Journal of the Neurological Sciences, 1977, 33:347-352
347
c) Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
ABSENCE OF A U T O R E G U L A T I O N IN P E R I P H E R A L N E R V E B L O O D F L O W
DONALD R. SMITH, A R T H U R 1. KOBRINE and H U G O V. R1ZZOLI
Department o[ Neurological Surgery, The George Washington University Medical Center, Washington, D.C. 20037 (U.S.A.) (Received 28 February, 1977)
SUMMARY
Blood flow was measured in the sciatic nerve of cats utilizing the method of hydrogen polarography. The mean baseline blood flow for all animals was found to be 47.1 ml/100 g/min ± 14.9 SD. The flow changes produced by lowering the blood pressure by exsanguination and elevation by the use of angiotensin were then evaluated. The highest (normal) levels of blood flow were observed between the mean blood pressures of 80-110 mm Hg. At mean systemic arterial pressures of less than 85, there was a marked decrease in peripheral nerve blood flow with no detectable flow being measured below mean systemic pressures of 50 m m Hg. Above 105 mm Hg mean arterial pressure, there was a very gradual and progressive decline in blood flow to the levels measured at 200 m m Hg. These findings indicate a complete absence of vascular autoregulation in the peripheral nerve trunks.
INTRODUCTION
Autoregulation of blood flow is a well recognized physiologic principle seen in the central nervous system (Lowell and Bloor 1971; Johnston, Rowan and Harper 1972; Standgaard, Olesen and Skinhoj 1973; Smith and Jacobson 1975; Kobrine, Doyle and Rizzoli 1976). Autoregulation has been observed by many investigators to be present in the brain and spinal cord between levels of systemic mean arterial pressure of approximately 50-140 mm Hg. Although there is some variance in the upper and lower limits between different laboratories, the general principle is universally accepted. This autoregulation allows preservation of normal central nervous system perfusion over a wide range of physiologic conditions which produce alterations in the systemic arterial blood pressure. It also clearly provides for preservation of normal brain blood flow with wide variations in intracranial pressure related either to physiologic or pathologic processes. We have recently become interested in the measurement of blood flow in the peripheral nervous system, and have found flow levels to be sur-
348 prisingly high in this tissue (Smith, Kobrine and Rizzoli 1977). In the present study the sciatic nerve of cats was evaluated for its autoregulation functions by measurement ot blood flow over a wide range of systemic arterial pressure. The arterial pressure was lowered by exsanguination and raised by the use of angiotensin. MATERIALS
AND METHODS
Blood flow was measured in the sciatic nerve of a single lower extremity in 9 mongrel cats in compliance with the Animal Welfare Act of 1970, PL91-544, PL91-579 and to meet criteria in the NIH Guide for Grants and Contracts. The animals were anesthetized initially with an intraperitoneal injection of 75 mg of ketamine*. This allowed anesthesia for cannulation of the femoral artery and vein in a single lower extremity. The arterial cannula was connected via catheters to a pressure transducer to allow constant monitoring of the systemic arterial pressure. The intravenous cannula was attached to an infusion pump to allow a constant infusion of an anesthetic mixture of 0.1 mg d-tubocurarine and 0.12 mg of ketamine at a constant flow rate of 0.2 ml per min. The arterial pCOa, ~02 and pH were monitored from the arterial blood line. Tracheostomy was performed and the tracheal cannula attached to a Harvard small animal respirator. This was regulated so as to maintain the pCOa at 35 & 2 torr. The ~02 and pH were also maintained in a normal range. The animal was positioned and the lower extremity opposite the vascular cannulas was dissected to expose the sciatic nerve. This was mobilized for a distance of about 6-7 cm. A small rubber dam was placed beneath the sciatic nerve to isolate from the underlying tissues. Platinum wires* * were inserted intrafascicularly to serve as hydrogen electrodes (Willis, Doyle and Ramirez 1974). They were positioned to provide approximately 3 cm distance between the two electrode sites. During insertion of the electrodes care was taken to avoid any visible extrinsic vascular channels. Once the electrodes had been positioned, they were maintained by a balanced connector