**4. Follow-up**

As aortic dissections often develop on a background of preexisting aortic aneurysms, this mandates regular follow-up in these patients to facilitate elective intervention when required. These elective operations carry less risks as the patient can be thoroughly prepared using the ideal imaging modalities and optimizing the patient's medical condition for major surgery. At the Department of Cardiothoracic Surgery, University Hospital Regensburg, Germany there is a regular aortic day-clinic available on weekly basis for preand postoperative follow-ups, that has been running for over a decade, which allows this endangered patient population to be monitored on a 6-monthly basis. Regular postoperative monitoring is essential to provide good long term results with the early discovery of endoleaks, progression of aortopathy, control of hypertension, etc. As the AAS population is

Recent Advances in the Management of Acute Aortic Syndrome 239

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young, average age of involved is sixty years [3], regular follow up contributes to the restoration of health in this still relatively active age group.

Patients with AAS have a long-term outcome which is less favorable when associated with a past medical history of previous cardiac surgery or generalized atherosclerosis [43]. Surgical repair has been recommended when maximal ascending aortic diameter reaches 50 mm (45 mm at Marfan´s syndrome) or 60 mm when involving the descending aorta, although decision making has to be individualized to patient and other comorbidities [10]. Blood pressure control is essential for these patients, with the aim of maintaining the blood pressure no more than 130/80 mmHg [44]. If there is a well know hereditary component present, the patient´s complete family should be offered the opportunity to be genetically tested and councilled.

Some recent publications have already highlighted the role of angiotensin II in progression of aortic aneurysms, although the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remain unknown. Habashi et al demonstrated that loss of AT2 expression accelerates the aberrant growth and rupture of aorta in a mouse model of Marfan`s syndrome. Losartan, a selective AT1 blocker reduces aneurysm progression in mice; a full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor enalapril, which limits signaling through both receptors, is less effective. Both drugs attenuated transforming growth factor-ß (TGF ß) signaling in the aorta, but losartan uniquely inhibited TGF ß-mediated activation of extracellular signal regulated kinase, by allowing continued signaling through AT2, which shows the protective nature of AT2 signaling and the choice of therapy in aortic aneurysms [45].

International multicentric studies are currently evaluating the possible pharmacological prevention and postoperative medical supportive therapy options in Marfan´s syndrome provided by AT1 blockers, especially losartan in a combination with a ß-blocker, such as nebivolol. The key molecule in aortic aneurysms, TGF ß, normally attached to extracellular matrix, is free and activated. Under experimental circumstances, TGF ß blockade prevents aortic wall damage and dilatation. AT1 blockers exert an anti-TGF ß effect; trials are now ongoing for evaluating the effect of losartan compared with atenolol or nebivolol. The third generation ß-blocker nebivolol retains the ß-adrenergic blocker effects on heart rate and further exerts antistiffness effects, typically increased in aortic aneurysms [46, 47].

After evaluation these ongoing human studies we have more insight to the pharmacological support of AAS and aortic aneurysms, which completes the surgical management possibilities of this severe disease group.

#### **5. References**


young, average age of involved is sixty years [3], regular follow up contributes to the

Patients with AAS have a long-term outcome which is less favorable when associated with a past medical history of previous cardiac surgery or generalized atherosclerosis [43]. Surgical repair has been recommended when maximal ascending aortic diameter reaches 50 mm (45 mm at Marfan´s syndrome) or 60 mm when involving the descending aorta, although decision making has to be individualized to patient and other comorbidities [10]. Blood pressure control is essential for these patients, with the aim of maintaining the blood pressure no more than 130/80 mmHg [44]. If there is a well know hereditary component present, the patient´s complete family should be offered the opportunity to be genetically

Some recent publications have already highlighted the role of angiotensin II in progression of aortic aneurysms, although the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remain unknown. Habashi et al demonstrated that loss of AT2 expression accelerates the aberrant growth and rupture of aorta in a mouse model of Marfan`s syndrome. Losartan, a selective AT1 blocker reduces aneurysm progression in mice; a full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor enalapril, which limits signaling through both receptors, is less effective. Both drugs attenuated transforming growth factor-ß (TGF ß) signaling in the aorta, but losartan uniquely inhibited TGF ß-mediated activation of extracellular signal regulated kinase, by allowing continued signaling through AT2, which shows the protective nature of AT2

International multicentric studies are currently evaluating the possible pharmacological prevention and postoperative medical supportive therapy options in Marfan´s syndrome provided by AT1 blockers, especially losartan in a combination with a ß-blocker, such as nebivolol. The key molecule in aortic aneurysms, TGF ß, normally attached to extracellular matrix, is free and activated. Under experimental circumstances, TGF ß blockade prevents aortic wall damage and dilatation. AT1 blockers exert an anti-TGF ß effect; trials are now ongoing for evaluating the effect of losartan compared with atenolol or nebivolol. The third generation ß-blocker nebivolol retains the ß-adrenergic blocker effects on heart rate and

After evaluation these ongoing human studies we have more insight to the pharmacological support of AAS and aortic aneurysms, which completes the surgical management

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**14** 

*Greece* 

**Circulatory Arrest** 

**Neurologic Injury Following Hypothermic** 

Cardiothoracic surgeons are faced with the challenge of protecting the brain during the sensitive time of interruption of normal cerebral blood flow. The brain is an exceptionally complex organ with a functional anatomy that is difficult both to understand and assess. Experimental and clinical studies have shown that the mechanism of neural injury is multifactorial. As such, discussions regarding the best surgical strategies for neuroprotection during circulatory arrest are formidable, at best. Although we are armed with excellent experimental and clinical studies that demonstrate the deleterious effects of prolonged exposure to cardiopulmonary bypass (CPB) on brain function and structure, the various neuroprotective strategies, particularly that of deep hypothermic circulatory arrest (DHCA) remain an issue of debate. This is related in part to the gap between the basic science understanding of brain injury caused by these events and the clinical application of various neuroprotective strategies and their subsequent clinical outcomes. The goal here is to address the current understanding of the mechanisms underlying brain injury after HCA and relevant strategies of neural protection, supported by primary experimental data from

The use of therapeutic hypothermia dates back to the ancient Egyptians, Greeks, and Romans. In modern times, the use of therapeutic hypothermia progressed from observation case reports to animal studies to clinical use in children and then adults. Initially there were observational reports of therapeutic use of hypothermia in patients with severe cerebral trauma, followed by experimental studies in dogs that suggested a therapeutic role for hypothermia for cerebral protection during cardiac surgery. Later, profound hypothermia (12° C, nasopharyngeal) with circulatory arrest (up to 1 hour) was used in children

undergoing surgical repair of the tetralogy of Fallot. (Apostolakis & Shuhaiber, 2007)

The use of deep hypothermic cardiopulmonary arrest (DHCA, 14-18°C) was first applied as a method for cerebral protection during the prosthetic replacement of the aortic arch.(Griepp et al, 1997) Later, the use of a DHCA was extended into other major vascular

**1. Introduction** 

our laboratory.

**2. Hypothermic ciruclatory arrest** 

Elizabeth O. Johnson, Antonia Charchanti, Maria Piagkou,

*Department of Anatomy, University of Athens, School of Medicine, Department of Anatomy, University of Ioannina, School of Medicine,* 

Theodore Xanthos and Theodore Troupis

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