Anesth A n a k 5 6 :817-821, 1977
817
Young, Fencl, Woods, e t a1
Cerebr.a1 Surface pH Changes During Asphyxia, Hypotension, and Circulatory Arrest in the Dog A. E. YOUNG, FRCS*
V. FENCL, MDt M. WOODS, MDS
J. DMOCHOWSKI, MDS N. P. COUCH, MD, FACSll Boston, Massachusetts* *
A technic is described for the measurement of cerebral surface pH i n acute experiments in anesthetized dogs. During asphyxia and circulatory arrest, cerebral surface pH fell promptly and more profoundly than arterial blood or muscle surface pH; during hypovolemic hypotension (30 to 50 torr) cerebral surface pH declined later and less than muscle surface pH. The cerebral surface pH reflects t h e pH of the
ONE
of the paramount features in mammalian homeostasis is the stability of acid-base balance in the brain. Only small variations of hydrogen ion activity are permitted by the normal brain, and these variations are intimately involved with the control of cerebral blood flow1 and respiration.2 A technic is reported for the experimental, continuous monitoring of hydrogen ion activity at the brain surface, together with studies of the effects on cerebral surface pH (pH,,) of asphyxia, hypovolemic hypotension, and circulatory arrest.
cortical interstitial fluid. Since the blood brain barrier is effectively impermeable to lactate, the changes recorded in the cerebral surface pH a re a useful index of cortical intracellular metabolism. Key Wards-AclD-BASE pH.
MENT~
pH.
pH.
pH' MEASURE-
METHODS AND MATERIALS Special apparatus included 7 0 - right~ angle glass p~ electrodes (fig 1) (Ingold Electrodes, Inc., Lexington, Mass., cat. no. 6300), p~ electrometers (Corning, Model 12), and a ,,hart recorder. Dogs were anesthetized with IV sodium pentobarbital (30 mg/kg) and a cuffed endotracheal tube placed. In those experiments where mechanical ventilation was employed, a normal minute volume was selected for each dog, on the basis of body
*Research Fellow; recipient of a grant from the Wellcome Foundation. ?Associate Professor of Physiology (Anesthesia). SResearch Fellow. %Associatein Surgery.
11 Associate
Professor of Surgery.
**Departments of Surgery and Anesthesia, Peter Bent Brigham Hospital and Haward Medical School, Boston, Massachusetts. Address reprint requests to N. P. Couch, Department of Surgery, Haivard Medical School, Boston, Massachusetts 02115. Accepted for publication: May 19, 1977
818
Cerebral Surface pH
I ND I CATOR ELECTRODE REFERENCE ELECTRODE
-
Anesth Analg 5 6 :817-821, 1977
was removed from the brain and a 2nd form of check was performed: a pledget of cotton wool soaked in 1.0 N butanol was applied to the cerebral surface for 10 minutes to damage the blood-brain barrier.4 The probe was then replaced and the response to another injection of 10 mEq bicarbonate was observed. If the acid response was reduced by more than 60 percent or had become an alkaline response, the blood-brain barrier was assumed to have been previously intact.
