Plasma fi endorphin activity was unusually high in our patients during vasodepressor syncope. It reached a value previously reported only in patients with septic shock.2 The pathophysiology of vasodepressor syncope is very complex. In the early phase, primary peripheral vasodilation probably predominates; subsequently, other mechanisms may be involved, such as lack of compensatory increase in cardiac rate and output, impairment of venous constriction and reflex-mediated vasodilation of skeletal muscle bed.’ Inhibition of the neuroadrenergic system may be an important factor. In fact, vasodepressor syncope can be experimentally induced by sudden interruption of sympathetic discharge.5 Moreover, norepinephrine activity does not increase during vasodepressor syncope3 Endogenous opioid peptides may inhibit the sympathetic system either centrally or peripherally.2-4~7*8 Moreover, endorphins may have a negative inotropic and chronotropic cardiac influence, reduce reflex discharge of cardiac or peripheral receptors, and exaggerate the response of J pulmonary receptors.214$7,8In our study, no independent measure of sympathetic activity was obtained. We also did not examine the effect of administration of naloxone or other opioid antagonists on the occur-

rence of syncope. However, the fact that hunger, fatigue and painful stimulation may induce vasodepressor syncope,’ as well as modify plasma fi endorphin activity,9,10 suggests some link between opioid peptides and vasodepressor syncope. This is supported by our data. Whether increase of plasma @endorphins during vasodepressor syncope is a primary etiologic event or a secondary phenomenon warrants further investigation. 1. Sobet BE, Roberts R. Hypotension and syncope. In: Braunwald E, ed. Heart Disease. Philadelphia: WB Saunders, 1988:884-89X 2. Holaday JW. Cardiovascular effects of endogenous opiate system. Ann Reo Pharmacol



3. Huges J. Peripheral

opiate receptor mechanism. Trends Pharmacol Sci 1981;2:21-24. 4. Feuerstein G, Sir& AL. The opioid system in cardiac and vascular regulation of normal and hypertensive states. Circulation 1987;75:125-129. 5. Wallin BG, Sundloff G. Sympathetic outflow to muscles during the vasovagal syncqe.

J Auton


Syst 1982,6:287-291.

6. Goldstein DS. Spanarkel M, Pitterman A, Taltzis R. Gratz E. Eostein S. Keiser HR. Circulatory control mechanisms in vasodepressor syncope. Am &art J 1982;104:1071-1075.

7. Martin WR. Pharmacology of opioids. Pharmacol Rev 1984;35:283-323. 6. Holaday JW. Cardiovascular consequences of endogenous opiate antagonism. Biochem



9. Reid LD. Endogenous opioid peptides and regulation of drinking and feeding. Am J Clin




10. Farrel PA. Exercise and endorphins-male

responses. Med Sci Sports



Paradoxical Increase in Heart Rate Before Conversion to Sinus Rhythm in Patients with Recent-Onset Atrial Fibrillation Anne A. Knowlton,

MD, and Rodney

H. Falk, MD

ecent-onset atria1 fibrillation (AF) has a high incidence of spontaneous conversion to sinus rhythm, R even if the ventricular rate is not slowed by pharmacologic means.’ In a study of the effects of digoxin in patients with recent-onset AF, Weiner et al* noted that the pulse rate before conversion to sinus rhythm did not differ significantly from that before digitalization. These data were based on hourly pulse rate measurements and did not take into account changes over a smaller time period. As part of a randomized double-blind study of the effect of digoxin in recent onset AF,’ we performed Holter monitoring. The present study describes our finding of a paradoxical increase in the ventricular response to AF occurring shortly before reversion to sinus rhythm in a subgroup of patients. The design of the study from which this subgroup of patients is drawn has been previously described.’ Briefly, 36 patients presenting with AF of 17 days’ duration, without clinical evidence of heart failure, were treated with oral digoxin solution in capsules (Lunoxicaps, Burroughs- Wellcome) or placebo. Echocardiography confirmed normal (>24%) or minimally impaired fractional shortening (20 to 24%) in 31 and 5 patients, respectively. Patients received an initial dose of 0.4 mg of Lanoxicaps followed by 0.4, 0.2 and 0.2 mg at 4, 8, 12 From

the Cardiology


Boston City


818 Harrison

Avenue, Boston, Massachusetts 02118, and Boston University School of Medicine, Boston. Manuscript received July 3, 1989; revised manuscript received August 23, 1989, and accepted August 25.







and 16 hours, respectively, or until conversion to sinus rhythm. This is equivalent to 0.75,0.5,0.25 and 0.25 mg of standard oral digoxin tablets.3 Patients receiving digoxin, /I blockers, calcium antagonists or antiarrhythmic agents were excludedfrom study. All patients were hospitalized and activity was minimized with patients generally confined to bedrest for the study period. Before digitalization, a Halter monitor was applied and a recording was taken for 18 to 24 hours or until reversion to sinus rhythm. To examine more carefully the effect of digoxin on heart rate, minimum, maximum and mean heart rates and total QRS complexes were analyzed every 15 minutes (rather than hourly) by a visual and computerized scanning system of validated accuracy for use in clinical studies (Cardio-Data Systems). If patients remained in AF after 18 hours the study code was broken. In those who had received placebo, Lanoxicaps were prescribed in the same doses already described, again with continuous Holter monitoring. To determine digoxin’s onset of action, mean heart rates for each I j-minute interval were compared to baseline in all patients studied (convertors and nonconuertors). Statistical analysis of heart rate response to digoxin versus placebo wasperformed by analysis of variance and paired t tests; a p value X0.05 indicated statistical significance. The mean heart rate at entry into the study was 117 f 6 beats/min. In patients remaining in AF who received

placebo there was no significant heart rate slowing in any 15-minute period compared to baseline. In those receiving digoxin the heart rate began to show statistically significant slowing 5.25 hours after the first dose of digoxin (mean heart rate 107 f 5 beats/min,p = 0.025 us baseline) and remained significantly slower thereafter. Based on these observed effects of digoxin on ventricular rate, subjects receiving digoxin were divided into those converting before the onset of ventricular slowing at 5 hours (group A, n = 8) and those converting after 5 hours (group B, n = 9). The mean time to conversion in group A was 1 .I f 0.4 hours and in group B it was 13.8 f 1.9 hours. There was no alteration in ventricular response to AF compared to baseline rates in group A patients. In contrast, group B patients had a significant decrease in mean heart rate by 1 hour before conversion (113 f 7 to 94.5 f 6 beatslmin, p

Paradoxical increase in heart rate before conversion to sinus rhythm in patients with recent-onset atrial fibrillation.

Plasma fi endorphin activity was unusually high in our patients during vasodepressor syncope. It reached a value previously reported only in patients...
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