Influence of Prolonged Hypothermia and Hyperthermia On Myocardial Sodium, Potassium and Chloride

Spurr, G. B.; Barlow, George

doi:10.1161/01.res.7.2.210

Cited by 19 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…concentrations with opposite effects to those described above for hypothermia. 8,25 This, in turn, results in high T wave amplitudes with peaked morphologies and shortened QTc as shown previously 26 and in the present study. Epinephrine administration was associated with QTca and JTpca shortening followed by a slow recovery.…”

Section: Discussionsupporting

confidence: 89%

Confounders and Pharmacological Characterization When Using the QT, JTp, and Tpe Intervals in Beagle Dogs

et al. 2020

View full text Add to dashboard Cite

Introduction: Corrected QT (QTc) interval is an essential proarrhythmic risk biomarker, but recent data have identified limitations to its use. The J to T-peak (JTp) interval is an alternative biomarker for evaluating drug-induced proarrhythmic risk. The aim of this study was to evaluate pharmacological effects using spatial magnitude leads and DII electrocardiogram (ECG) leads and common ECG confounders (ie, stress and body temperature changes) on covariate adjusted QT (QTca), covariate adjusted JTp (JTpca), and covariate adjusted T-peak to T-end (Tpeca) intervals. Methods: Beagle dogs were exposed to body hyper- (42 °C) or hypothermic (33 °C) conditions or were administered epinephrine to assess confounding effects on heart rate corrected QTca, JTpca, and Tpeca intervals. Dofetilide (0.1, 0.3, 1.0 mg/kg), ranolazine (100, 140, 200 mg/kg), and verapamil (7, 15, 30, 43, 62.5 mg/kg) were administered to evaluate pharmacological effects. Results: Covariate adjusted QT (slope −12.57 ms/°C) and JTpca (−14.79 ms/°C) were negatively correlated with body temperature but Tpeca was minimally affected. Epinephrine was associated with QTca and JTpca shortening, which could be related to undercorrection in the presence of tachycardia, while minimal effects were observed for Tpeca. There were no significant ECG change following ranolazine administration. Verapamil decreased QTca and JTpca intervals and increased Tpeca, whereas dofetilide increased QTca and JTpca intervals but had inconsistent effects on Tpeca. Conclusion: Results highlight potential confounders on QTc interval, but also on JTpca and Tpeca intervals in nonclinical studies. These potential confounding effects may be relevant to the interpretation of ECG data obtained from nonclinical drug safety studies with Beagle dogs.

show abstract

Section: Discussionsupporting

confidence: 89%

Confounders and Pharmacological Characterization When Using the QT, JTp, and Tpe Intervals in Beagle Dogs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Hypokalaemia causes a decrease in the resting membrane potential in ventricular cells, reduces the T‐wave amplitude and induces QT prolongation ( Slovis and Jenkins, 2002 ). Other investigators have noted that enhancement of the body temperature, induced by exercise‐dependent malignant hyperthermia ( Wappler et al ., 2000 ), or by artificially induced hyperthermia in dogs ( Spurr and Barlow, 1959 ), can lead to an increase in serum potassium concentrations. Hyperkalaemic states have an effect on the ECG, and the early signs are tall, narrow based, peaked and symmetric T waves (so called ‘tented’ T waves), and the QT interval is decreased ( Webster et al ., 2002 ).…”

Section: Discussionmentioning

confidence: 99%

“…Over‐correction or under‐correction may lead to artificial results, when body temperature is changed. Although the underlying mechanisms of QT interval changes associated with hypo‐ and hyperthermia are not fully understood, it is known that serum potassium concentrations can increase during hyperthermia in different species ( Spurr and Barlow, 1959 ; Sprung et al ., 1991 ), and during malignant hyperthermia in humans ( Wappler et al ., 2000 ). However, what role these electrolyte alterations have on cardiac repolarization during temperature change is also unknown, as action potential durations are also increased in in vitro studies—using tissue from guinea‐pigs ( Lathrop et al ., 1998 ), rabbits (unpublished data) and pigs ( Roscher et al ., 2001 ), where electrolyte levels are controlled through perfusion of physiological salt solutions.…”

Section: Introductionmentioning

confidence: 99%

The effect of changes in core body temperature on the QT interval in beagle dogs: a previously ignored phenomenon, with a method for correction

Linde

Deuren

Teisman

et al. 2008

British J Pharmacology

View full text Add to dashboard Cite

Background and purpose: Body core temperature (Tc) changes affect the QT interval, but correction for this has not been systematically investigated. It may be important to correct QT intervals for drug-induced changes in Tc. Experimental approach: Anaesthetized beagle dogs were artificially cooled (34.2 1C) or warmed (42.1 1C). The relationship between corrected QT intervals (QTcV; QT interval corrected according to the Van de Water formula) and Tc was analysed. This relationship was also examined in conscious dogs where Tc was increased by exercise. Key results: When QTcV intervals were plotted against changes in Tc, linear correlations were observed in all individual dogs. The slopes did not significantly differ between cooling (À14.85±2.08) or heating (À13.12±3.46) protocols. We propose a correction formula to compensate for the influence of Tc changes and standardize the QTcV duration to 37.5 1C: QTcVcT (QTcV corrected for changes in core temperature) ¼ QTcV-14 (37.5 -Tc). Furthermore, cooled dogs were re-warmed (from 34.2 to 40.0 1C) and marked QTcV shortening (À29%) was induced. After Tc correction, using the above formula, this decrease was abolished. In these re-warmed dogs, we observed significant increases in T-wave amplitude and in serum [K þ ] levels. No arrhythmias or increase in pro-arrhythmic biomarkers were observed. In exercising dogs, the above formula completely compensated QTcV for the temperature increase. Conclusions and implications:This study shows the importance of correcting QTcV intervals for changes in Tc, to avoid misleading interpretations of apparent QTcV interval changes. We recommend that all ICH S7A, conscious animal safety studies should routinely measure core body temperature and correct QTcV appropriately, if body temperature and heart rate changes are observed.

show abstract

“…Hyperkalemia, one of the leading causes of cardiac dysrhythmia (119), is usually an ominous sign of tissue hypoxia (93).…”

Section: Respiratory Systemmentioning

confidence: 99%

Limits of Tolerance to Hypothermia

Pozos

Iaizzo

Danzl

et al. 1996

Comprehensive Physiology

View full text Add to dashboard Cite

Influence of Prolonged Hypothermia and Hyperthermia On Myocardial Sodium, Potassium and Chloride

Cited by 19 publications

References 20 publications

Confounders and Pharmacological Characterization When Using the QT, JTp, and Tpe Intervals in Beagle Dogs

Confounders and Pharmacological Characterization When Using the QT, JTp, and Tpe Intervals in Beagle Dogs

The effect of changes in core body temperature on the QT interval in beagle dogs: a previously ignored phenomenon, with a method for correction

Limits of Tolerance to Hypothermia

Contact Info

Product

Resources

About