Prolonged bleeding time during nitric oxide inhalation in the rabbit

Högman, Marieann; Frostell, C.; Arnberg, Henrik; Sandhagen, Bo; Hedenstierna, Göran

doi:10.1111/j.1748-1716.1994.tb09728.x

Cited by 95 publications

(41 citation statements)

References 21 publications

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“…One hypothesis is that the hyperosmolarity per se may inactivate the NO molecule. Further support for this comes from previous rabbit studies, where inhalation of NO at a concentration of 300 ppm decreased the MAP and the lung compliance [6,18]. In this study, after hypertonic saline nebulization, these effects were abolished.…”

Section: Discussionsupporting

confidence: 69%

Increased airway osmolarity inhibits the action of nitric oxide in the rabbit

Högman

Hjoberg²,

Hedenstierna³

1998

Eur Respir J

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Endogenous nitric oxide modulates neural bronchoconstriction in both experimental animals [1] and humans [2]. NO is the only known neural bronchodilator of the inhibitory nonadrenergic noncholinergic nerves in human airways [3]. Inhalation of NO has been shown to reduce the response to bronchoconstricting agents in both animals [4][5][6][7] and humans [8,9]. In a study on asthmatic patients, inhalation of NO at a concentration of 80 parts per million (ppm) reduced the airway resistance [8]; however, there were large variations. In some patients, no improvement at all was observed in airway tone after inhalation of NO, while others showed the same dilatory effect as for a β 2 -agonist.Asthma is an inflammatory disease, characterized by the migration of inflammatory cells into the airway wall and the formation of oedema. The increase in the osmolarity of the airway surface liquid seen during hyperventilation has been proposed as the stimulus for exercise-induced bronchoconstriction [10]. In a rabbit model, hyperventilation with dry gas causes an increased response to histamine with respect to resistance [11]. During nebulization with hypertonic saline there is a shift in the ion content of the airway wall. This shift of ions causes fluid accumulation, and hence, a transient oedema is formed [12]. It was hypothesized that the blunted response to NO inhalation in some patients with asthma is caused by an oedema or increased osmolarity of the airway wall. Therefore, the effectiveness of inhaled NO in a rabbit model in countering bronchoconstriction was investigated after nebulization of hypertonic saline; and after hyperventilation with dry gas.In rabbits, as in humans, a concentration of Š80 ppm NO is needed to exert a relaxing effect on bronchial smooth muscle [5,6]. In this study, concentrations of 80-300 ppm NO were used. Methacholine (meth) was used to induce bronchoconstriction and evaluate the bronchoprotective effect of the inhaled NO. Materials and methodsNew Zealand White rabbits of both sexes with a body weight of 3.0-3.7 kg were used. They were vaccinated against pasteurella and bordetella and maintained on water and 75 g high-protein pellets·day -1 ad libitum. The protocol was approved by the regional ethics committee on animal experiments. The effect of NO inhalation on methacholine (meth)-induced airway constriction was investigated in a rabbit model. Oedema and a change in osmolarity of the airways was achieved by hypertonic saline nebulization and hyperventilation with dry gas. Anaesthesia and animal preparationThere was an increase in resistance to meth at a concentration of 3 mg·mL -1 , of 86±14 cmH 2 O·L -1 ·s (mean±SEM) after oedema formation, compared with 46±16 cmH 2 O·L -1 ·s without oedema. Inhalation of 80 parts per million (ppm) NO failed to counter the increase in resistance due to meth, 92±14 cmH 2 O·L -1 ·s after hypertonic saline nebulization. After hyperventilation of dry gas, the increase in resistance due to meth at 1 mg·mL -1 was 27±11 cmH 2 O·L -1 ·s with 80 ppm NO and 28±5 cmH 2 O...

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Section: Discussionsupporting

confidence: 69%

Increased airway osmolarity inhibits the action of nitric oxide in the rabbit

Högman

Hjoberg²,

Hedenstierna³

1998

Eur Respir J

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“…19,25,26 In this study, iNO therapy had a significant effect on BBB dysfunction as measured by EB extravasation, so the shown reduction of brain water content is most probably because of a combination of reduction of vasogenic and cytotoxic edema formation. Furthermore, NO inhalation has been shown to exert anti-platelet activity [38][39][40] and to act anti-inflammatorily. 29,41 We previously showed that microthrombus formation occurs in our model of murine CCI and further deteriorates CBF; 42 in the same study leukocyte-platelet aggregates were detected in cerebral venules.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Nitric Oxide Reduces Secondary Brain Damage after Traumatic Brain Injury in Mice

Terpolilli¹,

Kim²,

Thal³

et al. 2012

J Cereb Blood Flow Metab

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Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow (CBF) after TBI were not successful because of various reasons. We previously showed that nitric oxide (NO) applied by inhalation after experimental ischemic stroke is transported to the brain and induces vasodilatation in hypoxic brain regions, thus improving regional ischemia, thereby improving brain damage and neurological outcome. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage, the aim of the current study was to evaluate the effect of NO inhalation after experimental TBI. NO inhalation significantly improved CBF and reduced intracranial pressure after TBI in male C57 Bl/6 mice. Long-term application (24 hours NO inhalation) resulted in reduced lesion volume, reduced brain edema formation and less blood-brain barrier disruption, as well as improved neurological function. No adverse effects, e.g., on cerebral auto-regulation, systemic blood pressure, or oxidative damage were observed. NO inhalation might therefore be a safe and effective treatment option for TBI patients.

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“…inhaled NO [45,46]. The clinical significance of this remains unclear but inhaled NO should probably be used with caution in patients with bleeding diathesis and intracranial haemorrhage [47].…”

Section: Background and Controversiesmentioning

confidence: 99%