Inhaled aerosolised recombinant human activated protein C ameliorates endotoxin-induced lung injury in anaesthetised sheep.

INTRODUCTION: We recently demonstrated that intravenously infused recombinant human activated protein C (APC) attenuates ovine lipopolysaccharide (LPS)-induced lung injury. In this study, our aim was to find out whether treatment with inhaled aerosolised APC (inhAPC) prevents formation of increased lung densities and oedema and derangement of oxygenation during exposure to LPS. METHODS: Sheep were anaesthetised during placement of intravascular introducers. After one to four days of recovery from instrumentation, the animals were re-anaesthetised, endotracheally intubated and mechanically ventilated throughout a six-hour experiment where the sheep underwent quantitative lung computed tomography. Sheep were randomly assigned to one of three groups: a sham-operated group (n = 8) receiving inhaled aerosolised saline from two hours after the start of the experiment; a LPS group (n = 8) receiving an intravenous infusion of LPS 20 ng/kg per hour and, after two hours, inhaled aerosolised saline over the next four hours; a LPS+inhAPC group (n = 8) receiving an intravenous infusion of LPS 20 ng/kg per hour and, after two hours, aerosolised APC 48 microg/kg per hour inhaled throughout the experiment. Data were analysed with analysis of variance; P less than 0.05 was regarded as significant. RESULTS: An infusion of LPS was associated with a reduction of well-aerated lung volume and a rapid fall in arterial oxygenation that were both significantly antagonised by inhaled APC. Pulmonary vascular pressures and extravascular lung water index increased significantly during exposure to LPS, but inhaled APC had no effect on these changes. CONCLUSIONS: Inhalation of aerosolised APC attenuates LPS-induced lung injury in sheep by preventing a decline in the volume of aerated lung tissue and improving oxygenation.

Coronary artery disease cannot be reliably evaluated by 16-slice multidetector spiral computed tomography.

OBJECTIVES: Angiography by selective catheterization is the standard method for coronary artery imaging but carries a risk of rare, but serious complications. We investigated whether 16-slice multidetector spiral computed tomography (MDCT) could substitute for selective angiography for evaluation of coronary artery disease in surgically revascularized patients. DESIGN: In a setting closely resembling routine clinical practice, 45 patients who had been operated with coronary artery bypass grafting 508-1135 (mean 811) days before were examined with MDCT and conventional selective angiography on the same day. The interpreters were blinded to the results of the parallel imaging modality. RESULTS: Significant pathology (stenosis >/=50% or occlusion) in the larger coronary artery segments was detected by MDCT with a sensitivity of 70-98% (mean 87%) and a specificity of 0-37% (mean 21%). MDCT failed to identify three of ten left main stem stenoses. CONCLUSION: Sixteen-slice MDCT cannot routinely replace selective angiography for evaluation of coronary artery disease.

Coronary bypass graft patency cannot be determined by multidetector spiral computed tomography.

OBJECTIVES: Angiography by selective catheterization is the reference standard for coronary bypass graft patency assessment but carries a risk of serious complications. We have investigated whether 16-slice multidetector spiral computed tomography (MDCT) can substitute for selective angiography. DESIGN: Two to three years after coronary artery bypass grafting, 45 patients with a total of 156 bypasses (100 single and 28 sequential grafts) were examined with both MDCT and conventional selective angiography on the same day. The bypasses were classified as patent, stenotic or occluded. RESULTS: The likelihood ratio for MDCT-detected occlusion was 40, reflecting a fairly high combined sensitivity and specificity. However, 24% of the distal anastomoses could not be evaluated by MDCT, mainly because of respiratory movements, artifacts due to metal clips, and small vessel dimensions. Moreover, seven out of 117 bypasses (6%) deemed evaluable by MDCT were wrongly classified by this method. CONCLUSIONS: At present, 16-slice MDCT cannot replace selective angiography for assessment of coronary bypass graft patency since 24% of bypasses could not be evaluated by this method, and an error rate of 6% is unacceptable.