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Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness
Acta Astronautica Vol. 17, No. 2, pp. 253-256, 1988 Printed in Great Britain
0094-5765/88 $3.00 + 0.00 Pergamon Press plc
CORRELATION OF MACRO A N D MICRO CARDIOVASCULAR FUNCTION D U R I N G WEIGHTLESSNESS A N D SIMULATED WEIGHTLESSNESSt P. M. HUTCHINS, T. H. MARSHBURN, T. L. SMITH, S. W. OSBORNE, C. D. LYNCH and S. J. MOULTSBY Department of Physiology and Pharmacology, Wake Forest University Medical Center, Winston-Salem, NC 27103, U.S.A. (Received 27 May 1987) Abstract--The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermoneutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the preformed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.
I. INTRODUCTION
Understanding biomedical processes in the human during such stresses as weightlessness and heavy g loads is essential for the success of recent manned space flights of increasing frequency and duration. Understanding of hemodynamic processes could result in minimizing discomfort to astronauts, who may experience feelings of fullness in the face, sinus congestion, increased pressure in the eyes and head, and nausea during space flight, as well as reduced tolerance to positive non-zero g-loads upon return to Earth[l]. Better understanding of hemodynamic functioning has economic importance for the space program as well, since cardiovascular changes in the astronaut can adversely effect performance during a mission where maximum return for each flight is at a premium. Most importantly, this knowledge could be used to prevent any loss of function and subsequent catastrophe that could occur during the high stresses placed upon the cardiovascular system during reentry and recovery on Earth. Due to the high cost of space flight and the high demand for time and space on board the Shuttle,
opportunities for physiologic study in a weightless environment are extremely minimal. Ground-based simulations of zero-g conditions are therefore essential. Currently available simulations include lower body positive pressure application, water immersion, and bed rest[2]. Past studies have indicated, however, that antiorthostatic hypokinetic preparations with animal models closely approximate physiologic functioning in a weightless environment and are the easiest of the methods to maintain[3]. This report will describe a unique method of simultaneous observation of the macro- and microcirculation in the unanesthetized rat under antiorhostatic hypokinetic restraint[4]. Measurements of venous and arteriolar diameter have been made with direct monitoring of pulse pressure and heart rate. Parallel observations will be made during space flight aboard the space shuttle. Assessment o f ' t h e relevance of the antiorthostatic hypokinetic restraint model, and a better understanding of the complete hemodynamic functioning of the cardiovascular system during weightlessness, with any role venous neovascularization may play in that functioning, can then be obtained. 2. BACKGROUND
tPaper IAF/IAA-86-391 presented at the 37th Congress of the International Astronautical Federation, Innsbruck, Austria 4-11 October 1986. 253
Only the macroscopic effects of weightlessness and simulated weightlessness on the cardiovascular sys-
254
P.M. HUTCHINSet al. Weightlessness
D
Headward Redistribution of Fluid
Reduced Skeletal
Muscle Activity Increased Venous Return
Decreased Metabolic Demand
Increased
f CardiacOutput | Increased Tissue Volume Receptors
Long-term Autoregulation
Reduced Circulating Blood Volume
Microvascular Changes ~ # Arterioles; t # Venules
TOLERANCE
Fig. 1
tem have been previously studied. A grossly observable effect reported by astronauts during space flight has been a cephalad fluid shift, likely due to loss of gravity-based distending pressure in the vascular beds of the lower extremeties. This response surfaces as edematous swelling of the upper thorax and face during the zero-g period[5]. In studies using antiorhostatic hypokinesia with human subjects to simulate weightlessness, increases in heart rate of 25% over a period of several days have been reported, as well as concomitant increases in cardiac output manifested as a rise in heart rate[3, 6]. Chronic antiorthostatic hypokinetic studies with the rat show a return of cardiac output back to or below normal after several days, with initial decreases in mean arterial pressure returning to normal after two days[7]. Muscle blood flow in the lower extremeties has been shown to be reduced, apparently due to a combination of hypodynamia of antigravity muscles and cephalad fluid shift[8]. There is evidence that fluid normally sequestered in the lower extremities by gravity is translocated to the cardiopulmonary vasculature during space travel. This increase in cardiopulmonary volume manifests as an increase in central venous pressure and subsequently venous return. The elevated venous return then evokes an increase in cardiac output via the Frank-Starling relationship and the Bainbridge reflex. The augmented cardiac output must then produce overperfusion of the microcirculation in some vascular beds (Fig. 1). The resultant imbalance in blood flow supply/demand is known to initiate long-term autoregulatory alterations in microvascular number, lengths and diameters. Recent evidence in rats, exposed to head-down tilt, suggests that mild simulated weightlessness results in an approximate 4 mm Hg increase in central venous
