RESUMO
No validated method exists for measuring lidocaine and its metabolites in myocardial tissue. We modified a previously described high-performance liquid chromatographic assay and applied it to plasma and to homogenized myocardial samples obtained from dogs that had received lidocaine by a double-infusion technique. Recovery of lidocaine, monoethylglycylxylidide and glycylxylidide after homogenization and extraction is reported. Assay variability, sensitivity and linearity over a wide range of sample sizes are also described. The results obtained with high-performance liquid chromatographic analysis are compared to quantitation of 14C-labeled lidocaine plus metabolites measured by an oxidation-scintillation technique. Myocardium to plasma partition coefficients for lidocaine, monoethylglycylxylidide and glycylxylidide were 2.16, 4.27, and 2.91, respectively.
Assuntos
Lidocaína/metabolismo , Miocárdio/metabolismo , Animais , Biotransformação , Cromatografia Líquida de Alta Pressão/métodos , Cães , Feminino , Lidocaína/análogos & derivados , Lidocaína/sangue , Masculino , OxirreduçãoRESUMO
The relationship between the probability of sustaining ventricular fibrillation during occlusion or release of a canine coronary artery and the amount of myocardium made ischemic has never been carefully assessed. We occluded the left anterior descending coronary artery above or below the septal artery for 20 min and then released the ligation. The amount of left ventricle perfused by the ligated vessel was determined by injection of different color monastral dyes above and below the ligation. Despite careful ligature placement immediately proximal or distal to the septal artery, there was wide variation in the amount of left ventricle perfused by the ligated vessel, or myocardium "at risk." Myocardium at risk ranged between 24 and 51 g for ligations placed above the septal artery and 14 and 27 g for ligations placed below the septal artery. Ventricular fibrillation during occlusion and after release correlated significantly with the amount of myocardium at risk. This relationship was well described using the logistic risk regression model. The model predicts uniformly low and uniformly high probability of ventricular fibrillation with small and large amounts of myocardium at risk, respectively, and a direct correlation for midrange values of myocardium at risk. This relationship can account for a substantial portion of non-drug related variability in outcome of antiarrhythmic trials using the canine coronary occlusion or release model.
