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Circumference measurement as a criterion for capillary pressure determination
MICROVASCULAR
RESEARCH
6, l-4 (1973)
Circumference Capillary
Measurement as a Criterion Pressure Determination’*2
for
ARNOSTFRONEKANDTHOMAS H.WITZEL Department of AMES-Bioengineering School of Medicine, University of California, San Diego, La Jolla, California 92037 Received August 7,1972 A modification of the original Pappenheimer and Soto-Rivera’s isogravimetric method to determine effective capillary pressure (P,) is described. As a balancing criterion, the circumference rather than the weight change was utilized. In 120experimental runs on 17 cats, a very good correlation was found with the conventional isogravimetric technique over a wide range of capillary pressures. The potential areas of application of this technique are also compared with the isoconductometric technique.
In a previous report (5), we describedthe utilization of changesof electrical resistance of blood as a balancing criterion for the determination of capillary pressure similar to the weight changesutilized in Pappenheimer and Soto-Rivera’s isogravimetric method (7). The minimum withdrawal rate of blood (currently 4 ml/min) limits the application of this technique in vascular areas with small blood flow rates, or under induced lowflow conditions sincethe amount of blood continuously withdrawn must be a negligible fraction of the sampled blood flow. This drawback is circumvented in the technique to be described. Basically, weight monitoring is replaced by the continuous recording of the circumference of the investigated extremity. DESCRIPTION OF THE METHOD Experiments have been performed (Nembutal anesthesia30 mg/kg) in 17 cats using basically the methodology as described in the previous report (5). Weight changes were determined by a Statham force transducer3 and arterial and venous pressuresby a P23Db and P23BB Statham transducer, respectively. Blood flow was measured by a photoelectric drop counter and calibrated by timed collection of blood into a graduated cylinder. Blood was returned by a Masterflex pump4 activated by a photoelectric sensing device. After amputation of the hind limb, a mercury-in-rubber gauge5was placed around the hind limb below the knee joint (approximately at the midpoint of the gastrocnemius muscle) with a prestretch of 10 g r Presented in abbreviated form at the Meeting of the Microcirculatory Atlantic City, NJ. ’ Supported by N.I.H. Grant HL 1269044. 3 UCZ-green cell, Statham Instruments, Oxnard, Cal. 4 Cole & Palmer, Chicago, Illinois. ’ Parks Electronics, Reaverton, Oregon. Copyright8 1973 by Academic Press, Inc. 1 AU rights of reproduction in any form reserved. Printed
in Great
Britain
Society, April 9, 1972,
2
FRONEK AND WITZEL
FIG. 1. From top: (a) flow (drop counter); (b) arterial pressure; (c) weight; (d) circumference; (e) venous pressure. Panel on right: Demonstration of the effect of arterial and venous pressure changes of theinvestigated hind limbs. on the weight andcircumference
to insure a linear response(6, 8). The changesin electrical resistance of the gauge are detected by a low-ohm resistancebridge5 and accordingly amplified and recorded. All monitored functions were recorded on an Offner-Dynograph recorder. After a control steady-statelevel has been obtained for both the weight and circumference, the inflow and outflow pressureswere balanced as in the conventional isogravimetric procedure (7) (Fig. 1).
FIG. 2. Venous pressure plotted against corresponding flow rates under “isovolumetric” Sequences 1 and 2 are control values, while 3,4, and 5 were obtained after hemorrhage.
conditions.
