Evolution of Action Potential Alternans in Rabbit Heart during Acute Regional Ischemia

Abstract

This study investigates the development of the spatiotemporal pattern of action potential alternans during acute regional ischemia. Experiments were carried out in isolated Langendorff-perfused rabbit heart using a combination of optical mapping and microelectrode recordings. The alternans pattern significantly changed over time and had a biphasic character reaching maximum at 6–9 min after occlusion. Phase I (3–11 minutes of ischemia) is characterized by rapid increase in the alternans magnitude and expansion of the alternans territory. Phase I is followed by gradual decline of alternans (Phase II) in both magnitude and territory. During both phases we observed significant beat-to-beat variations of the optical action potential amplitude (OAPA) alternans. Simultaneous microelectrode recordings from subepicardial and subendocardial layers showed that OAPA alternans coincided with intramural 2 : 1 conduction blocks. Our findings are consistent with the modeling studies predicting that during acute regional ischemia alternans can be driven by 2 : 1 conduction blocks in the ischemic region.

In Silico Investigation into Cellular Mechanisms of Cardiac Alternans in Myocardial Ischemia

“…Previous study supports that the depolarization alternans is linked to conduction abnormalities in the ischemia region [22]. The conduction block occurs under hyperkalemic conditions.…”

George Ralph Mines (1886–1914): the dawn of cardiac nonlinear dynamics

“…; Martišienė et al . ). During acute myocardial ischaemia, a premature ventricular contraction (PVC), the compensatory pause following such a PVC, or an intentional pause in stimulation can initiate a phase of alternans or make alternans cease (Hellerstein & Liebow, ; Kataoka & Yoshimura, , Dilly & Lab, ).…”

“…; Martišienė et al . ). Concordant alternans, and more so discordant alternans, presages the transition to malignant ventricular arrhythmias such as ventricular tachycardia and fibrillation (Downar et al .…”

“…; Martišienė et al . ). There is thus a very close connection between the concordant alternans, the discordant alternans, and the bistability between these two rhythms that is seen during ischaemia and that which was described by Mines.…”

Mechanism for Amplitude Alternans in Electrocardiograms and the Initiation of Spatiotemporal Chaos

“…The numerical model showed that when paced in tissue at fast cycle lengths, it produces APA alternans in a single cell and resulted in conduction block in space. Recently Myles, et al [22] have shown that cellular alternans of action potential amplitude is notably present in rabbit hearts with heart failure and that APA is of particular importance in the initiation of VF, and in fact more important than APD alternans [22,33]. They showed that post-infarction hearts are more vulnerable to ventricular arrhythmias at rapid rates and that APA alternans were associated with conduction block and VF.…”