apparatus previously designed for measurement of spinal cord blood flow (Kobrine et al. 1976; Smith, Jacobson and Rizzoli 1977). The nerve preparation was then submerged in mineral oil to prevent evaporation and drying. The electrodes were then connected through pre-amplification (Willis et al. 1974) to a Hewlett Packard*** polygraph to allow recording of the current flow at the hydrogen electrodes. Hydrogen gas (100 %) was allowed to bubble into the tracheal inflow line. After adequate polygraph deflections were seen in flow channels, the Ha gas was discontinued and the voltage curves were recorded for hydrogen clearance. Flows were then calculated for each curve utilizing the formula (Aukland, Bower and Berliner 1963 ; Meyer, Fukuuchi and Kanda 1972): F=
IO.693 x 100 T*
where F = flow in ml/l00 g/min; A = tissue diffusion
coefficient (for
Hz N
* Ketalar - Parke-Davis. ** Pt. 30.0 JR Wire; Medwire Corp., 121 S. Columbus Avenue, Mt. Vernon, N.Y. 10553. * * * Hewlett Packard Corporation, Choke Cherry Road, Rockvilb, Md.
1) ;
349 0.693 = natural log function constant; T ~ -- half time for H2 tissue clearance. Each washout curve required approximately 15-20 rain to reach baseline. Following stabilization, the hydrogen was turned on and flows again determined. This repetition was continued over a total of 2 hr to verify the normal sciatic baseline blood flow. After determination of the baseline flows as above, alterations were then made in the blood pressure as described in the following. Four animals underwent exsanguination by withdrawal of blood aliquots from the femoral venous catheter. Resultant reduction in nerve blood flow levels caused this to be terminated in all animals at mean arterial pressure levels of no lower than 50 mm Hg. The cats varied somewhat in their tolerance to blood loss but the systemic arterial pressure could be reduced in all animals to a mean of 50 mm Hg by the withdrawal of no more than 40 ml of blood. The blood was heparinized as withdrawn and saved for reinfusion. Blood flow determinations were carried out after aliquots of blood were withdrawn and the blood pressure levels were recorded for each flow determination. At pressure levels of below 50 mm Hg, no deflection of the recorder pens could be obtained. This indicated no significant concentration of hydrogen within the nerve. This level was accepted as a zero flow rate for this method and pressures were not lowered below this point. Once reinfusion of the blood had been carried out, the baseline blood pressures and flow levels were re-established in all of the 4 animals. At this point, the blood pressure was incrementally increased by the infusion of a dilute solution of angiotensin regulated by a microdrop chamber. By careful regulation of the microdropper, it was possible to regulate the systematic arterial pressure at very precise levels up to about 175 mm Hg. Above this level the animal response was somewhat inconsistent as some animals developed cardiac arrhythmias precluding mean arterial pressure levels above this level. Flow determinations were run at the various levels of arterial pressure. As previously stated, 4 of the experimental animals underwent preliminary lowering of the blood pressure by blood withdrawal and after restoration of normal blood volume: the mean arterial pressures were then elevated by the use ofangiotensin. The remaining 5 animals underwent only elevation of the pressure by use of angiotensin and did not undergo any prior hypotension. Once the desired level of hypertension had been at chieved, the angiotensin was discontinued and in all animals the baseline blood pressure was again achieved after a lapse of only 5-10 rain. Baseline flow levels were again determined at the baseline arterial pressure. All animals were then sacrificed by intravenous injection of a bolus of KC1. The segment of the sciatic nerve was removed en bloc and fixed in 1 0 ~ formalin to allow microscopic sectioning. Transverse and longitudinal sections of all nerves were made and stained with hematoxylin and eosin. RESULTS
Baseline blood flows All of the flow results were calculated from 2 separate electrode sites in 9 animals. These figures were utilized to calculate the mean normal sciatic blood flow. The flow was determined to be 47 ml/100 g/min ~ 14.9 SD. This value compared very well with the flow levels previously determined by our laboratory on another series of
350 SCIATIC
BLOOD
FLOW
vs.
