**3.3.2 Experimental protocol**

The prototypes resulting from the above project phase will undergo "in vivo" animal experiments. Ideally these experiments should include long term (≥12 months) evaluation in an appropriate animal (sheep) models. These may consist in prototypes positioning in the thoraco-abdominal aorta (model 1) and in the aortic arch (model 2) surgically or, possibly, as endovascular procedure if the endovascular delivery system is realized and suitable with the animal model peripheral vascular diameter. Half surviving animals could be sacrificed at 12 months and examined to verify:


The remaining animals could be followed indefinitely and examined in case late complication or death.

#### **3.3.3 Preparation of clinical trial**

Ideally during the experimental phase will be identified and monitored Marfan patients with still normal or initial dilatation of any tract of the aorta in order to select those to be offered/accepting the prophylactic endovascular aortic strengthening. Obviously associated risk factors, in particular familiar history of aneurism and rupture, as well as other inclusion and exclusion criteria indicated by the Marfan Associations and clinical Institution Marfan Centers, will form the basis for planning the possible future clinical trial.

Marfan diseases is a condition where pure prophylaxis of aortic aneurism would be in most cases "per se" appropriate, due to its very high incidence and rather early in the patient life; on the other hand prophylactic surgical aortic substitution is an already considered option

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in occasional patients. Prophylaxis is then particularly suitable for these patients with this new method when its long term safety, efficacy, simplicity and predictably low cost are proved; the re-establishment of an artificial elastic network in fact will represent a logic, direct correction of the primary defect, i.e. fragmentation and destruction of vascular wall physiological elastin fibrils network (Gott et al 1996).

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The final goal is then the mininvasive, low cost, full prevention of the costly and still risky endovascular or surgical treatments of overt aortic aneurysm of any nature, ideally in all aortic tracts.

Fig. 27. Prophylactic or very early strengthening of Aortic Arch and Descending Aorta. Sketches illustrate an hypothetical application of the method in high risk aortic area as a pure prophylactic measure for example in Marfan patient. In extended descending aorta this method is the only one that may theoretically provide full prevention of spinal chord complications, not yet fully achieved neither by surgery nor by endovascular techniques. (From Nazari et al 1996b)

Last but not least this method could be the only one theoretically able to totally annul complications related to spinal chord ischemia due to critical intercostal collaterals, still a major problem not yet solved by any surgical nor endovascular technique.

## **4. References**


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The final goal is then the mininvasive, low cost, full prevention of the costly and still risky endovascular or surgical treatments of overt aortic aneurysm of any nature, ideally in all

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**Part 4** 

**General Thoracic Surgery** 


**Part 4** 

**General Thoracic Surgery** 

292 Front Lines of Thoracic Surgery

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**16** 

*USA* 

**Lung Transplantation** 

*Lung and Heart-Lung Transplantation, University of Chicago,* 

The foundation for lung transplantation was laid in the early 1900 by Guthrie and Carrel. In recognition of his work in vascular anastomosis, Dr. Carrel received the first Nobel Prize in Medicine. Following this early work, in 1946 Demikov in Russia performed a canine lung transplant as a unit. The dog subsequently died of bronchial dehiscence. The first human lung transplant was performed by Hardy at the University of Mississippi in 1963. Patient survived a few days and succumbed to complications. Derom in Belgium was credited with the first successful human lung transplantation when he reported 10 month survival of a patient who had undergone lung transplant for end-stage pulmonary fibrosis in 1971. By 1978, 38 lung transplants had been performed worldwide but Derom's patient was the only one that had approached a beneficial outcome. Consistently noted poor outcome in the 60s and 70s led to a moratorium on clinical lung transplantation in the late 70s. Rejection and infection were the common causes of death in this early group and bronchial anastomotic healing was the barrier for transplant survival beyond 2

Cyclosporine based immune suppression in kidney and liver transplantation in the early 1980s resulted in dramatic improvements in organ function and patient survival. With this experience Shumway and Reitz successfully transplanted heart-lung blocks using a cyclosporine based immune suppression on primates. Airway complications were rare in heart-lung transplantation due to the non coronary collaterals, where as this was a major drawback of isolated lung transplantation. The success of the Stanford group led to the

Meanwhile in Toronto, significant experimental work were done by Pearson and Cooper to solve the bronchial healing problem in animal models. The technique of omental wrap around the bronchial anastomosis was developed by Cooper et al. In 1986 the Toronto Lung Transplant Group reported successful single lung transplantation for pulmonary fibrosis in two patients (3). Technique of en-bloc double lung transplant failed due to the tracheal anastomotic complication related to ischemia. Finally bilateral sequential transplantation was developed as a method of transplanting both lungs without the heart. Currently around 147 centers perform over 2000 isolated lung transplants a year. The bronchial anastomotic technique has evolved since and bronchial wrapping is no longer

reinstitution of clinical heart-lung transplantation in the 80s (2).

**1. Introduction** 

**1.1 History** 

weeks (1).

considered necessary.

Wickii T. Vigneswaran
