Department of Cardiology Aarhus University Hospital Aarhus Denmark.
Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark.
J Am Heart Assoc. 2023 May 16;12(10):e028232. doi: 10.1161/JAHA.122.028232. Epub 2023 May 15.
Background Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3-hydroxybutyrate (3-OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3-OHB in patients with PAH or CTEPH. Methods and Results We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3-OHB infusion and placebo (saline) for 2 hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3-OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague-Dawley rats. Ketone body infusion increased circulating 3-OHB levels from 0.5±0.5 to 3.4±0.7 mmol/L (<0.001). Cardiac output improved by 1.2±0.1 L/min (27±3%, <0.001), and right ventricular annular systolic velocity increased by 1.4±0.4 cm/s (13±4%, =0.002). Pulmonary vascular resistance decreased by 1.3±0.3 Wood units (18%±4%, <0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3-OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12±2%, <0.001) and had no effect on right ventricular systolic pressures (=0.63), whereas pressures rose at a slower pace (dP/dtmax, =0.02). Conclusions In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long-term studies are warranted to assess the clinical role of hyperketonemia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04615754.
肺动脉高压（PAH）或慢性血栓栓塞性肺动脉高压（CTEPH）是两种死亡率较高的使人虚弱的疾病。尽管出现了新的治疗方法，但肺血管阻力仍经常升高。然而，酮体 3-羟基丁酸（3-OHB）可能会降低这些患者的肺血管阻力。因此，目的是评估 3-OHB 在 PAH 或 CTEPH 患者中的血液动力学效应。
我们招募了 10 名 PAH 患者和 10 名 CTEPH 患者，这些患者仍有残余肺动脉高压。他们在一项随机交叉研究中接受了 3-OHB 输注和安慰剂（生理盐水）2 小时。进行了侵入性血液动力学和超声心动图测量。此外，我们还研究了 3-OHB 对 Sprague-Dawley 大鼠离体心脏和离体肺动脉的影响。酮体输注使循环 3-OHB 水平从 0.5±0.5 增加到 3.4±0.7mmol/L（<0.001）。心输出量增加 1.2±0.1L/min（27±3%，<0.001），右心室环收缩速度增加 1.4±0.4cm/s（13±4%，=0.002）。肺血管阻力下降 1.3±0.3Wood 单位（18%±4%，<0.001），PAH 和 CTEPH 患者的反应无显著差异。在大鼠研究中，与生理盐水给药相比，3-OHB 给药与肺动脉张力降低相关（最大相对张力差：12±2%，<0.001），对右心室收缩压无影响（=0.63），而压力上升速度较慢（dP/dtmax，=0.02）。
在 PAH 或 CTEPH 患者中，酮体输注可提高心输出量并降低肺血管阻力。实验大鼠研究支持酮体使肺血管舒张。需要进行长期研究来评估高酮血症的临床作用。
