The role of the prostacyclin-thromboxane system in cerebral vasospasm following induced subarachnoid hemorrhage in the rabbit

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✓ Subarachnoid hemorrhage (SAH) was induced in 50 rabbits by injecting 1.25 cc/kg of autologous, well heparinized, fresh arterial blood into the cisterna magna, followed by suspending the animals in a head-down position at 30° for 15 minutes. The animals were evenly divided into five groups: a control group, or groups receiving post-SAH prostacyclin (PGI2), carbacyclin, thromboxane A2 (TXA2) synthetase inhibitor (OKY-1581), or nutralipid. Radiographic vertebrobasilar arterial spasm was demonstrated on the 3rd day post-SAH in the control animals. This was decreased in the prostacyclin and the carbacyclin groups and was absent in the OKY-1581 and the nutralipid groups. Cerebral blood flow (CBF) measurements on the 4th day post-SAH using the xenon-133 technique failed to reveal any significant difference between the prostacyclin, the carbacyclin, and the control groups, but flows in the nutralipid and the OKY-1581 groups were significantly higher. There was a good correlation between the clinical status and the CBF. Intracytoplasmic vacuolation and detachment of the vascular endothelium, seen ultrastructurally, may account for the impaired synthesis of prostacyclin. Exogenous prostacyclin and carbacyclin decreased vasospasm but failed to improve cerebral perfusion. OKY-1581 blocked the synthesis of the potent vasoconstrictor, TXA2, which is not only formed during platelet aggregation but also induces platelet aggregation. Nutralipid contains linolenic acid, a precursor of eicosapentaenoic acid (EPA), which is more potent in inhibiting platelet aggregation and in blocking TXA2 production. The various fatty acid constituents of nutralipid bind to albumin and thereby shorten the half-life of TXA2.

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Figures

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    Cerebral angiograms in the control group. A: Before subarachnoid hemorrhage (SAH), the vertebrobasilar system was well demonstrated. B: On the 3rd day post-SAH, there was poor visualization of both the distal vertebral and the proximal basilar arteries (arrow) secondary to vasospasm.

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    Changes in the average diameter of the basilar artery prior to subarachnoid hemorrhage (SAH), and on the 3rd day post-SAH.

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    Cerebral angiograms in the prostacyclin group (A) and carbacyclin group (B) on the 3rd day after subarachnoid hemorrhage. Reduction in cerebral arterial spasm of the vertebral and the basilar arteries was seen (arrows).

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    Cerebral angiograms in the OKY-1581 group (A) and nutralipid group (B) on the 3rd day after subarachnoid hemorrhage. The vertebral and basilar arteries (arrows) were well demonstrated.

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    Transmission electron micrographs in control group animals: transverse sections. A: Extensive “intracytoplasmic vacuolation” is seen. × 2280. B: There are frequent detachments of the endothelial cells from one another and from the internal elastic lamina. × 4320.

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    Transmission electron micrographs, transverse sections, showing mild to moderate degrees of “intracytoplasmic vacuolation” and endothelial detachments. A: Prostacyclin group section, × 2600. B: Carbacyclin group section, × 5600.

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    Transmission electron micrographs showing normal endothelium, internal elastic lamina, and the tunica media. A: OKY-1581 group, longitudinal section, × 2600. B: Nutralipid group, transverse section, × 2000.

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    A simplified scheme of prostaglandin (PG) and thromboxane (Tx) biosynthesis in the platelets.

References

1.

Aiken JWShebuski RJ: Comparison in anesthetized dogs of the anti-aggregatory and hemodynamic effects of prostacyclin and a chemically stable prostacyclin analog, 6a-carba-PGI2 (carbacyclin). Prostaglandins 19:6296431980Aiken JW Shebuski RJ: Comparison in anesthetized dogs of the anti-aggregatory and hemodynamic effects of prostacyclin and a chemically stable prostacyclin analog 6a-carba-PGI2 (carbacyclin). Prostaglandins 19:629–643 1980

2.

Allcock JMDrake CG: Ruptured intracranial aneurysms — the role of arterial spasm. J Neurosurg 22:21291965Allcock JM Drake CG: Ruptured intracranial aneurysms — the role of arterial spasm. J Neurosurg 22:21–29 1965

3.

