ARTERIAL HYPOTENSION AND ITS CONSEQUENCES FOR THE CEREBRAL CIRCULATION Lennart Hansson
INTRODUCTION The blood-flow of the human brain and its relation to arterial pressure has been studied extensively since Kety developed the inert gas method for determination of cerebral blood-flow (CBF) in 1945 (Kety & Schmidt 1945). The metabolic demands of the brain are comparatively high, resulting in a resting blood-flow of 50-60 ml per minute and 100 g of tissue under resting conditions. This means that approximately 750 ml per minute of arterial blood is needed for the maintenance of cerebral metabolism. This in turn, corresponds to almost 15 !& of the resting cardiac output, and due to the high oxygen extraction of the brain means that approximately 20 !& of the body’s total oxygen consumption goes to this organ (Folkow & Neil 1971).
AUTOREGULATION OF CEREBRAL BLOOD-FLOW As in so many other “peripheral” vascular beds, the blood-flow in the cerebral circulation is autoregulated. In other words the CBF is kept constant over a wide range of blood pressure and in this respect the brain is similar to e.g. skeletal muscle, kidney, liver and other organs or organ systems (Johnson 1964, Sivertsson 1978). Findings suggesting autoregulation of blood-flow was first made by Bayliss (1902) who among other things studied the relationship between arterial blood pressure changes and volume changes in the hind limbs of various animals. Bayliss also found autoregulation of blood-flow in other organs, such as the kidney, and concluded that it was independent of nervous influence(Bay1is.s 1902). Several theories have been put forward in order to explain the autoregulation of blood-flow. One o f these is the niyogenic theory, which has been discussed e.g. by Folkow (1964). 17
In brief, this theory depends on the concept that a basal tone exists in the blood vessels. A lowering of blood pressure would then represent a diminished stimulus and therefore lead to vasodilatation which in turn would tend to ‘keep the flow unchanged. Another theory put forward to explain flow autoregulation is the mefabolic flreory(Berne 1964).In brief, this theoj. is based on the concept that changes in perfusion pr&sure will cause metabolic changes in the tissues, e.g. accumulation of metabolites which in turn may induce changes of the vascular calibers so that flow is kept constant. The third main theory frequently referred to in discussions‘regarding autoregulation of CBF is the tis511e pressure tIteooly. This theory requires that the organ in question is surrounded by very rigid capsule such as the brain within the skull. Elevation ofthe perfusion pressure will thencause an outward filtration of fluid, which in turn will cause a raised tissue pressure which compresses the vessels to a certain extent thereby keeping flow constant. The ‘tissue pressure theory would seem to offer a logical explanation bf the autoregulation of CBF when arterial pressure is raised. However, it is much more difficult to apply this theory in order to explain BUtoregulation of CBF also when blood pressure is lowered, and for this reason the tissue pressure theory would appear to offer a less likely explanation. It isentirely possible that more than one mechanism of the above mentioned are involved in the autoregulation of CBF. Thus, Lassen has expressed the opinion that both the myogenic theory and the metabolic thebry are engaged (Lassen 1959, Lassen 1964). This view has also been expressed by others working in this field, e.g. Harper and HIggendal(1968). Findings supporting the myogenic theory have been reported, e.g. by Haggendal and Johansson (1966) and by Ekstrom-Jodal and co-workers (1969). Further support for the myog-
enic mechanism is offered by the finding that autoregulation takes place at a lower flow level with a pulsatile flow as compared to non-pulsatile flow with the same mean pressure (Held et al. 1969). It is interesting to note that the existence of autoregulation of the CBF has been denied by some distinguished researchers even into the 1960's (Sagawa & Guyton 1961). For further extensive discussions on the autoregulation of CBF. the reader is referred to references: Lassen 1959, Lassen 1964, Harper 1966 & Ekstrom-Jodal 1970.
