Effect of Sodium Nitroprusside on Cerebral Blood Flow

NCT03317652 | Completed DMC

• 1 other identifier: H-17017045
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The brain has a high energy demand and requires continuous blood flow. The blood flow to the brain appears to be unaffected by small changes in blood pressure, but brain blood flow may be reduced by a large reduction in blood pressure. Large reductions in blood pressure are common during anesthesia or bleeding. It is unclear, however, how a given reduction in blood pressure affects blood flow to the brain. In this study, medicine called sodium nitroprusside is used to dilate blood vessels and reduce blood pressure in twenty healthy young men. The study will evaluate whether blood flow to the brain is affected when sodium nitroprusside is used to induce a moderate and a large reduction in blood pressure. Blood flow to the brain is evaluated using ultrasound on the neck. During breathing, oxygen is inhaled and carbon dioxide is exhaled. Carbon dioxide increases brain blood flow whereby changes in respiration can affect the blood flow to the brain. Sodium nitroprusside causes mild hyperventilation, whereby more carbon dioxide is exhaled, which will contribute to a reduction in brain blood flow. Thus, the study will also evaluate how brain blood flow is affected by hyperventilation and by breathing a mix of air and carbon dioxide.

Conditions

Healthy Male Subjects

Outcome Measures

Primary Outcomes (1)

• Change in cerebral blood flow from baseline to when MAP (mean arterial pressure) is decreased by 40% by sodium nitroprusside

  Sum of unilateral internal carotid and vertebral artery blood flow \[ml/min\] by duplex ultrasound corrected for changes in arterial CO2 tension (PaCO2) from baseline

  Values are recorded during 2-3 min at 2 time points; at baseline and when MAP is reduced by 40% by sodium nitroprusside (approximately 2 hours after the baseline evaluation)

Secondary Outcomes (4)

• Change in cerebral blood flow from baseline to when MAP is decreased by 20% by sodium nitroprusside

  Values are recorded during 2-3 min at 2 time points; at baseline and when MAP is reduced by 20% by sodium nitroprusside (approximately 2 hours after the baseline evaluation)

• Relative reduction in internal carotid artery blood flow as compared to that of the vertebral artery from baseline to when MAP is reduced by 40% by sodium nitroprusside

  Values are recorded during 2-3 min at 2 time points; at baseline and when MAP is reduced by 40% by sodium nitroprusside (approximately 2 hours after the baseline evaluation)

• The CO2 reactivity of the internal carotid as compared to the vertebral artery

  Values are recorded during 2-3 min at 3 time points; at baseline, during hyperventilation for 6 min (approx 60 min after the baseline evaluation) and during 6% CO2 breathing for 6 min (approximately 60 min after the baseline evaluation)

• Comparison of the slope of linear regression of MAP and cerebral blood flow for the evaluations at baseline and when MAP is reduced by 20% by sodium nitroprusside and that of the evaluations when MAP is reduced by 20% and 40%

  Values are recorded during 2-3 min at 3 time points; at baseline and when MAP is reduced by 20% and 40% by sodium nitroprusside (both approximately 2 hours after the baseline evaluation)

Study Arms (1)

Sodium nitroprusside and CO2 reactivity

EXPERIMENTAL

The subject rests in the supine position throughout the study that lasts for approximately three hours. Interventions are: * Hyperventilation * 6% CO2 breathing * Infusion of sodium nitroprusside

Other: Hyperventilation; Other: 6% CO2 breathing; Drug: Infusion of sodium nitroprusside

Interventions

Hyperventilation OTHER

The subject is instructed to hyperventilate for 6 min to provoke a 0.7-1.2 kPa reduction in PaCO2, and the evaluation is repeated if the reduction in PaCO2 is not within this interval. The order of hyperventilation and 6% CO2 breathing is randomized.

Also known as: Evaluation of CO2 reactivity, hyperventilation

Sodium nitroprusside and CO2 reactivity

6% CO2 breathing OTHER

The subject breathes a mixture of 6% CO2 (with 21% O2 and 73% N2) from a bag and a face mask for 6 minutes. The order of hyperventilation and 6% CO2 breathing is randomized.

Also known as: Evaluation of CO2 reactivity, 6% CO2 breathing

Sodium nitroprusside and CO2 reactivity

Infusion of sodium nitroprusside DRUG

Using incremental intravenous infusion of sodium nitroprusside MAP is reduced by 20% (15%-25%) and then by 40% (35%-45%, MAP minimally at 50 mmHg).

Sodium nitroprusside and CO2 reactivity

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent
• Male
• Age 18-35 years

You may not qualify if:

• Alcohol intake ≥ 420 g / week
• Body mass index below 18 kg/m\^2 and above 25 kg/m\^2
• Smoking
• Beard on the neck
• Chronic cardiac, lung, liver, kidney or metabolic disease that require medication
• Vitamin B12 deficiency
• Anemia
• Leber's hereditary optic neuropathy
• Tobacco-alcohol amblyopia
• Stenosis that obstructs ≥ 16% of the internal carotid artery
• Intake of sildenafil or vardenafil for 24 hours and tadalafil for 48 timer prior to the experiment
• Intake of monoamine oxidase inhibitors
• Neurologic disease considered to affect cerebral blood flow, including epilepsy and multiple sclerosis

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Department of Anesthesia, Rigshospitalet 2043

Copenhagen, DK-2100, Denmark

Location

Related Publications (17)

• Edvinsson L, Owman C. Sympathetic innervation and adrenergic receptors in intraparenchymal cerebral arterioles of baboon. Acta Neurol Scand Suppl. 1977;64:304-5. No abstract available.