pressure and a 20% increase in cardiac output. The length of time required to adapt to head-down tilt depends in large part to the degree of tilt. We have shown that this level of increase in cardiac output and the resultant overperfusion of the microcirculation is associated with a doubling of the number of postcapillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. Since it is known that blood volume is contracted during space travel, then the increased venous capacity and reduced blood volume may contribute greatly to post-flight orthostatic intolerance (Fig. 1). Hence a thorough knowledge of the anatomical and physiological alterations in the microcirculation during weightlessness is crucial to a correct understanding of cardiovascular function during space flight. Cardiovascular alterations exert a controlling effect on the microcirculation and capillary fluid balance. Capillary hydrostatic pressure is most closely associated with the level of central venous pressure, capillary flow and post-capillary resistance. The pressure in the capillary (Pc) may be expressed as: P,. = F*
Roost + CVP,
where F, is capillary flow, Rpost is post-capillary resistance and CVP is central venous pressure. F, is determined by: F< = (P. - CVP)/Rore + Rp.... where Pa is arterial pressure and Rpre is pre-capillary resistance. Substituting the second expression into the first yields: P, = (R*P~ + CVP)/(I + R),
Cardiovascular function in weightlessness
~ \
BLOOD PRESSURE TRANSDUCER AMPLIFIERS - IEXCI a°° TATION
8 t)It T ~ DIGITAL
255
~OAESSSANYO MC I ROCOMPUTER WCC~L• Weesso
Fig. 2. Schematic of blood pressure monitoring system.
where R is the post- to pre-capillary resistance ratio. Since P~ is the primary regulator of capillary filtration and reabsorption in non-pathological conditions, then capillary fluid balance is determined by the arterial and venous pressures and the ratio of postto pre-capillary resistances. Arterial pressure is the multiplicative product of cardiac output (CO) and the total peripheral resistance (TPR), which is the sum of the pre-capillary and post-capillary resistances. Vascular resistance is determined by the length, number and diameter of the individual blood vessels, and the viscosity of blood. This laboratory has developed techniques for observing macro- and microcirculatory changes in the unanesthetized rat during weightlessness and simulated weightlessness. Quantitative measurements of vessel (arteriolar and venular) length, diameter and number, vascular patterns, branching ratios, vasomotion amplitude and frequency will be made to determine the microvascular response to weightlessness in an attempt to explain gross cardiovascular phenomena during spaceflight. 3. METHODS
The microcirculatory preparation consists of a lightweight, lexan chamber implanted around an intact, single layer of skeletal muscle on the back of the rat. The preformed microvasculature of the muscle cutaneous maximus (or m. cutaneous trunci) may be observed in the conscious, unanesthetized animal. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and direct arterial and venous pressures allows for the correlation of macroand microcirculatory changes at the same time and in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, rate-pressure product, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total carciovascular function may be obtained in the same animal without the complicating influence of anesthetics. AA
17 2
H
