The Effects of Laser Energy on the Arterial Wall

Basic Science in Vascular Surgery S e c t i o n E d i t o r - B r u c e L . G e w e r t z , M D , ( C h i c a g o , Illinois)

The Effects of Laser Energy on the Arterial Wall William E. Faught, MD, Peter F. Lawrence, MD, Salt Lake City, Utah

Laser energy has been proposed as a method of resecting atherosclerotic plaque since the mid 1960s. However, only over the past several years have we come to understand some of the unique interactions of the laser with cardiovascular tissue. In laser angioplasty a major challenge has been choosing the optimal laser and duration of laser exposure to achieve adequate resection of plaque, while minimizing such complications as thrombosis, perforation, embolization, aneurysm formation, and accelerated atherosclerosis. Ultimately we must develop a more selective laser that resects plaque while leaving adjacent arterial wall uninjured. This review describes the physics of laser energy, the different lasers available for use in the cardiovascular system, laser-arterial wall interactions, and some of the limitations of laser angioplasty. (Ann Vasc Surg 1990;4:198-207). KEY WORDS:

Laser energy; laser angioplasty; atherosclerosis; arterial wall.

flash-tamp pumped

Laser energy was first proposed as a means of resecting atherosclerotic plaque in arteries by McGuff and Bushnell in 1964 [1]. Since that time there have been many developments in both laser technology and our understanding of the effects of laser energy on cardiovascular tissue. To appreciate the potential as well as the limitations of laser angioplasty, we must understand the unique interactions that occur between the laser and the arterial wall. A laser is a device that converts energy into light. Laser radiation has three properties: (1) It is collimatedmall rays are parallel to each other; (2) it is coherent--all waves are in phase in both space and time; and (3) it is monochromatic--all radiation has the same wavelength. Wavelengths proposed for vascular use range from infrared CO 2 to ultraviolet excimer lasers (Fig. 1). Most lasers produce a

Fig. 1. Wavelengths of lasers in clinical and research use. -- clinical use, FDA approved. = clinical use, not FDA approved. = research use.

From the Department of Surgery, University of Utah, Salt Lake City, Utah. Reprint requests: Peter F. Lawrence, MD, University of Utah, Department of Surgery, 50 No. Medical Drive, Salt Lake City, Utah 84132.

single wavelength; however, dye and free electron lasers are capable of producing a band of wavelengths by modifications of the lasing medium. The process of delivery of laser energy is demonstrated in Figure 2. Generation of laser radiation

dye laser

HeCd XeClXeF

Nd-YAG

Ciz

/

i' 100

I 200

300

400

I 500

600

I

i

I

~k 700

800

I

I //

900 1,000

I 10,000

(nm)

198

VOLUME

4

BASIC S C I E N C E I N V A S C U L A R S U R G E R Y

N o 2 - 1990

199

DIAGRAM OF LASER Laser Medium

.,ll o Fully N~lo~tln|

~=rtiMly affecting

mirror

nirror

Laser fiber

Power supply

Fig. 4. Distribution of laser energy and spot size. With divergent beam, as laser tip is moved away from tissue, spot size increases, thereby reducing energy density. Energy density follows a Gaussian distribution as illustrated above.

Fig. 2. Components of a laser.

occurs when atoms of an active medium are excited by an energy source, raising electrons to a higher energy level. As the electrons in the excited state return to a lower energy state, photons are emitted. The emitted photon can interact with other electrons in the excited state, causing the emission of two photons of the same wavelength. This process is amplified in the laser chamber by mirrors at either end of the active medium, which reflect the photons back and forth. An aperture at one end of the laser allows a small portion of the light to escape. Once the light leaves the device, it is generally delivered to the tissue through quartz or silicon optical fibers. Some lasers, such as CO2, do not use fibers for delivery--the light is reflected by a series of mirrors to the treatment area.

LASER VARIABLES Lasers are capable of emitting light in four modes, each with a different effect on the arterial wall. When continuous energy is delivered, the laser is said to operate in the continuous wave (cw) mode (Fig. 3). The chopped mode delivers continuous thermal laser energy with periodic interruptions. The chopped mode allows better control of energy delivery and allows tissue to cool between

't

0-100 Watt

""

!

Time (sac.) Conti~uous Wave

I

!