Allen GSBanghart SB: Cerebral arterial spasm: Part 9. In vitro effects of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries. Neurosurgery 4:37421979Allen GS Banghart SB: Cerebral arterial spasm: Part 9. In vitro effects of nifedipine on serotonin- phenylephrine- and potassium-induced contractions of canine basilar and femoral arteries. Neurosurgery 4:37–42 1979

4.

Boullin DJBrandt LLjunggren Bet al: Vasoconstrictor activity in cerebrospinal fluid from patients subjected to early surgery for ruptured intracranial aneurysms. J Neurosurg 55:2372451981Boullin DJ Brandt L Ljunggren B et al: Vasoconstrictor activity in cerebrospinal fluid from patients subjected to early surgery for ruptured intracranial aneurysms. J Neurosurg 55:237–245 1981

5.

Boullin DJBunting SBlaso WPet al: Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man. Br J Clin Pharmacol 7:1391471979Boullin DJ Bunting S Blaso WP et al: Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man. Br J Clin Pharmacol 7:139–147 1979

6.

Brawley BWStrandness DE JrKelly WA: The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg 28:181968Brawley BW Strandness DE Jr Kelly WA: The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg 28:1–8 1968

7.

Chan RSchweigel JThompson G: The effect of prostacyclin in experimental traumatic paraplegia in rats. Can J Neurol Sci 8:1881981 (Abstract)Chan R Schweigel J Thompson G: The effect of prostacyclin in experimental traumatic paraplegia in rats. Can J Neurol Sci 8:188 1981 (Abstract)

8.

Chapleau CEWhite RP: Effects of prostacyclin on the canine isolated basilar artery. Prostaglandins 17:5735801979Chapleau CE White RP: Effects of prostacyclin on the canine isolated basilar artery. Prostaglandins 17:573–580 1979

9.

Dyerberg JBang HOStoffersen Eet al: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 2:1171191978Dyerberg J Bang HO Stoffersen E et al: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 2:117–119 1978

10.

Ellis EFNies ASOates JA: Cerebral arterial smooth muscle contraction by thromboxane A2. Stroke 8:4804831977Ellis EF Nies AS Oates JA: Cerebral arterial smooth muscle contraction by thromboxane A2. Stroke 8:480–483 1977

11.

Gryglewski RJSalmon JAUbatuba FBet al: Effects of all cis-5,8,11,14,17 eicosapentaenoic acid and PGH3 on platelet aggregation. Prostaglandins 18:4534781979Gryglewski RJ Salmon JA Ubatuba FB et al: Effects of all cis-58111417 eicosapentaenoic acid and PGH3 on platelet aggregation. Prostaglandins 18:453–478 1979

12.

Hamberg MSvensson JSamuelsson B: Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins. Proc Natl Acad Sci USA 71:382438281974Hamberg M Svensson J Samuelsson B: Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins. Proc Natl Acad Sci USA 71:3824–3828 1974

13.

Herman AGMoncada SVane JR: Formation of prostacyclin (PGI2) by different layers of the arterial wall. Arch Int Pharmacodyn 227:1621631977Herman AG Moncada S Vane JR: Formation of prostacyclin (PGI2) by different layers of the arterial wall. Arch Int Pharmacodyn 227:162–163 1977

14.

Hughes JTSchianchi PM: Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg 48:5155251978Hughes JT Schianchi PM: Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg 48:515–525 1978

15.

Hwang DHCarroll AE: Decreased formation of prostaglandins derived from arachidonic acid by dietary linolenate in rats. Am J Clin Nutr 33:5905971980Hwang DH Carroll AE: Decreased formation of prostaglandins derived from arachidonic acid by dietary linolenate in rats. Am J Clin Nutr 33:590–597 1980

16.

Ishii R: Regional cerebral blood flow in patients with ruptured intracranial aneurysms. J Neurosurg 50:5875941979Ishii R: Regional cerebral blood flow in patients with ruptured intracranial aneurysms. J Neurosurg 50:587–594 1979

17.

