Microvascular
Ballard, E. Taylor.
pressure profile of serosal vessels of rat trachea
STEPHEN
T. BALLARD,
Department
of Physiology,
Stephen
T., Randall
RANDALL University
H. Nations,
H. NATIONS,
of South Alabama,
and Aubrey
Microvascular pressure profile of serosal vessels of rat trachea. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1303-H1304, 1992.-The distribution of intravascular pressures within the pulmonary airway microcirculation is an important determinant of transvascular liquid balance. Intravascular pressures were measured in the serosal vessels of the trachea in anesthetized, ventilated rats. The ventral portion of the trachea was surgically exposed and suffused with warm (37°C) Krebs-Ringer bicarbonate. The serosal microvasculature was observed with a video microscope, and microvessel pressures and diameters were measured using the servo-null technique and video calipers, respectively. Mean arterial pressure (MAP) was monitored from the left femoral artery and averaged 106.1 t 5.2 mmHg (n = 14). The highest pressure (77% of MAP) was measured in a large (95pm diam) transverse arteriole. As arteriolar diameter decreased from 39 to 11 pm, pressures fell from 62 to 18% of MAP. Capillaries drained into venular networks that formed extensive arcades. Pressures in these postcapillary venules (20-75 pm diam) were 7.7 2 5.5% of MAP (n = 9). These vesselsin turn drained into large venous sinuses (120-425 pm diam) where pressures averaged 5.7 $2.3% of MAP (n = 7). A four-parameter logistical model of these data predicts that capillary pressures range from 27 to 15% of MAP. We conclude that 1) a substantial resistance exists across precapillary arterioles ~40 pm diam and 2) a small pressure drop occurs between systemic arteries and primary feed arterioles in this tissue. microvessels; tracheal microcirculation; servo-null technique; arterioles; venules; venous sinuses
WHILE THE PULMONARY MICROCIRCULATION has been studied extensively in recent years, the tracheal and bronchial circulations that supply blood to the airways have received comparatively little attention. Unlike the pulmonary circulation, the airway circulation arises from systemic arteries and is therefore subject to much greater intravascular pressures. Consequently, the pressures that influence airway transvascular liquid balance would be expected to more closely resemble those existing in systemic microvascular beds, such as skeletal muscle and intestine. Tracheal microvascular pressure, an important determinant for transvascular liquid movement, has been directly measured only in mucosal microvessels from rabbits (3). In this study, the authors observed that tracheal resection, which was required to access the tracheal mucosa, resulted in a significant inflammatory response. In the present study, the microvascular pressure profile was measured in serosal microvessels of the rat trachea, since these microvessels are parallel with the mucosal vessels and can be more easily accessed without 0363-6135/92
$2.00
Copyright
AND
AUBREY
College of Medicine,
E. TAYLOR Mobile, Alabama 36688
injuring the trachea. The pressures in the microvessels were measured using the servo-null technique and the microvessel diameters were determined using video calipers. METHODS
Sprague-Dawley rats (300-650 g) were anesthetized by injection of pentobarbital sodium (50-75 mg/kg ip). The left femoral artery and femoral vein were cannulated with polyethylene tubing for measurement of mean femoral artery pressure (MAP) and supplementation of anesthetic and paralytic drugs, respectively. The head was secured in a stereotaxic device to reduce movement, and the ventral serosal surface of the trachea was surgically exposed. The tracheal surface caudal to the thyroid was illuminated with a fiber-optic lamp, and the microcirculation was observed with a Zeiss ACM video microscope. Krebs-Ringer bicarbonate solution (37”C), gassed with N:! and CO, to maintain a solution pH of 7.35-7.45, was continuously suffused over the tracheal surface. To reduce motion associated with breathing, rats were intubated endotracheally and ventilated with O2 to maintain blood pH (7.3-7.5). Diaphragmatic muscles were paralyzed by administration of pancuronium bromide (1 mg/kg). Intravascular pressures of arterioles and venules were measured with a servo-nulling pressure system (model 5A, Instrumentation for Physiology and Medicine, San Diego, CA) as originally described by Wiederhielm (5). Micropipettes, pulled from l-mm-diam borosilicate glass pipettes (FHC, Brunswick, ME) and with tips beveled to -2 pm, were slowly advanced with a micromanipulator into the tissue until the tip penetrated the vessel lumen. Observation of a stable pressure signal that was insensitive to amplifier gain confirmed that the pipette had penetrated the vessel lumen. In arterioles and small venules, pulse pressure was observed that was synchronous with arterial pulse pressure. Pulse pressure was generally not observed in large venules. Microvessel diameters were measured on the video image with video calipers (Microcirculation Research Institute, Texas A&M University, College Station, TX). RESULTS
Transverse arterioles that feed the tracheal microcirculation arise from the posterior thyroid arteries which are located parallel to the trachea on both the right and left side. These entry vessels branch into small arterioles that feed numerous serosal capillaries. Most of these capillaries are located in the intracartilaginous spaces, although some form hairpin-like loops in the tissue overlying the cartilaginous rings. Capillaries drain into venular networks that form extensive arcades. These small venules in turn drain into large (100-425 pm diam) venous sinuses located in the intercartilaginous space.
