J. Garcia Campos

The pyrimido-pyrimidine derivatives, dipyridamole, mopidamol and RA-642, prevent from retinal vascular defects in experimental diabetes mellitus.

We compared the effects of dipyridamole, RA-642, and mopidamol on platelet activity and thromboxane/prostacyclin balance in relation to the degree of retinal vascularization in a model of experimental streptozotocin-induced diabetes in rats. After 3 months, collagen-induced platelet aggregation in whole blood was 25% higher in diabetic animals than in nondiabetics. Dipyridamole inhibited 43% platelet aggregation, mopidamol 39%, and RA-642 36%. Platelet production of thromboxane B2 was 87% higher in untreated diabetic rats. Mopidamol and RA-642 produced a 46% and 41% inhibition of thromboxane B2. Dipyridamole did not inhibited thromboxane B2 synthesis. Aortic production of 6-keto-PGF1 alpha was 43% lower in untreated diabetic animals and showed no change after treatment with either mopidamol or RA-642. In contrast, dipyridamole caused a 90% increase in aortic production of prostacyclin. Computerized analysis of retinal vascularization showed that untreated diabetic rats had a 81% decrease in the area occupied by peroxidase-labelled vessels as compared with nondiabetics. Treatment with dipyridamole, mopidamol, and RA-642 caused 2.5-fold, 2.8-fold and four-fold increases, respectively, in the percentage of retinal surface occupied by peroxidase-labelled vessels. Differences in retinal vascularization between diabetic animals given RA-642 and nondiabetic controls were negligible.

Effects of Ditazol on the Vascular Retinal Pattern in Experimental Diabetes in Rats

Platelets from diabetic patients are hypersensitive to aggregating agents. An imbalance in thromboxane/prostacyclin synthesis has been postulated as an antecedent to the development of diabetic retinopathy. We studied 3-month streptozotocin-diabetic rats (SDR) treated with 200 mg/kg/day p.o. of ditazol, an antiplatelet drug that inhibits thromoboxane formation. Thromboxane B2 (TxB2) production was higher and 6-keto-PGF1 alpha synthesis lower in SDR than nondiabetic rats (NDR). In treated animals, ditazol inhibited platelet aggregation by 66%, and TxB2 production by 58%, and increased vascular 6-keto-PGF 1 alpha by 45%. Furthermore, 13% of the retinal surface was covered by peroxidase-labelled vessels in NDR, 2.1% in nontreated SDR, and 8.9% in SDR treated with ditazol. We postulate that ditazol may prevent or reduce diabetic retinopathy.

P 334 Hyperactivity of platelet function in human diabetes mellitus is different according to the type of retinopathy

e. Then, are not references in the liiratura about th+ posibilitv that the platelet hvperanivitv in diabetic patients is different according to the tvpe of retinqmtbv. The aim d the pmumt studv is tq evatuat4 the platelet function in insulin-dependent diebetes meliitus (IDDM) with different tvpes of retinopatv. &U&A, The study was carried put on 20 healthy vok~ntews IHV), 20 tDDM patients withwt retirmpNbv IDWRI, 16 IDDM patients with background mtirmpathv fD6RI. 25 IDDM patkne with ischasmic-prdiative retinopathv IOIRI, and 19 IDDM patients with exudative mtirmpsthv (DERI. In blood samples. we studied platelet agOm&wnetry Msted in plate&t&h plasma -PRPand whole blood) indumd bv ADP and cdlag%n. platelet production of thromboune 6, ITx6,) and II-thmmbcgtobulin I6TG), platelet releaw of ATP. and ewthracvm uptake of tnimMiM. Em&a. Platdet aporwntion in PRP wa* not statisticallv diem between OWUM fp<O.Zl. In whole blood. the concentration of ADP tumc#L) that inhibiis 50% the maximal pht&t aqpmqation, was 1.61 *0.07 in HV, 1.26*0.00 in DWR,0.62tO.OBinDBR,0.56iD.04inDtR,ond0.36+0.02inDER.Platelet a~rtqattm induced bv edlew! , and the other parameters of platelet activation, &wad a qualitative similar bahwkwr that the ADP-induced pIat& awranatton. Ths ewthmcvta of th4 HV incmaead cdlwen-indwxd datelnt &&ion in FUP bv 23.6 * 1.6%. in DWR bv 27.1 i 2.2%. in. D6R by 30.8~35%. in DIR bv 35.3+3.B%. and in OER bv 46k3.396. Ervthmcvtn uptake of &n~sine &is hipher in.diabetics than. in HV. and th& wen, siqniliativr finssr cwrelatioru bawsen this parameter and all the others that indkxted pktmbt activation. CwM&&n& We conclude that the diibetic Dfatstet hvoeractivitv is related with mythtacyte ftmctlon. perhaps by its hiik capacity if keep out adenosine fmmthemediumintDDMwith re*lorwthv. Mwmr, in whda Mocd. plank4 EXPERIMENTAL DIABETIC RETINOPATHY: INFLUENCE OF SEVERAL ANTIPLATELET DRUGS

P 335 Experimental diabetic retinopathy: Influence of several antiplatelet drugs

e. Then, are not references in the liiratura about th+ posibilitv that the platelet hvperanivitv in diabetic patients is different according to the tvpe of retinqmtbv. The aim d the pmumt studv is tq evatuat4 the platelet function in insulin-dependent diebetes meliitus (IDDM) with different tvpes of retinopatv. &U&A, The study was carried put on 20 healthy vok~ntews IHV), 20 tDDM patients withwt retirmpNbv IDWRI, 16 IDDM patients with background mtirmpathv fD6RI. 25 IDDM patkne with ischasmic-prdiative retinopathv IOIRI, and 19 IDDM patients with exudative mtirmpsthv (DERI. In blood samples. we studied platelet agOm&wnetry Msted in plate&t&h plasma -PRPand whole blood) indumd bv ADP and cdlag%n. platelet production of thromboune 6, ITx6,) and II-thmmbcgtobulin I6TG), platelet releaw of ATP. and ewthracvm uptake of tnimMiM. Em&a. Platdet aporwntion in PRP wa* not statisticallv diem between OWUM fp<O.Zl. In whole blood. the concentration of ADP tumc#L) that inhibiis 50% the maximal pht&t aqpmqation, was 1.61 *0.07 in HV, 1.26*0.00 in DWR,0.62tO.OBinDBR,0.56iD.04inDtR,ond0.36+0.02inDER.Platelet a~rtqattm induced bv edlew! , and the other parameters of platelet activation, &wad a qualitative similar bahwkwr that the ADP-induced pIat& awranatton. Ths ewthmcvta of th4 HV incmaead cdlwen-indwxd datelnt &&ion in FUP bv 23.6 * 1.6%. in DWR bv 27.1 i 2.2%. in. D6R by 30.8~35%. in DIR bv 35.3+3.B%. and in OER bv 46k3.396. Ervthmcvtn uptake of &n~sine &is hipher in.diabetics than. in HV. and th& wen, siqniliativr finssr cwrelatioru bawsen this parameter and all the others that indkxted pktmbt activation. CwM&&n& We conclude that the diibetic Dfatstet hvoeractivitv is related with mythtacyte ftmctlon. perhaps by its hiik capacity if keep out adenosine fmmthemediumintDDMwith re*lorwthv. Mwmr, in whda Mocd. plank4 EXPERIMENTAL DIABETIC RETINOPATHY: INFLUENCE OF SEVERAL ANTIPLATELET DRUGS