Investigating the Acute Pulmonary Vascular Haemodynamic Effects of Apelin in Pulmonary Hypertension
试验速览
- 阶段
- 不适用
- 入组人数
- 63
- 试验地点
- 3
- 主要终点
- Change in pulmonary vascular resistance
研究概览
简要总结
The purpose of this study is to determine the effects of Apelin on the lung circulation. The investigators hypothesise that Apelin will relax the lung blood vessels and improve the pumping ability of the heart.
详细描述
Apelin is an endogenous peptide with physiological actions in the cardiovascular system and is abundantly expressed in the pulmonary vasculature. Pre-clinical models and preliminary clinical data indicate that Apelin deficiency may mediate or contribute to the pathogenesis of pulmonary hypertension and heart failure. Apelin causes peripheral vasodilatation and increased cardiac contractility. The investigators will determine the effects of Apelin on the pulmonary circulation in 3 groups; healthy control, people with pulmonary arterial hypertension and people with pulmonary hypertension due to heart failure. Each subject will receive both Apelin infusion and saline placebo infusion in a crossover design. The infusions will be given in a random order which the subject and the investigator will be blinded to. The investigators hypothesise that Apelin will have more marked pulmonary haemodynamic effects than that observed in the systemic circulation. Moreover, the investigators propose that Apelin will have a marked vasodilatory effect on the human pulmonary vasculature and reduce pulmonary vascular resistance in patients with pulmonary arterial hypertension or pulmonary hypertension due to left heart disease.
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Pulmonary Arterial Hypertension which is Idiopathic, Heritable, associated with connective tissue disease or associated with drugs/toxins
- •mean pulmonary artery pressure >/= 25mmHg
- •pulmonary capillary wedge pressure < 15 mmHg
- •normal/reduced cardiac output
- •WHO functional class II - IV
排除标准
- •significant left ventricular dysfunction
- •chronic lung disease (FEV1 < 60% or abnormal CT)
- •chronic thromboembolic pulmonary hypertension
- •HEART FAILURE
- •Inclusion Criteria:
- •stable on treatment for 3 months prior to study
- •NYHA grade II - IV
- •ejection fraction <35%, left ventricular end-diastolic diameter > 5.5 cm and/or shortening fraction < 20%
- •Tricuspid regurgitant velocity >/= 3.0 m/s
- •HEALTHY VOLUNTEERS
- •Inclusion Criteria:
- •mean pulmonary artery pressure < 25 mmHg
- •tricuspid regurgitant velocity < 2.5 m/s
- •Exclusion Criteria:
- •obstructive coronary artery disease
- •ALL SUBJECTS
- •Exclusion Criteria:
- •bleeding diathesis
- •women of childbearing potential without pregnancy test
- •systolic blood pressure > 190 mmHg or < 100 mmHg
- •malignant arrhythmias
- •renal or hepatic failure
- •haemodynamically significant valvular heart disease
- •severe or significant co-morbidity
- •pacemaker
- •already taking part in another trial
- •lack of informed consent
研究组 & 干预措施
Apelin/Saline
Apelin infusion then crossover to Saline infusion
干预措施: Apelin (Drug)
Apelin/Saline
Apelin infusion then crossover to Saline infusion
干预措施: Saline (Placebo) (Drug)
Saline/Apelin
Saline infusion then crossover to Apelin infusion
干预措施: Saline (Placebo) (Drug)
Saline/Apelin
Saline infusion then crossover to Apelin infusion
干预措施: Apelin (Drug)
结局指标
主要结局
Change in pulmonary vascular resistance
时间窗: 5,10,15 and 30 minutes after start of infusion
We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation
次要结局
- Change in systemic vascular resistance(5,10,15 and 30 minutes after start of infusion)
- Change in Cardiac Output(5,10,15 and 30 minutes after start of infusion)