Time (sec.) Chopped

I

I

Time (sec.) Pulsed

/

il

I

Time (sec.) Q-Switched

Fig. 3. Modes of delivery of laser energy.

energy delivery. The pulsed mode delivers energy with even shorter increments or pulses than the chopped mode. These lasers may achieve a higher intensity or power than those operating in the continuous mode. The Q-switched mode produces pulses of extremely short duration (nanoseconds) with the delivery of very high peak power. A fifth method of delivery occurs after the laser energy has entered the delivery fiber. The light can be converted back to heat via metal-capped or sapphire probes. Most lasers can be used in only one or two modes. There is no laser that can deliver energy in all four modes. The effect of laser energy on the arterial wall is determined largely by the energy density delivered. Energy density (joules/cm z) is defined as Power (watts) x Time (sec) Area (cm 2) and represents the amount of energy delivered per unit area. Power is a variable which significantly affects ablation of arterial wall plaque. For a given wavelength and unit area, the amount of power (watts) delivered determines the amount of energy delivered. For any given laser, with increasing power the effect of the laser on tissue is accelerated. Low power, i.e., 0.5 watts argon, is useful for arterial fusion laser assisted vascular anastomoses [2], while higher powers, i.e. 10-20 watts argon, of the same wavelength laser can be used for plaque ablation or tissue cutting. The effect of laser energy on the arterial wall can also be altered by varying laser spot size. Lasers have a Gaussian distribution of power over the spot area, with the greatest power at the center (Fig. 4). When the distance between the laser and tissue is increased, divergence of the laser beam will cause the area to increase and the energy to decrease. The

200

BASIC SCIENCE IN VASCULAR SURGERY

P(t} A

T

POWER

Tissue Temperature

/

i

I....

THERMAL i RELAXATION

]

T,ME

10~

Ppk

Pav 1

Temperature

--I

0 p/*,A Tissue THERMAL ~t Tern r t u r e RELAXATION p TTemp; a ~ TIME

TIME

2

. . . . . . . . . .

10 9

(t)

POWER pk Pay

ANNALS OF VASCULAR SURGERY

I i i

Temperature

Power 106 Density (W/cm) 103

TIME (t) Fig. 5. When thermal laser is used, time interval between pulses determines degree of tissue injury and cooling between pulses. If this interval is long (top), surrounding tissue effects are less than if interval is short and no cooling between pulses occurs (bottom). In addition average power (dotted line) is greater when interval between pulses of similar power are shorter.

formula, Power density = Power (W) × 100, d2 where d = beam diameter, demonstrates the critical variables of spot size or beam diameter on the energy delivered to the tissue. The distance between the laser and vascular wall is additionally important when the medium through which energy is delivered, e.g. blood, absorbs some of the laser energy. The length of time of delivery of continuous wave or pulsed laser energy is an additional critical factor which affects the laser arterial wall interaction [3]. With all other variables constant, an increase in the length of time of energy delivery causes an increase in the volume of tissue that is injured, heated, or ablated. Short pulsed delivery, with time between pulses to allow for cooling, reduces surrounding arterial wall injury (Fig. 5). Adjacent tissue injury is reduced because the duration of energy exposure is less than the thermal relaxation time (the characteristic time for first order thermal diffusion) of the irradiated tissue. These short delivery times with high peak power, as with excimer, pulsed CO2, and Q-switched Nd-YAG lasers, cause precise incisions in the arterial wall, with less surrounding thermal injury than with continuous wave lasers. In addition, there is some indirect evidence that very short pulses of high energy, i.e., 10-610 j5 sec, cause tissue ablation without thermal energy, so that precise cutting without heat can be accomplished. These lasers are sometimes called "cold lasers." The wavelength of the laser determines the components of the tissue which will absorb the energy and consequently the distribution of the laser en-

1 0 -3

10a2

10.9

10"~ 10"3 1 Interaction Time(s)

10 3

Fig. 6. Effect of laser energy on tissue is determined by length of time of delivery of energy dose. If time of delivery is short, electro-mechanical or photoablative tissue injury occurs. If delivery time is longer, thermal injury occurs. (Adapted from Boulnois JL: Photophysical processes in recent medical laser development. A review. Laser Med Sci 1986; 1:47-65).

ergy within the tissue. Each laser wavelength is absorbed differently by water, pigments, nucleic acids, and proteins within the tissue. Consequently, each wavelength has a different effect on the arterial wall, even with the same energy density. The effect of argon has been studied most extensively in cardiovascular tissue because it can be delivered through a flexible catheter, and it causes an intermediate depth of injury to the artery, due to its absorption by nucleic acids and red pigment. The Nd:YAG laser is poorly absorbed by water and causes the deepest penetration of the arterial wall. The CO2 and excimer lasers are absorbed by water and therefore cause a superficial injury to arterial wall; however, when the transmission medium, e.g. blood, has a high content of water, the medium absorption may reduce the amount of energy that is carried to the tissue. INTERACTION OF LIGHT WITH TISSUE Photomedical processes can be classified into four categories based upon the amount of time it takes to deliver an energy dose to the tissue (Fig. 6). The interaction between laser and tissue may be electromechanical (10 ps to 20 ns), photoablative (10 ns to 100 ns), thermal (I ns to I0 see), or photochemical (10 sec to 1000 see). Thermal interaction

Most surgical applications of the laser rely on the conversion of laser energy into thermal energy. The wavelength of the laser and absorption characteris-