0 1992 the American
Physiological
Society
H1303
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (132.210.236.020) on January 11, 2019.
H1304
TRACHEAL
MICROVASCULAR
The tracheal serosal microvascular pressure profile is depicted in Fig. 1. Pressures were measured in 28 vessels (12 arterioles and 16 venules) from 14 rats. No more than four measurements were taken from a single animal. MAP was 106.1 t 5.2 mmHg (n = 14). The highest microvascular pressure (77% of MAP) was measured in a large (95 pm diam), transverse entry arteriole. As arteriolar diameter decreased from 39 to 11 pm, pressures fell from 62 to 18% of MAP. Pressures in 20. to 75pm diam venules were 7.7 t 5.5% (n = 9), whereas pressures in the venous sinuses (120-425 pm diam) averaged 5.7 t 2.3% (n = 7) of MAP. These data were fit to a sigmoid four-parameter logistical function (Sigmaplot, version 4.1, Jandel Scientific, Corte Madera, CA)
f(x) = Na - d)/[l + b/dblI + d where a is 76.689 (asymptotic maximum), b is 9.803 (slope parameter), c is 24.810 (value at the inflection point), and d is 5.040 (asymptotic minimum). With the assumption that capillaries fall between lo-pm diam arterioles and venules, this model predicts that capillary pressures range from 27 to 15% of MAP. Therefore, with a maximum venous pressure of 5.1% of MAP, fractional precapillary (systemic to lo-pm arterioles), capillary (lopm diam arterioles to lo-pm diam venules), and postcapillary (lo-pm diam venules to large venules) resistances would represent 76.7, 12.4, and 10.9%, respectively, of the total microvascuIar resistance. DISCUSSION
These data demonstrate several important characteristics of the serosal tracheal microcirculation. First, a very large pressure drop occurs across precapillary arterioles between 50 and 10 pm, which identifies this region
PRESSURES
of the microcirculation as the major site of resistance in the tracheal circulation. Second, capillary pressures are in the range of 15-27% of MAP, which is similar to micropuncture pressures measured in other peripheral tissues (1). Third, pressures in the feed arteriole approach 80% of mean systemic pressure. Although feed arteriolar pressures exceeding 70% of MAP have been observed in cat mesentery and in bat wing and cat tenuissumus skeletal muscles, most microvascular beds exhibit a greater pressure drop between the central arteries and the primary feed arterioles (1). To our knowledge, only one other study has reported tracheal microvascular pressures. Nordin et al. (3) used micropuncture techniques to measure pressures in the rabbit tracheal mucosal microvessels and described loand 50-pm capillary pressures of 27.6 -+ 2.9 and 13.6 t 3.4 mmHg on the arterial and venous ends of the capillary, respectively. In the Nordin study the trachea was resected to gain access to the mucosal vessels and the authors reported evidence of inflammation; e.g., blood flow and interstitial protein concentrations were elevated. This could explain why microvessel pressures we report were slightly lower in vessels of similar size. In the present study, intravascular pressure in an U-pm arteriole was 22 mmHg (18.5% of MAP), whereas small (20-70 pm) venular pressures averaged 7.6 t 2.5 mmHg (7.7% of MAP). Because the mucosal and serosal vessels represent parallel components of the tracheal microcirculation (4), it is possible that some differences exist between the pressure profiles of the two vascular beds, and species differences could also contribute to the observed slight variation in the two sets of microvascular pressures. The authors thank Dr. Joseph Barnard for assisting with the data analysis. This work was supported by National Heart, Lung, and Blood Institute Grant HL-22549. R. Nations was supported by a Cancer Research Program Fellowship. Portions of this work have appeared in abstract form (2). Address for reprint requests: S. T. Ballard, Dept. of Physiology, MSB 3024, Univ. of South Alabama, Mobile, AL 36688. Received 16 December 1991; accepted in final form 24 January 1992.
