Hemodynamic Determinants of Cardiac Interoception

Abstract

Background. Many of the sensory receptors that encode touch, temperature, pain, and visual or auditory cues are well known. These exteroceptive receptors allow us to respond to external threats from the environment. The interoceptive sensory receptors that allow us to identify threats within the internal milieu, such as changes of our heart rate brought about by fright, gastric fullness with satiety, or breathing difficulty from increased respiratory resistance are not known. We postulated that the mechanosensitive piezo receptors in the heart are responsible for cardiac interoception in humans. If true, individual contrasts in cardiac contractility among the population sensed by these stretch receptors in the heart could explain the ability of some men and women to “feel” their heart rate without taking their pulse.Hypothesis. We postulate that individual differences in ventricular contractility assessed by measurements of stroke volume in subjects would correlate with cardiac interoceptive accuracy.Methods. First, to confirm whether the gene encoding Piezo 1 is highly expressed in ventricular tissue, we assessed Piezo 1 transcripts in rodent hearts. Subsequently, heart rates, blood pressures, and stroke volumes were measured non‐invasively in 18 healthy volunteers, without a history of hypertension, using a commercial photoplethysmography device (Finapres,™ Nova Instruments). Measurements were taken in resting subjects while supine, upright, and after three minutes of standing. Cardiac interoceptive accuracy (“IA”) was assessed using a heartbeat tracking task where participants counted their heartbeats during four separate trials after being instructed not to take their pulse or engage in any manipulation that could facilitate heartbeat detection while their EKG was surreptitiously being recorded.Results. Using RT‐PCR, we confirmed that heart, lung, and stomach had the highest expression of the Piezo 1 channel. Next, we found that “IA” correlated inversely with resting heart rate (r = ‐0.71, p = 0.0009, n = 18) and directly with resting heart rate variability as determined by the standard deviation of the inter‐beat interval (r = 0.68, p = 0.005, n = 15). As expected, high “IA” was associated with higher resting stroke volumes (r = 0.62, p = 0.01, n = 15). Most significantly, “IA” was highly correlated with standing‐induced changes in heart rate (r = 0.72, p = 0.0023, n = 15), and also, standing induced changes in stroke volume (r = 0.72, p = 0.0025, n = 15). The increased cardiac contractility was not associated with increased systemic vascular resistance (r = ‐0.50, p = 0.051, n = 16) or increased work of the heart. Indeed, the resting rate pressure product was inversely correlated “IA” (r = ‐0.65, p = 0.009, n = 15).Conclusions. Individuals with lower resting heart rates, lower resting rate‐pressure products, and higher heart rate variability and stroke volumes have greater interoceptive accuracy. These characteristics mimic the phenotype that results from exercise training. Similar to fitness trained individuals, lower heart rates allow increased ventricular filling and greater stroke volumes. Indeed, the inter‐beat intervals in our subjects at rest were positively correlated with greater stroke volumes. (r = 0.75, p=0.001, n=15). On the basis of these findings, we suggest that enhanced interoceptive accuracy will correlate with individuals having higher levels of fitness within the population.