Effect of ammonia intoxication on cerebral blood flow, its autoregulation and responsiveness to carbon dioxide and papaverine.

Chodobski, Adam; Szmydynger‐Chodobska, Joanna; Skolasińska, K

doi:10.1136/jnnp.49.3.302

Cited by 15 publications

(9 citation statements)

References 24 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that blood ammonia levels were significantly correlated with the cerebral vascular resistance, and that blood ammonia level is an independent predictive factor of cerebral vascular resistance. It has been reported that the intravenous infusion of ammonia results in the disappearance of CBF autoregulation 19 or in an increase in intracranial pressure 20 . Constant intravenous infusion of ammonia into normal rats caused brain edema 21 .…”

Section: Discussionmentioning

confidence: 99%

Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases

Kawakami¹,

Koda²,

Murawaki³

et al. 2001

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and Aim: Cerebral hemodynamic derangement is well known in patients with liver cirrhosis. The advent of transcranial Doppler enables a non‐invasive observation of cerebral hemodynamics. To evaluate the clinical usefulness we examined cross‐sectionally and longitudinally cerebral hemodynamic parameters in patients with cirrhosis. Methods: The subjects of the cross‐sectional study were 117 patients with cirrhosis, 15 patients with chronic hepatitis and 25 healthy controls. The longitudinal study included 26 cirrhotic patients without encephalopathy, and 27 cirrhotic patients with encephalopathy. The pulsatility and resistive indices of the right middle cerebral artery were used as parameters of cerebral hemodynamics. Results: Cerebral pulsatility and resistive indices were significantly higher in patients with cirrhosis (1.05 ± 0.23, P < 0.0001 and 0.63 ± 0.07, P < 0.0001, respectively) than in the controls (0.75 ± 0.11 and 0.55 ± 0.05, respectively) and patients with chronic hepatitis (0.81 ± 0.11 and 0.52 ± 0.05, respectively). Cerebral pulsatility and resistive indices were significantly related with the severity of liver cirrhosis. Patients with encephalopathy had higher cerebral pulsatility and resistive indices than patients without encephalopathy. In the longitudinal studies, cerebral pulsatility and resistive indices were changed in parallel with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices were significantly correlated with the blood ammonia level and serum levels of bilirubin and albumin. Conclusion: These cross‐sectional and longitudinal studies showed that cerebral vascular resistance indices measured by using transcranial Doppler were increased in association with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices are real‐time and useful parameters to assess and monitor cirrhotic patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases

Kawakami¹,

Koda²,

Murawaki³

et al. 2001

J of Gastro and Hepatol

View full text Add to dashboard Cite

show abstract

“…However, we have recently found that in cats hyperammonemia impairs neither cerebrovascular reactivity to papaverine nor autoregulatory properties of cerebral circulation. 6 The latter findings negate the hypothesis that intra-cranial hypertension accompanying hyperammonemia results from the cerebrovascular paralysis.…”

mentioning

confidence: 89%

Intracranial pressure, cerebral blood flow, and cerebrospinal fluid formation during hyperammonemia in cat

Chodobski¹,

Szmydynger‐Chodobska²,

Urbańska³

et al. 1986

Journal of Neurosurgery

View full text Add to dashboard Cite

Intracranial pressure (ICP), cerebral blood flow (CBF), and the cerebrospinal fluid (CSF) formation rate were examined in anesthetized cats during ammonia intoxication. Hyperammonemia, evoked by intravenous infusion of ammonium acetate, caused a significant increase in ICP when the arterial blood ammonia level exceeded 400 mumol X liter-1. A progressive elevation of blood ammonia concentration was followed by a gradual rise in CBF, measured by the xenon-133 clearance technique. At an arterial blood ammonia level exceeding 500 mumol X liter-1, the CBF reached a plateau at 30% above the mean control value. Increase in ICP correlated weakly, but significantly, with the increase in CBF (R = 0.489, p less than 0.005). Elevation of the arterial blood ammonia level to 780.4 +/- 25.5 mumol X liter-1 for 2 hours elicited a significant gradual increase in CSF formation rate, measured by the ventriculocisternal perfusion method with iodine-125-albumin as an indicator substance. A maximum increase in CSF flow of 81% was noted at the end of the ammonium acetate infusion. It is suggested that hyperammonemia increases ICP both by cerebral vasodilatation and by enhancement of the CSF formation rate.

