William Shapiro

Relationship of Plasma Digitoxin and Digoxin to Cardiac Response Following Intravenous Digitalization in Man

The value of plasma digitalis determinations will depend upon the accuracy with which they mirror the myocardial effects of digitalis. Ten volunteers received 0.8 mg of digitoxin intravenously, and after 2 hours the mean plasma digitoxin level was 45.6 ± 6 m&mgr;g/ml but declined over 4 to 6 hours during plasma-tissue equilibration. The cardiac response, as indicated by decreases in the left ventricular ejection time index (LVETI) and Q-S2 intervals (P < 0.01), was present at 2 hours and reached maximum at 4 to 6 hours. Subsequently, plasma level, LVETI, and Q-S2 changed in the same direction during slow excretion.Six subjects received 1.0 mg of digoxin intravenously. Mean plasma digoxin at 30 min was 6.8 ± 0.3 m&mgr;g/ml; it fell after 3 to 4 hours to levels usually seen during maintenance digoxin administration (<3 m&mgr;g/ml) and then declined more slowly. Correlation of individual digoxin levels with &Dgr;LVETI values during the first 4 hours was significant (P < 0.01). The half-life (T½) for the dominant slope of the plasma curve was 30.5 hours by plasma determinations and 29 hours by LVETI determination.Plasma levels of digitoxin and digoxin were related to their cardiac effects under the conditions studied. Prior to plasma-tissue equilibration, plasma determinations of digoxin and digitoxin will be higher than levels seen during maintenance administration of these drugs.

Technetium stannous pyrophosphate myocardial scintigrams in the recognition of myocardial infarction in patients undergoing coronary artery revascularization.

Myocardial imaging using technetium 99m stannous pyrophosphate (99mTc-PYP) has been utilized preoperatively and three to five days postoperatively to detect myocardial infarction in 48 patients undergoing aortocoronary bypass grafting, including 7 having valve replacement (5 aortic, 2 mitral) in addition to revascularization. In the total group of patients operated on there were 3 deaths (6%). Preoperatively, 26 patients had unstable angina and 10 had severe left main coronary artery disease. Eleven of the 48 (23%) were women. ECG and enzyme-proved infarctions occurred in 6 of the 48 patients (12%), but the addition of 99mTc-PYP myocardial imaging demonstrated scintigraphic evidence of infarction in 15 patients (31%), including 2 who died in the operating room. The 99mTc-PYP myocardial imaging technique, which has proved safe, simple, and relatively inexpensive in these patients, suggests that the incidence of infarction after coronary bypass operations is somewhat higher than has been previously recognized from just ECG and enzyme changes. This technique also has been of value in helping to exclude myocardial infarction in difficult clinical situations such as postoperative arrhythmias and the postpericardiotomy syndrome.

Observations on the Regulation of Cerebral Blood Flow in Complete Heart Block

The simultaneous effects of right ventricular pacing on cerebral blood flow (CBF) and cardiac function in complete heart block have not been reported. Catheters in the jugular bulb, right ventricle, and pulmonary and brachial arteries of five patients, aged 49 to 78 years, allowed studies at initial rates of 30 to 40 and during the tenth minute of pacing at 60, 70, 90, and 100 per minute. Mean initial cardiac output (CO) was 2.8 L per minute and increased 29% to 3.6 at a rate of 60 per minute (P<0.01). Simultaneous mean control CBF was also low, but rose to 118% of control with pacing (P<0.05). Systemic, cerebral, and pulmonary vascular resistances declined with these increases in flow as the elevated mean venous and arterial pressures remained stable. Mean arterial oxygen and carbon dioxide tensions and pH were normal at all rates. The parameters measured were not materially altered by pacing at rates above 60 per minute. The changes in CBF were well correlated with those of CO (r=0.81, P<0.01) and unrelated to simultaneous mean arterial or cerebral perfusion pressures. The alterations in CO were also unrelated to these pressures. The data clearly demonstrate a disturbance in CBF autoregulation, which may be a function of the low CO state.

The effect of diphenylhydantoin (Dilantin) and quinidine on left ventricular function in dogs.

Abstract The effect of Dilantin upon left ventricular performance was investigated in an open-chest dog preparation and compared to that of quinidine under identical conditions. An initial intravenous injection of Dilantin produced a transient negative inotropic effect upon the left ventricle. The magnitude of the negative inotropic effect was similar following comparable dose levels of quinidine base, but the duration of the effect was more transient after Dilantin. The maximal negative inotropic effect following a second Dilantin injection was greater than that following an initial injection. After the second injection of quinidine, however, the degree of myocardial depression was similar to that following the initial injection. Again, the duration of the effect after Dilantin was more transient than after quinidine. The results with Dilantin are in keeping with the fact that most potent antiarrhythmic agents depress ventricular function. Insofar as such data may be applied to clinical situations, one must weigh the harmful transient negative inotropic effect of Dilantin against its beneficial antiarrhythmic property.

Myocardial Infarction in Men in the Third Decade of Life

Excerpt Myocardial infarction is uncommon in the fourth decade and rare in the third decade of life. Our recent experience with several patients in the third decade of life led us to search for all...

Cardiac effects of diphenylhydantoin (Dilantin) in man

Abstract The effect of Dilantin (diphenylhydantoin sodium) on right ventricular function was evaluated in 5 patients undergoing diagnostic cardiac catheterization. A transient negative inotropic effect on the right ventricle and an apparently induced conduction disturbance were seen following administration of Dilantin. Nausea, vomiting and hypotension were also associated with the administration of Dilantin. These findings emphasize the need for more information in order to properly utilize Dilantin as an antiarrhythmic agent.

Comparative efficacy of bepridil versus placebo in angina pectoris : treatment and withdrawal studies

The efficacy and safety of once-daily doses of 200, 300, and 400 mg of bepridil hydrochloride were compared with placebo in a 14-week multi-center, double-blind parallel study. All doses of bepridil significantly reduced weekly anginal attacks and nitroglycerin consumption from baseline levels. Bepridil also significantly improved total exercise time, time to angina, time to 1 mm ST-segment depression, and total work. Reduction in heart rate (maximum mean decreases of 7-8 beats/min) and prolongation of QT and corrected QT (QTc) intervals were associated with bepridil therapy. Bepridil was well tolerated; most adverse reactions reported were mild and tolerable even at the 400-mg dose. This study provides strong support for the use of bepridil in patients with chronic stable angina pectoris that is not optimally controlled by other available antianginal therapies. A double-blind withdrawal study is also reported, in which patients stabilized on bepridil were randomized to either continue on bepridil therapy or receive placebo. Patients who were withdrawn from bepridil therapy showed significant increases in the number of weekly anginal attacks and nitroglycerin consumption compared with levels seen during long-term treatment. Patients withdrawn from bepridil therapy showed significant deterioration in exercise tolerance compared with baseline and with those maintained on bepridil.

Improved Exercise Myocardial Perfusion During Lidoflazine Therapy

Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administra tion of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.