bQ
200
100 ARTERIOLES
200
100 I\ CAP VESSEL
300
VENULES
DIAMETER
(pm)
Fig. 1. Pressure profile of serosal microvasculature of rat trachea. CAP, capillaries where diameter varied from 5 to 10 pm. Solid circles, aggregate pressures measured in serosal microvessels from 14 rats. Line, 4-parameter logistical function curve fit to these data (see RESULTS). Pressure in a 425-pm venous sinus was 2.9% of MAP (not shown above). Open circles, pressures (&SE) reported by Nordin et al. (3) and approximate diameters for mucosal vessels from rabbit trachea.
REFERENCES 1. Joyner, W. L., and M. J. Davis. Pressure profile along the microvascular network and its control. Federation Proc. 46: 266269,1987. 2. Nations, R. H., A. E. Taylor, and S. T. Ballard. Intravascular pressure profile of the tracheal microcirculation (Abstract). FASEB J. 6: A2043,1992. 3. Nordin, U., 0. Kallskog, C.-E. Lindholm, and M. Wolgast. Transvascular fluid exchange in the tracheal mucosa. Microuasc. Res. 15: 287-298, 1978. 4. Wanner, A. Circulation of the airway mucosa. J. Appl. Physiol. 67:917-925,1989. 5. Wiederhielm, C. A., J. W. Woodbury, S. Kirk, and R. F. Rushmer. Pulsatile pressures in the microcirculation of frog’s mesentery. Am. J. Physiol. 207: 173-176, 1964.
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (132.210.236.020) on January 11, 2019.
Ballard, E. Taylor.
pressure profile of serosal vessels of rat trachea
STEPHEN
T. BALLARD,
Department
of Physiology,
Stephen
T., Randall
RANDALL University
H. Nations,
H. NATIONS,
of South Alabama,
and Aubrey
Microvascular pressure profile of serosal vessels of rat trachea. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1303-H1304, 1992.-The distribution of intravascular pressures within the pulmonary airway microcirculation is an important determinant of transvascular liquid balance. Intravascular pressures were measured in the serosal vessels of the trachea in anesthetized, ventilated rats. The ventral portion of the trachea was surgically exposed and suffused with warm (37°C) Krebs-Ringer bicarbonate. The serosal microvasculature was observed with a video microscope, and microvessel pressures and diameters were measured using the servo-null technique and video calipers, respectively. Mean arterial pressure (MAP) was monitored from the left femoral artery and averaged 106.1 t 5.2 mmHg (n = 14). The highest pressure (77% of MAP) was measured in a large (95pm diam) transverse arteriole. As arteriolar diameter decreased from 39 to 11 pm, pressures fell from 62 to 18% of MAP. Capillaries drained into venular networks that formed extensive arcades. Pressures in these postcapillary venules (20-75 pm diam) were 7.7 2 5.5% of MAP (n = 9). These vesselsin turn drained into large venous sinuses (120-425 pm diam) where pressures averaged 5.7 $2.3% of MAP (n = 7). A four-parameter logistical model of these data predicts that capillary pressures range from 27 to 15% of MAP. We conclude that 1) a substantial resistance exists across precapillary arterioles ~40 pm diam and 2) a small pressure drop occurs between systemic arteries and primary feed arterioles in this tissue. microvessels; tracheal microcirculation; servo-null technique; arterioles; venules; venous sinuses
