Canine Cerebral Blood Flow Research Articles

Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow.

We tested the hypothesis that NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/- 4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE) ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10 micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x 100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L-NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O2 transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Postischemic Canine Cerebral Blood Flow is Coupled to Cerebral Metabolic Rate

Following complete global cerebral ischemia and reperfusion, a brief period of reactive hyperemia is followed by a prolonged period of low flow commonly referred to as the delayed postischemic hypoperfusion state. It is generally assumed that this low-flow state may be injurious because of inadequate substrate delivery, thus implying that flow is no longer coupled to metabolic needs. This relationship of CBF to CMRO2 was examined in six anesthetized dogs that were subjected to 12 min of complete ischemia induced either by CSF compression or aortic occlusion. Following reperfusion and onset of the low-flow state, which stabilized at 45 min postischemia, control normothermic (37 degrees C) measurements of CBF and CMRO2 were determined. Thereafter, femoral arterial blood was circulated through a heat exchanger (42.5 degrees C), and brain temperature was increased to 40 degrees C and measurements were repeated. The brain was then cooled back to 37 degrees C for a final set of normothermic measurements. Thereafter, brain biopsies were taken to determine the energy state of the brain. CMRO2 changed approximately 6%/degrees C. CBF paralleled the change in CMRO2. Accordingly, the ratio of CBF to CMRO2 remained constant throughout at a value of 8 to 9, demonstrating maintained coupling. The brain energy state was normal at the end of the study. The authors conclude that postischemic CBF is modulated by the brain's metabolic needs.

Postischemic Canine Cerebral Blood Flow Appears to Be Determined by Cerebral Metabolic Needs

Following a period of complete global cerebral ischemia and reperfusion there ensues a low flow state referred to as the delayed postischemic hypoperfusion state. It is unknown whether this low flow state contributes to neuronal injury or whether the magnitude of hypoperfusion correlates with the duration of ischemia. The latter question was addressed in 20 dogs in which complete global ischemia was induced by cerebrospinal fluid (CSF) compression for periods of 3, 9, 12, or 18 min. Following reperfusion, CBF (by sagittal sinus outflow) and CMRO2 were determined for 90 min, and results were correlated with the duration of ischemia. At 90 min postischemia the magnitude of decrease in CBF correlated crudely with the duration of ischemia (r = -0.67, p less than 0.01). For CMRO2 correlation of the magnitude of decrease with the duration of ischemia was more evident (r = -0.74, p less than 0.001). Furthermore, the postischemic ratio of CBF to CMRO2 was virtually identical for all dog groups regardless of the ischemic time. The adequacy of the ratio of CBF to CMRO2 was reflected by adequate oxygen levels in the sagittal sinus blood of all dogs. The authors conclude that the delayed postischemic hypoperfusion state is probably not an important determinant of neuronal injury since its magnitude appears to be primarily determined by the metabolic needs of the brain.

Effect of PEEP and jugular venous compression on canine cerebral blood flow and oxygen consumption in the head elevated position.

Cerebral blood flow (CBF) (radiolabelled microspheres) and oxygen consumption (CMRO2) were studied in nine dogs during 30 min of either neck vein compression or application of positive end-expiratory pressure (PEEP) ventilation. With the animal in the prone position, elevation of the head from horizontal to 30 cm above the heart markedly decreased cisterna magna (PCSF) and dorsal sagittal sinus pressure (PCV). With the head elevated, compression of neck veins using neck tourniquet (pressure 40 mmHg) increased PCSF and PCV from 3.6 +/- 2.2 to 6.8 +/- 4.8 and -2.5 +/- 2.7 to 2.3 +/- 2.3 mmHg (mean +/- SE, P less than 0.05), respectively, while total or regional CBF and CMRO2 remained unchanged. Application of PEEP (15 cm H2O) increased right atrial pressure (-4.7 +/- 1.7 to -0.1 +/- 3.4 mmHg, P less than 0.05), but did not affect PCSF or PCV (3.4 +/- 3.3 to 3.3 +/- 3.7 and -3.5 +/- 2.6 to -4.1 +/- 2.4 mmHg, respectively, P greater than 0.05). Total or regional CBF and CMRO2 were also unaffected. These data demonstrate that, although neither maneuver affects CBF or CMRO2, neck vein compression elevates PCV above atmospheric pressure, but PEEP does not. In patients at risk for cerebral venous embolism, intermittent neck vein compression should be used as a prophylactic measure to prevent air embolism.