VOLUME 4 N o 2 - 1990

BASIC S C I E N C E I N V A S C U L A R S U R G E R Y

tics of the tissue determine the depth of tissue penetration for a given energy dose. Absorption of energy occurs in free water, melanin and hemoglobin pigments, and in nucleic acids and aromatics. When tissue absorbs continuous wave laser energy, heating occurs [4]. At 45°C, tissue shrinkage due to protein conformational changes and membrane alterations occur. Beyond 60°C protein denaturation results in tissue coagulation. Carbonization of tissue occurs at approximately 80°C, and beyond 100°C vaporization occurs, primarily from heated free water. These thermal changes can be manipulated by peak temperature to obtain the desired effect, i.e. coagulation, hemostasis, or resection of tissue. In laser angioplasty the major challenge is adjusting the wavelength and duration of laser exposure to achieve resection of plaque while minimizing thermal damage to adjacent arterial wall. Thermal lasers are limited by their inability to vaporize the components of plaque, such as calcium, which have a very high vaporization temperature (> 700°C). Electromechanical interaction

In this type of reaction, high power laser energy is delivered in extremely short duration pulses. When focused at a target, this energy generates electric fields, which develop a microplasma or free electron mass. The shock wave created by the microplasma disrupts tissue with minimal surrounding thermal injury [5]. Nd:YAG lasers in the Qswitched mode have been used to investigate ablation of the atherosclerotic plaque. Precise cutting and removal of plaque, whether fibrous, fatty, or calcified can be accomplished with this laser. However, while initial studies are promising, the transport of this high peak power within optical fibers is currently not feasible and may limit its clinical value. Photoablative interaction

Photoablation is a nonthermal process through which direct breakage of intramolecular bonds in polymeric chains occurs upon exposure to ultraviolet radiation. Ultraviolet radiation is strongly absorbed by many biological molecules between 200 and 360 nm, allowing the energy to be highly absorbed by the surface tissue. This feature led to the development of the ultraviolet excimer laser, which produces precise cuts in a variety of tissues, including atherosclerotic plaque in human vascular tissues [6,7]. Excimer lasers are pulsed gas lasers which contain a rare gas and halogen within the active medium to produce pulses of short wavelength, high energy ultraviolet light. An appealing feature of the excimer laser is its ability to resect

201

both noncalcified and calcified plaque in vitro with its high peak powers (100-250 nJ) and short duration pulses, i.e. 150 ns, [7,8]. There are, however, two limitations of the excimer laser: (1) concern for the possibility of carcinogenicity of ultraviolet irradiation and (2) inability of commercially available fiberoptics, to transmit the high peak powers associated with this energy source, without damage to the fiberoptic system. However, Grundfest recently designed a flexible fiberoptic system consisting of three 300 micron fibers which may allow for the delivery of this energy through the 308 nm excimer laser, without damaging the fiberoptic system [9]. Further studies regarding these two liabilities are needed to prove the utility of the excimer laser in vivo in humans. Photochemical interaction

On one end of the exposure scale for extremely long interaction times and lower power densities are photochemical transformations. Photochemical interaction occurs when a chromophobe, a molecule capable of causing light-induced reactions, is sensitized by laser energy. Such photosensitizers as hematoporphyrin derivative (HPD) and tetracycline can be given intravenously, and these will concentrate within atherosclerotic plaque. It is postulated that when these photosensitizers are activated by laser energy, they cause injury or death of tissue through the generation of singlet oxygen [10]. Theoretically, photochemical removal of plaque could be accomplished with minimal or no injury to the surrounding normal wall. Spears was the first to show increased uptake of HPD in early atherosclerotic plaques in rabbits [11]. Straight demonstrated the localization of HPD in both early and advanced atherosclerotic plaques in swine [12]. In human aorta, it has been shown that plaque ablation caused by ultraviolet laser radiation was twice as extensive in tetracycline-treated plaque as compared to nontreated plaque [10]. Figure 7 demonstrates a 2:1 ratio of affinity of HPD for plaque. When HPD sensitized plaque is exposed to laser energy, the plaque is ablated, leaving normal-appearing artery intact. While the mechanism of HPD and tetraycline concentration within atheromas is unknown, it is postulated that uptake is through proliferating smooth muscle cells [13]. However, it remains to be demonstrated whether advanced, calcified plaque, which has few proliferating smooth muscle cells, will localize HPD or tetracycline and allow for selective ablation of the plaque. ACUTE EFFECTS ON THE ARTERIAL W A L L The general principles that have been discussed in the preceding sections can be applied to interac-

202

ANNALS OF VASCULAR SURGERY

BASIC SCIENCE I N VASCULAR S U R G E R Y

Reflection

Laser

/

Laser

",llmm,"

Absorption

Scattering

Scattering Tran., mission

IIIIIIII

III

Fig. 8. Distribution of laser energy within tissue. Fig. 7. Fluorescence photograph demonstrating increased affinity of hematoporphyrin derivative (HPD) for atherosclerotic plaque, This affinity may allow for selective laser resection. Plaque with HPD uptake has white fluorescent appearance in this photograph, and is different from surrounding intima. (Courtesy of J. M. Vincent).

tions between the laser and the arterial wall. Argon, COz, and Nd:YAG lasers have been studied most extensively because of their commercial availability. The six major determinants of each laser's effect on the arterial wall are: wavelength of the laser, laser power, duration of laser exposure, distance between the energy beam and target tissue, the media through which the energy is delivered and absorption characteristics of the target tissue.

