과산화수소가 일산화탄소혈색소 해리에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

최근 20여년간 우리나라에서는 무연탄을 가정연료로 많이 사용함에 따라 일산화탄소중독이 국민건강에 큰 위협이 되고있다. 일산화탄소중독 치료의 목표는 조직으로의 산소운반기능을 상실한 일산화탄소혈색소(이하 HbCO)에서 CO해리를 촉진시켜서 저산소상태에서 속히 벗어나게 하는 것이다. HbCO해리를 가장 촉진시키는 방법으로 고압산소요법이 쓰이고 있으나 산소중독, 청력장애 및 시설부족이 문제가 되며 이보다 간편하면서도 효과가

좋은 치료방법의 개발이 필요하다. 과산화수소수가 폐외산소공급원으로서 혈중 산소분압을 증가시킨다는 여러 연구보고가 있었다. 특히 Ackerman 및 Brinkley(1968)는 0.2%과산화수소수를 매분 0.5∼2ml의 속도로 동맥에 주입하면 혈장 산소분압이 3∼8기압의 고압산소환경과 동일할 정도로 증가한다고 보고하였고 최등(1980)은 일산화탄소중독에 의한 저산소상태에 과산화수소수관장을 하여 HbCO 해리에 유의한 효과가 있음을 보고하였다.

따라서 저자는 과산화수소수가 혈중 산소분압을 증가시킬 수 있으므로 혈중 HbCO 해리에 효과가 있을 것으로 생각하여 과산화수소수관장보다 효과가 빠르고 확실한 과산화수소

수 정주를 하여 HbCO 해리속도에 미치는 영향을 관찰하며 임상적용의 가능성을 규명코저 실험적으로 연구하여 보았다.

실험재료 및 방법

1. 실험 동물은 성숙 자웅가토를 사용하였다.

2. CO가스는 Matheson Gas Products의 100% CO가스 일정량을 실내공기와 혼합하여 0.5% CO가스로 만들고 과산화수소수는 3% 과산화수소수를 생리식염수에 희석하여 0.1, 0.2 및 0.3% 과산화수소수로 만들어 사용하였다.

3. 실험동물은 채혈을 위해 편측고동맥에 cut-down set를 삽관한 후 밀폐된 chamber속에서 0.5% CO가스에 40분간 폭로시킨후 대조군과 실험군으로 나누어 대조군은 실내공기중에 방치한 자연해리군과 증류수정주군으로 하였고 실험군은 0.1, 0.2, 0.3% 과산화수소수

정주군으로 하여 7군으로 하였다.

4. 과산화수소수 정주방법은 0.1 및 0.2% 과산화수소수는 체중 매 kg당 5cc를 CO가스 폭로종료후 15분에 10분간에 걸쳐 이변정맥을 통해 서서히 정주하였고 0.3% 과산화수소수는 정주시작시간, 속도 및 총량에 따라 5군으로 나누어 정주하였다. 즉

1) CO가스 폭로종료 후 15∼25분에 정주군(3cc/kg).

2) CO가스 폭로종료 후 30∼60분에 정주군(3cc/kg)

3) CO가스 폭로종료 후 20∼60분에 정주군(3cc/kg).

4) 3회 분활정주군(CO가스 폭로 종료 후 15∼25분, 30∼40분, 45∼55분에 각기 10분간에 걸쳐 정주, 매회 1cc/kg).

5) CO가스 폭로종료 후 15∼25분에 소량단회 정주군(1.5cc).

5. 대조군과 실험군은 모두 CO가스 폭로종료직후부터 채혈하기 시작하여 40분까지 5분 간격으로 8회 채혈하였고 이후로는 50, 60, 70, 85, 100, 120분에 채혈하였다.

6. 채혈한 혈액은 CO-oximeter I.L. type 182를 사용하여 HbCO포화도 및 Hb농도를 측정하여 HbCO 해리율을 비교하였다.

실험성적

1. 자연해리군과 증류수정주군의 HbCO 해리는 CO가스 폭로종료후 15분에 가장 해리가 현저하였으며 반감기는 양군에서 CO가스 폭로종료후 각기 85분과 90분이였다.

