Chronic Heart Failure Abolishes Circadian Rhythms in Resting and Chemoreflex Breathing

Abstract

Physiological systems often display 24hr rhythms that vary with the light/dark cycle. Disruption of circadian physiological rhythms have been linked to the progression of various cardiovascular diseases, and advances in the understanding of these rhythms have led to novel interventions and improved clinical outcomes. Although respiratory function has been known to vary between the light and dark periods, circadian rhythms in breathing have been understudied in clinical conditions. In the current study, we have begun to assess light/dark variations in respiration in chronic heart failure (CHF), a condition associated with abnormal resting and chemoreflex breathing as well as exercise intolerance. CHF was induced using coronary artery ligation and verified using echocardiography. Sham animals underwent a thoracotomy without coronary artery ligation. Tidal volume, respiratory frequency, and minute ventilation were all determined by whole body plethysmography under resting conditions and in response to chemoreflex challenges during the light and dark periods. Light/dark differences in voluntary exercise were assessed using a running wheel. The sham control group showed light/dark differences in resting and chemoreflex breathing, as well as arterial pressure, and these effects were eliminated in the CHF group. Both groups completed more rotations on the running wheel during the dark period compared to during the light period. The data suggest that CHF disrupts cardiovascular and respiratory circadian rhythms.

Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm

“…In a study of 717 patients after MI, decreased cyclic variation amplitude was a predictor of mortality ( 58 ). Diurnal variations in respiration and arterial BP were abolished in HF with reduced ejection fraction (HFrEF) ( 59 ). Circadian oscillations in calcineurin-dependent activities in the left ventricle of normal mice showed that calcineurin-dependent transcript levels and nuclear occupancy of the nuclear factor of activated T-cells fluctuate over the course of a day, peaking in the morning when mice enter a period of rest ( 60 ).…”