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Original Articles

Short-Term Memory and Restitution During Ventricular Fibrillation in Human Hearts

An In Vivo Study

Satish C. Toal, MD; Talha A. Farid, MD; Raja Selvaraj, MD; Vijay S. Chauhan, MD; Stephane Masse, MASc; Joan Ivanov, PhD; Louise Harris, MD; Eugene Downar, MD; Michael R. Franz, MD and Kumaraswamy Nanthakumar, MD

From the Division of Cardiology, Toronto General Hospital (S.C.T., T.F., R.S., V.S.C., S.M., J.I., L.H., E.D., K.N.), Toronto, Canada; and Veterans Affairs Medical Center (M.R.F.), Washington, DC.

Correspondence to Kumaraswamy Nanthakumar, MD, Hull Family Cardiac Fibrillation Management Laboratory, Division of Cardiology, Toronto General Hospital, 150 Gerrard St West, Gerrard Wing, 3-522b, Toronto, Ontario, Canada M5G 2C4. E-mail k.nanthakumar{at}uhn.on.ca

Received November 5, 2008; accepted June 1, 2009.

Background— Action potential duration (APD) variation is an important determinant of wave break and reentry. The determinants of APD variability during early ventricular fibrillation (VF) in myopathic human hearts have not been studied. The objective of this study was to study the role of APD restitution and short-term cardiac memory on variation in human VF.

Methods and Results— The study consisted of 7 patients (67±9 years old) with ejection fraction <35%. Monophasic action potentials were recorded from the right and/or left ventricular septum during VF. APD_60/90 was measured in sinus beat preceding induction of VF, and its amplitude was used to define 60%/90% repolarization in VF. The monophasic action potential upstroke (dV/dt_max) was used to characterize local excitability. Simple linear regression showed that variability in APD_n60 was determined by APD/diastolic interval restitution (R²=0.48, P<0.0001) and short-term memory (APD₆₀ n–1, n–2, n–3, n–4; R²=0.55, 0.40, 0.33, and 0.27 respectively; P<0.001). Using multiple stepwise regression, short-term memory and restitution accounted for 62% of variance in APD₆₀ (P<0.001). Individually, memory effect had the greatest contribution to APD variability (R²=0.55, P<0.0001).

Conclusions— In early human VF, short-term memory and APD/diastolic interval restitution explain most of the APD variability, with memory effects predominating. This suggests that in early human VF, short-term cardiac memory may provide a novel therapeutic target to modulate progression of VF in myopathic patients.

Key Words: fibrillation • action potentials • sudden death

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CLINICAL PERSPECTIVE

Drs Toal and Farid contributed equally to this study.