Allograft-induced arterial wall injury and response in normotensive and spontaneously hypertensive rats.

Plissonnier, Didier; Lévy, Bernard; Salzmann, Jean-Loup; Nochy, Dominique; Watelet, J; Michel, Jean Baptiste

doi:10.1161/01.atv.11.6.1690

Cited by 36 publications

(18 citation statements)

References 36 publications

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“…The present study confirms our previous histological descriptions 8 and those of Schmitz-Rixen et al, 5 Mennander et al, 712 and Hayry et al 6 Chronic arterial allograft rejection is a model of immune response-induced arterial wall injury. The medial necrosis is the consequence of the immune injury, whereas intimal proliferation represents the arterial wall response.…”

Section: Discussionsupporting

confidence: 92%

“…In our first study, 8 we demonstrated that the isografts did not significantly differ from the aortas of shamoperated control animals. Therefore, 10 syngeneic isografts were performed for each strain (SHR and WKY), which served as controls.…”

Section: Experimental Designmentioning

confidence: 79%

“…In this aortic allograft model, adventitial inflammatory cell infiltration provides evidence of the rejection process, injury is indicated by medial smooth muscle cell necrosis and breaks in the medial extracellular matrix, and intimal cellular proliferation and extracellular matrix accumulation are a measure of the vascular wall response. 8 Hypertension increases the intimal proliferative response, and vasodilatator treatment, which induces a fall in blood pressure, decreases the intimal thickness in this model 9 in the same way that hypertension and its treatment modify the intimal response to balloon-induced deendothelialization and smooth muscle stretch. 10 ' 11 High doses of cyclosporin prevent immune injury in this model of the aortic allograft in rats.…”

mentioning

confidence: 73%

“…There were also some differences between the two strains; these have been described in more detail in our first study. 8 Allografted aortas were characterized by a significant increase in adventitial cell density (Table 4). The relation between rejection and arterial wall injury and response was indicated by the positive correlation between the intima/ media thickness ratio and the density of adventitial inflammatory cells in untreated allografts (r=0.53, F=5.5, p<0.01) and the positive correlation between adventitial inflammatory cell and medial smooth muscle cell densities (r=0.7, F=12.5,/?<0.005).…”

Section: Morphological and Morphometric Resultsmentioning

confidence: 99%

“…), and the aortic graft volumes were determined by in vivo catheterization and isolation of the grafted segments. 8 The catheter was filled with Evans blue dye and connected to a pressure transducer for simultaneous measurement of pressure and volume. The volume of the aortic segment at a pressure of 75 mm Hg was recorded for each rat.…”

Section: Measurement Of Aortic Graft Volumesmentioning

confidence: 99%

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Additive and synergistic effects of a low-molecular-weight, heparin-like molecule and low doses of cyclosporin in preventing arterial graft rejection in rats.

Plissonnier

Amichot

Lecagneux

et al. 1993

Arterioscler Thromb

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Arteriosclerotic intimal proliferation is one of the main long-term complications of organ transplantation. Low-molecular-weight, heparin-like molecules prevent myointimal proliferation in arterial wall injury and limit rejection in skin allografts. Cyclosporin limits rejection but has no major effect on intimal proliferation. Therefore, an experimental protocol was designed to test whether heparin-like molecules interacted with low doses of cyclosporin to prevent arterial wall immune system injury and response in a model of arterial graft rejection in normotensive and hypertensive rats. Aortic allografts were performed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats. Four groups of 10 allografted (SHR and WKY) rats were used: one group was treated with placebo, one with low doses of cyclosporin (2 nig/kg body wt per day), one with low-molecular-weight, heparin-like molecule (1 nig/kg body wt per hour), and one with low doses of cyclosporin plus low-molecular-weight, heparin-like molecule. Ten SHRs and 10 WKYs were isografted and served as the control groups. All rats were killed 8 weeks after aortic grafting. Structural parameters of the grafted segment were measured by morphometric analysis on formalin-fixed sections with specific stains. The classical signs of immune system injury and response were present in the untreated allografts in SHRs and WKYs: inflammatory infiltration of the adventitia, medial injury, and intimal proliferative response. Low doses of cyclosporin had a significant beneficial effect on immune medial injury by increasing medial thickness and the number of remaining smooth muscle cells and decreasing the extracellular matrix injury. Cyclosporin had no protective effect on intimal proliferation. Low-molecularweight, heparin-like molecules had a beneficial effect on both the medial injury and the intimal proliferative response that was independent of blood pressure. Heparin-like molecules increased medial thickness and partially prevented smooth muscle cell loss and extracellular matrix attack. They also significantly decreased the intimal thickness by acting more on the collagen content than on the smooth muscle cell density. Low doses of cyclosporin plus heparin-like molecules had a marked effect in preventing the arterial wall injury and response. This combination resulted in a normal medial appearance, increased medial thickness and smooth muscle cell number, and no intimal proliferation or adventitial inflammation. Thus, heparin-like molecules appear to act in concert with low doses of cyclosporin in preventing rejection-induced arterial wall remodeling in an experimental model of aortic allograft in rats, and their effects are independent of blood pressure. (Arteriosclerosis and Thrombosis 1993;13:112-119)

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Section: Discussionsupporting

confidence: 92%

Section: Experimental Designmentioning

confidence: 79%

mentioning

confidence: 73%

Section: Morphological and Morphometric Resultsmentioning

confidence: 99%

Section: Measurement Of Aortic Graft Volumesmentioning

confidence: 99%

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