Johnson RAMorton DRKinner JHet al: The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12:9159281976Johnson RA Morton DR Kinner JH et al: The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12:915–928 1976

18.

Kondo KOkuno TSaruta Tet al: Effects of intracerebroventricular administration of prostaglandins I2, E2, F2α and indomethacin on blood pressure in the rat. Prostaglandins 17:7697741979Kondo K Okuno T Saruta T et al: Effects of intracerebroventricular administration of prostaglandins I2 E2 F2α and indomethacin on blood pressure in the rat. Prostaglandins 17:769–774 1979

19.

Lagarde MVelardo BBlanc Met al: Fatty acids bound to serum albumin decrease the half-life of thromboxane A2. Prostaglandins 20:2752831980Lagarde M Velardo B Blanc M et al: Fatty acids bound to serum albumin decrease the half-life of thromboxane A2. Prostaglandins 20:275–283 1980

20.

Lewis MGKaduce TLSpector AA: Effect of essential polyunsaturated fatty acid modifications on prostaglandin production by mock canine kidney cells. Prostaglandins 22:7477601981Lewis MG Kaduce TL Spector AA: Effect of essential polyunsaturated fatty acid modifications on prostaglandin production by mock canine kidney cells. Prostaglandins 22:747–760 1981

21.

Linder MAlksne JF: Prevention of persistent cerebral smooth muscle contraction in response to whole blood. Stroke 9:4724771978Linder M Alksne JF: Prevention of persistent cerebral smooth muscle contraction in response to whole blood. Stroke 9:472–477 1978

22.

Lobato RDMarín JSalaices Met al: Cerebrovascular reactivity to noradrenaline and serotonin following experimental subarachnoid hemorrhage. J Neurosurg 53:4804851980Lobato RD Marín J Salaices M et al: Cerebrovascular reactivity to noradrenaline and serotonin following experimental subarachnoid hemorrhage. J Neurosurg 53:480–485 1980

23.

Lye RHPaul KSForster CMet al: Effect of fibrin-fibrinogen degradation products on human basilar artery preparations. Possible role in the etiology of cerebral arterial spasm. J Neurosurg 56:3393431982Lye RH Paul KS Forster CM et al: Effect of fibrin-fibrinogen degradation products on human basilar artery preparations. Possible role in the etiology of cerebral arterial spasm. J Neurosurg 56:339–343 1982

24.

Mayberg MRHouser OWSundt TM Jr: Ultrastructural changes in feline arterial endothelium following subarachnoid hemorrhage. J Neurosurg 48:49571978Mayberg MR Houser OW Sundt TM Jr: Ultrastructural changes in feline arterial endothelium following subarachnoid hemorrhage. J Neurosurg 48:49–57 1978

25.

Moncada SVane JR: The role of prostacyclin in vascular tissue. Fed Proc 38:66711979Moncada S Vane JR: The role of prostacyclin in vascular tissue. Fed Proc 38:66–71 1979

26.

Ozaki NMullan S: Possible role of the erythrocyte in causing prolonged cerebral vasospasm. J Neurosurg 51:7737781979Ozaki N Mullan S: Possible role of the erythrocyte in causing prolonged cerebral vasospasm. J Neurosurg 51:773–778 1979

27.

Petruk KCWest GRMarriott MRet al: Cerebral blood flow following induced subarachnoid hemorrhage in the monkey. J Neurosurg 37:3163241972Petruk KC West GR Marriott MR et al: Cerebral blood flow following induced subarachnoid hemorrhage in the monkey. J Neurosurg 37:316–324 1972

28.

Rothberg CWeir BOverton Tet al: Responses to experimental subarachnoid hemorrhage in the spontaneously breathing primate. J Neurosurg 52:3023081980Rothberg C Weir B Overton T et al: Responses to experimental subarachnoid hemorrhage in the spontaneously breathing primate. J Neurosurg 52:302–308 1980

29.

Sasaki TMurota SWakai Set al: Evaluation of prostaglandin biosynthetic activity in canine basilar artery following subarachnoid injection of blood. J Neurosurg 55:7717781981Sasaki T Murota S Wakai S et al: Evaluation of prostaglandin biosynthetic activity in canine basilar artery following subarachnoid injection of blood. J Neurosurg 55:771–778 1981

30.

