Biomedical Engineering Reference
In-Depth Information
Beat-to-beat fluctuations in cardiac action potential duration (
APD alternans
,or
voltage alternans
) caused by beat-to-beat changes in amplitude of calcium transients
(Ca
2
+
alternans) can generate arrhythmias [
391
].
When a cardiomyocyte is periodically stimulated, periodic changes in
plasmalemmal voltage and cytosolic Ca
2
+
concentration enable a normal
excitation-contraction coupling. However, for high-frequency and abnormal
stimulations, the periodic behavior can degenerate into 2-period dynamics.
The action potential duration alternates in a long-short—long-short trace; the
peak cytosolic calcium concentration alternates in a large-small—large-small
pattern [
398
].
At high pacing cycle periods, alternans have the same phase in every cell.
However, at low pacing cycle durations (period l80-210 ms), alternans may be out
of phase in neighboring cells as well as may appear in a cell region, but not another,
and may be out of phase in 2 regions of the same cell (
subcellular alternans
)[
391
].
According to the sign and magnitude of calcium-APD coupling, calcium alternans
can be spatially synchronized or desynchronized, in or out of phase with action
potential duration alternans [
398
].
Spatially concordant Ca
2
+
alternans
are Ca
2
+
alternans with the same phase
throughout the cardiomyocyte. The situation in which Ca
2
+
and APD alternans
are in phase, i.e., a large-small calcium pattern coupled to a long-short action
potential duration pattern is the most common (electromechanically concordant
alternans) [
398
].
Spatially discordant Ca
2
+
alternans
result from uniform APD
alternans in the cell due to a fast voltage change with slow calcium diffusion
that enable Ca
2
+
alternans with opposite phase in different regions of the cell.
Calcium and APD alternans can be out of phase, but spatially synchronized over the
entire cell. Electromechanically discordant alternans refers to a small-large calcium
pattern coupled to a long-short action potential duration pattern [
398
].
Irregular, asynchronous Ca
2
+
release generates Ca
2
+
alternans. Calcium
alternans are determined by 3 features of Ca
2
+
sparks from Ca
2
+
-release
couplons [
396
,
397
]: (1) randomness of Ca
2
+
spark; (2) refractoriness of a
couplon after a Ca
2
+
spark during a refractory period; and (3) recruitment of
Ca
2
+
sparks from neighboring couplons (spark-induced sparks). The steep non-
linear dependence of systolic Ca
2
+
release from the sarcoplasmic reticulum on
diastolic Ca
2
+
load immediately preceding the release results from the collective
behavior of Ca
2
+
sparks [
397
]. Calcium alternans may be explained by this steep
non-linear relationship, when diastolic Ca
2
+
loading alternates concomitantly with
Ca
2
+
release.
5.6
Endocrine Function
The cardiac pump has secondary functions. The heart actually behaves as an
endocrine organ that secretes different types of hormones directly into the blood
stream, thereby ensuring a remote control.
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