A Simple, Quantifiable, and Accurate Method for Applying a Noxious ...
TECHNICAL COMMUNICATIONS
A Simple, Quantifiable, and Accurate Method for Applying a Noxious Mechanical Stimulus Joseph F. Antognini,
MD*,
and Earl Carstens,
PhDt
*Department of Anesthesiology, tsection of Neurobiology, Physiology and Behavior, University of California-Davis, Davis, California
I
n animals, anesthetic requirements for a supramaximal noxious stimulus are usually determined using a hemostat applied to the tail or extremity (1,2). Although a generally accepted technique, the applied force is either not stated or unknown. Furthermore, when a noxious mechanical stimulus is applied to determine neurophysiological responses (e.g., dorsal horn activity), the force is often varied and must be accurately known. We sought to determine whether spring-activated A-clamps could be used to reproducibly apply a known force. The force (F) required to deform a spring is proportional to the spring constant (k). In the case of compressing or stretching a spring a certain distance (x), F = -kx. Springs in A-clamps apply force as the result of twisting along the longitudinal axis, with the force proportional to the amount of twisting. Additionally, adjusting the area of the A-clamp in contact with the tissue can vary the force applied per unit area of tissue.
The force generated by each clamp was determined by attaching one handle of the clamp to a block of metal, which was then placed in a vise, leaving the other handle free. A small rope was attached to the end of this free handle. Weights were hung from the rope, and the distance between the handles was determined for each weight (Fig. 1). The maximal distance the handles could travel toward each other varied according to the size of each clamp. After multiple measurements with different weights, the actual force generated by the clamp was determined using a small force gage (Model 13/2443-08; Sensotec, Inc., Columbus, OH) placed in the tip of the clamp. Metal spacers of different sizes were placed in the clamp with the gage to determine the forces generated by each clamp over a wide range of spring displacement. Reproducibility was determined by placing the force gage in each clamp 25 times.
Methods Six A-clamps (Brink and Cotton 1 and 3; Warren Tool Group, Inc, Garrettsville, OH; Pony 3201 and 3202; Adjustable Clamp Company, Chicago, IL; Radio Shack 270342; Tandy Corp., Fort Worth, TX; generic brand, Harbor Freight Tools, Carmichael, CA) were purchased from local hardware stores. The tips of each clamp were bent slightly so that they were approximately parallel to each other when the clamp was closed. Holes were drilled through the tips of the Pony 3201 clamp, through which bolts were placed. The bolts had been machined to a flat surface with an area of 50 mm’.
This work was supported in part by the Foundation for Anesthesia Education and Research with a grant from Abbott Laboratories. Accepted for publication July 31, 1998. Address correspondence to Joseph F. Antognini, MD, Department of Anesthesiology, TB-170, University of California-Davis, Davis, CA 95616.
1446
Figure 1. The experimental
method. The A-clamp was secured, and weights were applied to the up-arm of the clamp. The distance between the arms was measured for each weight over a wide range. The distance from the hinge to each end of the arm (where the weights were applied and where the gage was placed) was measured. Because of the lever-like action of the longer arm, a conversion (B/A) was necessary to compare the force determined by the gage and the weight applied. The angle of the weight and the optimal force vector was also determined. The weight was multiplied by cosine [0] to estimate the force generated by the clamp. 01998
An&h
Analg
1998;87:1446-9
by the International
Anesthesia
Research Society 0003.2999/98/$5.00
ANESTH
ANALG
TECHNICAL
COMMUNICATIONS CLAMP
1998;87:1446-9
Table
-
1. Correlation
of Handle
Brink and Cotton Brink and Cotton Pony 3201 Pony 3202 Radio Shack Generic
Displacement
and Calculated
Force and Measured Correlation of handle displacement and measured force
-0.97 -0.99 -0.97 -0.98 -0.98 -0.97
-0.96 -0.98 -0.98 -0.99 -0.96 -0.98
Brink and Cotton 1 and 3; Warren Tool Group, Inc, Garrettsville, Tandy Corp., Fort Worth, TX; generic brand, Hdrbor Freight Tools, ” Determined by placing a force gage in the clamp 25 times.
OH; Pow Carmichael,
3201 and CA
3202;
Reproducibility (mean
Clamp
Company,
Chicago,
fr;r# %Y.YYQ j“‘a, ., 80,. ,.,.,.,.I. I.I.#,_, ,.,_, ,_. ,,_, *I.
