PROPRANOLOL AND LIDOCAINE INHIBIT NEURAL NOREPINEPHRINE RELEASE IN HEARTS WITH INCREASED EXTRACELLULAR POTASSIUM AND ISCHEMIA

Article

关键词: ACUTE MYOCARDIAL-INFARCTION;    VENTRICULAR-FIBRILLATION;    NORADRENALINE RELEASE;    BETA-BLOCKADE;    MODULATION;    PLASMA;    RAT;    PH;    EPINEPHRINE;    SUPPRESSION;   

DOI  :  10.1161/01.CIR.88.4.1885

来源: SCIE

【 摘 要 】

Background. Propranolol and lidocaine are effective antiarrhythmic drugs in Myocardial ischemia and infarction. As sympathetic nerve activation and norepinephrine release in ischemic hearts are arrhythmogenic, we tested the possibility that both agents inhibit neural norepinephrine release following sympathetic activation in the ischemic environment. Methods and Results. The model used was an in situ perfused innervated rat heart. Norepinephrine release was induced by electrical stimulation of the left cervicothoracic stellate ganglion and analyzed using radioenzymatic assay or high-performance liquid chromatography. In normoxically perfused hearts, evoked norepinephrine release was not affected by either of the two agents at doses of 1 to 10 mumol/L when extracellular K+ concentration was 4 mmol/L but dose-dependently reduced at 10 mmol/L K+ (D,L-propranolol: -53+/-4% at 1 mumol/L and -64+/-6% at 10 mumol/L; lidocaine: -37+/-11% at 0.1 mumol/L, -67+/-5% at 1 mumol/L, and -75+/-6% at 10 mumol/L). At 10 mmol/L K+, norepinephrine release was not affected by timolol or atenolol (both 10 mumol/L but was equally inhibited by D- or L-propranolol at 10 mumol/L (-56+/-5% and -53+/-9%, respectively), indicating a beta-blocking-independent mechanism. In hearts with metabolic acidosis (pH 6.85) at K+ of 4 mmol/L, neural norepinephrine release was also reduced by propranolol at 10 mumol/L (-37%). Finally, in hearts perfused with 4 mmol/L K+ and subjected to 6-minute periods of ischemia, neural norepinephrine release was similarly suppressed by D,L-propranolol (38+/-6% at 0.1 mumol/L, -44+/-5% at 1 mumol/L, and -78+/-3% at 10 mumol/L) or lidocaine (-39+/-7% at 0.1 mumol/L, -58+/-9% at 1 mumol/L, and -91+/-3% at 10 mumol/L). Conclusions. These data indicate that propranolol and lidocaine inhibit neural norepinephrine release via a Na+ channel-blocking mechanism that is synergistic with changes induced by ischemia, primarily raised extracellular K+. This mechanism may contribute to the anti-ischemic and antiarrhythmic properties of both agents in acute myocardial ischemia, which induces increased extracellular K+ and sympathetic activation.

【 授权许可】

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