MEAN
ARTERIAL
PRESSURE
I
80-
Represents one standard deviation
70o
60-
~
5o-
~ .E
40-
,-;-
30" 2010-
,
,
f
i
,
,
p
,
~
e-
°
MAP
(mean systemic arterial pressure)
Fig. 1. Mean sciatic nerve blood flow at various levels of systemic arterial pressure. The shaded area represents one standard deviation from the mean.
animals which was 43 ml/100 g/min (Smith et ai. 1977). The hypotension produced by blood withdrawal produced a very prompt and profound decrease in sciatic nerve blood flow in all animals. This drop was precipitous (Fig. 1) and in all animals below a systemic arterial pressure of 50 mm Hg, no flow could be demonstrated in the sciatic nerve. Maximum blood flow values were observed in the range of 80--110 mm Hg. Above systemic arterial pressures of 110 mm Hg, there was a gradual but progressive decline in nerve flow until at levels of 175-200 mm Hg, the flow level had declined to approximately 26 ml/100 g/min (Fig. 1). These results seem to indicate a total lack of autoregulation existing in the peripheral nerve. Restoration of normal blood volume following hypotension by reinfusion of the withdrawn blood resulted in a prompt return to normal baseline flows at the respective electrode sites. This same resumption of normal flow occurred after termination of the angiotensin with resultant drop of the blood pressure from hypertensive levels to its former baseline level for the particular animal studied. It would appear, therefore, that utilizing blood withdrawal or angiotensin for these brief experimental periods did not significantly alter the normal vascular tone. Microscopic inspection of the nerve segments revealed only some occasional small focal hemorrhages within the nerve fibers. The electrode tracts could not otherwise be specifically identified. DISCUSSION
Autoregulation of cerebral and spinal cord blood flow is a well accepted physiologic mechanism in both clinical and laboratory experience (Lowell et al. 1971; Johnston et al. 1972; Standgaard et al. 1973; Smith and Jacobson 1975; Kobrine et al,
351 1976). This autoregulation of flow in the central nervous system is defined as a constancy of flow with variations in the mean arterial pressure over a wide physiologic range. This autoregulation is felt to be invariably present in the normal human and certainly in the physiologic animal laboratory preparations under a wide range of systemic arterial pressure. Although there is some variance in the exact upper and lower limits of this mechanism under laboratory conditions, it is generally accepted that stability of blood flow in the central nervous system exists between mean pressures of 50-140 mm Hg. Previous studies in this laboratory (Smith and Jacobson 1975) have indicated that the central autoregulation is probably a property of the local vascular bed rather than a centrally-mediated mechanism. This protective mechanism seems to rely on the precise physiologic milieu of the local area including perhaps pH, lactic acid concentration, pO2 and pCOz to mention only a few of the metabolic possibilities. It is also thought that neural control through adrenergic and cholinergic endings on the larger vessels does play some role in central autoregulation. This condition which exists in the central nervous system is known to be at variance with flow conditions existing in other body organs. Trauma incurred by the nerve during dissection might influence not only the flow rate but alter autoregulation. This artifactual change seems quite unlikely in view of the operative technique used. The results were also quite uniform throughout this animal series and it is difficult to introduce such reproducible artifacts by trauma which may occur randomly. From the present study, it would appear that peripheral nerves lie outside the sphere of central nervous system autoregulation. Hypotension, as produced here by decreasing blood volume, caused a marked decrease in peripheral nerve blood flow. Presumably the vascular supply to the peripheral nerves takes part in the general peripheral vasoconstriction which occurs in an effort to maintain perfusion of more vital organs including the central nervous system. Angiotensin achieves its hypertensive effect by a direct action on the smooth muscle of the arterial wall. This effect, of course, results in a vasoconstriction. Again from the present study it would appear that the vessels of the peripheral nerves are not immune to this vasoconstrictive effect. The central nervous system vessels on the other hand, have been shown on multiple occasions to maintain their autoregulation in the face of systemic hypertension induced by the infusion of angiotensin.