IlO-
k*..
90
240
70
40;.,
7
8
9
DISTANCE
10
11
BETWEEN
12
13
14
HANDLES
15
#
7
9
II
13
15
+- 0.8 + 2.4 2 2.1 t 2.7 2 0.4 t 1.3
IL; Radio
0 0..
Shack
270-342;
.
\
'I .'*., r.1
1.m-r 3.0
2.0
17
SD)
B-Cl *.‘P0 . 0’
50-.-s
5
force (N) 2
62.6 108.2 68.7 69.9 27 43.9
Adjustable
1447
CARSTENS STIMULUS
Force
Correlation of handle displacement and calculated force 1 3
ANTOGNINI AND AND NOXIOUS
4.0
5.0
(cm)
1601
160
r~~‘~~~~ 0
12
DISTANCE
3 BETWEEN
HANDLES
3
4
4
5
5
6
6
7
8
9
(cm)
Figure 2. Correlation of the force applied by the weight and the actual force measured. With some clamps, there was error, but with others, there was almost perfect correlation between the measured force (0) and the calculated force (0) The small systematic error could be due to frictional forces resulting from the handles touching each other at the point Brink and Cotton 1 and 3; Warren Tool Group, Inc, Garrettsville, OH; Pony 3201 and 3202; Adjustable Clamp Company, Shack 270-342; Tandy Corp., Fort Worth, TX; generic brand, Harbor Freight Tools, Carmichael, CA.
We also determined the force generated by a typical-l0 in. surgical hemostat, which has a locking mechanism that uses ratchets on each handle that prevent the hemostat from opening. We determined how force varied as the gage was moved along the jaws of the hemostat. We compared the forces measured with the force gage and those calculated by placing weights on the clamp handle, The handle acts like a lever, with the fulcrum at the hinge of the clamp. The ratio of the distances between the hinge and each end of the clamp was multiplied by the weight applied to the clamp (Fig. 1). Additionally, because the weights were not in line with the optimal force vector, the weight was multiplied by the cosine [01,where [01is the angle marked by the rope and
a small systematic using the weights. of rotation (hinge). Chicago, IL; Radio
the true optimal vector. A linear correlation was made between the force calculated from the weights and the force measured by using the force gage.
Results Each of the clamps generated accurate, precise, and reproducible forces when determined over a large range of spring displacement. In Table 1, the correlation of the distance between the handles and the weight applied for each clamp demonstrates correlation coefficients
(Y) = -0.96
to -0.99.
The forces
gen-
erated by the clamps are reproducible (Table 1). Figure 2 demonstrates the linear correlation of each clamp to
1448
TECHNICAL CLAMP AND
COMMUNICATIONS NOXIOUS STIMULUS
ANTOGNINI
AND
CARSTENS
ANESTH ANALG 1998;87:1446-9
3407 32030028026024022020018016014012010060604020-
:
5 set
01
the spring displacement, as indirectly measured by the distance between the handles. Comparison of the measured force and the calculated force (determined using the weights) demonstrate accuracy to within 15% in the case of the Pony 3202 clamp and to within l%-2% with the Brink & Cotton 1 clamp. For all clamps combined, the calculated force was 104% + 8% of the measured force. The practicality of this device was demonstrated by placing a force gage on the skin web between the thumb and index finger (Fig. 3). There was rapid upswing and decline, which is desirable when performing neurophysiological experiments when the stimulus must be constant, but capable of being quickly applied and withdrawn. The force generated by the hemostat as a function of movement of the force gage along the jaws of the hemostat is shown in Figure 4. As the gage was moved towards the hinge, force increased in a nonlinear fashion. The jaws of the hemostat acted like cantilevers, and displacement (and therefore force) varied as a function of the distance (d) from the hinge: F CCl/d3 (see Figure 4). An individual example of the generated force is shown in Figure 5.
