Venous pressure and dyspnea on exertion in cardiac failure: was Tinsley Randolph Harrison right?

More than 70 years ago, Harrison and his group proposed that in the absence of pulmonary edema, an increased systemic venous pressure could be a major source of dyspnea upon exertion in cardiac patients. Harrison provided evidence that in resting animals systemic venous pressure can affect ventilatory control through afferent information originating from the right side of the central circulation (i.e. right ventricle and large veins) via the vagus nerves. This review explores the concept that "increased venous pressure acts as a cause of dyspnea", which emerged from the remarkable work performed by Harrison and co-workers. Their conclusion will be however extended by developing the hypothesis that the load imposed on the venous blood returning from the skeletal muscles during any muscular activity is sensed by slow conducting muscle afferent fibers and provides a source of dyspnea in heart failure patients.