  PMID: 409067 BACKGROUND

• Evans DH. On the measurement of the mean velocity of blood flow over the cardiac cycle using Doppler ultrasound. Ultrasound Med Biol. 1985 Sep-Oct;11(5):735-41. doi: 10.1016/0301-5629(85)90107-3.

  PMID: 2932831 BACKGROUND

• Henriksen L, Paulson OB. The effects of sodium nitroprusside on cerebral blood flow and cerebral venous blood gases. II. Observations in awake man during successive blood pressure reduction. Eur J Clin Invest. 1982 Oct;12(5):389-93. doi: 10.1111/j.1365-2362.1982.tb00685.x.

  PMID: 6816609 BACKGROUND

• Hoiland RL, Ainslie PN. CrossTalk proposal: The middle cerebral artery diameter does change during alterations in arterial blood gases and blood pressure. J Physiol. 2016 Aug 1;594(15):4073-5. doi: 10.1113/JP271981. Epub 2016 Mar 24. No abstract available.

  PMID: 27010010 BACKGROUND

• Jorgensen LG, Perko M, Perko G, Secher NH. Middle cerebral artery velocity during head-up tilt induced hypovolaemic shock in humans. Clin Physiol. 1993 Jul;13(4):323-36. doi: 10.1111/j.1475-097x.1993.tb00333.x.

  PMID: 8370233 BACKGROUND

• LASSEN NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959 Apr;39(2):183-238. doi: 10.1152/physrev.1959.39.2.183. No abstract available.

  PMID: 13645234 BACKGROUND

• Lewis NC, Smith KJ, Bain AR, Wildfong KW, Numan T, Ainslie PN. Impact of transient hypotension on regional cerebral blood flow in humans. Clin Sci (Lond). 2015 Jul;129(2):169-78. doi: 10.1042/CS20140751.

  PMID: 25697830 BACKGROUND

• Liu J, Zhu YS, Hill C, Armstrong K, Tarumi T, Hodics T, Hynan LS, Zhang R. Cerebral autoregulation of blood velocity and volumetric flow during steady-state changes in arterial pressure. Hypertension. 2013 Nov;62(5):973-9. doi: 10.1161/HYPERTENSIONAHA.113.01867. Epub 2013 Sep 16.

  PMID: 24041946 BACKGROUND

• Lucas SJ, Tzeng YC, Galvin SD, Thomas KN, Ogoh S, Ainslie PN. Influence of changes in blood pressure on cerebral perfusion and oxygenation. Hypertension. 2010 Mar;55(3):698-705. doi: 10.1161/HYPERTENSIONAHA.109.146290. Epub 2010 Jan 18.

  PMID: 20083726 BACKGROUND

• Meng L, Hou W, Chui J, Han R, Gelb AW. Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans. Anesthesiology. 2015 Nov;123(5):1198-208. doi: 10.1097/ALN.0000000000000872.

  PMID: 26402848 BACKGROUND

• Panerai RB. Assessment of cerebral pressure autoregulation in humans--a review of measurement methods. Physiol Meas. 1998 Aug;19(3):305-38. doi: 10.1088/0967-3334/19/3/001.

  PMID: 9735883 BACKGROUND

• Sato K, Fisher JP, Seifert T, Overgaard M, Secher NH, Ogoh S. Blood flow in internal carotid and vertebral arteries during orthostatic stress. Exp Physiol. 2012 Dec;97(12):1272-80. doi: 10.1113/expphysiol.2012.064774. Epub 2012 Jun 11.

  PMID: 22689443 BACKGROUND

• Sato K, Sadamoto T, Hirasawa A, Oue A, Subudhi AW, Miyazawa T, Ogoh S. Differential blood flow responses to CO(2) in human internal and external carotid and vertebral arteries. J Physiol. 2012 Jul 15;590(14):3277-90. doi: 10.1113/jphysiol.2012.230425. Epub 2012 Apr 23.

  PMID: 22526884 BACKGROUND

• Thomas KN, Lewis NC, Hill BG, Ainslie PN. Technical recommendations for the use of carotid duplex ultrasound for the assessment of extracranial blood flow. Am J Physiol Regul Integr Comp Physiol. 2015 Oct;309(7):R707-20. doi: 10.1152/ajpregu.00211.2015. Epub 2015 Jul 8.

  PMID: 26157060 BACKGROUND

• Torella F, McCollum CN. Regional haemoglobin oxygen saturation during surgical haemorrhage. Minerva Med. 2004 Oct;95(5):461-7.

  PMID: 15467521 BACKGROUND

• Verbree J, Bronzwaer AS, Ghariq E, Versluis MJ, Daemen MJ, van Buchem MA, Dahan A, van Lieshout JJ, van Osch MJ. Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI. J Appl Physiol (1985). 2014 Nov 15;117(10):1084-9. doi: 10.1152/japplphysiol.00651.2014. Epub 2014 Sep 4.

  PMID: 25190741 BACKGROUND

• Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg. 1982 Dec;57(6):769-74. doi: 10.3171/jns.1982.57.6.0769.

  PMID: 7143059 BACKGROUND

Study Officials

• Niels D Olesen, MD

  Department of Anesthesia, Rigshospitalet 2043, DK-2100 Copenhagen Ø, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 23, 2017
• Study Start: November 3, 2017
• Primary Completion: December 4, 2017
• Study Completion: December 4, 2017
• Last Updated: December 8, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)