Development of a near anesthetic-free isolated canine hindlimb model. The effects of halothane and atropine sulfate on vascular resistance.

A denervated, isolated canine hindlimb (HL) model was developed to minimize residual anesthetic contamination. To test the preparation, we determined the peripheral arterial vascular effects of atropine sulfate and the effect of the basal anesthetic on arterial resistance. In four dogs that were under halothane and oxygen anesthesia, the HL was prepared to allow either vascular isolation of the limb or continuity with the systemic circulation. During isolation the HL was perfused by roller pump at a preset flow rate through an infant oxygenator. Inspired gas fed to the oxygenator contained either 0%, 1.25%, or 2.5% halothane to determine that anesthetic's effect on HL arterial vascular resistance. No halothane (0%) was used in the oxygenator inflow during the atropine measurements. Vascular resistance was calculated from HL arterial pressure at constant flow. Halothane caused a significant stepwise fall in vascular resistance, with a decrease of 68% at 2.5% inspired concentration (p less than 0.01). Atropine produced a progressive attenuation of resistance that decreased by 18% after the 2.5 mg/kg dose (p less than 0.01). The model proved stable over time and demonstrated an apparent direct, dose-dependent vasodilating effect of both atropine and halothane in the canine HL muscle arterial bed.

Decrease in vascular resistance in the isolated canine hindlimb after graded doses of alfentanil, fentanyl, and sufentanil.

Under halothane anesthesia five dogs were prepared with both hindlimbs isolated from the systemic circulation to allow intermittent placement on extracorporeal perfusion at constant flow. One limb of each dog was surgically denervated. In this relatively anesthetic-free preparation, graded equivalent doses of alfentanil, fentanyl, and sufentanil were infused over 30 s, and vascular resistance was measured. Increasing opioid administration caused a progressive diminution in peripheral resistance. By the high dose level, alfentanil (500 micrograms/kg), fentanyl (50 micrograms/kg), and sufentanil (6 micrograms/kg) caused equal and significant decreases of 48%, 48%, and 44% in resistance, respectively. There was no difference among the opioids in effects on resistance at equivalent dosages. Neither pretreatment with naloxone nor denervation changed the response to the narcotics. We conclude that the three synthetic opioids produce vasodilation by direct action on the peripheral vascular smooth muscle.

Hyperbaric oxygen increases survival following carotid ligation in gerbils.

We studied the effects of graded exposure to hyperbaric (1,875 mm Hg) oxygen therapy in an acute stroke model prepared by unilateral carotid artery interruption in gerbils. Pentobarbital alone, superoxide dismutase alone, two periods of hyperbaric oxygen alone, and each agent combined with hyperbaric oxygen were administered to investigate possible mechanisms of protection from cerebral ischemia. Survival rates and neurologic deficit scores over 5 days in all treated groups were compared with those in a control group. Survival rates in the groups subjected to 2 (63.9 +/- 4.0%) and 4 hours (70.1 +/- 5.2%) of hyperbaric oxygen alone were significantly higher than in the control group (53.6 +/- 4.2%). The group treated with pentobarbital alone also demonstrated increased survival (69.8 +/- 7.0%), but the combination of therapeutic regimens offered no apparent additive protection. By 5 days there were no differences in the neurologic deficit scores of the survivors in the groups. The toxic pulmonary effects of hyperbaric oxygen were assessed in a pilot LD50 study. The pressure used caused no mortality during 4 hours of exposure, and the calculated LD50 was 7.26 hours. This investigation demonstrates that graded doses of hyperbaric oxygen given after the insult increase survival in a gerbil model of stroke.