CLINICAL IMPLICATIONS . When the lower limit ofCBF autoregulation is reached
a number of symptoms occur (Table I). Likewise, as blood pressure is increased to above the upper limit of CBF autoregulation, increasingly severe symptoms will be seen (Table 11). Due to the shifted autoregulation curve hypertensive individuals will tolerate higher blood pressure levels before they experience the symptoms and consequences described in Table 11. On theother hand they will alsobe moresusceptible to blood pressure reductions. Particularly when reducing very high blood pressures rapidly symptoms of EFFECTS OF BLOOD PRESSURE CHANGE ON reduced cerebral perfusion have been reported. Thus, THE CEREBRAL BLOOD-FLOW Graham reported two patients with malignant hyperAs already mentioned CBF is kept constant over a tension who both became unconscious after having wide range of blood pressure. In fact Lassen suggests had their blood pressure reduced from 240/140 mm that CBF is unchanged at arterial pressures between Hg to 120/85 mm Hg and from 2401170 mm Hg to 60-170 mm Hg (1959). This is supported by studies 120/100 mm Hg respectively by administration oforal showing that neither essential hypertension (Moyer bethanidine and intravenous pentholinium respectivet al. 1953, Moyer & Morris 1954, Hakenschiel el ely (Graham 1975). Particularly in elderly hypertensive al. 1954). nor drug-induced hypertension (Moyer et patients care should be taken not to lower arterial presal. 1954) was associated with any significant change sure too rapidly (Jones & Graham 1977). of CBF. Moreover, moderate reduction of blood presCertain drugs seem to require more care than other. sure did not cause a significant change of CBF (Moyer Thus, sodium nitroprusside has been shown to in& Morris 1954, McCall 1953). crease intracranial pressure (Turner et al. 1977). This That autoregulation of CBF cannot be maintained is probably due to the powerful vasodilating action at low arterial pressure has been known for several of this compound which could cause edema of the decades (Lassen 1959). Later studies have demonstnt- brain in spite of the reduction in perfusion pressure. ed a breakthrough of autoregulation also at high blood In a series of 44 patients undergoing neurosurgery sodpressures (Strandgaard el al. 1973). Of great interest ium nitroprusside was shown togive an initial increase is the fact that the whole autoregulation curve of CBF in intracranial pressure whereas treatment with the is shifted to the right in hypertension (Figure I). This has been demonstrated in hypertensive patients using CBF Iml/min. 100 g1 angiotensin II and the ganglion blocker trimetaphan ' 60in order to raise and lower blood pressure respectively (Strandgaard el al. 1973). Studies in normotensive ba- 50boons and in baboons with two-kidney-Goldblatthypertension have confirmed this shift of the curve 40both as regards the upper (Strandgaard et al. 1975) and the lower limit of CBF autoregulation (Jones et al. 1976).It has been suggested (Strandgaard 1978)that 203 rnm Hg the shift of the autoregulation curve in hypertension Figure 1. Cerebral blood-now autoregulation curves in norto the right is due to structural vascular changes in motension and hypertension. Note shift of curve to the right the precapillary resistance vessels leading to an in- in hypertension due to structural changes in the precapillary resistance vessels. (Based on Lassen 1959, Ekstr6m-Jodal creased wall to lumen ratio (Folkow et al. 1973) 1970, Moyer & Morris 1954, Strandgaardet al. 1973 and Jones et al. 1976.) (Figure 1). 18
ganglion blocker trimetaphan did not have this effect (Turner et al. 1977). Furthermore, treatment with sodium nitroprusside may give rise to rapid changes in arterial pressure which are too Fist for the autoregulation process to be maintained (Fitch 1977). It has
Table I. Effects of reduced cerebral blood-flow. Discomfort ~ i Sleepiness
~
i
~
~
~
Nausea
Syncope
coma
also been claimed that CBF autoregulation is lost altogether during treatment with thiscompound (Crockard et al. 1976). From a practical point of view it therefore appears that special care should be taken when using sodium nitroprusside in situations requiring acute reduction of arterial pressure. During chronic treatment of hypertension particular care is recommended when using peripheral sympatholytic agents, which occasionally may reduce blood pressure drastically, e.g. in the standing position or during exposure to heat, with ensuing risks of reduced CBF leading to dizziness or syncope. On the other hand prolonged and gradual reduction of elevated arterial pressure in hypertension will tend to shift the autoregulation curve ofCBF back towards normal (Strandgaard to be published). This is probably due to reversibility to the structural vascular changes in the precapillary resistance vessels of the kind described in other vascular beds (Hansson & Sivertsson 1975).
