Pathophysiological Effects of Cold Environment on Gastrointestinal Blast Combined Injury in Beagle Dogs

doi:10.12300/j.issn.1674-5817.2025.179

Abstract

Abstract:

Objective To investigate the impact of a cold environment on the pathophysiological changes in dogs after abdominal gastrointestinal blast injury. Methods Eight healthy common-grade adult male Beagles were selected and randomly divided into a cold group and a normal temperature group, with 4 dogs in each group. Prior to surgery, Beagles dogs were fasted and deprived of water for 12 hours; after establishing a vein at the edge of the ear, propofol （2 mg·kg^-1·min^-1） was continuously infused using a microinfusion pump to maintain anesthesia. Tracheal intubation was performed while preserving spontaneous breathing, and the electroencephalogram bifrequency index was maintained at 40-60 to ensure stable anesthesia. A model of abdominal gastrointestinal blast injury in Beagle dogs was established using a multifunctional combat trauma modeling platform. After blast injury, the cold group was exposed to a cold chamber at -20 ℃ combined with 10% body surface area ice water immersion for 40 min, while the normal temperature group was kept in an environment at (25±2) ℃ for 40 min after blast injury. Vital signs such as heart rate, blood pressure, and blood oxygen saturation were monitored in both groups before blast injury, immediately after blast injury, and 40 min after blast injury. And arterial blood gas parameters, including pH, partial pressure of oxygen in arterial blood (PaO₂), partial pressure of carbon dioxide in arterial blood (PaCO₂), actual bicarbonate radical (HCO₃^-), lactic acid (Lac), and blood base excess (BEb), were measured. After the experiment, gastrointestinal tissues (gastric antrum and upper jejunum 5 cm distal to the suspensory ligament of the duodenum) were harvested for pathological analysis via hematoxylin-eosin (HE) staining combined with semi-quantitative scoring. Results Physiological indicators showed that the body temperature of the cold group was significantly lower than that of the normal temperature group (P<0.01), and the heart rate and systolic blood pressure of the cold group were significantly higher than those of the normal temperature group (P<0.000 1). PaCO₂ was markedly elevated and BEb was markedly decreased in the cold group relative to the normal temperature group (P<0.000 1), suggesting aggravated respiratory acidosis and metabolic acidosis. Pathological analysis showed that gastro-intestinal tissue damage was more severe in the cold group: the gastric mucosal epithelial shedding rate was > 60% (vs. <25% in the normal temperature group), the necrosis rate of the epithelial cells at the tips of intestinal villi reached more than 70% (vs. < 30% in the normal temperature group), and inflammatory cell infiltration involved the submucosa (vs. limited to the superficial mucosa in the normal temperature group). The semi-quantitative scoring results were consistent with the pathological analysis results, further confirming that the cold environment exacerbated gastrointestinal tissue damage caused by abdominal gastrointestinal blast injury. Conclusion A cold environment can exacerbate circulatory dysfunction and gastrointestinal tissue damage in Beagle dogs after blast injury, providing experimental evidence for early rewarming intervention for combat trauma in cold regions.

Key words: Cold environment, Gastrointestinal tissue, Blast injury, Combined injury, Beagle dogs

CLC Number:

R-332

GONG Tiantian,WANG Xinpei,GUO Tiange,et al. Pathophysiological Effects of Cold Environment on Gastrointestinal Blast Combined Injury in Beagle Dogs[J]. Laboratory Animal and Comparative Medicine, 2026, 46(4): 507-514. DOI: 10.12300/j.issn.1674-5817.2025.179.

Figures/Tables 5

Table 1 Semi-quantitative scoring standard for gastrointestinal tissue injury

评估维度 Assessment dimension	0分（正常） 0 points （Normal）	1分（轻度损伤） 1 point （Mild injury）	2分（中度损伤） 2 points （Moderate injury）	3分（重度损伤） 3 points （Severe injury）
黏膜完整性 Mucosal integrity	结构完整、无破损	局灶性黏膜破损	多处黏膜破损	大面积破损、黏膜下层裸露
上皮细胞脱落情况 Epithelial cell desquamation status	排列整齐、无脱落	局灶性脱落	片状脱落	大面积脱落
炎症细胞浸润情况 Inflammatory cell infiltration status	无或有少量固有层淋巴细胞	黏膜浅层局灶性浸润	黏膜全层片状浸润	黏膜和黏膜下层广泛浸润
固有层水肿情况 Lamina propria edema status	结构清晰、无水肿	轻度水肿	中度水肿	结构紊乱、重度水肿
细胞坏死情况 Cell necrosis status	无坏死细胞	个别上皮细胞坏死	局部细胞坏死	大片细胞坏死

Note： T， body temperature； HR， heart rate； SO?， peripheral blood oxygen saturation； SBP， systolic blood pressure； DBP， diastolic blood pressure. Compared with normal temperature group， ^nsP>0.05， ^**P<0.01， ^****P<0.000 1.
">

Figure 1 Comparison of basic physiological indicators of Beagle dogs in the normal temperature group and cold group before blast， immediately after blast and 40 min after blast
Note： T， body temperature； HR， heart rate； SO?， peripheral blood oxygen saturation； SBP， systolic blood pressure； DBP， diastolic blood pressure. Compared with normal temperature group， ^nsP>0.05， ^**P<0.01， ^****P<0.000 1.

Note： PaO₂， partial pressure of oxygen in arterial blood； PaCO₂， partial pressure of carbon dioxide in arterial blood； HCO₃^-， actual bicarbonate radical； Lac， lactic acid； BEb， blood base excess. Compared with normal temperature group， ^nsP>0.05， ^****P<0.000 1.
">

Figure 2 Comparison of blood gas-related indicators of Beagle dogs in the normal temperature group and cold group before blast， immediately after blast and 40 min after blast
Note： PaO₂， partial pressure of oxygen in arterial blood； PaCO₂， partial pressure of carbon dioxide in arterial blood； HCO₃^-， actual bicarbonate radical； Lac， lactic acid； BEb， blood base excess. Compared with normal temperature group， ^nsP>0.05， ^****P<0.000 1.

Note： A， gastric tissue section of the cold group； B， gastric tissue section of the normal temperature group； C， small intestinal tissue section of the cold group； D， small intestinal tissue section of the normal temperature group. The scale bars in the first and second columns are 100 μm and 20 μm， respectively.
">

Figure 3 HE-stained images of gastrointestinal tissue of Beagle dogs in the normal temperature group and cold group
Note： A， gastric tissue section of the cold group； B， gastric tissue section of the normal temperature group； C， small intestinal tissue section of the cold group； D， small intestinal tissue section of the normal temperature group. The scale bars in the first and second columns are 100 μm and 20 μm， respectively.

Table 2 Semi-quantitative scoring of gastrointestinal tissue injury in Beagle dogs of normal temperature group and cold group

检测指标 Detection indicators		常温组 Normal temperature group				寒冷组 Cold group
检测指标 Detection indicators		A1	A2	A3	A4	C1	C2	C3	C4
胃组织 Gastric tissue	黏膜完整性 Mucosal integrity	3	1	2	2	2	3	2	3
	上皮细胞脱落情况 Epithelial cell desquamation status	2	2	3	1	3	2	3	2
	炎症细胞浸润情况 Inflammatory cell infiltration status	1	2	3	2	3	3	2	3
	固有层水肿情况 Lamina propria edema status	2	1	2	1	3	2	3	3
	细胞坏死情况 Cell necrosis status	1	2	1	3	2	3	2	3
	总分 Total score	9	8	11	9	13	13	12	14
	$x ¯ ± s$	9.25±1.26				13.00±0.82*
小肠组织 Small intestinal tissue	黏膜完整性 Mucosal integrity	2	3	2	2	3	3	3	3
	上皮细胞脱落情况 Epithelial cell desquamation status	2	1	3	2	3	3	3	3
	炎症细胞浸润情况 Inflammatory cell infiltration status	3	2	2	3	3	2	2	3
	固有层水肿情况 Lamina propria edema status	2	3	3	3	3	3	2	3
	细胞坏死情况 Cell necrosis status	2	2	2	2	3	3	3	3
	总分 Total score	11	11	12	12	15	14	13	15
	$x ¯ ± s$	11.5±0.56				14.25±0.96^*

Table 2 Semi-quantitative scoring of gastrointestinal tissue injury in Beagle dogs of normal temperature group and cold group

检测指标 Detection indicators		常温组 Normal temperature group				寒冷组 Cold group
检测指标 Detection indicators		A1	A2	A3	A4	C1	C2	C3	C4
胃组织 Gastric tissue	黏膜完整性 Mucosal integrity	3	1	2	2	2	3	2	3
	上皮细胞脱落情况 Epithelial cell desquamation status	2	2	3	1	3	2	3	2
	炎症细胞浸润情况 Inflammatory cell infiltration status	1	2	3	2	3	3	2	3
	固有层水肿情况 Lamina propria edema status	2	1	2	1	3	2	3	3
	细胞坏死情况 Cell necrosis status	1	2	1	3	2	3	2	3
	总分 Total score	9	8	11	9	13	13	12	14
	$x ¯ ± s$	9.25±1.26				13.00±0.82*
小肠组织 Small intestinal tissue	黏膜完整性 Mucosal integrity	2	3	2	2	3	3	3	3
	上皮细胞脱落情况 Epithelial cell desquamation status	2	1	3	2	3	3	3	3
	炎症细胞浸润情况 Inflammatory cell infiltration status	3	2	2	3	3	2	2	3
	固有层水肿情况 Lamina propria edema status	2	3	3	3	3	3	2	3
	细胞坏死情况 Cell necrosis status	2	2	2	2	3	3	3	3
	总分 Total score	11	11	12	12	15	14	13	15
	$x ¯ ± s$	11.5±0.56				14.25±0.96^*

