Modulation of Ventilatory Reflex Control by Cardiac Resynchronization Therapy

Abstract

Background Heart failure (HF) is characterized by heightened sensitivity of the CO2 chemoreflex and the ergoreflex which promote increased ventilatory drive manifest as increased minute ventilation per volume of expired CO2 (VE/VCO2). The aims of this study were to evaluate the effects of cardiac resynchronization therapy (CRT) on carbon dioxide (CO2) chemosensitivity and the arterial CO2 setpoint. Methods and results Consecutive HF patients (n=35) who underwent clinically-indicated CRT were investigated by cardiopulmonary exercise testing and CO2 chemosensitivity by a rebreathe method before and 4-6 months post-CRT. Pre- and post-CRT measures were compared by either paired t-test or Wilcoxon test. Decreased peak VE/VCO2 (44±10 vs. 40±8; p<0.01), CO2 chemosensitivity (2.2±1.1 vs. 1.7±0.8 L/min/mmHg; p=0.04) and increased peak end-tidal CO2 (29±5 vs. 31±5 mmHg; p<0.01) were also observed post-CRT. Multivariate analysis adjusted for age and gender showed the decrease of peak VE/VCO2 from pre- to post-CRT was most strongly associated with the increase of peak end-tidal CO2 (b=-0.84; F=21.5; p<0.0001). Conclusion Decrease of VE/VCO2 post-CRT is associated with decreased CO2 chemosensitivity and increase of the arterial CO2 setpoint consistent with decreased activation of both the CO2 chemoreflex and the ergoreflex.

Resting End-Tidal Carbon Dioxide Predicts Respiratory Complications in Patients Undergoing Thoracic Surgical Procedures

“…In our study, _ VE/ _ VCO 2 slope correlated with peak exercise PETCO 2 (rho ¼ À0.79; p < 0.01) and also with resting PETCO 2 (rho ¼ À0.59; p < 0.01), a finding suggesting that the mechanisms underlying elevated _ VE/ _ VCO 2 and decreased PETCO 2 may not be limited to exercise and may also be present at rest. This concept is supported by other studies showing that patients with high _ VE/ _ VCO 2 and low PETCO 2 at peak exercise had increased _ VE/ _ VCO 2 and low PETCO 2 at rest [6,7]. Therefore, the common underlying mechanisms of _ VE/ _ VCO 2 and PETCO 2 may explain the PETCO 2 association with pulmonary complications and may justify its use as a prognostic marker for perioperative risk assessment.…”

“…Underlying mechanisms that alter _ VE/ _ VCO 2 seem to operate during exercise as well as at rest. Indeed, patients with an increased _ VE/ _ VCO 2 ratio and a low partial pressure of end-tidal CO 2 (PETCO 2 ) during peak exercise have been shown to have an increased _ VE/ _ VCO 2 ratio and a low PETCO 2 at rest also [6,7], a finding suggesting that resting ventilatory measurements may have value for risk prediction. Identification of a simple, easy to obtain resting ventilatory measurements that effectively predicts respiratory complications and death after thoracotomy may be useful because many patients are not able or are unwilling to perform CPET [8].…”

Inhibition of peripheral chemoreceptors improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction − a role of tonic activity and acute reflex response

“…In the paper by Chua et al blockade of peripheral chemoreceptors with dihydrocodeine led to decrease in V˙E/V˙CO 2 slope from 34.19 ± 2.35 to 30.85 ± 1.91 ( p = 0.01) ( Chua, Harrington et al, 1997 ). Modulation of peripheral chemoreflex with cardiac resynchronization therapy (4-6 months after device implantation) led to decline in V˙E/V˙CO 2 from 44 ± 10 to 40 ± 8, p < 0.01 ( Cundrle et al, 2015 ). Treatment with carvedilol was also associated with numerically small difference in V˙E/V˙CO 2 slope when compared to patients taking bisoprolol (29.7 ± 0.4 vs. 31.6 ± 0.5, p = 0.023) ( Agostoni et al, 2010 ).…”

Pulmonary Limitations in Heart Failure

“…P ET CO 2 may be decreased by hyperventilation and by increased dead space ventilation, i.e., by the same factors which determine V E /VCO 2 6 , suggesting the parameters are closely related 61 . In our previous studies we have shown HF patients with low P ET CO 2 and increased V E /VCO 2 at peak exercise also exhibit low P ET CO 2 and increased V E /VCO 2 at rest 7,66 suggesting factors which promote high V E /VCO 2 and low P ET CO 2 may not be limited to exercise.…”