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Peripheral and central chemoreflexes are the dominant autonomic mechanisms regulating ventilatory patterns in response to changes in partial pressures of oxygen and carbon dioxide in arterial blood and exert powerful effects on neural circulatory control. Both reflex pathways are capable of eliciting increases in sympathetic nerve traffic and consequent increases in blood pressure. Chronic heart failure is accompanied by a sustained elevation in sympathetic nerve traffic, which is thought to be an important component in the pathophysiology and progression of the disease. The role of chemoreflex mechanisms in the control of sympathetic function during heart failure is an important topic for which there are many questions and few answers. This review summarizes available evidence documenting peripheral and central chemoreflex function in heart failure, possible mechanisms for their alteration, and their possible contribution to ventilatory, and circulatory abnormalities that occur in heart failure.

Stimulation of cardiac vagal afferent endings evokes reflex hypotension and bradycardia, also known as a Bezold-Jarisch effect. The physiological importance of this reflex pathway remains uncertain today, but it is increasingly apparent that cardiac vagal afferents can play an important role in modulating cardiovascular control in pathophysiological states, particularly myocardial ischemia. The afferent endings that compose this vagal input are functionally diverse. Ventricular endings exist that are stimulated by wall motion. However, cardiac chemosensitive endings, stimulated by a variety of metabolically active substances known to be produced by the stressed myocardium (e.g., bradykinin, prostaglandins, reactive oxygen species), play a major role in mediating reflex adjustments during myocardial ischemia. Data are presented highlighting the importance of arachidonic acid metabolites and oxygen radicals in activating cardiac vagal endings during myocardial ischemia and reperfusion, and their role in modulating cardiac afferent sensitivity in the disease states of heart failure and insulin-dependent diabetes.

Ischemia of the myocardium stimulates cardiac sensory nerve endings resulting in the local release of neuropeptides. The significance of the release of neuropeptides, such as substance P (SP), for the function of the heart during ischemia and reperfusion is not known. We examined the effects of both chronic and acute neuropeptide depletion and of SP administration on contractile function and rhythmicity of the isolated rat heart during global ischemia and subsequent reperfusion.Experiments were conducted on the isolated perfused heart from vehicle and capsaicin-pretreated rats (100 mg/kg) to deplete neuropeptides from peripheral nerve terminals. The hearts were perfused with Krebs-Henseleit solution (95%O2 + 5% CO2, 37 degrees C, at constant pressure of 90 cmH2O). Left ventricular developed and diastolic pressures (LVDevP and LVEDP), heart rate (HR) and coronary flow (CF) were measured. Hearts were subjected to 20 min global no-flow ischemia and 30 min reperfusion.Prior to interrupting coronary flow, LV pressures, HR and CF did not differ between vehicle and capsaicin-pretreated rats. However, throughout the reperfusion period, the recovery of LVDevP, HR and CF in hearts from capsaicin-pretreated rats was consistently less than in control hearts (P0.05), and the incidence of fibrillation during reperfusion was higher (P0.05). In other experiments, acute perfusion of isolated hearts with capsaicin (10(-6) M) for 5 min before ischemia had a similar limiting effect during reperfusion. Administration of SP (10(-6)-10(-9) M) to capsaicin-pretreated hearts before ischemia restored their ability to recover contractile function and CF during reperfusion. Administration of SP to untreated hearts before ischemia also improved their recovery above normal during reperfusion and decreased the incidence of fibrillation without affecting postischemic CF. The beneficial effects of SP were abolished by an NK-1 receptor antagonist, CP-96,345 (10(-6) M).These data indicate that sensory neuropeptides play a role in protection of the isolated heart against ischemic damage and suggest a role of SP in the resistance of the myocardium to ischemia and reperfusion injury.

The present experiments were designed to measure and characterize direct hemodynamic effects of propranolol on vascularly isolated carotid sinuses. dl-Propranolol, when restricted to the isolated carotid sinuses, inhibited in a dose-dependent manner the reflex increases in heart rate and mean arterial pressure during carotid sinus hypotension. When perfused through isolated sinuses at a concentration of 10 micrograms/ml, the drug totally abolished reflex changes to carotid sinus hypotension. Perfusion of the sinuses with d-propranolol or procaine at the same doses also totally inhibited the response. On the other hand, perfusion of the sinuses with sotalol, an adrenergic blocker without membrane stabilizing effects, did not alter resting levels of arterial pressure or heart rate and did not affect reflex changes during sinus hypotension. These results suggest that propranolol at high doses may affect baroreceptor afferents and inhibit the baroreceptor reflex through membrane-stabilizing and local anesthetic properties rather than through hypothesized beta receptors. It seems unlikely that these pathways contribute to the antihypertensive actions of the drug.