Differential effects of four xylidine derivatives in the model of ischemia- and re-perfusion-induced arrhythmias in rats in vivo.
The aim of our study was to find the most effective xylidine derivative, which reduced mortality, reduced incidence and duration of severe arrhythmias and had a beneficial influence on hemodynamic parameters in an in vivo setting. We compared the action of lidocaine, articaine, ropivacaine and mepivacaine in a dose 2.5 or 5mg/kg/ml/h infused from 10min before left anterior descending coronary artery occlusion until the end of the experiment. In the rat ischemia- and re-perfusion-induced arrhythmia models, the following parameters were measured or calculated: mortality index, ventricular fibrillation and tachycardia incidence and duration, systolic, diastolic and mean arterial blood pressure, heart rate and pressure rate product. Lidocaine produced the most significant reduction in mortality index (P<0.05) after both doses. At the higher dose, lidocaine and articaine shortened ventricular fibrillation and tachycardia duration (P<0.05-P<0.001), while ropivacaine prolonged them. A hypertensive effect was observed after a lower dose of lidocaine during occlusion and early re-perfusion as compared to others (P<0.05). Beneficial effects were mainly observed with lidocaine, which protected against sudden cardiac death. The novelty was lidocaine's dose independent protection against blood pressure drop in early re-perfusion, which could be linked to the effects observed on the other end-points. Articaine showed beneficial effects but they weren't as pronounced as that of lidocaine. Nevertheless, in the light of our results, articaine could supposedly be used as a substitute for lidocaine in patients with hypertension.
Krzemiński
Tadeusz F
TF
Department of Pharmacology, Cardiovascular Research Division, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze, Poland. tadkrzem@ka.onet.pl
Mitrega
Katarzyna
K
Zorniak
Michał
M
Porc
Maurycy
M
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D001794:Blood Pressure / Q000187:drug effects; D002355:Carticaine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008619:Mepivacaine / Q000008:administration & dosage / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D012720:Severity of Illness Index; D013610:Tachycardia / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology
D000577:Amides; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000077212:Ropivacaine; D008012:Lidocaine; D008619:Mepivacaine; D002355:Carticaine