Inhaled nitric oxide induces cerebrovascular effects in anesthetized pigs

doi:10.1016/S0304-3940(03)00722-5

Neuroscience Letters

Volume 348, Issue 2, 11 September 2003, Pages 85-88

https://doi.org/10.1016/S0304-3940(03)00722-5 Get rights and content

Abstract

Although inhaled nitric oxide (NO_i) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO_i have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO_i in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO_i increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO_i in the cerebral vasculature, which may occur preferentially in the venous compartment.

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Acknowledgements

This study was supported by research grants from the Medical Faculty of the University of Munich (FöFoLe, Reg.-Nos. 79 & 136), Germany.

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Early NO-donor treatment improves acute perfusion deficit and brain damage after experimental subarachnoid hemorrhage in rats
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Currently, NO inhalation is practiced as a “local” treatment in patients with pulmonary hypertension, ARDS, and in transplant patients. Inhalative NO has been reported to have cerebrovascular effects [47] and reduce brain damage after experimental stroke and SAH [46,48]. However, the delivery of inhaled NO into the cerebral circulation and brain tissue has not been entirely clarified [49].
A lack of nitric oxide (NO) may be a possible factor in the pathogenesis of an acute decrease of cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether early therapy with an NO-donor can improve CBF and offer neuroprotection after experimental SAH in rats. Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated with 1.5 μg/kg/min of intravenous sodium nitroprusside (SNP) or vehicle (n = 10) starting 15 min after induction of SAH until 180 min thereafter. SNP caused a moderate decrease of arterial blood pressure and cerebral perfusion pressure. Conversely, CBF measured by laser-Doppler flowmetry increased significantly in SNP-treated animals. The rate of injured neurons in the hippocampal CA1-field was significantly reduced in SNP-treated animals (10.5 ± 5%) compared to controls (14.2 ± 7%), as well as the number of Caspase-3 positive neurons. Low-dose treatment with SNP can attenuate an early perfusion deficit after SAH and reduce neuronal damage in spite of a hypotensive side effect. This may reflect the reversal of an early NO-deficit. In the clinical setting, the moderate hypotensive effect may be welcome since SAH-patients frequently present with elevated blood pressure.
Evaluation of inhaled {radical dot}NO in a model of rat neonate brain injury caused by hypoxia-ischaemia
2010, Injury
Citation Excerpt :
Recent trials with adequate changes in inhaled delivery protocol further emphasise the efficacy of inhaled NO in pre-term NHRF.1,5,10 The biological action of inhaled NO is not restricted to lung, and via reversible binding to oxy-haemoglobin cysβ93 residue, blood transport and delivery, this action may extend to extra-pulmonary tissues including brain12. In this respect, modulation of local NO via the use of NO synthase inhibitors and NO donors has proven to be quite effective strategies to influence brain integrity in either curative or toxic ways6,8,25.
Inhaled NO (INO), at 5–40 parts per million (ppm) in the air, is indicated for treating neonatal hypoxic respiratory failure. Whether these doses of INO are protective or toxic towards brain was here evaluated in laboratory animals.
In rat neonates (postnatal day 7), a brain injury based on permanent right carotid artery occlusion plus transient (90 min) respiratory hypoxia (8% O₂) was challenged by two NO dosages (10 and 40 ppm) given either before, during or after transient hypoxia. Three weeks later, animal brains were studied for the loss of cerebral matter (infarct or atrophy).
In right hemispheres, significant increases (26–39%) in lesion sizes were induced by 40 and not 10 ppm INO, whatever the inhalation period. The two doses reduced significantly the left hemisphere volume only when NO was inhaled at the re-oxygenation period.
Our results suggest that high doses of INO, brain damaging events and inhalation at re-oxygenation might affect brain integrity when these conditions are cumulated. However, the clinical relevance of this (infarct or atrophy) and previously described (haematomas) brain toxicity associated with INO remains to be clarified in the human neonates, for instance through non-invasive cerebral imagery follow-up of patients given INO.
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There has been an explosive increase in the amount of interesting information about the physiologic and pathophysiologic roles of nitric oxide in cardiovascular, nervous, and immune systems. The possible involvement of the nitric oxide–cyclic guanosine monophosphate pathway in the effects of anesthetic agents has been the focus of many investigators. Relaxations of cerebral and peripheral arterial smooth muscle as well as increases in cerebral and other regional blood flows induced by anesthetic agents are mediated mainly via nitric oxide released from the endothelium and/or the nitrergic nerve and also via prostaglandin I₂ or endothelium-derived hyperpolarizing factor. Preconditioning with volatile anesthetics protects against ischemia-reperfusion–induced myocardial dysfunction and cell death or neurotoxicity, possibly through nitric oxide release. Inhibition of nitric oxide synthase decreases the anesthetic requirement. Involvement of nitric oxide in the effects of volatile, intravenous, and local anesthetics differs. This review article includes a summary of information about the sites and mechanisms by which various anesthetic agents interact with the nitric oxide–cyclic guanosine monophosphate system.
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¹: Present address: Clinic of Anasthesiology, Intensive Care and Pain Medicine, University of Frankfurt, Frankfurt, Germany.

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Inhaled nitric oxide induces cerebrovascular effects in anesthetized pigs

Abstract

Section snippets

Acknowledgements

Life Sci.

J. Neurosci. Methods

J. Biol. Chem.

Br. J. Anaesth.

Evaluation of a near-infrared spectrometer (NIRO 300) for the detection of intracranial oxygenation changes in the adult head

Stroke

Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery

J. Clin. Invest.

Evaluation of regional cerebral circulation based on absolute mean transit times in radionuclide cerebral angiography

Phys. Med. Biol.

Near infrared determined cerebral transit time and oxy- and deoxyhemoglobin relationships during hemorrhagic hypotension in the dog

Adv. Exp. Med. Biol.

Inhaled NO reaches distal vasculatures to inhibit endothelium- but not leukocyte-dependent cell adhesion

Am. J. Physiol.

Cerebral Pathophysiology