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Elastin, collagen, and some mechanical aspects of arterial aneurysms
396
9.
10.
11.
12. 13. 14.
15.
]o~n~of VASCULAR SURGERY
Special communication
NMR blood flowmeter--applications. Med Phys 1981;8: 452-8. Mills CM, Brant-Zawadzki M, Crooks LE, et al. Nuclear magentic resonance: principles of blood flow imaging. AJR 1984;142:165-70. Herfkens RJ, Higgins CB, Hricak H, et al. Nuclear magnetic resonance imaging of the cardiovascular system: normal and pathologic findings. Radiology 1983;147:749-59. Herfkens RJ, Higgins CB, Hricak H, et al. Nuclear magnetic resonance imaging of atherosclerotic disease. Radiology 1983; 148:161-6. Flak B, Li DK, Ho BY, et al. Magnetic resonance imaging of aneurysms of the abdominal aorta. AIR 1985;144:991-6. Hricak H, Amparo E, Fisher MR, et al. Abdominal venous system: assessment using MR. Radiology 1985;156:415-22. Kaufman L, Crooks LE, Sheldon PE, et al. Evaluation of NMR imaging for detection and quantification of obstruction in vessels. Invest Radiol 1982;17:554-60. Goldberg HI, Spagnoli MV, Grossman R,I, et al. MRI characteristics of carotid artery plaques. AJNR 1986;7:541.
ELASTIN, COLLAGEN, AND SOME MEC~ICAL ASPECTS OF ARTERIAL ANEURYSMS One of the most dramatic changes that occur to arteries is the formation of aneurysm. Vessels that become aneurysmal exhibit three mechanical characteristics: they increase in diameter, they become stiffer, ~,2 and they tend to become tortuous. The studies described herein were undertaken to examine the role o f elastin and collagen
in the formation o f aneurysms and the development of tortuosity. Common carotid arteries were exposed in dogs immediately after death. Segments 6 to 7 cm in length were measured and excised. Segments of human iliac arteries, approximately 3 cm in length, were similarly obtained from human subjects at post mortem examination. The arterial segments were placed in buffered Krebs-Ringer solution at 37 ° C, p H 7.4. The vessels were cannulated at both ends and mounted horizontally in a tissue bath. Diameter was measured with a linear-displacement transducer, and longitudinal retractive force was measured with a Grass force transducer (Grass Instrument Co.; Quincy, Mass.). The vessels were pressurized in 25 mm H g steps up to 300 mm H g to relax them. Then they were treated intraluminally with elastase (8 units/m/ for the dog vessels; 40 units/ml for the human vessels) or collagenase (64 units/ml for the dog vessels; 320 units/ml for the human vessels). The arteries then were distended by pressure steps or were held at 0 mm H g and subjected to stepwise longitudinal extension. Results demonstrate that degradation o f elastin causes aneurysmal dilatation (Fig. 1) and increased stiffness as the load is shifted to collagen? None of them ruptured. By contrast, degradation o f collagen causes a small amount of dilatation and decreased stiffness (Fig. 1). All of these vessels ruptured? Human internal iliac arteries are more prone to develop aneurysms than are the external iliac arteries, and the former exhibit dramatic responses to enzymatic treatment, especially degradation of collagen (Fig. 2). 3
0.90
N=18
N=18
N=18
COLLAGENASE 0.80
ELASTASE
E
o 070 n. I,M I5 <{
COLLAGENASE
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.J
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0.50
0.40
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0.30 i 0
| 5'0
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| 150
|
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|
i 100
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mm
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| 150
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| 150
Fig. 1. Pressure-diameter curves for dog carotid arteries. Treatment with elastase caused dilatation and increasing stiffness but not rupture. Treatment with collagenase caused slight dilatation, decreasing stiffness, and rupture. (From Dobrin et al. Arch Surg 1984; 119:405-9.)
Volume 9 Number 2 February 1989
Special communication
397
1,3d
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Fig. 2. Pressure-diameter curves for human internal iliac arteries. The format was the same as that in Fig. 1. Results show dramatic effects after treatment with collagenase. (From Dobrin et al. Arch Surg 1984;119:405-9.) Why do aneurysms not rupture immediately? Analysis of stability of aneurysms indicates that (1) the load is shifted from elastin to previously unloaded collagen and (2) the change in shape from a cylinder to a sphere reduces he wall stress by one half. The presence of laminated thrombus in the lumen does not contribute to the stability of aneurysmal vessel wall. Aneurysmal vessels also tend to become tortuous. Most arteries are under longitudinal traction (stretch). With pressurization the traction force fails, but the vessels undergo little change in length. 4The longitudinal force caused by pressures is given by pressure × (radius).4 Therefore as a vessel dilates the longitudinal force rises exponentially. For example, the longitudinal force is 10 times as great in an 8 cm aortic aneurysm as it is in a 2.5 cm normal aorta. This increased longitudinal force may cause the vessel to elongate between constraining branches. This causes vessel buckling (i.e., tortuosity). 4 Longitudinal extension of unpressurized arteries demonstrates that degradation o f elastin markedly reduces longitudinal retractive force exerted by the artery. By contrast, degradation of collagen has only a slight effect on longitudinal retractive force. Thus failure of elastin causes an-
eurysmal dilatation; this increases the longitudinal distending force. Loss of elastin also decreases longitudinal retractive force. All of these factors predispose to vessel elongation and the development of tortuosity. In conclusion, elastin bears loads in the circumferential and longitudinal directions. Failure of elastin causes vessels to become ancurysmal and, by several mechanisms, to become tortuous. Collagen bears loads only in the circumferential direction and only at large dimensions. Failure of collagen permits vessels to dilate only slightly but compromiscs their tensile strength. These studies demonstrate that a critical early step in the development of aneurysms involves failure of wall elastin. This agrees with estimates of the load borne by the elastic lamellae in normal and aneurysmal vessels2 ,~An extensive discussion of the various mechanical and hemodynamic factors contributing to the pathogenesis of abdominal aortic aneurysms is given elsewhere.'
