Antegrade selective cerebral perfusion at moderate hypothermia of 28 ̊C - how safe is the spinal cord? [Elektronische Ressource] / von Maximilian Lühr

Aus der Abteilung für Herz- und Gefäßchirurgie der Chirurgischen Universitätsklinik der Albert-Ludwigs-Universität Freiburg im Breisgau und der Abteilung für Herz- und Thoraxchirurgie der Mount Sinai School of Medicine in New York, USA Antegrade Selective Cerebral Perfusion at Moderate Hypothermia of 28 °C - How Safe is the Spinal Cord? INAUGURAL-DISSERTATION zur Erlangung des Medizinischen Doktorgrades der Medizinischen Fakultät der Albert-Ludwigs-Universität Freiburg im Breisgau Vorgelegt im Jahr 2010 von Maximilian Lühr geboren in MünchenDekan: Prof. Dr. Dr. h.c. mult. Herbert Blum 1. Gutachter: Prof. Dr. med. Dr. h. c. Friedhelm Beyersdorf 2. Gutachter: Ass. Prof. Dr. Christian D. Etz Jahr der Promotion: 2010Index 1 INTRODUCTION ...…………………………………………………………………… 6 1.1 Thoracic aortic aneurysms………………………………………………… 6 1.2 Thoracic aortic dissections 8 1.3 Endovascular stent-grafting for aortic arch pathology………………. 9 1.4 Aortic arch surgery……………………………………………………......... 10 1.4.1 Surgical indications………………………………………………. 10 1.4.2 Cerebral protection ……………………………………………… 10 1.4.3 Cerotection techniques…………………………………. 10 1.4.3.1 Various stages of hypothermia……...……………… 11 1.4.3.2 Hypothermic circulatory arrest (HCA)………………. 11 1.4.3.3 Antegrade selective cerebral perfusion (aSCP)……. 11 1.4.3.4 Retrograde cerebral perfusion (RCP)………………. 12 1.4.3.5 Axillary and femoral artery cannulation…………….. 13 1.
Publié le : vendredi 1 janvier 2010
Lecture(s) : 15
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Source : D-NB.INFO/1010821342/34
Nombre de pages : 71
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Aus der Abteilung für
Herz- und Gefäßchirurgie der Chirurgischen Universitätsklinik
der Albert-Ludwigs-Universität Freiburg im Breisgau
und
der Abteilung für Herz- und Thoraxchirurgie
der Mount Sinai School of Medicine in New York, USA




Antegrade Selective Cerebral Perfusion at Moderate
Hypothermia of 28 °C - How Safe is the Spinal Cord?





INAUGURAL-DISSERTATION
zur
Erlangung des Medizinischen Doktorgrades
der Medizinischen Fakultät
der Albert-Ludwigs-Universität Freiburg im Breisgau




Vorgelegt im Jahr 2010
von Maximilian Lühr
geboren in MünchenDekan: Prof. Dr. Dr. h.c. mult. Herbert Blum
1. Gutachter: Prof. Dr. med. Dr. h. c. Friedhelm Beyersdorf
2. Gutachter: Ass. Prof. Dr. Christian D. Etz

Jahr der Promotion: 2010Index

1 INTRODUCTION ...…………………………………………………………………… 6
1.1 Thoracic aortic aneurysms………………………………………………… 6
1.2 Thoracic aortic dissections 8
1.3 Endovascular stent-grafting for aortic arch pathology………………. 9
1.4 Aortic arch surgery……………………………………………………......... 10
1.4.1 Surgical indications………………………………………………. 10
1.4.2 Cerebral protection ……………………………………………… 10
1.4.3 Cerotection techniques…………………………………. 10
1.4.3.1 Various stages of hypothermia……...……………… 11
1.4.3.2 Hypothermic circulatory arrest (HCA)………………. 11
1.4.3.3 Antegrade selective cerebral perfusion (aSCP)……. 11
1.4.3.4 Retrograde cerebral perfusion (RCP)………………. 12
1.4.3.5 Axillary and femoral artery cannulation…………….. 13
1.4.3.6 pH-Management during CPB and HCA…………… 13
1.5 Paraplegia in aortic surgery……………………………………………….. 14
1.6 Moderate hypothermia during aortic arch repair…………..………….. 14
1.7 The need for experimental evaluation………………………………....… 14
1.8 Study design.....……………………………………………..……………….. 15
1.9 The porcine model for cardiovascular research…………………......... 18
1.9.1 Aortic arch and the supraaortic vessels………………………… 18
1.9.2 Thoracic and abdominal aortic segmental arteries (SA)……….. 20

