People: S. Sau, D. Gauthier, W. Krassowska Neu, R. Oliver
Collaborators: S. Idriss (Pediatric Cardiology)
Additional information: Quantum Electronics Laboratory Web Page
Summary:
Our most recent study
yields experimental evidence that the slope of the dynamic restitution
curve does not determine the stability of the response pattern to periodic
stimuli. Bullfrog ventricular tissue in vitro was paced at decreasing
basic cycle lengths (BCLs). Action potential duration (APD) and
the preceding diastolic interval (DI) were measured at each BCL
and bifurcation diagrams and restitution curves were drawn.
The figure below shows a representative bifurcation diagram
from a preparation that exhibits alternans. For all BCLs from 1000 ms
to 450 ms, the
tissue responds with stable 1:1 behavior. At 425 ms, the bifurcation to
alternans occurs followed by aperiodic responses before the transition to 2:1
locking at 350 ms. The slope of the corresponding dynamic restitution curve
exceeds one for
all DIs less than 250 ms, which corresponds to all BCLs below 850 ms.
The slope reaches a maximum of 2.8 just before the
bifurcation to alternans (BCL = 425 ms). The slope exceeds one over a wide
range of BCLs where the response is 1:1 (50 to 425 ms, span of 425 ms).
The bifurcation pattern seen in the figure(1:1 to 2:2 to 2:1)
was seen in 3 of 6 bullfrogs. In all remaining trials, only a 1:1 to 2:1
transition occurred, often with aperiodic responses at the transition BCL.
Slope steeper that one during stable 1:1 response was observed in 4 out of
6 animals; in the remaining 2, the maximum slope was below or equal to one.
Therefore,
our in-vitro experiments demonstrate that the tissue can respond with
a stable 1:1 pattern even as the slope of the restitution curve exceeds one,
indicating that tissue dynamics is not governed solely by the
one-dimensional restitution relationship.
Key Publications:
S. Sau, W. Krassowska, and D. Gauthier, Restitution properties and stability of response patterns in cardiac muscle, Annual APS March Meeting 2002, Indianapolis, IN, p. 948, 2002.
R. A. Oliver and W. Krassowska, Concentration drift and rate-dependent restitution in the CRN atrial membrane model, Annual APS March Meeting 2002, Indianapolis, IN, p. 949, 2002.
Support: NSF Grant NSF-9982860
People: R. Oliver, W. Krassowska Neu
Collaborators: D. Gauthier (Physics), P. Wolf (BME), C. Henriquez (BME)
Summary:
In 15 out of 21 trials and in all sheep, idiopathic
wavefronts emanating from outside the mapped region passed through the
mapped region. In 13 of those trials, the idiopathic wavefronts occurred
at BCLs within the bistability window or within 35 ms of its upper or
lower limit (figure below). This result
suggests a connection between bistability and arrhythmogenesis.
We are currently investigating this connection
using computer simulations.
Key Publications:
R. A. Oliver, G. M. Hall, S. Bahar, W. Krassowska, P. D. Wolf,
E. Dixon-Tulloch, and D. J. Gauthier,
Existence of bistability and correlation with arrhythmogenesis
in paced sheep atria,
J. Cardiovasc. Electrophysiol., 11: 797-805, 2000.
Support: NSF Grant NSF-9982860 and NC Supercomputing Center
This study investigated
the response of sheep atria in vivo to rapid pacing.
A 504-electrode mapping plaque was affixed to the right atrium in 6 sheep.
Cathodal pacing stimuli were delivered to the center of the plaque.
The pacing period BCL was decreased from 275 +- 25 ms to 75 +- 25 ms
and then increased to 230 +- 70 ms in steps of either 5 or 10 ms.
In all 21 trials in 6 sheep, the atrium responded in a 1:1 pattern at longer
BCLs and in a 2:1 pattern at shorter BCLs. As the BCL was decreased,
the response
reverted to 2:1 at a particular BCL. Conversely, as the BCL was increased,
the response switched back to 1:1 at a particular BCL. Over 21 trials,
the 1:1 to 2:1 and 2:1 to 1:1 transitions occurred at 119.5 +- 18.8 ms
and 130.0 +- 19.1 ms, respectively. This hysteretic behavior yielded
bistability windows, 10.5 +- 7.2 ms wide, wherein 1:1 and 2:1 responses
existed at the same BCL. Combined with the previous study on bullfrog
ventricles in vitro (Hall et al., Phys. Rev. Lett., 82: 2995-2998, 1999),
these studies imply that bistability occurs
in many species, tissue types, and experimental preparations.
Response patterns and idiopathic wavefronts in six sheep. For
each animal (numbers on the right), the two horizontal
lines show the range of BCLs where the response was 1:1 (upper line)
and 2:1 (lower line). Diamonds show BCLs at
which idiopathic wavefronts were observed. The leftmost diamonds
in animal 6 were associated with the 2:1 to 3:1 transition.
Send comments to
wanda.krassowska@duke.edu
Last updated June 4, 2004