Discussion A variety of noxious stimuli has been used to determine anesthetic requirements. Eger et al. (1) used a hemostat and an electrical stimulus. Since then, a hemostat has been the standard stimulus for anesthetic requirement studies. Sobair et al. (3) used a pneumatic device that can precisely apply a noxious mechanical stimulus. They also used a heat stimulus applied to a rabbit’s ear and determined that it can be used as a supramaximal stimulus for determination of anesthetic requirements (4). They reasoned that a heat stimulus applied at approximately 52°C would minimize tissue damage, unlike a hemostat, which can cause extensive damage when applied in a supramaximal fashion. However, as they
I
3
Figure 3. Clamp applied to the skin web between thumb and index finger, with a force gage placed on the skin. Note the rapidity and reproducibility with which the clamp can be applied and removed.
,
4
I
,
5
I
,
6
I
,
7
I
,
I
6
,
9
DISTANCE FROM HINGE (CM) Figure 4. Correlation of movement of the gage along the jaws of the hemostat and the force applied. Five measurements were made at each point. Error bars are not shown; standard deviation was usually l%-2% of the mean and never >7%. Each line represents closing the hemostat at one, two, three, or four ratchets. As the gage was moved closer to the hinge, the force increased nonlinearly. Correlation coefficients for each line = 0.99. The inset shows the force (first ratchet data only) as a function of the reciprocal of the distance (d) from the hinge: F = l/d3; Y = 0.99. This is consistent with the deflection of a cantilever beam (6) and is the basic description of the force applied by the hemostat.
150 zz
100
x 2
5o 0
Figure 5. An individual example of movement of the force gage along the jaws of the hemostat. At the left, the gage is at the very end of the hemostat. In the middle, the gage has been moved 1.3 cm toward the hinge. At the right, the gage has been moved a further 1.3 cm closer to the hinge. The step-like increases in force occur as the result of going from one ratchet to the next, up to the fourth (and last) ratchet. This represents the point at which the maximal force can be applied and is termed “full ratchet lock.” All ratchets are engaged, and the hemostat cannot be closed further. The small overshoot at each ratchet signifies the teeth slipping over the edge into the ratchet.
noted, no one has quantitatively documented the supramaximal stimulus (3). Regarding a mechanical noxious stimulus, tissue damage might occur at the supramaxima1 threshold. An electrical current (e.g., 60 mA at 50100 Hz for 60 s) is easily quantifiable and does not injure tissue (2). Investigators have used the hemostat in a consistent fashion, but even slight alterations of placing the tail or distal extremity in the clamp can affect the applied force. Thus, it is important to position the tail or extremity in the clamp at the same spot, as we have
ANESTH ANALG 1998;87:1446-9
done in our studies (5). Nonetheless, it is difficult to determine exactly how much force is being applied using this method. Using an A-clamp, an investigator can apply force that is easily determined and accurately known. Adjusting the size of the clamp heads and their distance from each other can also vary the force. In the present study, one clamp (Pony 3201) had bolts attached; by adjusting the length of the bolt, the force applied to tissue could be increased or decreased. Because the force varies as a function of the irregularity of the tissue, clamp heads can be customized to accommodate the particular experiment. For example, flat heads might cause a round tail to slip out of the clamp. By using concave heads, the tail can be securely clamped. In summary, an A-clamp can be used to apply an easily quantifiable, reproducible, and noxious mechanical stimulus suitable for determination of anesthetic requirements. This method can also be used to apply force as a near-square wave function, which is desirable for neurophysiological studies.
TECHNICAL
COMMUNICATIONS CLAMP
ANTOGNINI AND AND NOXIOUS
CARSTENS STIMULUS
The authors acknowledge the helpful comments of Albert BS, MS, Dennis Fung, MD, and Richard Landers, PhD.
1449
A. Erkel,
References 1. Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 1963;26:756 63. 2. Laster MT, Liu T. Eeer EI II. Taheri S. Electrical stimulation as a substitute for the tail clamp in determination of minimum alveolar concentration. Anesth Analg 1993;76:1310P2. 3. Sobair ATH, Cottrell DF, Camburn MA. A mechanical stimulator for the determination of the minimum alveolar concentration (MAC) of halothane in the rabbit. Vet Res Commun 1993; 17:375-85. 4. Sobair ATH, Cottrell DF, Camburn MA. Focal heat stimulation for determination of the minimum alveolar concentration (MAC) of halothane in the rabbit. Vet Res Commun 1997;21: 149-59. 5. Antognini JF, Carstens E, Tabo E, Buzin V. Effect of differential delivery of isoflurane to head and torso on lumbar dorsal horn activity. Anesthesiology 1998;88:1055-61. 6. American Institute of Steel Construction. Steel construction. New York: AISC, 1960:373.
