A Severe Vicious Cycle in Uncontrolled Subarachnoid Hemorrhage: The Effects on Cerebral Blood Flow and Hemodynamic Responses upon Intracranial Hypertension

Chain-Fa Su；Yi-Ling Yang；Ming-Che Lee；Hsing I Chen

cushing response ； intracranial pressure ； systemic arterial pressure ； cerebral blood flow ； hemodynamic changes ； vicious cycle ； adrenergic blocker ； vasodilator

The Chinese Journal of Physiology

49卷1期（2006 / 02 / 28）

56 - 63

英文

In subarachnoid hemorrhage (SAH), Cushing postulated that the increase in systemic arterial pressure (SAP) in response to elevation of intracranial pressure (ICP) was beneficial to cerebral perfusion. However, in uncontrolled SAH, the increased SAP may cause more bleeding into the subarachnoid space and further increase the ICP. We created an animal model to simulate SAH by connecting a femoral arterial catheter to the subarachnoid space. The global cerebral blood flow (CBF) was measured with a venous outflow method. The purposes were to observe the CBF change under the simulated SAH, and to evaluate the effects of an adrenergic blocker and a vasodilator. In addition, spectral analysis of the aortic pressure and flow was employed for the analysis of hemodynamic changes at various ICP levels. When the femoral arterial blood was allowed to flow into the subarachnoid space, the ICP was elevated. The Cushing response to increased ICP caused an increase in SAP. A vicious cycle was generated between ICP and SAP. The CBF under the vicious cycle was greatly depressed. The dog developed pulmonary edema (PE) within 5 mins. An α-adrenergic blocker (phentolamine) and a vasodilator (nitroprusside) were beneficial to the reduction of SAP and ICP, improvement of CBF, and prevention of PE. Hemodynamic analysis revealed that graded increases in ICP caused increases in SAP, total peripheral resistance, arterial impedance, and pulse reflection with decreases in stroke volume, cardiac output and arterial compliance. The hemodynamic changes may contribute to acute left ventricular failure that leads to pressure and volume loading in the lung circulation, and finally acute PE.