CIRCUMFERENCE
MEASUREMENT
AND
P, DETERMINATION
3
The venous pressures obtained under the “isovolumetric”6 conditions are plotted against the corresponding flow rates (Fig. 2). Capillary pressure was determined by extrapolation to zero flow, as in the conventional isogravimetric procedure. Each run in which the weight was considered as a balancing criterion was followed by an isovolumetric run in which the circumference was considered as the balancing criterion. RESULTS Altogether 120 experimental sequences were performed in 17 cats. Those runs in which the weight response coincided exactly with that of the circumference (as reproduced in Fig. 1) are represented on the line of identity in Fig. 3. In instances in which the
I 10
20 PC-WT
30 (cm
40
H,O)
FIG. 3. Extrapolated capillary pressuresobtained by the circumferencetechnique(P,-Circ) plotted againstpressuresobtained isogravimetrically (PC-WT). weight or circumference criterion was lagging, the isovolumetrically determined PC was compared with the preceding isogravimetrically determined PCvalue. In order to obtain a wider range of values, hemorrhage and pharmacologically induced changes were also initiated-isoproterenol and levophed infusions, 1 pm/kg/min and 2 pm/kg/ min, respectively. The results of all experiments including those obtained during hemorrhage, isoproterenol and levophed infusions are presented in Fig. 3. The correlation of PCvalues determined by both techniques is very close (r = 0.955) and the average difference in percent is 2.8 %, SD + 13.3 % and SE i 1.2 %. DISCUSSION The application of the mercury-in-rubber gauge (8) to indicate volume changes is basically an extrapolation of the conventional isogravimetric technique for determining 6 “Isovolumetric” condition is here defined as indicating no circumferencechange. Details see under Discussion.
4
FRONEK
AND
WITZEL
the capillary pressure(7). The closerelationship betweenlimb volume and circumference measurementshas been established in a number of studies (l-4). In order to study the effect of the underlying skin on the circumferential changesand on the extrapolated P, values as well, the mercury-in-rubber loop has been placed in five catsin direct contact with the musclesby cutting out a corresponding circumferential strip of skin. No significant difference was observed in both groups. The question may be raised to what extent the extrapolated PCobtained from the circumferential measurement in one plane represents the overall effective capillary pressure of the adjacent anatomical structures. It can be assumedthat the isogravimetrically determined PCrepresents the average value of the predominant anatomical structures, in this casethe skeletal muscles of the hind limb. Similar reasoning can be applied to the circumference determination and its relationship to the volume changes of the underlying muscle tissues. We feel that both types of capillary pressure determination, the conductometric as well as the isovolumetric technique, have different potential areas of application. The former has the advantage of reflecting the filtration or absorption changes directly without the intravascular volume component but its application is currently limited to larger animals or to larger vascular areassincethe withdrawal rate of blood through the conductivity cell must represent only a negligible fraction of the total outflow of blood in order not to interfere with the balancing procedure. It seems,therefore, that the isovolumetric technique may be of advantage in smaller animals such as cats, rabbits, etc. It has, in addition, the advantage of doing away with blood sampling and it fulfills to some extent the requirement of a less invasive procedure. In contrast to the original isogravimetric technique, both the conductivity and isovolumetric modifications do not require that the limb be amputated thereby improving the viability of the preparation. REFERENCES 1. BRAKKEE, A. J. M., AND VENDRIK, A. J. H. (1966). Strain-gauge plethysmography; theoretical and practical notes on a new design. J. Appl. Physiol. 21,701-704. 2. BURGER, H. C., HOREMAN, H. W., AND BRAKKEE, A. J. M. (1959). Comparison of some methods for measuring peripheral blood flow. Phys. Med. Biol. 4,68-175. 3. CLARKE,R. S. J., AND HELLON,R. F. (1957). Venous collection in forearm and hand measured by the strain-gauge and volume plethysmograph. Clin. Sci. 16, 103-l 17. 4. DAHN, I., AND HALLBOOK, T. (1970). Simultaneous blood flow measurements by water and strain gauge plethysmography. Stand. J. Clin. Lab. Invest. 25, l-10. 5. FRONEK,A. (1971). Isoconductometric estimation of effective capillary pressure in isolated hind limb. Amer. J. Physiol. 220,1005-1008. 6. HOLLING, H. E., BLAND, H. C., AND Russ, E. (1961). Investigation of arterial obstruction using a mercury-in-rubber strain gauge. Amer. Heart J. 62,194-205. 7. PAPPENHEIMER,J. R., AND SOT+RIVERA, A. (1948). Effective osmotic pressure of the plasma proteins and other quantities associated with the capillary circulation in the hindlimbs of cats and dogs. Amer. J. Physiol. 152,471-491. 8. WHITNEY,R. J. (1953). The measurement of volume changes in human limbs. J. Physiol. 121, l-27.
