89594
document
Effects of frusemide and hypoxia on the pulmonary vascular bed in man . AIMS Diuretic therapy is conventionally used to treat oedema in patients with hypoxic cor pulmonale . This condition is associated with activation of the renin angiotensin system ( RAS ) with elevated levels of angiotensin II ( ANG II ) , a potent pulmonary pressor agent . We explored the hypothesis that RAS activation by diuretic therapy might therefore worsen hypoxic pulmonary vasoconstriction via the effects of ANG II on the pulmonary vascular bed . METHODS Eight normal volunteers were studied on 2 separate days . They either received 40 mg frusemide daily or placebo for 4 days and were then rendered hypoxaemic , by breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85-90 % adjusted for a further 20 min to achieve an SaO2 of 75-80 % . Pulsed wave doppler echocardiography was used to measure mean pulmonary artery pressure , cardiac output and hence pulmonary vascular resistance ( PVR ) . RESULTS Plasma renin activity ( PRA ) was significantly ( P < 0.01 ) increased after prior treatment with frusemide compared with placebo at all time points . Prior treatment with frusemide significantly ( P < 0.05 ) increased PVR compared with placebo at baseline : 185 +/- 17 vs 132 +/- 10 dyn s cm-5 at an SaO2 of 85-90 % : 291 +/- 18 vs 229 +/- 16 dyn s cm-5 and at SaO2 of 75-80 % : 356 +/- 12 vs 296 +/- 17 dyn s cm-5 respectively . However , the delta-PVR response to hypoxaemia was not significantly altered by frusemide compared with placebo . In contrast to its effect on the pulmonary vasculature prior treatment with frusemide did not significantly alter systemic haemodynamic parameters either at baseline or during hypoxia . CONCLUSIONS Thus , prior treatment with frusemide increased baseline pulmonary vascular resistance and significantly augmented the hypoxaemic pulmonary vascular response in additive fashion . It is hypothesised that this effect of frusemide may be due to RAS activation with ANG II mediated pulmonary vasoconstriction .
89595
Intervention_Pharmacological
frusemide
89596
Intervention_Pharmacological
Diuretic
89597
Intervention_Pharmacological
40 mg frusemide daily or placebo
89598
Intervention_Pharmacological
frusemide
89599
Intervention_Pharmacological
placebo
89600
Intervention_Pharmacological
frusemide
89601
Intervention_Pharmacological
placebo
89602
Intervention_Pharmacological
frusemide
89603
Intervention_Pharmacological
placebo
89604
Intervention_Pharmacological
frusemide
89605
Intervention_Pharmacological
frusemide
89606
Intervention_Pharmacological
frusemide
89607
Outcome_Physical
mean pulmonary artery pressure , cardiac output
89608
Outcome_Physical
pulmonary vascular resistance ( PVR ) .
89609
Outcome_Physical
Plasma renin activity ( PRA )
89610
Outcome_Physical
PVR
89611
Outcome_Physical
delta-PVR response to hypoxaemia
89612
Outcome_Physical
systemic haemodynamic parameters
89613
Outcome_Physical
pulmonary vascular resistance
89614
Outcome_Physical
hypoxaemic pulmonary vascular response
89615
Participant_Condition
pulmonary vascular bed
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Participant_Sex
man
89617
Participant_Condition
oedema
89618
Participant_Condition
hypoxic cor pulmonale
89619
Participant_Sample-size
Eight