Injury, Int. J. Care Injured (2005) 36, 963—969
www.elsevier.com/locate/injury
An experimental model of reproducible liver trauma ˇijev d, Jana Wahl a, Dean Ravnik c, Milosˇ Wahl a,*, Eldar M. Gadz ˇar b, Alojz Pleskovic ˇa Jani Pec a
Medical Centre Ljubljana, Department of Abdominal Surgery, Zalosˇka 7, 1000 Ljubljana, Slovenia University of Ljubljana, Veterinary Faculty, Cesta v Mestni log 47, 1000 Ljubljana, Slovenia c University of Ljubljana, Medical Faculty, Institute of Anatomy, Korytkova 2, 1000 Ljubljana, Slovenia d Maribor Teaching Hospital, Slovenia b
Accepted 2 November 2004
KEYWORDS Liver trauma; Experimental surgery; Pig
Summary The aim of the study was to create an experimental model of reproducible and controllable liver trauma in pigs. The few reported experimental models of liver trauma use the ‘‘clamp and crush’’ mechanism of injury and do not cause reproducible liver injury. In the present study, force was applied through the thoracic wall to mimic a chest injury. Nine pigs were used as experimental animals. In anaesthetised animals, blunt liver trauma was caused with a crossbow using an arrow with a spherical aluminium head as a projectile. Liver injuries of stages II to III according to liver injury scale were inflicted on all the animals. The stage of liver trauma was proportional to the pressure impulse (ratio between the product of the arrow’s mass (m) and the velocity (v) and the contact surface area of the arrow (S)). The presented model of controllable liver injury will enable the study of various aspects of liver trauma since the experiment can be designed in such a way to produce a spectrum of liver injuries. # 2004 Elsevier Ltd. All rights reserved.
Introduction Despite advances in diagnostics and treatment, liver injuries still present a serious medical problem and mortality of high-grade liver injuries remains
* Corresponding author. Present address: Medical Centre Ljubljana, Department of Abdominal Surgery, Peter Drzaj Hospital, Vodnikova 62, 1000 Ljubljana, Slovenia. Tel.: +386 1 522 5561; fax: +386 1 522 5601. E-mail address:
[email protected] (M. Wahl).
high.2,11,12,16,17,20,21 The strategy of liver injury management changed several times in the last three decades; nowadays conservative treatment is advocated in haemodinamically stable patients.5,6,14,17,20 Liver resection in haemodynamically unstable patients carries high mortality rates and is no longer advocated.3,7,8,13,18,24 Most of the experience with liver trauma has come from clinical experience with injured patients and only a few animal models of liver trauma have been reported to date.1,9,10,22,23 Bakker et al.1 published a paper on an experimental study in
0020–1383/$ — see front matter # 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2004.11.003
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Figure 1
The arrow on its way to the chest wall.
which liver trauma was induced with the crush— clamping method. A similar method was used in a report of aprotinin trial in liver crush injury presented by Thomae et al.23 Crush—clamping has also been used to injure liver in our early reports from 1996—1997.9,10 Stevens reported an experimental study on eight pigs in which liver injury was inflicted in a similar way and mesh wrapping performed on half of the animals.22 To our knowledge, these are the sole reports of experimentally induced liver trauma. The aim of the present experiment was to create an animal model that would authentically reproduce the force directed to the lower parts of the thorax causing blunt liver injury. Since the experiment is designed in a way that various grades of liver injury can be predictable produced it enables further evaluation of effects of liver trauma. Crossbow is a medieval type of bow fixed to a shaft with a mechanism of pulling back and releasing the string. The modern compound crossbow (see Fig. 1) is designed in a way that with its limb system it can store more energy than classic crossbow or bow. The laser scope and metallic support, which was used in our experiment, enable very accurate shooting while the spherical top of the arrow that was designed exclusively for this experiment assures non-penetrant injury of the chest wall. In our experiments, the compound crossbow has proven as a superior tool for producing liver injury since it is well calibrated and the energy can be easily controlled with the weight of the arrow. Rubber crossbow arrows used by police have been reported to
produce liver trauma25 and there was also a report on incidental injury caused by crossbow.19 For the reasons of similarity of liver anatomy and convenience pigs were chosen as experimental animals.4
Materials and methods Nine Swedish Landrace pigs, 20—35 kg in weight, were used as experimental animals. In accordance with the Ethical Committee’s provisions experimental animals were premedicated and general anaesthesia was induced and supported according to anaesthetic protocol. Animals were premedicated with midazolam (Dormicum 5 mg/5 ml, Roche) 3 mg/kg i.m., ketamine (Ketamin 10%, Veyx-Pharma GmbH) 10 mg/kg i.m. and xilazine (Rompun 2%, Bayer, 20 mg/ml) 0.5 mg/kg i.m. Pigs were induced with thiopentone (Nesdonal 1 g, Merial) 5—10 mg/ kg i.v. and intubated with endotracheal tube (I.D. 8 mm). They were connected to the anaesthesia machine using circle circuit. During spontaneous breathing they were oxygenated with 100% O2 (FiO2 = 1.0) 4 l/min. Soon after induction morphine (Morphini hydrochloridium 20 mg/ml, Alkaloid Skopje) was administered at dose 0.2 mg/kg i.m. General anesthesia was maintained with i.v. boluses of thiopenthone (50 mg). Animals received 1500 ml of lactated Ringer’s solution (Hartman solution, Braun) during anaesthesia and in postoperative period. Postoperative analgesia was maintained with morphine (0.2 mg/ kg i.m./6 h).
