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L Zezina

Publications and source records attributed to L Zezina.

11 recordsLinked to original sources
PubMed2001

Candesartan cilexetil reduces graft arteriosclerosis in aortic transplantation model in rat.

To date established treatment of transplant arteriosclerosis is basically missing and there is a need for new therapeutic approaches. Angiotensin II (Ang II) and Ang II receptor type 1 (AT) are present in the vascular wall. Blocking of the AT1 receptor by pharmacological agents may inhibit damaging effects of Ang II on endothelial and smooth muscle cells. The purpose of the study was to evaluate the effect of the AT1 receptor blocker Candesartan cilexetil on the development of graft arteriosclerosis in a rat aortic transplant model. Two strain combinations were used for aortic transplantation: DA to PVG; and PVG to PVG. The animals received Candesartan cilexetil treatment (9.5 + 1.4 mg/kg/day) for 8 weeks. Candesartan cilexetil treatment reduced neointimal formation both in allografts (Qint 30.2 +/- 8.8% vs. 22.1 +/- 8.7%, P < 0.05) and in isografts (Qint 15.5 +/- 4.4% vs. 6.7 +/- 3.3%, P = 0.0001). Blocking of the AT1 receptor signalling by Candesartan cilexetil was also associated with a reduced expression of TGF-beta1. Macrophage infiltration was not affected by the treatment. Candesartan cilexetil treatment leads to reduced neointimal formation in aortic transplant. The positive effect of the drug might be partly explained by a reduction of TGF-beta1 expression in the grafts. Candesartan treatment may provide another possibility for prevention of transplant arteriosclerosis and chronic rejection.

Animals↗
PubMed1999

Carvedilol treatment of kidney graft recipients with chronic rejection.

Carvedilol is an antihypertensive drug with properties that may be potentially beneficial for kidney graft recipients. The purpose of the study was to investigate if progression of an established chronic rejection may be attenuated or reversed by carvedilol. An open, single-centre, phase II, pilot study, with a 2-yr follow-up, was performed in 25 kidney graft recipients with chronic rejection or accelerated transplant atherosclerosis. Seventeen patients had stable graft function assessed by serum creatinine levels. Eight patients withdrew from the study due to lack of efficacy (increase in serum creatinine 174-477 micromol/L (46-191%) from the initial levels). However. these patients had higher serum creatinine levels and proteinuria already at the start of the study. Both systolic and diastolic blood pressure, as well as heart rate, were stable in all study patients. Low density lipoprotein (LDL)/high density lipoprotein (HDL) cholesterol ratio decreased from 4.7 +/- 1.9 at 1 month to 3.5 +/- 1.2 at 18 months (p < 0.05), and MDA plasma levels decreased from 0.714 +/- 0.119 to 0.493 +/- 0.073 micromol/L after 3 months of carvedilol treatment (p < 0.05). No attenuation of progression of chronic graft rejection by carvedilol treatment was observed in the study. It is suggested that the process of chronic rejection could not be reversed by carvedilol because the patients included in the study already had severe morphological and functional changes of the graft. In conclusion, our study demonstrated that carvedilol provides a good control of blood pressure in renal transplanted patients. Carvedilol treatment had a beneficial effect on lipid pattern and reduced lipid oxidation, but there was no obvious effect on progression of chronic rejection.

Adult↗
PubMed1997

Elevation of cyclosporin A blood levels during carvedilol treatment in renal transplant patients.

In a consecutive study of 21 renal transplant patients suffering from chronic vascular rejection (CVR) we added the beta-receptor-blocking drug carvedilol to their regular medication. The purpose was to investigate possible pharmacokinetic interactions between carvedilol and cyclosporine (CsA), since carvedilol will soon be used in clinical trials in renal transplant patients with CVR. On the first day of the study the patients received 6.25 mg of carvedilol added to their daily medication. The dose was increased stepwise to 50 mg while the doses of other beta-blocking drugs were decreased. The goal was to exchange atenolol with carvedilol at a ratio of 2:1 when substituting atenolol with carvedilol. The patients' blood pressure was the final determinant of the dose of carvedilol. The trough levels of CsA were measured on days 1, 14, 30, 90 and 180. It was found that the blood levels of CsA increased when carvedilol was introduced. Thus, the doses of CsA had to be reduced in order to keep the blood levels within the therapeutic range. At 90 d, the daily doses of CsA had been reduced from 3.7 +/- 0.3 to 3.0 +/- 0.2 mg/kg BW (p < 0.001). The present results suggest an interaction between carvedilol and CsA that demands a 20% average reduction of CsA doses to maintain the CsA blood levels within the therapeutic range. However, the interaction shows a great interindividual variation, calling for careful monitoring of the CsA blood levels.

Adrenergic beta-Antagonists↗