In the experiments to be described, muscle surface pH (pH,,) was measured by a pH electrode placed on the surface of the gracFIG1. Diagram of the right-angled organ surface ilis muscle through a small skin incision.5 pH monitoring probe and its position when used Arterial blood gases and arterial pressure for monitoring pHcs. were measured by means of a cannula placed in the femoral artery. In 15 mongrel dogs weighing 10 to 15 kg, weight, from the Kleinman Radford ventilation graph. Minor adjustments to ven- the effects of asphyxia, hypovolemic hypotilation were made if necessary so as to tension, and circulatory arrest were studied. maintain the arterial blood gases within the In all experiments, arterial 0, and C 0 2 tennormal range. A midline incision was made sions, pH (pH,), blood pressure, pH.,, and from the root of the muzzle to the midneck, pH,, were stable and in the normal range and the temporalis muscle was lifted from at the start of the experiment. the skull with a periosteal elevator. A 2-cm Asphyxia was induced on 10 occasions in burr hole was made in the center of 1 pa5 spontaneously breathing dogs by clamping rietal bone using a handbrace, care being the endotracheal tube for 5 minutes. During taken to avoid injury to the brain surface. When the burr had penetrated the inner asphyxia, lactate levels were measured, in table of the skull, the hole was enlarged with addition to the other variables mentioned. bone forceps. The dura mater having been Hypovolemic hypotension was produced exposed, its vessels were coagulated with in 4 paralyzed (succinylcholine) and venminimal electrodiathermy current. An inci- tilated dogs by arterial bleeding until a sion was made in the dura just large enough mean blood pressure of 40 torr was achieved. to accommodate the indicator electrode, and The bleeding was subsequently repeated in this was gently placed on the pia mater. small amounts sufficient to maintain the The probe was so positioned that the refer- mean blood pressure between 30 and 50 torr ence electrode was on the dura, rather than for 1 hour. the pia mater (fig 1 ) . The burr hole around Circulatory arrest was produced in 6 parthe probe was packed with the corners of alyzed and ventilated dogs by rapid infugauze sponges to absorb cerebrospinal fluid and blood from the region of the probe. sion of 300 mg of sodium pentobarbital into When the pHcs was stable, the integrity of the inferior vena cava. Cessation of heart the system was checked by I V injection of beat occurred within 10 seconds in all ani10 mEq of sodium bicarbonate (in 10 ml). mals. Where this produced a transient acid reRESULTS sponse on the brain surface, it was assumed During asphyxia the blood pressure rose that the blood-brain barrier was i n t a ~ t I.f~ rapidly, the average increase being 47 torr such a response did not occur, the bloodbrain barrier was considered to be damaged from a mean control blood pressure of 131 and a new burr hole was made over the torr. Changes in arterial pco,, PO,, and lacopposite cortex. This bicarbonate test was tate and in pH,,, pH,,, and pH, are shown also used at the end of each experiment. in fig 2. The pHcs decreased to lower levels The magnitude of the 2nd response was than did pH,, or pH, after 5 minutes of sometimes slightly different than that of the asphyxia. Changes during hypovolemic hypotension lst, but this was attributable to changes in acid-base status during the experiment. Af- are shown in fig 3. The pH, began to deter completion of the experiment, the probe crease when mean blood pressure was below DURA MATER
Anesth Analg 56 :517-821, 19'77
819
Young, Fend, Woods, et a1
7.4-
O
T
MUSCLE CEREBRAL
7270-
l\
i 69-j
PH 68 -
i
CEREBRAL
6.6-
6 4ARTERIAL BLOOD GASES
MM L
1'
0
-
~
0
ASPHYXIA
6.2 _-
0 2 5 MINUTES OF ARREST
lo
FIG4. Changes in pHAcand pH,, during the 1st 10 minutes of circulatory arrest (6 dogs: means and SEMI.
ARTERIAL BLOOD LACTATE
5 MINUTES
FIG2. Effects of total asphyxia of 5 minutes duration. Hatched bars show PO,, black bars show pco, (5 dogs: means and SEM).
P
0.6
v
more slowly, from 7.14 to 7.05, as shown in fig 4 and 5.
DISCUSSION Cerebral energy production is almost entirely fueled by the oxidative metabolism of glucose. When cerebral anoxia occurs, energy is derived from the anaerobic conversion of glucose to lactate by the Embden-Myerhof pathway.6 Since cerebral tissue metabolic rates are high and intracerebral buffering capacity is limited,? cerebral intracellular pH (pH,) falls early during tissue hypoxia.x,s The pHcs as measured in these experiments also changed rapidly and profoundly during all 3 varieties of hypoxic challenge. The magnitude of the changes was considerably greater than those occurring in pH,. The pH,, was measured at the pia mater,
TORR. I00 5 0 s
MINUTES:
0 5 10
0' 30
0'a site normally bathed by cerebrospinal 60
fluid. The changes seen in pHCs, however, were not those seen in ventricular or cisternal cerebrospinal fluid, where metabolic alterations occur slowly and then only with drastic shifts in blood or cerebral chemjstry.1"-13 The cerebrospinal fluid communicates through the pial membranes with the cerebral interstitial fluid,'* and it may therefore be assumed that, under the special conditions of these experiments, the 100 torr, but pHcs remained stable until pH,, as measured approximated to that of mean blood pressure was less than 50 torr. the interstitial fluid of the cerebral cortical During complete circulatory arrest, the surface. Changes in pH,, are mostly attribpHcs decreased rapidly from a mean of 7.26 utable to local changes of lactic acid, carto 6.44 after 10 minutes, while pH, declined bonic acid, and bicarbonate concentrations.
