Autoregulation of Spinal Cord Blood Flow* ARTHUR
I.
KOBRINE,
lVI.D., THOMAS F. DOYLE, B.S., N. MARTINS, M.D.
AND ALBERT
Before one can accurately study the various pathophysiological mechanisms affecting any organ system, the normal physiological responses to certain variables must be known. The following set of experiments was undertaken to define first the response of spinal cord blood flow (SCBF) to changes in arterial pC0 2 (pAC0 2 ) under normotensive conditions, and second the changes in SCBF which accompany changes in mean arterial blood pressure (l\IAP) under normocapnic conditions. METHODS AND MATERIALS
Fourteen adult Rhesus monkeys were used in this experiment. The animals were initially anesthetized with 0.5 ml. of phencyclidine hydrochloride (Sernylan, Biocentric Laboratories Inc., St. Joseph, lV10.) and 1.0 ml. of sodium pentobarbital (Nembutal, Abbott Laboratories, North Chicago, Ill.). Catheters were inserted into the femoral artery for continuous blood pressure monitoring and periodic blood gas determination, and into the femoral vein for fluid replacement and for the administration of pharmacological agents. The animals were then intubated, placed on a volume respirator, and curarized. They received N 20 and O2 in a 2: 1 mixture for the remainder of the experiment. Temperature was continuously monitored by a rectal probe, and was kept at 37 to 39° C., using a heating pad when necessary. The pA0 2 was kept at 100 to 125 mm. Hg. A dorsal laminectomy was performed in the standard fashion, exposing the dura mater from T-7 to T -11. Three platinum electrodes, 250 microns in diameter, were then placed into the spinal cord through the intact dura. The electrodes, approximately 1 cm. apart, were placed into the cord at a point midway between the midline and lateral border, and were advanced to a depth of 2 mm. (Fig. 36.1). These coordinates placed the electrode tips in the lateral funiculus of the Rhesus spinal cord (10). The hydrogen clearance apparatus used in our laboratory for blood flow determination is similar to that described by Aukland and associates (1). However, the circuitry has been modified somewhat to stabilize the base line (17). This method, based on the Fick principle, has been shown to measure blood flow in a discrete volume of tissue, less than 0.5 cu. mm. (13).
* First Annual Resident Award, Congress of Neurological Surgeons. 573
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CHAPTER 36
574
CLINICAL NEUROSURGERY
Blood flow measurements were obtained in the following manner. Ten per cent hydrogen gas was added to the inspired air mixture for several minutes. During this time the "wash in" of hydrogen was monitored on the polygraph. Upon cessation of the hydrogen inhalation, the washout of hydrogen was recorded on the polygraph as a mono exponential tissue desaturation curve (Fig. 36.2), which was subsequently analyzed by hand, as well as by computer, programmed for a linear regression analysis that gave the least squares best fit of the monoexponential equation to the washout curve. The flow was then calculated from the slope of the curve. In the first group of seven animals, blood pressure remained constant and in the normal range. The pAC02 was lowered by hyperventilation or raised by the addition of CO 2 to the inspired air mixture. Each time the pAC02 was altered, the animal was allowed to stabilize for 15 minutes before blood flow determinations were made. Blood gases were obtained both before and after each determination. In each animal, the pAC02 was either progressively raised or lowered. Blood flows were never obtained at an abnormally low pAC02 subsequent to determinationsat an abnormally highpAC02 , or vice versa. In the second group of seven animals, the CO 2 content of the inspired
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FIG. 36.1. Artist's drawing of the experimental design. Insert shows detail of electrode placement. (From A. I. Kobrine, T. F. Doyle, and A. N. Martins: Spinal cord blood flow in the Rhesus monkey by the hydrogen clearance method. Surg. Neurol., 2: 197-200, 1974.)
