HEMODYNAMIC AND ANTIARRHYTHMIC EFFECTS OF ORAL AND PARENTERAL MEXILETIN THERAPY IN PATIENTS WITH NORMAL AND IMPAIRED LEFT-VENTRICULAR FUNCTION AND VENTRICULAR ARRHYTHMIAS

The hemodynamik effects and the rhythm profile of oral and parenteral therapy with mexiletine were investigated in 28 patients with clinical signs of ventricular arrhythmias using right heart catheterization, T c-99m ventriculography and ambulatory ECG recordings. Mexiletine plasm a concentrations were measured in addition at fixed time points. 16 pa tients with normal ventricular function (EF 53 +/- 8 %; Group I) and 1 2 patients with considerably impaired left ventricular function (EF 22 +/- 6 %, Group II) received an oral dairy dose of 3 x 300 mg mexileti ne over 7 days with additional acute intravenous application of mexile tine (3 mg/kg BW) in Group II. The study results revealed no significa nt effects being exerted by mexiletine therapy on the hemodynamic para meters such as ejection fraction, cardiac output, the pressure values in the pulmonary artery, and vascular resistances compared to initial values either in the group with normal or in that with impaired ventri cular function (Group I: EF 53.5 vs 53 %; CO 7.3 vs 6.7 l/min; PAPm 17 vs 17 mmHg; SVR 1265 vs 1304 dyn.sec.cm(-5). Group II: EF 22 vs 22 %; CO 5.8 vs 4.8 l/min; PAPm 23 vs 21 mmHg; SVR 1235 vs 1909 dyn.sec.cm( -5) p > 0.05). There were also no significant hemodynamic changes seen after intravenous application of mexiletine in patients with impaired LV function, as compared to initial values (EF 21 vs 22 %; CO 4.9 vs 4.8 l/min; PAPm 24 vs 21 mmHg; SVR 1522 vs 1900 dyn.sec.cm(-5)). The r espective exercise values of the two groups showed no cardiodepressive effects either. Most of the patients, except for two, demonstrated si gnificantly less VES and ventricular couplets under mexiletine therapy . The plasma concentration of mexiletine at the time of hemodynamic me asurement after oral therapy was within the therapeutic range at 1133 ng/ml in Group I and 945 ng/ml in Group II. Being well tolerated, mexi letine proved to induce favorable hemodynamic and antiarrhythmic effec ts both in patients with normal and in those with considerably impaire d left ventricular function. Mexiletine provoked no hemodynamic deteri oration in patients with strongly impaired ventricular function.