RESUMO
The effect of aprotinin, a protease inhibitor, on myocardial interleukin-8 (IL-8) production after ischemia-reperfusion injury was investigated. Twenty patients who had elective coronary artery bypass grafting were included in this study. Patients were randomly divided into two groups (n = 10 in each). Group A patients received high dose aprotinin (20,000 IU/kg as pretreatment followed by 7500 IU/kg for 6 h) and Group B patients received normal saline as a control. Serum IL-8 levels after the termination of cardiopulmonary bypass (CPB) showed a significant improvement in aprotinin treated group compared to control group (70 +/- 42.6 vs 360.71 +/- 87.9 ng/ml) (P < 0.005). Levels were also significantly higher at post-operative 24th hour in patients who did not received aprotinin (340.16 +/- 92.10 vs 96.13 +/- 34.33 ng/ml). However at post-operative 48th hour levels were again higher in control (untreated) group, but the difference was not statistically significant (78.8 +/- 34.4 vs 42.8 +/- 9.29 ng/ml). Aprotinin prevented the IL-8 release from myocytes in ischemia-reperfusion injury. The mechanism is highly dependent on anti-protease activity of aprotinin.
Assuntos
Aprotinina/administração & dosagem , Ponte de Artéria Coronária , Interleucina-8/sangue , Traumatismo por Reperfusão Miocárdica/imunologia , Complicações Pós-Operatórias/imunologia , Adulto , Idoso , Aprotinina/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/diagnóstico , Miocárdio/imunologia , Complicações Pós-Operatórias/diagnósticoRESUMO
There is substantial evidence that Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase enzymes would effect the membrane integrity. Forty guinea pig (n=10 in each group) hearts were studied in an isolated Krebs-Henseleit solution perfused Langendorff cardiac model. The first group was utilized as the control group. Group 2 hearts were arrested with captopril (200micromol/l) added St Thomas Hospital Cardioplegic Solution (STHCS). Group 3 animals were pretreated with oral captopril (0.3mg/kg/twice a day) for 10days and then arrested with STHCS. Group 4 hearts were again pretreated with oral captopril (0.3mg/kg/twice a day for 10days) arrested with STHCS and reperfused with captopril added Krebs-Henseleit solution (200micromol/l). Hearts were subjected to normothermic global ischemia for 90min and than were reperfused at 37 degrees C. When the treated groups were compared with control, best results were achived by group 4. The Na(+)K(+) and Ca(2+)/Mg(2+) ATPase levels increased from 466.38+/-5.99 to 564.13+/-7.77 and 884.69+/-9.13 to 1254.29+/-5.75 nmol Pi/mg/prot/h respectively (P<0.05). These results suggest that captopril protects the membrane integrity and thus played a role at the recovery of depressed membrane bound Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase activity and also in ischemia-reperfusion injury.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Membrana Celular/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Bicarbonatos/farmacologia , Cloreto de Cálcio/farmacologia , Captopril/administração & dosagem , Soluções Cardioplégicas/farmacologia , Membrana Celular/enzimologia , Estudos de Avaliação como Assunto , Glucose/farmacologia , Cobaias , Técnicas In Vitro , Magnésio/farmacologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Cloreto de Potássio/farmacologia , Distribuição Aleatória , Cloreto de Sódio/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico , Trometamina/farmacologiaRESUMO
An insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) is associated with myocardial infarction and other cardiac pathology. There is evidence for a role of the renin-angiotensin system in cell growth and in the repair of damaged arterial walls, so the ACE gene is postulated to be a candidate gene affecting the important clinical problem of coronary artery disease (CAD). In view of the clinical importance of the ACE as a major marker of cardiovascular diseases, we investigated the I/D polymorphism of the ACE gene in Turkish CAD patients in comparison with control subjects to evaluate a possible association between CAD and the gene encoding ACE. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used to determine the ACE genotype in 58 subjects. The frequencies of ACE D and ACE I allele among the patients with CAD were 62.26% and 37.73 % and in the control subjects were 49.3% and 50.76%, respectively. The greater frequency of deletion allele (D) was in the CAD group than in the control subjects was significant (P < 0.01).
Assuntos
Doença das Coronárias/enzimologia , Doença das Coronárias/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , TurquiaRESUMO
In humans, thrombosis and neointimal hyperplasia are the major factors responsible for prosthetic graft occlusion. Previous studies suggest that the renin-angiotensin system is one of the key enzymes in the vascular system and has been implicated in the pathogenesis of thrombosis and neointimal hyperplasia. We conducted a case-control study to determine the frequency of the different angiotensin-converting enzyme (ACE) genotypes among the patients who had PTFE graft implantation for hemodialysis access. Between 1997 and 1999, 30 graft implantations were performed. Twelve individuals (40%) developed thrombotic complications, 8 of the 12 patients had ACE ID polymorphism, and 2 patients had DD and 2 patients had II polymorphism. The ID polymorphism was significantly more frequent in the thrombosed arteriovenous (A-V) grafts than in nonthrombosed A-V grafts (chi2 = 7.57 and p = 0.02). Overall, the frequency of the D and I alleles was 66.6 and 33.3%, respectively. In conclusion, ID polymorphism of the ACE gene plays an important role in the pathogenesis of vascular access thrombosis in subjects undergoing hemodialysis for chronic renal failure.