salicylates and Arrhythmias--Cardiac

Topics: Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Brain Diseases; Brain Edema; Diazepam; Gastric Lavage; Humans; Hypotension; Myocardial Infarction; Pacemaker, Artificial; Physostigmine; Pyridostigmine Bromide; Respiration, Artificial; Salicylates

Reactive oxygen species (ROS)-induced ROS release (RIRR) is a fundamental mechanism by which cardiac mitochondria respond to elevated ROS levels by stimulating endogenous ROS production in a regenerative, autocatalytic process that ultimately results in global oxidative stress (OS), cellular dysfunction and death. Despite elegant studies describing the phenomenon of RIRR under artificial conditions such as photo-induced oxidation of discrete regions within cardiomyocytes, the existence, biophysical properties and functional consequences of RIRR in intact myocardium remain unclear. Here, we used a semi-quantitative approach of optical superoxide (O(2)(-)) mapping using dihydroethidium (DHE) fluorescence to explore RIRR, its arrhythmic consequences and underlying mechanisms in intact myocardium. Initially, perfusion of rat hearts with 200 μM H(2)O(2) for 40 min (n = 4) elicited two distinct O(2)(-) peaks that were readily distinguished by their timing and amplitude. The first peak (P1), which was generated rapidly (within 5-8 min of H(2)O(2) perfusion) was associated with a relatively limited (10 ± 2%) rise in normalized O(2)(-) levels relative to baseline. In contrast, the second peak (P2) occurred 19-26 min following onset of H(2)O(2) perfusion and was associated with a significantly greater amplitude compared to P1. Spatio-temporal ROS mapping during P2 revealed active O(2)(-) propagation across the myocardium at a velocity of ~20 μm s(-1). Exposure of hearts (n = 18) to a short (10 min) episode of H(2)O(2) perfusion revealed consistent generation of P2 by high (≥200 μM, 8/8) but not lower (≤100 μM, 3/8) H(2)O(2) concentrations (P < 0.03). In these hearts, onset of P2 occurred following, not during, the 10 min OS protocol, consistent with RIRR. Importantly, P2 (+) hearts exhibited a markedly greater (by 3.8-fold, P < 0.001) arrhythmia score compared to P2 (-) hearts. To explore the mechanism underlying RIRR in intact myocardium, hearts were perfused with either cyclosporin A (CsA) or 4-chlorodiazepam (4-Cl-DZP) to inhibit the mitochondrial permeability transition pore (mPTP) or the inner membrane anion channel (IMAC), respectively. Surprisingly, perfusion with CsA failed to suppress (P = 0.75, n.s.) or even delay H(2)O(2)-induced P2 or the incidence of arrhythmias compared to untreated hearts. In sharp contrast, perfusion with 4-Cl-DZP markedly blunted O(2)(-) levels during P2, and suppressed the incidence of sustained ventricular tachycardia or ventricu

Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Cyclosporine; Diazepam; Ethidium; Fluorescence; Fluorescent Dyes; Hydrogen Peroxide; In Vitro Techniques; Intracellular Membranes; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardium; Organometallic Compounds; Oxidants; Oxidative Stress; Rats; Salicylates; Superoxides; Voltage-Dependent Anion Channels

Antiarrhythmic activity of a membrane-protecting agent Sal'magin was studied in rats with aconitine-induced cardiac arrhythmias. The test preparation was more potent than amiodaron in producing the antiarrhythmic effect in rats with Na(+)-induced cardiac arrhythmias. The absence of side effects, low toxicity, and high animal survival rate under experimental conditions suggest that Sal'magin holds much promise as an antiarrhythmic drug in clinical practice.

Topics: Aconitine; Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Female; Male; Rats; Salicylates; Sodium Channels

Recent studies have shown the ability of salicylic acid (SA) to trap hydroxyl radicals (OH.) generated during reperfusion in ischemic myocardium. Since OH. is implicated in the pathogenesis of reperfusion injury, we examined the effect of SA on reperfusion-induced arrhythmias and postischemic ventricular dysfunction. Isolated rat hearts perfused by the Langendorff technique were preperfused with Krebs-Henseleit buffer containing SA for 10 min. Hearts were then made ischemic for 30 min, followed by 30 min of reperfusion. In a separate group, SA was administered only at the onset of reperfusion. The left ventricular contractile functions, left ventricular developed pressure (LVDP) and its first derivative (LV dP/dt), coronary flow (CF), and creatine kinase (CK) release were determined before and after ischemia. Epicardial electrocardiogram (ECG) was also recorded to analyze the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF). SA improved LVDP, LV dp/dt, and CF recovery and reduced CK release compared to the control group. The incidence of VT and VF during reperfusion was also significantly reduced by SA. Analysis of tissue thiobarbituric acid-reactive products indicates that SA decreased oxidative stress during reperfusion. In conclusion, these results suggest that SA reduces myocardial reperfusion injury and attenuates ventricular arrhythmias by trapping OH. radicals upon reperfusion in isolated rat hearts.

Topics: Animals; Arrhythmias, Cardiac; Creatine Kinase; Electrocardiography; In Vitro Techniques; Male; Rats; Rats, Inbred Strains; Reperfusion Injury; Salicylates; Salicylic Acid; Ventricular Function, Left

Topics: Aged; Arrhythmias, Cardiac; Diazepam; Female; Heart Arrest; Humans; Male; Middle Aged; Respiratory Insufficiency; Salicylates

Certain basic principles are applicable to most drug overdose emergencies. These include emptying the stomach, administering activated charcoal, supporting vital functions, protecting target organs and using specific antidotes in appropriate cases. There are certain steps to be taken automatically in an unconscious patient with an unknown overdose. Drug screens rarely affect management. Special situations involve overdoses of acetaminophen, salicylates, tricyclic antidepressants, anticholinergics and narcotics.

Topics: Acetaminophen; Acetylcysteine; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cathartics; Charcoal; Humans; Hypnotics and Sedatives; Ipecac; Naloxone; Narcotics; Parasympatholytics; Poisoning; Salicylates

Topics: Adult; Amitriptyline; Arrhythmias, Cardiac; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Parasympatholytics; Physostigmine; Reflex, Babinski; Salicylates

Topics: Acidosis; Aged; Alcoholic Intoxication; Alkalosis; Alkalosis, Respiratory; Arrhythmias, Cardiac; Coma; Diabetic Ketoacidosis; Diagnosis, Differential; Encephalitis, Arbovirus; Humans; Male; Myocardial Infarction; Poisoning; Salicylates; Stomach Neoplasms; Sweating

Topics: Acute Disease; Adult; Antidepressive Agents; Arrhythmias, Cardiac; Barbiturates; Body Temperature; Carbon Monoxide Poisoning; Child, Preschool; Female; Hospitalization; Humans; Hypnotics and Sedatives; Hypotension; Intensive Care Units; Intubation, Intratracheal; Male; Middle Aged; Poisoning; Rectum; Respiration; Salicylates; Seasons; Tranquilizing Agents; Unconsciousness