Cardiac output by MR imaging: an experimental study comparing right ventricle and left ventricle with thermodilution

Cardiac output was measured by gated magnetic resonance imaging (MRI) and by thermodilution in four mongrel dogs. The entire heart was examined in contiguous slices at end-diastole and end-systole in a plane parallel to the interventricular septum. Each set of images was analyzed for chamber volume using a custom computer program to evaluate each pixel. No geometric assumptions were made. Cardiac output was calculated for right and left ventricles and compared with the thermodilution data. We found that the cardiac output of the right ventricle compared well with that of the left ventricle and that both fell within the range measured by thermodilution. Cardiac-gated MRI has the potential to assess the cardiac output of both the right and left ventricles. Comparison between right ventricular and left ventricular function will permit quantification of left to right shunting or unilateral ventricular volume overload.     

Acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system.

BACKGROUND: A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. METHODS: Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for alphavbeta3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of alphavbeta3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p < 0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy specimens, and 3 of 14 patients experienced hemodynamic compromise and graft dysfunction and died within 3 weeks of transplant. Another patient died at 10 months after transplant. CONCLUSIONS: Acute vascular rejection is associated with up-regulation of alphavbeta3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.     

Prostacyclin acts in rat gastric (fundic) mucosa via the intracellular ‘second messenger system’

Using a specific radioimmunoassay technique it seems that Prostacyclin (PG-I₂) has a strong effect on the cyclic nucleotide content of the rat gastric (fundic) mucosa. 1 min after an intragastric application of 100 g/kg PG-I₂ the cAMP-content and in the 5th min the cGMP-content showed a highly significant decrease. It seems that the basic mechanism of action of PG-I₂ is a typical hit and run effect, acting on the intracellular second messenger system.     

Cyclooxygenase-2 expression in colorectal cancer liver metastases

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n=25; score 2, n=29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan–Meier survival analysis and log rank test, both P=0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.