Background
: Cardiac resynchronization therapy (CRT) using bi-ventricular (bi-V) pacing improves cardiac function and mortality in patients with heart failure and dyssynchronous contraction (DHF). However, the mechanisms by which bi-V pacing restores DHF-induced electrophysiological remodeling remain controversial. We test the hypothesis that bi-V pacing has enhanced beneficial effects on DHF beyond resynchronization of contraction.
Methods and Results
: Adult dogs underwent RV pacing (190–200 bpm) for 6 weeks (DHF: n = 6), or 3-week DHF followed by 3 weeks of resynchronization by either bi-V pacing (n = 6) or RA pacing (A-pace: n = 5) at the same pacing rate. Myocytes were isolated from LV anterior (ANT) and lateral (LTR) walls in non-failing (NF), DHF, bi-V and A-pace dogs. Whole cell patch clamp was performed to measure action potential (AP), transient outward (I
to
), inward rectifier (I
K1
) and delayed rectifier K
+
currents (I
K
). L-type Ca
2+
current (I
Ca,L
) and [Ca
2+
]
i
transients (CaT) were measured in the absence (baseline) and presence of isoproterenol (ISO) (35°C). The QRS duration was wider in bi-V than in A-pace, the other ECG and hemodynamic parameters were not statistically different between Bi-V and A-pace dogs. Bi-V abbreviated DHF-induced prolongation of APD in the LTR but not ANT cells and diminished the regional gradient of APD, whereas A-pace less abbreviated APD in the LTR cells and still remained the gradient. Bi-V partially restored the DHF-induced down regulation of I
K1
and I
K
but not I
to
, whereas A-pace restored only I
K1
but not I
K
and I
to
. Furthermore, bi-V fully restored the DHF-induced reduction of I
Ca,L
at baseline and its ISO response, whereas A-pace did not restore I
Ca,L
at baseline but restored its ISO responsiveness. The CaT amplitude at baseline and in ISO were partially restored by both bi-V and A-pace but the restoration was more complete with bi-V compared to A-pace.
Conclusion
: Although both bi-V and A-pace resynchronize the LV contraction, DHF-induced downregulation of K
+
currents, Ca
2+
current and handling were less completely restored by A-pace compared with bi-V pace, suggesting bi-V pacing not only resynchronizes LV contraction but improves regional heterogeneity of repolarization and Ca
2+
homeostasis in DHF.
GW28-e1233 Effect of cardiac resynchronization therapy on myocardial fibrosis and relevant cytokines in a canine model with experimental heart failure
