The Pharmacology and Clinical Use of Lidocaine and Procainamide

Both procainamide and lidocaine are useful for acutely treating cardiac arrhythmias, and procainamide can be useful in chronic antiarrhythmic regimens. Successful management of cardiac arrhythmias requires knowledge of: 1) the mechanism and natural history of the arrhythmia, 2) the physiologic state of the patient, and 3) the cardiac effects, pharmacodynamics, and general pharmacology of the antiarrhythmic drugs

Risk Stratification in Post-MI Patients Based on Left Ventricular Ejection Fraction and Heart-Rate Turbulence

Objectives: Development of risk stratification criteria for predicting mortality in post-infarction patients taking into account LVEF and heart-rate turbulence (HRT). Methods: Based on previous results the two parameters LVEF (continuously) and turbulence slope (TS) as an indicator of the HRT were combined for risk stratification. The method has been applied within two independent data sets (the MPIP-trial and the EMIAT-study). Results: The criteria were defined in order to match the outcome of applying LVEF ( 30 % in sensitivity. In the MPIP trial the optimal criteria selected are TS normal and LVEF ( 21 % or TS abnormal and LVEF ( 40 %. Within the placebo group of the EMIAT-study the corresponding criteria are: TS normal and LVEF ( 23 % or TS abnormal and LVEF ( 40 %. Combining both studies the following criteria could be obtained: TS normal and LVEF ( 20 % or TS abnormal and LVEF ( 40 %. In the MPIP study 83 out of the 581 patients (= 14.3 %) are fulfilling these criteria. Within this group 30 patients have died during the follow-up. In the EMIAT-trial 218 out of the 591 patients (= 37.9 %) are classified as high risk patients with 53 deaths. Combining both studies the high risk group contains 301 patients with 83 deaths (ppv = 27.7 %). Using the MADIT-criterion as classification rule (LVEF ( 30 %) a sample of 375 patients with 85 deaths (ppv = 24 %) can be selected. Conclusions: The stratification rule based on LVEF and TS is able to select high risk patients suitable for implanting an ICD. The rule performs better than the classical one with LVEF alone. The high risk group applying the new criteria is smaller with about the same number of deaths and therefor with a higher positive predictive value. The classification criteria have been validated within a bootstrap study with 100 replications. In all samples the rule based on TS and LVEF (= NEW) was superior to LVEV alone, the high risk group has been smaller (( s: 301 ( 14.5 (NEW) vs. 375 ( 14.5 (LVEF)) and the positive predictive value was larger (( s: 27.2 ( 2.6 % (NEW) vs. 23.3 ( 2.2 % (LVEF)). The new criteria are less expensive due to a reduced number of high risk patients selected

A Statistical Model for Risk Stratification on the Basis of Left Ventricular Ejection Fraction and Heart-Rate Turbulence

The MPIP data set was used to obtain a model for mortality risk stratification of acute myocardial infarction patients. The predictors heart rate turbulence (HRT) and left-ventricular ejection fraction (LVEF) were employed. HRT was a categorical variable of three levels; LVEF was continuous and its influence on the relative risk was explained by the natural logarithm function (found using fractional polynomials). Cox - PH model with HRT and lnLVEF was constructed and used for risk stratification. The model can be used to divide the patients into two or more groups according to mortality risk. It also describes the relationship between risk and predictors by a (continuous) function, which allows the calculation of individual mortality risk

The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts

The clinical effects of hypokalemia including action potential prolongation and arrhythmogenicity suppressible by lidocaine were reproduced in hypokalemic (3.0 mM K(+)) Langendorff-perfused murine hearts before and after exposure to lidocaine (10 μM). Novel limiting criteria for local and transmural, epicardial, and endocardial re-excitation involving action potential duration (at 90% repolarization, APD(90)), ventricular effective refractory period (VERP), and transmural conduction time (Δlatency), where appropriate, were applied to normokalemic (5.2 mM K(+)) and hypokalemic hearts. Hypokalemia increased epicardial APD(90) from 46.6 ± 1.2 to 53.1 ± 0.7 ms yet decreased epicardial VERP from 41 ± 4 to 29 ± 1 ms, left endocardial APD(90) unchanged (58.2 ± 3.7 to 56.9 ± 4.0 ms) yet decreased endocardial VERP from 48 ± 4 to 29 ± 2 ms, and left Δlatency unchanged (1.6 ± 1.4 to 1.1 ± 1.1 ms; eight normokalemic and five hypokalemic hearts). These findings precisely matched computational predictions based on previous reports of altered ion channel gating and membrane hyperpolarization. Hypokalemia thus shifted all re-excitation criteria in the positive direction. In contrast, hypokalemia spared epicardial APD(90) (54.8 ± 2.7 to 60.6 ± 2.7 ms), epicardial VERP (84 ± 5 to 81 ± 7 ms), endocardial APD(90) (56.6 ± 4.2 to 63.7 ± 6.4 ms), endocardial VERP (80 ± 2 to 84 ± 4 ms), and Δlatency (12.5 ± 6.2 to 7.6 ± 3.4 ms; five hearts in each case) in lidocaine-treated hearts. Exposure to lidocaine thus consistently shifted all re-excitation criteria in the negative direction, again precisely agreeing with the arrhythmogenic findings. In contrast, established analyses invoking transmural dispersion of repolarization failed to account for any of these findings. We thus establish novel, more general, criteria predictive of arrhythmogenicity that may be particularly useful where APD(90) might diverge sharply from VERP

Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs

Abstract PURPOSE: To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms. METHODS: Twenty-eight mechanically ventilated pigs were randomized to four groups of seven each: control; acute intracranial hypertension (AICH); acute respiratory distress syndrome (ARDS); acute respiratory distress syndrome in combination with acute intracranial hypertension (ARDS + AICH). AICH was induced with an intracranial balloon catheter and the inflation volume was adjusted to keep intracranial pressure (ICP) at 30-40 cmH2O. ARDS was induced by oleic acid infusion. Respiratory function, hemodynamics, extravascular lung water index (ELWI), lung and brain computed tomography (CT) scans, as well as inflammatory mediators, S100B, and neuronal serum enolase (NSE) were measured over a 4-h period. Lung and brain tissue were collected and examined at the end of the experiment. RESULTS: In both healthy and injured lungs, AICH caused increases in NSE and TNF-alpha plasma concentrations, extravascular lung water, and lung density in CT, the extent of poorly aerated (dystelectatic) and atelectatic lung regions, and an increase in the brain tissue water content. ARDS and AICH in combination induced damage in the hippocampus and decreased density in brain CT. CONCLUSIONS: AICH induces lung injury and also exacerbates pre-existing damage. Increased extravascular lung water is an early marker. ARDS has a detrimental effect on the brain and acts synergistically with intracranial hypertension to cause histological hippocampal damage