Research on some of biological changes and effects of recompression treament in experimental decompression sickness

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 
VIETNAM MILITARY MEDICAL UNIVERSITY 
CAO HONG PHUC 
RESEARCH ON SOME OF BIOLOGICAL CHANGES AND 
EFFECTS OF RECOMPRESSION TREAMENT IN 
EXPERIMENTAL DECOMPRESSION SICKNESS 
MEDICAL DORTOR PHILOSOPHY THESIS 
HA NOI-2018 
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 
VIETNAM MILITARY MEDICAL UNIVERSITY 
CAO HONG PHUC 
RESEARCH ON SOME OF BIOLOGICAL CHANGES AND 
EFFECTS OF RECOMPRESSION TREAMENT IN 
EXPERIMENTAL DECOMPRESSION SICKNESS 
Branch: Bio - Medicine Sciense 
Code: 972 01 01 
MEDICAL DORTOR PHILOSOPHY THESIS 
SUPERVISORS: 
1. Assoc.Prof. Nguyen Tung Linh, PhD 
2. Assoc.Prof. Dang Quoc Bao, PhD 
HA NOI-2018
i 
COMMITMENT 
I declare that this is my onw thesis which was carried out by scientific 
supports of superviors. 
All results that were presented in this thesis have been authentic and 
published in scientific articles. The thesis is not repeated to previous thesises 
or projects. If there is something wrong, I will take my responsibility. 
 Author 
Cao Hong Phuc 
ii 
ACKNOWLEGEMEND 
After years of in-depth research, this thesis has been completed. I would 
like to show my sincerely thanks to the Party Committee, Broad of Directors: 
Vietnam Military Medical University, Military Hospital No 103, National 
Institute Of Hygiene And Epidemiology for their facilitation. 
I would also like to thank: Department of Medicine of Arms, Department 
of Medical Physiology, Department of Experimental Operation, Department of 
Medical Physics (Vietnam Military Medical University), Departemt of 
Hematology and Tranfusion, Patho-Histology and Judical Medicine (Military 
Medical No 103), Laboratory of Micro-Structure (Virus Department, National 
Institute Of Hygiene And Epidemiology), Department of Post - Graduate 
Training for their technical help in my study. 
In addition, I am completely grateful to my suppervisors: Asscoc.Prof 
Nguyen Tung Linh, PhD (first suppervios), Asscoc.Prof Dang Quoc Bao, PhD 
(second suppervios). The doors of their offices were always open whenever I 
ran into a trouble spot about my reseach. They consistently allowed this paper 
to be my own work, steered me in the right direction in experimental period. 
They also set good examples for me to follow in doing all scientific tasks. 
Besides, I would like to express my heartfelt gratitude to my parents and 
parents - in - law for their bringing up and supporting me to make this work 
possible. Last but not least, I am deeply indebted to my wife and my son for 
being on my side, encouraging me a lots throughout my years of study. 
 AUTHOR 
Cao Hong Phuc 
iii 
CONTENT 
SUBTITLE PAGE 
COMMITMENT ................................................................................................ i 
ACKNOWLEGEMEND ................................................................................... ii 
CONTENT ....................................................................................................... iii 
ABBREVIATIONS AND DEFINITIONS .................................................... viii 
LIST OF TABLES .......................................................................................... xii 
LIST OF FIGURES ........................................................................................ xvi 
INTRODUTION ............................................................................................... 1 
CHAPTER 1. OVERVIEW .............................................................................. 3 
1.1. CLINICAL, INVESTIGATING CHARACTERISTICS OF 
ACUTE DECOMPRESSION SICKNESS ..................................... 3 
1.1.1. Causes and risk factors ............................................................... 3 
1.1.2. Clinical characteristics ................................................................ 7 
1.1.3. Investigating characteristics ...................................................... 12 
1.1.4. Diagnosis and classification ...................................................... 14 
1.1.5. Treatment .................................................................................. 16 
1.2. INFLUENCES OF THE BUBBLES IN DECOMPRESSION 
