Detrimental effects ofverapamil inpatientswith primary pulmonary hypertension

SUMMARY Calcium channel blockade provides a logical approach tothetreatmentofpulmonary hypertension because these drugs exertdirect vasodilator effects inthehighly constricted pulmonary circulation. Todetermine theeffectiveness ofverapanilinthetreatmentofprimary pulmonary hypertension thehaemodynamic effects ofthedrugwere evaluated inseven patients withthis disorder; 10mg wasgiven intravenously tosixpatients and120mg orallytoone patient. Verapamil produced a20%decline inpulmonary vascular resistance anda 27%decrease inmean pulmonary arterial pressurewithout significant changes insystemic vascular resistance. Onepatient who received verapanil480mg orally daily forthree months showedsustained haemodynamic and clinical improvement. Concomitant withits beneficial effects on thepulmonary circulation, however,verapamilproduced apronounced decrease inright ventricular stroke workindex (42%) and increase inright ventricular filling pressure(50%), indicating adirect depressant effect ofthedrug on right ventricular function. Inonepatient these cardiodepressant effects weresufficiently pronounced toproduce severehypotension andcardiac arrest. Inconclusion, although verapanilappearstoexertpreferential vasodilator effects onthepulmonarycirculation, its negative inotropic effects may beparticularly detrimental topatients withprimary pulmonaryhypertension whohavepre-existing right ventricular dysfunction; hence, treatmentwithverapamil isnotrecommended insuch cases. Because pulmonary vasoconstriction hasbeenthought toplayanimportant contributory roleinthe pathophysiology ofprimary pulmonary hypertension' 3several vasodilator drugs havebeenusedin patients withthis disorder inanattempt toreduce pulmonary artery pressure andpulmonary vascular resistance.4 Although occasionally haemodynamic andclinical benefit have followed treatment with variousvasodilator agents,4-7 there remains nosatisfactory pharmacological approach tothemanagement of these patients. Themajorlimitation topresently available drugs isthat mostagents havepotent systemic vasodilator effects that exceed themagnitude of their effects onthepulmonary circulation; these systemic effects mayresult insevere hypotension before any appreciable improvement in pulmonary haemodynamic indices occurs.4 89