Effects of high-dose corticosteroids on the pulmonary circulation.
A major controversy in the treatment of the Adult Respiratory Distress Syndrome (ARDS) is the role of steroids, which may attenuate permeability as well as pulmonary vascular resistance (PVR). Empirically methylprednisolone (MP) in high doses (30 mg/kg) has been "the steroid of choice" in clinical practice. By autoradiography MP has been shown to penetrate more easily into lung tissue than other steroids tested. MP prevented the late phase increase in lung vascular permeability to endotoxin in sheep, whereas the inhibition of the pulmonary hypertensive response was far less pronounced. In human septic ARDS MP reduced both PVR and the increased vascular permeability. However, a few patients characterized by more severe ARDS did not respond to MP. There is some evidence that steroids may modulate both pre- and postcapillary vasomotion in the lungs. MP was found to inhibit pulmonary venoconstriction as well as pulmonary erythrocyte sludging in canine hemorrhagic shock. Oleic acid induced edema also appears to be attenuated by MP. This effect is partly due to a lowering of hydrostatic pressure in the lung capillaries, because MP blocks the downstream resistance increase. Hypoxic pulmonary vasoconstriction has predominantly a precapillary localisation. MP inhibits hypoxic vasoconstriction in a dose-dependent fashion in isolated rat lungs, but does not cause a general dampening of vascular reactivity, as the pulmonary constrictor response to angiotensin II is unchanged. However, MP inhibits histamine-induced vasoconstriction in isolated canine lung lobes. The increased vascular resistance in atelectatic lungs is also inhibited by MP. Corticosteroids may alter the reaction of the pulmonary vasculature to various stimuli or agents by influencing the release of mediators, for instance, the cyclooxygenase and lipoxygenase products of arachidonic acid, modulate the action of mediators, reducing the activation of leukocytes and/or platelets, or changing the state of the pulmonary vascular muscle cells. Which mechanisms are active in the various situations are at present objects of pure speculation. However, in most situations with ARDS a reduction in pulmonary arterial pressure and PVR may be regarded as beneficial.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007773:Lactates / Q000097:blood; D008775:Methylprednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D001261:Pulmonary Atelectasis / Q000188:drug therapy / Q000209:etiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012772:Shock, Septic / Q000150:complications; D012774:Shock, Traumatic / Q000097:blood / Q000150:complications / Q000188:drug therapy; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D007773:Lactates; D008775:Methylprednisolone