REFERENCES Aukland, K., B. F. Bower and R. N. Berliner (1963) Measurement of local blood flow with hydrogen gas, Cireulat. Res., 14: 164-187. Johnston, 1. H., J. P. Rowan and A. M. Harper (1972) Raised intracranial pressure and cerebral blood flow, Part 1 (Cisterna magna infusion in primates), J. Neurol. Neurosurg. Psychiat., 35: 285-296. Kobrine, A. 1., T. F. Doyle and H. V. Rizzoli (1976) Spinal cord blood flow as affected by changes in systemic arterial blood pressure, J. Neurosurg., 44: 12-15. Lowell, H. M. and B. M. Bloor (1971) The effect of increased intracranial pressure on cerebrovascular hemodynamics, J. Neurosurg., 34: 760-769. Meyer, J. S., Y. Fukuuchi and T. Kanda (1972) Regional cerebral blood flow measured by intracarotid injection of hydrogen - - Comparison of regional vasomotor capacitance from cerebral infarction versus compression, Neurology (Minneap.), 22: 571-584.
352 Smith, D. R. and J. Jacobson (1975) Regional cerebral blood flow and autoregulation with supra tentorial mass lesions, Surg. Forum, 26: 487489. Smith, D. R., J. Jacobson and H. V. Rizzoli (1977) Spinal cord blood flow - - Effects of trauma and mannitol, In preparation. Smith, D. R., A. 1. Kobrine and H. V. Rizzoli (1977) Blood flow in peripheral nerves - - Normal and post severance flow rates, J. neurol. Sci., 33: 341-346. Standgaard, S., J. Olesen and E. Skinhoj (1973) Autoregulation of brain circulation in severe arterial hypertension, Brit. reed. J., 1 : 507-510. Willis, J. A., T. F. Doyle and A. Ramirez (1974) A practical circuit for hydrogen clearance blood flow measurement, Armed Forces Radiobiological Research Technical Note, A F R R I T N 74-2.
347
c) Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
ABSENCE OF A U T O R E G U L A T I O N IN P E R I P H E R A L N E R V E B L O O D F L O W
DONALD R. SMITH, A R T H U R 1. KOBRINE and H U G O V. R1ZZOLI
Department o[ Neurological Surgery, The George Washington University Medical Center, Washington, D.C. 20037 (U.S.A.) (Received 28 February, 1977)
SUMMARY
Blood flow was measured in the sciatic nerve of cats utilizing the method of hydrogen polarography. The mean baseline blood flow for all animals was found to be 47.1 ml/100 g/min ± 14.9 SD. The flow changes produced by lowering the blood pressure by exsanguination and elevation by the use of angiotensin were then evaluated. The highest (normal) levels of blood flow were observed between the mean blood pressures of 80-110 mm Hg. At mean systemic arterial pressures of less than 85, there was a marked decrease in peripheral nerve blood flow with no detectable flow being measured below mean systemic pressures of 50 m m Hg. Above 105 mm Hg mean arterial pressure, there was a very gradual and progressive decline in blood flow to the levels measured at 200 m m Hg. These findings indicate a complete absence of vascular autoregulation in the peripheral nerve trunks.
