Heart QT Interval Research Articles

Thaliporphine, an alkaloid from Neolitsea konishii, exerts antioxidant, anti-inflammatory, and anti-apoptotic responses in guinea pig during cardiovascular collapse in inflammatory disease

Excessive production of inflammatory cytokines and reactive oxygen species causes circulatory abnormalities leading to insufficient oxygen supply, which results in organ ischaemia and failure. Cardiovascular collapse enhances the risk of death in inflammatory disease. The present study examined the protective effects of thaliporphine, an alkaloid derived from Neolitsea konishii, during cardiovascular collapse in inflammatory disease, which was induced by LPS injection following coronary artery occlusion in guinea pig. Thaliporphine alleviated oxidative stress by preserving SOD activity and accompanied with the alleviation in inflammatory response, was observed to decrease NO, TNF-α secretion and hyperglycaemic response. In addition, thaliporphine inhibited cell death-related pathways activation, as seen by reduced JNK phosphorylation, bax expression, and capase-3 activity, leading to the reduction of myocardial infarct size and prolongation of QT interval in heart. The findings indicate that thaliporphine induces antioxidant, anti-inflammatory, and anti-apoptotic effects and may be developed for the prevention of inflammatory disease with cardiovascular system disorder.

A novel approach to data processing of the QT interval response in the conscious telemetered beagle dog

Introduction: Drug-induced QT interval prolongation may lead to ventricular arrhythmias. The aim of the study was to optimize QT interval data processing to quantify drug-induced QT interval prolongation in the telemetry instrumented conscious dog model. Methods: The test substances cisapride, dofetilide, haloperidol, and terfenadine and corresponding vehicles were given to male and female beagle dogs during two consecutive 90-min intravenous infusions. Cardiovascular parameters were recorded for 24 h and exposure to the drugs was measured. The delayed response in the QT interval after an abrupt change in heart rate was investigated. Eight mathematical models to describe the QT interval–heart rate relationship were compared and different sets of covariates were used to quantify the drug-induced effect on the QT interval. Results: After an abrupt decrease in heart rate, a 75% adaptation of the QT interval was reached after 54 ± 9 s. A linear model was preferred to correct the drug-induced effect on the QT interval for heart rate, vehicle effect, serial correlation, plasma concentration and time of day. All test substances significantly prolonged the QT interval. Discussion: To optimize the processing of QT interval data, the delay in QT interval response after an abrupt change in heart rate should be considered. The QT interval–heart rate relationship and vehicle response were individual-specific and corrections were therefore made individually. When estimating the drug-induced effect on the QT interval it is considered advantageous to use plasma concentration as a covariate, as well as adjusting for vehicle effect and serial correlation in measurements. The conscious dog model detected significant increases in the QT interval for all test substances investigated.

Noxious arousal induces T-wave changes in healthy subjects

Background Sudden arousal has been associated with sudden cardiac death in individuals with ischemic heart disease, cardiac arrhythmias, and the congenital long QT syndrome. This study aimed to determine the effects of arousal on ventricular repolarization in normal individuals by examining the dynamic QT interval–heart rate relationship and T-wave morphology changes under various “arousal” scenarios. Methods Eighteen healthy subjects (6 women and 12 men; median age, 22 years) underwent 4 separate 24-hour electrocardiogram recordings using 2-channel Holter recorders. The protocol contained 5 different arousal events: (1) natural waking (woke naturally, then stood up), (2) morning alarm (woken by alarm in the morning, then stood up); (3) night alarm (woken by alarm during the night, then stood up), (4) morning alarm–remain lying (woken by alarm in the morning but remained supine), and (5) lying to standing (stood up from a supine position during the day). Holter recordings were analyzed using a commercial package for dynamic assessment of the QT/RR relationship. Results In the 20 minutes after arousal, no changes were seen in overall QT/RR relationship in any of the groups. However, marked T-wave morphology changes, including T-wave inversion, were observed in all the arousal events. Postural changes only accounted for a small proportion of change in T-wave morphology. Conclusions In healthy subjects, noxious arousal causes marked changes in the morphology of the T wave. This may reflect abnormal adaptation of repolarization to sudden changes in heart rate and autonomic tone.

How to correct the QT interval for the effects of heart rate in clinical studies

Much inter- and intra-subject variability in the QT interval in health and disease is accounted for by differences in heart rate, leading to difficulties when determining the effects of disease and drugs on the QT interval. Traditionally, heart rate correction formulae have been used to overcome this problem in man. However, the commonly used Bazett's heart rate correction formulae (QT=QT C√RR interval) does not remove the effect of heart rate; indeed, it overcorrects at high heart rates. Fredericia's formula (QT=QT C× 3√RR interval) does remove the effects of heart rate; this is the preferable formula, if one is to be used. However, all formulae make assumptions about the nature of the QT–heart rate relationship, assumptions that may not apply to those with disease or on drugs. A more intellectually rigorous approach to QT interval–heart rate correction is to determine the QT–heart relationship for each individual, using data obtained from exercise tests or 24-h Holter tapes. The best mathematical relationship (linear, exponential, etc.) is obtained from analysis of this data, and is used to determine the QT interval at a heart rate of 60 bpm, the QT 60. The QT 60 measure makes no assumptions about the nature of the QT interval–heart rate relationship, removes the dependence of QT interval on heart rate, and maintains genuine biological differences in the QT interval. It should become the standard in QT interval–heart rate correction.

A new physiological method for heart rate correction of the QT interval

AIMTo reassess QT interval rate correction.BACKGROUNDThe QT interval is strongly and inversely related to heart rate. To compare QT intervals between different subjects with different heart rates requires the application...