The heart rate is primarily decreased as a result of peripheral chemoreceptor stimulation, which excites the medullary vagal center in the brainstem (Fig. 18.9). This stimulation also affects the respiratory center in the brainstem, leading to hypocapnia (reduced carbon dioxide levels) and increased lung inflation. These secondary effects inhibit the medullary vagal center, thereby attenuating the primary reflex effect of peripheral chemoreceptor stimulation on heart rate. The interaction between the respiratory and cardiac centers in the brainstem, as well as reflexes originating from stretch receptors in the lungs and right atrium, and baroreceptors in the carotid sinuses and aortic arch, contribute to the generation of respiratory sinus arrhythmia (Fig. 18.8).

The cardiac response to peripheral chemoreceptor stimulation involves both primary and secondary reflex mechanisms (Fig. 18.9). The primary reflex stimulation primarily excites the medullary vagal center, leading to a decrease in heart rate. On the other hand, the respiratory system mediates secondary reflex effects. The respiratory stimulation caused by arterial chemoreceptors tends to inhibit the medullary vagal center, and the extent of inhibition depends on the level of respiratory stimulation. Small increases in respiration slightly inhibit the vagal center, while large increases inhibit it more profoundly.

An example of the primary inhibitory influence can be observed when the lungs are completely collapsed and blood oxygenation is achieved using an artificial oxygenator. Stimulation of carotid chemoreceptors in this scenario results in intense bradycardia and some degree of atrioventricular block. These effects are primarily mediated by efferent vagal fibers.

Pulmonary hyperventilation, which is usually evoked by carotid chemoreceptor stimulation, has secondary effects on heart rate. It initiates more pronounced pulmonary inflation reflexes and leads to hypocapnia, both of which tend to depress the primary cardiac response to chemoreceptor stimulation and therefore accelerate the heart rate (Fig. 18.9). Consequently, when pulmonary hyperventilation is not prevented, the primary and secondary effects counteract each other, resulting in only a moderate effect on heart rate due to carotid chemoreceptor stimulation.

Similar reflex effects to those elicited by carotid chemoreceptor stimulation can be initiated by sensory receptors located near the endocardial surfaces of the ventricles.
•Fig. 18.9 The Primary Effect of Stimulation of Peripheral Chemoreceptors on the Heart Rate Is to Excite the Cardiac Vagal Center in the Medulla and Thus to Decrease the Heart Rate. Peripheralchemoreceptorstimulationalsoexcitestherespiratorycenterinthemedulla.Thiseffectproduceshypocapniaandincreaseslunginflation,bothofwhichsecondarilyinhibitthemedullaryvagalcenter.Thusthesesecondaryinfluencesattenuatetheprimaryreflexeffectofperipheralchemoreceptorstimulationonheartrate.Medullary vagal center Peripheral chemoreceptors Respiratory activity Primary effect (+) Secondary effects (–) (+) (–) (–) Hypocapnia Increased lung stretch Heart rate •Fig. 18.8 Respiratorysinusarrhythmiaisgeneratedbyadirectinteractionbetweentherespiratoryandcardiaccentersinthemedulla,aswellasbyreflexesthatoriginatefromstretchreceptorsinthelungs,fromstretchreceptorsintherightatrium(theBainbridgereflex),andfrombaroreceptorsinthecarotidsinusesandaorticarch.Cardiac vagal center (medulla) Respiratory center (medulla) Change in intrathoracic pressure Change in venous return Change in arterial pressure Baroreceptor reflex Heart rate Change in lung volume (stretch receptors) Bainbridge reflex
The cardiac response to peripheral chemoreceptor stimulation is the result of primary and secondary reflex mechanisms (
Fig. 18.9). The principal effect of the primary reflex stimulation is to excite the medullary vagal center and thereby decrease the heart rate. The respiratory system mediates secondary reflex effects. The respiratory stimulation by arterial chemoreceptors tends to inhibit the medullary vagal center. This inhibition varies with the level of concomitant stimulation of respiration; small increases in respiration inhibit the vagal center slightly, whereas large increases in ventilation inhibit the vagal center more profoundly.
An example of the primary inhibitory influence is shown in
Fig. 18.10 . In this example, the lungs are completely collapsed, and blood oxygenation is accomplished with an artificial oxygenator. When the carotid chemoreceptors are stimulated, intense bradycardia and some degree of AV block ensue. Such effects are mediated primarily by efferent vagal fibers.
The pulmonary hyperventilation that is ordinarily evoked by carotid chemoreceptor stimulation influences the heart rate secondarily, both by initiating more pronounced pulmonary inflation reflexes and by producing hypocapnia (see
Fig. 18.9). Both influences tend to depress the primary cardiac response to chemoreceptor stimulation and thereby accelerate the heart rate. Hence, when pulmonary hyper- ventilation is not prevented, the primary and secondary effects neutralize each other, and carotid chemoreceptor stimulation affects the heart rate only moderately.
Sensory receptors located near the endocardial surfaces of the ventricles initiate reflex effects similar to those elicited •Fig. 18.10 Changes in Heart Rate With Carotid Chemoreceptor Stimulation During Total Heart Bypass. Thelungsremaindeflated,andrespiratorygasexchangeisaccomplishedbyanartificialoxygenator.Thelowertracingrepresentstheoxygensaturationofthebloodperfusingthecarotidchemoreceptors.Thebloodperfusingtheremainderofthebody,includingthemyocardium,isfullysaturatedwithoxygen.(ModifiedfromLevyMN,etal.Circ Res. 1966;18:67.)