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대량의 Hydrocortisone 투여가 뇌혈류역학에 미치는 영향

Other Titles
 (The) effect of massive doses of hydrocortisone on cerebral hemodynamics 
Issue Date
1975
Description
의학과/박사
Abstract
[한글] Steroid가 항염증성 작용이 있으며 여러원인으로 부종을 일으킨 각종 질환에서 사용되고 있음은 물론, 신경외과 영역에서 광범위하게 사용되고 있다. Prados등(1945)이 고양이의 뇌를 공기중에 노출시켜 뇌부종을 만들어 steroid를 투여함으로서 뇌부종이 감소되었고 동시에 뇌순환혈관의 투과성이 변화되었음을 보고한 것은 유명한 사실이다. 그후 많은 연구자들이 steroid가 임상적으로나 실험적으로 뇌부종에 효과가 있음을 보고하였다. (Hume and Moore, 1951; Ingraham et al., 1952; Grenell and Mendelson, 1954: Raimondi et al., 1959: Lippert et al,, 1960: Rasmussen and Gulati, 1962: Taylor et al., 1964, 1965; French and Galicich, 1964: Rovit and Hagen, 1968; Pappius and McCann, 1969: Dougherty and Schneebeli, 1970; Maxwell et al., 1971 : Hague et al., 1972: Renaudin et al,, 1973). 최근에 와서는 대량의 steroid를 쇽환자에 투여함으로써 심박출량의 증가 및 말초혈관 저항이 감소됨을 보고하였고(Sambhi et al.,1975: Wilson and Fisher, 1968), 신경외과 영역에서도 대량의 steroid를 투여함으로써 환자의 증상이 최단시간내에 호전됨을 보고하였다(Reulen et al., 1972: Renaudin et al., 1973: Hashi and Shim, 1975). 이는 steroid 투여가 뇌부종을 경감시키기 보다는 뇌헐류역학 및 뇌대사의 다른 변화에 기인한다고 추측되므로 이를 규명코저 본실험을 시행하였다. 즉 임상환자 및 동물실험을 대상으로 하여 대량의 hydrocortisone(뇌종양환자 500mg, 정상견 100mg/kg)을 투여 (133 )**Xe clearance technique를 사용하여 뇌혈류를 측정함으로서 뇌혈관계의 변화를 관찰하고 동시에 동맥혈압 및 동맥혈의 pO^^2, pCO^^2 및 pH를 측정하였다. 임상환자군 및 동물실험군에서 hydrocortisone을 투여시 공히 뇌혈류는 의의있게 증가되었고 뇌혈관계 저항은 현저히 감소하여 뇌혈관화장이 나타남을 볼 수 있었다. 동물실험에서의 동맥혈압은 hydrocortisone주사 즉시 급격히 감소하였다가 다시 정상으로 회복되 었으나 임상환자군에서는 별 변화를 볼 수 없었다. 한편 동물실험군에서는 두개강내압은 급속히 상승하였다가 점차적으로 회복되었다. 동맥혈의 pO^^2 는 임상환자군에서 대량의 hydrocortisone을 투여함으로서 의의있게 증가하였으며 pC0^^2 및 pH는 별 변화를 볼 수 없었다.
