Humoral adaptation mechanisms and clinical outcome during vasodilator therapy

Administration of hydralazine and isosorbide dinitrate leads to a reduction of one-year mortality by 38%. However, a major disappointment has been the inability to predict the individual patient's response to these drugs. The aim of the present study, therefore, was to evaluate possible predictors for a favourable response to hydralazine treatment on the basis of the acute humoral and haemodynamic response to the drug. Stroke volume increased in all 37 patients with severe left ventricular dysfunction in response to acute intravenous hydralazine (0.4 mg kg^-1). However, when re-investigated after 2 months of chronic oral hydralazine therapy, sustained haemodynamic and clinical improvement was observed in only 16 patients. Pretreatment values of either left ventricular filling pressure, cardiac index or systemic vascular resistance were not useful in predicting the outcome of treatment. However, when patients were subdivided on the basis of their heart rate response to acute hydralazine, better discrimination for a beneficial response, was possible. It is concluded that the haemodynamic responses to acute intravenous hydralazine allow discrimination between patients not responding to chronic vasodilator treatment and those who are likely to benefit. A reflex excitation of sympathetic outflow in response to acute vasodilation (indicated by a reflex acceleration of heart rate and increase in plasma noradrenaline levels) characterised best those patients who did not benefit from oral hydralazine. The data indicate a detrimental role of reflex sympathetic stimulation which may blunt at least part of the direct beneficial drug-induced effect in chronic vasodilator therapy.