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临床试验/NCT03945643
NCT03945643已完成早期 1 期

Is Blood Flow Through IPAVA and PFO Related to Breath-hold and SCUBA Diving-induced Pulmonary Hypertension?

University of Oregon1 个研究点 分布在 1 个国家目标入组 82 人开始时间: 2019年7月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
早期 1 期
状态
已完成
入组人数
82
试验地点
1
主要终点
Change in Q-IPAVA

研究概览

简要总结

In summary, the investigators propose to study elite Croatian breath-hold and SCUBA divers. The investigators will quantify breath-hold hypoxia- and SCUBA diving-induced pulmonary hypertension and right heart function to investigate the relationships between PFO and IPAVA blood flow. The investigators will use a placebo-controlled intervention (sildenafil) to reduce pulmonary arterial pressure in these subjects to examine the impact of the change in pressure (or absence of change) on the relationships determined above.

详细描述

Pulmonary arterial hypertension (increased lung blood pressure) is a multifactorial disease without a cure. Investigating reversible forms of pulmonary hypertension induced under extreme conditions such as a prolonged breath-hold and/or SCUBA diving may help to better understand why some individuals develop this devastating disease, and others do not.

Pulmonary arterial pressure is typically very low in healthy humans. Low oxygen levels (hypoxia) cause a constriction of the lung blood vessels resulting in smaller diameters, but lung blood flow stays constant or increases. Having constant flow with smaller vessel diameters causes pulmonary arterial pressure to increase but it will return to normal once normal oxygen levels are restored. Moreover, there is an association with patent foramen ovale (PFO, small hole between the atria in the heart) and excessive pulmonary arterial pressures in low oxygen conditions. However, the reasons for the exacerbated increase in pulmonary arterial pressure in these subjects with a PFO (PFO+) is unknown, but may be due to an exaggerated constriction response to low oxygen.

During a breath-hold, the oxygen in the lung decreases and in elite breath-hold divers, it decreases to very low levels. Compared to subjects without a PFO (PFO-), the oxygen may drop even lower in those PFO+ subjects because deoxygenated blood travels through the small hole to mix with oxygenated blood, exacerbating the level to which blood oxygen decreases. Thus, using a breath-hold model of lung hypoxia is one approach to examining a hypoxia-induced increase in pulmonary arterial pressure - a method critically dependent upon the elite breath-hold diver's ability to hold their breath for significant durations.

Intrapulmonary arteriovenous anastomoses (IPAVA) are vessels within the lung that bypass capillaries. The investigator's group has investigated the possible roles these unique vessels may have in physiological and pathophysiological conditions. The investigators have found that IPAVA blood flow occurs when healthy subjects breathe low oxygen gas. The investigators have also found that IPAVA blood flow is inversely related to pulmonary arterial pressure. Specifically, individuals with high pulmonary arterial pressures have low IPAVA blood flow and vice versa.

The right ventricle of the heart pumps blood through the pulmonary artery to the lungs. Under resting conditions the right heart performs a minimal amount of work because the pressure in the lung blood vessels is low. When pulmonary arterial pressure increases, the work of the right side of the heart has to increase substantially to keep blood pumping through the lung. Thus, high pulmonary arterial pressures will increase the work of the right heart and may lead to right heart dysfunction thereby limiting the amount of blood the heart can pump. If the pressure is high enough to limit the amount of blood flowing through the lung then this can be detected by a reduction in pulmonary blood flow and/or changes in the function of the heart during contraction (systole) and relaxation (diastole). Accordingly, an intervention that reduces pulmonary arterial pressures during a breath-hold may have a beneficial effect on right heart function.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Basic Science
盲法
Double (Participant, Outcomes Assessor)

盲法说明

Utilization of placebo to mask drug administration.

入排标准

年龄范围
18 Years 至 65 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Reside in geographic location near Split, Croatia
  • Elite breath hold divers
  • Experienced SCUBA divers

排除标准

  • Previous history of coronary artery disease
  • Currently taking medication or herbal supplement for any heart or respiratory disease that cannot be ceased for 48 hours prior to testing
  • Women who are pregnant or trying to become pregnant
  • Previous history of any condition that would prevent the subject from performing a breath hold
  • Taking sildenafil or products similar to sildenafil
  • Taking Nitrates or other nitric oxide donors
  • Control breath hold divers can't have previous breath hold diving experience

研究组 & 干预措施

Sildenafil administration

Active Comparator

Administration of 50mg sildenafil one time, one hour prior to measurements

干预措施: Sildenafil (Drug)

Placebo administration

Placebo Comparator

Administration of 50mg placebo one time, one hour prior to measurements

干预措施: Placebo (Other)

结局指标

主要结局

Change in Q-IPAVA

时间窗: 1 hour post intervention

Minute bloodflow through intrapulmonary arteriovenous anastamoses

Concentration of MMP-9

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of Cystatin C

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of Myoglobin

时间窗: 1 hour post intervention

Inflammatory cytokine

Pulmonary Pressure

时间窗: 1 hour post intervention

Pulmonary arterial pressure measured by ultrasound techniques

Concentration of MRP8/14

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration Of MMP-2

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of IGFBP-4

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of ICAM-1

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of VCAM-1

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration Of SAA

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of NGAL

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration Of CRP

时间窗: 1 hour post intervention

Inflammatory cytokine

Concentration of OPN

时间窗: 1 hour post intervention

Inflammatory cytokine

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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