SICKNESS ....................................................................................... 20 
1.2.1. Bubble formation in the decompression sickness ..................... 21 
1.2.2. Influences of the bubbles in decompression sickness .............. 22 
1.3. STUDIES ON ANIMAL MODELS AND BIOLOGICAL 
CHANGES IN ACUTE DECOMPRESSION SICKNESS ......... 24 
iv 
1.3.1. Studies on animal models in decompression sickness .............. 24 
1.3.2. Some studies of peripheral blood cell changes in acute 
decompression sickness .......................................................... 26 
1.3.3. Some studies of coagulation changes in decompression 
sickness ................................................................................... 28 
1.3.4. Some studies of biochemical changes in acute decompression 
sickness .................................................................................... 30 
CHAPTER 2. SUBJECTS AND METHODS ................................................ 34 
2.1. SUBJIECTS ...................................................................................... 34 
2.1.1. Subjects ..................................................................................... 34 
2.1.2. Laboratories .............................................................................. 34 
2.1.3. Period ........................................................................................ 35 
2.2. METHODS ....................................................................................... 35 
2.2.1. Study design .............................................................................. 35 
2.2.2. Study Issues .............................................................................. 40 
2.2.3. Study equipments ...................................................................... 40 
2.2.4. Research indexes and methods ................................................. 42 
2.2.5. Data Analysis ............................................................................ 53 
CHAPTER 3. RESULTS ................................................................................ 55 
3.1. ETABLISHING THE EXPERIMENTAL ACUTE 
DECOMPRESSION SICKNESS MODEL .................................. 55 
3.1.1. Influence of some diving factors on acute decompression 
sickness ................................................................................... 55 
v 
3.1.2. Comparision the efficacy of models to cause the 
decompression sickness .......................................................... 60 
3.2. CHANGES IN HEMATOLOGICAL, BIOCHEMICAL AND 
PATHOHISTOLOGICAL INDEXES IN ACUTE 
DECOMPRESSION SICKNESS .......................................................... 62 
3.2.1. Changes in hematological indexes in acute decompression 
sickness rabbits ....................................................................... 62 
3.2.2. Changes in some of biochemical indexes in acute 
decompression sickness rabbits .............................................. 72 
3.2.4. Some of pathohistological characteristics in acute 
decompression sickness rabbits .............................................. 73 
3.3. EFFECTS OF RECOMPRESSION TREATMENT IN 
ACUTE DECOMPRESSION SICKNESS ................................... 83 
3.3.1. Effects on clinical symptoms in acute decompression 
sickness rabbits ....................................................................... 83 
3.3.2. Effects on hematological index in acute decompression 
sickness rabbits ........................................................................ 85 
3.3.3. Effects of recompression treatment on some biochemical 
indexes in in acute decompression sickness rabbits ............... 94 
CHAPTER 4. DISCUSSION .......................................................................... 97 
4.1. ANIMAL MODEL OF EXPERIMENTAL ACUTE 
DECOMPRESSION SICKNESS ............................................... 97 
4.1.1. Influence of some diving factors on experimental acute 
decompression sickness .......................................................... 97 
vi 
4.1.2. Effecting comparison of experimental acute 
decompression sickness of models .................................... 101 
4.2. CHANGES IN SOME HEMATOLOGICAL, 
BIOCHEMICAL, AND PATHOHISTOLOGICAL 
INDEXES IN EXPERIMENTAL ACUTE 
DECOMPRESSION SICKNESS ................................................ 104 
