Vasomotor response to hormonal norepinephrine in canine cerebral and hindlimb vessels.

We calculated the percent change in initial vascular resistance during open loop intra-arterial infusions of norepinephrine (NE) in 12 acutely denervated isolated canine brains and 5 acutely denervated perfused hindlimbs. The studies were repeated on seven chronically denervated brains devoid of perivascular sympathetic fibers. All tissues were free of residual anesthetic. Half-maximal responses were obtained at similar plasma NE concentrations in both the control brains (ED50 13.1 +/- 3.8 X 10(-6) M) and hindlimbs (ED50 9.22 +/- 2.3 X 10(-6). The maximal response was much greater in the limb vasculature (490.3 +/- 30.1%) than in the cerebral vasculature (107.2 +/- 9.5%). A fourfold increase in cerebral vascular sensitivity was noted 3 days after sympathetic gangliectomy (ED50 3.44 +/- 0.74 X 10(-6) M), without any significant change in the maximal response (101.3 +/- 5.7%). Plasma levels of NE observed in resting dogs did not constrict either vascular bed; elevated levels of NE observed in stress dogs would minimally constrict limb vessels but not acute or chronically denervated cerebral vessels. These in situ results confirm that NE does not play a significant role as a physiological vasomotor hormone and suggest that prejunctional neuronal uptake of NE is not responsible for the observed differences in cerebral and hindlimb vascular response. Furthermore, it is unlikely that denervation hypersensitivity to circulating NE plays a role in pathological cerebral vasoconstriction (vasospasm) following subarachnoid hemorrhage.

Cerebral oxygen and energy metabolism during and after 30 minutes of moderate hypoxia.

Sixty-four isolated canine brain preparations were subjected to either 15 or 30 min of perfusion with blood equilibrated at either Pao2 30 mmHg or Pao2 40 mmHg followed by up to 60 min of reoxygenation with blood having a Pao2 greater than 100 mmHg. Pao2 30 mmHg perfusion decreased oxygen availability and the cerebral metabolic rate for oxygen (CMRo2) to 44 and 49% of normal, respectively, whereas Pao2 40 mmHg perfusion decreased oxygen availability and CMRo2 to 64 and 70% of normal, respectively. Creatine phosphate was markedly decreased (0.6 and 4% of normal, respectively) and ATP was only slightly decreased (73 and 90% of normal, respectively) in these preparations during the hypoxic period. Although ATP returned to normal during the reoxygenation period in both groups, creatine phosphate and CMRo2 returned to normal only in the Pao2 40 mmHg preparations. In brains perfused at various Pao2 levels for periods ranging from 6 to 30 min, the total oxygen deficit (the cumulative difference over time between normal and actual CMRo2) rather than tissue lactate levels appeared to influence the restoration of CMRo2 to normal following hypoxia. An oxygen deficit in excess of 25 mumol/g precluded return to a normal CMRo2 following reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral glucose metabolism during 30 minutes of moderate hypoxia and reoxygenation.

In 50 separate experiments, isolated canine brain preparations were subjected to 15 or 30 min of either PaO2 30 mmHg or PaO2 40 mmHg perfusion followed by up to 60 min of reoxygenation at a normal PaO2. The cerebral metabolic rate for glucose (CMRGlu) increased 70-80% after 2 min of hypoxia but then returned to nearly the normal rate by the end of the 30-min period of hypoxia. Glycolytic flux appeared to be facilitated in both groups initially but was inhibited as the hypoxic period continued. This slowing of glycolysis after 15 or 30 min of hypoxia appears to be modulated by the regulatory enzyme phosphofructokinase. Glucose equivalents metabolized, based on CMRGlu plus brain glucose and glycogen disappearance, far exceed the glucose equivalents that can be accounted for on the basis of oxygen utilization and brain lactate formation. Thus, during hypoxia, some of the glucose equivalents must be utilized for synthesis of other metabolites. The glycolytic intermediates returned to normal after reoxygenation in the PaO2 40 mmHg preparations, but the PaO2 30 mmHg preparations continued to show evidence of decreased glycolysis and a lingering lactacidosis. Although posthypoxic oxygen uptake was sufficient to oxidize all glucose entering the brain, there was no significant release of accumulated lactate into the blood. Thus, the decrease in brain tissue lactate must have been the result of lactate oxidation. A significant amount of the glucose entering the brain during the posthypoxic period appears to be used for metabolite synthesis rather than energy production.