FIG 3. Changes in pH,, and pHl, during hypovolemic hypotension (4 dogs: means and SEM). Mean blood pressure and time are recorded on the abscissa. When blood pressure was 100 torr. mean pHcs was 7.28 and pH, was 7.22. A pH was recorded when the blood pressure reached 50 torr and then after 5, 10, 30, and 60 minutes of hypotension.
820
Anesth Anala
Cerebral Surface pH 7’3:
\ \
72
.-.-.+-- -.-.-._.
7.1 7.0 .
PH
\
6.9-
6.8 . 6.7
56 :817-821,1977
\
-
*\.
6.6. 65.
‘..‘ .
6,4-
I 0
5
,
‘. a
-.
WSCLE SURFACE
= -*.-
CEREBRAL SURFACE
‘
-------.-.-. I
I
10
15
I
20
25
I
50
35
WRATION OF ARREST MINUTES
FIG5. Changes in pHy and pHcs in a 16.5-kg dog during circulatory arrest.
The lactate molecules responsible for changes in hydrogen ion activity must be primarily derived from cerebral tissues, because the blood-brain barrier has a low permeability to lactatelo and the barrier was shown to remain intact during the experiments. A transport mechanism for lactate is present in the blood-brain barrier, but its capacity is small and incapable of moving enough lactate to account for the large declines in pH,, found in these studies.lS In a study of brain metabolites in asphyxiated rats, Kaasik, Nilsson, and Siesjo calculated intracellular brain “pH” from estimates of cerebral lactate and bicarbonate concentrations.8 After 3 minutes of asphyxia, the computed intracellular “pH’ decreased by 0.6 pH units, but after that it fell no further. In the present experiments, the fall in pHcs was not initially as great, but the decrease continued for longer than 3 minutes although the degree of asphyxia, as determined by blood gas measurement, was similar. The delay in increase of pial hydrogen ion activity, as compared with that of the cellular interior, may be attributable to the factors governing movement of the lactate molecules through the cell membranes and in the interstitial fluid. In circulatory arrest, a condition in which tissue anoxia is more nearly total than in simple asphyxia, and in which there is no “washout” of molecular C 0 2 , the pH,, fell most steeply. Anaerobic metabolism is limited by the availability of substrate, a concept supported by studies with rat and mouse brain”16 that have shown that, after
6 minutes of anoxia, intracellular glucose stores are almost exhausted and lactate production ceases. In addition, a falling pH acts to inhibit glucolysis.8 The fact that pH,, continues to fall longer (fig 3 ) suggests that equilibration between intra- and extra-cellular fluids is continuing.
During hypotension, the increase of cerebral surface hydrogen ion activity began as the mean arterial pressure fell below approximately 50 torr. Other investigators have demonstrated an increase in cerebral intracellular lactate production as blood pressure fell below 100 torr.l7 The 50 torr level is, however, the point at which autoregulation of cerebral blood flow is known to fail1 and a t which a drop in cerebral intracellular “pH’ is first appreciable.9 During asphyxia and circulatory arrest, the fall in pH, was less than that seen in pH,, because of the low metabolic rate of muscle in the anesthetized animal. During hypotension, however, pH,, fell more promptly and further than pH,,, confirming the “low-priority” status of muscle and the effect of increased catecholamines on muscle blood flow and anaerobic metabolic pathways. The pHII has been repeatedly shown to be a good index of peripheral perfusion and of metabolic or respiratory acidosis or alkaThe present studies, as well as several others,20J1 suggest that pH,, is a similarly sensitive measure of brain perfusion and metabolism. Although the recording of pH,, is invasive, there is no damage
Anesth Analg 5 6 317-821, 1977
Young, Fencl, Woods, et a1
to cerebral tissue itself. The cerebral response to respiratory, metabolic, and hemodynamic changes arising elsewhere in the body may therefore be continuously assessed. The measurement of pHcg is primarily of value in animal experiments but might also find use, in a neurosurgical context, for the assessment of head injuries and in studying the effects of anesthetic agents on cerebral perfusion and metabolism.
