Abstract
Patients after repair of tetralogy of Fallot are at increased risk of arrhythmic death. Clinical data suggest that pulmonary regurgitation predisposes to these arrhythmias, although the cellular electrophysiologic effects of pulmonary regurgitation are unknown. We induced pulmonary regurgitation in lambs, and 3 mo later, having quantified the pulmonary regurgitant (PR) fraction, studied right ventricular mechanical and electrophysiologic properties in vivo and in vitro. The PR fraction was greater in PR (75 ± 10%) than in sham-operated animals (8 ± 4%; p < 0.01). In vivo, monophasic action potential duration and activation time, at rest and during acute right ventricular stretch, were similar in both groups. However, the dispersion of activation time was greater in PR animals at rest (13 ± 1.1 versus 8 ± 1.1 ms; p < 0.05). Furthermore, the dispersion of activation increased during right ventricular stretch in PR, but not in sham-operated animals. In vitro, myocardial force-frequency responses were similar in both groups, indicating preserved systolic performance, but mechanical restitution studies showed a prolonged refractory period (447 ± 22 versus 370 ± 26 ms; p < 0.05) and a decreased recovery time constant (184 ± 19 versus 265 ± 20 ms; p < 0.001) in PR animals, indicating altered calcium cycling. Furthermore, the myocardial conduction velocity was reduced in PR animals (31 ± 3.58 versus 47.9 ± 5.1 cm/s; p < 0.01), resulting from a 2-fold increase in intracellular resistance (437.25 ± 125.93 versus 194 ± 43.27 Ω · cm; p = 0.025). Chronic PR leads to inhomogeneity of right ventricular activation, alters myocardial calcium cycling, reduces conduction velocity, and increases intracellular resistivity. These may contribute to the development of arrhythmias associated with PR, including those in patients after tetralogy repair.
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Abbreviations
- MEF:
-
mechanoelectric feedback
- PR:
-
pulmonary regurgitation
- RV:
-
right ventricular
- LV:
-
left ventricular
- SO:
-
sham operated
- MAP:
-
monophasic action potential
- AT:
-
activation time
- AP:
-
action potential
- APD:
-
action potential duration
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Funded by The British Heart Foundation. G.G. was supported by The Norwegian Research Council.
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Gray, R., Greve, G., Chen, R. et al. Right Ventricular Myocardial Responses to Chronic Pulmonary Regurgitation in Lambs: Disturbances of Activation and Conduction. Pediatr Res 54, 529–535 (2003). https://doi.org/10.1203/01.PDR.0000084829.67270.FA
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DOI: https://doi.org/10.1203/01.PDR.0000084829.67270.FA
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