TRANSMISSION MEDIUM VARIABLES The absorption coefficient of the medium through which a given burst of laser energy travels in route to the plaque contributes to the effect on the arterial wall. For example, with the argon laser, which is readily absorbed by hemoglobin pigments within blood, red blood cells must be removed from the field, generally by irrigation with saline because it is an excellent medium for transmitting argon laser energy. Otherwise, the red blood cells within the medium would absorb 99% of the argon energy. If a medium avidly absorbs a laser wavelength, the laser beam must be placed close to or in direct contact with the tissue. For example, the CO2 laser, which is avidly absorbed by water, requires a blood and saline free medium, such as air, or direct contact with the plaque to avoid complete absorption of CO 2 energy by the medium. Nd:YAG laser energy is best transmitted through a dilute blood perfusion medium, allowing for effective ablation of plaque. Thus, choosing the appropriate medium for trans-

mission of laser energy is important to successful plaque removal.

TISSUE VARIABLES The composition of the tissue that receives laser energy determines the distribution of that energy within the tissue. When laser light is directed at tissue, the tissue can reflect, absorb, transmit, or scatter the light (Fig. 8). One of the key questions is whether atherosclerotic plaque and normal human aorta absorb similar laser wavelengths differently, i.e. whether there is selective absorption by plaque at any wavelength. Prince and associates studied the absorption coefficient of a small number of normal human aortas and fibrous aortic plaques and found there was differential absorption of laser energy between plaque and normal arterial wall with wavelengths between approximately 420 and 530 nm [14] (Fig. 9). Beta-carotene, a component of many atherosclerotic plaques, absorbs laser energy within this absorption spectrum and may account for this differential effect. This differential absorption may have importance clinically because a laser which has a wavelength between 400 and 500 nm, such as argon or pulsed dye, can be used to selectively resect the plaque, with less injury to surrounding normal arterial wall. Orme and colleagues, however, have found great individual sample variability within normal aorta, fibrofatty plaque, and calcified plaque, and no clear wavelengths of selective absorption [15] (Fig. 10). There may also be differences in absorption between large and small arteries, i.e., the aorta versus coronary arteries, because of differences in smooth muscle and elastic tissue content [ 14]. Similarly, as calcified plaque has the highest thermal conductivity and thermal diffusivity, it requires the greatest

VOLUME 4

BASIC SCIENCE IN VASCULAR SURGERY

N o 2 - 1990

203

200180-

E

1602 140 ~

e,,, 0

0 ¢.>

,"

120loo-

80-

0

6o0 o~

,<

roma

40Normal

200 "1 4O0

I

!

I

!

~ |

, !

!

I

!

'!

I

!

!

500

!

!

!

!

575

Wavelength (nm) Fig. 9. Comparison of absorption coefficients between normal and atheromatous aorta. There is increased absorption of laser energy between 430 to 540 nm in atheromatous plaque. Argon laser operates at a wavelength that may take advantage of this selective absorption by plaque. (Adapted from Prince MR: Preferential light absorption in atheromas in vitro: Implications for laser angioplasty. Clin lies 1985;33.'218A).

Fig. 11. Interaction of continuous wave thermal laser with calcified plaque. This type of laser is unable to penetrate calcium within plaque and often causes severe thermal injury to surrounding wall and media. (Schematic depicts energy of 300, 500, and 800 J/cm=).