INTRODUCTION
Autoregulation of blood flow is a well recognized physiologic principle seen in the central nervous system (Lowell and Bloor 1971; Johnston, Rowan and Harper 1972; Standgaard, Olesen and Skinhoj 1973; Smith and Jacobson 1975; Kobrine, Doyle and Rizzoli 1976). Autoregulation has been observed by many investigators to be present in the brain and spinal cord between levels of systemic mean arterial pressure of approximately 50-140 mm Hg. Although there is some variance in the upper and lower limits between different laboratories, the general principle is universally accepted. This autoregulation allows preservation of normal central nervous system perfusion over a wide range of physiologic conditions which produce alterations in the systemic arterial blood pressure. It also clearly provides for preservation of normal brain blood flow with wide variations in intracranial pressure related either to physiologic or pathologic processes. We have recently become interested in the measurement of blood flow in the peripheral nervous system, and have found flow levels to be sur-
348 prisingly high in this tissue (Smith, Kobrine and Rizzoli 1977). In the present study the sciatic nerve of cats was evaluated for its autoregulation functions by measurement ot blood flow over a wide range of systemic arterial pressure. The arterial pressure was lowered by exsanguination and raised by the use of angiotensin. MATERIALS
AND METHODS
Blood flow was measured in the sciatic nerve of a single lower extremity in 9 mongrel cats in compliance with the Animal Welfare Act of 1970, PL91-544, PL91-579 and to meet criteria in the NIH Guide for Grants and Contracts. The animals were anesthetized initially with an intraperitoneal injection of 75 mg of ketamine*. This allowed anesthesia for cannulation of the femoral artery and vein in a single lower extremity. The arterial cannula was connected via catheters to a pressure transducer to allow constant monitoring of the systemic arterial pressure. The intravenous cannula was attached to an infusion pump to allow a constant infusion of an anesthetic mixture of 0.1 mg d-tubocurarine and 0.12 mg of ketamine at a constant flow rate of 0.2 ml per min. The arterial pCOa, ~02 and pH were monitored from the arterial blood line. Tracheostomy was performed and the tracheal cannula attached to a Harvard small animal respirator. This was regulated so as to maintain the pCOa at 35 & 2 torr. The ~02 and pH were also maintained in a normal range. The animal was positioned and the lower extremity opposite the vascular cannulas was dissected to expose the sciatic nerve. This was mobilized for a distance of about 6-7 cm. A small rubber dam was placed beneath the sciatic nerve to isolate from the underlying tissues. Platinum wires* * were inserted intrafascicularly to serve as hydrogen electrodes (Willis, Doyle and Ramirez 1974). They were positioned to provide approximately 3 cm distance between the two electrode sites. During insertion of the electrodes care was taken to avoid any visible extrinsic vascular channels. Once the electrodes had been positioned, they were maintained by a balanced connector apparatus previously designed for measurement of spinal cord blood flow (Kobrine et al. 1976; Smith, Jacobson and Rizzoli 1977). The nerve preparation was then submerged in mineral oil to prevent evaporation and drying. The electrodes were then connected through pre-amplification (Willis et al. 1974) to a Hewlett Packard*** polygraph to allow recording of the current flow at the hydrogen electrodes. Hydrogen gas (100 %) was allowed to bubble into the tracheal inflow line. After adequate polygraph deflections were seen in flow channels, the Ha gas was discontinued and the voltage curves were recorded for hydrogen clearance. Flows were then calculated for each curve utilizing the formula (Aukland, Bower and Berliner 1963 ; Meyer, Fukuuchi and Kanda 1972): F=
IO.693 x 100 T*
where F = flow in ml/l00 g/min; A = tissue diffusion
coefficient (for
Hz N
* Ketalar - Parke-Davis. ** Pt. 30.0 JR Wire; Medwire Corp., 121 S. Columbus Avenue, Mt. Vernon, N.Y. 10553. * * * Hewlett Packard Corporation, Choke Cherry Road, Rockvilb, Md.