2 MATERIALS AND METHODS…………………………………………………….… 21
2.1 Introduction…………………………………………………………………… 21
2.2 Housing and animal care…………………………………………………… 21
2.3 Perioperative management………………………………………………… 22
2.3.1 Ventilation and anesthesia……………………………………...... 22
2.3.2 Monitoring………………………………………………………… 23
2.4 Operative technique………………………………………………………… 23
2.4.1 Catheter placement for microsphere injections………………… 23
2.4.2 Intracranial pressure measurement……………………………… 25
2.4.3 Cannulation and cardiopulmonary bypass (CPB)……………… 26
2.4.4 Antegrade selective cerebral perfusion (aSCP)……………...…. 26
2.4.5 Rewarming and decannulation…………………………………. 27
2.4.6 End of operation………………………………………………….. 28
2.4.7 Weaning from ventilation and anesthesia………………………. 30
2.4.8 Postoperative monitoring and intensive care…………………… 30 2.5 Spinal cord blood flow (SCBF) determination………………………….. 30
2.5.1 Fluorescent microspheres……………………………………….. 30
2.5.2 Microsphere injections…………………………………………… 31
2.5.3 Tissue harvesting…………………………………………………. 31
2.5.4 Analysis for spinal cord blood flow (SCBF)……………………... 35
2.6 Postoperative neurobehavioral assessment…………………………….35
2.6.1 Physical therapy and mobilization………………………………..35
2.6.2 Videotaping and scoring………………………………………..... 35
2.7 Histopathological evaluation…………………………………………........ 36
2.8 Data analysis…………………………………………………………………. 38
2.8.1 Survival……………………………………………………………. 38
2.8.2 Histology and neurological outcome…………………………..... 38
2.8.3 Physiologic and hemodynamic parameters……………………..38
2.8.4 Regional blood flow………………………………………………. 38

3 RESULTS………………………………………………………………………………. 40
3.1 Experimental groups…………………………………………………………40
3.1.1 Comparability of the experimental groups……………………… 40
3.2 Intraoperative parameters…………………………………………………. 40
3.2.1 Cardiopulmonary bypass (CPB)…………………………………. 40
3.2.2 Antegrade selective cerebral perfusion (aSCP)……………….…41
3.3 Postoperative survival………………………………………………………. 42
3.4 Neurologic outcome 43
3.5 Spinal cord blood flow (SCBF)…………………………………………….. 45
3.6 Ischemic spinal cord damage……………………………………………... 47

4 DISCUSSION………………………………………………………………………….. 50
4.1 Previous experimental studies51
4.2 The results of this experiment 51
4.3 Comparison with previous experiments….………………………………52
4.4 Experimental results in clinical context…………………………………. 53
4.5 Impaired neurological outcome – prolonged ischemia
and/or reperfusion injury?...................................................................... 55
4.6 Moderate versus deep hypothermia………………………………………57
4.7 Conclusion…………………………………………………………….…….…59
5 ABSTRACT…………………………………………………………………………….. 60
5.1 English abstract……………………………………………………………… 60
5.2 German abstract……………………………………………………………... 61

6 ADDENDUM…………………………………………………………………………… 62
6.1 List of abbreviations……………………………………………………….... 62
6.2 Semantics……………………………………………………………………... 62