tissue injury may vary. Several investigators have shown that normal artery develops a superficial energy for ablation with all other variables constant injury when subjected to approximately 300 J/cm 2 [16]. of energy from a continuous wave thermal laser such as CO2, argon or Nd:YAG [17]. The major microscopic findings are swelling of the intima, HISTOLOGY OF ACUTE LASER INJURIES subintima, and superficial media of the artery. The lateral injury is determined by the length of time Studies have shown that all lasers can effectively resect noncalcified atheromas, although the rate of over which the energy is delivered. As power ablation, depth of injury, and degree of surrounding increases to 600-900 J/cm 2, the laser begins to cut through arterial wall. There are four characteristic histological findings with continuous wave laser injury. A central area of vaporization is surrounded by an area of necrotic tissue, which is in turn Fibrol|Ity Plaque surrounded by an area of thermal and acoustical injury. Carbonization on the cut edges of the arterial wall is generally present. In the presence of calcification, lasers which operate in the continuous mode are unable to penetrate the calcium, yet there is often extensive thermal injury to surrounding " arterial wall and media (Fig. 11). There is a nonlinear relationship between energy density and ablation rate with continuous wave lasers so that long exposure times with lower power ,o ~ ~ _-~ cause greater thermal injury than high power with 3SO ~00 .~0 SO0 550 ~00 ~50 700 rSO 8O short delivery times. This may explain the problem W...,l..th 1..) of controlling tissue ablation and avoiding vascular perforation with cw lasers [18]. Fig. 10. Comparison of absorption coefficients with In contrast to thermal lasers operating in the same specimen of fibrofatty plaque. Notice marked continuous wave mode, pulsed lasers can resect variation in absorption, despite sampling from within same segment of vessel. (Courtesy of E. C. Orme). both fibrous and calcified plaque, with less injury to

!1

if10

204

BASIC SCIENCE I N VASCULAR S U R G E R Y

Fig. 12. Interaction of pulsed laser with calcified plaque. Pulsed lasers can resect calcified plaque with minimal injury to surrounding arterial wall. (Schematic depicts energy of 300, 500, and 800 J/cm~). the surrounding arterial wall (Fig. 12). Pulsed lasers used clinically include CO z, Nd:YAG, argon, and excimer lasers. The relationship between energy density and ablation rate is linear for pulsed lasers. Deckelbaum has shown that chopped pulse COz lasers, with an interval of cooling between pulses, will ablate both fibrous and calcified plaque by means of a thermal interaction with minimal surrounding arterial wall injury [19]. Because of the interval between pulses there is minimal conduction of thermal energy to surrounding artery; on histological section the incision appears clean with little carbonization or injury. Grundfest and Litvack have also investigated the effect of pulsed lasers on the arterial wall [20]. They demonstrated that irradiation in the 10 to 145 ns range using the pulsed ultraviolet excimer laser at 308 nm caused ablation of the arterial wall by a different mechanism than with continuous lasers. Excimer lasers ablate plaque by a photoablative mechanism (the breakage of molecular bonds) rather than by a thermal mechanism. They also found that pulsed lasers with wavelengths greater than 308 nm, i.e., argon and Nd:YAG pulsed lasers, produced unpredictable ablation. Using the excimer laser, the depth of penetration for any given amount of energy was directly proportional to the number of pulses. The width of the incision did not change. Finally, they also demonstrated the ability of the excimer laser to resect calcified atheroma without adjacent arterial wall injury, although the rate of calcium resection is markedly slower than through noncalcified plaque.

ANNALS OF VASCULAR SURGERY

Fig. 13. Interaction of metal probe with calcified arterial wall. Hot tip laser distributes heat energy in a uniform fashion but cannot ablate calcified plaque. Instead plaque is compressed and displaced away from the metal probe. (Schematic depicts energy of 300, 500, and 800 J/cmZ).

Hot-tipped laser effects on vascular tissue

Direct beam thermal and pulsed lasers have had problems resecting a significant volume of plaque, as well as having a relatively high incidence of perforation of the vessel wall. This led Sanborn and coworkers to investigate the "hot-tipped" laser [21]. This laser is comprised of a fiberoptic laser system with a metal cap on the end. The laser, typically argon or Nd:YAG, transmits the laser energy down a flexible fiber to a metal cap which is heated, converting the laser energy into thermal energy. The metal cap causes uniform distribution of heat, while the mechanical effect of forcing the smooth metal probe through the plaque may result in a smoother, less thrombogenic arterial wall surface than when direct laser energy is used (Fig. 13). Factors that have been shown to correlate with successful recanalization of a vessel with the hottipped laser without wall perforation include heating the cap to at least 200°C (optimally 300--400°C for rapid ablation), and a probe/vessel ratio of less than 0.75. Commonly used hot-tipped diameters are generally 2.0-3.0 mm, although tips as small as 0.8 mm and as large as 3.5 mm have also been used. The hot-tipped laser rapidly heats and cools as laser energy is delivered and discontinued. Sanborn and others have shown that by light and electron microscopy, there is minimal endothelial denudation, minimal charring, and thinner, less extensive thrombus formation with hot-tipped lasers as compared to bare-tipped lasers [21]. There have been

