Biomedical Engineering Reference
In-Depth Information
ated with a search through the space of possible interactions to find the one best
suited to current physiologic challenges.
Experimental manipulation of the connections suggests that physiologic
optima do indeed exist. Hayano and colleagues experimentally interrogated the
relationship among cardiac cycles, respiratory cycles, and the vagally mediated
respiratory sinus arrhythmia that reflects central respiratory drive and the lung
inflation reflex in dogs (17). These investigators electrically paced the dia-
phragm, applied electrical stimuli to the vagus nerve to simulate normal, absent,
or inverse respiratory sinus arrhythmia, and measured the matching of lung ven-
tilation with perfusion, which is critical to healthy physiology. The data showed
that normal respiratory sinus arrhythmia (i.e., physiologic coupling of respira-
tory and cardiac cycles) minimized wasted ventilation (dead space) and perfu-
sion (shunt fraction), whereas the inverse arrhythmia was physiologically much
less efficient. These investigators suggest that respiratory sinus arrhythmia is an
intrinsic resting function of the cardiopulmonary system that provides a continu-
ous fitness maximum for the coupled heart-lung system (18).
3.2. MODS: Uncoupled Oscillators?
MODS is not a disease but rather a syndrome, a common pathway that is all
too often final. Yet some patients do recover. Two features of recovery are in-
variant. First, the time to recover is significantly longer than the time to become
ill. Second, measured physiologic parameters do not retrace their paths, imply-
ing hysteresis in the clinical trajectory. These features led to speculation that
MODS did not follow a specific event, but rather reflected a more general phe-
nomenon of network failure at multiple levels of granularity. What kind of net-
works might fail at the level of organ physiology? We observed that most organs
had characteristic varying time signals, and further speculated that network fail-
ure might represent failure of the uncoupling/recoupling process of these bio-
logical oscillators (19). Several lines of evidence support such a conjecture.
4.
RESULTS
First, it is possible to directly estimate coupling among select physiologic
systems from common continuous clinical measurements such as heart rate and
blood pressure. Goldstein's studies of critically ill children as diverse as those
with sepsis (20) and with severe head injury (21) suggest loss of heart rate/blood
pressure coupling as patients deteriorate, and recovery of transfer function as the
patients themselves recover. Second, Pincus' conjecture—that loss of variability
implies greater system isolation (uncoupling) between systems that contain sto-
chastic components—allows for additional inferences based on heart rate infor-
