Enhanced Sympathetic and Ventilatory Responses to Central Chemoreflex Activation in Heart Failure

Abstract

Background-Sympathetic activation and respiratory abnormalities may each be implicated in the pathophysiology of congestive heart failure (CHF). Chemoreflexes are an important mechanism regulating both sympathetic drive and breathing. We therefore tested the hypothesis that chemoreflex function is altered in CHF. Methods and Results-We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia, and the cold pressor test in 9 patients with CHF and 9 control subjects matched for age and body mass index. Baseline muscle sympathetic nerve activity (MSNA) was higher in the patients with CHF compared with control subjects (47Ϯ8 versus 23Ϯ3 bursts per minute, PϽ0.01). During hypercapnia, patients with CHF had greater increases in minute ventilation (6.7Ϯ1.4 versus 2.7Ϯ0.9 L/min, Pϭ0.03) and heart rate (7.0Ϯ2.1 versus 0.6Ϯ1.2 bpm, Pϭ0.02). Despite higher ventilation, which inhibits sympathetic activity, the MSNA increase in patients with CHF was also greater than that in control subjects (58Ϯ12% versus 21Ϯ9%, Pϭ0.03). Ventilatory, autonomic, and blood pressure responses to hypoxia and the cold pressor test in CHF patients were not different from those in control subjects. Conclusions-Chronic heart failure is characterized by a selective potentiation of ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia. (Circulation. 1999;100:262-267.)

Carotid body function in heart failure

“…But the ventilatory response to isocapnic hypoxia, an index of peripheral chemoreflex function, in CHF patients seems less clear. Peripheral chemoreflex responses to hypoxia were not enhanced in patients with mild NYHA Class II-III CHF distinguished by dyspnea to mild (III) or moderate (II) exercise (Narkiewicz et al 1999). Similarly, other clinical studies (Haque et al 1996,van de Borne et al 1996 reported that suppression of peripheral chemoreceptor activity by hyperoxia had no effect on muscle sympathetic nerve activity or arterial pressure.…”

“…Several lines of evidence also make it clear that augmented excitatory reflexes further boost activation of sympathetic outflow in CHF. These reflexes encompass sympathetic excitatory cardiac (Wang et al 1999), somatic (Sinoway and Li, 2004), peripheral ,Sun et al 1999a) and central chemoreceptor reflexes (Narkiewicz et al 1999). …”

Sympathetic Neural Outflow and Chemoreflex Sensitivity Are Related to Spontaneous Breathing Rate in Normal Men

“…Sympathetic activation has been implicated in the pathogenesis of hypertension, obstructive sleep apnea, and congestive heart failure. [1][2][3][4] In healthy humans, muscle sympathetic nervous activity (MSNA) varies widely across subjects but is relatively reproducible within the same individual. 5,6 The substantial between-subject variance in sympathetic traffic can be only partially explained by age, body mass index, blood pressure, reflex mechanisms, and genetic factors.…”

“…2,3 The correlation between respiratory rate and sympathetic traffic may be, however, secondary to impairment of reflex mechanisms, or severity of heart failure, with consequent tachypnea, in patients with heart failure. 3,4 The relationship between spontaneous breathing rate and direct measures of sympathetic traffic in healthy humans has not been studied previously. We, therefore, tested the hypothesis that respiratory rate is linked to MSNA and chemoreflex sensitivity in normal subjects, independent of other variables, including age, body mass index, and blood pressure.…”

Cardiopulmonary Exercise Testing in Patients With Left Bundle Branch Block and Preserved Ejection Fraction

“…The main variables assessed with this methodology are: peak oxygen consumption (VO 2 peak), VO 2 at the anaerobic threshold, oxygen pulse (PO 2 ), ΔVO 2 /Δload, relation between ventilation and carbon dioxide production (VE/VCO 2 Cardiopulmonary testing and left bundle branch block Int J Cardiovasc Sci. 2017;30(1): [11][12][13][14][15][16][17][18][19] Original Article slope) and VO 2 recovery kinetics. On the other hand, it has been documented that LVEF assessed through echocardiogram does not show a satisfactory relation to VO 2 , 5,6 and thus does not constitute a good predictor of functional capacity.…”