1) ;
349 0.693 = natural log function constant; T ~ -- half time for H2 tissue clearance. Each washout curve required approximately 15-20 rain to reach baseline. Following stabilization, the hydrogen was turned on and flows again determined. This repetition was continued over a total of 2 hr to verify the normal sciatic baseline blood flow. After determination of the baseline flows as above, alterations were then made in the blood pressure as described in the following. Four animals underwent exsanguination by withdrawal of blood aliquots from the femoral venous catheter. Resultant reduction in nerve blood flow levels caused this to be terminated in all animals at mean arterial pressure levels of no lower than 50 mm Hg. The cats varied somewhat in their tolerance to blood loss but the systemic arterial pressure could be reduced in all animals to a mean of 50 mm Hg by the withdrawal of no more than 40 ml of blood. The blood was heparinized as withdrawn and saved for reinfusion. Blood flow determinations were carried out after aliquots of blood were withdrawn and the blood pressure levels were recorded for each flow determination. At pressure levels of below 50 mm Hg, no deflection of the recorder pens could be obtained. This indicated no significant concentration of hydrogen within the nerve. This level was accepted as a zero flow rate for this method and pressures were not lowered below this point. Once reinfusion of the blood had been carried out, the baseline blood pressures and flow levels were re-established in all of the 4 animals. At this point, the blood pressure was incrementally increased by the infusion of a dilute solution of angiotensin regulated by a microdrop chamber. By careful regulation of the microdropper, it was possible to regulate the systematic arterial pressure at very precise levels up to about 175 mm Hg. Above this level the animal response was somewhat inconsistent as some animals developed cardiac arrhythmias precluding mean arterial pressure levels above this level. Flow determinations were run at the various levels of arterial pressure. As previously stated, 4 of the experimental animals underwent preliminary lowering of the blood pressure by blood withdrawal and after restoration of normal blood volume: the mean arterial pressures were then elevated by the use ofangiotensin. The remaining 5 animals underwent only elevation of the pressure by use of angiotensin and did not undergo any prior hypotension. Once the desired level of hypertension had been at chieved, the angiotensin was discontinued and in all animals the baseline blood pressure was again achieved after a lapse of only 5-10 rain. Baseline flow levels were again determined at the baseline arterial pressure. All animals were then sacrificed by intravenous injection of a bolus of KC1. The segment of the sciatic nerve was removed en bloc and fixed in 1 0 ~ formalin to allow microscopic sectioning. Transverse and longitudinal sections of all nerves were made and stained with hematoxylin and eosin. RESULTS
Baseline blood flows All of the flow results were calculated from 2 separate electrode sites in 9 animals. These figures were utilized to calculate the mean normal sciatic blood flow. The flow was determined to be 47 ml/100 g/min ~ 14.9 SD. This value compared very well with the flow levels previously determined by our laboratory on another series of
350 SCIATIC
BLOOD
FLOW
vs.
MEAN
ARTERIAL
PRESSURE
I
80-
Represents one standard deviation
70o
60-
~
5o-
~ .E
40-
,-;-
30" 2010-
,
,
f
i
,
,
p
,
~
e-
°
MAP
(mean systemic arterial pressure)
Fig. 1. Mean sciatic nerve blood flow at various levels of systemic arterial pressure. The shaded area represents one standard deviation from the mean.
animals which was 43 ml/100 g/min (Smith et ai. 1977). The hypotension produced by blood withdrawal produced a very prompt and profound decrease in sciatic nerve blood flow in all animals. This drop was precipitous (Fig. 1) and in all animals below a systemic arterial pressure of 50 mm Hg, no flow could be demonstrated in the sciatic nerve. Maximum blood flow values were observed in the range of 80--110 mm Hg. Above systemic arterial pressures of 110 mm Hg, there was a gradual but progressive decline in nerve flow until at levels of 175-200 mm Hg, the flow level had declined to approximately 26 ml/100 g/min (Fig. 1). These results seem to indicate a total lack of autoregulation existing in the peripheral nerve. Restoration of normal blood volume following hypotension by reinfusion of the withdrawn blood resulted in a prompt return to normal baseline flows at the respective electrode sites. This same resumption of normal flow occurred after termination of the angiotensin with resultant drop of the blood pressure from hypertensive levels to its former baseline level for the particular animal studied. It would appear, therefore, that utilizing blood withdrawal or angiotensin for these brief experimental periods did not significantly alter the normal vascular tone. Microscopic inspection of the nerve segments revealed only some occasional small focal hemorrhages within the nerve fibers. The electrode tracts could not otherwise be specifically identified. DISCUSSION
