RESUMO
BACKGROUND: Haemoglobin-based oxygen carriers (HBOC) seem to increase the risk of mortality and myocardial infarction in clinical trials. Therefore, we designed this randomized placebo-controlled animal study to evaluate the effects of prophylactic and therapeutic administration of HBOC in a myocardial ischaemia-reperfusion model with respect to infarct size and areas of impaired perfusion (no reflow, NR). METHODS: Thirty-two anaesthetized, mechanically ventilated rabbits were randomized to one of the four groups. Group G1 received 0.4 g kg(-1) i.v. HBOC-200 25 min before coronary artery occlusion, G2 received the same dose i.v. 10 min after occlusion, and G3 and 4 received i.v. saline. G1, 2, and 3 were subjected to 30 min occlusion of left coronary artery followed by 240 min of reperfusion. G4 was treated without ischaemia-reperfusion. Measurement included assessment of the area at risk and infarct size using triphenyltetrazolium chloride stain and areas of NR using thioflavin stain. Ischaemia-reperfusion was confirmed by microspheres technique. RESULTS: Infarct size as a percentage of the area at risk was significantly reduced in G1 [25 (sd 13)%, P=0.026] and G2 [22 (20)%, P=0.009] compared with G3 [48 (17)%]. The areas of NR in percentage of the area at risk [G1, 26 (15)%; G2, 34 (22)%; G3, 36 (12)%; G4, 5 (3)%] did not differ between the groups of animals undergoing coronary occlusion and reperfusion. CONCLUSIONS: Prophylactic and therapeutic administration of HBOC-200 reduces infarct size in myocardial ischaemia and reperfusion in rabbits. This reduction of infarct size is not accompanied by an improvement of areas of NR.
Assuntos
Substitutos Sanguíneos/uso terapêutico , Hemoglobinas/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Bovinos , Circulação Coronária/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Oxigênio/sangue , Pressão Parcial , CoelhosRESUMO
A theoretical account is given of methods for validation of diagnostic procedures, with reference being made to literature quoted in surgical journals. Wider use of those methods is recommended to ensure more economy, effectiveness, and higher scientific standards in every-day routine.