Death
Table 11. E f f a t s of increased cerebral blood-flow. Discomfort Headaches Nausea Mental confusion Convulsions Coma Death (apoplexy)
tensive patients due to structural vascular changes in the precapillary resistance vessels. When reducing blood pressure below the lower limit ofautoregulation, potentially dangerous effects may arise such as syncope or unconsciousness. These risks should be born in mind particularly when employing powerful and fast acting antihypertensive agents. On the other hand, prolonged and gradual reduction of arterial presCONCLUSlONS sure through the use of oral antihypertensive agents Cerebral blood-flow is autoregulated over a wide range will tend to shift the autoregulation curve ofCBF back of arterial pressure. This autoregulation of CBF is shift- towards normal thereby minimizing the risk of cerebral ed towards a higher blood pressure range in hyper- complications due to reduced CBF.
REFERENCES Bayliss W M: On the local reactions of the arterial wall to changes of internal pressure. J Physiol28: 220-231, 1902.
to the mechanism responsible for central blood flow autoregulation. Acta Physiol %and suppl 350, 1970.
Berne R M: Metabolic regulation of blood flow. Circ Res 15 SUPPI 1: 261-268, 1964.
Fitch W: Editorial. Sodium nitroprusside and the cerebral circulation. Br J Anaesth 49: 399-400, 1977.
Crockard H A, Brown F D & Mullen J F: Effects of trimetaphan and sodium nitroprusside on cerebral blood flow in rhesus monkeys. Acta Neurochir 35: 85-89, 1976.
Folkow B Description of the myogenic hypothesis. Circ Res 15 suppl 1: 279-287, 1964. Folkow B & Neil E: Cerebral Circulation. In: Circulation. pp 434448. Oxford University Press. New York, London. Toronto 1971. Folkow B, Hallback M,Lundgren Y,Sivertsson R & Weiss L: Importance of adaptive changes in vascular design for establishment of primary hypertension, studied in man and in spontaneously hypertensive rats. Circ Res 32/33 suppl 1: 2-13. 1973. Graham D I: lschaemic brain damage of cerebral perfusion
Ekstrom-Jodal B, Haggendal E. Nilsson N J & Norblck B: Changes of the transmural pressure - The probable stimulus to cerebral flow autoregulation. In: Cerebral blood flow, pp 89-93. Eds: M Brock, C Fieschi, D H Ingvar, N A Lassen & K Schiirmann, Springer-Verlag. Berlin, Heidelberg, New York 1969. Ekstrom-Jodal B: On the relation between blood pressure and blood flow in the canine brain with particular regard
19
~
Lassen N A: Autoregulation of cerebral blood flow. Circ Res 15 suppl 1: 1-204. 1964.
failure type after treatment of severe hypertension. Br Med J 4: 739, 1975. Hafkenschiel J H. Friedland C K & Zintel H A: Blood flow and oxygen consumption of the brain in patients with essential hypertension before and after adrenalectomy. J Clin Invest 33: 57-62. 1954.
McCall M L: Cerebral circulation and metabolism in toxemia of pregnancy. Observations on the effect of Veratrum viride and Apresoline. A m J Obstet Gynecol 66: 1015-1030, 1953. Moyer J H & Morris Jr G C: Cerebral hemodynamics during controlled hypotension induced by a continuous infusion of ganglionic blocking agents. J Clin Invest 33: 1081-1088,
Hansson L & Sivensson R: Reversibility of structural vascular changes in human essential hypertension. In: Pathophysiology and management of arterial hypertension, pp 114-121. Eds: G Beglund, L Hansson & L Werkd. A Lindgren & Sijner AB. Molndat 1975.
1954.
Moyer J H, Morris G & Snyder H: Comparison of the cerebral hemodynamic response to Aramine and norepinephrine in normotensive and hypotensive subject. Circulation 10: 265-270, 1954.
Harper A M: Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiatry 29:
Moyer J H. Miller S I, Tashnek A B, Snyder H & Bowman R 0: Malignant hypertension and hypertensive encephalopathy; cerebral hemodynamic studies and therapeutic response to continuous infusion of intravenous veriloid. Am J Med 14: 175-183. 1953.
398403. 1966.