REFERENCES 1. Lassen NA: The control of cerebral circulation in health and disease. Circ Res 34:749-760, 1974
2. Loeschcke HH, ed: Acid-Base Homeostasis of the Brain Extracellular Fluid and the Respiratory Control System. Stuttgart, G. Thieme, 1976 3. Rapoport SI: Cortical p H and the bloodbrain barrier. J Physiol 170:238-249, 1964
821
phosphocreatine and adenine iiucleotides in anaesthetized rats. Acta Physiol Scand 78:448-458, 1970 10. Weyne JF, Leusen I: Lactate in c.s.f. in relation to brain and blood, Fluid Environment of the Brain. Edited by J D Cserr, J D Fenstermacber, V Fencl. New York, Academic Press, 1975
11. Fencl V, Miller TB, Pappenheimer J R : Studies on the respiratory response to disturbances of acid-base balance with deductions concerning the ionic composition of cerebral interstitial fluid. Am J Physiol 210:459-472, 1966
12. Pavlin EG, Hornbein TF: Distribution of H+ and HCO, between CSF and blood during metabolic acidosis in dogs. Am J Physiol 228:1136-1140, 1975 13. Pavlin EG, Hornbein TF: Distribution of H+ and HCO., between CSF and blood during metabolic alkalosis in dogs. Am J Physiol 228:1141-1144, 1975 14. Brightman MD: The distribution within the brain of ferritin injected into the cerebro-spinal fluid. J Cell Biol 26:99-123, 1965
4. Rapoport SI: The effect of topically applied substances on the blood-brain barrier. J Pharmacol Exp Ther 144:310-315, 1964
15. Nemoto EM, Hoff JT, Severinghaus JW: Lactate uptake and metabolism by brain during hyperlactatemia and hypoglycemia. Stroke 5: 48-53, 1974
5. Couch NP, Dmochowski JR, Van de Water dA, et al: Muscle surface pH as an index of periphoral perfusion in man. Ann Surg 173:173-183, 1971
16. Nilsson L, Busto R: Anoxia and brain metabolism during the process of dying. Acta Anaesthesiol Scand 20: 57-64, 1976
6. Lowry OH, Passonneau JV, Hasselberger FX, et al: Effect of ischemia on known substrates and co-factors of the glycolytic pathways in the brain. J Biol Chem 239:18-30, 1964
17. Siesjo BK, Zwetnow NN: The effects of hypovolaemic hypotension on extra and intracellular acid base parameters and energy metabolites in the rat brain. Acta Physiol Scand 79:114-124, 1970
7. Siesjo BK, Messeter K: Factors of determining intracellular pH, Ion Homeostasis of the Brain. Edited by BK Siesjo and SC Sorenson. New York, Academic Press, 1971, pp 244262
18. Smith RN, Lemieux MD, Couch NP: Effects of acidosis and alkalosis on surface skeletal muscle pH. Surg Gynecol Obstet 128:533-538, 1969
8. Kaasik AE, Nilsson L, Siesjo BK: The effects of asphyxia upon the lactate, pyruvate and bicarbonate concentrations of brain tissue and cistei-nal csf, and upon the concentrations of phosphocreatine and adenine nucleotides in anaesthetized rats. Acta Physiol Scand 78:433-447, 1970 9. Kaasik AE, Nilsson L, Siesjo BK: The effects of arterial hypotension upon lactate, pyruvate and
bicarbonate concentrations of brain tissue and cisternal csf and upon the tissue concentrations of
19. Filler RM, Das JB, Espinosa HM: Clinical experience with continuous muscle pH monitoring as an index of tissue perfusion and oxygenation and acid-base status. Surgery 72: 23-33, 1972 20. Bctz E, Heuser D: Cerebral cortical blood flow during changes of acid-base equilibrium of the brain. J Appl Physiol 23: 726-733, 1967
21. Rogers LA, Bcrman IR: Cortical surface pH as a means of determining regional brain perfusion. Surg Gynecol Obstet 134:799-802, 1972
817
Young, Fencl, Woods, e t a1
Cerebr.a1 Surface pH Changes During Asphyxia, Hypotension, and Circulatory Arrest in the Dog A. E. YOUNG, FRCS*
V. FENCL, MDt M. WOODS, MDS
J. DMOCHOWSKI, MDS N. P. COUCH, MD, FACSll Boston, Massachusetts* *
A technic is described for the measurement of cerebral surface pH i n acute experiments in anesthetized dogs. During asphyxia and circulatory arrest, cerebral surface pH fell promptly and more profoundly than arterial blood or muscle surface pH; during hypovolemic hypotension (30 to 50 torr) cerebral surface pH declined later and less than muscle surface pH. The cerebral surface pH reflects t h e pH of the
ONE
of the paramount features in mammalian homeostasis is the stability of acid-base balance in the brain. Only small variations of hydrogen ion activity are permitted by the normal brain, and these variations are intimately involved with the control of cerebral blood flow1 and respiration.2 A technic is reported for the experimental, continuous monitoring of hydrogen ion activity at the brain surface, together with studies of the effects on cerebral surface pH (pH,,) of asphyxia, hypovolemic hypotension, and circulatory arrest.
