Pulmonary artery pressure: flow relationships in hyperoxic and in hypoxic dogs. Effects of methylprednisolone
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1Department of Intensive Care, Erasme University Hospital, Brussels, Belgium.
Abstract:
Methylprednisolone has been reported to impair hypoxic pulmonary vasoconstriction in isolated lungs, possibly by inhibiting the generation of vasoconstricting products of arachidonic acid metabolism. We investigated the effects of methylprednisolone on mean pulmonary artery pressure (PAP):cardiac index (Q) relationships in intact pentobarbital anaesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FiO2 0.4) and in hypoxia (FiO2 0.1). Cardiac output was increased by opening an arterio-venous femoral fistula or reduced by stepwise inflations of a balloon in the inferior vena cava. Five point PAP:Q relationships were found to be rectilinear in all experimental conditions. Over the entire range of Q studied (2 to 5 l/min.m2), hypoxia increased PAP in seven dogs ("responders") and did not affect PAP in three other dogs ("non-responders"). A hypoxic pulmonary pressor response was restored in these three "non-responders" by administration of 1 g acetylsalicylic acid iv. Methylprednisolone 30 mg/kg iv had no effect on hyperoxic and on hypoxic pulmonary vascular tone in the "responders" and in the "non-responders" treated with acetylsalicylic acid. An additional dog pretreated with methylprednisolone 30 mg/kg iv 24 h before the experiment still had a marked hypoxia-induced increase in PAP over the entire range of Q studied. Thus a large dose of methylprednisolone does not affect hypoxic or hyperoxic pulmonary vascular tone in intact dogs. These data do not support the hypothesis that products of arachidonic acid metabolism mediate hypoxic pulmonary vasoconstriction.
Insights
Methylprednisolone did not affect pulmonary vascular tone in dogs during hypoxia or hyperoxia. These findings do not support the idea that arachidonic acid metabolism products cause hypoxic pulmonary vasoconstriction.
Area of Science:
- Pulmonary Circulation
- Pharmacology
- Respiratory Physiology
Background:
- Hypoxic pulmonary vasoconstriction (HPV) is a critical circulatory mechanism.
- Previous studies suggested methylprednisolone might impair HPV by affecting arachidonic acid metabolism.
Purpose of the Study:
- To investigate the effect of methylprednisolone on pulmonary vascular tone in intact dogs under hyperoxic and hypoxic conditions.
- To determine if methylprednisolone influences the pulmonary arterial pressure (PAP) to cardiac index (Q) relationship.
Main Methods:
- Intact pentobarbital-anesthetized dogs were ventilated in hyperoxia (FiO2 0.4) and hypoxia (FiO2 0.1).
- Pulmonary artery pressure (PAP) and cardiac index (Q) relationships were assessed by altering cardiac output.
- Acetylsalicylic acid was used to restore hypoxic response in some dogs.
- Methylprednisolone was administered intravenously.
Main Results:
- Hypoxia increased PAP in most dogs ('responders'), while some ('non-responders') showed no change.
- Acetylsalicylic acid restored the hypoxic pulmonary pressor response in 'non-responders'.
- Methylprednisolone (30 mg/kg IV) did not alter hyperoxic or hypoxic pulmonary vascular tone in either 'responders' or 'non-responders' treated with acetylsalicylic acid.
Conclusions:
- High-dose methylprednisolone does not affect pulmonary vascular tone in intact dogs under hyperoxic or hypoxic conditions.
- The results do not support the hypothesis that arachidonic acid metabolism products mediate hypoxic pulmonary vasoconstriction.