Harper A M & Haggendal E: Discussion and comments to section V on autoregulation of CBF. In: Cerebral blood flow and cerebro-spinal fluid 111. Scand J Clin Lab Invest 22 suppl 102: 102, 1968.
Sagawa K & Guyton A C: Pressure-flow relationships in isolated canine cerebral circulation. Am J Physiol 200:
Held K U. Gottstein U & Niedermayer W: CBF in nonpulsatile perfusion. In: Cerebral Blood Flow. pp 94-95. Eds: M Biock, C Fieschi, D H Ingvar. N A Lassen & K Schiirmann. Springer-Verlag. Berlin, Heidelberg, New York 1969.
71 1-714. 1961.
Sivertsson R: Effect of blood pressure reduction on tissue perfusion. Acta Med Scand suppl 628: 13-16, 1978. (This volume).
Haggendal E & Johansson B: Effects of arterial carbon dioxide tension and oxygen saturation on cerebral blood flow autoregulation in dogs. Acta Physiol %and 66 suppl 258:
Strandgaard S : Academic Dissertation. University of Copenhagen. In press 1978.
27-53, 1966.
Strandgaard S , Olesen J. Skinhej E & Lassen N A: Autoregulation of brain circulation in severe arterial hypertension. Br Med J I : 507-510, 1973.
Johnson P C: Review of previous studies and current theories of autoregulation. Circ Res I5 suppl 1: 2-9, 1964. Jones J V & Graham D I: Inappropriate antihypertensive therapy in the elderly. Lancet 1: 425, 1977.
Strandgaard S , Jones J V, Mackenzie E T & Harper A M: Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res
Jones J V, Fitch W. Mackenzie E T. Strandgaard S & Harper A M: Lower limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res 39: 555-557, 1976.
37: 164-167. 1975.
Turner J M. Powell D. Gibson R M & McDowall D G : Intracranial pressure changes in neurosurgical patients during hypotension induced with sodium nitroprusside or trimetaphan. Br J Anaesth 49: 419-426, 1977.
Kety S S & Schmidt C F: The determination of cerebral blood flow in man by use of nitrous oxide in low concentrations. Am J Physiol 143: 53-66. 1945. Lassen N A: Cerebral blood flow and oxygen consumption in man. Physiol Rev 39: 183-238, 1959.
20
INTRODUCTION The blood-flow of the human brain and its relation to arterial pressure has been studied extensively since Kety developed the inert gas method for determination of cerebral blood-flow (CBF) in 1945 (Kety & Schmidt 1945). The metabolic demands of the brain are comparatively high, resulting in a resting blood-flow of 50-60 ml per minute and 100 g of tissue under resting conditions. This means that approximately 750 ml per minute of arterial blood is needed for the maintenance of cerebral metabolism. This in turn, corresponds to almost 15 !& of the resting cardiac output, and due to the high oxygen extraction of the brain means that approximately 20 !& of the body’s total oxygen consumption goes to this organ (Folkow & Neil 1971).
AUTOREGULATION OF CEREBRAL BLOOD-FLOW As in so many other “peripheral” vascular beds, the blood-flow in the cerebral circulation is autoregulated. In other words the CBF is kept constant over a wide range of blood pressure and in this respect the brain is similar to e.g. skeletal muscle, kidney, liver and other organs or organ systems (Johnson 1964, Sivertsson 1978). Findings suggesting autoregulation of blood-flow was first made by Bayliss (1902) who among other things studied the relationship between arterial blood pressure changes and volume changes in the hind limbs of various animals. Bayliss also found autoregulation of blood-flow in other organs, such as the kidney, and concluded that it was independent of nervous influence(Bay1is.s 1902). Several theories have been put forward in order to explain the autoregulation of blood-flow. One o f these is the niyogenic theory, which has been discussed e.g. by Folkow (1964). 17
In brief, this theory depends on the concept that a basal tone exists in the blood vessels. A lowering of blood pressure would then represent a diminished stimulus and therefore lead to vasodilatation which in turn would tend to ‘keep the flow unchanged. Another theory put forward to explain flow autoregulation is the mefabolic flreory(Berne 1964).In brief, this theoj. is based on the concept that changes in perfusion pr&sure will cause metabolic changes in the tissues, e.g. accumulation of metabolites which in turn may induce changes of the vascular calibers so that flow is kept constant. The third main theory frequently referred to in discussions‘regarding autoregulation of CBF is the tis511e pressure tIteooly. This theory requires that the organ in question is surrounded by very rigid capsule such as the brain within the