Prevention of postischemic hypoperfusion after canine cardiac arrest by nicardipine.

We studied the effect of nicardipine (NC) on canine cerebral blood flow (CBF) after cerebral ischemia induced by cardiac arrest. Cerebral ischemia was produced by 10 min of electrically mediated ventricular fibrillation. An iv injection of NC (10 micrograms/kg) bolus was followed by continuous NC infusion (0.33 micrograms/kg X min) immediately after the circulation re-established itself. Local CBF was measured using the hydrogen-gas clearance method. The administration of NC maintained CBF at the pre-arrest level during postischemia, thus preventing the hypoperfusion observed in the control group with no NC. However, in the controls, CBF, reduced at 180 min after re-circulation, was not improved by NC infusion. Consequently, administering NC immediately after re-establishment of circulation may help maintain CBF during the postresuscitation period.

Time-dependent effects of prolonged hypercapnia on cerebrovascular parameters in dogs: acid-base chemistry.

Prolonged normoxic hypercapnia initially caused an increase in canine cerebral blood flow, as measured by the radioactive microsphere technique, accompanied by a decrease in cerebrovascular resistance. These effects persisted for 3 hours. An adaptive decrease in cerebral blood flow and increase in cerebrovascular resistance were seen when hypercapnia was maintained for an additional 3 hours. Regional variations occurred; those areas with the greatest initial hypercapnic blood flow (cortex, caudate nucleus) showed a greater rate of decay of flow over time. Cerebrospinal fluid pH, initially acidotic during hypercapnia, increased over the subsequent 5 hours from 6.99 +/- 0.02 to 7.13 +/- 0.02. This was accompanied by an increase in the cerebrospinal fluid bicarbonate ion concentration from a normocapnic baseline of 19.6 +/- 0.6 to 26.2 +/- 4 mEq/l. Total and regional cerebral blood flow were linearly related to cerebrospinal fluid pH (R2 = 0.97). Extrapolation of a full adaptive return of flow to baseline indicated a shift in the cerebrovascular sensitivity to extracellular hydrogen ion concentration during prolonged hypercapnia.

The effects of gammahydroxybutyric acid on canine cerebral blood flow and metabolism.

Gammahydroxybutyric acid has been proposed as an alternative to high-dose barbiturate therapy for protecting the brain after ischemic or traumatic insult. The cerebral and systemic metabolic and vascular effects of gammahydroxybutyrate and its lactone analogue, gammabutyrolactone, are addressed in this paper. In anesthetized normal dogs, gammahydroxybutyrate or gammabutyrolactone was infused intravenously at a rate of 1 gm/kg/hr. Cerebral blood flow (CBF) decreased progressively with increasing doses of either agent. Cerebral metabolic rate of oxygen (CMRO2) increased initially with gammahydroxybutyrate, but not following gammabutyrolactone. Reduction in CBF exceeded that of CMRO2 at all doses in both series. The primary systemic effect noted was a severe, lethal metabolic acidosis resulting from infusion of gammabutyrolactone. Gammahydroxybutyrate did not cause a similar acidosis. The imbalance of the CBG-CMRO2 reduction following gammahydroxybutyrate administration suggests that it has no advantage over barbiturates in the management of patients with cerebral vascular insufficiency or intracranial hypertension.

Effects of cyclopropane on canine cerebral blood flow and metabolism: modification by catecholamine suppression.

Effects of cyclopropane on canine cerebral blood flow and metabolism: modification by catecholamine suppression.

Effects of Ketamine on Canine Cerebral Blood Flow and Metabolism

Effects of Ketamine on Canine Cerebral Blood Flow and Metabolism