18 research outputs found
In vivo colon wall imaging using endoluminal coils: feasibility study on rabbits
International audienc
Effect of chronic oral supplementation with alpha-tocopherol on myocardial stunning in the dog.
International audienceRecent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly understood in humans. Reperfusion-associated myocardial injury, and particularly the phenomenon of stunning, is important because it occurs in clinical settings and may condition the prognosis after short ischemic insult. We studied the effects of chronic (3 months) alpha-tocopherol supplementation with a large oral dose (500 mg daily) on myocardial contractility (stunning) and ventricular arrhythmias in a dog model of short ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha-tocopherol supplemented or a control group. After 3 months, dogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-performance liquid chromatography in all dogs. Twelve dogs (seven supplemented and five controls) developed ventricular fibrillation at reperfusion, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were similar in the two groups. Regional systolic segment shortening in the ischemic area was similar during ischemia and reperfusion in both groups, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-term large dose of alpha-tocopherol had no significant effect on postischaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supplementation might be useful to improve the prognosis of coronary patients, it is likely not by interfering with the stunning phenomenon
Effect of chronic severe diabetes on myocardial stunning in the dog.
International audienceIn this study, we examined whether chronic severe diabetes may affect ischaemic and post-ischaemic regional myocardial dysfunction in vivo in the dog. Diabetes was chemically induced in randomized animals and major metabolic alterations were observed confirming the severity and chronicity of the diabetes. After 70 days, halothane-anaesthetized dogs underwent a 20-min coronary occlusion, followed by reperfusion. During ischaemia, global left ventricle function (dP/dtmax) was more altered (P<0.005) in diabetics ( n=10) than in controls (n=10), whereas area-at-risk (29+/-2.5% of the left ventricle in diabetics v 32.4+/-1.9% in controls) and ischaemic subendocardial myocardial blood flow (radioactive microsphere technique, 0.11+/-0.02 v 0.10+/-0.03 ml/min/g) were similar. During reperfusion, both groups developed significant (P<0.05) regional myocardial dysfunction (somomicrometry, 41+/-14% of baseline in controls and 66+/-8% in diabetics), whereas the difference between groups was not significant. No dog of either group developed myocardial cell necrosis on tissue histology. Multivariate analyses, including the severity of prior ischaemia and the occurrence of ventricular fibrillation as covariables, confirmed that myocardial stunning was not increased in diabetics, although ischaemia was clearly less-well-tolerated in diabetic dogs as global (dP/dtmax) as well as regional myocardial function were significantly (P<0.05) more altered in diabetics during ischaemia. Whilst alteration of arachidonate and cholesterol metabolism may partly explain this apparent paradox, further studies are required to resolve this issue
Improved myocardial tolerance to ischaemia in the diabetic rabbit.
International audienceBecause cardiac complications after myocardial infarction are more frequent in diabetics, we tested whether experimentally-induced diabetes may increase ischaemic myocardial injury in 23 rabbits. Diabetes was induced in randomized rabbits with the alloxan method. After 2 months, diabetic rabbits underwent a 30-min coronary occlusion followed by 3-h reperfusion and were compared with controls. Collateral flow was measured by the radioactive microsphere technique and infarct size by tetrazolium staining. Infarct size represented 28.6+/-4% of area-at-risk in controls and 16.5+/-3% in diabetics (P<0.05). Collateral flow (0.06+/-0.03 ml/min/g in controls and 0.014+/-0.004 ml/min/g in diabetics) and area-at-risk (50.2+/-4.2% of left ventricle in controls and 53.9+/-5. 4% in diabetics) were similar in both groups. There was a significant positive correlation between area-at-risk and infarct size in both groups (r=0.60 and 0.70, respectively) and for a given area-at-risk, diabetic rabbits developed smaller myocardial infarction than controls (covariance analysis, P<0.01). In additional experiments, hyperglycemia induced by intravenous glucose infusion in non-diabetic rabbits did not protect the ischaemic myocardium (infarct size: 37.9+/-12.5%). In conclusion, diabetes in the rabbit induces a chronic and metabolic form of preconditioning. Further studies are needed to explore the mechanism and time course of this protection
Effect of chronic oral supplementation with alpha-tocopherol on myocardial stunning in the dog.
