Dynamic Evaluation of Vinorelbine-Induced Phlebitis of Dorsalis Pedis Vein in a Rat Model

doi:10.12300/j.issn.1674-5817.2024.163

Abstract

Abstract:

Objective To dynamically observe the clinical symptoms and pathological changes in a rat model of vinorelbine-induced phlebitis via injection into the dorsalis pedis vein. Methods Twenty-eight 11-week-old male SPF-grade SD rats were randomly divided into a model group (n=20) and a control group (n=8). The model group received a single injection of 0.1 mL vinorelbine solution (4 mg/mL) via the right hind limb dorsalis pedis vein, while the control group received an equal volume of normal saline via the same method. The occurrence and grading of phlebitis in both groups were observed and recorded daily. The volume of the injured limb was measured by the drainage method to calculate the swelling rate. The weight-bearing ratio of the injured limb was assessed using a bipedal balance pain meter, and the skin temperature of the injured limb was measured by infrared thermal imaging. These measurements were conducted for 9 consecutive days. Starting from day 1, three rats from the model group were euthanized every other day. A 1-cm segment of the vein extending proximally from the injection site was collected. Pathological changes in the vein tissue were examined by hematoxylin-eosin staining, and ultrastructural changes of the vascular endothelium were observed using scanning electron microscopy. Results Compared to the control group, the injected hindlimb of model rats showed redness and swelling on day 1, with the swelling rate peaking at (81.89±15.75) % on day 3 (P<0.001), then gradually alleviating and decreasing to (15.41±0.33) % by day 9 (P<0.01). Pain was observed in the affected limbs of model rats on day 1 and worsened markedly on day 3, with the weight-bearing ratio decreasing to (36.35±4.91)% (P<0.001). Meanwhile, the skin temperature of the lesion site increased, reaching (36.36±0.40) ℃ on day 5 (P<0.001). Both pain and fever returned to near normal levels by day 9. Phlebitis grading in the model group showed that 75.0% of rats were grade Ⅱ on day 1; grade Ⅲ and Ⅳ each accounted for 37.5% on day 3; from days 5 to 9, most rats exhibited cord-like veins, predominantly grade III. Venous tissue showed peripheral edema and inflammatory cell infiltration on day 1, which gradually progressed to intimal rupture, vessel wall thickening, and even lumen narrowing from day 3 to 9. The venous intima exhibited destruction of tight junctions between endothelial cells and adhesion of blood cells, progressing to roughened, wrinkled, and protruding intimal surfaces. Conclusion The vinorelbine-induced phlebitis of dorsal foot vein in rat model is characterized by local redness, swelling, warmth, and pain from days 3 to 5, which largely resolve by day 9, although cord-like veins can still be observed. With disease progression, venous tissue develops edema, vessel wall thickening, and lumen narrowing. The venous intima shows rupture, roughening, and in some cases, complete loss.

Key words: Phlebitis, Dorsalis pedis vein, Vinorelbine, Rats

CLC Number:

Q95-33

JIANG Meng,HAO Shulan,TONG Liguo,et al. Dynamic Evaluation of Vinorelbine-Induced Phlebitis of Dorsalis Pedis Vein in a Rat Model[J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 251-258. DOI: 10.12300/j.issn.1674-5817.2024.163.

Figures/Tables 4

Figure 1 Appearances （A） and infrared thermal images （B） of the injured limbs of phlebitis model rats at different time pointsNote： A， appearance of the injured hindlimb； B， infrared thermal imaging （average temperature： >35.5 ℃ and ≤35.9 ℃， green； >35.9 ℃ and ≤36.5 ℃， blue； >36.5 ℃， red）. The control group rats were injected with 0.1 mL of saline solution into the dorsal vein of the right hind limb， while the model group rats were injected with 0.1 mL of vinorelbine solution （4 mg/mL）. Observation continued for 9 consecutive days. Day 1， Day 3， Day 5， Day 7， and Day 9 refer to the first， third， fifth， seventh， and ninth day after modeling， respectively.

Table 1 Swelling rate, weight-bearing ratio, and average temperature of the injured limb of phlebitis model rats at different time points

时间点 Time points	肿胀率/% Swelling rate/%		承重占比/% Proportion of weight-bearing capacity/%		平均温度/℃ Average temperature/℃
时间点 Time points	对照组 Control group	模型组 Model group	对照组 Control group	模型组 Model group	对照组 Control group	模型组 Model group
Day 1	0.91±0.89	25.49±7.93^**	51.44±0.04	44.58±0.86^**	34.35±0.58	34.75±0.68
Day 3	0.99±0.53	81.89±15.75^***	49.92±1.75	36.35±4.91^***	33.85±0.42	35.17±0.81^**
Day 5	1.51±0.30	63.03±1.41^***	49.49±0.09	44.29±0.08^**	34.03±0.77	36.36±0.40^***
Day 7	1.58±0.44	29.75±5.91^**	49.90±1.85	47.71±0.25	35.10±0.43	35.28±0.80
Day 9	0.30±0.17	15.41±0.33^**	50.86±1.49	49.67±1.19	34.40±0.44	34.88±0.63

Table 2 Grading of phlebitis model rats at different time points

组别 Groups	0级 0 grade	Ⅰ级 Ⅰ grade	Ⅱ级 Ⅱ grade	Ⅲ级 Ⅲ grade	Ⅳ级 Ⅳ grade	P值 P value
Control group	8 (100.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	-
Day 1	0 (0.0)	2 (25.0)	6 (75.0)	0 (0.0)	0 (0.0)	1.000
Day 3	0 (0.0)	0 (0.0)	2 (25.0)	3 (37.5)	3 (37.5)	0.001^***
Day 5	0 (0.0)	0 (0.0)	2 (25.0)	4 (50.0)	2 (25.0)	0.001^***
Day 7	0 (0.0)	0 (0.0)	3 (37.5)	5 (62.5)	0 (0.0)	0.014^*
Day 9	0 (0.0)	0 (0.0)	3 (37.5)	5 (62.5)	0 (0.0)	0.014^*

Figure 2 Histopathology of vein tissues （×400） and microstructure of vascular intima （×1 000） in phlebitis model rats at different time pointsNote： A， histopathological changes of vein tissue stained by hematoxylin-eosin （HE）（green arrows indicate irregular rupture of the inner membrane； black arrows indicate intimal fibrous hyperplasia； red arrows indicate thrombosis）； B， microstructure of vascular intima observed by scanning electron microscopy （SEM）（green arrows indicate inner membrane rupture； black arrows indicate adhesion of blood cells； red arrows indicate elevated endothelial cells）. The control group rats were injected with 0.1 mL of saline solution into the dorsal vein of the right hind limb， while the model group rats were injected with 0.1 mL of vinorelbine solution （4 mg/mL）. Observation continued for 9 consecutive days. Day 1， Day 3， Day 5， Day 7， and Day 9 refer to the first， third， fifth， seventh， and ninth days after modeling， respectively.

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