Symptomatic and pathological features in chemical phlebitis rat model by injection vinorelbine via dorsal pedal vein.

Abstract

Intravenous administration of vesicants or irritants frequently leads to chemical phlebitis. We aimed to establish a chemical phlebitis rat model by injection vinorelbine via dorsal pedal vein and evaluate the general symptoms as well as the pathological features of lesion venous tissues. Rats in 6 groups with each 8 were injected 0.1 mL saline or vinorelbine (1-5 mg/mL) via the dorsalis pedis vein in hind paw, respectively. The edema and pain were assessed daily by swelling rates (water displacement) and weight-bearing ratio (bipedal balance test), respectively. Phlebitis severity was evaluated by phlebitis scale. Venous tissues harvested on day 7 were underwent histopathological and ultrastructural evaluation. Vinorelbine administration elicited dose-dependent inflammatory responses, with erythema, edema, pain, palpable cord formation, and purulent drainage. Edema and pain peaked on day 3, as evidenced by increased swelling rates and reduced weight-bearing ratios. Persistent symptomatology was observed in the 3-5 mg/mL groups through day 7. Histopathological analysis demonstrated venous wall thickening characterized by intimal hyperplasia and collagen deposition, along with vascular lumen stenosis accompanied by thrombosis. Furthermore, disruption of the intimal lining was observed, with shrunken endothelial cells interspersed among extracellular matrix. These pathological changes also exhibited a dose-dependent exacerbation with increasing concentrations of vinorelbine. Dorsal pedal vein injection of 0.1 mL vinorelbine (3-5 mg/mL) successfully induced chemical phlebitis in rats, mimicking human clinical presentations. Furthermore, vinorelbine-induced endothelial damage resulted in distinct venous lesions, characterized by vascular wall thickening with intimal hyperplasia, luminal stenosis and thrombus.