Biomedical subjects
Publications and source records attributed to R C Garrett.
Femoral vein injury in a newborn infant after cardiac catheterization resulted in a threat of limb loss because of a compartment syndrome. The limb was saved by full-length medial and lateral skin and fascial incisions.
Lipoxygenase products (leukotrienes) have been proposed as the mediators of pulmonary hypoxic vasoconstriction. However, the supporting data are inconclusive because the lipoxygenase and leukotriene receptor blockers that reduce hypoxic vasoconstriction (such as diethylcarbamazine and the FPL's) have confounding effects. We investigated BW 755C, a potent inhibitor of both lipoxygenase and cyclooxygenase, in eight intact anesthetized dogs with acute left lower lobe atelectasis. We examined two manifestations of hypoxic vasoconstriction: shunt fraction, as an inverse indicator of regional constriction in response to local hypoxia, and the pulmonary pressor response to global alveolar hypoxia, as an index of general hypoxic vasoconstriction. During normoxia, shunt fraction, measured using a sulfur hexafluoride infusion, was 32.0 +/- 7.0%. The pulmonary pressor response to hypoxia, defined as the increase in pulmonary end-diastolic gradient produced by 10% O2 inhalation, averaged 4.5 +/- 1.8 mmHg. Then, during normoxia, BW 755C was administered. Shunt fraction fell in all eight dogs from the previous mean of 32% to 25.5 +/- 6.1% (t = 6.5, P less than 0.0005). The hypoxic pressor response rose in all dogs, from the previous 4.5 mmHg to 9.0 +/- 3.5 mmHg (t = 4.5, P less than 0.005). BW 755C enhances hypoxic vasoconstriction, an effect consistent with its activity as a cyclooxygenase inhibitor. These data do not support a substantive role for the lipoxygenase pathway in hypoxic vasoconstriction.
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In dogs with acute lobar atelectasis, meclofenamate administration decreases shunt fraction uniformly and moderately without abolishing the wide variation of strength of hypoxic vasoconstriction and resultant variability of shunt fraction (J. Appl. Physiol. 54: 284-289, 1983). To further assess the role of prostanoids, we measured prostanoid metabolites as well as shunt fraction and pressor response to alveolar hypoxia. In six intact anesthetized dogs with acute left lower lobe atelectasis, shunt fraction during normoxia was measured with SF6. Levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 in arterial, mixed venous, and left lower lobe venous blood were measured with the double antibody radioimmunoassay technique. Ten percent O2 was administered to assess pressor response. Twenty-one percent O2 was restarted, meclofenamate was administered, and measurements were repeated 30 min later. Atelectasis did not elevate levels of prostanoid metabolites. 6-Keto-PGF1 alpha averaged 88 +/- 65 pg/ml prior to atelectasis and 81 +/- 73 pg/ml after atelectasis (F = 0.7, P = NS). Likewise, thromboxane B2 values were normal. No transpulmonary concentration differences were found. 6-Keto-PGF1 alpha did not correlate with shunt values, which ranged from 14 to 35% (mean 21%). Meclofenamate effectively blocked cyclooxygenase, as demonstrated by decreases in prostanoid metabolite levels. It seems likely that in dogs with acute atelectasis prostacyclin localized in the pulmonary vasculature decreases strength of hypoxic vasoconstriction modestly and uniformly without raising blood levels of prostacyclin metabolite.
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We investigated the degree to which strength of pulmonary hypoxic vasoconstriction affects perfusion of pulmonary shunt pathways in acute atelectasis. In 17 intact supine dogs (anesthetized, paralyzed, and ventilated) we produced left lower lobe atelectasis by occluding the lobar bronchus during oxygen inhalation. Subsequently, shunt fraction (reflecting perfusion of that lobe) was measured using an SF6 infusion while the dogs breathed room air; the mean was 26% (range 14-40%). Pulmonary pressor response to hypoxia was assessed in 13 dogs using the increase in pulmonary end-diastolic gradient (PDG) produced by inhalation of 10% oxygen. Those animals with the largest increase in pulmonary diastolic gradient had the smallest shunt fraction while breathing room air, whereas those with the smallest response had the largest shunt fraction. The contribution of local hypoxia to vasoconstriction in the shunt pathway was assessed in 13 dogs breathing room air by measuring the increase in shunt fraction produced by infusing prostaglandin E1 (PGE1). Those with the largest increase in shunt fraction had the smallest pre-PGE1 shunt fraction. Thus the strength of pulmonary vascular reactivity to hypoxia markedly influences the degree of vasoconstriction in shunt pathways and is a major determinant of shunt pathway perfusion.
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