Changes in cerebral CO2 responsivity over time during isoflurane anesthesia in the dog

We assessed cerebrovascular responsivity to changes in arterial carbon dioxide tension (PaCO2) during 3 h of 1 MAC isoflurane anesthesia to determine whether it parallels previously reported time-dependent decrease in normocapnic cerebral blood flow (CBF). Twelve dogs were studied under pentobarbital anesthesia (30 mg kg iv bolus) and twelve dogs under isoflurane anesthesia (1.4% end-tidal). In six animals of each anesthetic group, hypocapnia was compared to normocapnia; in the remaining six animals, hypercapnia was compared to normocapnia. At 1, 2, and 3 h after anesthesia induction, and again 10 min after blood gas alteration (hypocapnia or hypercapnia) normocapnic CBF was determined by the radiolabelled microsphere method. In animals receiving pentobarbital, total CBF during normocapnia, hypocapnia, and hypercapnia at 1 h was 40 +/- 4, 24 +/- 3, and 113 +/- 13 ml min 100g, respectively, and there was no significant change (p >0.05) at each respective level of CO2 over the 3 h of the study. Cerebral metabolic rate for oxygen (CMRO2) was unchanged with time or CO2 alteration. CO2 responsivity (change in CBF/change in PaCO2) during hypercapnia was 0.8 +/- 0.2 ml min 100g mm Hg and during hypercapnia was 3.4 +/- 0.6 ml min 100g mm Hg at 1 h and both were unchanged from those value at 3 h. In animals receiving isoflurane and subjected to hypocapnia, total CBF during normocapnia at 1 h was 97 +/- 10 ml min 100 g and declined to 56 +/- 9 ml min 100 g at 3 hr (p <0.05). Over the same time period (1-3 h), hypocapnic CBF decreased from 44 + 5 to 27 +/- 3 ml min 100g (p <0.05). In animals receiving isoflurane and subjected to hypercapnia, normocapnic CBF decreased from 68 +/- 10 to 46 +/- 6 ml min 100 g at 3 h (p <0.05) and hypercapnic flow over the same time declined from 184 +/- 24 ml min 100 g to 135 +/- 18 ml min 100g (p <0.05). CMRO2 was not changed by either time or CO2 alteration. Between 1 and 3 h, CO2 responsivity during hypecapnia decreased from 4.1 +/- 0.9 to 1.8 +/- 0.4 ml min 100 g mm Hg (p <0.05). CO2 responsivity during hypocapnia decreased from over the same period decreased from 9.0 +/- 1.0 to 5.1 +/- 0.9 ml min 100 g mm Hg (p <0.05). Similar time-dependent trends were observed in most brain regions. We conclude that normocapnic CBF and cerebral CO2 responsivity decrease over time during isoflurane anesthesia and that these changes are not caused by changes in brain metabolism.