Acute myocardial infarction in dogs with experimental diabetes.

International audienceOBJECTIVE: The aim was to examine whether diabetes interferes with the development of myocardial injury in a canine ischaemia-reperfusion model. METHODS: Non-insulin-requiring diabetes was induced in dogs by the streptozotocin-alloxan method. After 75 d, the dogs were anaesthetised and myocardial infarction was provoked by occluding the left anterior descending coronary artery for 2 h followed by 6 h reperfusion. RESULTS: Diabetic dogs had higher blood glucose [9.4(SEM 1) mmol.litre-1], fructosamine [417(57) mumol.litre-1], and glycated haemoglobin [3.3(0.7)%], than control dogs [5.5(0.6), p = 0.04, 243(15), p = 0.01, and 0.7(0.2), p = 0.003, respectively], and they also had higher serum lipids (p = 0.001) and platelet aggregation (p = 0.03). Area at risk was similar in diabetic and control dogs but in contrast to controls (r = 0.78, p = 0.007), area at risk and infarct size were not correlated in diabetics (r = 0.08). In both groups, collateral flow was the major determinant of infarct size: r = -0.73 in controls (p = 0.02) and -0.97 in diabetics (p = 0.001). In spite of higher subendocardial collateral flow in diabetics [representing 21.6(6)% of the flow in the corresponding non-ischaemic zone] than in controls [11.2(6)%], infarct size was similar in both groups. However, the mean observed infarct size in the diabetic group [7.5(2.8)% of the left ventricle] was significantly (p < 0.03) larger than the mean predicted infarct size [5.2(2)%]. Multivariate analysis confirmed that diabetes, as well as collateral flow, is an independent (p = 0.03) predictor of infarct size. CONCLUSIONS: For a given collateral flow, diabetic dogs develop larger infarcts than controls. Further studies are required to investigate the biochemical mechanism(s) underlying this deleterious effect. However, this may partly explain the poor prognosis of myocardial infarction in diabetic persons

Acute myocardial infarction in dogs with experimental diabetes.

International audienceOBJECTIVE: The aim was to examine whether diabetes interferes with the development of myocardial injury in a canine ischaemia-reperfusion model. METHODS: Non-insulin-requiring diabetes was induced in dogs by the streptozotocin-alloxan method. After 75 d, the dogs were anaesthetised and myocardial infarction was provoked by occluding the left anterior descending coronary artery for 2 h followed by 6 h reperfusion. RESULTS: Diabetic dogs had higher blood glucose [9.4(SEM 1) mmol.litre-1], fructosamine [417(57) mumol.litre-1], and glycated haemoglobin [3.3(0.7)%], than control dogs [5.5(0.6), p = 0.04, 243(15), p = 0.01, and 0.7(0.2), p = 0.003, respectively], and they also had higher serum lipids (p = 0.001) and platelet aggregation (p = 0.03). Area at risk was similar in diabetic and control dogs but in contrast to controls (r = 0.78, p = 0.007), area at risk and infarct size were not correlated in diabetics (r = 0.08). In both groups, collateral flow was the major determinant of infarct size: r = -0.73 in controls (p = 0.02) and -0.97 in diabetics (p = 0.001). In spite of higher subendocardial collateral flow in diabetics [representing 21.6(6)% of the flow in the corresponding non-ischaemic zone] than in controls [11.2(6)%], infarct size was similar in both groups. However, the mean observed infarct size in the diabetic group [7.5(2.8)% of the left ventricle] was significantly (p < 0.03) larger than the mean predicted infarct size [5.2(2)%]. Multivariate analysis confirmed that diabetes, as well as collateral flow, is an independent (p = 0.03) predictor of infarct size. CONCLUSIONS: For a given collateral flow, diabetic dogs develop larger infarcts than controls. Further studies are required to investigate the biochemical mechanism(s) underlying this deleterious effect. However, this may partly explain the poor prognosis of myocardial infarction in diabetic persons

Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects

Three independent, phase 1 clinical trials were conducted in Australia and in USA to assess the safety and immunogenicity of sanofi pasteur dengue vaccine candidates. In this context, Dengue 1-4 and Yellow Fever 17D-204 (YF 17D)-specific CD4 and CD8 cellular responses induced by tetravalent chimeric dengue vaccines (CYD) were analyzed in flavivirus-naive or flavivirus-immune patients. Tetravalent CYD vaccine did not trigger detectable changes in serum pro-inflammatory cytokines, whatever the vaccinees immune status, while inducing significant YF 17D NS3-specific CD8 responses and dengue serotype-specific T helper responses. These responses were dominated by serotype 4 in naive individuals, but a booster vaccination (dose #2) performed 4 months following dose #1 broadened serotype-specific responses. A similar, broader response was seen after primary tetravalent immunization in subjects with pre-existing dengue 1 or 2 immunity caused by prior monovalent live-attenuated dengue vaccination. In all three trials, the profile of induced response was similar, whatever the subjects' immune status, i.e. an absence of Th2 response, and an IFN-gamma/TNF-alpha ratio dominated by IFN-gamma, for both CD4 and CD8 responses. Our results also showed an absence of cross-reactivity between YF 17D or Dengue NS3-specific CD8 responses, and allowed the identification of 3 new CD8 epitopes in the YF 17D NS3 antigen. These data are consistent with the previously demonstrated excellent safety of these dengue vaccines in flavivirus-naive and primed individuals.Bruno Guy, Nolwenn Nougarede, Sarah Begue, Violette Sanchez, Nadia Souag, Murielle Carre, Laurent Chambonneau, Dennis N. Morrisson, David Shaw, Ming Qiao, Rafaele Dumas, Jean Lang and Remi Forra