SPINAL CORD BLOOD FLOW
575
air mixture was adjusted to maintain the pAC0 2 constant at physiological levels of 30 to 35 mm. Hg (14). The MAP was raised by an infusion of norepinephrine or lowered by bleeding. Blood flow determinations were made after a IS-minute period of stabilization at each l\1AP value. As in the previous group, the MAP was either raised or lowered in each animal; flows were not obtained in an animal at an abnormally low MAP subsequent to determinations at an abnormally high l\1AP, or vice versa. RESULTS
SCBF remained essentially constant and in the normal range with pAC02 values from 10 to 50 mm. Hg (Fig. 36.3, A, B). As the pAC02 was raised from 50 to 90 mm. Hg, SCBF increased. Further increases in the pAC02 above 90 mm. Hg had no effect on SCBF. SCBF remained constant and in the normal range with an MAP of 50 to 135 mm. Hg. Above an MAP of 135 mm. Hg, the SCBF increased with further increases in l\1AP; below an l\1AP of 50 mm. Hg, SCBF fell directly with further decreases in lVIAP (Fig. 36.4, A, B). DISCUSSION
It is now well recognized that one of the greatest factors responsible for the control of cerebral blood flow (CBF) is the pAC0 2 (7). Minor deviations from the normal pAC02 of 40 mm. Hg in humans result in relatively large corresponding changes in CBF. Most investigators now feel that the critical factor responsible for this control is the tissue and extracellular pH, which is altered by changes in the pAC02 (12). Although we have shown that a
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
FIG. 36.2 Polygraph tracing demonstrating simultaneous washout curves from three spinal cord electrodes.
576
CLINICAL NEUROSURGERY
OJ 60
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80
90
100
110
120
60 B
50
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t
NORMAL PaC02
=31 mm Hg
10.19 20-29 30-39 04Q049 50-59 ro·69 70-79 80·89 90-99 100·109110-120
PaC02 (mm Hg)
36.3. A, scatter diagram showing relationship of spinal cord blood flow to arterial pC02. B, best fitting line through the means of the previous data arranged in increments of 10 mm. Hg (pAC0 2) . FIG.
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
70
577
SPINAL CORD BLOOD FLOW 60
50
40
30
20
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..
10
10
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40
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1.10 119
1?0 129
1~0
139
140 149
150 159
160 169
170 179
MEAN ARTERIAL PRESSURE (mm Hg) FIG. 36.4. A, scatter diagram demonstrating relationship of spinal cord blood flow to mean arterial blood pressure. B, best fitting line through the means of the previous data arranged in increments of 10 mm. Hg (MAP).
similar relationship does exist between SCBF and pAC02 in the Rhesus monkey, some notable differences are present. SCBF never fell below the normal range, even at a pAC02 of 13 mm. Hg. The normal pAC02 of the Rhesus monkey, as stated earlier, has been shown to be 30 to 35 mm. Hg,
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
A
578
CLINICAL NEUROSURGERY
BLOOD FLOW = perfusion pressure/vascular resistance (VR). Since the brain is enclosed in a nonexpansive cranial vault, perfusion pressure is dependent upon the intracranial pressure (ICP) as well as the ~IAP. Therefore, CBF can be expressed by the equation: CBF = MAP - ICP VR However, the spinal cord is not similarly enclosed in a restrictive bony environment' and therefore SCBF is expressed by the equation: SCBF = MAP VR
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somewhat lower than the corresponding value in humans (14). Furthermore, in order to elicit a significant rise in SCBF"', the pAC0 2 had to be raised to 50 mm. Hg, an abnormally high value in the Rhesus monkey. It appears that the sigmoid shaped curve as seen in Figure 36.3, B is shifted to the right, when compared with the corresponding curve for CBF changes in humans, with SCBF at a normal pAC02 lying on the lower level of the sigmoid curve. These data are in general agreement with previous reports. Kindt and co-workers demonstrated a similar response of SCBF and CBF to changes in pAC02 , using a surface device which measured