4.2.1. Changes of some hematological indexes in experimental 
acute decompression sickness rabbits ................................... 104 
4.2.2. Platelet activation in experimental acute decompression 
sickness ................................................................................. 114 
4.2.3. Changes of some biochemical indexes in acute 
decompression sickness rabbits ............................................ 118 
4.2.4. Changes of pathohistological indexes in experimental 
acute decompression sickness rabbit .................................... 120 
4.3. EFFECTS OF RECOMPRESSION TREATMENT ON 
EXPERIMENTAL ACUTE DECOMPRESSION 
SICKNESS ..................................................................................... 123 
4.3.1. Effects of recompression treatment on clinical symptoms 
in experimental acute decompression sickness rabbits ........ 123 
4.3.2. Effects of the recompression treatment on haematological 
indexes in acute decompression sickness rabbits ................. 128 
4.3.3. Effect of recompression treatment on biochemical indices 
in acute decompression sickness rabbit ................................ 134 
CONCLUSION ............................................................................................. 137 
vii 
SUGGESSTIONS ......................................................................................... 139 
LIST OF PUBLISHED ARTICLES RELATED TO 
RESULTS OF THESIS ................................................................................. 140 
REFFERENCES............................................................................................ 141 
APPENDIXES .............................................................................................. 158 
viii 
ABBREVIATIONS AND DEFINITIONS 
Num Abbre Deffinition Vietnamese Meaning 
1. 2D Two Dimension Hai chiều 
2. ADP Adenosine diphosphate 
3. ALT Alanine transaminase Enzym chuyển amin 
Alanine 
4. APTT Activated Partial 
Thromboplastin Time 
 Thời gian thromboplastin 
hoạt hóa từng phần 
5. Ar Argon Khí argon 
6. ARN Acid Ribonucleic A-xít Ribonucleic 
7. AST Aspartate transaminase Enzym chuyển amin 
Aspartate 
8. ATA Atmospheres Absolute Áp suất khí quyển tuyệt đối 
9. ATP Adenosine triphosphate 
10. Aβ β-amyloid 
11. BTG Beta thromboglobulin 
12. Conc Concentration Nồng độ 
13. CPK Creatine phosphokinase 
14. CSF 
T-tau 
Cerebrospinal fluid T-Tau Protein T-Tau trong dịch 
não tủy 
15. CT Computerized 
Tomography 
 Chụp cắt lớp vi tính 
16. DCS Decompression sickness Bệnh giảm áp 
ix 
Num Abbre Deffinition Vietnamese Meaning 
17. DWI Diffusion Weighted 
Imaging 
18. EDTA Ethylene diamine tetra 
acetic acid 
 Chất chống đông EDTA 
19. ET-1 Endothelin 1 
20. Fib Fibrinogen 
21. FSF Fibrin Stabilizing Factor Yếu tố ổn định Fibrin 
22. G Group Nhóm 
23. GFAP Glial fibrillary acidic 
protein 
24. Hb Hemoglobin 
25. HCl Hydrochloric acid A-xit Clohydric 
26. Hct Hematocrit 
27. HE Hematoxylin-Eosin Thuốc nhuộm 
Hematoxylin-Eosin 
28. HMWK High Molecular Weight 
Kininogen 
 Kininogen khối lượng 
phân tử cao 
29. HRP Horseradish peroxidase 
30. HSP 70 Heat Shock Protein 70 Protein sốc nhiệt 70 
31. ICAM-1 Intercellular Cell Adhesion 
Mollecular - 1 
 Chất liên kết tế bào 1 
32. IL-1β Interleukin 1 beta 
33. IL-6 Interleukin 6 
34. KLPT Khối lượng phân tử 
x 
Num Abbre Deffinition Vietnamese Meaning 
35. LDH Lactate dehydrogenase 
36. MCH Mean corpuscular 
hemoglobin 
 Hàm lượng hemoglobin 
trung bình hồng cầu 
37. MCHC Mean corpuscular 
hemoglobin concentration 
 Nồng độ hemoglobin 
trung bình hồng cầu 
38. MCV Mean corpuscular volume Thể tích trung bình hồng 
cầu 
39. MDA Malodialdehyde 
40. MH Mô hình 
41. MPV Mean platelet volume Thể tích trung bình tiểu 
cầu 
42. NSE Neuron-Specific Enolase 
43. OR Odd Ratio Tỷ suất chênh 
44. Para Paralysis Liệt 
45. PF4 Platelet Factor 4 Yếu tố 4 tiểu cầu 
46. Post Post-experiment Sau gây bệnh 
47. Pre Pre-experiment Trước gây bệnh 
48. PT Prothrombin Time Thời gian prothrombin 
49. RR Relative risk Nguy cơ tương đối 
50. sGPV Soluble Glycoprotein V Glycoprotein V hòa tan 
51. T2WI T2 Weighted Image 
52. TAT Thrombin-Antithrombin 
Complex 
 Phức hợp thrombin - 
antithrombin 
53. TNF-α Tumor necrosis factor 
alpha 
 Yếu tố hoại tử u alpha 
xi 
Num Abbre Deffinition Vietnamese Meaning 
54. TT Thrombin Time Thời gian thrombin 
