muscles was significantly better than control muscles (65.5 +/- 2.8% vs. 54.9 +/- 5.0%, P < 0.01). Exogenously administered beta-adrenergic antagonists did not attenuate stunning in control muscles; whereas forskolin and carbachol exacerbated stunning. These results indicate that catecholamine released during ischemia exacerbates myocardial stunning and overrides the effect of clinically relevant concentrations of beta-adrenergic antagonists, which may limit their ability to protect myocardium from acute ischemic insult. The effect of endogenous catecholamine was simulated by forskolin, but not attenuated by carbachol, which suggests that changes in the contractile apparatus activated by excess cyclic AMP were relevant to the mechanical dysfunction that developed.
Ishiguro
Y
Y
Department of Anesthesia and Critical Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Morgan
J P
JP
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D005289:Ferrets; D005466:Fluorocarbons / Q000494:pharmacology; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D008955:Models, Cardiovascular; D017682:Myocardial Stunning / Q000139:chemically induced / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D005466:Fluorocarbons; D005576:Colforsin; D012110:Reserpine; D002217:Carbachol; D011433:Propranolol