Stimulating a rabbit ventricular cell with a train of current pulses at a long basic cycle length (BCL) and high pulse amplitude (PA) leads to a 1:1 rhythm, where each injected pulse generates an action potential. With a fixed BCL (BCL = 300 ms at 34--36°C and BCL = 1000 ms at 22--24°C), as PA is decreased, there is a transition from 1:1 rhythm to Wenckebach rhythms. These rhythms are characterized by a beat-to-beat increment in latency and action potential duration (APD) culminating in a skipped beat. Using voltage and action potential clamp, as well as a specific channel blocker, I show that the transient outward current (Ito) is implicated in the generation of these APD increments, and is responsible for the periodicity of these rhythms. When PA is raised, a direct transition from 1:1 to 2:1 rhythm can be observed by varying BCL. With the use of an ionic model, hysteresis between 1:1 and 2:1 rhythms is shown and compared to similar hysteresis observed previously in experiments with rabbit ventricular cells. When the BCL is within the hysteresis range, the addition of stimulus pulses flips 1:1 to 2:1 rhythm and vice versa, providing evidence for bistability. With the ionic model, the substraction of a single pulse also flipped 1:1 to 2:1 rhythm. Iteration of a finite-difference equation, derived using the steady-state APD restitution curve, predicts the direct {1:1 ↔ 2:1} transition, as well as bistability, in both the experimental and modeling work. Finally, I show in an ionic model that the transition from 1:1 to 2:1 rhythms: (1) is interrupted by Wenckebach rhythms at low PAs; (2) is direct without hysteresis at one specific higher PA value; (3) is direct with hystersis at still higher PAs. While iteration of the APD restitution curve predicted {1:1 ↔ 2:1} bistability at higher PA, iteration of the latency restitution curve predicted Wenckebach rhythms at lower PA, confirming the importance of latency for the existence of Wenckebach rhythms
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.36738 |
| Date | January 1999 |
| Creators | Yehia, Ali. |
| Contributors | Guevara, M. R. (advisor), Shrier, A. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001754126, proquestno: NQ64700, Theses scanned by UMI/ProQuest. |
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