Autoregulation of cerebral and spinal cord blood flow is a well accepted physiologic mechanism in both clinical and laboratory experience (Lowell et al. 1971; Johnston et al. 1972; Standgaard et al. 1973; Smith and Jacobson 1975; Kobrine et al,
351 1976). This autoregulation of flow in the central nervous system is defined as a constancy of flow with variations in the mean arterial pressure over a wide physiologic range. This autoregulation is felt to be invariably present in the normal human and certainly in the physiologic animal laboratory preparations under a wide range of systemic arterial pressure. Although there is some variance in the exact upper and lower limits of this mechanism under laboratory conditions, it is generally accepted that stability of blood flow in the central nervous system exists between mean pressures of 50-140 mm Hg. Previous studies in this laboratory (Smith and Jacobson 1975) have indicated that the central autoregulation is probably a property of the local vascular bed rather than a centrally-mediated mechanism. This protective mechanism seems to rely on the precise physiologic milieu of the local area including perhaps pH, lactic acid concentration, pO2 and pCOz to mention only a few of the metabolic possibilities. It is also thought that neural control through adrenergic and cholinergic endings on the larger vessels does play some role in central autoregulation. This condition which exists in the central nervous system is known to be at variance with flow conditions existing in other body organs. Trauma incurred by the nerve during dissection might influence not only the flow rate but alter autoregulation. This artifactual change seems quite unlikely in view of the operative technique used. The results were also quite uniform throughout this animal series and it is difficult to introduce such reproducible artifacts by trauma which may occur randomly. From the present study, it would appear that peripheral nerves lie outside the sphere of central nervous system autoregulation. Hypotension, as produced here by decreasing blood volume, caused a marked decrease in peripheral nerve blood flow. Presumably the vascular supply to the peripheral nerves takes part in the general peripheral vasoconstriction which occurs in an effort to maintain perfusion of more vital organs including the central nervous system. Angiotensin achieves its hypertensive effect by a direct action on the smooth muscle of the arterial wall. This effect, of course, results in a vasoconstriction. Again from the present study it would appear that the vessels of the peripheral nerves are not immune to this vasoconstrictive effect. The central nervous system vessels on the other hand, have been shown on multiple occasions to maintain their autoregulation in the face of systemic hypertension induced by the infusion of angiotensin.
REFERENCES Aukland, K., B. F. Bower and R. N. Berliner (1963) Measurement of local blood flow with hydrogen gas, Cireulat. Res., 14: 164-187. Johnston, 1. H., J. P. Rowan and A. M. Harper (1972) Raised intracranial pressure and cerebral blood flow, Part 1 (Cisterna magna infusion in primates), J. Neurol. Neurosurg. Psychiat., 35: 285-296. Kobrine, A. 1., T. F. Doyle and H. V. Rizzoli (1976) Spinal cord blood flow as affected by changes in systemic arterial blood pressure, J. Neurosurg., 44: 12-15. Lowell, H. M. and B. M. Bloor (1971) The effect of increased intracranial pressure on cerebrovascular hemodynamics, J. Neurosurg., 34: 760-769. Meyer, J. S., Y. Fukuuchi and T. Kanda (1972) Regional cerebral blood flow measured by intracarotid injection of hydrogen - - Comparison of regional vasomotor capacitance from cerebral infarction versus compression, Neurology (Minneap.), 22: 571-584.
352 Smith, D. R. and J. Jacobson (1975) Regional cerebral blood flow and autoregulation with supra tentorial mass lesions, Surg. Forum, 26: 487489. Smith, D. R., J. Jacobson and H. V. Rizzoli (1977) Spinal cord blood flow - - Effects of trauma and mannitol, In preparation. Smith, D. R., A. 1. Kobrine and H. V. Rizzoli (1977) Blood flow in peripheral nerves - - Normal and post severance flow rates, J. neurol. Sci., 33: 341-346. Standgaard, S., J. Olesen and E. Skinhoj (1973) Autoregulation of brain circulation in severe arterial hypertension, Brit. reed. J., 1 : 507-510. Willis, J. A., T. F. Doyle and A. Ramirez (1974) A practical circuit for hydrogen clearance blood flow measurement, Armed Forces Radiobiological Research Technical Note, A F R R I T N 74-2.