RESEARCH
6, l-4 (1973)
Circumference Capillary
Measurement as a Criterion Pressure Determination’*2
for
ARNOSTFRONEKANDTHOMAS H.WITZEL Department of AMES-Bioengineering School of Medicine, University of California, San Diego, La Jolla, California 92037 Received August 7,1972 A modification of the original Pappenheimer and Soto-Rivera’s isogravimetric method to determine effective capillary pressure (P,) is described. As a balancing criterion, the circumference rather than the weight change was utilized. In 120experimental runs on 17 cats, a very good correlation was found with the conventional isogravimetric technique over a wide range of capillary pressures. The potential areas of application of this technique are also compared with the isoconductometric technique.
In a previous report (5), we describedthe utilization of changesof electrical resistance of blood as a balancing criterion for the determination of capillary pressure similar to the weight changesutilized in Pappenheimer and Soto-Rivera’s isogravimetric method (7). The minimum withdrawal rate of blood (currently 4 ml/min) limits the application of this technique in vascular areas with small blood flow rates, or under induced lowflow conditions sincethe amount of blood continuously withdrawn must be a negligible fraction of the sampled blood flow. This drawback is circumvented in the technique to be described. Basically, weight monitoring is replaced by the continuous recording of the circumference of the investigated extremity. DESCRIPTION OF THE METHOD Experiments have been performed (Nembutal anesthesia30 mg/kg) in 17 cats using basically the methodology as described in the previous report (5). Weight changes were determined by a Statham force transducer3 and arterial and venous pressuresby a P23Db and P23BB Statham transducer, respectively. Blood flow was measured by a photoelectric drop counter and calibrated by timed collection of blood into a graduated cylinder. Blood was returned by a Masterflex pump4 activated by a photoelectric sensing device. After amputation of the hind limb, a mercury-in-rubber gauge5was placed around the hind limb below the knee joint (approximately at the midpoint of the gastrocnemius muscle) with a prestretch of 10 g r Presented in abbreviated form at the Meeting of the Microcirculatory Atlantic City, NJ. ’ Supported by N.I.H. Grant HL 1269044. 3 UCZ-green cell, Statham Instruments, Oxnard, Cal. 4 Cole & Palmer, Chicago, Illinois. ’ Parks Electronics, Reaverton, Oregon. Copyright8 1973 by Academic Press, Inc. 1 AU rights of reproduction in any form reserved. Printed
in Great
Britain
Society, April 9, 1972,
2
FRONEK AND WITZEL
FIG. 1. From top: (a) flow (drop counter); (b) arterial pressure; (c) weight; (d) circumference; (e) venous pressure. Panel on right: Demonstration of the effect of arterial and venous pressure changes of theinvestigated hind limbs. on the weight andcircumference
to insure a linear response(6, 8). The changesin electrical resistance of the gauge are detected by a low-ohm resistancebridge5 and accordingly amplified and recorded. All monitored functions were recorded on an Offner-Dynograph recorder. After a control steady-statelevel has been obtained for both the weight and circumference, the inflow and outflow pressureswere balanced as in the conventional isogravimetric procedure (7) (Fig. 1).
FIG. 2. Venous pressure plotted against corresponding flow rates under “isovolumetric” Sequences 1 and 2 are control values, while 3,4, and 5 were obtained after hemorrhage.
conditions.
