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. 2000 Oct;84(4):365–369. doi: 10.1136/heart.84.4.365

Repolarisation and refractoriness during early ischaemia in humans

P Sutton 1, P Taggart 1, T Opthof 1, R Coronel 1, R Trimlett 1, W Pugsley 1, P Kallis 1
PMCID: PMC1729435  PMID: 10995401

Abstract

OBJECTIVES—To determine whether effective refractory period (ERP) shortens or lengthens in the first minutes of ischaemia in humans, and the relation between ERP changes and action potential duration (APD).
METHODS—ERP and monophasic action potential duration (MAPD) were measured from a single left ventricular epicardial site in 26 patients undergoing coronary artery surgery. Cardiopulmonary bypass was instituted and normothermia maintained. Refractory period was determined by the extrastimulus technique at a basic cycle length of 500 ms, at four times (group 1, 15 patients) or two times (group 2, 11 patients) the preischaemic diastolic threshold. A three minute period of ischaemia was instituted by aortic cross clamping between the input from the pump oxygenator and the heart.
RESULTS—After three minutes of ischaemia, mean (SEM) ERP lengthened from 232 (5) ms (control) to 246 (7) ms (p < 0.005) in group 1, and from 256 (10) ms (control) to 348 (25) ms (p < 0.005) in group 2. In the same time MAPD shortened from 256 (5) ms (control) to 189 (9) ms (p < 0.001) with no difference between groups. Thus postrepolarisation refractoriness developed during ischaemia. Before ischaemia, ERP showed a good correlation with APD (R2 = 0.64) but by one minute of ischaemia the correlation was poor (R2 = 0.29).
CONCLUSIONS—These results show that during the first three minutes of global ischaemia in patients with coronary artery disease: (1) ERP lengthened in response to both a low and a high stimulus strength; and (2) there was a good correlation between ERP and APD before ischaemia, which was lost by one minute as APD decreased and ERP increased. These findings may have important implications in arrhythmogenesis.


Keywords: refractoriness; ischaemia; repolarisation

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Figure 1  .

Figure 1  

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Monophasic action potential (MAP) recordings (last S1 and S2) during control (top) and ischaemia (below). The single MAPs on the right show the last MAP in the subsequent S1 train in which the S1-S2 interval is 10 ms shorter and S2 is unable to elicit a response. During ischaemia effective refractory period becomes longer than control and a gap is present between the repolarisation of the steady state beat (S1) and depolarisation of the premature beat (S2).

Figure 2  .

Figure 2  

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Monophasic action potential at 90% repolarisation (MAPD90) of the left ventricular epicardium in patients with coronary artery disease during control conditions and after one, two, and three minutes of ischaemia (cycle length 500 ms). Values are shown separately for group 1, paced at four times preischaemic diastolic threshold, and group 2, paced at two times preischaemic diastolic threshold. Action potential duration (APD) shortened progressively during ischaemia. Values are means, error bars = SEM.

Figure 3  .

Figure 3  

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Effective refractory period (ERP) on the left ventricular epicardium in patients with coronary artery disease during control conditions and after one, two, and three minutes of ischaemia. Mean values for ERP showed a small increase during ischaemia in group 1 (high pacing stimulus) and a substantial increase in group 2 (low pacing stimulus). Values are means, error bars = SEM.

Figure 4  .

Figure 4  

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The relation between action potential duration (APD) and refractoriness is shown as effective refractory period (ERP) minus APD for group 1 and group 2 patients. Under control conditions ERP was shorter than APD. During ischaemia this relation rapidly reversed, ERP outlasting APD (postrepolarisation refractoriness). This effect is more pronounced in group 2 patients (low stimulus strength).

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