1. Chen, H.I.,Chai, C.Y.(1974).Pulmonary edema and hemorrhage as a consequence of systemic vasoconstriction.Am. J. Physiol,227,144-151.
2. Chen, H.I.,Hu, C.T.(1997).Endogenous nitric oxide on arterial hemodynamics: a comparison between normotensive and hypertensive rats.Am. J. Physiol. Heart Circ. Physiol,273,1816-1823.
3. Chen, H.I.,Liao, J.F.,Kuo, L.,Ho, S.T.(1980).Centrogenic pulmonary hemorrhagic edema induced by cerebral compression in rats. Mechanism of volume and pressure loading in the pulmonary circulation.Circ. Res.,47,366-373.
4. Chen, H.I.,Lin, J.D.,Liao, J.F.(1981).Participation of regional sympathetic outflows in the centrogenic pulmonary pathology.Am. J. Physiol. Heart Circ. Physiol,240,109-115.
5. Chen, H.I.,Sun, S.C.,Chai, C.Y.(1973).Pulmonary edema and hemorrhage resulting from cerebral compression.Am. J. Physiol,224,223-229.
6. Chen, H.I.,Wang, D.J.(1984).Systemic and pulmonary hemodynamic responses to intracranial hypertension.Am. J. Physiol. Heart Circ. Physiol,247,715-721.
7. Chern, C.M.,Kuo, T.B.,Sheng, W.Y.,Wong, W.J.,Luk, Y.O.,Hsu, L.C.,Hu, H.H.(1999).Spectral analysis of arterial blood pressure and cerebral blood flow velocity during supine rest and orthostasis.J. Cereb. Blood Flow Metab,19,1136-1141.
8. Cushing, H.(1901).Concerning a definite regulatory mechanism of the vasomotor center which controls blood pressure during cerebral compression.Bull Johns Hopkins Hosp,12,290-292.
9. Cushing, H.(1902).Some experimental and clinical observations concerning states of increased intracranial tension.Am. J. Med. Sci,124,375-400.
10. Darby, J.M.,Yonas, H.,Marks, E.C.,Durham, S.,Snyder, R.W.,Nemoto, E.M.(1994).Acute cerebral blood flow response to dopamineinduced hypertension after subarachnoid hemorrhage.J. Neurosurg,80,857-864.
11. Davis, D.H.,Sundt, T.M.(1980).Relationship of cerebral blood flow to cardiac output, mean arterial pressure, blood volume, and alpha and beta blockade in cats.J. Neurosurg,52,745-754.
12. Deehan, S.C.,Grant, I.S.(1996).Haemodynamic changes in neurogenic pulmonary oedema: effect of dobutamine.Intensive Care Med,22,672-676.
13. Di Pasquale, G.,Andreoli, A.,Lusa, A.M.,Urbinati, S.,Biancoli, S.,Cere, E.,Borgatti, M.L.,Pinelli, G.(1998).Cardiologic complications of subarachnoid hemorrhage.J Neurosurg. Sci,42,33-36.
14. Ducker, T.B.(1968).Increased intracranial pressure and pulmonary edema. 1. Clinical study of 11 patients..J. Neurosurg,28,112-117.
15. Ducker, T.B.,Simmons, RL.(1968).Increased intracranial pressure and pulmonary edema. 2. The hemodynamic response of dogs and monkeys to increased intracranial pressure.J. Neurosurg,28,118-123.
16. Fontes, R.B.,Aguiar, P.H.,Zanetti, M.V.,Andrade, F.,Mandel, M.,Teixeira, M.J.(2003).Acute neurogenic pulmonary edema: case reports and literature review.J. Neurosurg. Anesthesiol,15,144-150.
17. Gaehtgens, P.,Marx, P.(1987).Hemorheological aspects of the pathophysiology of cerebral ischemia.J. Cereb. Blood Flow Metab,7,259-265.
18. Hsu, Y.H.,Kao, S.J.,Lee, R.P.,Chen, H.I.(2003).Acute pulmonary oedema: rare causes and possible mechanisms.Clin. Sci. (Lond),104,259-264.
19. Hu, C.T.,Chang, K.C.,Wu, C.Y.,Chen, H.I.(1997).Acute effects of nitric oxide blockade with L-NAME on arterial haemodynamics in the rat.Br. J. Pharmacol,122,1237-1243.
20. Hu, H.H.,Kuo, T.B.,Wong, W.J.,Luk, Y.O.,Chern, C.M.,Hsu, L.C.,Sheng, W.Y.(1999).Transfer function analysis of cerebral hemodynamics in patients with carotid stenosis.J. Cereb. Blood Flow Metab,19,460-465.
21. Jakobsen, M.,Skjodt, T.,Enevoldsen, E.(1991).Cerebral blood flow and metabolism following subarachnoid haemorrhage: effect of subarachnoid blood.Acta. Neurol. Scand,83,226-233.
22. Kassell, N.F.,Peerless, S.J.,Durward, Q.J.,Beck, D.W.,Drake, C.G.,Adams, H.P.(1982).Treatment of ischemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension.Neurosurgery,11,337-343.
23. Kassell, N.F.,Sasaki, T.,Colohan, A.R.,Nazar, G.(1985).Cerebral vasospasm following aneurysmal subarachnoid hemorrhage.Stroke,16,562-572.
24. Lam, K.K.,Hu, C.T.,Ou, T.Y.,Yen, M.H.,Chen, H.I.(2002).Effects of oestrogen replacement on steady and pulsatile haemodynamics in ovariectomized rats.Br. J. Pharmacol,136,811-818.
25. Maeda, M.,Mori, K.(1993).Hypervolemic hemodilution therapy for clinical vasospasm after subarachnoid hemorrhage.Nippon. Rinsho,51,412-419.
26. Rapela, C.E.,Green, H.D.(1964).Autoregulation of canine cerebral blood flow..Circ. Res.,15,205-212.
27. Schievink, W.I.,Wijdicks, E.F.,Parisi, J.E.,Piepgras, D.G.,Whisnant, J.P.(1995).Sudden death from aneurysmal subarachnoid hemorrhage.Neurology,45,871-874.
28. Smith, W.S.,Matthay, M.A.(1997).Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema.Chest,111,1326-1333.
29. Walder, B.,Brundler, M.A.,Totsch, M.,Elia, N.,Morel, D.R.(2002).Influence of the type and rate of subarachnoid fluid infusion on lethal neurogenic pulmonary edema in rats.J. Neurosurg. Anesthesiol,14,194-203.
30. Wood, J.H.,Kee, D.B.(1985).Hemorheology of the cerebral circulation in stroke.Stroke,16,765-772.
31. Wood, J.H.,Simeone, F.A.,Kron, R.E.,Snyder, L.L.(1984).Experimental hypervolemic hemodilution: physiological correlations of cortical blood flow, cardiac output, and intracranial pressure with fresh blood viscosity and plasma volume.Neurosurgery,14,709-723.
32. Woolf, P.D.,Hamill, R.W.,Lee, L.A.,Cox, C.,McDonald, J.V.(1987).The predictive value of catecholamines in assessing outcome in traumatic brain injury.J. Neurosurg,66,875-882.

1. Hsu, Yung-Hsiang,Chen, Hsing-I(2008).Acute Respiratory Distress Syndrome Associated with Hypercalcemia without Parathyroid Disorders.Chinese Journal of Physiology,51(6),414-418.
2. (2009).From Neurogenic Pulmonary Edema to Fat Embolism Syndrome: A Brief Review of Experimental and Clinical Investigations of Acute Lung Injury and Acute Respiratory Distress Syndrome.Chinese Journal of Physiology,52(5),339-344.