55. TTR Transthyretin 
xii 
LIST OF TABLES 
Num Table Page 
2.1. Classification of clinical severity in experimental acute 
decompression sickness rabbits .................................................. 44 
2.2. Paralysis classification in acute decompression sickness rabbits ........ 44 
2.3. Classification of post-treatment response ................................... 44 
2.4. Bubble grade in experimental decompression sickness .............. 52 
3.1. The rabbit number of decompression sickness with variable 
bottom time ................................................................................. 55 
3.2. Clinical severity of rabbits after experiment .............................. 56 
3.3. The number of death rabbit after experiment with variable 
bottom time ................................................................................. 56 
3.4. The rabbit number of decompression sickness with variable 
ascent rate.................................................................................... 57 
3.5. Clinical severity of decompression sickness ............................. 57 
3.6. The number of death rabbits after decompression ...................... 58 
3.7. The rabbit number of decompression sickness .......................... 58 
3.8. Clinical severity and consecutive compression ......................... 59 
3.9. The number of death rabbit and consecutive compression ........ 59 
3.10. Influence of some diving factors on decompression sickness ... 60 
3.11. The rate of decompression sickness and survival of rabbits 
after compressing as four models ............................................... 61 
3.12. Clinical severity of rabbit after compressing as four models .... 61 
3.13. Bubble grade of rabbit after compressing as four models ......... 62 
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158 
APPENDIXES 
1
st 
APPENDIX 
LIST OF SUBJECTS 
Ordinal number Rabbit Historical number 
1
st
 PHASE: 
EVALUATION THE INFLUENCE OF DIVING FACTORS ON DECOMPRESSION SICKNESS 
Protocol 1 
1. A1 MH11A1 
2. A2 MH12A2 
3. A3 MH13A3 
4. A4 MH14A4 
5. A6 MH15A6 
6. A110 MH16A110 
7. A120 MH17A120 
8. A121 MH18A121 
9. A122 MH19A122 
10. A123 MH110A123 
Protocol 2 
11. A13 MH21A13 
12. A14 MH22A14 
13. A15 MH23A15 
14. A16 MH24A16 
15. A132 MH25A132 
16. A133 MH26A133 
17. A134 MH27A134 
18. A155 MH28A155 
19. A156 MH29A156 
20. A157 MH210A157 
Protocol 3 
21. A9 MH31A9 
22. A12 MH32A12 
23. A17 MH33A17 
24. A18 MH34A18 
25. A19 MH35A19 
26. A20 MH36A20 
27. A22 MH37A22 
28. A23 MH38A23 
29. A24 MH39A24 
30. A27 MH310A27 
159 
Ordinal number Rabbit Historical number 
Mô hình 4 
31. B1 MH41B1 
32. B2 MH42B2 
33. B3 MH43B3 
34. B4 MH44B4 
35. B5 MH45B5 
36. B6 MH46B6 
37. B7 MH47B7 
38. B8 MH48B8 
39. B9 MH49B9 
40. B10 MH410B10 
2
ST
 PHASE: 
DECOMPRESSION SICKNESS AND NON TREATMENT 
41. A31 BGA01 
42. A32 BGA02 
43. A33 BGA03 
44. A36 BGA04 
45. A37 BGA05 
46. A38 BGA06 
47. A39 BGA07 
48. A40 BGA08 
49. A41 BGA09 
50. A42 BGA10 
51. A43 BGA11 
52. A44 BGA12 
53. A45 BGA13 
54. A46 BGA14 
55. A47 BGA15 
56. A48 BGA16 
57. A49 BGA17 
58. A50 BGA18 
59. A51 BGA19 
60. A52 BGA20 
61. A55 BGA23 
62. A56 BGA24 
63. A61 BGA25 
64. A64 BGA26 
65. A66 BGA28 
66. A67 BGA29 
67. A70 BGA30 
68. A71 BGA31 
69. A72 BGA32 
70. A73 BGA33 
71. A74 BGA34 
72. A75 BGA35 
73. A76 BGA36 
74. A77 BGA37 
160 
Ordinal number Rabbit Historical number 
75. A78 BGA38 
76. A79 BGA39 
77. A80 BGA40 
78. A81 BGA41 
79. A82 BGA42 
80. A83 BGA43 
81. A84 BGA44 
82. A85 BGA45 
83. A86 BGA46 
84. A87 BGA47 
85. A88 BGA48 
86. A90 BGA50 
87. A91 BGA51 
88. A92 BGA52 
89. A93 BGA53 
90. A94 BGA54 
91. A95 BGA55 
92. A96 BGA56 
93. A97 BGA57 
94. A98 BGA58 
95. A99 BGA59 
96. A100 BGA60 
97. A101 BGA61 
98. A102 BGA62 
99. A144 BGA63 
100. A145 BGA64 
101. A146 BGA65 
102. A147 BGA66 
103. A148 BGA67 
104. A150 BGA68 
105. A152 BGA69 
106. A153 BGA70 
107. A154 BGA71 
2
ST
 PHASE: 
DECOMPRESSION SICKNESS AND TREATMENT 
108. A166 ĐT01 
109. A175 ĐT02 
110. A177 ĐT03 
111. A178 ĐT04 
112. A179 ĐT05 
113. A182 ĐT06 
114. A185 ĐT07 
115. A186 ĐT08 
116. A189 ĐT09 
117. A190 ĐT10 
118. A191 ĐT11 
119. A192 ĐT12 
161 
162 
2ST Appendix 
EXPERIMENTAL HISTORY OF RABBIT 
163 
3rd Appendix 
DEMONSTRATION OF BUBBLE GRADE 
164 
 4th Appendix 
AMERICAN NAVY RECOMPRESSION TREATMENT