Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury

Douglas A. Coe, Julie A. Freischlag, Dawn Johnson, Junaid H. Mudaliar, Scott A. Kosciesza, David K. Traul, Phillip C. Chiang, Robert A. Cambria, Gary R. Seabrook, Jonathan B. Towne

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background. Endothelial injury after ischemia and reperfusion is characterized by an increase in permeability, cellular edema, and loss of acetylcholine-mediated vasorelaxation. Three hours of ischemia followed by 2 hr of reperfusion in the New Zealand white rabbit hindlimb has been shown to result in loss of acetylcholine-induced superficial femoral artery vasorelaxation. The purpose of this study was to evaluate the effect of intraarterial pentoxyfylline (PTX) on this endothelial injury. Methods. New Zealand white rabbits underwent 3 hr of complete hindlimb ischemia followed by 2 hr of reperfusion. Twenty milliliters of either 100 μM PTX or normal saline was infused over 20 min via the circumflex iliac artery at initiation of reperfusion. Superficial femoral artery rings were then evaluated in vitro for endothelial cell-mediated relaxation. Rings were exposed to standardized incremental doses of acetylcholine after norepinephrine-induced contraction and percentage relaxation was measured. Sections of arteries were also sent for hematoxylin and eosin staining. Results. Similar contraction responses following NE stimulation were observed between control and PTX-treated rings. Control rings relaxed a mean of 14.97 ± 3.64, 23.17 ± 5.61, and 31.84 ± 8.43% in response to acetylcholine doses of 6 x 10-8, 1 x 10-7, and 1.5 x 10-7 M, respectively. In contrast, PTX-treated segments relaxed a mean of 47.52 ± 8.88, 62.32 ± 6.83, and 76.73 ± 4.91% to the same doses of acetylcholine. Differences in relaxation between control and PTX-treated vessels were significantly different at each dose (P < 0.05, Student's t test). Histologic examination of the PTX-treated and control arteries revealed an intact endothelium without morphologic differences between the two groups. Conclusion. In this model of rabbit hindlimb ischemia, endothelial cell-mediated vasorelaxation was preserved with the administration of intraarterial PTX during reperfusion compared to controls. The different relaxation responses could not be attributed to altered arterial contractility in response to norepinephrine, or explained by histologic changes in the arterial wall. These studies demonstrate a potential modality for therapeutic intervention to reduce reperfusion injury after acute limb ischemia.

Original languageEnglish (US)
Pages (from-to)21-25
Number of pages5
JournalJournal of Surgical Research
Volume67
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

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Pentoxifylline
Reperfusion Injury
Acetylcholine
Reperfusion
Hindlimb
Ischemia
Vasodilation
Femoral Artery
Rabbits
Norepinephrine
Endothelial Cells
Arteries
Iliac Artery
Hematoxylin
Eosine Yellowish-(YS)
Endothelium
Permeability
Edema
Extremities
Staining and Labeling

ASJC Scopus subject areas

  • Surgery

Cite this

Coe, D. A., Freischlag, J. A., Johnson, D., Mudaliar, J. H., Kosciesza, S. A., Traul, D. K., ... Towne, J. B. (1997). Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. Journal of Surgical Research, 67(1), 21-25. https://doi.org/10.1006/jsre.1996.4940

Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. / Coe, Douglas A.; Freischlag, Julie A.; Johnson, Dawn; Mudaliar, Junaid H.; Kosciesza, Scott A.; Traul, David K.; Chiang, Phillip C.; Cambria, Robert A.; Seabrook, Gary R.; Towne, Jonathan B.

In: Journal of Surgical Research, Vol. 67, No. 1, 01.1997, p. 21-25.

Research output: Contribution to journalArticle

Coe, DA, Freischlag, JA, Johnson, D, Mudaliar, JH, Kosciesza, SA, Traul, DK, Chiang, PC, Cambria, RA, Seabrook, GR & Towne, JB 1997, 'Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury', Journal of Surgical Research, vol. 67, no. 1, pp. 21-25. https://doi.org/10.1006/jsre.1996.4940
Coe DA, Freischlag JA, Johnson D, Mudaliar JH, Kosciesza SA, Traul DK et al. Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. Journal of Surgical Research. 1997 Jan;67(1):21-25. https://doi.org/10.1006/jsre.1996.4940
Coe, Douglas A. ; Freischlag, Julie A. ; Johnson, Dawn ; Mudaliar, Junaid H. ; Kosciesza, Scott A. ; Traul, David K. ; Chiang, Phillip C. ; Cambria, Robert A. ; Seabrook, Gary R. ; Towne, Jonathan B. / Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. In: Journal of Surgical Research. 1997 ; Vol. 67, No. 1. pp. 21-25.
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AU - Freischlag, Julie A.

AU - Johnson, Dawn

AU - Mudaliar, Junaid H.

AU - Kosciesza, Scott A.

AU - Traul, David K.

AU - Chiang, Phillip C.

AU - Cambria, Robert A.

AU - Seabrook, Gary R.

AU - Towne, Jonathan B.

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N2 - Background. Endothelial injury after ischemia and reperfusion is characterized by an increase in permeability, cellular edema, and loss of acetylcholine-mediated vasorelaxation. Three hours of ischemia followed by 2 hr of reperfusion in the New Zealand white rabbit hindlimb has been shown to result in loss of acetylcholine-induced superficial femoral artery vasorelaxation. The purpose of this study was to evaluate the effect of intraarterial pentoxyfylline (PTX) on this endothelial injury. Methods. New Zealand white rabbits underwent 3 hr of complete hindlimb ischemia followed by 2 hr of reperfusion. Twenty milliliters of either 100 μM PTX or normal saline was infused over 20 min via the circumflex iliac artery at initiation of reperfusion. Superficial femoral artery rings were then evaluated in vitro for endothelial cell-mediated relaxation. Rings were exposed to standardized incremental doses of acetylcholine after norepinephrine-induced contraction and percentage relaxation was measured. Sections of arteries were also sent for hematoxylin and eosin staining. Results. Similar contraction responses following NE stimulation were observed between control and PTX-treated rings. Control rings relaxed a mean of 14.97 ± 3.64, 23.17 ± 5.61, and 31.84 ± 8.43% in response to acetylcholine doses of 6 x 10-8, 1 x 10-7, and 1.5 x 10-7 M, respectively. In contrast, PTX-treated segments relaxed a mean of 47.52 ± 8.88, 62.32 ± 6.83, and 76.73 ± 4.91% to the same doses of acetylcholine. Differences in relaxation between control and PTX-treated vessels were significantly different at each dose (P < 0.05, Student's t test). Histologic examination of the PTX-treated and control arteries revealed an intact endothelium without morphologic differences between the two groups. Conclusion. In this model of rabbit hindlimb ischemia, endothelial cell-mediated vasorelaxation was preserved with the administration of intraarterial PTX during reperfusion compared to controls. The different relaxation responses could not be attributed to altered arterial contractility in response to norepinephrine, or explained by histologic changes in the arterial wall. These studies demonstrate a potential modality for therapeutic intervention to reduce reperfusion injury after acute limb ischemia.

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