VOLUME 4 N o 2 - 1990

BASIC SCIENCE I N V A S C U L A R S U R G E R Y

few studies of the effect of the hot-tipped laser on ablation of calcified plaque; however, calcified plaque must be raised to > 700°C for ablation, and this is not feasible with a hot-tipped laser. The potential advantages of hot-tipped lasers are absence of beam dispersion, circumferential distribution of energy, decreased incidence of perforation with less mechanical trauma, and an increased diameter of plaque ablation [22]. Potential disadvantages include carbonization of the metal tip and adherence of atherosclerotic debris with secondary tearing of the vessel wall [20]. Geschwind and Lammer have studied a modification of the hot tipped laser, a so-called sapphire contact probe which uses Nd:YAG laser energy delivered to a sapphire lens on the tip of the fiber with results comparable to those achieved with the metal probe. This they ascribe to the combination of the sapphire probe's bare fiber irradiation plus direct laser tissue interaction [23,24]. There is also a "hybrid" device, which has a combination of a metal cap and an aperture at its tip, beyond which is a recessed lens that allows approximately 20% of the direct laser energy to pass; the remaining energy is converted to heat as in the other probes [25]. This tends to create a larger channel relative to its own diameter than does the thermal probe.

ADVERSE EFFECTS ON THE ARTERIAL WALL Thrombosis

Any procedure that removes intima and plaque will create a thrombogenic arterial wall by leaving exposed collagen fibers and eliminating the fibrinolytic system of the intact vascular endothelium. Pollack and associates evaluated thrombogenicity post-atherectomy and found that laser angioplasty of the arterial surface was significantly more thrombogenic than laser endarterectomy of the same surface [26]. Conventional endarterectomy and laser endarterectomy were similar in their thrombogenicity. In addition, the laser can fuse the endarterectomy end points, reducing the chances of intimal flap formation. Ragimov and colleagues, however, evaluated the thrombogenic properties of the arterial wall following continuous wave Nd:YAG, argon, pulsed excimer, and the laser heated metal probe using scanning electron microscopy [27]. They found similar thrombogenic properties of the arterial wall, regardless of which type of laser was used--thermal or pulsed excimer. If there is reduced thrombogenicity of the hot tip recanalized vessel, it may be due to the smooth, compressed surface which the hot tip produces. Because of increased thrombogenicity of

205

the arterial wall following any type of laser injury, it has been suggested that anticoagulation following laser recanalization may be useful [26]. Perforation

Perforation of the arterial wall is a well recognized complication of laser angioplasty. In early clinical studies perforation occurred in one-half to two-thirds of cases. The incidence of perforation of the arterial wall was great with early lasers which utilized the bare fiber system. It appears that the risk of vessel wall perforation is least with the metallic probe laser, followed by the pulsed laser and lastly, the continuous wave thermal lasers. With the cw lasers, Choy demonstrated that perforation was minimized with the argon laser by maintaining a coaxial position between the laser and the arterial wall [28]. This principle is applied clinically with a centering balloon. While argon laser energy is absorbed by a thin layer of tissue along the vessel wall, Nd:YAG laser energy has higher tissue penetration and often resuits in a higher frequency of perforation. Perforation is also dependent upon characteristics of the plaque itself, such as the degree of calcification. Subintimal hemorrhage causes the absorption of laser energy and consequently increases the risk of perforation [17]. With pulsed lasers the depth of penetration is more readily controllable and there is cooling of the tissue between pulses, which reduces injury and the risk of perforation [17]. With the metal probes, perforation rates are reduced by the blunt tip of the metal cap, the circumferential and equal distribution of energy, and the decreased surrounding tissue damage. Also of importance is the ratio of probe-to-vessel diameter. As this ratio approaches unity, the rate of radial heating increases, which means that an increasingly shorter energy duration will deliver the thermal energy necessary for perforation [29]. EmboU

Embolization of tissue fragments after laser angioplasty is another potential complication. Byproducts of laser ablation of plaque include water vapor, CO 2, Nz, H2, light-chain hydrocarbon fragments, and small protein fragments in solution [30]. Solid phase debris has been studied less often. Two recent reports found that no filterable debris was generated [28,31], whereas others describe the carbonized residue on the surface as the only solid phase by-products [32]. In a study by Labs and coworkers, using a cw argon laser, at least 2.7% (fatty streaks) and as much as 7.9% (calcified plaque) of ablated tissue by weight resulted in solid phase debris [31]. However, ablation of plaque does

206

ANNALS OF VASCULAR SURGERY

BASIC SCIENCE I N VASCULAR S URGER Y

not clinically produce debris of sufficient size to cause macro-obstruction of distal arterial beds. There may however, be a potential for transient obstruction of the microcirculation [31]. In addition, with a more sensitive organ such as the brain, the effects of laser angioplasty emboli might become clinically significant.

coworkers lased 19 vessels in rabbits with the laser probe (argon) and found no aneurysm formation at four weeks [36]. On the other hand, Lee and associates found aortic aneurysms in two of four rabbits 14 days after laser angioplasty [32].

