Dyspnea in patients with hyperbradykininism and excessive venous pooling

In the original description of the syndrome of hyperbradykininism, dyspnea on exertion was not described. However, in five women with the syndrome, ages 31 to 58, four of whom had at least one elevated value of blood kinin as determined by radioimmunoassay, dyspnea on exertion was a prominent complaint. During treadmill walking at a constant power requirement against gravity, expired air gas collections and equilibrium carbon dioxide rebreathing were performed. Seventeen apparently healthy women, ages 18 to 48, served as control subjects. Although oxygen uptake was the same in both groups by design (oxygen uptake 0.91 liters per minute, 0.11 standard deviation [SD], in the control subjects; oxygen uptake 0.97 liters per minute, 0.12 [SD] in the patients), cardiac output was significantly reduced in the patients (cardiac output 8.4 liters per minute, 1.3 [SD], in the control subjects; cardiac output 6.3 liters per minute, 0.9 [SD], in the patients, p less than 0.01). End-tidal carbon dioxide tension was significantly lower in the patients (end-tidal carbon dioxide tension 41 torr, 3 [SD], for the control subjects; end-tidal carbon dioxide tension 33 torr, 7 [SD], for the patients). In one patient, repeated studies over a 12-month period demonstrated a positive relationship between end-tidal carbon dioxide tension and the respiratory exchange ratio. (Respiratory exchange ratio = 0.01 + 0.027 X end-tidal carbon dioxide tension, 0.073 standard error of the estimate [SEE], 0.71 regular correlation coefficient, n = 20). This relationship was opposite to that expected with voluntary overbreathing; it was interpreted to mean that reduced cardiac output with exercise occurred to a variable degree and was the cause of hyperpnea and hypocapnia. In the same patient, studies at exercise with and without the Jobst (antigravity) garment and studies at exercise in the supine and erect position were consistent with the hypothesis that dyspnea and exercise intolerance were caused by venous pooling when standing. It is concluded that hyperbradykininism is characterized not only by orthostatic hypotension and tachycardia with light-headedness, as originally described, but also by severe dyspnea on exertion with exercise intolerance. The mechanism remains obscure, and the treatment is unsatisfactory, but temporary improvement in the abnormal physiology can be achieved in some patients with the use of an antigravity garment.