cortical interstitial fluid. Since the blood brain barrier is effectively impermeable to lactate, the changes recorded in the cerebral surface pH a re a useful index of cortical intracellular metabolism. Key Wards-AclD-BASE pH.
MENT~
pH.
pH.
pH' MEASURE-
METHODS AND MATERIALS Special apparatus included 7 0 - right~ angle glass p~ electrodes (fig 1) (Ingold Electrodes, Inc., Lexington, Mass., cat. no. 6300), p~ electrometers (Corning, Model 12), and a ,,hart recorder. Dogs were anesthetized with IV sodium pentobarbital (30 mg/kg) and a cuffed endotracheal tube placed. In those experiments where mechanical ventilation was employed, a normal minute volume was selected for each dog, on the basis of body
*Research Fellow; recipient of a grant from the Wellcome Foundation. ?Associate Professor of Physiology (Anesthesia). SResearch Fellow. %Associatein Surgery.
11 Associate
Professor of Surgery.
**Departments of Surgery and Anesthesia, Peter Bent Brigham Hospital and Haward Medical School, Boston, Massachusetts. Address reprint requests to N. P. Couch, Department of Surgery, Haivard Medical School, Boston, Massachusetts 02115. Accepted for publication: May 19, 1977
818
Cerebral Surface pH
I ND I CATOR ELECTRODE REFERENCE ELECTRODE
-
Anesth Analg 5 6 :817-821, 1977
was removed from the brain and a 2nd form of check was performed: a pledget of cotton wool soaked in 1.0 N butanol was applied to the cerebral surface for 10 minutes to damage the blood-brain barrier.4 The probe was then replaced and the response to another injection of 10 mEq bicarbonate was observed. If the acid response was reduced by more than 60 percent or had become an alkaline response, the blood-brain barrier was assumed to have been previously intact.
