Documented sudden cardiac death in prolonged QT syndrome.

Documentation of the mechanism of sudden death is described in a patient with a prolonged QT interval. Ventricular tachycardia was initiated by a ventricular premature beat (VPB) with a prematurity index similar to previous isolated VPBs. This event occurred despite the fact that the patient was receiving phenytoin sodium, a drug known to shorten the QT interval.

Superior bioavailability of digoxin solution in capsules.

The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers. Digoxin tablets that were 97% dissolved in 1 hr in vitro were not significantly better absorbed than tablets with a dissolution rate of 78%. A solution given in capsule form had greater bioavailability than tablets of 97% dissolution rate; serum and urinary glycoside levels after 0.4 mg doses of the encapsulated solution were similar to those attained after 0.5 mg doses of tablets with dissolution rates of 78% and 97%. The bioavailability of the solution in capsule form exceeded that of equal doses of the same solution given as a liquid or that of a standard elixir. No increase in gastrointestinal or cardiac toxicity was detected. Inter- and intrasubject variation in bioavailability was not decreased. Above a certain level, dissolution rate is no longer the limiting factor in digoxin absorption. The mechanism of the enhanced bioavailability of concentrated liquid digoxin in capsule form remains to be determined. Such a preparation deserves further consideration as a possible replacement for digoxin tablets.

Comparison of lorcainide and quinidine in the treatment of ventricular ectopy.

Lorcainide, a new type I antiarrhythmic agent, was compared to quinidine in respect to antiarrhythmic efficacy and clinical safety. Thirteen subjects completed an open, randomized, crossover study with analysis of 24-hour ambulatory ECG monitoring and drug blood levels. The QRS and Q-T intervals increased with both lorcainide and quinidine. The mean reduction in total ventricular premature beats (VPBs) with quinidine was 16 percent compared to 68 percent with lorcainide (p less than .05). With lorcainide eight of 13 subjects had a significant (greater than 82 percent) reduction in VPBs compared to only three of 13 subjects taking quinidine (p less than .05). This same relationship was observed when mean VPB/1,000 heartbeats was analyzed. Ventricular tachycardia was no longer present in five of nine subjects taking lorcainide and in two of nine taking quinidine. No relationship could be established between drug level and arrhythmia suppression in this small population. Some CNS effects were reported in both groups, but no significant hematologic, chemical, or urinary adverse effects were seen with either drug. Thus, lorcainide compares favorably to quinidine in regard to arrhythmia suppression, but was limited in its clinical utility by CNS side effects.

Effects of anesthetics containing epinephrine on catecholamine levels during periodontal surgery.

Nine stable cardiovascular disease patients were evaluated in a double-blind cross-over trial during periodontal surgery using 2% lidocaine with epinephrine 1:100,000 or lidocaine alone. In the lidocaine with epinephrine group, epinephrine levels increased from 198 +/- 54 pg/ml to 592 +/- 166 pg/ml at 2 minutes post-injection. In the lidocaine alone group, epinephrine levels increased from a baseline of 115 +/- 34 pg/ml to 150 +/- 34 pg/ml at 2 minutes post-injection. Despite these elevations in epinephrine, no significant changes in heart rate or mean arterial pressure were noted. Plain lidocaine provided unsatisfactory levels of hemostasis and/or anesthesia during periodontal surgery. This study documents acute elevations in plasma epinephrine levels following local dental anesthesia for periodontal surgery. These elevations in plasma epinephrine failed to produce a significant cardiovascular response in a group of stable cardiovascular disease patients. This suggests that the cardiac effects of local anesthetics containing epinephrine are small and that they can be safely used in stable cardiovascular disease patients.

The effect of limited handrail support on total treadmill time and the prediction of VO2 max.

Holding onto the front handrail during treadmill testing significantly increases total treadmill time (TT) and predicted VO2max when compared with tests without front handrail support. By limiting the amount of handrail support to the tips of two fingers of one hand, the difference in TT can be substantially reduced. In the present study, the difference in TT between tests with and without handrail support for healthy men was not significantly different. However, this was not true for healthy women and for male patients with coronary artery disease and myocardial infarction.

Intravenous and oral lorcainide: assessment of central nervous system toxicity and antiarrhythmic efficacy.

Twenty-eight subjects underwent evaluation of drug toxicity and antiarrhythmic efficacy with oral and intravenous lorcainide. Lorcainide, a new type 1C antiarrhythmic drug, has an active metabolite, norlorcainide, which accumulates after oral but not significantly after intravenous administration. Group 1 consisted of 14 subjects who received intravenous lorcainide with an initial bolus of 2 mg/kg at a rate of 2 mg/min followed by 0.14 mg/min or 200 mg/24 hours. The lorcainide level after bolus was 0.432 micrograms/ml and fell to 0.178 micrograms/ml at 4 to 6 hours despite constant drug infusion. Prior work has demonstrated no detectable norlorcainide levels after intravenous infusion. Group II consisted of 14 subjects who received oral lorcainide, 100 mg orally every 8 hours. Mean lorcainide levels were 0.287 micrograms/ml and mean norlorcainide levels were 0.377 micrograms/ml. Only 2 of 12 subjects in group I experienced headache, dizziness, or sleep disturbance, compared to 12 of 14 subjects in group II (p less than 0.01). Intravenous lorcainide has a lower incidence of central nervous system side effects than oral lorcainide. These effects may be attributable to the accumulation of the norlorcainide metabolite with oral therapy.