skull. Elevation ofthe perfusion pressure will thencause an outward filtration of fluid, which in turn will cause a raised tissue pressure which compresses the vessels to a certain extent thereby keeping flow constant. The ‘tissue pressure theory would seem to offer a logical explanation bf the autoregulation of CBF when arterial pressure is raised. However, it is much more difficult to apply this theory in order to explain BUtoregulation of CBF also when blood pressure is lowered, and for this reason the tissue pressure theory would appear to offer a less likely explanation. It isentirely possible that more than one mechanism of the above mentioned are involved in the autoregulation of CBF. Thus, Lassen has expressed the opinion that both the myogenic theory and the metabolic thebry are engaged (Lassen 1959, Lassen 1964). This view has also been expressed by others working in this field, e.g. Harper and HIggendal(1968). Findings supporting the myogenic theory have been reported, e.g. by Haggendal and Johansson (1966) and by Ekstrom-Jodal and co-workers (1969). Further support for the myog-
enic mechanism is offered by the finding that autoregulation takes place at a lower flow level with a pulsatile flow as compared to non-pulsatile flow with the same mean pressure (Held et al. 1969). It is interesting to note that the existence of autoregulation of the CBF has been denied by some distinguished researchers even into the 1960's (Sagawa & Guyton 1961). For further extensive discussions on the autoregulation of CBF. the reader is referred to references: Lassen 1959, Lassen 1964, Harper 1966 & Ekstrom-Jodal 1970.
CLINICAL IMPLICATIONS . When the lower limit ofCBF autoregulation is reached
a number of symptoms occur (Table I). Likewise, as blood pressure is increased to above the upper limit of CBF autoregulation, increasingly severe symptoms will be seen (Table 11). Due to the shifted autoregulation curve hypertensive individuals will tolerate higher blood pressure levels before they experience the symptoms and consequences described in Table 11. On theother hand they will alsobe moresusceptible to blood pressure reductions. Particularly when reducing very high blood pressures rapidly symptoms of EFFECTS OF BLOOD PRESSURE CHANGE ON reduced cerebral perfusion have been reported. Thus, THE CEREBRAL BLOOD-FLOW Graham reported two patients with malignant hyperAs already mentioned CBF is kept constant over a tension who both became unconscious after having wide range of blood pressure. In fact Lassen suggests had their blood pressure reduced from 240/140 mm that CBF is unchanged at arterial pressures between Hg to 120/85 mm Hg and from 2401170 mm Hg to 60-170 mm Hg (1959). This is supported by studies 120/100 mm Hg respectively by administration oforal showing that neither essential hypertension (Moyer bethanidine and intravenous pentholinium respectivet al. 1953, Moyer & Morris 1954, Hakenschiel el ely (Graham 1975). Particularly in elderly hypertensive al. 1954). nor drug-induced hypertension (Moyer et patients care should be taken not to lower arterial presal. 1954) was associated with any significant change sure too rapidly (Jones & Graham 1977). of CBF. Moreover, moderate reduction of blood presCertain drugs seem to require more care than other. sure did not cause a significant change of CBF (Moyer Thus, sodium nitroprusside has been shown to in& Morris 1954, McCall 1953). crease intracranial pressure (Turner et al. 1977). This That autoregulation of CBF cannot be maintained is probably due to the powerful vasodilating action at low arterial pressure has been known for several of this compound which could cause edema of the decades (Lassen 1959). Later studies have demonstnt- brain in spite of the reduction in perfusion pressure. ed a breakthrough of autoregulation also at high blood In a series of 44 patients undergoing neurosurgery sodpressures (Strandgaard el al. 1973). Of great interest ium nitroprusside was shown togive an initial increase is the fact that the whole autoregulation curve of CBF in intracranial pressure whereas treatment with the is shifted to the right in hypertension (Figure I). This has been demonstrated in hypertensive patients using CBF Iml/min. 100 g1 angiotensin II and the ganglion blocker trimetaphan ' 60in order to raise and lower blood pressure respectively (Strandgaard el al. 1973). Studies in normotensive ba- 50boons and in baboons with two-kidney-Goldblatthypertension have confirmed this shift of the curve 40both as regards the upper (Strandgaard et al. 1975) and the lower limit of CBF autoregulation (Jones et al. 1976).It has been suggested (Strandgaard 1978)that 203 rnm Hg the shift of the autoregulation curve in hypertension Figure 1. Cerebral blood-now autoregulation curves in norto the right is due to structural vascular changes in motension and hypertension. Note shift of curve to the right the precapillary resistance vessels leading to an in- in hypertension due to structural changes in the precapillary resistance vessels. (Based on Lassen 1959, Ekstr6m-Jodal creased wall to lumen ratio (Folkow et al. 1973) 1970, Moyer & Morris 1954, Strandgaardet al. 1973 and Jones et al. 1976.) (Figure 1). 18