THE FUTURE OF LASER ANGIOPLASTY LONG-TERM EFFECTS ON THE ARTERIAL WALL Although there has been a great deal of study on the short-term effects of the laser on the arterial wall, the tong-term effects are still largely unknown. The long-term complications, which may include myointimal hyperplasia, aneurysm formation, and accelerated atherosclerosis, may be more important than the acute effects in determining the efficacy and durability of laser angioplasty. The time, duration, wavelength, and total energy delivered to vascular tissue determine the extent of injury to the remaining arterial wall. Abela has shown that the cw argon laser in dogs and monkeys results in an injured arterial wall filled with a coagulum of blood and cellular debris, with few adherent platelets, at four days. There was also a minimal inflammatory response which involved fibroblasts and smooth muscle cells. Re-endothelization was seen at seven to 14 days after lasing and was complete at 30 to 60 days. Finally, within this period, there was no evidence of accelerated atherosclerosis [33]. Treat and associates studying the effect of cw CO2 lasers in rabbit aorta, found that at two weeks there was complete healing of the arterial wall with reconstitution of the previously disrupted internal elastic lamella [34]. There was no evidence of thrombus within these vessels. Theis and colleagues, evaluating the laser probe in monkeys, found that three months after lasing a fibrotic scar was present within the arterial wall. However, other evidence of thermal injury was nonexistent, and reendothelization had occurred. There was no thrombosis, embolism, aneurysm formation, or accelerated atherosclerosis [35]. Recent clinical studies, however, have shown that recanalized vessels may close many months after initial treatment, indicating that late arterial wall changes do occur. Intimal hyperplasia results when the arterial wall has been injured but not weakened. Thermal injury can be minimized by choosing the appropriate laser and wavelength and limiting laser-arterial wall contact time. The same principles can be applied to decrease the incidence of aneurysm formation which results when the media of the arterial wall is damaged, disrupting elastin and collagen. When large areas of plaque are removed, clinically significant aneurysms may also develop. Sanborn and

To optimally utilize the laser in cardiovascular and peripheral vascular surgery, one must understand the fundamentals of the interaction between the laser and the arterial wall. With further clinical and laboratory studies, we may be able to identify the optimal wavelength and optimal laser to be used under a given situation, as well as the appropriate energy density and pulse interval. Ablation of calcified plaque is a domain which requires further developments. At present the pulsed lasers are the most efficient at ablating calcified plaque; however, recanalized calcified channels are often inadequate in diameter for long term patency. Whether photosensitizers such as HPD and tetracycline will be useful in ablating calcified plaque needs further investigation in humans. Lastly, the complication rate of lasers needs improvement. With the pulsed and metal probe lasers, we have seen a decrease in the incidence of thrombosis and perforation. The long-term consequences of laser angioplasty are still undetermined. Decreasing the thrombogenicity of the arterial wall appears to be a key element in solving these problems. Post-laser angioplasty anticoagulation may prove to be useful. Ultimately, we must continue to develop a more selective laser that resects greater volumes of plaque while leaving the remaining arterial wall uninjured.

REFERENCES t. McGUFF PE, B U S H N E L L D. Studies of the surgical applications of the laser. Surg Forum 1963;14:143-145. 2. WHITE RA. Technical frontiers for the vascular surgeon: laser anastomotic welding and angioscopy-assisted intraluminal instrumentation. J Vasc Surg 1987;5:673--680. 3. LITVACK F, GRUNDFEST WS, GOLDENBERG T, et al. Pulsed laser angioplasty: wavelength, power, and energy dependencies relevant to clinical application. Lasers Surg Med t988;8:60-65. 4. SLINEY DH. Laser-tissue interactions. Cl Chest Med 1985; 2:203-208. 5. PULIAFITO CA, STEINERT RF. Short-pulsed Nd:YAG laser microsurgery of the eye: biophysical considerations. 1EEE J Quantum Electron 1984;20 12:1442. 6. RONN A. Laser chemistry. Sci Am 1979;240:114-130. 7. GRUNDFEST WS, LITVACK F, FORRESTER JS, et al. Laser ablation of human atherosclerotic plaque without adjacent tissue injury. JAAC 1985"5(4):929-933. 8. ISNER JM, DONALDSON RF, DECKELBAUM LI, et al. The Excimer Laser: Gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease. JACC 1985 ;6(5): 1102-1109.

