Assuntos
Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Argentina/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/terapia , Ensaios Clínicos como Assunto , Educação Médica/estatística & dados numéricos , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , América Latina/epidemiologiaRESUMO
BACKGROUND: Blood substitutes are being developed using molecular solutions of modified free hemoglobin; however, anaphylactic reactions, severe renal toxicity, and hypertension have been reported in experimental models and human beings. Hypertension remains as an obstacle to the clinical use of most blood substitutes. Several investigators suggest that this effect is due to the interaction between nitric oxide and hemoglobin into the endothelial cells; hence, prevention of hemoglobin extravasation would avoid vasoconstriction. The forms of hemoglobin likely to prevent extravasation include polymerized and encapsulated Hb. Another alternative and significantly less expensive approach is the hydroxyethyl starch Hb-polymer. The aim of the present study was to compare the effect of hydroxyethyl-starch-hemoglobin with that of stroma-free hemoglobin on the in vitro contractile activity of aortic rings isolated from adult male rats. METHODS: The hemoglobin-based oxygen carrier was made using stroma-free hemoglobin prepared from outdated human red cells and conjugated with 10% hydroxyethyl starch 200-260 MW. The experiments were made in thoracic segments of the aortic rings incubated with hemoglobin, starch-hemoglobin or Ringer Krebs-Bicarbonate solution (RKB) during 30 min. Smooth muscle contraction with phenylephrine and subsequent inhibition of contraction with carbachol were performed before and after incubation with hemoglobin, starch-hemoglobin, or vehicle. RESULTS: Incubation with hemoglobin and starch-hemoglobin significantly increased the contractile response to phenylephrine of aortic rings compared with RKB solution. The maximal response to carbachol was significantly decreased in the aortic rings incubated with either hemoglobin or starch-hemoglobin in comparison with the RKB-incubated tissues. There were no differences between the aortic rings incubated with either hemoglobin, or starch-hemoglobin. CONCLUSIONS: These results show that there are no differences between the effects of stroma-free hemoglobin and starch-hemoglobin on the in vitro contractile activity of aortic rings isolated from adult male rats. Our findings do not support the hypothesis that an increase in the size of the hemoglobin molecule prevents hemoglobin extravasation, and the consequent vasoconstriction due to the scavenging of nitric oxide by stroma free hemoglobin in the cellular space between endothelium and smooth muscle.
Assuntos
Aorta/fisiologia , Substitutos Sanguíneos/farmacologia , Hemoglobinas/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Amido/farmacologia , Animais , Substitutos Sanguíneos/química , Hemoglobinas/química , Masculino , Contração Muscular/fisiologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Amido/químicaRESUMO
INTRODUCTION: Approximately 5% of all cerebrovascular events (CVE), and 10% of those occurring in young patients, are due to hematological disorders. Hypercoagulability states are related to CVE in young patients, deep vein thrombosis, recurrent thromboses, pulmonary embolism, a family history of thrombosis and unusual venous and arterial thromboses. DEVELOPMENT: The conditions related to increased risk of thrombosis are: the congenital thrombophilias due to deficiency of protein C, protein S or antithrombin III, resistance to protein C activated by Leiden's factor V--cofactor of protein C with genetic mutation--; the primary antiphospholipid syndrome with anticardiolipin antibodies and lupus inhibitor; platelet disorders, deficit of heparin cofactor II, deficit of plasminogen and plasminogen tissue activator (t-PA) and increase in the inhibitor of plasminogen tissue activator (PAI-I); alterations in factors of coagulation such as deficits of factor VII and factor XIII, mutation of prothrombin 20210-->A, increase in factor VIII. Hyperfibrinogenemia and hyperhomocysteinemia are also independent risk factors for CVE. CONCLUSION: The patients, especially young patients, with recurrent thrombosis or thrombosis of unknown origin should be assessed seeking clinical and serological signs of the primary antiphospholipid syndrome or other coagulopathies. Although we still have no results of controlled prospective studies regarding these conditions, long term anticoagulation is recommended on the findings of small-scale retrospective studies.