Humanity took a long and winding road to comprehend the nature of blood circulation

(Figure 15). All the aforementioned scientists were visionaries. Each persisted on searching for the Truth to the best of his capabilities. Each strived to pass on his scientific message to the future generations and Humanity after him. “When hearing something Receptor Tyrosine Kinase unusual, do not preemptively reject it, for that would be folly. Indeed, unconventional things may be true, and familiar and praised things may prove to be lies. Truth is truth unto itself, not because many people say it is.” 17,18 (Figure 16) Figure 16. A photograph of the first page of the commentary on the Canon of Avicenna by Ibn Al-Nafis. Source: Zeidan Y. The rediscovery of Ibn Al-Nafis. 2008. ISBN: 9971442120. Ibn Al-Nafis, “Commentary on Anatomy in Avicenna’s Canon” Figure 15. The road to the discovery of circulation.
The regulation of vascular tone in the pulmonary circulation is a complex and multifactorial process that involves the dispensability of the pulmonary vasculature, the function of the heart, concentration of oxygen in the blood and the capacity of the endothelium to release vasoactive substances. All these mechanisms combine to determine pulmonary vascular resistance and to ensure that

the pulmonary circulation is maintained as a low pressure, high blood flow circuit. This prevents the passage of fluid into the interstitial space and allows the right ventricle to operate under optimal conditions. Changes in the pulmonary vascular resistance, which is defined as difference between mean

pulmonary artery pressure and left atrial pressure, divided by the cardiac output, can lead to changes in the function of the lungs and eventually the right ventricle. Pulmonary arterial hypertension (PAH) is defined as a pulmonary artery pressure greater or equal to 25 mmHg at rest. 1 The increased pressure in the lung has a knock-on effect on the right ventricle, leading to right ventricular hypertrophy and eventually right heart failure. Symptoms of the condition include shortness of breath, fatigue, a non-productive cough, angina pectoris, syncope and peripheral oedema. While this is a rare condition affecting 15-50 people per million of the population, its incidence is associated with other morbidities such as HIV (0.5% of patients), systemic sclerosis (7–12% GSK-3 of patients), sickle cell anaemia (2–3.75% of patients) mixed connective tissue disease (10–45% of patients) and systemic lupus erythematosus (1–14% of patients). 2–9 Despite the apparent rareness of the condition, PAH has been classified by the World Health Organistaion (WHO) into 5 distinct categories based on the current understanding of the disease (Table 1). 1 Table 1 Clinical Classification of Pulmonary Hypertension. (ALK1, activin receptor-like kinase type 1; BMPR, bone morphogenetic protein receptor type 2; HIV, human immunodeficiency virus) (Dana Point, 2008).