A Simple, Quantifiable, and Accurate Method for Applying a Noxious Mechanical Stimulus Joseph F. Antognini,
MD*,
and Earl Carstens,
PhDt
*Department of Anesthesiology, tsection of Neurobiology, Physiology and Behavior, University of California-Davis, Davis, California
I
n animals, anesthetic requirements for a supramaximal noxious stimulus are usually determined using a hemostat applied to the tail or extremity (1,2). Although a generally accepted technique, the applied force is either not stated or unknown. Furthermore, when a noxious mechanical stimulus is applied to determine neurophysiological responses (e.g., dorsal horn activity), the force is often varied and must be accurately known. We sought to determine whether spring-activated A-clamps could be used to reproducibly apply a known force. The force (F) required to deform a spring is proportional to the spring constant (k). In the case of compressing or stretching a spring a certain distance (x), F = -kx. Springs in A-clamps apply force as the result of twisting along the longitudinal axis, with the force proportional to the amount of twisting. Additionally, adjusting the area of the A-clamp in contact with the tissue can vary the force applied per unit area of tissue.
The force generated by each clamp was determined by attaching one handle of the clamp to a block of metal, which was then placed in a vise, leaving the other handle free. A small rope was attached to the end of this free handle. Weights were hung from the rope, and the distance between the handles was determined for each weight (Fig. 1). The maximal distance the handles could travel toward each other varied according to the size of each clamp. After multiple measurements with different weights, the actual force generated by the clamp was determined using a small force gage (Model 13/2443-08; Sensotec, Inc., Columbus, OH) placed in the tip of the clamp. Metal spacers of different sizes were placed in the clamp with the gage to determine the forces generated by each clamp over a wide range of spring displacement. Reproducibility was determined by placing the force gage in each clamp 25 times.
Methods Six A-clamps (Brink and Cotton 1 and 3; Warren Tool Group, Inc, Garrettsville, OH; Pony 3201 and 3202; Adjustable Clamp Company, Chicago, IL; Radio Shack 270342; Tandy Corp., Fort Worth, TX; generic brand, Harbor Freight Tools, Carmichael, CA) were purchased from local hardware stores. The tips of each clamp were bent slightly so that they were approximately parallel to each other when the clamp was closed. Holes were drilled through the tips of the Pony 3201 clamp, through which bolts were placed. The bolts had been machined to a flat surface with an area of 50 mm’.
This work was supported in part by the Foundation for Anesthesia Education and Research with a grant from Abbott Laboratories. Accepted for publication July 31, 1998. Address correspondence to Joseph F. Antognini, MD, Department of Anesthesiology, TB-170, University of California-Davis, Davis, CA 95616.
1446
Figure 1. The experimental
method. The A-clamp was secured, and weights were applied to the up-arm of the clamp. The distance between the arms was measured for each weight over a wide range. The distance from the hinge to each end of the arm (where the weights were applied and where the gage was placed) was measured. Because of the lever-like action of the longer arm, a conversion (B/A) was necessary to compare the force determined by the gage and the weight applied. The angle of the weight and the optimal force vector was also determined. The weight was multiplied by cosine [0] to estimate the force generated by the clamp. 01998
An&h
Analg
1998;87:1446-9
by the International
Anesthesia
Research Society 0003.2999/98/$5.00
ANESTH
ANALG
TECHNICAL
COMMUNICATIONS CLAMP
1998;87:1446-9
Table
-
1. Correlation
of Handle
Brink and Cotton Brink and Cotton Pony 3201 Pony 3202 Radio Shack Generic
Displacement
and Calculated
Force and Measured Correlation of handle displacement and measured force
-0.97 -0.99 -0.97 -0.98 -0.98 -0.97
-0.96 -0.98 -0.98 -0.99 -0.96 -0.98
Brink and Cotton 1 and 3; Warren Tool Group, Inc, Garrettsville, Tandy Corp., Fort Worth, TX; generic brand, Hdrbor Freight Tools, ” Determined by placing a force gage in the clamp 25 times.
OH; Pow Carmichael,
3201 and CA
3202;
Reproducibility (mean
Clamp
Company,
Chicago,
fr;r# %Y.YYQ j“‘a, ., 80,. ,.,.,.,.I. I.I.#,_, ,.,_, ,_. ,,_, *I.
