Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

Which is best method for instillation of topical therapy to the upper urinary tract? An in vivo porcine study to evaluate three delivery methods

ABSTRACT Purpose: To compare the staining intensity of the upper urinary tract (UUT) urothelium among three UUT delivery methods in an in vivo porcine model. Materials and methods: A fluorescent dye solution (indigo carmine) was delivered to the UUT via three different methods: antegrade perfusion, vesico-ureteral reflux via in-dwelling ureteric stent and retrograde perfusion via a 5F open-ended ureteral catheter. Twelve renal units were tested with 4 in each method. After a 2-hour delivery time, the renal-ureter units were harvested en bloc. Time from harvesting to analysis was also standardised to be 2 hours in each arm. Three urothelium samples of the same weight and size were taken from each of the 6 pre-defined points (upper pole, mid pole, lower pole, renal pelvis, mid ureter and distal ureter) and the amount of fluorescence was measured with a spectrometer. Results: The mean fluorescence detected at all 6 predefined points of the UUT urothelium was the highest for the retrograde method. This was statistically significant with p-value less than <0.05 at all 6 points. Conclusions: Retrograde infusion of UUT by an open ended ureteral catheter resulted in highest mean fluorescence detected at all 6 pre-defined points of the UUT urothelium compared to antegrade infusion and vesico-ureteral reflux via indwelling ureteric stents indicating retrograde method ideal for topical therapy throughout the UUT urothelium. More clinical studies are needed to demonstrate if retrograde method could lead to better clinical outcomes compared to the other two methods.