Endomyocardial upregulation of beta1 adrenoreceptor gene expression and myocardial contractile reserve following cardiac resynchronization therapy.
BACKGROUND
Congestive heart failure (CHF) is associated with a blunted force-frequency relation (FFR) and myocardial contractile reserve (MCR) partially from a downregulation of beta1-adrenoreceptors (beta1-AR). We investigated whether acute and chronic cardiac resynchronization therapy (CRT) was capable of reversing the blunted FFR and MCR and if this was associated with upregulation of beta1-AR.


RESULTS
Left ventricle dP/dtmax was invasively measured in 10 CHF patients (New York Heart Association class > or =3; ejection fraction <25%) during incremental dual chamber (DDD)-CRT pacing at 70, 90, 110, and 130 beats/min, with and without continuous infusion of intravenous dobutamine, immediately after CRT implantation (BL) and 4 months later (FU). In a subgroup of 5 patients, serial left ventricle beta1 and beta2-AR gene expression was measured using reverse transcriptase-polymerase chain reaction. Four months after the initiation of resynchronization therapy, DDD-CRT pacing results in a significant upward shift of the heart rate versus LV dP/dtmax relationship (P < .01) with force frequency amplification as evidenced by the steeper slope of the force frequency response (P = .04). Infusion of dobutamine recruits myocardial contractile reserve and increases the heart rate versus LV dP/dtmax relationship at BL and at FU (both P < .05). However, only at follow-up was an additional force frequency amplification noticed (P < .05) during dobutamine infusion. This observation was paralleled by a significant upregulation of beta1-AR gene expression (P = .02).


CONCLUSIONS
Chronic CRT is associated with a partial restoration of the FFR and with a recruitment in myocardial contractile reserve, which is paralleled by upregulation of beta1-AR.
Vanderheyden
Marc
M
Cardiovascular Center, Molecular Cardiology Unit and Cardiovascular Research Center, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium.
Mullens
Wilfried
W
Delrue
Leen
L
Goethals
Marc
M
Verstreken
Sofie
S
Wijns
William
W
de Bruyne
Bernard
B
Bartunek
Jozef
J
D000368:Aged; D002303:Cardiac Output, Low; D002304:Cardiac Pacing, Artificial; D004280:Dobutamine / Q000494:pharmacology; D004699:Endocardium / Q000502:physiology*; D017079:Exercise Tolerance; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009200:Myocardial Contraction / Q000235:genetics* / Q000502:physiology; D009206:Myocardium; D011941:Receptors, Adrenergic / Q000235:genetics* / Q000502:physiology; D013318:Stroke Volume; D016277:Ventricular Function, Left
D011941:Receptors, Adrenergic; D004280:Dobutamine