Model Of Acute Hypoxia Research Articles

Nitric oxide attenuates leukocyte-endothelial cells interactions in the mesenteric microcirculation seen with acute hypoxia. † 885

The purpose of this study was to determine if nitric oxide reduces the increased leukocyte-endothelial interactions observed with acute hypoxia in the mesenteric microcirculation. We studied the effects of the NO donor nitrosylated glutathione (GSNO) in a murine model of acute hypoxia. The microcirculation of two groups of Sprague-Dawley rats was observed via intravital microscopy. After 20 minutes of baseline observation, rats received an intravenous bolus of either GSH (n=3) or GSNO (n=3) at a dose of 20μg/kg followed by continuous infusion of 20 μg/kg/hr via external jugular venous catheter. After 10 minutes, rats were then acutely exposed to 30 minutes of 12% oxygen via hood and then returned to 21% oxygen for an additional 60 minutes. Serial video recordings with play back analysis off-line were taken for data recording. Statistical analysis was via two-way repeated measures ANOVA. Exposure to acute hypoxia caused increased rolling and adherence of leukocytes to the post-capillary venule in the GSH group similar to rats exposed to hypoxia, without intravenous administration of GSH(data not shown). However, when compared to the GSH group, the addition of GSNO significantly attenuated leukocyte rolling during and after hypoxic exposure (during hypoxia 96±14.8 vs. 20±14.8 cells/minute; after hypoxia: 88±14.8 vs. 45.4±14.8 cells/minute; mean±SEM; GSH vs. GSNO; p=0.02). Leukocyte adherence in animals treated with GSH increased during and after hypoxic exposure; this increase was inhibitted in animals given GSNO (during hypoxia 4±1 vs. 0.23±1 cells/100μm; after hypoxia: 5.4±1 vs. 0.23±1 cells/100μm; mean ±SEM; GSH vs. GSNO; p=0.003). There was no difference in systemic mean arterial blood pressure (p=.928) or shear stress (p=.14) between the two groups throughout the experiment. We speculate that the increased interaction of leukocytes with the endothelial cell of the post-capillary venule seen during and after acute exposure to hypoxia may be, in part, due to a loss of NO.

Synthetic anticonvulsants, antihypoxics, and liver monooxygenase system inducers based on amides and urea. IV. Antihypoxic activity of benzhydrylurea and its haloid derivatives

We have previously observed high levels of anticonvulsive activity among the benzhydrylureas, and have demonstrated a quantitative relationship between changes in their anticonvulsive properties and structural and other parameters. The relationship between the antihypoxic activity of benzhydrylureas and chemical structure has not yet been described. This, along with the lack of highly effective antihypoxic preparations has provided considerable impetus to the search for new substances able to correct acid insufficiency elicited by a variety of extreme conditions. The aim of the present work was to study the antihypoxic properties of benzhydrylureas, and to assess qualitative and quantitative relationships between changes in their antihypoxic activities and structures. Benzhydrylureas I-XVI were synthesized as described in [2, 3], where their physicochemical properties are also described. R R 'C~H3 (R2CGH4) CH NHCON H2 I--XVI R=Ri=R2=H(I); RI=R~=H, R=o-F(II),m-F(III),P~F(IV), o-CI(V), m-CI(VI),P-CI(VII), o-Br(Vlll), m-Br (IX),P~Br(X) o-l(Xl),m-l(Xll); R2=H, R=o-Cb RI=p~I(XIII); R~=H, R=~-CI, R'=p~I(XIV); R=H, R'=R2=p-CI(XV); Rl=lI, R=o-CI, RT=p-CI (XVI). Antihypoxic activity of benzhydrylureas I-XVI was determined using the following models: acute hemic hypoxia (sodium nitrite, 300 mg/kg), acute histotoxic hypoxia (sodium nitroprusside, 25 mg/kg), and hypoxic hypoxia with hypercapnia (in a hermetic chamber); activity was assessed in terms of survival rates. Data were analyzed statistically and are presented in Table I. Overall, the vast majority of these compounds had antihypoxic activity in all three models of acute hypoxia. More detailed consideration of the antihypoxic activity of compounds I-XVI using separate screening tests reveals a number of qualitative relationships (see Table

Protective effects of “cerebroactive drugs” in a model of acute hypoxia

1. A systematic study of the hypobaric hypoxia method was carried out, using a wide range of vasodilators and metabolic modifiers. 2. In general cerebral metabolic modifiers have a more effective antihypoxic action than cerebral vasodilators. 3. After a discussion, the conclusion is that hypobaric hypoxia is useful as an initial screening procedure.

Adenyl cyclase system and cerebral energy state.

The energy charge potential of the cerebral adenylate system, the cerebral lactate: pyruvate system, and the cerebral glycogen level were used to characterize the cerebral energy state of the brain. Cerebral adenyl cyclase activity and cyclic AMP concentrations were investigated to evaluate their possible influence on the regulatory processes in brain metabolism. These biochemical parameters were evaluated on the cortical motor area of the brain of the beagle dog in hypovolaemic hypotension during acute hypoxia (obtained by altering the composition of the inhalation mixture) and during the post-hypoxic recovery (three minutes after the restoration of normal ventilation). This experimental model of acute hypoxia was also used for investigating the action of some substances acting at beta-adrenergic receptor level or at vascular level. The substances were perfused into the carotid artery at the rate of 0.5 ml/min for three to six minutes. During the first stage of hypoxia, the adenyl cyclase system is probably an important biochemical regulatory factor. This system becomes less important when a critical threshold is crossed (oxygen arterial partial pressure less than 25-20 mmHg) below which other factors become rate-limiting. A beta-receptor stimulating agent enhanced the mechanisms of physiological post-hypoxic recovery; inhibition of this action was obtained with a beta-receptor blocking agent. Under these experimental conditions, no correlation existed between the vascular effects of the agents and brain metabolism.