ganglion blocker trimetaphan did not have this effect (Turner et al. 1977). Furthermore, treatment with sodium nitroprusside may give rise to rapid changes in arterial pressure which are too Fist for the autoregulation process to be maintained (Fitch 1977). It has
Table I. Effects of reduced cerebral blood-flow. Discomfort ~ i Sleepiness
~
i
~
~
~
Nausea
Syncope
coma
also been claimed that CBF autoregulation is lost altogether during treatment with thiscompound (Crockard et al. 1976). From a practical point of view it therefore appears that special care should be taken when using sodium nitroprusside in situations requiring acute reduction of arterial pressure. During chronic treatment of hypertension particular care is recommended when using peripheral sympatholytic agents, which occasionally may reduce blood pressure drastically, e.g. in the standing position or during exposure to heat, with ensuing risks of reduced CBF leading to dizziness or syncope. On the other hand prolonged and gradual reduction of elevated arterial pressure in hypertension will tend to shift the autoregulation curve ofCBF back towards normal (Strandgaard to be published). This is probably due to reversibility to the structural vascular changes in the precapillary resistance vessels of the kind described in other vascular beds (Hansson & Sivertsson 1975).
Death
Table 11. E f f a t s of increased cerebral blood-flow. Discomfort Headaches Nausea Mental confusion Convulsions Coma Death (apoplexy)
tensive patients due to structural vascular changes in the precapillary resistance vessels. When reducing blood pressure below the lower limit ofautoregulation, potentially dangerous effects may arise such as syncope or unconsciousness. These risks should be born in mind particularly when employing powerful and fast acting antihypertensive agents. On the other hand, prolonged and gradual reduction of arterial presCONCLUSlONS sure through the use of oral antihypertensive agents Cerebral blood-flow is autoregulated over a wide range will tend to shift the autoregulation curve ofCBF back of arterial pressure. This autoregulation of CBF is shift- towards normal thereby minimizing the risk of cerebral ed towards a higher blood pressure range in hyper- complications due to reduced CBF.
REFERENCES Bayliss W M: On the local reactions of the arterial wall to changes of internal pressure. J Physiol28: 220-231, 1902.
to the mechanism responsible for central blood flow autoregulation. Acta Physiol %and suppl 350, 1970.
Berne R M: Metabolic regulation of blood flow. Circ Res 15 SUPPI 1: 261-268, 1964.
Fitch W: Editorial. Sodium nitroprusside and the cerebral circulation. Br J Anaesth 49: 399-400, 1977.
Crockard H A, Brown F D & Mullen J F: Effects of trimetaphan and sodium nitroprusside on cerebral blood flow in rhesus monkeys. Acta Neurochir 35: 85-89, 1976.
Folkow B Description of the myogenic hypothesis. Circ Res 15 suppl 1: 279-287, 1964. Folkow B & Neil E: Cerebral Circulation. In: Circulation. pp 434448. Oxford University Press. New York, London. Toronto 1971. Folkow B, Hallback M,Lundgren Y,Sivertsson R & Weiss L: Importance of adaptive changes in vascular design for establishment of primary hypertension, studied in man and in spontaneously hypertensive rats. Circ Res 32/33 suppl 1: 2-13. 1973. Graham D I: lschaemic brain damage of cerebral perfusion
Ekstrom-Jodal B, Haggendal E. Nilsson N J & Norblck B: Changes of the transmural pressure - The probable stimulus to cerebral flow autoregulation. In: Cerebral blood flow, pp 89-93. Eds: M Brock, C Fieschi, D H Ingvar, N A Lassen & K Schiirmann, Springer-Verlag. Berlin, Heidelberg, New York 1969. Ekstrom-Jodal B: On the relation between blood pressure and blood flow in the canine brain with particular regard
19
~
Lassen N A: Autoregulation of cerebral blood flow. Circ Res 15 suppl 1: 1-204. 1964.
