THORACIC AORTIC STIFFENING ELICITED BY PROLONGED PROPRANOLOL TREATMENT IN AN ANIMAL MODEL Konstantinos M. Lampropoulos, 1,2 Dimitrios P. Sokolis, 1  1 Laboratory of Biomechanics, Foundation of Biomedical Research, Academy of Athens, Athens, Greece. 2 Department of Cardiology, 251 General Air Force Hospital, Athens, Greece.  35 Lefkados Street, 15354 Glyka Nera, Athens, Greece. Tel.: +30-210-6659730 dimitrissokolis@ath.forthnet.gr ABSTRACT This study assessed the long-term effect of propranolol administration on the elastic and failure properties of the thoracic aorta. Control rats (n=5) received only water with their food, whereas beta-blockade was produced in another 5 rats by administering 100 mg/kg/day propranolol in their drinking water. The animals were sacrificed after 3 months and the descending thoracic aorta was resected, cut into specimens with circumferential (CIRC) and longitudinal (LONG) orientation, and submitted to evaluation of elastic and failure properties. Our observations indicated a stiffer and stronger thoracic aorta in propranolol-treated rats, mostly in the LONG direction, at physiologic and high stresses. Thoracic aortic stiffening, elicited by prolonged b- blocker treatment, warrants further clinical investigation. KEY WORDS Biomechanics; b-blockers; elastic properties; rupture; aortic wall; mathematical model. 1. Introduction There is currently growing interest in the evaluation of the elastic properties of aortic wall and their association to cardiovascular pathology [1,2]. The aorta serves two major tasks: it first acts as a conduit delivering blood from the heart to peripheral tissues and it secondly transforms the pulsatile blood flow caused by ventricular ejection to a continuous flow in the periphery. The elastic properties of vessel wall are crucial to its normal function. The elastic properties of conduit vessels differ strikingly throughout the arterial tree, with more elastic central arteries and stiffer peripheral arteries. This non-uniformity is caused by the histological microstructure of arterial wall, varying among the different parts of the circulation [1-6]. Importantly, the elastic properties of aortic wall assume pivotal roles in the pathogenesis of normal aging and cardiovascular disease, such as hypertension, atherosclerosis, and abnormalities of aortic wall. Aortic compliance is impaired, i.e. decreased, in all these states, and all existing data recommend that early detection of this dysfunction might offer a tool for early identification of cardiovascular pathology [1,2]. Propranolol and other b-adrenergic blockers (BBs) have been long used in the treatment of hypertension, angina pectoris, and various arrhythmias, while the hemodynamic effects of BBs have been used in the management of aortic dissection [7]. Propranolol has also been shown to inhibit aortic root dilatation in patients with Marfan's syndrome when administered in dosages that lower dp/dt [8]. Long-term administration of BBs may therefore protect against abdominal aortic aneurysm (AAA) expansion by reducing the hemodynamic stresses acted on aortic wall. Numerous studies have confirmed that the low rate of AAA expansion among patients receiving BBs was not related to decreased mean, systolic, or diastolic blood pressure [9-11]. Evidence from other studies implied that specific BBs may interact metabolically with aortic tissue [12-14]. Propranolol in particular suppressed the formation of aortic aneurysm in b-aminoproprionitrile fed turkeys [12]; this effect was not dependent on changes in heart rate, blood pressure, or dp/dt [13]. Supplementary data revealed that it augmented the tensile strength of aortic wall by stimulating lysyl oxidase activity and promoting collagen and elastin cross-linking [14]. In view of the above, the influence of propranolol in turkeys fed b-aminoproprionitrile may rely on the direct interaction with b2-receptors situated in non-cardiac vascular tissues. This study was set to address the effect of prolonged propranolol treatment on the elastic properties of aortic wall in an animal model, as limited information is presently available in the literature. Such information is vital for understanding the consequences of BB therapy for the entire circulation, because propranolol is a pharmaceutical commonly administered to patients with a wide range of pathologies [15]. 2. Materials and Methods 2.1 Animal Model, Propranolol Administration, and Tissue Preparation Ten male Wistar rats (350-400 g) were used in this study. The rats were housed individually in the animal facility at a constant room temperature (19-21°C), relative humidity (55%), under an artificial 12-hour light:12-hour dark 680-040 334