Can carotid body perfusion act as a respiratory controller?

The carotid bodies contain chemoreceptor cells that respond to hypoxia and hypercapnia/acidosis of the arterial blood. Since the carotid bodies receive exceptionally high blood perfusion through branches of the external carotid artery, their impulse activity to the respiratory center is thought to be determined mainly by the arterial partial pressures of oxygen (O(2)) and carbon dioxide (CO(2)). However, this paradigm explains the observed increase in ventilation neither during mentally agitated states nor physical exercise. The objective of the work was to test whether physiologically feasible reductions in carotid body perfusion could explain such respiratory overdrive using a flow-sensitive mathematical model of the carotid body chemoreception. The model is based on the law of mass balance and on the description of the chemical reactions in the arterial blood and inside the receptor cells. The neural response to the arterial O(2) and CO(2) levels is assumed to be mediated via the controller's intracellular O(2) partial pressure and pH. The model predicts that the O(2) response is affected even by moderate changes in blood flow, whereas the CO(2) response is not altered until blood flow is severely limited. Reducing blood flow increases neural stimulus but decreases sensitivity to changes in the partial pressures of arterial O(2) and CO(2). An example is given in which relatively small changes in blood flow significantly modify the carotid body sensitivity to CO(2). These results suggest that limiting perfusion of the carotid bodies through vasoconstriction can offer a powerful mechanism to drive breathing beyond metabolic needs. This observation may provide important insight into the control of ventilation, e.g., during transition from wakefulness to sleep, before physical exercise or during panic attack.