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Published on: June 19, 2018
Analysis of ketamine responses in the pulmonary vascular bed of the cat
A D Kaye1, R E Banister, C J Fox
1Department of Anesthesiology, Tulane University Medical School, New Orleans, Louisiana, USA. aneadk@ttu.hsc.edu
Objective:
To test the hypothesis that pulmonary vasodilator responses of ketamine are dependent on activation of L-type calcium channels, independent of synthesis of nitric oxide from L-arginine, activation of adenosine triphosphate-sensitive potassium channels, and the release of cyclooxygenase products.
Design:
Prospective study.
Setting:
Research laboratory.
Subjects:
Isolated lobar lung preparation, mongrel cats.
Interventions:
In separate experiments, the effects of nicardipine; N omega-I-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase; glibenclamide, an adenosine triphosphate-sensitive potassium channel antagonist; and meclofenamate, a cyclooxygenase blocker, were investigated in the pulmonary vascular bed of the cat. The effects of these agents were evaluated on the pulmonary arterial responses of ketamine, acetylcholine, and isoproterenol during elevated tone conditions induced by the thromboxane A2 mimic, U46619 (Upjohn, Kalamazoo, MI).
Measurements:
Lobar arterial perfusion pressure, systemic pressure, and left atrial pressure were continuously monitored, electronically averaged, and permanently recorded.
Main Results:
Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, N omega-I-nitro-L-arginine methyl ester, glibenclamide, and meclofenamate had no significant effect on the vasodilator responses to ketamine. Nicardipine, in a dose that reduced significantly vasopressor effects to BAY K 8644, a calcium-channel opener, attenuated significantly vasodilator responses to ketamine, whereas the L-type calcium-channel blocker had no significant effects on responses to acetylcholine and to isoproterenol.
Conclusions:
These data show that ketamine has significant vasodilator activity in the pulmonary vascular bed of the cat. The present data also suggest that responses to ketamine during elevated tone conditions may in part be mediated by the activation of L-type calcium channels.