2. 0.1% 과산화수소수정주군, 0.3% 과산화수소수 소량단회 (1.5cc) 정주군 및 0.3% 과산화수소수를 CO가스 폭로종료 후 30∼60분에 정주한 군에서 HbCO해리는 각기 정주직후에 해리가 일시적으로 촉진되었으나 그 지속시간이 짧았고 이후는 오히려 자연해리군보다

해리가 늦어져서 HbCO 반감기가 각기 150,140 및 110분으로 자연해리군보다 지연되었다.

3. 0.2% 과산화수소수 정주군은 HbCO 해리가 정주직후 일시적으로 촉진되었고 반감기는 자연해리군과 유사하였다.

4. 0.3% 과산화수소수를 CO가스 폭로종료후 20∼60분사이 정주군에서 HbCO해리는 정주직후 15분간 유의하게 촉진되었으나 이후는 오히려 HbCO의 재증가 및 빈호흡을 보이면서 대부분의 가토가 죽었다.

5. 0.3% 과산화수소수를 3회 분활정주군에서 HbCO해리는 전실험군들중에서 가장 유의하게 해리되었고 반감기는 40분으로 자연해리군보다 45분 단축되었으나 과산화수소수 정주직후 일시적인 HbCO의 재증가가 있었다.

6. 0.3% 과산화수소수를 CO가스 폭로종료후 15∼25분 사이 정주군에서 HbCO해리는 정주직후부터 유의하게 해리되었고 계속하여 자연해리군보다 HbCO해리가 촉진되었으며 반감기는 60분으로 자연해리군보다 25분 단축되었다. 과산화수소수 정주군들중 HbCO해리 촉진효과가 가장 오래 지속되었고 안전하였다.

Effects of Hydrogen Peroxide on the Carboxyhemoglobin Clearance in Rabbits

Moon Hee Joo

Department of Medical Science, The Graduate School, Yonsei University

(Directed by prof. Chae Won Kim, M.D.)

The carbon monoxide poisoning has been considered to he a serious health problem

in Korea, particularly in view of the wide usage of anthracite briquets for home

heating during these 20 years.

Although the hyperbaric oxygen therapy had been confirmed to be one of the

effective treatments for the clearance of carboxyhemoglobin, its feasibility was

limited due to the requirements of specific eqipments and the some untoward effects

such as oxygen toxicity and hearing disturbance etc. The simpler and more easily

available methods of treatment for carbon monoxide poisoning have been sought.

There are several reports on hydrogen peroxide which increases the partial oxygen

pressure of blood as a source of extrapulmonary oxygen. Ackerman and Brinckley

(1968) reported the increase to 3 to 8 atmospheric pressure of oxygen in blood

after injection of 0.2% hydrogen peroxide to the artery at the rate of 0.5 to 2

ml/minute. Choi et al (1980) had reported the significant effect on clearance of

carhoxyhemoglobin by the enema of hydrogen peroxide on carbon monoxide poisoning

The hydrogen peroxide can increase partial oxygen pressure of blood and could be

effective on carboxyhemoglobin clearance. Accordingly, an experimental study of the

effects of intravenous hydrogen peroxide on the carboxyhemoglobin clearance was

conducted.

Materials and methods

1. The mature rabbits of both sexes were used for this experiment.

2. 100% CO gas of Matheson Gas Products was reduced to 0.5% mixture with room

air. 3% hydrogen peroxide was diluted with normal saline to 0.1%, 0.2% and 0.3%

respectively.

3. The polyethylene tube was inserted into one of both femoral arteries for the

blood samplings. 0.5% CO gas was exposed to the experimental animals for 40 minutes

in the closed chamber and then divided into control group and experimental group.

The control group was subdivided into spontaneous clearance group which was

exposed to the room air, and distilled water I.V. group. Hydrogen peroxide

solution, 5cc/kg, was injected intravenously for a period of 10 minutes through the

marginal ear vein 15 minutes after completion of CO gas exposure. 0.1% 0.2% and

0.3% of hydrogen peroxide solution was used. 0.3% hydrogen peroxide group was

further divided into 5 subgroups.

