George E. Locke

Cerebral Spinal Fluid Lactic Acid Following Circulatory Arrest

CSF lactic acid rises quickly and then gradually declines toward normal after severe cerebral ischemia in the dog. In animals in whom recovery can be postulated, the increase in lactic acid would appear to be transitory, and more severe insults produce higher levels. The increase in blood levels of lactic acid occurs more rapidly than that in the CSF, and the blood level returns to normal sooner than the CSF.

Cerebral and spinal fluid anaerobism during circulatory arrest

RESTRICTION of canine cerebral circulation leads to an accumulation of tissue lactate proportional to time up to about ten minutes of total substrate deprivation.1 Following severe cerebral stress of almost any etiological category with or without obvious cerebral nutrient and oxygen deficiency, cerebrospinal fluid (CSF) lactate levels have been noted to be elevated., Following restoration of circulation after vascular interruption, CSF lactate levels are also increased.3 Both the rapidity of lactate egress from brain tissue to CSF and the absolute amount of lactate in CSF during acute ischemia are unknown. Since CSF lactate concentration may be a measure of “brain death,” knowledge of CSF lactate concentration with known cerebral tissue lactate (CTL) accumulation may be valuable during an extended and known period of circulatory deprivation. Also, such comparison may afford information regarding the mechanism and rapidity of the transfer of this important metabolite across the brain-CSF barrier. CSF has been considered representative of brain extracellular space for many constituent elements, and CSF lactate levels have been utilized to indicate cerebral metabolic pe r fo r rnan~e .~ ,~ This investigation casts doubt upon the validity of the CSF lactate content, during extended circulatory arrest, as being entirely representative of conditions existing within brain tissue. Also, relative rates of lactate accumulation in brain, CSF, and blood have been substantiated.

Intracranial pressure during circulatory arrest.

Summary Anoxic cerebral functional derangement commonly results from extracranial arterial obstruction or cardiac arrest and magnitude of alteration of intracranial pressure is useful in assessing pathological intracranial relationships. Absolute intracranial pressure was quantified in dogs during acute occlusion of major intrathoracic vessels and ventricular fibrillation. Raised intracranial pressure resulted within 2 min of circulatory cessation in each case and average rises were 35 cm H2O when all major vessels were ligated, 25 cm during ventricular fibrillation, 10 cm with superior and inferior vena caval occlusion, 4 cm with superior vena cava blockage, and no effect was observed with ligation of azygos vein or inferior vena cava. Intracranial hypertension was sustained for up to 5 min. Visual observations of cerebral surface vessels with acute circulatory arrest showed no change in diameter of small arteries and veins so that elevated intracranial pressure is most likely a primary result of venous back pressure due to cardiac failure or venous obstruction since there is a concordant rise in central venous pressure. Other possible sources of increased intracranial pressure which may be of lesser importance include intrinsic or extrinsic neurogenic vasodilatation, cerebral edema, or increased cerebrospinal fluid production.

Blood and cerebrospinal fluid lactate during induced hypotension.

Abstract Cerebral anaerobism during induced arterial hypotension to mean arterial pressure (HOH) and trimethaphan infusion (TIH) was evaluated in 11 dogs by comparison of lactate in cerebrospinal fluid (CSF) and arterial blood. In six HOH dogs average normotensive control CSF and blood lactates were 1.79 (range 1.45–2.2) and 1.21 (range 0.7–1.8) mmoles/liter. At 5, 30, and 60 min posthypotension, average CSF and blood lactates were 1.93 (range 1.4–2.7), 2.33 (range 2.1–2.6), 3.16 (range 2.6–4.8) mmoles/liter and 2.35 (range 1.4–3.9), 6.30 (range 2.4–12.4), 8.54 (range 5.0–12.6) mmoles/liter, respectively. In five TIH dogs average control CSF and blood lactates were 1.74 (range 1.5–1.9) and 1.18 (range (0.32–2.10) mmoles/liter. At 5, 30, and 60 min posthypotension average CSF and blood lactates were 1.74 (range 1.4–2.1), 2.48 (range 1.6–3.5), 2.68 (range 1.9–3.7) and 1.56 (range 0.79–2.60), 3.76 (range 1.6–5.4), 4.16 (range 2.3–5.4) mmoles/liter respectively. Statistical analysis of CSF data shows that there is no significant difference between HOH and TIH lactate accumulation, and that 5–30 min are required for significant elevation over controls. Analysis of blood lactate shows significant elevation over controls during HOH by 5 min and during TIH by 30 min, with greater lactate accumulation in HOH than TIH by 60 min. Futility of using CSF lactate and advantage of employing blood lactate to monitor cerebral metabolism during hypotension is demonstrated.