In the experiments to be described, muscle surface pH (pH,,) was measured by a pH electrode placed on the surface of the gracFIG1. Diagram of the right-angled organ surface ilis muscle through a small skin incision.5 pH monitoring probe and its position when used Arterial blood gases and arterial pressure for monitoring pHcs. were measured by means of a cannula placed in the femoral artery. In 15 mongrel dogs weighing 10 to 15 kg, weight, from the Kleinman Radford ventilation graph. Minor adjustments to ven- the effects of asphyxia, hypovolemic hypotilation were made if necessary so as to tension, and circulatory arrest were studied. maintain the arterial blood gases within the In all experiments, arterial 0, and C 0 2 tennormal range. A midline incision was made sions, pH (pH,), blood pressure, pH.,, and from the root of the muzzle to the midneck, pH,, were stable and in the normal range and the temporalis muscle was lifted from at the start of the experiment. the skull with a periosteal elevator. A 2-cm Asphyxia was induced on 10 occasions in burr hole was made in the center of 1 pa5 spontaneously breathing dogs by clamping rietal bone using a handbrace, care being the endotracheal tube for 5 minutes. During taken to avoid injury to the brain surface. When the burr had penetrated the inner asphyxia, lactate levels were measured, in table of the skull, the hole was enlarged with addition to the other variables mentioned. bone forceps. The dura mater having been Hypovolemic hypotension was produced exposed, its vessels were coagulated with in 4 paralyzed (succinylcholine) and venminimal electrodiathermy current. An inci- tilated dogs by arterial bleeding until a sion was made in the dura just large enough mean blood pressure of 40 torr was achieved. to accommodate the indicator electrode, and The bleeding was subsequently repeated in this was gently placed on the pia mater. small amounts sufficient to maintain the The probe was so positioned that the refer- mean blood pressure between 30 and 50 torr ence electrode was on the dura, rather than for 1 hour. the pia mater (fig 1 ) . The burr hole around Circulatory arrest was produced in 6 parthe probe was packed with the corners of alyzed and ventilated dogs by rapid infugauze sponges to absorb cerebrospinal fluid and blood from the region of the probe. sion of 300 mg of sodium pentobarbital into When the pHcs was stable, the integrity of the inferior vena cava. Cessation of heart the system was checked by I V injection of beat occurred within 10 seconds in all ani10 mEq of sodium bicarbonate (in 10 ml). mals. Where this produced a transient acid reRESULTS sponse on the brain surface, it was assumed During asphyxia the blood pressure rose that the blood-brain barrier was i n t a ~ t I.f~ rapidly, the average increase being 47 torr such a response did not occur, the bloodbrain barrier was considered to be damaged from a mean control blood pressure of 131 and a new burr hole was made over the torr. Changes in arterial pco,, PO,, and lacopposite cortex. This bicarbonate test was tate and in pH,,, pH,,, and pH, are shown also used at the end of each experiment. in fig 2. The pHcs decreased to lower levels The magnitude of the 2nd response was than did pH,, or pH, after 5 minutes of sometimes slightly different than that of the asphyxia. Changes during hypovolemic hypotension lst, but this was attributable to changes in acid-base status during the experiment. Af- are shown in fig 3. The pH, began to deter completion of the experiment, the probe crease when mean blood pressure was below DURA MATER
Anesth Analg 56 :517-821, 19'77
819
Young, Fend, Woods, et a1
7.4-
O
T
MUSCLE CEREBRAL
7270-
l\
i 69-j
PH 68 -
i
CEREBRAL
6.6-
6 4ARTERIAL BLOOD GASES
MM L
1'
0
-
~
0
ASPHYXIA
6.2 _-
0 2 5 MINUTES OF ARREST
lo
FIG4. Changes in pHAcand pH,, during the 1st 10 minutes of circulatory arrest (6 dogs: means and SEMI.
ARTERIAL BLOOD LACTATE
5 MINUTES
FIG2. Effects of total asphyxia of 5 minutes duration. Hatched bars show PO,, black bars show pco, (5 dogs: means and SEM).
P
0.6
v
more slowly, from 7.14 to 7.05, as shown in fig 4 and 5.
DISCUSSION Cerebral energy production is almost entirely fueled by the oxidative metabolism of glucose. When cerebral anoxia occurs, energy is derived from the anaerobic conversion of glucose to lactate by the Embden-Myerhof pathway.6 Since cerebral tissue metabolic rates are high and intracerebral buffering capacity is limited,? cerebral intracellular pH (pH,) falls early during tissue hypoxia.x,s The pHcs as measured in these experiments also changed rapidly and profoundly during all 3 varieties of hypoxic challenge. The magnitude of the changes was considerably greater than those occurring in pH,. The pH,, was measured at the pia mater,
TORR. I00 5 0 s
MINUTES:
0 5 10
0' 30
0'a site normally bathed by cerebrospinal 60
fluid. The changes seen in pHCs, however, were not those seen in ventricular or cisternal cerebrospinal fluid, where metabolic alterations occur slowly and then only with drastic shifts in blood or cerebral chemjstry.1"-13 The cerebrospinal fluid communicates through the pial membranes with the cerebral interstitial fluid,'* and it may therefore be assumed that, under the special conditions of these experiments, the 100 torr, but pHcs remained stable until pH,, as measured approximated to that of mean blood pressure was less than 50 torr. the interstitial fluid of the cerebral cortical During complete circulatory arrest, the surface. Changes in pH,, are mostly attribpHcs decreased rapidly from a mean of 7.26 utable to local changes of lactic acid, carto 6.44 after 10 minutes, while pH, declined bonic acid, and bicarbonate concentrations.