[영문] The beneficial effect of steroid in patients with cerebral edema was been well established both by animal experiments and in clinical triads(Prados et al., 1945; Grenell and McCawley. 1947; Grenell and Medelson, 1954; Raimondi et al., 1959, Lippert et at., 1960; Galicich and French, 1961; Rasmussen and Gulati, 1962: Long, 1964; Long et al., 1966; Taylor et al., 1964, 1965; French and Galcich, 1964; Rovit and Hagen, 1968; Pappius and McCann, 1969: Dougherty and Schneebeli, 1970; Maxwell et al., 1971; Hague et al., 1972: Renaudin et al., 1973). The mechanism by which steroid exerts its action or cerebral edema is generally believed to be an improvement of abnormal cerebrovascular permeability (Long, 1964: Long et al., 1966; Hammargern et al., 1965; Rovit and Hagen. 1968; Motsay et al., 1970: Maxwell et al., 1971) and a stabilizing effect upon the lysosomes, which may be important in the production. spread, or resolution of cerebral edema (de Duve et al., 1961: do Duve, 1963: Weissmann and Dingle, 1961: Weissmann and Thomas, 1963; Weissmann, 1964: Replog1e et al., 1966) Clinically, however it is not infrequently observed that a single injection of a large dose of steroid can lead dramatically to clinical improvement within a few hours in patients who had previously been unconscious and neurological deficits due to brain edema. From recent experience it is very hard to explain why it only relieves brain edema, because steroids are not useful for the acute reduction of general edema and clinical effects are rarely noted before 24 hours (Clasen et al., 1957; Pappius and McCann, 1969; Maxwell et al., 1971) Therefore this dramatically favorable effect may suggest that an immediate change in cerebral hemodynamics or metabolism might occur fellowing steroid, by same mechanism other than the relief of brain edema. For this purpose, Hashi and Shim (1975) have studied patients with train tumor and found a significant increase in cerebral blood flow(CBF) by (l33)^^Xe clearance technique, following intravenous injection of steroid (hydrocortisone 500 mg). The assumption that a large dose of steroid may directly influence cerebral blond flew is also suggested by the effectiveness of this drug in the treatment of shock. For patients in shock there have been at least three effects reported for corticosteroid: 1) A direct myocardial isotropic effect(Sambhi et al., 1965), 2) A vasodilatory effect, either as an alpha adrenergic blocker or directly as a peripheral vasodilator (Dietzman and Lillehei, 1968; Lillehei et al., 1970), 3) A lysosomal stabilizing effect (Weissman, 1964: Replogle et at., 1966). Lillehei et al. (1970) have stated that vasodilatation caused by a massive dose of corticosteroid is mediated through at least three different ways: 1) It slows nerve impulse transmission in pustganglionic sympathetic nerves. 2) It preserves the integrity of small vessels with less leakage from microcirculation. 3) It decreases platelet adhesiveness and preserves their integrity. It is important to emphasize that the glucosteroids are used in shock not for physiological replacement but for their pharmacological effects, three of which are listed above. But there are undoubtedly other effects that are as yet unknown. Unfortunately, there huts been little informations on _the cerebral hemodynamic effect of a large dose of steroid, particularly about the acute effects after its adminstration . The purpose of this study in brain tumor and normal dogs is to investigate the cerebral hemodynamic effect of steroid and possible to clarify characteristics of the effect in relation to its alpha blocking action. Materials and methods. The study is divided into two parts, clinical and experimental. a) Ten mongrel dogs weighing 15-20 kg were anesthetized with pentobarbital sodium (30mg/kg) and maintained under spontaneous respiration. A polyethylene catheter was placed in the abdominal descending aorta to monitor blood pressure and obtain arterial blood pressure. Arterial blood pressure was monitored via a pressure transducer connected to a polygraph(Multipolygraph RM-150, Nihon Kohden). Intracranial pressure was continuously measured as sagittal sinus wedge pressure after the anterior portion of the sagittal sinus was punctured and connected to the same polygraph. Arterial p0^^2 , pC0^^2 and pH were measured at intervals with an Astrop physiological gab analyser during this procedure. A thin polyethylene catheter was placed in the common carotid artery through the right superior thyroid artery after stripping off soft tissue of the skull, the head was positioned and the lateral surface was against the scintillation counter (Toshiba Model GCA-101). 5mC^^1 of (133)^^Xe was injected. before and 30 minutes after hydrocortisone(170 mg/kg), via a catheter placed in the common carotid artery and the clearance curve was recorded for about 15 minutes with renographic apparatus. In certain cases in which the topographic display revealed regional areas of special interest, detailed measurements were obtained by replaying the tape. Cerebral blood flow was calculated from the clearance curves of (l33)^^Xe using the stochastic (weight over area) method (Zierler, 1965). The effect of atropine was also studied. b) Premedication in each patient consisted of phenobarbital 50mg and atropine 0.4mg. A conventional plastic needle was used for selective puncturing under local anesthesia of the internal carotid artery high up in the carotid triangle. The patient's head was securely positioned with adhesive tape. Otherwise details were the same as in the previously decribed method. The results obtained are summerized as follows: 1. In clinical and experimental study cerebral blood flow(CBF) was significantly increased following injection of a large dose of hydrocortisone due to cerebral vasodilatation. Cerebral vascular resistance (CVR) was remarkably decreased. 2. In normal dogs a profound fall in arterial blood pressure to the level of 50% of the original value was observed immediately following injection of hydrocortisone and they began to recover in a few minutes, but in brain tumor patients there was no changes in arterial blood pressure. 3. Intracranial pressure (ICP) rapidly increased by approximately 100mm H^^2O, then gradually returned to normal levels in normal dogs. 4. Arterial PO^^2 was significantly increased in the brain tumor patients but in normal dugs there was no remarkable change. Arterial pCO^^2 and pH were within normal limits.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/116185
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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