4. The experimental group was subdivided into 7 groups.

1) 3cc/kg I.V. group at 15 to 25 minutes after completion of exposure to CO gas

2) 3cc/kg I.V. group at 30∼60 minutes after completion of exposure to CO gas

3) 3cc/kg I.V. group at 20∼60 minutes after completion of exposure to CO gas

4) 3cc/kg I.V. three divided injection during 15∼25, 30∼40 and 45∼55 minutes

respectively after completion of CO gas exposure

5) 1.5cc I.V. group during 15∼25 minutes after completion of exposure to CO gab

5. The blood samplings were done for 8 times from the completion of CO gas

exposure, with five minutes intervals until 40 minutes, and thereafter at 50, 60,

70, 85, 100 and 120 minutes respectively.

6. Carboxyhemoglobin percentage and hemoglobin concentration were determined

directly in a CO oximeter I.L. type 182.

The results were summarized as follows :

1. Carboxyhemoglobin clearance in spontaneous clearance group and distilled water

I.V. group was the most marked at 15 minutes after completion of exposure to CO gas

and half clearance time was 85 and 90 minutes respectively after completion of

exposure to CO gas.

2. In 0.1%, 0.2% and 0.3% hydrogen peroxide group injected during 30∼60 minutes

after completion of exposure to CO gas and 1.5cc I.V. groups carboxyhemoglobin

clearance was enhanced temporary immediately after hydrogen peroxide injection, but

sustaining period was short and thereafter clearance was stowed down in comparing

to the spontaneous clearance group and therefore half clearance time of

carboxyhemoglobin was prolonged to 150,140 and 110 minutes respectively.

3. In 0.2% hydrogen peroxide I.V. group carboxyhemoglobin clearance was temporary

enhanced immediately after hydrogen peroxide injection and half clearance time was

similar to the spontaneous clearance group.

4. When 0.3% hydrogen peroxide was injected during 20∼60 minutes after

completion of exposure to CO gas carboxyhemoglobin clearance was significantly

enhanced during 15 minutes after hydrogen peroxide injection but thereafter

carboxyhemoglobin was increased again by rebound phenomenon and almost all animals

died with tachypnea.

5. When 0.3% hydrogen peroxide wag given in 3 times during 10 minutes at 5 minute

intervals carboxyhemoglobin clearance was enhanced most significantly in all the

experimental groups and half clearance time was 40 minutes which was 45 minutes

shorter than the spontaneous clearance group. But cartoxyhemoglobin was temporary

increased again immediately after injection of hydrogen peroxide.

6. When 0.3% hydrogen peroxide was injected during 15∼25 minutes after

completion of exposure to CO gas carboxyhemoglobin clearance wart enhanced

significantly during 10minutes after injection and thereafter clearance wart

continuously enhanced in comparing to the spontaneous clearance group. The half

clearance time of carboxyhemoglobin was 60 minutes which was 25 minutes shorter

than the spontaneous clearance group.

[영문]

The carbon monoxide poisoning has been considered to he a serious health problem in Korea, particularly in view of the wide usage of anthracite briquets for home heating during these 20 years.

Although the hyperbaric oxygen therapy had been confirmed to be one of the effective treatments for the clearance of carboxyhemoglobin, its feasibility was limited due to the requirements of specific eqipments and the some untoward effects

such as oxygen toxicity and hearing disturbance etc. The simpler and more easily available methods of treatment for carbon monoxide poisoning have been sought.

There are several reports on hydrogen peroxide which increases the partial oxygen pressure of blood as a source of extrapulmonary oxygen. Ackerman and Brinckley (1968) reported the increase to 3 to 8 atmospheric pressure of oxygen in blood

after injection of 0.2% hydrogen peroxide to the artery at the rate of 0.5 to 2 ml/minute. Choi et al (1980) had reported the significant effect on clearance of carhoxyhemoglobin by the enema of hydrogen peroxide on carbon monoxide poisoning

The hydrogen peroxide can increase partial oxygen pressure of blood and could be effective on carboxyhemoglobin clearance. Accordingly, an experimental study of the effects of intravenous hydrogen peroxide on the carboxyhemoglobin clearance was conducted.

