Several years ago, we suggested that the networks of organ systems that
collectively constitute macrophysiology are not only coupled, but also that the
couplings are intrinsically unstable (15). Subsequently, Schaefer and colleagues
presented data in support of this conjecture: analysis of the interaction between
cardiac and respiratory cycles in healthy athletes at rest suggested that the coupling
between heart and lungs was not fixed but rather dynamic (16). These athletes'
organs would couple (for example, 5 heartbeats for 2 respirations), then
uncouple, then recouple at the same or a different ratio (for example, 6 heartbeats
for every 2 respiratory cycles). The inference is that health may be associated 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 diaphragm,
applied electrical stimuli to the vagus nerve to simulate normal, absent,
or inverse respiratory sinus arrhythmia, and measured the matching of lung ventilation
with perfusion, which is critical to healthy physiology. The data showed
that normal respiratory sinus arrhythmia (i.e., physiologic coupling of respiratory
and cardiac cycles) minimized wasted ventilation (dead space) and perfusion
(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 continuous
fitness maximum for the coupled heart–lung system (18).