qualitative blood flow changes (9). Flohr and associates (3) were able to show a decreasing vascular resistance in the spinal cord with increases in pAC02 , using the particle distribution technique of blood flow measurement. Griffiths (5) and Smith and colleagues (15) demonstrated a similar response of SCBF"' and CBF to changes in pAC0 2 • In these experiments, however, blood flow was measured by the direct injections of a tracer into the spinal cord parenchyma, a technique not wholly agreed upon as acceptable (10). Figure 36.4, A, B depicts the changes observed in SCB}' accompanying corresponding changes in l\IAP. As can easily be seen from the graph, SCBF remained relatively constant and in the normal range during an l\1:AP of 50 to 135 mm. Hg. Therefore, autoregulation was in operation. The concept of autoregulation implies that the blood vessels in an organ possess the capability of changing their caliber, hence resistance, in order to maintain a constant blood flow during changes in perfusion pressure of the organ. Cerebral autoregulation was first described by Fog (4), who observed changes in the caliber of pial vessels in response to changes in systemic arterial blood pressure. Blood flow in an organ can be expressed by the equation:
SPINAL CORD Bl.OOD FLOW
579 Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
As can be seen from this equation, when increases in IVIAP are accompanied by corresponding increases in vascular resistance, and vice versa, SCBF will remain constant and autoregulation will be said to have been in effect. Three main theories exist which attempt to explain the mechanism of autoregulation. In 1902 Bayliss (2) suggested that the smooth muscle of blood vessels possesses an inherent ability to constrict in response to a rise in intraluminal pressure, and to dilate in response to a decrease in pressure. He appropriately termed this the myogenic theory. The metabolic, or chemical, theory is based on the premise that a time lag occurs after the blood pressure is lowered, before the vessels dilate. Supporters of this theory suggest that the period of hypotension causes a transient ischemia which leads to a local decrease in tissue and extracellular fluid pH. The increased H+ would then act directly on the blood vessels, causing vasodilation (18). Central neural control, via the sympathetic nervous system, has been suggested as one of the major mechanisms of autoregulation of CBF; this is termed the neurogenic theory. Support of this theory is based on the anatomical finding that the cerebrovascular tree is accompanied by sympathetic nerve fibers (8). Harper and associates (8) have recently suggested that autoregulation in the brain is governed by dual mechanisms, a neural control via the sympathetics operating on the extraparenchymal vessels, and a chemical control, as outlined above, controlling the caliber and hence resistance of the intraparenchymal vessels. However, preliminary studies done in this laboratory have yielded some evidence contrary to the neural theory, by demonstrating preserved autoregulation in the Rhesus spinal cord after high cervical cord section (11). In these animals, therefore, the central control of the sympathetic outflow was interrupted, and yet autoregulation remained intact. One can reasonably assume that the mechanisms responsible for autoregulation in the brain and spinal cord are quite similar, if not identical, since the histology and embryological derivation of both are the same. The above model would seem, therefore, to be well suited for the continuing study of the mechanisms responsible for autoregulation in the nervous system. As can be seen from Figure 36.4, A, B, at an MAP greater than 135 mm. Hg there is a breakthrough of autoregulation, with further increases in l\iAP effecting a significant increase in SCBF. At MAP levels less than 50 mn1. Hg, the vessels are maximally dilated, vascular resistance is minimal, and SCBF is passively controlled by MAP. Similarly, Strandgaard (16) demonstrated intact autoregulatory mechanisms in the brains of baboons up to an MAP of 120 to 140 mm. Hg, above which CBF increased directly with further increases in l\1:AP.
