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Home The Effect of Tyrosine Kinase Activators and Inhibitors on the Q-T Interval of an Electrocardiogram

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The Effect of Tyrosine Kinase Activators and Inhibitors on the Q-T Interval of an Electrocardiogram

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Identifier	Thesis 1722
Author	Donaldson, Cynthia D. K.
Title	The Effect of Tyrosine Kinase Activators and Inhibitors on the Q-T Interval of an Electrocardiogram
Publisher	Central Connecticut State University
Date	2004
Resource Type	Master's Thesis
Notes	In human hypertrophy and heart failure, death often occurs following an arrhythmia. Researchers are still looking for the underlying causes of these arrhythmias. It has been determined that ion channels control cardiac rhythm, and that phosphorylation can alter ion channel function (Lev, et al., 1995). In this study, we are looking for changes in the Q-T interval. Changes in the action potential are a result of changes in ion channel current. We can monitor these changes in electrical conduction through observation of the electrocardiogram (ECG). Nineteen Spontaneously-Hypertensive rats were used for ECG acquisition and a heart physical characteristic comparison. Nine Sprague-Dawley rats were used for the heart physical characteristic comparison. Each animal was weighed prior to treatment for dose calculations and for use in a body weight to heart weight ratio. Animals were treated with angiotensin II, sodium orthovanadate, TB44, TBST or chelerythrine chloride and electrocardiograms were acquired. Angiotensin II and sodium orthovanadate are known to activate tyrosine kinase and TB44 and TBST are known to inhibit tyrosine kinase activity. Chelerythrine chloride is a selective PKC inhibitor. Measurements for Q-T intervals for both control and treatment were obtained. Data was then normalized and comparisons made by unpaired T-tests. Treatment with angiotensin II and sodium orthovanadate resulted in statistically significant increases in the Q-T interval. Treatment with TB44 and TBST showed no change, while chelerythrine chloride produced a significantly decreased Q-T interval. This indicates that the repolarization phase of the ventricle had been affected. Prolongation of the Q-T interval and increased Q-T variability are associated with potentially lethal dysrhythmias. Comparisons between the two rats strains showed that there was a significant difference in body weight to heart weight ratio. The lower ratio in Spontaneously-Hypertensive rats illustrates the higher percentage of overall body mass that a hypertrophied heart will comprise. The changes in Q-T interval for the hypertensive animals followed the same pattern as the Spraque-Dawleys. However, the extent of the treatment effects appeared to be less in the hypertensives. This could indicate that the hypertrophied heart reacts differently than a normal heart to the treatments. We can conclude that since we have seen a change in the Q-T interval duration after the administration of tyrosine kinase activators and inhibitors that we have affected the ventricular activity of the animal. We can also conclude that the cardiac action potential is modulated by a mechanism that includes a tyrosine kinase.
Subject	Protein-tyrosine kinase Electrocardiography
Department	Department of Biology
Advisor	Watson, Cheryl L
Type	Text
Digital Format	application/pdf
Language	eng
OCLC number	713735088
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The Effect of Tyrosine Kinase Activators and Inhibitors on the Q-T Interval of an Electrocardiogram

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