Effect of Sodium Nitroprusside on Cerebral Blood Flow
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in cerebral blood flow from baseline to when MAP (mean arterial pressure) is decreased by 40% by sodium nitroprusside
研究概览
简要总结
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.
详细描述
Background Cerebral autoregulation is generally considered to maintain cerebral blood flow (CBF) if mean arterial pressure (MAP) is between 60 and 150 mmHg. Yet, it is controversial whether there is a plateau for CBF. Thus, blood velocity of the middle cerebral artery (MCA Vmean), as an index of CBF, is affected by pharmacological changes in MAP between approximately 40-125 mmHg. In contrast, internal carotid artery blood flow is unaffected by a moderate decrease in blood pressure.
The brain is supplied by the internal carotid and vertebral arteries that have different regulation with higher CO2 reactivity and larger orthostatic reduction for the internal carotid than the vertebral artery. The different regulation of the two arteries may reflect higher sympathetic innervation of arteries that originate from the internal carotid artery than those of the vertebral artery. The internal carotid artery may contribute to cerebral autoregulation as the vessel dilates during a moderate decrease in MAP while internal carotid artery blood flow is maintained. The arterial CO2 tension (PaCO2) is an important regulator of CBF and also maintenance of central blood volume and cardiac output is important for regulation of CBF. In the present study, internal carotid and vertebral artery blood flow is evaluated using duplex ultrasound in 20 healthy men when MAP is reduced by sodium nitroprusside, a potent short-lasting vasodilator.
Objective The purpose of the study is to evaluate whether CBF is affected by 20% and 40% reductions in MAP by sodium nitroprusside. The CO2 reactivity of the internal carotid and vertebral arteries is evaluated in order to control for hyperventilation during sodium nitroprusside induced hypotension. Further, the study will evaluate whether changes in internal carotid and vertebral artery blood flow by a 40% reduction in MAP are different and whether the arteries have different CO2 reactivity. Lastly, the study will evaluate whether the slope of the linear regression of CBF and MAP is higher for the evaluations when MAP is reduced by 40% and 20% than that of the evaluations at baseline and when MAP is reduced by 20%.
Hypotheses
- Sodium nitroprusside-induced reduction in MAP by 40% reduces CBF
- Sodium nitroprusside-induced reduction in MAP by 20% reduces CBF
- Sodium nitroprusside-induced reduction in MAP by 40% causes a larger relative reduction in internal carotid artery blood flow than that of the vertebral artery
- The CO2 reactivity of the internal carotid artery is higher than that of the vertebral artery
- The slope of linear regression of MAP and CBF at the evaluations when MAP is reduced by 20% and 40% by sodium nitroprusside is higher than that of the evaluations at baseline and when MAP is reduced by 20%
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Informed consent
- •Age 18-35 years
排除标准
- •Alcohol intake ≥ 420 g / week
- •Body mass index below 18 kg/m^2 and above 25 kg/m^2
- •Beard on the neck
- •Chronic cardiac, lung, liver, kidney or metabolic disease that require medication
- •Vitamin B12 deficiency
- •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
研究组 & 干预措施
Sodium nitroprusside and CO2 reactivity
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
干预措施: Hyperventilation (Other)
Sodium nitroprusside and CO2 reactivity
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
干预措施: 6% CO2 breathing (Other)
Sodium nitroprusside and CO2 reactivity
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
干预措施: Infusion of sodium nitroprusside (Drug)
结局指标
主要结局
Change in cerebral blood flow from baseline to when MAP (mean arterial pressure) is decreased by 40% by sodium nitroprusside
时间窗: 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)
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
次要结局
- 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))
研究者
Niels Damkjær Olesen
Principal investigator
Rigshospitalet, Denmark