580
CLINICAL NEUROSURGERY
SUMMARY
The response of SCBF to changes in pAC0 2 was tested in Rhesus monkeys under normotensive conditions. A sigmoid shaped response was demonstrated. At a pAC02 of 10 to 50 mm. Hg, SCBF remained constant and in the normal range. As the pAC02 was raised from 50 to 90 mm. Hg, SCBF increased. Further increases in the pAC02 above 90 mm. Hg failed to effect further changes in SCBF. We conclude from these data that SCBF is somewhat less responsive than CBF to changes in pAC02 • N ext, the effect of changes in l\1AP on SCBF ","as studied under normocapnic conditions. SCBF remained constant and in the normal range with an MAP of 50 to 135 mm. Hg. Above 135 mm. Hg, SCBF rose with further increases in l\1AP. With decreases in lVIAP below 50 mm. Hg, SCBF fell passively. It is our conclusion that autoregulation exists in the lateral white matter of the spinal cord and follows a pattern similar to that suggested for the cerebrum. REFERENCES 1. Aukland , K., Bower, B. F., and Berliner, R. W. Measurement of local blood flow with hydrogen gas. Circ. Res., 14: 164-187,1964. 2. Bayliss, W. M. On the local reactions of the arterial wall to changes of internal pressure. J. Physiol. (Lond.), 28: 220-231, 1902. 3. Flohr, H., Poll, W., and Brock, M. Regulation of spinal cord blood flow. In Brain and Blood Flow, edited by R. W. R. Russell, pp. 406-409. Pitman, London, 1971. 4. Fog, M. The relationship between blood pressure and tonic regulation of the pial arteries. J. N eurol. Psychiatry, 1: 187-197, 1938. 5. Griffiths,!. R. Spinal cord blood flow in dogs. 2. The effect of the blood gases. J. Neurol. Neurosurg. Psychiatry, 36: 42-49, 1973. 6. Griffiths, I. R. Spinal cord blood flow in dogs: the effect of blood pressure. J. Neurol. Neurosurg. Psychiatry, 36: 914-920, 1973. 7. Harper, A. M. General physiology of cerebral circulation. In Cerebral Circulation, edited by D. G. McDowall, pp. 473-507. Little, Brown and Co., Boston, 1969. 8. Harper, A. M., Deshmukh, V. D., Rowan, J. 0., and Jennett, W. B. The influence of sympathetic nervous activity on cerebral blood flow. Arch. Neurol., 27: 1-6, 1972. 9. Kindt, G. W., Ducker, T. B., and Huddlestone, J. Regulation of spinal cord blood flow. In Brain and Blood Flow, edited by R. W. R. Russell, pp. 401-40.5. Pitman, London, 1971.
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Other investigators have addressed themselves to the question of autoregulation in the spinal cord. Using such methods as the particle distribution technique, surface flow measuring devices, and the intraparenchymal injection of tracer substances, they have generally agreed that autoregulation exists in the spinal cord and is not unlike that described for the brain (3, 6, 9).
SPINAL CORD BLOOD FLOW
581 Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
10. Kobrine, A.!., Doyle, T. F., and Martins, A. N. Spinal cord blood flow in the Rhesus monkey by the hydrogen clearance method. Surg. Neurol., 2: 197-200, 1974. 11. Kobrine, A. I., Doyle, T. F., and Martins, A. N. Preserved autoregulation in the Rhesus spinal cord after high cervical section. In preparation. ~2. Lassen, N. A. Brain extracellular pH: the main factor controlling cerebral blood flow. Scand. J. Clin. Lab. Invest., 22: 247-251, 1968. 13. Meyer, J. S., Fukuuchi, Y., Kanda, T., and Shimazu, K. Regional measurements of cerebral blood flow and metabolism using intracarotid injection of hydrogen, with comments on intracerebral steal. In Brain and Blood Flow, edited by R. W. R. Russell, pp. 71-80. Pitman, London, 1971. 14. Popovic, N. A., Mullane, J. F., Vick, J. A., and Kobrine, A. I. Effect of phencyclidine hydrochloride on certain cardiorespiratory values of the Rhesus monkey (Macaca mulatta). Am. J. Vet. Res., 33: 1649-1657, 1972. 15. Smith, A. L., Pender, J. W., and Alexander, S. C. Effects of PC0 2 on spinal cord blood flow. Am. J. Physiol., 216: 1158-1163, 1969. 16. Strandgaard, S. The lower and upper limit for autoregulation of cerebral blood flow. Stroke, 4: 323, 1973. 17. Willis, J. A., Doyle, T. F., Ramirez, A., Kobrine, A.!., and Martins, A. N. A Practical Circuit for Hydrogen Clearance Blood-flow Measurement, 10 pp. Armed Forces Radiobiology Research Institute, Bethesda, Md., 1974. 18. Zwetnow, N., Kjallquist, A., and Siesjo , B. K. Elimination of autoregulation following a period of pronounced intracranial hypertension: is hypoxia involved? Scand. J. Clin. Lab. Invest. 22: suppl. 102, V: F, 1968.
I.