IlO-
k*..
90
240
70
40;.,
7
8
9
DISTANCE
10
11
BETWEEN
12
13
14
HANDLES
15
#
7
9
II
13
15
+- 0.8 + 2.4 2 2.1 t 2.7 2 0.4 t 1.3
IL; Radio
0 0..
Shack
270-342;
.
\
'I .'*., r.1
1.m-r 3.0
2.0
17
SD)
B-Cl *.‘P0 . 0’
50-.-s
5
force (N) 2
62.6 108.2 68.7 69.9 27 43.9
Adjustable
1447
CARSTENS STIMULUS
Force
Correlation of handle displacement and calculated force 1 3
ANTOGNINI AND AND NOXIOUS
4.0
5.0
(cm)
1601
160
r~~‘~~~~ 0
12
DISTANCE
3 BETWEEN
HANDLES
3
4
4
5
5
6
6
7
8
9
(cm)
Figure 2. Correlation of the force applied by the weight and the actual force measured. With some clamps, there was error, but with others, there was almost perfect correlation between the measured force (0) and the calculated force (0) The small systematic error could be due to frictional forces resulting from the handles touching each other at the point Brink and Cotton 1 and 3; Warren Tool Group, Inc, Garrettsville, OH; Pony 3201 and 3202; Adjustable Clamp Company, Shack 270-342; Tandy Corp., Fort Worth, TX; generic brand, Harbor Freight Tools, Carmichael, CA.
We also determined the force generated by a typical-l0 in. surgical hemostat, which has a locking mechanism that uses ratchets on each handle that prevent the hemostat from opening. We determined how force varied as the gage was moved along the jaws of the hemostat. We compared the forces measured with the force gage and those calculated by placing weights on the clamp handle, The handle acts like a lever, with the fulcrum at the hinge of the clamp. The ratio of the distances between the hinge and each end of the clamp was multiplied by the weight applied to the clamp (Fig. 1). Additionally, because the weights were not in line with the optimal force vector, the weight was multiplied by the cosine [01,where [01is the angle marked by the rope and
a small systematic using the weights. of rotation (hinge). Chicago, IL; Radio
the true optimal vector. A linear correlation was made between the force calculated from the weights and the force measured by using the force gage.
Results Each of the clamps generated accurate, precise, and reproducible forces when determined over a large range of spring displacement. In Table 1, the correlation of the distance between the handles and the weight applied for each clamp demonstrates correlation coefficients
(Y) = -0.96
to -0.99.
The forces
gen-
erated by the clamps are reproducible (Table 1). Figure 2 demonstrates the linear correlation of each clamp to
1448
TECHNICAL CLAMP AND
COMMUNICATIONS NOXIOUS STIMULUS
ANTOGNINI
AND
CARSTENS
ANESTH ANALG 1998;87:1446-9
3407 32030028026024022020018016014012010060604020-
:
5 set
01
the spring displacement, as indirectly measured by the distance between the handles. Comparison of the measured force and the calculated force (determined using the weights) demonstrate accuracy to within 15% in the case of the Pony 3202 clamp and to within l%-2% with the Brink & Cotton 1 clamp. For all clamps combined, the calculated force was 104% + 8% of the measured force. The practicality of this device was demonstrated by placing a force gage on the skin web between the thumb and index finger (Fig. 3). There was rapid upswing and decline, which is desirable when performing neurophysiological experiments when the stimulus must be constant, but capable of being quickly applied and withdrawn. The force generated by the hemostat as a function of movement of the force gage along the jaws of the hemostat is shown in Figure 4. As the gage was moved towards the hinge, force increased in a nonlinear fashion. The jaws of the hemostat acted like cantilevers, and displacement (and therefore force) varied as a function of the distance (d) from the hinge: F CCl/d3 (see Figure 4). An individual example of the generated force is shown in Figure 5.
Discussion A variety of noxious stimuli has been used to determine anesthetic requirements. Eger et al. (1) used a hemostat and an electrical stimulus. Since then, a hemostat has been the standard stimulus for anesthetic requirement studies. Sobair et al. (3) used a pneumatic device that can precisely apply a noxious mechanical stimulus. They also used a heat stimulus applied to a rabbit’s ear and determined that it can be used as a supramaximal stimulus for determination of anesthetic requirements (4). They reasoned that a heat stimulus applied at approximately 52°C would minimize tissue damage, unlike a hemostat, which can cause extensive damage when applied in a supramaximal fashion. However, as they
I
3
Figure 3. Clamp applied to the skin web between thumb and index finger, with a force gage placed on the skin. Note the rapidity and reproducibility with which the clamp can be applied and removed.