Philip B. Dobrin, ZcID, PhD Department of Surgery Loyola University and Hines Veterans Administration Hospital Hines, Illinois
398
Special communication
REFERENCES 1. Glagov S. Pathology of large arteries. In: Abramson DI, Dobrin PB, eds. Blood vessels and lymphatics in organ systems. New York: Academic Press, 1984:39-53. 2. Sumner DS, Hokanson DE, Strandness DE Jr. Stress-strain characteristics and coUagen-elastin content of abdominal aortic aneurysms. Surg Gynecol Obstet 1970;130:459-66. 3. Dobrin PB, Baker WH, Gley WC. Elastolytic and collagenolytic studies of arteries: implications for the mechanical properties of aneurysms. Arch Surg 1984;119:405-9.
Journal of VASCULAR SURGERY
4. Dobrin PB, Baker WH, Schwarcz TH. Mechanisms of arterial and aneurysmal tortuosity. Surgery 1988; 104: 568-71. 5. Wolinsky H, Glagov S. A lamellar unit of aortic medial structure and fimction in mammals. Circ Res 1967;20:99-111. 6. Zatina MA, Zarins CK, Gewertz BL, et al. Role of medial lamellar architecture in the pathogenesis of aortic aneurysrns. J VAsc SURG 1984;1:442-8. 7. Dobrin PB. Pathophysiology and pathogenesis of atherosclerotic aneurysms: current concepts. Surg Clin North Am. (In press.)
9.
10.
11.
12. 13. 14.
15.
]o~n~of VASCULAR SURGERY
Special communication
NMR blood flowmeter--applications. Med Phys 1981;8: 452-8. Mills CM, Brant-Zawadzki M, Crooks LE, et al. Nuclear magentic resonance: principles of blood flow imaging. AJR 1984;142:165-70. Herfkens RJ, Higgins CB, Hricak H, et al. Nuclear magnetic resonance imaging of the cardiovascular system: normal and pathologic findings. Radiology 1983;147:749-59. Herfkens RJ, Higgins CB, Hricak H, et al. Nuclear magnetic resonance imaging of atherosclerotic disease. Radiology 1983; 148:161-6. Flak B, Li DK, Ho BY, et al. Magnetic resonance imaging of aneurysms of the abdominal aorta. AIR 1985;144:991-6. Hricak H, Amparo E, Fisher MR, et al. Abdominal venous system: assessment using MR. Radiology 1985;156:415-22. Kaufman L, Crooks LE, Sheldon PE, et al. Evaluation of NMR imaging for detection and quantification of obstruction in vessels. Invest Radiol 1982;17:554-60. Goldberg HI, Spagnoli MV, Grossman R,I, et al. MRI characteristics of carotid artery plaques. AJNR 1986;7:541.
ELASTIN, COLLAGEN, AND SOME MEC~ICAL ASPECTS OF ARTERIAL ANEURYSMS One of the most dramatic changes that occur to arteries is the formation of aneurysm. Vessels that become aneurysmal exhibit three mechanical characteristics: they increase in diameter, they become stiffer, ~,2 and they tend to become tortuous. The studies described herein were undertaken to examine the role o f elastin and collagen
in the formation o f aneurysms and the development of tortuosity. Common carotid arteries were exposed in dogs immediately after death. Segments 6 to 7 cm in length were measured and excised. Segments of human iliac arteries, approximately 3 cm in length, were similarly obtained from human subjects at post mortem examination. The arterial segments were placed in buffered Krebs-Ringer solution at 37 ° C, p H 7.4. The vessels were cannulated at both ends and mounted horizontally in a tissue bath. Diameter was measured with a linear-displacement transducer, and longitudinal retractive force was measured with a Grass force transducer (Grass Instrument Co.; Quincy, Mass.). The vessels were pressurized in 25 mm H g steps up to 300 mm H g to relax them. Then they were treated intraluminally with elastase (8 units/m/ for the dog vessels; 40 units/ml for the human vessels) or collagenase (64 units/ml for the dog vessels; 320 units/ml for the human vessels). The arteries then were distended by pressure steps or were held at 0 mm H g and subjected to stepwise longitudinal extension. Results demonstrate that degradation o f elastin causes aneurysmal dilatation (Fig. 1) and increased stiffness as the load is shifted to collagen? None of them ruptured. By contrast, degradation o f collagen causes a small amount of dilatation and decreased stiffness (Fig. 1). All of these vessels ruptured? Human internal iliac arteries are more prone to develop aneurysms than are the external iliac arteries, and the former exhibit dramatic responses to enzymatic treatment, especially degradation of collagen (Fig. 2). 3
0.90
N=18
N=18
N=18
COLLAGENASE 0.80
ELASTASE
E
o 070 n. I,M I5 <{
COLLAGENASE
0.6O
~
.J
Z RuJ iX uJ
0.50
0.40
L
0.30 i 0
| 5'0
| 1()0
| 150
|
/
50 PRESSURE
|
i 100
i
mm
Hg
| 150
| 0
! 50
i
! 100
|
| 150
Fig. 1. Pressure-diameter curves for dog carotid arteries. Treatment with elastase caused dilatation and increasing stiffness but not rupture. Treatment with collagenase caused slight dilatation, decreasing stiffness, and rupture. (From Dobrin et al. Arch Surg 1984; 119:405-9.)