FIG 3. Changes in pH,, and pHl, during hypovolemic hypotension (4 dogs: means and SEM). Mean blood pressure and time are recorded on the abscissa. When blood pressure was 100 torr. mean pHcs was 7.28 and pH, was 7.22. A pH was recorded when the blood pressure reached 50 torr and then after 5, 10, 30, and 60 minutes of hypotension.
820
Anesth Anala
Cerebral Surface pH 7’3:
\ \
72
.-.-.+-- -.-.-._.
7.1 7.0 .
PH
\
6.9-
6.8 . 6.7
56 :817-821,1977
\
-
*\.
6.6. 65.
‘..‘ .
6,4-
I 0
5
,
‘. a
-.
WSCLE SURFACE
= -*.-
CEREBRAL SURFACE
‘
-------.-.-. I
I
10
15
I
20
25
I
50
35
WRATION OF ARREST MINUTES
FIG5. Changes in pHy and pHcs in a 16.5-kg dog during circulatory arrest.
The lactate molecules responsible for changes in hydrogen ion activity must be primarily derived from cerebral tissues, because the blood-brain barrier has a low permeability to lactatelo and the barrier was shown to remain intact during the experiments. A transport mechanism for lactate is present in the blood-brain barrier, but its capacity is small and incapable of moving enough lactate to account for the large declines in pH,, found in these studies.lS In a study of brain metabolites in asphyxiated rats, Kaasik, Nilsson, and Siesjo calculated intracellular brain “pH” from estimates of cerebral lactate and bicarbonate concentrations.8 After 3 minutes of asphyxia, the computed intracellular “pH’ decreased by 0.6 pH units, but after that it fell no further. In the present experiments, the fall in pHcs was not initially as great, but the decrease continued for longer than 3 minutes although the degree of asphyxia, as determined by blood gas measurement, was similar. The delay in increase of pial hydrogen ion activity, as compared with that of the cellular interior, may be attributable to the factors governing movement of the lactate molecules through the cell membranes and in the interstitial fluid. In circulatory arrest, a condition in which tissue anoxia is more nearly total than in simple asphyxia, and in which there is no “washout” of molecular C 0 2 , the pH,, fell most steeply. Anaerobic metabolism is limited by the availability of substrate, a concept supported by studies with rat and mouse brain”16 that have shown that, after
6 minutes of anoxia, intracellular glucose stores are almost exhausted and lactate production ceases. In addition, a falling pH acts to inhibit glucolysis.8 The fact that pH,, continues to fall longer (fig 3 ) suggests that equilibration between intra- and extra-cellular fluids is continuing.
During hypotension, the increase of cerebral surface hydrogen ion activity began as the mean arterial pressure fell below approximately 50 torr. Other investigators have demonstrated an increase in cerebral intracellular lactate production as blood pressure fell below 100 torr.l7 The 50 torr level is, however, the point at which autoregulation of cerebral blood flow is known to fail1 and a t which a drop in cerebral intracellular “pH’ is first appreciable.9 During asphyxia and circulatory arrest, the fall in pH, was less than that seen in pH,, because of the low metabolic rate of muscle in the anesthetized animal. During hypotension, however, pH,, fell more promptly and further than pH,,, confirming the “low-priority” status of muscle and the effect of increased catecholamines on muscle blood flow and anaerobic metabolic pathways. The pHII has been repeatedly shown to be a good index of peripheral perfusion and of metabolic or respiratory acidosis or alkaThe present studies, as well as several others,20J1 suggest that pH,, is a similarly sensitive measure of brain perfusion and metabolism. Although the recording of pH,, is invasive, there is no damage
Anesth Analg 5 6 317-821, 1977
Young, Fencl, Woods, et a1
to cerebral tissue itself. The cerebral response to respiratory, metabolic, and hemodynamic changes arising elsewhere in the body may therefore be continuously assessed. The measurement of pHcg is primarily of value in animal experiments but might also find use, in a neurosurgical context, for the assessment of head injuries and in studying the effects of anesthetic agents on cerebral perfusion and metabolism.