,
4
I
,
5
I
,
6
I
,
7
I
,
I
6
,
9
DISTANCE FROM HINGE (CM) Figure 4. Correlation of movement of the gage along the jaws of the hemostat and the force applied. Five measurements were made at each point. Error bars are not shown; standard deviation was usually l%-2% of the mean and never >7%. Each line represents closing the hemostat at one, two, three, or four ratchets. As the gage was moved closer to the hinge, the force increased nonlinearly. Correlation coefficients for each line = 0.99. The inset shows the force (first ratchet data only) as a function of the reciprocal of the distance (d) from the hinge: F = l/d3; Y = 0.99. This is consistent with the deflection of a cantilever beam (6) and is the basic description of the force applied by the hemostat.
150 zz
100
x 2
5o 0
Figure 5. An individual example of movement of the force gage along the jaws of the hemostat. At the left, the gage is at the very end of the hemostat. In the middle, the gage has been moved 1.3 cm toward the hinge. At the right, the gage has been moved a further 1.3 cm closer to the hinge. The step-like increases in force occur as the result of going from one ratchet to the next, up to the fourth (and last) ratchet. This represents the point at which the maximal force can be applied and is termed “full ratchet lock.” All ratchets are engaged, and the hemostat cannot be closed further. The small overshoot at each ratchet signifies the teeth slipping over the edge into the ratchet.
noted, no one has quantitatively documented the supramaximal stimulus (3). Regarding a mechanical noxious stimulus, tissue damage might occur at the supramaxima1 threshold. An electrical current (e.g., 60 mA at 50100 Hz for 60 s) is easily quantifiable and does not injure tissue (2). Investigators have used the hemostat in a consistent fashion, but even slight alterations of placing the tail or distal extremity in the clamp can affect the applied force. Thus, it is important to position the tail or extremity in the clamp at the same spot, as we have
ANESTH ANALG 1998;87:1446-9
done in our studies (5). Nonetheless, it is difficult to determine exactly how much force is being applied using this method. Using an A-clamp, an investigator can apply force that is easily determined and accurately known. Adjusting the size of the clamp heads and their distance from each other can also vary the force. In the present study, one clamp (Pony 3201) had bolts attached; by adjusting the length of the bolt, the force applied to tissue could be increased or decreased. Because the force varies as a function of the irregularity of the tissue, clamp heads can be customized to accommodate the particular experiment. For example, flat heads might cause a round tail to slip out of the clamp. By using concave heads, the tail can be securely clamped. In summary, an A-clamp can be used to apply an easily quantifiable, reproducible, and noxious mechanical stimulus suitable for determination of anesthetic requirements. This method can also be used to apply force as a near-square wave function, which is desirable for neurophysiological studies.
TECHNICAL
COMMUNICATIONS CLAMP
ANTOGNINI AND AND NOXIOUS
CARSTENS STIMULUS
The authors acknowledge the helpful comments of Albert BS, MS, Dennis Fung, MD, and Richard Landers, PhD.
1449
A. Erkel,
References 1. Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 1963;26:756 63. 2. Laster MT, Liu T. Eeer EI II. Taheri S. Electrical stimulation as a substitute for the tail clamp in determination of minimum alveolar concentration. Anesth Analg 1993;76:1310P2. 3. Sobair ATH, Cottrell DF, Camburn MA. A mechanical stimulator for the determination of the minimum alveolar concentration (MAC) of halothane in the rabbit. Vet Res Commun 1993; 17:375-85. 4. Sobair ATH, Cottrell DF, Camburn MA. Focal heat stimulation for determination of the minimum alveolar concentration (MAC) of halothane in the rabbit. Vet Res Commun 1997;21: 149-59. 5. Antognini JF, Carstens E, Tabo E, Buzin V. Effect of differential delivery of isoflurane to head and torso on lumbar dorsal horn activity. Anesthesiology 1998;88:1055-61. 6. American Institute of Steel Construction. Steel construction. New York: AISC, 1960:373.