References 24

[1]	MARTINDALE S L, ORD A S, RULE L G, et al. Effects of blast exposure on psychiatric and health symptoms in combat veterans[J]. J Psychiatr Res, 2021, 143: 189-195. DOI: 10.1016/j.jpsychires.2021.09.021 .
[2]	EDWARDS D S, MCMENEMY L, STAPLEY S A, et al. 40 years of terrorist bombings-A meta-analysis of the casualty and injury profile[J]. Injury, 2016, 47(3): 646-652. DOI: 10.1016/j.injury.2015.12.021 .
[3]	OWERS C, MORGAN J L, GARNER J P. Abdominal trauma in primary blast injury[J]. Br J Surg, 2011, 98(2): 168-179. DOI: 10.1002/bjs.7268 .
[4]	PUMIGLIA L, WILLIAMS J M, PREY B J, et al. Hypothermia and the global war on terror: 18 years of minimal progress[J]. Mil Med, 2024, 189(): 190-195. DOI: 10.1093/milmed/usae072 .
[5]	陈园, 王占鹏, 李庆新. 爆炸伤合并冻复合伤相关机制研究进展[J]. 医学理论与实践, 2023, 36(4): 582-585. DOI: 10.19381/j.issn.1001-7585.2023.04.013 .
	CHEN Y, WANG Z P, LI Q X. Research progress on related mechanism of explosive injury combined with frozen combined injury[J]. J Med Theory Pract, 2023, 36(4): 582-585. DOI: 10.19381/j.issn.1001-7585.2023.04.013 .
[6]	FENG Z H, HU Y, YU S, et al. Exercise in cold: Friend than foe to cardiovascular health[J]. Life Sci, 2023, 328: 121923. DOI: 10.1016/j.lfs.2023.121923 .
[7]	杨志焕, 朱佩芳, 蒋建新, 等. 水下冲击波致犬腹部脏器损伤的病理形态学改变[J]. 中国危重病急救医学, 2004, 16(4): 226-228. DOI: 10.3760/j.issn: 1003-0603.2004.04.010 .
	YANG Z H, ZHU P F, JIANG J X, et al. Pathomorphological changes in abdominal viscerae in dogs subjected to underwater blast wave injury[J]. Chin Crit Care Med, 2004, 16(4): 226-228. DOI: 10.3760/j.issn: 1003-0603.2004.04.010 .
[8]	PENG Y Y, LU X M, LI S, et al. Effects and mechanisms of extremely cold environment on body response after trauma[J]. J Therm Biol, 2023, 114: 103570. DOI: 10.1016/j.jtherbio. 2023.103570 .
[9]	CILSAL E. In newly diagnosed hypertensive children, increased arterial stiffness and reduced heart rate variability were associated with a non-dipping blood pressure pattern[J]. Rev Port Cardiol (Engl Ed), 2020, 39(6): 331-338. DOI: 10.1016/j.repc. 2020.02.009 .
[10]	MOORE E E, COGBILL T H, MALANGONI M A, et al. Organ injury scaling, Ⅱ: Pancreas, duodenum, small bowel, colon, and rectum[J]. J Trauma, 1990, 30(11): 1427-1429.
[11]	CHIU C J. Intestinal mucosal lesion in low-flow states. Ⅰ. Amorphological, hemodynamic, and metabolic reappraisal[J]. Arch Surg, 1970, 101(4): 478. DOI: 10.1001/archsurg. 1970. 01340280030009 .
[12]	SIEBERT U, STÜRZNICKEL J, SCHAFFELD T, et al. Blast injury on harbour porpoises (Phocoena phocoena) from the Baltic Sea after explosions of deposits of World War Ⅱ ammunition[J]. Environ Int, 2022, 159: 107014. DOI: 10.1016/j.envint.2021. 107014 .
[13]	CARDI M, IBRAHIM K, ALIZAI S W, et al. Injury patterns and causes of death in 953 patients with penetrating abdominal war wounds in a civilian independent non-governmental organization hospital in Lashkargah, Afghanistan[J]. World J Emerg Surg, 2019, 14: 51. DOI: 10.1186/s13017-019-0272-z .
[14]	PAWLAK-CHOMICKA R, URUSKI P, KRAUZE T, et al. Arterial blood pressure features of hypertensive patients with typical and atypical 460 nm skin fluorescence response to transient ischaemia[J]. J Clin Med, 2023, 12(18): 5886. DOI: 10.3390/jcm12185886 .
[15]	KENNEY M J, CLAASSEN D E, FELS R J, et al. Cold stress alters characteristics of sympathetic nerve discharge bursts[J]. J Appl Physiol, 1999, 87(2): 732-742. DOI: 10.1152/jappl. 1999.87.2.732 .
[16]	CHENG H M, LI G, DAI J F, et al. A fluid-structure interaction model accounting arterial vessels as a key part of the blood-flow engine for the analysis of cardiovascular diseases[J]. Front Bioeng Biotechnol, 2022, 10: 981187. DOI: 10.3389/fbioe. 2022.981187 .
[17]	王温, 孙嘉岑, 谭兴, 等. 寒冷对心血管疾病的影响: 现状与机制[J]. 海军军医大学学报, 2023, 44(6): 741-748. DOI: 10.16781/j.CN31-2187/R.20230140 .
	WANG W, SUN J C, TAN X, et al. Effects of cold exposure on cardiovascular diseases: status and mechanism[J]. Acad J Nav Med Univ, 2023, 44(6): 741-748. DOI: 10.16781/j.CN31-2187/R.20230140 .
[18]	PATEL P N, HORENSTEIN M S, ZWIBEL H. Exercise physiology[M]. Treasure Island (FL): StatPearls Publishing, 2025.
[19]	VAN VEELEN M J, BRODMANN MAEDER M. Hypothermia in trauma[J]. Int J Environ Res Public Health, 2021, 18(16): 8719. DOI: 10.3390/ijerph18168719 .
[20]	GROESSL S, KALIS R, SNAEBJORNSSON M T, et al. Acidosis orchestrates adaptations of energy metabolism in tumors[J]. Science, 2025, 390(6769): eadp7603. DOI: 10.1126/science.adp7603 .
[21]	ROLVER M G, CAMACHO-RODA J, DAI Y F, et al. Tumor microenvironment acidosis favors pancreatic cancer stem cell properties and in vivo metastasis[J]. iScience, 2025, 28(3): 111956. DOI: 10.1016/j.isci.2025.111956 .
[22]	FERNÁNDEZ L G. Treatment of complex thoracic and abdominal trauma patients: a review of literature and negative pressure wound therapy treatment options[J]. Adv Wound Care, 2024, 13(8): 416-423. DOI: 10.1089/wound. 2023. 0113 .
[23]	LA H BROWN T, SKINNER A M. Burn injury care for Special Forces and far-forward deployed troops[J]. Mil Med, 2005, 170(11): 919-920. DOI: 10.7205/milmed.170.11.919 .
[24]	SAXENA B, SINGH S. Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease[J]. Drug Discov Ther, 2017, 11(2): 98-103. DOI: 10.5582/DDT.2016.01081 .