Volume 9 Number 2 February 1989
Special communication
397
1,3d
l
1.2¢
COLLAGENASE 1.K
1.0.m
1.0( oE
COLLAGENASE
0.9,'
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ELASt'ASE ELASTASE
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,
.
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PRESSURE
i
260
'
~i
340 0
100
200
300
m m Hg
Fig. 2. Pressure-diameter curves for human internal iliac arteries. The format was the same as that in Fig. 1. Results show dramatic effects after treatment with collagenase. (From Dobrin et al. Arch Surg 1984;119:405-9.) Why do aneurysms not rupture immediately? Analysis of stability of aneurysms indicates that (1) the load is shifted from elastin to previously unloaded collagen and (2) the change in shape from a cylinder to a sphere reduces he wall stress by one half. The presence of laminated thrombus in the lumen does not contribute to the stability of aneurysmal vessel wall. Aneurysmal vessels also tend to become tortuous. Most arteries are under longitudinal traction (stretch). With pressurization the traction force fails, but the vessels undergo little change in length. 4The longitudinal force caused by pressures is given by pressure × (radius).4 Therefore as a vessel dilates the longitudinal force rises exponentially. For example, the longitudinal force is 10 times as great in an 8 cm aortic aneurysm as it is in a 2.5 cm normal aorta. This increased longitudinal force may cause the vessel to elongate between constraining branches. This causes vessel buckling (i.e., tortuosity). 4 Longitudinal extension of unpressurized arteries demonstrates that degradation o f elastin markedly reduces longitudinal retractive force exerted by the artery. By contrast, degradation of collagen has only a slight effect on longitudinal retractive force. Thus failure of elastin causes an-
eurysmal dilatation; this increases the longitudinal distending force. Loss of elastin also decreases longitudinal retractive force. All of these factors predispose to vessel elongation and the development of tortuosity. In conclusion, elastin bears loads in the circumferential and longitudinal directions. Failure of elastin causes vessels to become ancurysmal and, by several mechanisms, to become tortuous. Collagen bears loads only in the circumferential direction and only at large dimensions. Failure of collagen permits vessels to dilate only slightly but compromiscs their tensile strength. These studies demonstrate that a critical early step in the development of aneurysms involves failure of wall elastin. This agrees with estimates of the load borne by the elastic lamellae in normal and aneurysmal vessels2 ,~An extensive discussion of the various mechanical and hemodynamic factors contributing to the pathogenesis of abdominal aortic aneurysms is given elsewhere.'
Philip B. Dobrin, ZcID, PhD Department of Surgery Loyola University and Hines Veterans Administration Hospital Hines, Illinois
398
Special communication
REFERENCES 1. Glagov S. Pathology of large arteries. In: Abramson DI, Dobrin PB, eds. Blood vessels and lymphatics in organ systems. New York: Academic Press, 1984:39-53. 2. Sumner DS, Hokanson DE, Strandness DE Jr. Stress-strain characteristics and coUagen-elastin content of abdominal aortic aneurysms. Surg Gynecol Obstet 1970;130:459-66. 3. Dobrin PB, Baker WH, Gley WC. Elastolytic and collagenolytic studies of arteries: implications for the mechanical properties of aneurysms. Arch Surg 1984;119:405-9.
Journal of VASCULAR SURGERY
4. Dobrin PB, Baker WH, Schwarcz TH. Mechanisms of arterial and aneurysmal tortuosity. Surgery 1988; 104: 568-71. 5. Wolinsky H, Glagov S. A lamellar unit of aortic medial structure and fimction in mammals. Circ Res 1967;20:99-111. 6. Zatina MA, Zarins CK, Gewertz BL, et al. Role of medial lamellar architecture in the pathogenesis of aortic aneurysrns. J VAsc SURG 1984;1:442-8. 7. Dobrin PB. Pathophysiology and pathogenesis of atherosclerotic aneurysms: current concepts. Surg Clin North Am. (In press.)