Abstract
Protamine administration may induce arterial hypoxaemia in dogs and humans. However, the responsible mechanism has not been established. Protamine, as it is a pulmonary vasoactive substance, may interfere with normal hypoxic pulmonary vasoconstriction (HPVj and cause arterial hypoxaemia. This possibility was tested in dogs utilizing a one tung hypoxic model. One lung hypoxic ventilation decreased pulmonary blood flow in the hypoxic lung from 1022 ± 96 ml*min-1 (mean ± SEM) to 846 ± 39 ml*min-1(p < 0.05) while increasing blood flow from 833 ± 85 ml*min-1to 1109 ± 101 ml*min-1 (p < 0.05) in the normoxic lung, resulting in 24 per cent effective diversion of blood flow. Protamine infusion, after heparinization, markedly elevated pulmonary vascular resistance in both lungs but preferentially in the normoxic lung (102 ± 27 per cent increase in normoxic lung, 60 ± 6.4 per cent increase in hypoxic lung) and significantly reversed the pulmonary blood flow shift induced by one lung hypoxic ventilation (effective diversion of blood flow was reduced to four per cent). Concurrently, arterial PO2 further decreased. Our results demonstrate that protamine interferes with effectiveness of pre-existing HPV and suggest that this mechanism, at least in part, may be responsible for arterial hypoxaemia observed after protamine infusion. The marked generalized pulmonary vasoconstriction with protamine appears to be the direct force that interferes with pre-existing auto-regulatory HPV. In addition to the well known haemodynamic effects of protamine, protamine infusion may also cause arterial hypoxaemia in those patients in whom HPV plays a significant role in maintaining arterial oxygenation.
Résumé
L’administration de protamine peut provoquer de l’hypoxémie artérielle chez le chien et chez les humains par un mécanisme qu’on n’a pas encore élucidé. La protamine qui possède une activité sur la circulation pulmonaire peut interférer avec le réflexe vasoconstricleur hypoxique (HPV) et ainsi causer de l’hypoxémie. Cette hypothèse a été vérifiée chez des chiens grâce au modèle expérimental à un seul poumon hypoxique. Le poumon à ventilation hypoxique a vu sa circulation sanguine diminuer de 1022 ± 96mlmin-1(± SEM)àS46 ± 39 ml*min-1(p < 0.05) pendant que la circulation dans le poumon normal a augmenté de 833 ± 85 ml*min-1 à 1109 ± 101 ml*min-1(p < 0.05) ce qui représente une dérivation du flux sanguin de l’ordre de 24 pour cent. L’infusion de protamine après héparinisation a élevé la résistance pulmonaire dans les deux poumons mais surtout dans le poumon à ventilation normale (102 ±27 pour cent d’augmentation contre 60 ± 6.4 pour cent). Ces modifications de résistance ont réduit à quatre pour cent la partie du flux sanguin dérivée par la ventilation hypoxique. Une nouvelle baisse de la PO2 artérielle a accompagné le phénomène. Ce résultat montre donc que la protamine interfère avec le réflexe vasoconslricteur hypoxique ce qui explique, en partie du moins, l’hypoxémie artérielle qu’on observe après l’infusion de protamine. C’est par l’entremise d’une vasoconstriction pulmonaire généralisée que la protamine semble exercer son action sur le HPV. En conclusion, en plus de ces effets hémodynamiques bien connus, la protamine peut donc causer de l’hypoxémie artérielle chez un patient qui compte sur le réflexe vasoconslricteur hypoxique pour maintenir son oxygénation artérielle.
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Kim, Y.D., Michalik, R., Lees, D.E. et al. Protamine induced arterial hypoxaemia: The relationship to hypoxic pulmonary vasoconstriction. Can. Anaesth. Soc. J. 32, 5–11 (1985). https://doi.org/10.1007/BF03008531
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DOI: https://doi.org/10.1007/BF03008531