KOBRINE,
lVI.D., THOMAS F. DOYLE, B.S., N. MARTINS, M.D.
AND ALBERT
Before one can accurately study the various pathophysiological mechanisms affecting any organ system, the normal physiological responses to certain variables must be known. The following set of experiments was undertaken to define first the response of spinal cord blood flow (SCBF) to changes in arterial pC0 2 (pAC0 2 ) under normotensive conditions, and second the changes in SCBF which accompany changes in mean arterial blood pressure (l\IAP) under normocapnic conditions. METHODS AND MATERIALS
Fourteen adult Rhesus monkeys were used in this experiment. The animals were initially anesthetized with 0.5 ml. of phencyclidine hydrochloride (Sernylan, Biocentric Laboratories Inc., St. Joseph, lV10.) and 1.0 ml. of sodium pentobarbital (Nembutal, Abbott Laboratories, North Chicago, Ill.). Catheters were inserted into the femoral artery for continuous blood pressure monitoring and periodic blood gas determination, and into the femoral vein for fluid replacement and for the administration of pharmacological agents. The animals were then intubated, placed on a volume respirator, and curarized. They received N 20 and O2 in a 2: 1 mixture for the remainder of the experiment. Temperature was continuously monitored by a rectal probe, and was kept at 37 to 39° C., using a heating pad when necessary. The pA0 2 was kept at 100 to 125 mm. Hg. A dorsal laminectomy was performed in the standard fashion, exposing the dura mater from T-7 to T -11. Three platinum electrodes, 250 microns in diameter, were then placed into the spinal cord through the intact dura. The electrodes, approximately 1 cm. apart, were placed into the cord at a point midway between the midline and lateral border, and were advanced to a depth of 2 mm. (Fig. 36.1). These coordinates placed the electrode tips in the lateral funiculus of the Rhesus spinal cord (10). The hydrogen clearance apparatus used in our laboratory for blood flow determination is similar to that described by Aukland and associates (1). However, the circuitry has been modified somewhat to stabilize the base line (17). This method, based on the Fick principle, has been shown to measure blood flow in a discrete volume of tissue, less than 0.5 cu. mm. (13).
* First Annual Resident Award, Congress of Neurological Surgeons. 573
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CHAPTER 36
574
CLINICAL NEUROSURGERY
Blood flow measurements were obtained in the following manner. Ten per cent hydrogen gas was added to the inspired air mixture for several minutes. During this time the "wash in" of hydrogen was monitored on the polygraph. Upon cessation of the hydrogen inhalation, the washout of hydrogen was recorded on the polygraph as a mono exponential tissue desaturation curve (Fig. 36.2), which was subsequently analyzed by hand, as well as by computer, programmed for a linear regression analysis that gave the least squares best fit of the monoexponential equation to the washout curve. The flow was then calculated from the slope of the curve. In the first group of seven animals, blood pressure remained constant and in the normal range. The pAC02 was lowered by hyperventilation or raised by the addition of CO 2 to the inspired air mixture. Each time the pAC02 was altered, the animal was allowed to stabilize for 15 minutes before blood flow determinations were made. Blood gases were obtained both before and after each determination. In each animal, the pAC02 was either progressively raised or lowered. Blood flows were never obtained at an abnormally low pAC02 subsequent to determinationsat an abnormally highpAC02 , or vice versa. In the second group of seven animals, the CO 2 content of the inspired
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
FIG. 36.1. Artist's drawing of the experimental design. Insert shows detail of electrode placement. (From A. I. Kobrine, T. F. Doyle, and A. N. Martins: Spinal cord blood flow in the Rhesus monkey by the hydrogen clearance method. Surg. Neurol., 2: 197-200, 1974.)