VOLUME 4

No 2 - 1990

BASIC SCIENCE I N VASCULAR S U R G E R Y

9. GRUNDFEST WS, LITVACK F, HICKEY A. The current status of angioscopy and laser angioplasty. J Vasc Surg 1987;5(4):667-672. 10. MURPHY-CHUTORIAN D, KOSEK J, MOK W, et al. Selective absorption of ultraviolet laser energy by human atherosclerotic plaque treated with tetracycline. A m J Cardiol 1985;55:1293-1297. 11. SPEARS JR, SERUR J, SHROPSHIRE D, et al. Fluorescence of experimental atheromatous plaques with hematoporphyrin derivative. J Clin Invest 1983;71:395-399. 12. STRAIGHT RC, VINCENT GM, HAMMOND EH, et al. Porphyrin retention and photodynamic treatment of diet induced atherosclerotic lesions in pigs: photodynamic therapy of tumors and other disease. Padova, Italy, Libreria Progetto, 1985, pp. 350--352. 13. LITVACK F, GRUNDFEST WS, FORRESTER JS, et al. Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits. Am J Cardiol 1985; 56:667-671. 14. PRINCE MR, DEUTSCH TF, MATHEWS-ROTH MM, et al. Preferential light absorption in atheromas in vitro: implications for laser angioplasty. Clin Res 1985;33:218A. 15. ORME EC. Personal communication, 1989. 16. WELCH AJ, VALVANO JW, PEARCE JA, et al. Effect of laser radiation on tissue during laser angioplasty. Lasers Surg Med 1985 ;5:25 t-264. 17. LAWRENCE PF, DRIES DJ, MOATAMED F, et al. Acute effects of argon laser on human atherosclerotic plaque. J Vasc Surg 1984;1:852--859. 18. FARRELL EM, HIGGINSON AJ, NIP WS, et al. Pulsed excimer laser angioplasty of human cadaveric arteries. J Vasc Surg 1986;3:284-287. 19. DECKELBAUM LI, ISNER JM, DONALDSON RF, et al. Use of pulsed energy delivery to minimize tissue injury resulting from carbon dioxide laser irradiation of cardiovascular tissues. JACC 1986;7(4):898-908. 20. GRUNDFEST WS, LITVACK IF, GOLDENBERG T, et al. Pulsed ultraviolet lasers and the potential for safe laser angioplasty. Am J Surg 1985;150:220-226. 21. SANBORN TA. The use of thermal-tip laser probe in occluded arteries. In arterial surgery: New diagnostic and operative techniques. Orlando, FL: Grune and Stratton, 1988, pp 69-77, 22. ABELA GS, FENECH A, CREA F, et al. "Hot-Tip": Another method of laser vascular recanalization. Lasers Surg Med 1985;5:327-335. 23. GESCHWIND HJ, BLAIR JD, MONGKOLSMAI D, et al.

24. 25.

26. 27.

28. 29. 30. 31.

32.

33.

34. 35.

36.

11118

207

Development and experimental application of contact probe catheter for laser angioplasty. JACC 1987;9(1):101-107. LAMMER J, KARNEL F. Percutaneous transluminal laser angioplasty with contact probes. Radiology 1988;168:733737. ABELA GS, SEEGER JM, BARBIERI E, et al. Laser angioplasty with angioscopic guidance in humans. J Am Coil Cardiol 1986;8:184-192. POLLACK ME, E U G E N E J, HAMMER-WILSON M, et al. The thrombogenic potential of argon ion laser endarterectomy. J Surg Research 1987;42:153-158. RAG1MOV SE, BELYAEU AA, VERTEPA IA, et al. Comparison of different lasers in terms of thrombogenicity of the laser treated vascular wall. Lasers Surg Med 1988; 8:77-82. CHOY DSJ, STARTZER S, LOUBEAU JM, et al. Embolization and vessel wall perforation in argon laser recanalization. Lasers Surg M e d 1985;5:297-308. LABS JD, WHITE RI, ANDERSON JH, et al. Thermodynamic correlates of hot tip laser angioplasty. Investigative Radiology 1987;22:954-959. CASE RB, CHOY DS, DWYER EM, et al. Absence of distal emboli during in vivo laser recanalization. Lasers Surg Med 1985;5:281-289. LABS JD, MERILLAT JC, WILLIAMS GM. Analysis of solid phase debris from laser angioplasty. Potential risks of atheroembolism. J Vasc Surg 1988;7:326-335. LEE G, IKEDA RM, THEIS JH, et al. Acute and chronic complications of laser angioplasty: vascular wall damage and formation of aneurysms in the atherosclerotic rabbit. A m J Cardiol 1984;53:290-293. ABELA GS, CREA F, SEEGER JM, et al. The healing process in normal canine arteries and in atherosclerotic monkey arteries after transluminal laser irradiation. A m J Cardiot 1985;56:983-988. TREAT MR, WELD FM, WHITE JV, et al. Effect of C02 laser on the luminal surface of blood vessels in vivo. Lasers Surg Med 1983;3:247-254. THEIS JH, LEE G, CHUN MC, et al. Effects of simultaneous viewing and vaporization of plaques using the steerable laser-heated metal cap in the atherosclerotic money model. Lasers Surg Med 1987;7:414---420. SANBORN TA, HAUDENSCHILD CC, GARBER GR, et al. Angiographic and histologic consequences of laser thermal angioplasty: comparison with balloon angioplasty. Circulation 1987;75(6): 1281-1286.