7 REFERENCES………………………………………………………………….......…. 63

CURRICULUM VITAE………………………………………………………………..… 71
English…………………………………………………………………………....... 71
German………………………………………………………………………......... 72
Publications………………………………………………………………….....… 74
8.3.1 Authorships……………………………………………………….. 74
8.3.2 Co-Authorships…………………………………………………… 74
8.3.3 Abstracts………………………………………………………..… 77
8.3.4 Poster presentations……………………………………………… 81

ACKNOWLEGMENT……………………………………………………………….……83Antegrade Selective Cerebral Perfusion at Moderate Hypothermia of 28 °C -
How Safe is the Spinal Cord?
1 Introduction
1 Introduction
Treatment and management of thoracic aortic disease such as aortic
aneurysms or dissections remains a challenge for cardiothoracic and
vascular surgeons, especially when the aortic arch is involved and open
surgery becomes necessary.
The incidence of thoracic aortic aneurysms was reported to be 5.9 cases
per 100.000 person-years in 1982 [1]. In 2006, a study based on 14.000
cases by Olsson et al. reported an increase of thoracic aortic disease (TAD)
by 52 % in men and by 28 % in women to reach 16.3 per 100.000 per year
and 9.1 per 100.000 per year, respectively [2]. This increase in industrialized
countries appears to be a result of implemented routine screening studies,
improved imaging modalities, and increased clinical awareness.
1.1 Thoracic aortic aneurysms
Thoracic aortic aneurysms (TAA) do not occur as often as abdominal
aortic aneurysms [3]. However, they may be caused by several different
disease processes, especially in respect to their location which is distinctly
connected with the cause, course, and treatment of a TAA. The ascending
thoracic aorta is the most common location of a TAA (60 %), followed
by the descending segment (40 %), then the arch (10 %) [3]. Aortic
arch lesions may involve the proximal, transverse or distal arch. (Fig. 1)

Descending aortic aneurysms are most often associated with atherosclerosis
which generally plays an important role in aneurysmal disease [4]. The
most common cause for ascending aortic aneurysms is cystic medial
degeneration [5]. Genetic disorders which affect the connective tissue, such
as Marfan’s disease, Loeys-Dietz syndrome and Ehlers-Danlos syndrome,
are also associated with ascending aortic aneurysms [6-9]. Rare causes
of TAA include infections or syphilis [10]. Involvement of the aortic arch
often occurs by continuation of an ascending and/ or descending aortic
aneurysm. Aortic arch aneurysms can also be associated with Takayasu’s
arteritis [11] or atherosclerosis.
Page 6Antegrade Selective Cerebral Perfusion at Moderate Hypothermia of 28 °C -
How Safe is the Spinal Cord?
1 Introduction
Figure 1: Schematic figure of the anatomic segments of the aorta. Occurrence of thoracic aortic aneurysms
differs between the ascending (60 %), descending (40 %) and arch (10 %) segment [3]. Aortic arch lesions may
be categorized as proximal (A), distal (B), or total (C).
Page 7Antegrade Selective Cerebral Perfusion at Moderate Hypothermia of 28 °C -
How Safe is the Spinal Cord?
1 Introduction
1.2 Thoracic aortic dissections
Thoracic aortic dissections occur if the aortic blood flow is redirected via
an intimal tear into the media of the aortic wall. In this way the intima is
separated from the overlying adventitia by a dissection membrane, creating
a so-called “false lumen” along a variable length within the aortic media.