SPINAL CORD BLOOD FLOW
575
air mixture was adjusted to maintain the pAC0 2 constant at physiological levels of 30 to 35 mm. Hg (14). The MAP was raised by an infusion of norepinephrine or lowered by bleeding. Blood flow determinations were made after a IS-minute period of stabilization at each l\1AP value. As in the previous group, the MAP was either raised or lowered in each animal; flows were not obtained in an animal at an abnormally low MAP subsequent to determinations at an abnormally high l\1AP, or vice versa. RESULTS
SCBF remained essentially constant and in the normal range with pAC02 values from 10 to 50 mm. Hg (Fig. 36.3, A, B). As the pAC02 was raised from 50 to 90 mm. Hg, SCBF increased. Further increases in the pAC02 above 90 mm. Hg had no effect on SCBF. SCBF remained constant and in the normal range with an MAP of 50 to 135 mm. Hg. Above an MAP of 135 mm. Hg, the SCBF increased with further increases in l\1AP; below an l\1AP of 50 mm. Hg, SCBF fell directly with further decreases in lVIAP (Fig. 36.4, A, B). DISCUSSION
It is now well recognized that one of the greatest factors responsible for the control of cerebral blood flow (CBF) is the pAC0 2 (7). Minor deviations from the normal pAC02 of 40 mm. Hg in humans result in relatively large corresponding changes in CBF. Most investigators now feel that the critical factor responsible for this control is the tissue and extracellular pH, which is altered by changes in the pAC02 (12). Although we have shown that a
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
FIG. 36.2 Polygraph tracing demonstrating simultaneous washout curves from three spinal cord electrodes.
576
CLINICAL NEUROSURGERY
OJ 60
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80
90
100
110
120
60 B
50
·-I-I.. . I 10
t
NORMAL PaC02
=31 mm Hg
10.19 20-29 30-39 04Q049 50-59 ro·69 70-79 80·89 90-99 100·109110-120
PaC02 (mm Hg)
36.3. A, scatter diagram showing relationship of spinal cord blood flow to arterial pC02. B, best fitting line through the means of the previous data arranged in increments of 10 mm. Hg (pAC0 2) . FIG.
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
70
577
SPINAL CORD BLOOD FLOW 60
50
40
30
20
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..
10
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30
40
50
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1.10 119
1?0 129
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140 149
150 159
160 169
170 179
MEAN ARTERIAL PRESSURE (mm Hg) FIG. 36.4. A, scatter diagram demonstrating relationship of spinal cord blood flow to mean arterial blood pressure. B, best fitting line through the means of the previous data arranged in increments of 10 mm. Hg (MAP).
similar relationship does exist between SCBF and pAC02 in the Rhesus monkey, some notable differences are present. SCBF never fell below the normal range, even at a pAC02 of 13 mm. Hg. The normal pAC02 of the Rhesus monkey, as stated earlier, has been shown to be 30 to 35 mm. Hg,
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
A
578
CLINICAL NEUROSURGERY
BLOOD FLOW = perfusion pressure/vascular resistance (VR). Since the brain is enclosed in a nonexpansive cranial vault, perfusion pressure is dependent upon the intracranial pressure (ICP) as well as the ~IAP. Therefore, CBF can be expressed by the equation: CBF = MAP - ICP VR However, the spinal cord is not similarly enclosed in a restrictive bony environment' and therefore SCBF is expressed by the equation: SCBF = MAP VR
Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
somewhat lower than the corresponding value in humans (14). Furthermore, in order to elicit a significant rise in SCBF"', the pAC0 2 had to be raised to 50 mm. Hg, an abnormally high value in the Rhesus monkey. It appears that the sigmoid shaped curve as seen in Figure 36.3, B is shifted to the right, when compared with the corresponding curve for CBF changes in humans, with SCBF at a normal pAC02 lying on the lower level of the sigmoid curve. These data are in general agreement with previous reports. Kindt and co-workers demonstrated a similar response of SCBF and CBF to changes in pAC02 , using a surface device which measured qualitative blood flow changes (9). Flohr and associates (3) were able to show a decreasing vascular resistance in the spinal cord with increases in pAC02 , using the particle distribution technique of blood flow measurement. Griffiths (5) and Smith and colleagues (15) demonstrated a similar response of SCBF"' and CBF to changes in pAC0 2 • In these experiments, however, blood flow was measured by the direct injections of a tracer into the spinal cord parenchyma, a technique not wholly agreed upon as acceptable (10). Figure 36.4, A, B depicts the changes observed in SCB}' accompanying corresponding changes in l\IAP. As can easily be seen from the graph, SCBF remained relatively constant and in the normal range during an l\1:AP of 50 to 135 mm. Hg. Therefore, autoregulation was in operation. The concept of autoregulation implies that the blood vessels in an organ possess the capability of changing their caliber, hence resistance, in order to maintain a constant blood flow during changes in perfusion pressure of the organ. Cerebral autoregulation was first described by Fog (4), who observed changes in the caliber of pial vessels in response to changes in systemic arterial blood pressure. Blood flow in an organ can be expressed by the equation:
SPINAL CORD Bl.OOD FLOW
579 Downloaded from https://academic.oup.com/neurosurgery/article-abstract/22/CN_suppl_1/573/4099464 by guest on 24 October 2019
As can be seen from this equation, when increases in IVIAP are accompanied by corresponding increases in vascular resistance, and vice versa, SCBF will remain constant and autoregulation will be said to have been in effect. Three main theories exist which attempt to explain the mechanism of autoregulation. In 1902 Bayliss (2) suggested that the smooth muscle of blood vessels possesses an inherent ability to constrict in response to a rise in intraluminal pressure, and to dilate in response to a decrease in pressure. He appropriately termed this the myogenic theory. The metabolic, or chemical, theory is based on the premise that a time lag occurs after the blood pressure is lowered, before the vessels dilate. Supporters of this theory suggest that the period of hypotension causes a transient ischemia which leads to a local decrease in tissue and extracellular fluid pH. The increased H+ would then act directly on the blood vessels, causing vasodilation (18). Central neural control, via the sympathetic nervous system, has been suggested as one of the major mechanisms of autoregulation of CBF; this is termed the neurogenic theory. Support of this theory is based on the anatomical finding that the cerebrovascular tree is accompanied by sympathetic nerve fibers (8). Harper and associates (8) have recently suggested that autoregulation in the brain is governed by dual mechanisms, a neural control via the sympathetics operating on the extraparenchymal vessels, and a chemical control, as outlined above, controlling the caliber and hence resistance of the intraparenchymal vessels. However, preliminary studies done in this laboratory have yielded some evidence contrary to the neural theory, by demonstrating preserved autoregulation in the Rhesus spinal cord after high cervical cord section (11). In these animals, therefore, the central control of the sympathetic outflow was interrupted, and yet autoregulation remained intact. One can reasonably assume that the mechanisms responsible for autoregulation in the brain and spinal cord are quite similar, if not identical, since the histology and embryological derivation of both are the same. The above model would seem, therefore, to be well suited for the continuing study of the mechanisms responsible for autoregulation in the nervous system. As can be seen from Figure 36.4, A, B, at an MAP greater than 135 mm. Hg there is a breakthrough of autoregulation, with further increases in l\iAP effecting a significant increase in SCBF. At MAP levels less than 50 mn1. Hg, the vessels are maximally dilated, vascular resistance is minimal, and SCBF is passively controlled by MAP. Similarly, Strandgaard (16) demonstrated intact autoregulatory mechanisms in the brains of baboons up to an MAP of 120 to 140 mm. Hg, above which CBF increased directly with further increases in l\1:AP.