failure type after treatment of severe hypertension. Br Med J 4: 739, 1975. Hafkenschiel J H. Friedland C K & Zintel H A: Blood flow and oxygen consumption of the brain in patients with essential hypertension before and after adrenalectomy. J Clin Invest 33: 57-62. 1954.
McCall M L: Cerebral circulation and metabolism in toxemia of pregnancy. Observations on the effect of Veratrum viride and Apresoline. A m J Obstet Gynecol 66: 1015-1030, 1953. Moyer J H & Morris Jr G C: Cerebral hemodynamics during controlled hypotension induced by a continuous infusion of ganglionic blocking agents. J Clin Invest 33: 1081-1088,
Hansson L & Sivensson R: Reversibility of structural vascular changes in human essential hypertension. In: Pathophysiology and management of arterial hypertension, pp 114-121. Eds: G Beglund, L Hansson & L Werkd. A Lindgren & Sijner AB. Molndat 1975.
1954.
Moyer J H, Morris G & Snyder H: Comparison of the cerebral hemodynamic response to Aramine and norepinephrine in normotensive and hypotensive subject. Circulation 10: 265-270, 1954.
Harper A M: Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiatry 29:
Moyer J H. Miller S I, Tashnek A B, Snyder H & Bowman R 0: Malignant hypertension and hypertensive encephalopathy; cerebral hemodynamic studies and therapeutic response to continuous infusion of intravenous veriloid. Am J Med 14: 175-183. 1953.
398403. 1966.
Harper A M & Haggendal E: Discussion and comments to section V on autoregulation of CBF. In: Cerebral blood flow and cerebro-spinal fluid 111. Scand J Clin Lab Invest 22 suppl 102: 102, 1968.
Sagawa K & Guyton A C: Pressure-flow relationships in isolated canine cerebral circulation. Am J Physiol 200:
Held K U. Gottstein U & Niedermayer W: CBF in nonpulsatile perfusion. In: Cerebral Blood Flow. pp 94-95. Eds: M Biock, C Fieschi, D H Ingvar. N A Lassen & K Schiirmann. Springer-Verlag. Berlin, Heidelberg, New York 1969.
71 1-714. 1961.
Sivertsson R: Effect of blood pressure reduction on tissue perfusion. Acta Med Scand suppl 628: 13-16, 1978. (This volume).
Haggendal E & Johansson B: Effects of arterial carbon dioxide tension and oxygen saturation on cerebral blood flow autoregulation in dogs. Acta Physiol %and 66 suppl 258:
Strandgaard S : Academic Dissertation. University of Copenhagen. In press 1978.
27-53, 1966.
Strandgaard S , Olesen J. Skinhej E & Lassen N A: Autoregulation of brain circulation in severe arterial hypertension. Br Med J I : 507-510, 1973.
Johnson P C: Review of previous studies and current theories of autoregulation. Circ Res I5 suppl 1: 2-9, 1964. Jones J V & Graham D I: Inappropriate antihypertensive therapy in the elderly. Lancet 1: 425, 1977.
Strandgaard S , Jones J V, Mackenzie E T & Harper A M: Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res
Jones J V, Fitch W. Mackenzie E T. Strandgaard S & Harper A M: Lower limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res 39: 555-557, 1976.
37: 164-167. 1975.
Turner J M. Powell D. Gibson R M & McDowall D G : Intracranial pressure changes in neurosurgical patients during hypotension induced with sodium nitroprusside or trimetaphan. Br J Anaesth 49: 419-426, 1977.
Kety S S & Schmidt C F: The determination of cerebral blood flow in man by use of nitrous oxide in low concentrations. Am J Physiol 143: 53-66. 1945. Lassen N A: Cerebral blood flow and oxygen consumption in man. Physiol Rev 39: 183-238, 1959.
20
