Abstract• The effect of blood injected into either subarachnoid space or subcortical brain tissue upon lactate and pyruvate concentrations as well as acid-base balance of cerebrospinal fluid (CSF) was studied in the anesthetized dog.CSF lactate and lactate/pyruvate ratio (L/P ratio) increased progressively following the intracranial injection of blood and reached the maximum level at six hours after injection. These changes were significantly greater in animals with intracerebral hematoma than in those with subarachnoid hemorrhage (SAH). An increase in CSF lactate and L/P ratio in hemorrhagic CSF seems to be caused by two different factors. Shed blood cells per se produce lactate and pyruvate, and blood in the subarachnoid space and intracerebral hematomas cause secondary changes in brain tissue metabolism by a probable reduction of cerebral blood flow. Therefore, an increase in CSF lactate with a concomitant rise in CSF L/P ratio is a useful indicator for brain tissue hypoxia, even when CSF is hemorrhagic.The association of an increase in CSF lactate to a disproportionate decrease in CSF HCO 3 was also observed in these animals. Additional Key Wordscerebral hypoxia lactate/pyruvate ratio anaerobic glycolysis

Effects of• Brain lactate, pyruvate, and arterial acid-base balance were measured in normotensive rats (NTR) and spontaneously hypertensive rats (SHR) 60 minutes after bilateral carotid artery ligation. Brain lactate and lactate-pyruvate ratios were significantly increased in both SHR and NTR following carotid occlusion, although lactate increase in the former was six and one-half times greater than in the latter. These findings suggest that bilateral carotid occlusion in SHR may cause more severe circulatory changes which result in increased anaerobic metabolism. Furthermore, higher brain lactate was concomitant with lower arterial carbon dioxide tension. The mechanism of spontaneous hyperventilation following cerebral ischemia was discussed. Additional Key Wordsspontaneous hyperventilation cerebral ischemia hypocapnia anaerobic metabolism

Abstract• Lactate and pyruvate concentrations and acid-base balance in cerebrospinal fluid (CSF) and arterial blood were determined in patients with intracranial hemorrhages (28 subarachnoid hemorrhages and 15 intracerebral hemorrhages).A greater increase in CSF lactate and lactate-pyruvate ratio (L/P ratio) was observed in patients with impairment of consciousness, focal neurological deficits, poor prognosis, or CSF pressures higher than 300 mm H 2 O. A combination of CSF lactate greater than 2.5 mM per liter, L/P ratio above 20, bicarbonate less than 20.4 mEq per liter, pH below 7.276, or arterial PCO2 below 31.5 mm Hg seems to indicate a poor prognosis from intracranial hemorrhage.The mechanism of hyperventilation in acute cerebrovascular diseases and of CSF pH regulation in acid-base disturbances was also discussed.

SYNOPSIS Mortality and cerebral glycolytic metabolism were studied after bilateral ligation of the common carotid artery in normotensive Wistar rats (NTR), and spontaneously hypertensive rats (SHR) derived from Wistar strain. In the first 24 hours after occlusion of carotid arteries, 72% of 108 SHR died, whereas it was fatal in only 1600 of 43 NTR. In SHR, cerebral lactate and cerebral lactate/pyruvate ratio (L/P ratio) increased by 12.4 and 12.1 times the control, respectively at five to six hours after ligation, and remained raised even in rats surviving for two to three days thereafter. Changes in cerebral lactate and L/P ratio were minimal in NTR. Cerebral ATP decreased markedly at five to six hours after ligation in SHR studied. These results indicate that bilateral carotid artery ligation causes severe brain damage in SHR but not in NTR, suggesting hypertension per se to be operative for the development of cerebral ischaemia.In Wistar rats, it is difficult to cause a consistent ischaemic damage of the brain by bilateral ligation of the common carotid artery only (Payan et al., 1965), but it is possible to induce ischaemic anoxic lesions by a combination of unilateral carotid ligation and anoxic exposure (Levine, 1960;Plum et al., 1963). A similar study has not been made in spontaneously hypertensive rats (SHR), derived from the Wistar strain by Okamoto and Aoki (1963).The present study was undertaken to determine mortality and chronological changes in cerebral glycolytic metabolism after bilateral ligation of the carotid artery in SHR and in normotensive Wistar rats (NTR) as a control group. METHODMORTALITY One hundred and eight SHR and 43 NTR males, weighing between 200 and 450 g, aged from 4 to 9 months, were anaesthetized with intra-1 Address for correspondence: The Second Department of Internal Medicine, The Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka City 812, Japan. (Accepted 14 October 1975.) 212 peritoneal amylobarbitone (10 mg/100 g of body weight). Both common carotid arteries were exposed through ventral midline cervical incisions, separated from the vagosympathetic trunks, and doubly ligated at the same time. After the skin incision was closed with silk sutures, the animals were returned to their cages and were observed for the development of neurological deficits in the form of abnormal circling movements or rolling seizures. Mortality was recorded at 24 hours, and daily to seven days after ligations.ARTERIAL ACID-BASE BALANCE AND CEREBRAL METABOLISM In 22 SHR and 21 NTR, arterial acidbase balance, arterial blood pressure, and cerebral lactate and pyruvate concentrations were determined before, five to six hours, and two to three days after bilateral ligation of the carotid artery. In each ligated rat, reanaesthetized with amylobarbitone before being killed, one femoral artery was cannulated for blood pressure recording with an electromanometer, and also for anaerobic sampling for blood gas analysis. Arterial P02, pCO2, and pH were determined by an IL meter m...

Moderate unilateral cerebral ischemia was produced by microembolism in 24 adult cats. Two million plastic microspheres with a diameter of 15 +/- 5 microns were injected into the left common carotid artery via the lingual artery. The physiological and metabolic responses to embolism were accessed by electrocorticography and by determining the cerebral energy state. Embolism caused an immediate slowing and voltage reduction of the ipsilateral electrocorticogram with a gradual recovery after 30 to 60 min. Some animals also had an immediate and short depression of the contralateral electrocorticogram. In spite of the market functional suppression, metabolites of the cerebral energy-producing metabolism in most of the animals changed only slightly. In the embolized hemisphere pyruvate increased from 0.06 to 0.10 mumol/g and lactate from 1.9 to 4.6 mumol/g within 5 min after embolization and remained at this level during the 4 h observation period. Phosphocreatine, adenosine triphosphate and the energy charge of the adenylate pool remained uncharged during this period. However, there was a slight increase of ATP in the non-embolized hemisphere during the early postembolic period. In two animals, the initial slowing of the electrocorticogram recurred and spread to the contralateral hemisphere, followed by bilateral flattening after a few hours. This delayed functional deterioration was accomplished by complete loss of energy-rich phosphates. These animals also had a progressive increase of cerebrospinal fluid (CSF) pressure and considerable brain swelling with cerebellar herniation after 4 h. It is concluded that unilateral cerebral embolism in the above concentration leads only to a slight increase of anerobic glycolysis without significant perturbation of the cerebral energy state, unless progressive brain swelling with cerebrellat herniation supervenes. This supports previous findings, that brain edema and not initial ischemia is the main pathogenetic factor for tissue damage in cerebral microembolism.