The cause of aortic dissection is still under investigation. Several risk
factors which may be associated with thoracic aortic dissection include
hypertension, connective tissue disorders (Marfan’s disease, Ehlers-Danlos
syndrome, Turner’s syndrome, and bicuspid aortic valve), cystic medial
degeneration, aortitis, atherosclerosis, pre-existing thoracic aortic aneurysm,
trauma, intramural hematoma, coarctation of the aorta, hypervolemia, and
polycystic kidney disease [7, 8, 12-16]. In addition, surgical manipulations
during cardiovascular operations, such as cannulation for cardiopulmonary
bypass, aortic cross-clamping, valve replacement, CABG, endovascular
stent-grafting and placement of intra-aortic balloon pumps have also been
reported to result in dissection [17, 18]. More recently drug use, e.g. cocaine,
has also been associated with aortic dissections [19].
Thoracic aortic dissections are described by their presentation as acute
(within two weeks), chronic (two months after initial event) and more recently
as subacute (between two weeks and two months) [20]. Two classification
systems are commonly used in clinical practice for thoracic aortic dissections
based on the location and extent of dissection: the De Bakey [21] and the
Stanford [22] classification. Aortic dissections involving the ascending
aorta, arch, and descending aorta are classified as De Bakey type I and
Stanford type A. De Bakey type II selectively describes dissections of the
ascending aorta. Dissections that originate in the descending thoracic and
thoracoabdominal aorta regardless of any retrograde involvement of the
arch are described by De Bakey type III (a or b) and Stanford type B. (Fig. 2)

Page 8Antegrade Selective Cerebral Perfusion at Moderate Hypothermia of 28 °C -
How Safe is the Spinal Cord?
1 Introduction
BA
II I IIIa IIIb
Figure 2:
Stanford (A+B) and De
Bakey (I-III) classifications
for thoracic aortic
aneurysms.
1.3 Endovascular stent-grafting for aortic arch pathology
As the development of endovascular stent-graft devices proceeds, increasing
numbers of cardiac surgeons have adopted endovascular techniques to treat
thoracic aortic pathologies in high risk patients [20]. Although endovascular
stent-grafting of descending aortic aneurysms in high risk patients has been
commonly accepted, the use of endovascular stent-grafts for complex
thoracic aortic arch pathologies remains controversial [23-25].
The technical challenges of stent-graft deployment in the aortic arch such
Page 9Antegrade Selective Cerebral Perfusion at Moderate Hypothermia of 28 °C -
How Safe is the Spinal Cord?
1 Introduction
as proximity to the great vessels and arch tortuosity necessitate continuous
device enhancement. More recently, repairs of aortic arch aneurysms have
been accomplished by using both open and endovascular techniques
[26, 27]. These “hybrid procedures” still lack long-term follow-up [26, 28].
Therefore, currently open surgery remains the “gold standard” for elective
treatment of complex aortic arch aneurysms and Stanford type A dissections.
1.4 Aortic arch surgery

1.4.1 Surgical indications
Depending on severity of the aortic pathologies involving the aortic arch,
urgent or elective surgery is indicated. Urgent indications include rupture
of an atherosclerotic aneurysm, rupture of the false lumen or extensive
intimal tears in the arch of a Stanford type A aortic dissection, or
occurrence of a mycotic arch aneurysm [20]. Elective indications include
large arch aneurysms (>6 cm), rapid enlargement of saccular aneurysms
(>1 cm/ year) or occurrence of symptoms (pain or hoarseness) [6, 20]. In
Marfan’s disease, a family history of aortic rupture or dissection, elective
surgery should be considered at an aortic diameter of 5 cm [6, 20, 29].

1.4.2 Cerebral protection
Open aortic arch surgery requires cannulation for cardiopulmonary
bypass (CPB) and is associated with increased risks for cerebral injury
due to possible embolisation by air and atheromatous debris [20].
Specific considerations concerning cerebral protection are therefore
required [30-33]. Beside prevention of any neurological damage due to
embolisation it is mandatory to minimize ischemic injury during the required
cardiac arrest. The question of how best to protect the brain during
aortic arch surgery is still a subject of controversy and research [34, 35].

1.4.3 Cerebral protection techniques
The main concepts of cerebral protection during aortic arch surgery comprise
total body hypothermia and different perfusion techniques for prevention of global
ischemia as well as additional methods to minimize possible embolic damage.
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