PEROXYNITRITE: A MEDIATOR OF INCREASED MICROVASCULAR PERMEABILITY?

1. Increased expression of inducible nitric oxide synthase (iNOS) and subsequent elevation of nitric oxide (NO) levels at inflammatory sites have led to the suggestion that peroxynitrite (the reaction product of superoxide and NO) is involved in proinflammatory processes. The present study has investigated the ability of peroxynitrite to induce oedema formation in the rat cutaneous microvasculature. 2. Peroxynitrite was synthesized from hydrogen peroxide and acidified nitrite. Spectrophotometry was used to measure the concentration and breakdown of peroxynitrite. It was also used to determine maximum amounts of hydrogen peroxide and sodium nitrite remaining after synthesis. 3. Oedema formation in response to intradermall. (i.d.) injected peroxynitrite, hydrogen peroxide and sodium nitrite was measured by the extra vascular accumulation of i.v. [¹²⁵I]-albumin in the anaesthetized rat. 4. Peroxynitrite (40,100 and 200 nmol/site) acted in a dose-dependent manner to cause a mean (± SEM) increase in plasma extravasation of 24 ± 2,55 ± 5 and 69 ± 6 μL, respectivel. (n= 4), with resulting inflammatory oedema. Peroxynitrite induced significantly larger plasma extravasation than equivalent vehicle controls at doses of 100 (P > 0.05) and 200 nmol (P > 0.001). This increased extravasation appears to be a direct microvascular response to peroxynitrite administration and not due to either a raised pH, necessary to stabilize the peroxynitrite, or contaminating concentrations of hydrogen peroxide or sodium nitrite from which peroxynitrite is formed. 5. These results suggest that peroxynitrite acts to increase microvascular permeability and oedema formation. Therefore, peroxynitrite may mediate vascular pro-inflammatory effects in addition to its direct cytotoxic activity.     

Survival and recovery of human platelets stored for five days in a non- plasma medium

Human blood platelets were stored for five days as concentrates in 60 mL of: (a) plasma; (b) non-plasma medium with anticoagulant; and (c) non-plasma medium without anticoagulant. All preparations were equally functional when tested for platelet aggregation and release reaction in response to single agonist or synergistic pairs of agonists in vitro. Platelets stored in non-plasma medium with anti-coagulant had lower kallikrein, fibrino(gen)peptide A, lactate, and beta-thromboglobulin than did plasma controls after five days. In vivo recovery and survival of platelets stored in non-plasma medium with anticoagulant were 51.2% +/- 4.3% and 8.7 +/- 0.3 days, respectively, which were not statistically different from plasma controls of 39.2% +/- 4.9% and 7.2 +/- 0.8 days, respectively. It is concluded that platelets can be stored for five days in a non-plasma medium and still have good in vivo recoveries and survivals.     

Pulmonary angiography with iopamidol: patient comfort, image quality, and hemodynamics

The choice of a contrast agent for pulmonary angiography has important implications for patient comfort, image quality, and perhaps the safety of the procedure, particularly for "high-risk" patients. In a prospective study the nonionic, low-osmolality agent iopamidol eliminated the problem of image degradation due to coughing, and patients showed excellent tolerance for it. However, pressure measurements obtained within 3-5 minutes of injection of iopamidol and diatrizoate sodium meglumine 76% showed no significant difference in the hemodynamic effects of the two contrast agents, either for normotensive or for pulmonary hypertensive patients. Contrary to a common presumption, pulmonary hypertension by itself did not appear to increase the risk of pulmonary angiography. The theoretic presumption of greater hemodynamic stability with low-osmolality contrast agents was not clinically evident in this trial with iopamidol. At present, enhanced patient comfort and improved image quality remain the only confirmed bases for choosing this contrast agent for pulmonary angiography.