Geert Kleinnibbelink

General Introduction and Outline of Thesis 15 1 about that of a fist and weighs approximately 250-350 grams (250-300 grams for females, 300-350 grams for males). The shape similar to a pinecone, broad at the base and tapered to the apex, and it is enclosed with the pericardium, a double-walled sac consisting of a serious and a fibrous layer. 3 The heart consists of four compartments: the right and left atria and ventricles. For a long time, it was assumed that the RV was not a significant contributor to maintain the circulation and therefore its importance has been neglected for decades. 5 Studies have strongly focused on the LA and LV, and their ability to acutely and chronically adjust and adapt to physiological and pathological stimuli. 6-8 However, over time, increasing evidence supports a separate view and interest on the right side of the heart. 6 It became increasingly clear to scientists and clinicians that the RV is anatomically and functionally different from the LV. 5, 9 The direct consequence is that this insight rejected the concept to extrapolate physiological and pathophysiological knowledge of the LV to the RV, which was routinely done in the past. In this thesis, a strong focus is placed on the ability of the right ventricle to acutely and chronically adapt to (patho)physiological stimuli. For this reason, a short introduction into the RV is provided below. The RV is crescent-shaped and is wrapped-around the LV. 10 The RV has a thinner wall (3-5 mm), is 1/3 to 1/6 smaller in mass, but the cavity has 10-15% larger volume than the LV ( Figure 3A ). 11, 12 The RV is uniformly trabeculated, has multiple papillary muscles, a moderator band and a full muscular outflow tract. Thereby is the myoarchitecture between both ventricles different. 10, 11 Where the LV has three distinct layers of aggregated cardiomyocytes, the RV only has two. The RV wall consists of longitudinal, transverse and oblique oriented muscle fibers. 10 The superficial layer of the RV free wall is composed of predominantly transverse fibers with the subendocardial layer composed of scanty longitudinal fibers, while the septal wall consists of oblique helical fibers. 10 In contrast, the whole LV (free wall and septal wall) consists of oblique helical fibers. 10 Coiling and shortening of the longitudinal and helical-shaped oblique fibers determine the shortening of the RV, producing 80% of RV systolic function. In contrast, contraction of the transverse fibers accounts for just 20% of RV systolic function. In a healthy RV, contraction is therefore predominantly driven by shortening of the RV in the longitudinal direction, highlighting the importance of examining longitudinal function in clinical and research