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Tachycardia‐Induced Heart Failure Does Not Alter Myocardial P‐glycoprotein Expression
Author(s) -
Sims J. Jason,
Neudeck Brien L.,
Loeb Jennifer M.,
Wiegert Nicholas A.
Publication year - 2004
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.24.1.1.34809
Subject(s) - heart failure , medicine , ejection fraction , cardiology , tachycardia
Study Objective. To determine the effects of tachycardia‐induced heart failure on myocardial P‐glycoprotein (P‐gp) expression. Design. Nonblinded, parallel, sham‐controlled, animal model study. Setting. University laboratory. Animals. Thirty mongrel dogs. Intervention. Heart failure was induced by rapid ventricular pacing over 4 weeks; sham procedures were performed for the control group. Measurements and Main Results. Myocardial biopsies were taken from the left ventricular lateral wall and prepared for P‐gp quantification by laser‐induced fluorescence. The relative amount of P‐gp messenger RNA (mRNA) was assessed by reverse transcriptase polymerase chain reaction. Rapid ventricular pacing produced heart failure and reduced the area ejection fraction from 48% ± 6% to 21% ± 6% (p<0.05 vs baseline). However, heart failure did not alter the quantity of myocardial P‐gp (0.20 ± 0.02 μg/ml for the control group vs 0.23 ± 0.02 μg/ml for the intervention group, p=0.4). Furthermore, heart failure did not alter P‐gp expression significantly. Conclusion. Myocardial P‐gp does not change in response to tachycardia‐induced heart failure. Thus, there is a low likelihood for P‐gp–related drug resistance during a syndrome similar to tachycardia‐induced heart failure.