An experimental model of reproducible liver trauma
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The pig was fixed in a recumbent position with its limbs fixed to the table. Approximately 20 min after induction liver injury was preceded by ketamine administration at the dose of 1 mg/kg i.v. Blunt liver injury was inflicted with a crossbow shot directed toward the lower thoracic wall, between the fourth and the sixth intercostal space. The arrow had either a rubber (first three cases) or an aluminium spherical tip with a diameter of 35 mm and weight of 95 g for the aluminium arrow and 45 g for the rubber arrow. In all cases, the distance from the arrow to the chest wall was 1 m and the heights from the table to the target point approximately 10 cm. A laser pointer and metallic support were used to make the shot precise (cf. Fig. 1). Following the crossbow shot, minimal laparatomy was performed to verify the injury. In the last case, laparoscopy was conducted instead of laparatomy to verify the injury. The first six pigs were then harvested while the last three pigs were kept alive until the next day. Animals were sacrificed using T61 (Intervet) 0.3 ml/ kg i.v. To study the action of the arrow to the pig’s chest wall, a simplified model was developed. For study purposes, the crossbow shot was divided into three distinct phases:
3. At the time of impact there is no rebounding of the arrow (Fig. 1). Therefore, the arrow’s kinetic energy is transformed to the deformation energy of the tissue. It is very important that only part of the energy is transformed to the actual tearing of tissue, the rest is used to push the fluid through the tissue (which produces warming).
1. In the first phase the arrow touches the skin. Due to the elasticity of the skin, the pressure inside the liver rises slowly. 2. In the second phase the arrow pushes the tissue and the pressure in the liver parenchyma rises rapidly. In liver, unlike in a balloon filled with water, due to specific architecture the pressure rise at the point of impact is larger than in other parts of the liver. If the speed of the arrow is great enough, the pressure difference rises beyond the critical value thus damaging the tissue. 3. In the third phase the pressure falls rapidly and the pressure in the different parts of the liver equalises.
Results
The model uses the following premises: 1. Since the mass of the arrow is much smaller than that of the pig and the pig is well fixed to the table, the counteraction of the pig at the arrow can be neglected. 2. The energy of the arrow is crucial in determining the stage of injury. The distance of the crossbow from the point of impact is unimportant in this respect. The crossbow type determines the maximum energy of the arrow. The energy loss of the arrow on its way depends on air resistance and the shape of the arrow (p d2/4).
According to the above-mentioned speculations, the value that directly determines the stage of liver injury is proportional to the pressure impulse, which in turn is the ratio of force impulse (product of massarrow velocityarrow) divided by the area of the arrow head (S). force impulse Pressure impulse ¼ S massarrow velocityarrow ¼ S We believe that this ratio includes all measured parameters and is better for determining the stage of injury than the sole energy of the arrow itself. For example, much greater energy could slowly be applied to the chest wall and still there would be no injury.
The force of a magnitude of 580 N directed to the lower lateral aspect of the chest wall left the skin undamaged and caused subcutaneous haematoma and fracture of ribs. In the liver, there were lacerations of grades II to III according to the liver injury scale.15 In four animals, there were four ribs fractured, in three there was one fractured rib and in two animals there were no fractures of the ribs. There were no cases when bleeding would be caused by the laceration of peritoneum. Two animals had contusion of lung. The results are summarised in Table 1 and illustrated in Figs. 2—5.
