Tachycardia-induced heart failure does not alter myocardial P-glycoprotein expression.
OBJECTIVE
To determine the effects of tachycardia-induced heart failure on myocardial P-glycoprotein (P-gp) expression.


METHODS
Nonblinded, parallel, sham-controlled, animal model study.


METHODS
University laboratory.


METHODS
Thirty mongrel dogs.


METHODS
Heart failure was induced by rapid ventricular pacing over 4 weeks; sham procedures were performed for the control group.


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.


CONCLUSIONS
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.
Sims
J Jason
JJ
University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin 53705, USA. jjsims@pharmacy.wisc.edu
Neudeck
Brien L
BL
Loeb
Jennifer M
JM
Wiegert
Nicholas A
NA
D000818:Animals; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000209:etiology* / Q000503:physiopathology; D004285:Dogs; D004452:Echocardiography; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000737:chemistry* / Q000502:physiology; D006352:Heart Ventricles / Q000737:chemistry* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013610:Tachycardia / Q000150:complications* / Q000503:physiopathology; D013997:Time Factors
D006023:Glycoproteins