Differential effects of isoflurane and ketamine/inactin anesthesia on cAMP and cardiac function in FVB/N mice during basal state and beta-adrenergic stimulation.

We evaluated the effect of the inhalant anesthetic isoflurane and the injectable combination of anesthetics ketamine/inactin on cardiac function by measuring left ventricular (LV) pressure in situ during control conditions and during beta-adrenergic stimulation with isoproterenol (ISO). The control heart rate (HR) and the maximal rate of contraction were significantly higher in the isoflurane group, but there was no difference in the rate of relaxation. During the ISO (0.32 ng g body wt(-1) min(-1)) stimulation the developed pressure (DP) increased 9.8 +/- 1.8% (n = 11) in the ketamine/inactin group and was unchanged in the isoflurane group. The HR increased 28.4 +/- 4.8% (n = 11) in the ketamine/inactin group and only 3.4 +/- 0.6% (n = 11) in the isoflurane group. The rate of contraction increased 103.2 +/- 9.3% (n = 11) and 13.6 +/- 4.6% (n = 11) in the ketamine/inactin and isoflurane groups, respectively. At this dose of ISO the rate of relaxation did not change significantly. In control conditions there was no difference in levels of cAMP between the groups (2.29 +/- 0.25 pmol/mg protein (n = 5) in the ketamine/inactin group and 2.79 +/- 0.35 pmol/mg protein (n = 6) in the isoflurane group). However, during the ISO stimulation the cAMP level increased only in the ketamine/ inactin group of animals (3.50 +/- 0.30 pmol/mg protein; n = 5). This level was significantly higher than the level in the isoflurane group stimulated with ISO (2.22 +/- 0.30 pmol/mg protein; n = 6). In summary, our results indicate that the anesthetics differ significantly in the extent of depression of the basal and beta-adrenergic stimulated state with the second messenger cAMP playing a prominent role.