REFERENCES 1. Lassen NA: The control of cerebral circulation in health and disease. Circ Res 34:749-760, 1974
2. Loeschcke HH, ed: Acid-Base Homeostasis of the Brain Extracellular Fluid and the Respiratory Control System. Stuttgart, G. Thieme, 1976 3. Rapoport SI: Cortical p H and the bloodbrain barrier. J Physiol 170:238-249, 1964
821
phosphocreatine and adenine iiucleotides in anaesthetized rats. Acta Physiol Scand 78:448-458, 1970 10. Weyne JF, Leusen I: Lactate in c.s.f. in relation to brain and blood, Fluid Environment of the Brain. Edited by J D Cserr, J D Fenstermacber, V Fencl. New York, Academic Press, 1975
11. Fencl V, Miller TB, Pappenheimer J R : Studies on the respiratory response to disturbances of acid-base balance with deductions concerning the ionic composition of cerebral interstitial fluid. Am J Physiol 210:459-472, 1966
12. Pavlin EG, Hornbein TF: Distribution of H+ and HCO, between CSF and blood during metabolic acidosis in dogs. Am J Physiol 228:1136-1140, 1975 13. Pavlin EG, Hornbein TF: Distribution of H+ and HCO., between CSF and blood during metabolic alkalosis in dogs. Am J Physiol 228:1141-1144, 1975 14. Brightman MD: The distribution within the brain of ferritin injected into the cerebro-spinal fluid. J Cell Biol 26:99-123, 1965
4. Rapoport SI: The effect of topically applied substances on the blood-brain barrier. J Pharmacol Exp Ther 144:310-315, 1964
15. Nemoto EM, Hoff JT, Severinghaus JW: Lactate uptake and metabolism by brain during hyperlactatemia and hypoglycemia. Stroke 5: 48-53, 1974
5. Couch NP, Dmochowski JR, Van de Water dA, et al: Muscle surface pH as an index of periphoral perfusion in man. Ann Surg 173:173-183, 1971
16. Nilsson L, Busto R: Anoxia and brain metabolism during the process of dying. Acta Anaesthesiol Scand 20: 57-64, 1976
6. Lowry OH, Passonneau JV, Hasselberger FX, et al: Effect of ischemia on known substrates and co-factors of the glycolytic pathways in the brain. J Biol Chem 239:18-30, 1964
17. Siesjo BK, Zwetnow NN: The effects of hypovolaemic hypotension on extra and intracellular acid base parameters and energy metabolites in the rat brain. Acta Physiol Scand 79:114-124, 1970
7. Siesjo BK, Messeter K: Factors of determining intracellular pH, Ion Homeostasis of the Brain. Edited by BK Siesjo and SC Sorenson. New York, Academic Press, 1971, pp 244262
18. Smith RN, Lemieux MD, Couch NP: Effects of acidosis and alkalosis on surface skeletal muscle pH. Surg Gynecol Obstet 128:533-538, 1969
8. Kaasik AE, Nilsson L, Siesjo BK: The effects of asphyxia upon the lactate, pyruvate and bicarbonate concentrations of brain tissue and cistei-nal csf, and upon the concentrations of phosphocreatine and adenine nucleotides in anaesthetized rats. Acta Physiol Scand 78:433-447, 1970 9. Kaasik AE, Nilsson L, Siesjo BK: The effects of arterial hypotension upon lactate, pyruvate and
bicarbonate concentrations of brain tissue and cisternal csf and upon the tissue concentrations of
19. Filler RM, Das JB, Espinosa HM: Clinical experience with continuous muscle pH monitoring as an index of tissue perfusion and oxygenation and acid-base status. Surgery 72: 23-33, 1972 20. Bctz E, Heuser D: Cerebral cortical blood flow during changes of acid-base equilibrium of the brain. J Appl Physiol 23: 726-733, 1967
21. Rogers LA, Bcrman IR: Cortical surface pH as a means of determining regional brain perfusion. Surg Gynecol Obstet 134:799-802, 1972
