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Tachycardia-induced heart failure does not alter myocardial P-glycoprotein expression
J Jason Sims1, Brien L Neudeck, Jennifer M Loeb
1University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin 53705, USA. jjsims@pharmacy.wisc.edu
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 microg/ml for the control group vs 0.23 +/- 0.02 microg/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.