International audienceRecent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly understood in humans. Reperfusion-associated myocardial injury, and particularly the phenomenon of stunning, is important because it occurs in clinical settings and may condition the prognosis after short ischemic insult. We studied the effects of chronic (3 months) alpha-tocopherol supplementation with a large oral dose (500 mg daily) on myocardial contractility (stunning) and ventricular arrhythmias in a dog model of short ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha-tocopherol supplemented or a control group. After 3 months, dogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-performance liquid chromatography in all dogs. Twelve dogs (seven supplemented and five controls) developed ventricular fibrillation at reperfusion, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were similar in the two groups. Regional systolic segment shortening in the ischemic area was similar during ischemia and reperfusion in both groups, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-term large dose of alpha-tocopherol had no significant effect on postischaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supplementation might be useful to improve the prognosis of coronary patients, it is likely not by interfering with the stunning phenomenon
Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion.
International audienceMyocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent postischemic myocardial neutrophil accumulation, and reduce infarct size (IS). Twenty-four dogs were randomized to either a control (saline administration) or a colchicine (1 mg/kg intravenously, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronary artery occlusion followed by 6-h reperfusion. Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex vivo production of reactive oxygen species by chemiluminescence. Myocardial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutrophils (p < 0.01), neutrophil cytotoxicity (p < 0.05), and neutrophil myocardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase was similar in both groups during ischemia /reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were similar in control and treated dogs, there was no reduction in IS: 37.1 +/- 7% of AAR in controls and 37.4 +/- 8% in treated dogs. Despite marked reduction of neutrophil toxicity and postischemic myocardial neutrophil accumulation, no myocardial protection could be detected in this dog model
Cerebral death: Myocardial consequences, an experimental study on pigs
It is well known that brain death is responsible for major problems encountered in the clinical setting that may alter heart graft viability before transplantation. To investigate these myocardial dysfunctions, a model of brain death was prepared in pigs. Anaesthetised pigs were ventilated with FiO2 of 50% through an endotracheal tube. Animals were monitored by measuring systemic arterial pressure, pulmonary artery pressure, cardiac output, left ventricular developed pressure and dP/dT (Millar probe), cardiac contractility (sonomicrometers crystals), ECG, myocardial tissue oedema (impedance spectroscopy) and heart rate. Blood samples were drawn to assess arterial blood gases, serum electrolytes, plasma catecholamine levels, LDH isoenzymes and ascorbil free radicals production. Myocardial high energy contents (adenosine triphosphate, creatine phosphate) were measured by spectroscopy MRI. After 30 minutes stabilisation, brain death was induced by ligation of the supra-aortic vessels. To assess myocardial impairment all the parameters mentioned were recorded at baseline, 1′, 30′, 60′, 120′ and 180′ following the brain death. Results showed initial tachycardia and a significant increase (p < 0.05) in cardiac function at 1′ and 30′, related to the cathecolamine level variations, followed by a significant depression (p < 0.05) of cardiac contractility by the end of the third hour; there was no modification whatsoever of myocardial high energy contents and of ascorbil free radical and LDH isoenzymes productions. In this pig model of brain death the observed myocardial dysfunction was directly related to the induced catecholamine secretion without any myocardial high energy substrate depletion up until 180′. Such results could be taken into account when evaluating a donor heart, allowing to use organs judged nowadays not feasible, and could be of some help in lowering the number of the "défaillances" of the transplanted hearts
Cardiovascular effect of increasing levels of free hemoglobin during cardiopulmonary bypass in swine
Contrast enhancement in atherosclerosis development in a mouse model : in vivo results at 2 Tesla
International audienceTo develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE(-/-) mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T I spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 mu m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice