Intravenous Cocaine Decreases Cardiac Vagal Tone, Vagal Index (Derived in Lorenz Space), and Heart Period Complexity (Approximate Entropy) in Cocaine Abusers

Abstract

We assessed the effects of i.v. cocaine on parasympathetic and sympathetic nervous system activity, and on the complexity vs. regularity of changes in heart rate over time. Fourteen otherwise healthy men with histories of i.v. cocaine abuse received bolus injections of cocaine (20 mg or 40 mg) and placebo (saline) on different days.Cardiovascular measures derived from the electrocardiogram, including heart rate, Porges' vagal tone (respiratory sinus arrhythmia), the 0.10 Hz rhythm, Toichi's vagal index, Toichi's sympathetic index, and approximate entropy (ApEn), were measured continuously. As predicted, cocaine produced tachycardia, accompanied by pronounced decreases in response to 40 mg cocaine in two different vagal tone indexes that precisely mirrored the increases in heart rate. The measure of sympathetic (and vagal) neural influences on the heart (0.10 Hz wave) also decreased in response to cocaine. Converging evidence from Toichi's vagal index supported the conclusion that the tachycardia from cocaine was due to withdrawal of cardiac vagal tone. These findings, and evidence that cocaine decreased cardiovascular complexity, contradict the prevailing assumption that the mechanism by which cocaine produces tachycardia is sympathetic (beta-adrenergic Cocaine is a widely abused drug with pronounced subjective and cardiovascular effects (Fischman et al. 1976;Johanson and Fischman 1989). Early human research on cocaine (Fischman et al. 1976;Resnick et al. 1977) revealed dose-dependent positive chronotropic effects on the heart, reaching a mean increase in heart rate of 38 bpm in response to 32 mg i.v. cocaine. Effects on the cardiovascular system can be remarkable in some subjects. Increases in heart rate have been reported to occur in response to doses as low as 13 mg i.v. cocaine; these increases ranged from 15 to 46 bpm (Ambre et al. 1988). The magnitude of these effects has led to the conclusion that cardiotoxicity from cocaine may be a major factor in death due to cocaine overdose (Billman 1990).The cardiotoxicity of cocaine has directed interest toward the autonomic mechanism by which the drug produces cardiovascular arousal. It has been assumed (Billman 1990;Ritchie and Greene 1990) that the cardiovascular response to cocaine is due primarily to activation of sympathetic autonomic mechanisms. This view stems in part from evidence that cocaine directly blocks reuptake of catecholamines in the periphery (Ritchie and Greene 1990 that propranolol (a beta-adrenergic blocker) and phentolamine (an alpha-adrenergic blocker) may partially reverse cardiovascular arousal in cocaine overdose (Rappolt et al. 1977). However, controlled studies at moderate dosages of cocaine in humans would be needed to confirm these observations. Furthermore, there is conflicting evidence in animal research concerning the role of the sympathetic nervous system in the response to cocaine in the intact organism. Recent findings indicate that central administration of cocaine actually decreases peripheral sympathetic neural activity in c...

Cardiac Dysrhythmia Associated with the Immediate Postictal State after Maximal Electroshock in Freely Moving Rat

“…The ApEn reflects the repetition of complex patterns (for review: 7) in the fluctuation of the beat-to-beat periods. Clinical investigations have reported that ApEn decreases during cocaine-evoked arrhythmia (16), general anesthesia (17), in infants that have had episodes of aborted suddeninfant-death syndrome (18), in patients with high risk of sudden cardiac death (10), and in heart transplant patients (19). Our result established that the immediate postictal stage, characterized by a transient loss of entropy in beat-to-beat periods, might consist of a short episode with putative risk of lethal cardiac complication in epilepsy patients.…”

“…This process was repeated for m ‫ס‬ 3, and ApEn was the difference between the values at m ‫ס‬ 2 and m ‫ס‬ 3. To normalize r to a fixed percentage of the time-series SD, which is the standard implementation of ApEn, gives ApEn a translation and scale invariance (18), so it remains unchanged under uniform process magnification, reduction, or constant shift, and it is decorrelated from SD analysis (14)(15)(16)(17).…”

“…We used the Friedman test (z, value of Friedman's statistic; DLL, degrees of freedom; p, probability) to compare the calculated parameters before and after MES; following the z value, the Wilcoxon test was used for post hoc comparisons (14)(15)(16)(17).…”

Sex Differences and Heritability of Two Indices of Heart Rate Dynamics: A Twin Study

“…This and other 'chaos' derived parameters have proven valuable in the area of cardiovascular pathology, for example in discriminating cardiac patient groups with respect to the dynamics of their cardiovascular system. RSA and ApEn have been found to be significantly correlated (Newlin et al, 2000), but are by no means identical. For example, their mathematical foundation is quite different.…”

Heart rate complexity during the temporary systems dedifferentiation

“…Можно предполагать, что при более длительной регистрации сердечного ритма (до трех часов) будет наблюдаться постепен-ное возрастание его сложности, но более медленное, чем первоначальное снижение, так как фаза элиминации в кинетике этанола значительно более длительная, чем фаза резорбции. Интересным является тот факт, что подобное наблюдаемому в наших данных снижение сложности сердечного ритма показано и для острого введения кокаина (вероятно, еще од-ного «дедифференциатора»), причем ApEn снижается в этом случае тем больше, чем выше вводимая доза (Newlin et al, 2000). Таким образом, снижение сложности сердечного ритма не только качественно отражает наличие системной дедифференциации, но и, по всей ви-димости, количественно связано с ее степенью.…”