WHILE THE PULMONARY MICROCIRCULATION has been studied extensively in recent years, the tracheal and bronchial circulations that supply blood to the airways have received comparatively little attention. Unlike the pulmonary circulation, the airway circulation arises from systemic arteries and is therefore subject to much greater intravascular pressures. Consequently, the pressures that influence airway transvascular liquid balance would be expected to more closely resemble those existing in systemic microvascular beds, such as skeletal muscle and intestine. Tracheal microvascular pressure, an important determinant for transvascular liquid movement, has been directly measured only in mucosal microvessels from rabbits (3). In this study, the authors observed that tracheal resection, which was required to access the tracheal mucosa, resulted in a significant inflammatory response. In the present study, the microvascular pressure profile was measured in serosal microvessels of the rat trachea, since these microvessels are parallel with the mucosal vessels and can be more easily accessed without 0363-6135/92
$2.00
Copyright
AND
AUBREY
College of Medicine,
E. TAYLOR Mobile, Alabama 36688
injuring the trachea. The pressures in the microvessels were measured using the servo-null technique and the microvessel diameters were determined using video calipers. METHODS
Sprague-Dawley rats (300-650 g) were anesthetized by injection of pentobarbital sodium (50-75 mg/kg ip). The left femoral artery and femoral vein were cannulated with polyethylene tubing for measurement of mean femoral artery pressure (MAP) and supplementation of anesthetic and paralytic drugs, respectively. The head was secured in a stereotaxic device to reduce movement, and the ventral serosal surface of the trachea was surgically exposed. The tracheal surface caudal to the thyroid was illuminated with a fiber-optic lamp, and the microcirculation was observed with a Zeiss ACM video microscope. Krebs-Ringer bicarbonate solution (37”C), gassed with N:! and CO, to maintain a solution pH of 7.35-7.45, was continuously suffused over the tracheal surface. To reduce motion associated with breathing, rats were intubated endotracheally and ventilated with O2 to maintain blood pH (7.3-7.5). Diaphragmatic muscles were paralyzed by administration of pancuronium bromide (1 mg/kg). Intravascular pressures of arterioles and venules were measured with a servo-nulling pressure system (model 5A, Instrumentation for Physiology and Medicine, San Diego, CA) as originally described by Wiederhielm (5). Micropipettes, pulled from l-mm-diam borosilicate glass pipettes (FHC, Brunswick, ME) and with tips beveled to -2 pm, were slowly advanced with a micromanipulator into the tissue until the tip penetrated the vessel lumen. Observation of a stable pressure signal that was insensitive to amplifier gain confirmed that the pipette had penetrated the vessel lumen. In arterioles and small venules, pulse pressure was observed that was synchronous with arterial pulse pressure. Pulse pressure was generally not observed in large venules. Microvessel diameters were measured on the video image with video calipers (Microcirculation Research Institute, Texas A&M University, College Station, TX). RESULTS
Transverse arterioles that feed the tracheal microcirculation arise from the posterior thyroid arteries which are located parallel to the trachea on both the right and left side. These entry vessels branch into small arterioles that feed numerous serosal capillaries. Most of these capillaries are located in the intracartilaginous spaces, although some form hairpin-like loops in the tissue overlying the cartilaginous rings. Capillaries drain into venular networks that form extensive arcades. These small venules in turn drain into large (100-425 pm diam) venous sinuses located in the intercartilaginous space.
0 1992 the American
Physiological
Society
H1303
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (132.210.236.020) on January 11, 2019.