580
CLINICAL NEUROSURGERY
SUMMARY
The response of SCBF to changes in pAC0 2 was tested in Rhesus monkeys under normotensive conditions. A sigmoid shaped response was demonstrated. At a pAC02 of 10 to 50 mm. Hg, SCBF remained constant and in the normal range. As the pAC02 was raised from 50 to 90 mm. Hg, SCBF increased. Further increases in the pAC02 above 90 mm. Hg failed to effect further changes in SCBF. We conclude from these data that SCBF is somewhat less responsive than CBF to changes in pAC02 • N ext, the effect of changes in l\1AP on SCBF ","as studied under normocapnic conditions. SCBF remained constant and in the normal range with an MAP of 50 to 135 mm. Hg. Above 135 mm. Hg, SCBF rose with further increases in l\1AP. With decreases in lVIAP below 50 mm. Hg, SCBF fell passively. It is our conclusion that autoregulation exists in the lateral white matter of the spinal cord and follows a pattern similar to that suggested for the cerebrum. REFERENCES 1. Aukland , K., Bower, B. F., and Berliner, R. W. Measurement of local blood flow with hydrogen gas. Circ. Res., 14: 164-187,1964. 2. Bayliss, W. M. On the local reactions of the arterial wall to changes of internal pressure. J. Physiol. (Lond.), 28: 220-231, 1902. 3. Flohr, H., Poll, W., and Brock, M. Regulation of spinal cord blood flow. In Brain and Blood Flow, edited by R. W. R. Russell, pp. 406-409. Pitman, London, 1971. 4. Fog, M. The relationship between blood pressure and tonic regulation of the pial arteries. J. N eurol. Psychiatry, 1: 187-197, 1938. 5. Griffiths,!. R. Spinal cord blood flow in dogs. 2. The effect of the blood gases. J. Neurol. Neurosurg. Psychiatry, 36: 42-49, 1973. 6. Griffiths, I. R. Spinal cord blood flow in dogs: the effect of blood pressure. J. Neurol. Neurosurg. Psychiatry, 36: 914-920, 1973. 7. Harper, A. M. General physiology of cerebral circulation. In Cerebral Circulation, edited by D. G. McDowall, pp. 473-507. Little, Brown and Co., Boston, 1969. 8. Harper, A. M., Deshmukh, V. D., Rowan, J. 0., and Jennett, W. B. The influence of sympathetic nervous activity on cerebral blood flow. Arch. Neurol., 27: 1-6, 1972. 9. Kindt, G. W., Ducker, T. B., and Huddlestone, J. Regulation of spinal cord blood flow. In Brain and Blood Flow, edited by R. W. R. Russell, pp. 401-40.5. Pitman, London, 1971.
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Other investigators have addressed themselves to the question of autoregulation in the spinal cord. Using such methods as the particle distribution technique, surface flow measuring devices, and the intraparenchymal injection of tracer substances, they have generally agreed that autoregulation exists in the spinal cord and is not unlike that described for the brain (3, 6, 9).
SPINAL CORD BLOOD FLOW
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10. Kobrine, A.!., Doyle, T. F., and Martins, A. N. Spinal cord blood flow in the Rhesus monkey by the hydrogen clearance method. Surg. Neurol., 2: 197-200, 1974. 11. Kobrine, A. I., Doyle, T. F., and Martins, A. N. Preserved autoregulation in the Rhesus spinal cord after high cervical section. In preparation. ~2. Lassen, N. A. Brain extracellular pH: the main factor controlling cerebral blood flow. Scand. J. Clin. Lab. Invest., 22: 247-251, 1968. 13. Meyer, J. S., Fukuuchi, Y., Kanda, T., and Shimazu, K. Regional measurements of cerebral blood flow and metabolism using intracarotid injection of hydrogen, with comments on intracerebral steal. In Brain and Blood Flow, edited by R. W. R. Russell, pp. 71-80. Pitman, London, 1971. 14. Popovic, N. A., Mullane, J. F., Vick, J. A., and Kobrine, A. I. Effect of phencyclidine hydrochloride on certain cardiorespiratory values of the Rhesus monkey (Macaca mulatta). Am. J. Vet. Res., 33: 1649-1657, 1972. 15. Smith, A. L., Pender, J. W., and Alexander, S. C. Effects of PC0 2 on spinal cord blood flow. Am. J. Physiol., 216: 1158-1163, 1969. 16. Strandgaard, S. The lower and upper limit for autoregulation of cerebral blood flow. Stroke, 4: 323, 1973. 17. Willis, J. A., Doyle, T. F., Ramirez, A., Kobrine, A.!., and Martins, A. N. A Practical Circuit for Hydrogen Clearance Blood-flow Measurement, 10 pp. Armed Forces Radiobiology Research Institute, Bethesda, Md., 1974. 18. Zwetnow, N., Kjallquist, A., and Siesjo , B. K. Elimination of autoregulation following a period of pronounced intracranial hypertension: is hypoxia involved? Scand. J. Clin. Lab. Invest. 22: suppl. 102, V: F, 1968.
