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

Critical Scale-invariance in Healthy Human Heart Rate

We demonstrate the robust scale-invariance in the probability density function (PDF) of detrended healthy human heart rate increments, which is preserved not only in a quiescent condition, but also in a dynamic state where the mean level of heart rate is dramatically changing. This scale-independent and fractal structure is markedly different from the scale-dependent PDF evolution observed in a turbulent-like, cascade heart rate model. These results strongly support the view that healthy human heart rate is controlled to converge continually to a critical state.Comment: 9 pages, 3 figures. Phys. Rev. Lett., to appear (2004

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

Effects of antidepressant treatment on heart rate variability in major depression: A quantitative review

<p>Abstract</p> <p>Background</p> <p>The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed.</p> <p>Methods</p> <p>Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately.</p> <p>Results</p> <p>Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times.</p> <p>Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported.</p> <p>Limitations</p> <p>Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies.</p> <p>Conclusion</p> <p>We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.</p

Intraaortic Balloon Pump Counterpulsation and Cerebral Autoregulation: an observational study

The use of Intra-aortic counterpulsation is a well established supportive therapy for patients in cardiac failure or after cardiac surgery. Blood pressure variations induced by counterpulsation are transmitted to the cerebral arteries, challenging cerebral autoregulatory mechanisms in order to maintain a stable cerebral blood flow. This study aims to assess the effects on cerebral autoregulation and variability of cerebral blood flow due to intra-aortic balloon pump and inflation ratio weaning

Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response

Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response