Severe Cutaneous and Venous Damage after DIC Therapy

Yuasa, Tetsuya; Taniguchi, Yoshiki; Yamada, Eigo; Inachi, Shin; Shimizu, Masayuki

doi:10.1111/j.1346-8138.1997.tb02821.x

Cited by 10 publications

(6 citation statements)

References 8 publications

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“…Moreover, swelling and roundness were observed in cells treated with GM at the same dose. In clinical studies, intravenous infusion of GM at 0.2% (this concentration corresponds to 4.78 mM) or more often causes serious vascular injury (4). The present results suggest that endothelial cell injury contributes to the vascular adverse effects of GM.…”

Section: Discussionmentioning

confidence: 49%

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Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

et al. 2008

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Abstract. Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury, when injected in high concentration. In the present study, we investigated the mechanisms for the cytotoxicity of GM on porcine aorta endothelial cells (PAECs). GM (0.5 -5.0 mM) decreased cell viability in a dose-dependent manner and caused cell injury, whilst nafamostat mesilate (NM), another serine protease inhibitor, or mesilate itself had no effect on cell viability. zVAD-fmk, a pancaspase inhibitor, or zDEVD-fmk, a caspase-3 inhibitor, did not affect the GM (1.5 mM)-induced decrease of cell viability. Apoptotic cells or DNA fragmentation were also not observed after GM treatment. Moreover, Ca 2+ chelators, a nitric oxide (NO) synthase inhibitor, antioxidants, and radical scavengers had no effect on the GM-induced cell injury. On the other hand, cellular ATP content was decreased in the GM (2.0 mM)-treated cells. Surprisingly, GM (2.0 mM) immediately increased cellular uptake of propidium iodine. These findings suggest that GM induces necrotic cell death via injury of the cell membrane.

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Section: Discussionmentioning

confidence: 49%

“…However, the intravenous injection of GM often causes vascular related adverse reactions such as local pain, phlebitis, and edema. When the symptoms are severe, surgery such as debridement or skin grafting is carried out (4). GM has also been reported to cause vascular injury in rabbit ear veins (5).…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

et al. 2008

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“…Although these attractive pharmacological profiles, one of the dose-limiting factors of NIC is severe peripheral vascular injury after intravenous injection (Wallin et al, 1988). In severe cases, surgery such as debridement or skin grafting must be carried out (Yuasa et al, 1997). Thus, reduction of vascular injury after intravenous injection of NIC would facilitate treatment and improve the patient's quality of life.…”

Section: Introductionmentioning

confidence: 99%

Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

Ochi¹,

Kawai

Tanaka³

et al. 2015

J. Toxicol. Sci.

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-Nicardipine hydrochloride (NIC), a dihydropyridine calcium-channel blocking agent, has been widely used for the treatment of hypertension. Especially, nicardipine hydrochloride injection is used as first-line therapy for emergency treatment of abnormally high blood pressure. Although NIC has an attractive pharmacological profile, one of the dose-limiting factors of NIC is severe peripheral vascular injury after intravenous injection. The goal of this study was to better understand and thereby reduce NIC-mediated vascular injury. Here, we investigated the mechanism of NIC-induced vascular injury using human dermal microvascular endothelial cells (HMVECs). NIC decreased cell viability and increased percent of dead cells in a dose-dependent manner (10-30 μg/mL). Although cell membrane injury was not significant over 9 hr exposure, significant changes of cell morphology and increases in vacuoles in HMVECs were observed within 30 min of NIC exposure (30 μg/mL). Autophagosome labeling with monodansylcadaverine revealed increased autophagosomes in the NIC-treated cells, whereas caspase 3/7 activity was not increased in the NIC-treated cells (30 μg/mL). Additionally, NIC-induced reduction of cell viability was inhibited by 3-methyladenine, an inhibitor of autophagosome formation. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy could contribute to the reduction of NIC-induced vascular injury.

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“…However, NIC injection causes peripheral vascular injury at the injection site (Wallin et al, 1988). In severe cases, surgery such as debridement or skin grafting must be carried out (Yuasa et al, 1997), placing increased demands on the medical staff's time and raising medical costs. Thus, reducing vascular injury after intravenous injection of NIC would improve the patient's quality of life and reduce complications.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of <i>N</i>-acetylcysteine against nicardipine hydrochloride-induced autophagic cell death of human vascular endothelial cells

Ochi¹,

Tanaka²,

Toyoda³

2015

J. Toxicol. Sci.

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-Nicardipine hydrochloride (NIC) injection has been widely used for emergency treatment of abnormally high blood pressure. However, NIC injection often causes severe peripheral vascular injury. The purpose of the present study was to reduce the NIC-induced cell injury in human vascular endothelial cells by use of clinical agents. The mechanism of NIC-induced cell injury was evaluated by time-lapse microscopic imaging, autophagosome staining with monodansylcadaverine, immunostaining of light chain 3 isoform B (LC-3B) and assessment of cell viability after exposure to NIC with or without an inhibitor of autophagosome formation (3-methyladenine, 3-MA). Results from autophagosome labeling and immunostaining of LC-3B revealed an increase of autophagosomes and LC-3B in NIC-treated cells. NIC-mediated reduction of cell viability was inhibited by 3-methyladenine. Moreover, we found that N-acetylcysteine (NAC) reduced NIC-induced cell injury in human vascular endothelial cells. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy with NAC could contribute to the reduction of NIC-induced vascular injury.

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Severe Cutaneous and Venous Damage after DIC Therapy

Cited by 10 publications

References 8 publications

Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

Protective effect of <i>N</i>-acetylcysteine against nicardipine hydrochloride-induced autophagic cell death of human vascular endothelial cells

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