Differential effects of scopolamine on nocturnal cortisol secretion, sleep architecture, and REM latency in normal volunteers: relation to sleep and cortisol abnormalities in depression

Scopolamine (SCOP) (3.0 mu/kg and 6.0 micrograms/kg) and saline were administered intramuscularly at 11:00 PM to eight normal male volunteers in a randomized design, and the effects on the sleep electroencephalogram (EEG) and nocturnal cortisol secretion (via blood sampling every 15 min) were evaluated. Compared to saline, SCOP produced a significant dose-related delay in rapid eye movement (REM) latency. In contrast, neither dose of SCOP significantly affected nocturnal plasma cortisol concentrations. These results suggest that the central cholinergic system that regulates the onset of REM sleep is more sensitive to dysregulation than the cholinergic system that controls the degree of nocturnal cortisol secretion. If central cholinergic overactivity is responsible for both the REM sleep latency and cortisol abnormalities in depressed patients, then our findings with SCOP might help explain why the incidences of these abnormalities are different.     

Defibrotide, an antithrombotic substance that preserves postsynaptic alpha- and beta-adrenergic function in post acute infarcted rabbit hearts

Defibrotide, a simple strand polydeoxyribonucleotide of mammalian origin with a molecular weight of 20,000 daltons, given intravenously to the rabbit before and after production of left ventricular infarction, prevents the alteration of the contractile response to postsynaptic adrenergic stimulation tested in isolated perfused heart preparations 3 days after coronary artery occlusion. According to the dose-response curves for isoproterenol and tyramine, left ventricular dP/dtmax was significantly depressed in infarcted hearts, whereas the dose-response curve for the inotropic effect of phenylephrine was markedly enhanced. These alterations were prevented by pretreatment of the rabbits with defibrotide (32 mg/kg/h i.v. for 6 h). In fact the potency ratios, calculated from the dose-response curves related to dP/dtmax of isoproterenol, tyramine, and phenylephrine in infarcted and control hearts excised from defibrotide treated and shamoperated rabbits, are nearly 1. The observed alterations in myocardial contractility in infarcted hearts seem to be specific for postsynaptic alpha and beta-adrenoceptors since the dose-response curve of left ventricular dP/dtmax for histamine is not different from control. The results obtained with defibrotide reflect the ability of this substance to protect the myocardial tissue from ischemic damage: this is also supported by the capacity of defibrotide (8 mg/kg/h i.v. for 6.5 h) to prevent the reduction of CPK-activity in the infarcted ventricle. Finally, we suggest that the observed beneficial effect of defibrotide in rabbit heart may also be explained by the antithrombotic effect of this substance, which is based on its profibrinolytic activity and PGI2-release.     

Relationship between REM sleep latency and nocturnal cortisol concentrations in depressed patients

SUMMARY  Due to conflicting reports on the possible association between shortening of rapid eye movement (REM) latency and increased cortisol secretion in patients with severe depression, this study examined the relationship between REM sleep latency and nocturnal cortisol concentration in 12 outpatients with major depression. The results showed a significant inverse correlation ( r = —0.71, P <0.01) between REM sleep latency and mean (23.00 hours-03.00 hours) plasma cortisol concentration. Age and severity of depression did not contribute to the inverse relationship. REM activity and density during the first REM period showed no significant correlations with the cortisol measures. A review of the literature suggests that this relationship might be unique to subjects with major depression, and again raises the possibility that these biological disruptions may have a common neurochemical basis.     

Polymorphous ventricular tachycardia as undesirable effect of the association of quinidine treatment with hysteresis ventricular inhibited pacing

Holter monitoring in a 75-year-old man with a VVI pacemaker with rate hysteresis and concomitant quinidine treatment documented the occurrence of several episodes of non-sustained polymorphous ventricular tachycardia, triggered by each first paced beat following the longer escape interval. These arrhythmias disappeared when quinidine was withdrawn or when the pacemaker was reprogrammed without hysteresis. We hypothesize that the association of the different effects produced by hysteresis and quinidine created the electrophysiologic substrate for the observed arrhythmias.     

Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia; long-term outcome in relation to acute electrophysiological findings.

AIMS: Radiofrequency catheter ablation is effective at terminating ventricular tachycardia, but the overall clinical role of the technique in patients with a prior myocardial infarction is still debated, due to the uncertainties of the long-term reliability of the procedure. The purpose of this study was to prospectively investigate the relationship between acute results obtained by catheter ablation and long-term outcome in a homogeneous population of patients with post-myocardial infarction ventricular tachycardia. METHODS AND RESULTS: One hundred and twenty-four consecutive patients with recurrent, drug-refractory, haemodynamically tolerated ventricular tachycardia were included in the study. This population accounted for 30% of the patients with post-myocardial infarction ventricular tachycardia admitted between April 1992 and September 1997 to the investigating centres. The ablation was successful in eliminating sustained ventricular tachycardia in 91 of them (73%); a partial result was obtained in 21 (17%) and failure in 12 (10%). Low dose amiodarone and/or beta-blockers were maintained in 86% of the patients. Over a median follow-up of 41.5 months (interquartile range 30.5-59.5 months), there were 15 deaths (12%), three of which were sudden (2.4%); the 12 remaining patients died of heart failure. Event-free survival analysis showed a significantly lower ventricular tachycardia recurrence rate in patients with a successful procedure as compared to those with failure or a partial result (19% vs 53% at one year and 27% vs 60% at 3 years, P=0.003). A repeat procedure was performed in 15 patients with early recurrences and was followed in all by long-term success. Of those who submitted to a second procedure, 93/124 patients (75%) are free of ventricular tachycardia recurrences. An implantable cardioverter-defibrillator (ICD), following procedure failure, was implanted in 13 patients (11%) of the study population. CONCLUSIONS: Radiofrequency catheter ablation is effective in a wide population of patients with recurrent tolerated ventricular tachycardia, with very low sudden death and cardiac mortality rates over the long-term. Persistent ventricular tachycardia inducibility after catheter ablation requires an ICD implant and/or repeat ablation.     

Usefulness of excitable gap and pattern of resetting in atrial flutter for determining reentry circuit location

Clinical and experimental data show that type I atrial flutter is due to a reentry mechanism with an excitable gap. To define the location of the reentry circuit of atrial flutter, width of excitable gap, poststimulation cycle and pattern of reset after premature stimulus were analyzed in 18 patients during atrial flutter at multiple atrial sites (high, lateral, posterior and septal right atrium, and coronary sinus). The pattern of reset was defined as flat or increasing whether the return cycle remained unchanged or prolonged with increasing prematurity. Shorter values of the excitable gap were found at the coronary sinus (33 +/- 8 ms) and high right atrium (30 +/- 10 ms) than at the posterior (43 +/- 9 ms) or septal right atrium (45 +/- 11 ms). Intermediate values (36 +/- 8 ms) were measured at the lateral right atrium. Poststimulation cycle, corrected for atrial flutter cycle length, was shorter in the posterior (6 +/- 7 ms) and septal right atrium (5 +/- 7 ms) than in the coronary sinus (35 +/- 9 ms), and the high (23 +/- 10 ms) and lateral right atrium (15 +/- 9 ms). A flat pattern of resetting occurred more frequently at the septal (18 of 18 patients) and posterior right atrium (15 of 18) than at the lateral (8 of 18) and high right atrium (2 of 17), and was never observed at the coronary sinus. Atrial flutter was successfully terminated by overdrive atrial pacing in 15 of 18 patients, and termination was more easily obtained from the septal and posterior right atrium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac and arrhythmic complications in patients with COVID‐19

In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.