show abstract

“…Depressed cerebral vasodilation to hypercapnia also has been observed in experimental models of acute hyperammonemia in a variety of species, including monkey, dog, cat, and rat (2,6,15,16,33 Hyperammonemia produces substantial increases in brain glutamine concentration (7). Inhibition of glutamine synthetase preserves cerebrovascular reactivity to hypercapnia and hypocapnia during acute hyperammonemia (13,15).…”

Section: Introductionmentioning

confidence: 99%

Glutamine-dependent inhibition of pial arteriolar dilation to acetylcholine with and without hyperammonemia in the rat

Kawaguchi¹,

Brusilow²,

Traystman³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Glutamine has been shown to influence endothelial-dependent relaxation and nitric oxide production in vitro, possibly by limiting arginine availability, but its effects in vivo have not been well studied. Hyperammonemia is a pathophysiological condition in which glutamine is elevated and contributes to depressed CO 2 reactivity of cerebral arterioles. We tested thehypothesis that acute hyperammonemia decreases pial arteriolar dilation to acetylcholine in vivo and that this decrease could be prevented by inhibiting glutamine synthetase with L-methionine-S-sulfoximine (MSO) or by intravenous infusion of L-arginine. Pial arteriolar diameter responses to topical superfusion of acetylcholine were measured in anesthetized rats before and at 6 h of infusion of either sodium or ammonium acetate. Ammonium acetate infusion increased plasma ammonia concentration from 3 0 to ~ 600 μM and increased cerebral glutamine concentration fourfold. Arteriolar dilation to acetylcholine was intact after infusion of sodium acetate in groups pretreated with vehicle or with MSO plus methionine, which was coadministered to prevent MSO-induced seizures. In contrast, dilation in response to acetylcholine was completely blocked in hyperammonemic groups pretreated with vehicle or methionine alone. However, MSO plus methionine administration before hyperammonemia, which maintained cerebral glutamine concentration at control values, preserved acetylcholine dilation. Intravenous infusion of L-arginine during the last 2 h of the ammonium acetate infusion partially restored dilation to acetylcholine without reducing cerebral glutamine accumulation. Superfusion of 1 or 2 mM L-glutamine through the cranial window for 1 h in the absence of hyperammonemia attenuated acetylcholine dilation but had no effect on endothelialindependent dilation to nitroprusside. We conclude that 1) hyperammonemia reduces acetylcholineevoked dilation in cerebral arterioles, 2) this reduction depends on increased glutamine rather than ammonium ions, and 3) increasing arginine partially overcomes the inhibitory effect of glutamine. Keywordsarginine; cerebral circulation; endothelial-dependent dilation; hepatic encephalopathy; hyperammonemia; nitric oxide Patients with hepatic failure have been reported to have a depressed cerebrovascular response to hypercapnia (9). Depressed cerebral vasodilation to hypercapnia also has been observed in experimental models of acute hyperammonemia in a variety of species, including monkey, dog, cat, and rat (2,6,15,16,33 Hyperammonemia produces substantial increases in brain glutamine concentration (7). Inhibition of glutamine synthetase preserves cerebrovascular reactivity to hypercapnia and hypocapnia during acute hyperammonemia (13,15). Thus the loss of CO 2 reactivity is related to glutamine accumulation rather than to direct vascular effects of ammonium ions. Moreover, intravenous infusion of glutamine in the absence of hyperammonemia decreases hypercapnic vasodilation, although not to the same extent as hyperammonemia (22). The...

show abstract

Effect of ammonia intoxication on cerebral blood flow, its autoregulation and responsiveness to carbon dioxide and papaverine.

Cited by 15 publications

References 24 publications

Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases

Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases

Intracranial pressure, cerebral blood flow, and cerebrospinal fluid formation during hyperammonemia in cat

Glutamine-dependent inhibition of pial arteriolar dilation to acetylcholine with and without hyperammonemia in the rat

Contact Info

Product

Resources

About