Magnesium attenuates isoproterenol-induced acute cardiac dysfunction and beta-adrenergic desensitization.
Sympathetic nervous activation is a crucial compensatory mechanism in heart failure. However, excess catecholamine may induce cardiac dysfunction and beta-adrenergic desensitization. Although magnesium is known to be a cardioprotective agent, its beneficial effects on acute cardiac dysfunction remain to be elucidated. We examined the effects of magnesium on left ventricular (LV) dysfunction induced by a large dose of isoproterenol in dogs. Sixteen anesthetized dogs underwent a continuous infusion of isoproterenol (1 micro g.kg(-1).min(-1)) with or without a magnesium infusion (1 mg.kg(-1).min(-1)). The dose response to small doses of isoproterenol (0.025-0.2 micro g.kg(-1).min(-1)) was tested hourly. A large dose of isoproterenol decreased LV systolic function, increased the time constant of LV isovolumic relaxation, and suppressed the dose response to small doses of isoproterenol in a time-dependent manner. Magnesium significantly attenuated isoproterenol-induced LV systolic and diastolic dysfunction and preserved the dose response to isoproterenol. Serum-ionized calcium significantly decreased with a large dose of isoproterenol but was fully maintained at baseline level with magnesium. A large dose of isoproterenol increased serum lipid peroxide levels and serological markers of myocardial damage, which were significantly suppressed by magnesium. In conclusion, magnesium significantly attenuated excess isoproterenol-induced acute cardiac dysfunction and beta-adrenergic desensitization.
Jin
Yin-Tie
YT
Dept of Internal Medicine, Division of Cardiology, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, Japan.
Hasebe
Naoyuki
N
Matsusaka
Tomoyuki
T
Natori
Shunsuke
S
Ohta
Takafumi
T
Tsuji
Shiro
S
Kikuchi
Kenjiro
K
D000818:Animals; D001013:Aorta, Thoracic; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006331:Heart Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D007545:Isoproterenol / Q000633:toxicity*; D008274:Magnesium / Q000627:therapeutic use*; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013599:Systole / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology
D011943:Receptors, Adrenergic, beta; D008274:Magnesium; D007545:Isoproterenol