Materials and methods

1. The mature rabbits of both sexes were used for this experiment.

2. 100% CO gas of Matheson Gas Products was reduced to 0.5% mixture with room air. 3% hydrogen peroxide was diluted with normal saline to 0.1%, 0.2% and 0.3% respectively.

3. The polyethylene tube was inserted into one of both femoral arteries for the blood samplings. 0.5% CO gas was exposed to the experimental animals for 40 minutes in the closed chamber and then divided into control group and experimental group.

The control group was subdivided into spontaneous clearance group which was exposed to the room air, and distilled water I.V. group. Hydrogen peroxide solution, 5cc/kg, was injected intravenously for a period of 10 minutes through the

marginal ear vein 15 minutes after completion of CO gas exposure. 0.1% 0.2% and 0.3% of hydrogen peroxide solution was used. 0.3% hydrogen peroxide group was further divided into 5 subgroups.

4. The experimental group was subdivided into 7 groups.

1) 3cc/kg I.V. group at 15 to 25 minutes after completion of exposure to CO gas

2) 3cc/kg I.V. group at 30∼60 minutes after completion of exposure to CO gas

3) 3cc/kg I.V. group at 20∼60 minutes after completion of exposure to CO gas

4) 3cc/kg I.V. three divided injection during 15∼25, 30∼40 and 45∼55 minutes respectively after completion of CO gas exposure

5) 1.5cc I.V. group during 15∼25 minutes after completion of exposure to CO gab

5. The blood samplings were done for 8 times from the completion of CO gas exposure, with five minutes intervals until 40 minutes, and thereafter at 50, 60, 70, 85, 100 and 120 minutes respectively.

6. Carboxyhemoglobin percentage and hemoglobin concentration were determined directly in a CO oximeter I.L. type 182.

The results were summarized as follows :

1. Carboxyhemoglobin clearance in spontaneous clearance group and distilled water I.V. group was the most marked at 15 minutes after completion of exposure to CO gas and half clearance time was 85 and 90 minutes respectively after completion of exposure to CO gas.

2. In 0.1%, 0.2% and 0.3% hydrogen peroxide group injected during 30∼60 minutes after completion of exposure to CO gas and 1.5cc I.V. groups carboxyhemoglobin clearance was enhanced temporary immediately after hydrogen peroxide injection, but

sustaining period was short and thereafter clearance was stowed down in comparing to the spontaneous clearance group and therefore half clearance time of carboxyhemoglobin was prolonged to 150,140 and 110 minutes respectively.

3. In 0.2% hydrogen peroxide I.V. group carboxyhemoglobin clearance was temporary enhanced immediately after hydrogen peroxide injection and half clearance time was similar to the spontaneous clearance group.

4. When 0.3% hydrogen peroxide was injected during 20∼60 minutes after completion of exposure to CO gas carboxyhemoglobin clearance was significantly enhanced during 15 minutes after hydrogen peroxide injection but thereafter carboxyhemoglobin was increased again by rebound phenomenon and almost all animals

died with tachypnea.

5. When 0.3% hydrogen peroxide wag given in 3 times during 10 minutes at 5 minute intervals carboxyhemoglobin clearance was enhanced most significantly in all the experimental groups and half clearance time was 40 minutes which was 45 minutes

shorter than the spontaneous clearance group. But cartoxyhemoglobin was temporary increased again immediately after injection of hydrogen peroxide.

6. When 0.3% hydrogen peroxide was injected during 15∼25 minutes after completion of exposure to CO gas carboxyhemoglobin clearance wart enhanced significantly during 10minutes after injection and thereafter clearance wart continuously enhanced in comparing to the spontaneous clearance group. The half

clearance time of carboxyhemoglobin was 60 minutes which was 25 minutes shorter than the spontaneous clearance group.