Sasaki TWakai SAsano Tet al: Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor, OKY-1581. J Neurosurg 57:74821982Sasaki T Wakai S Asano T et al: Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor OKY-1581. J Neurosurg 57:74–82 1982

31.

Shigeno T: Norepinephrine in cerebrospinal fluid of patients with cerebral vasospasm. J Neurosurg 56:3443491982Shigeno T: Norepinephrine in cerebrospinal fluid of patients with cerebral vasospasm. J Neurosurg 56:344–349 1982

32.

Smith JBJubiz W: OKY-1581: a selective inhibitor of thromboxane synthesis in vivo and in vitro. Prostaglandins 22:3533631981Smith JB Jubiz W: OKY-1581: a selective inhibitor of thromboxane synthesis in vivo and in vitro. Prostaglandins 22:353–363 1981

33.

Spector AA: Fatty acid binding to plasma albumin. J Lipid Res 16:1651791975Spector AA: Fatty acid binding to plasma albumin. J Lipid Res 16:165–179 1975

34.

Szczeklik AGryglewski RJNizankowski Ret al: Circulatory and anti-platelet effects of intravenous prostacyclin in healthy men. Pharm Res Commun 10:5455561978Szczeklik A Gryglewski RJ Nizankowski R et al: Circulatory and anti-platelet effects of intravenous prostacyclin in healthy men. Pharm Res Commun 10:545–556 1978

35.

Tanabe YSakata KYamada Het al: Cerebral vasospasm and ultrastructural changes in cerebral arterial wall. An experimental study. J Neurosurg 49:2292381978Tanabe Y Sakata K Yamada H et al: Cerebral vasospasm and ultrastructural changes in cerebral arterial wall. An experimental study. J Neurosurg 49:229–238 1978

36.

Tanishima T: Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries. J Neurosurg 53:7877931980Tanishima T: Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries. J Neurosurg 53:787–793 1980

37.

Toda NShimizu KOhta T: Mechanism of cerebral arterial contraction induced by blood constituents. J Neurosurg 53:3123221980Toda N Shimizu K Ohta T: Mechanism of cerebral arterial contraction induced by blood constituents. J Neurosurg 53:312–322 1980

38.

Vane JRMcGiff JC: Possible contributions of endogenous prostaglandins to the control of blood pressure. Circ Res 36 (Suppl 1):68751975Vane JR McGiff JC: Possible contributions of endogenous prostaglandins to the control of blood pressure. Circ Res 36 (Suppl 1):68–75 1975

39.

Waltz AGWanek ARAnderson RE: Comparison of analytic methods for calculation of cerebral blood flow after intracarotid injection of 133Xe. J Nucl Med 13:66721972Waltz AG Wanek AR Anderson RE: Comparison of analytic methods for calculation of cerebral blood flow after intracarotid injection of 133Xe. J Nucl Med 13:66–72 1972

40.

Weir BErasmo RMiller Jet al: Vasospasm in response to repeated subarachnoid hemorrhages in the monkey. J Neurosurg 33:3954061970Weir B Erasmo R Miller J et al: Vasospasm in response to repeated subarachnoid hemorrhages in the monkey. J Neurosurg 33:395–406 1970

41.

Wilkins RH: Attempted prevention or treatment of intracranial arterial spasm: a survey. Neurosurgery 6:1982101980Wilkins RH: Attempted prevention or treatment of intracranial arterial spasm: a survey. Neurosurgery 6:198–210 1980

42.

Wilkins RHLevitt P: Intracranial arterial spasm in the dog. A chronic experimental model. J Neurosurg 33:2602691970Wilkins RH Levitt P: Intracranial arterial spasm in the dog. A chronic experimental model. J Neurosurg 33:260–269 1970

43.

Wilkins RHLevitt P: Potassium and the pathogenesis of cerebral arterial spasm in dog and man. J Neurosurg 35:45501971Wilkins RH Levitt P: Potassium and the pathogenesis of cerebral arterial spasm in dog and man. J Neurosurg 35:45–50 1971

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