In vitro basilar and common carotid artery reactivity to alpha and beta stimulation.

INVESTIGATIONS INTO PROBLEMS of intracranial vascular physiology have been stimulated by a multiplicity of clinical difficulties encountered in cerebral vascular disease. One of these which has recently been found of great significance is arterial vasospasm. This is a vascular smooth muscle contraction of unusual magnitude and duration which is not reversed by known vasoactive substances. I t is essential to distinguish spasm from physiological vasoconstriction with mural tension changes readily influenced by a multitude of vasoactive substa1ices.l The consequences of vasospasm include brain infarction from decreased cerebral blood flow in the distribution of the spastic artery. The cause of spasm is not known but occurs in conjunction with subarachnoid hemorrhage, occlusive disease, and surgical manipulation.2 Also, although it is well known that large and small cerebral vessels react to numerous physiological environmental alterations, exact mechanisms are unknown. Prompted by the work of others3-7 on smaller cerebral vessels, the intrinsic myogenic properties of large vessels from dogs and monkeys in physiological environs were investigated in vitro. Thereby, extrinsic neural, autacoidal, and metabolic parameters which cannot be controlled adequately in vivo can be avoided. A large intracranial vessel, the basilar artery, was utilized, since in man this vessel is involved in vasospasm, angiographically and under direct observation,z.z as a result of primary disease processes.

Cerebral tissue lactate in trimethaphan-induced hypotension☆

Abstract Ischemic effects of profound sustained hypotension upon the brain utilizing trimethaphan have been investigated because of frequent clinical utilization by surgeons. In ten dogs hypotension (30 to 40 mm Hg MAP) was sustained for one hour. Cerebral tissue lactate accumulation was assessed at five, thirty, and sixty minutes. By thirty minutes lactate rose to four to five times control levels but this did not increase in extent by sixty minutes. During profound trimethaphan-induced hypotension the brain incurs a progressive and marked oxygen debt. After thirty minutes and up to one hour of sustained hypotension hypoxic levels of lactate are attained, possibly indicating irreversibility.

Clotting Factors with Cerebral Ischemia in Dogs

In the setting of total cessation of cerebral blood flow, the brain is irreversibly damaged in a matter of minutes. There is marked difference in the extent of damage depending upon the pre-existing state of the animal as far as oxygenation and general homeostatis.’ Following cessation of cerebral blood flow, and particularly in a setting of &dquo;brain death&dquo;, changes in spinal fluid lactic acid have been found.2 It has been suggested that these changes are related to inability of the blood supply of the brain to remove metabolites, and may in turn reflect clotting in the microcirculation of the brain. &dquo;Brain death&dquo; is known to be associated with such clotting as well as with endothelial thickening and swelling of the supporting elements of the brain and blood vessels. There is failure of adequate passage of radio-contrast material under circumstances of brain death following cerebral ischemia.3 These studies report investigations of some clotting factors in dogs which have been subjected to total cessation of blood flow. Procedure and Results: Twelve adult mongrel dogs were utilized, following adequate anesthesia with Nembutal intravenously. While supported with an endotrachial tube and Harvard respirator, the chest was opened and the inferior and superior vena cava, as well as the aorta, were abruptly occluded. A catheter was inserted into the inferior vena cava and femoral artery. A small bur hole and catheter were also placed in the occipital region with penetration of the torcula. In most cases the latter opening was occluded with bone wax, and the catheter was re-inserted at the time of removal of specimens. Animals were monitored with EKG’s and with arterial pressures to assure adequate total ischemia. Four of the 12 underwent the same surgery but were not clamped for control evaluation. Material was obtained in appropriate specimen tubes, and a prothrombin time, partial thromboplastin time, thrombin time and platelet count performed. The major technical difficulty was the tendency of the blood to clot during the period of occlusion or immediately thereafter. This was particularly true in the sagittal sinus, and it was also difficult to obtain blood from the

Cerebral ischemia during cardiac resuscitation

Abstract The adequacy of cardiac massage during ventricular fibrillation for prevention of cerebral ischemia was assessed in dogs. Systolic blood pressure was maintained above 80 mm Hg and extent of cerebral tissue lactate accumulation was determined for periods up to 40 min. Lactate, as an indicator of hypoxia, was present in large amounts but protection, as compared to levels present during circulatory arrest and oligemic hypotension (30 mm Hg), was demonstrated.