Discussion While the majority of knowledge about liver trauma comes from the clinical data of injured patients some important clinical problems like organ failure in patients after liver transplantation and ICU jaundice warrant the need for the model of reproducible liver trauma. During our experiments with perihepatic pack placements and measurements of the pressure of the packing,9,10 the need arose for an improved model of controllable and reproducible liver trauma. The ‘‘clamp and crush’’ mechanism of injury as used and described in pre-
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Table 1 Reproducible liver trauma in pigs Parameter
Case no. 1
2
3
4
5
6
7
8
9
Sex Weight (kg) Weight of the arrowhead (g) Height from the table (cm) Target intercostal space (from bottom)
F 20 45
M 25 45
M 20 45
F 25 95
M 27 95
F 35 95
F 25 95
F 26 95
F 28 95
11
10
11
11
12
10
10
10
10
Sixth
Fifth
Fifth
Fourth
Sixth
Fifth
Fourth
Fifth
Fifth
Skin Subcutaneous tissue Ribs
Contusion Haematoma —
Contusion Haematoma Fracture of one rib
Contusion Haematoma Fracture of one rib
Contusion Haematoma Fracture of two ribs
Contusion Haematoma Fracture of one rib
Contusion Haematoma —
Contusion Haematoma Fracture of two ribs
Contusion Haematoma Fracture of two ribs
Contusion Haematoma Fracture of two ribs
Lungs
0
0
0
Contusion *
0
0
0
0
Bleeding to abdomen
Bleeding, lung contusion 0
0
Less than 100 ml
100 ml
Minimal bleeding
Minimal bleeding
150 ml
Minimal bleeding
Liver injury
None
2 cm shallow laceration of the median lobe
2 cm shallow laceration at the top of the right lobe
5 cm starlike laceration on the periphery of the right lobe Pringle manoeuvre to control bleeding (5 min)
3 cm laceration at the top of the right lobe * Blood aspirated from lungs
3 cm haematoma of the right lobe, 2 cm laceration of the median lobe ** ** Injury of the two adjacent lobes
Bleeding 150—200 ml 5 5 starlike laceration right lobe periphery
Deep laceration 5 4 cm, margin of the right lobe
3 cm shallow laceration at the top of the median lobe
Comments
Diameter of the arrow head was 35 mm in all cases. 580 N crossbow type was used in all cases. In the first three animals a 45 g rubber arrow head was used, while in the last six cases it was replaced by a 95 g aluminium arrow head. When other parameters are kept constant (body weight, distance from animal, distance from the floor), the stage of the injury can be determined by pressure impulse which is the ratio of force impulse (produce of massarrow velocityarrow) divided by the area of the arrow head (S). At a constant speed of the arrow (35 m/s) and diameter (d) of the arrow head (35 mm) the stage of the injury can be determined by the mass of the arrow head. Surface area of the arrow head (S) = p d2/4. Fo = maximal force of the crossbow = 130 lbs = 580 N.
M. Wahl et al.
An experimental model of reproducible liver trauma
Figure 2
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Case no. 4: At laparatomy, 5 cm large starlike laceration can be seen on the periphery of the right lobe.
vious reports does not seem to reproduce the real mechanism of blunt liver injury. We therefore wanted to create an animal model that would reproduce the mechanism of liver injury by controlling the force applied at the chest wall. In animals of the same species and weight this should reproduce liver injury of a predictable stage while with use of different force we could change the stage of injury. In 1995, our early experiments on beagle dogs in which liver trauma was inflicted with
Figure 3
a butcher’s pistol were unsuccessful since the majority of injuries were too extensive (LIS grade IV—V) to permit successful resuscitation. A classic bow with 50 pounds force at 27 inches (hand held bow scale) on the contrary caused only minor liver injury, which was insufficient for our study purposes. A crossbow with an aluminium spherical arrowhead proved to be the optimal tool to produce a second to third stage blunt liver injury. A case of blunt liver injury has been described as a case in
Case no. 5: 3 cm laceration at the top of the right lobe. Laparatomy immediately after injury.
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Figure 4 Case no. 8: Deep 5 cm 4 cm laceration at the periphery of the right lobe. Specimen taken at the time of harvesting.
which heavier rubber crossbow projectiles (135 g) of similar shape were used against demonstrators in Ireland.25 The velocity of projectiles must be great enough to overcome the elasticity of the thoracic wall and enable absorption of energy. The results of the present experiment show that the stage of liver trauma is proportional to the pressure impulse, which is defined as the ratio between the product
Figure 5
of the arrow’s mass and the velocity and the contact surface area of the arrow. When other parameters are kept constant, the mass of the arrow predicts the stage of liver injury. We believe that the model of controllable and reproducible liver injury will offer an opportunity to study various aspects of liver trauma, including aetiology, different treatments, as well as prognos-
Case no. 8: Liver from the backside after removal: a clot can be seen at the site of injury.
An experimental model of reproducible liver trauma
tic indices together with other problems concerning liver injury. With the use of a heavier arrow, the model will give an opportunity to inflict more extensive liver injury and study different treatment modalities, while with less extensive injuries enabling the survival of experimental animals, the morphologic, pathophysiologic and micromorphologic changes of injured liver parenchyma could be followed up.
Acknowledgement The work was financially supported by Nova Ljubljanska banka, d.d. The authors wish to thank Mr Urosˇ Bohinjec for his valuable suggestions during development of liver injury model.
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11.
12.
13.
14. 15.
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