Antiarrhythmic Pharmacology · Foundation Module 3 of 3Class Ib · Mechanism · Refractoriness and PRR

When refractoriness outlasts repolarization

Repolarization can finish before excitability returns. The interval between APD₉₀ and ERP is post-repolarization refractoriness (PRR).Refractoriness is set by voltage, not by a fixed fraction of the action potential. ERP runs from phase 0 through mid-to-late phase 3 and ends at roughly −55 mV, the point at which enough Nav1.5 has recovered to support a propagating response — normally just before 90% repolarization, so the ratio sits a little under 1.0. Give a slowly-dissociating blocker and the two quantities come apart: the membrane is back at rest and the channels are still occupied.

APD₉₀
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ERP
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PRR
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ERP / APD₉₀
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ERP / APD₉₀ ratio: above 1.0 indicates PRR

Reading the ratio

ERP / APD₉₀StateElectrophysiological meaning
0.85 – 0.98Normal baselineNav1.5 recovers in a strictly voltage-dependent way as repolarization finishes. Excitability returns at about −55 mV, leaving a very narrow window before the membrane reaches resting potential.
< 0.80Increased vulnerabilityERP has shortened out of proportion to APD. A larger excitable gap opens, and premature stimuli can conduct slowly through incompletely repolarized tissue — the condition that facilitates reentry.
> 1.00Post-repolarization refractorinessRefractoriness now extends past complete repolarization into phase 4. The membrane is back at −85 to −90 mV and the tissue is still inexcitable, because channels remain drug-bound.

The derivation to hold onto

ObservationFollows from
Class Ib shortens APD in normal ventricle yet prolongs ERP in ischemic tissueInactivated-state binding + depolarized RMP holding more channels inactivated
Class Ic widens QRS at rest, not just during tachycardiaτ > 10 s exceeds the diastolic interval at any physiological rate, so block never fully washes out
Class Ib has almost no ECG signature in healthy myocardiumτ < 1 s permits near-complete recovery during a normal diastolic interval
Reentry can terminate without any change in APDPRR raises ERP independently of repolarization — the wavefront meets refractory tissue