CIRCUMFERENCE
MEASUREMENT
AND
P, DETERMINATION
3
The venous pressures obtained under the “isovolumetric”6 conditions are plotted against the corresponding flow rates (Fig. 2). Capillary pressure was determined by extrapolation to zero flow, as in the conventional isogravimetric procedure. Each run in which the weight was considered as a balancing criterion was followed by an isovolumetric run in which the circumference was considered as the balancing criterion. RESULTS Altogether 120 experimental sequences were performed in 17 cats. Those runs in which the weight response coincided exactly with that of the circumference (as reproduced in Fig. 1) are represented on the line of identity in Fig. 3. In instances in which the
I 10
20 PC-WT
30 (cm
40
H,O)
FIG. 3. Extrapolated capillary pressuresobtained by the circumferencetechnique(P,-Circ) plotted againstpressuresobtained isogravimetrically (PC-WT). weight or circumference criterion was lagging, the isovolumetrically determined PC was compared with the preceding isogravimetrically determined PCvalue. In order to obtain a wider range of values, hemorrhage and pharmacologically induced changes were also initiated-isoproterenol and levophed infusions, 1 pm/kg/min and 2 pm/kg/ min, respectively. The results of all experiments including those obtained during hemorrhage, isoproterenol and levophed infusions are presented in Fig. 3. The correlation of PCvalues determined by both techniques is very close (r = 0.955) and the average difference in percent is 2.8 %, SD + 13.3 % and SE i 1.2 %. DISCUSSION The application of the mercury-in-rubber gauge (8) to indicate volume changes is basically an extrapolation of the conventional isogravimetric technique for determining 6 “Isovolumetric” condition is here defined as indicating no circumferencechange. Details see under Discussion.
4
FRONEK
AND
WITZEL
the capillary pressure(7). The closerelationship betweenlimb volume and circumference measurementshas been established in a number of studies (l-4). In order to study the effect of the underlying skin on the circumferential changesand on the extrapolated P, values as well, the mercury-in-rubber loop has been placed in five catsin direct contact with the musclesby cutting out a corresponding circumferential strip of skin. No significant difference was observed in both groups. The question may be raised to what extent the extrapolated PCobtained from the circumferential measurement in one plane represents the overall effective capillary pressure of the adjacent anatomical structures. It can be assumedthat the isogravimetrically determined PCrepresents the average value of the predominant anatomical structures, in this casethe skeletal muscles of the hind limb. Similar reasoning can be applied to the circumference determination and its relationship to the volume changes of the underlying muscle tissues. We feel that both types of capillary pressure determination, the conductometric as well as the isovolumetric technique, have different potential areas of application. The former has the advantage of reflecting the filtration or absorption changes directly without the intravascular volume component but its application is currently limited to larger animals or to larger vascular areassincethe withdrawal rate of blood through the conductivity cell must represent only a negligible fraction of the total outflow of blood in order not to interfere with the balancing procedure. It seems,therefore, that the isovolumetric technique may be of advantage in smaller animals such as cats, rabbits, etc. It has, in addition, the advantage of doing away with blood sampling and it fulfills to some extent the requirement of a less invasive procedure. In contrast to the original isogravimetric technique, both the conductivity and isovolumetric modifications do not require that the limb be amputated thereby improving the viability of the preparation. REFERENCES 1. BRAKKEE, A. J. M., AND VENDRIK, A. J. H. (1966). Strain-gauge plethysmography; theoretical and practical notes on a new design. J. Appl. Physiol. 21,701-704. 2. BURGER, H. C., HOREMAN, H. W., AND BRAKKEE, A. J. M. (1959). Comparison of some methods for measuring peripheral blood flow. Phys. Med. Biol. 4,68-175. 3. CLARKE,R. S. J., AND HELLON,R. F. (1957). Venous collection in forearm and hand measured by the strain-gauge and volume plethysmograph. Clin. Sci. 16, 103-l 17. 4. DAHN, I., AND HALLBOOK, T. (1970). Simultaneous blood flow measurements by water and strain gauge plethysmography. Stand. J. Clin. Lab. Invest. 25, l-10. 5. FRONEK,A. (1971). Isoconductometric estimation of effective capillary pressure in isolated hind limb. Amer. J. Physiol. 220,1005-1008. 6. HOLLING, H. E., BLAND, H. C., AND Russ, E. (1961). Investigation of arterial obstruction using a mercury-in-rubber strain gauge. Amer. Heart J. 62,194-205. 7. PAPPENHEIMER,J. R., AND SOT+RIVERA, A. (1948). Effective osmotic pressure of the plasma proteins and other quantities associated with the capillary circulation in the hindlimbs of cats and dogs. Amer. J. Physiol. 152,471-491. 8. WHITNEY,R. J. (1953). The measurement of volume changes in human limbs. J. Physiol. 121, l-27.