Gadolinium:nonionic contrast media (1:1) coronary angiography in patients with impaired renal function

This study was to test safety and efficacy of 1:1 mixture of gadolinium:nonionic contrast media in avoiding contrast nephropathy during coronary angiography in patients with renal dysfunction. Although "off label" for x-ray angiography, gadolinium has drawn attention for its potential to avoid contrast nephropathy during coronary angiography. Initial data seem promising. Patients with a baseline creatinine of 1.5 mg/dl or more were included. In order to minimize contrast nephropathy risk, all patients were thoroughly hydrated and treated by N-acetylcysteine. After coronary angiography and/or percutaneous coronary intervention, renal function tests were remeasured on days 1, 2, and 3. A rise of 0.5 mg/dl or more in creatinine value in the following 3 days or the need for dialysis were considered as a contrast nephropathy event. Twenty-six patients were enrolled in this study. Ten were women and 16 were men. The mean age was 65.7 +/- 11. Baseline creatinine value was 2.47 +/- 0.74 mg/dl. The total amount of contrast medium used on 1:1 fashion was 57.1 +/- 27.2 ml. No procedure-related cardiac complication or contrast nephropathy event occurred in this study. Although there was a slight loss in image quality, we felt that the results were adequate for interpretation. Although "off label," using gadolinium contrast media in a 1:1 mixture with standard nonionic low osmolar contrast media seems to be a viable option in decreasing the likelihood of contrast nephropathy. Further evaluation appears to be warranted.     

Nitrite directly vasodilates hypoxic vasculature via nitric oxide-dependent and -independent pathways

Background and purpose:

It is postulated that nitrite requires reduction to nitric oxide in order to exert its relaxant effect upon isolated hypoxic vessels. Herein, we evaluate the relative contribution of nitric oxide and characterize the downstream mechanisms of nitrite-induced vasorelaxation.

Experimental approach:

Aortic rings were treated with pharmacological agents and exposed to hypoxia (<1% O₂). Following pre-constriction, nitrite (10 µM final) was added to appropriate baths; isometric tension was recorded throughout.

Key results:

Nitrite (under hypoxic conditions at physiological pH) is capable of exerting physiological effects that cannot be completely inhibited by the inhibitor of soluble guanylate cyclase (sGC), 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or a nitric oxide scavenger (carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide). Simultaneous blockade of both sGC and cyclooxygenase (COX) completely inhibited the response to nitrite. With regard to the nitric oxide-dependent component, we confirm that aldehyde oxidase, but not xanthine oxidase or endothelial nitric oxide synthase, was important for the actions of nitrite in our model.

Conclusions and implications:

Nitric oxide generated from nitrite is not exclusively responsible for the physiological actions observed in isolated hypoxic vessels. Nitrite operates via different pathways dependent on the presence or absence of endothelium to produce vasorelaxation. In intact vessels, both sGC and COX enzymes appear to be important. Irrespective of this difference in relaxation mechanism, nitrite is capable of producing the same maximum relaxation, regardless of the presence of endothelium. Having investigated possible nitrite reduction sites, we confirm that aldehyde oxidase is important for the actions of nitrite.     

Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients

BACKGROUND: There is increasing evidence for acute traumatic coagulopathy occurring prior to emergency room (ER) admission but detailed information is lacking. PATIENTS AND METHODS: A retrospective analysis using the German Trauma Registry database including 17,200 multiple injured patients was conducted to determine (a) to what extent clinically relevant coagulopathy has already been established upon ER admission, and whether its presence was associated (b) with the amount of intravenous fluids (i.v.) administered pre-clinically, (c) with the magnitude of injury, and (d) with impaired outcome and mortality. Eight thousand seven hundred and twenty-four patients with complete data sets were screened. RESULTS: Coagulopathy upon ER admission as defined by prothrombin time test (Quick's value) <70% and/or platelets <100,000 microl(-1), was present in 34.2% of all patients. There was an increasing incidence for coagulopathy with increasing amounts of i.v. fluids administered pre-clinically. Coagulopathy was observed in >40% of patients with >2000 ml, in >50% with >3000 ml, and in >70% with >4000 ml administered. Ten percentage of patients presented with clotting disorders although pre-clinical resuscitation was limited to 500 ml of i.v. fluids maximum. The mean ISS score in the coagulopathy group was 30 (S.D. 15) versus 21 (S.D. 12) (p<0.001). Twenty-nine percentage of patients with coagulopathy developed multi organ failure (p<0.001). Early in-hospital mortality (<24h) was 13% in patients with coagulopathy (p<0.001) and overall in-hospital mortality totalled 28% (p<0.001). CONCLUSION: There is a high frequency of established coagulopathy in multiple injury upon ER admission. The presence of early traumatic coagulopathy was associated with the amount of intravenous fluids administered pre-clinically, magnitude of injury, and impaired outcome.     

Sustained long-term benefit of sildenafil in primary pulmonary hypertension

Primary pulmonary hypertension is a rare disease with an ominous prognosis for which new therapeutic options are being developed. Recently, there have been case reports indicating that sildenafil may be of benefit in short- to midterm follow-up. However, long-term clinical data of sildenafil in primary pulmonary hypertensive patients is lacking. We report a patient with primary pulmonary hypertension treated with sildenafil 200 mg/day for 50 months with a sustained clinical response.