Effects of Metabolism Inhibited by Deoxyglucose on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung

Ahn, Won Sik; Kim, Seong Deok; Huh, Jin

Abstract

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is a defense mechanism to maintain adequate oxygenation. It has been reported that metabolism inhibition augments HPV. The purpose of the present study was, therefore, to determine the effect of metabolism inhibition on HPV in a rabbit model of isolated lung perfusion with exclusion of the influential factors on HPV.
METHODS
In adult rabbits, lungs were isolated and perfused with a constant pulmonary perfusate flow. Acid-base status and temperature of perfusate was also constantly maintained. Thirty minutes after, the baseline hypoxic pressor response (HPR) was measured as the difference of pulmonary artery pressure (PAP) between a period of 21% normoxic gas inhalation and that of 3% hypoxic gas inhalation. After another thirty minutes, 2-deoxy-D-glucose 100 mg was mixed with the perfusate, and then HPR was measured three times. After checking metabolism inhibition effects, D-glucose 300 mg was mixed to the perfusate to reverse metabolism inhibition, and then HPR was measured three times again.
RESULTS
Metabolism inhibition increased the basal PAP compared to the noninhibition state, but it didn't increase HPV response, so the peak PAP responding to hypoxic gas was the same as the noninhibition state. The absolute HPV response was decreased. After reversal of the inhibition state with a large amount of glucose, the basal PAP decreased to the original value and the HPV response recovered to the previous value.
CONCLUSIONS
Deoxyglucose-induced metabolism inhibition increased the PAP ventilated with 21% O2, but it didn't increase the PAP ventilated with 3% O2. As a result, the absolute HPV response was decreased.