H1304
TRACHEAL
MICROVASCULAR
The tracheal serosal microvascular pressure profile is depicted in Fig. 1. Pressures were measured in 28 vessels (12 arterioles and 16 venules) from 14 rats. No more than four measurements were taken from a single animal. MAP was 106.1 t 5.2 mmHg (n = 14). The highest microvascular pressure (77% of MAP) was measured in a large (95 pm diam), transverse entry arteriole. As arteriolar diameter decreased from 39 to 11 pm, pressures fell from 62 to 18% of MAP. Pressures in 20. to 75pm diam venules were 7.7 t 5.5% (n = 9), whereas pressures in the venous sinuses (120-425 pm diam) averaged 5.7 t 2.3% (n = 7) of MAP. These data were fit to a sigmoid four-parameter logistical function (Sigmaplot, version 4.1, Jandel Scientific, Corte Madera, CA)
f(x) = Na - d)/[l + b/dblI + d where a is 76.689 (asymptotic maximum), b is 9.803 (slope parameter), c is 24.810 (value at the inflection point), and d is 5.040 (asymptotic minimum). With the assumption that capillaries fall between lo-pm diam arterioles and venules, this model predicts that capillary pressures range from 27 to 15% of MAP. Therefore, with a maximum venous pressure of 5.1% of MAP, fractional precapillary (systemic to lo-pm arterioles), capillary (lopm diam arterioles to lo-pm diam venules), and postcapillary (lo-pm diam venules to large venules) resistances would represent 76.7, 12.4, and 10.9%, respectively, of the total microvascuIar resistance. DISCUSSION
These data demonstrate several important characteristics of the serosal tracheal microcirculation. First, a very large pressure drop occurs across precapillary arterioles between 50 and 10 pm, which identifies this region
PRESSURES
of the microcirculation as the major site of resistance in the tracheal circulation. Second, capillary pressures are in the range of 15-27% of MAP, which is similar to micropuncture pressures measured in other peripheral tissues (1). Third, pressures in the feed arteriole approach 80% of mean systemic pressure. Although feed arteriolar pressures exceeding 70% of MAP have been observed in cat mesentery and in bat wing and cat tenuissumus skeletal muscles, most microvascular beds exhibit a greater pressure drop between the central arteries and the primary feed arterioles (1). To our knowledge, only one other study has reported tracheal microvascular pressures. Nordin et al. (3) used micropuncture techniques to measure pressures in the rabbit tracheal mucosal microvessels and described loand 50-pm capillary pressures of 27.6 -+ 2.9 and 13.6 t 3.4 mmHg on the arterial and venous ends of the capillary, respectively. In the Nordin study the trachea was resected to gain access to the mucosal vessels and the authors reported evidence of inflammation; e.g., blood flow and interstitial protein concentrations were elevated. This could explain why microvessel pressures we report were slightly lower in vessels of similar size. In the present study, intravascular pressure in an U-pm arteriole was 22 mmHg (18.5% of MAP), whereas small (20-70 pm) venular pressures averaged 7.6 t 2.5 mmHg (7.7% of MAP). Because the mucosal and serosal vessels represent parallel components of the tracheal microcirculation (4), it is possible that some differences exist between the pressure profiles of the two vascular beds, and species differences could also contribute to the observed slight variation in the two sets of microvascular pressures. The authors thank Dr. Joseph Barnard for assisting with the data analysis. This work was supported by National Heart, Lung, and Blood Institute Grant HL-22549. R. Nations was supported by a Cancer Research Program Fellowship. Portions of this work have appeared in abstract form (2). Address for reprint requests: S. T. Ballard, Dept. of Physiology, MSB 3024, Univ. of South Alabama, Mobile, AL 36688. Received 16 December 1991; accepted in final form 24 January 1992.
bQ
200
100 ARTERIOLES
200
100 I\ CAP VESSEL
300
VENULES
DIAMETER
(pm)
Fig. 1. Pressure profile of serosal microvasculature of rat trachea. CAP, capillaries where diameter varied from 5 to 10 pm. Solid circles, aggregate pressures measured in serosal microvessels from 14 rats. Line, 4-parameter logistical function curve fit to these data (see RESULTS). Pressure in a 425-pm venous sinus was 2.9% of MAP (not shown above). Open circles, pressures (&SE) reported by Nordin et al. (3) and approximate diameters for mucosal vessels from rabbit trachea.
REFERENCES 1. Joyner, W. L., and M. J. Davis. Pressure profile along the microvascular network and its control. Federation Proc. 46: 266269,1987. 2. Nations, R. H., A. E. Taylor, and S. T. Ballard. Intravascular pressure profile of the tracheal microcirculation (Abstract). FASEB J. 6: A2043,1992. 3. Nordin, U., 0. Kallskog, C.-E. Lindholm, and M. Wolgast. Transvascular fluid exchange in the tracheal mucosa. Microuasc. Res. 15: 287-298, 1978. 4. Wanner, A. Circulation of the airway mucosa. J. Appl. Physiol. 67:917-925,1989. 5. Wiederhielm, C. A., J. W. Woodbury, S. Kirk, and R. F. Rushmer. Pulsatile pressures in the microcirculation of frog’s mesentery. Am. J. Physiol. 207: 173-176, 1964.
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