For some experiments, arterial pressure was the only large-scale hemodynamic variable monitored. In these experiments, pressure was obtained using a catheter inserted into the caudal artery to the level of the aorta. The caudal artery surgical procedures are performed under aseptic conditions. Animals are anesthetized using a 1:! mixture of Rompun (20 mg/ml) and Ketamine hydrochloride (100 mg/ml) at a dose of 0.1 cc/100g body wt. Prior to surgery, the hair of the proximal part of the tail is clipped and a small part of the skin covering the ventral tail artery and tail vein shaven. This area is cleaned with Phisohex and swabbed with Betadine solution. A midline incision is made on the ventral side of the tail and the ventral tail artery exposed. The artery is then ligated, cut, and a PE 10 catheter inserted and advanced 8-9 cm. The catheter is secured in the artery with a 5-0 silk thread ligature. The catheter is checked for viability (i.e. does blood flow back into it.9). A small amount of penicillin is applied into the wound to prevent infection. The wound is then closed using Vetafil. A protective cuff is placed around the tail so that the wound is covered. Care is given not to compress the tail. The catheter is connected to a flow-through swivel and to a pressure transducer (MS20-AA21 AKS, Electromedics) and amplifier that will continuously monitor pressure (Fig. 2). The analog-to-digital converter and microcomputer allow sampling of each pressure waveform 2400 times each minute and the real-time calculation of mean systolic and diastolic pressure, mean arterial pressure, heart rate, rate-pressure product and physiologic baroreceptor index. The data are computed and stored each 10 s. Ground-based studies also included testing of the Animal Enclosure Module (AEM) and observations of acute and chronic exposure of rats to antiorthostatic hypokinesia. The acute preparation involved video recording and photographing of the dorsal backflap of the eight rats as described above during a control period and then at 10, 20 and 30 min intervals during a head down tilt of fifteen degrees. The photomicrographs were used to measure diameters of the most distinct venules and arterioles in the preparations (50-200 microns), using the methods
256
P.M. HUTCHINSet al.
described above+ Frequency and amplitude measurements of the vasodilation of a selected arteriole in each rat were also made using the video records. For the chronic measurements, rats were suspended by the tail at the same 15 deg angle. Control photomicrographs and videorecordings were made on the first day of the head down tilt, and once daily thereafter. The preparation was discontinued after three days. 4. R E S U L T S
For the acute and chronic exposures to antiorthostatic hypokinesia, results were determined by averaging the percent of controls of each vessel diameter for each rat during each of the 10, 20 and 30 min periods in the acute preparation, and once daily for two days after the control period in the chronic preparation. Arterioles and venules were treated separately. Using the Student t-test, the arterioles showed a significant increase (P < 0.05) in vessel diameter of 10% during the 3 0 m i n period following initiation of the head down tilt. The venules showed no significant changes in diameter. A percent of control for the frequency and amplitude of vasomotion for the selected arteriole was also determined for each rat in the acute preparation. No significant variation of either parameter was observed after subjecting the data to a two-way analysis of variance. In the chronic preparation, a 20% increase in venular diameter was observed 1 day after the control period (P < 0.001), and a 2% increase after 2 days (P < 0.01). The arterioles exhibited a significant increase in diameter 1 day after the control (P < 0.05), but not after 2 days. Heart rate and mean arterial blood pressure increased slightly ( < 10%) during the first hour after head down tilt, however both were returned to control by the second hour (Fig. 3). Heart rate-pulse pressure product increased 68% during the first hour but was returned to control by the third hour. The baro-receptor reflex index was reduced to approximately 50% of control for the first two hours and rebounded to almost 3 times control by the third hour. This indicates that although gross hemodynamic measurements are changed relatively little, cardiovascular function is altered significantly during the acute phase of head down tilting.
300 A I' /
250
I
/ 200
I
X
I' 15o
~"
/
Xx
I'
"'"
\
100
50
0
~°~
I ....i
I
I
I
I
1
2
3
4
I
Hours a f t e r t i l t
Fig. 3. Cardiovascular alterations due to 15 deg head-down tilt. Mean arterial pressure ( ); heart rate ( - - - ) ; ratepressure product (. . . . ); baroreceptor index ( . . . . ).
Acknowledgements--Supported in part by NAS 2-10523, NIH HL-13936, HL-31151 and HL-7304.
REFERENCES
1. G. Gibson, Skylab 4 crew observations. In Biomedical Results from Skylab (Edited by R. S. Johnston and L. F. Dietlein), pp. 23-24. NASA Scientific and Technical Information Otfice (1977). 2. H. Sandier, Low-g simulation in mammalian research. The Physiologist 22, S19-22 (1979). 3. L. I. Kakurin et al., Antiorthostatic hypokinesia as a method of weightlessness simulation. Aviat. Space Environ. Med. 47, 1083-1086 (1976). 4. T. Smith et al., Long-term micro- and macrocirculatory measurements in conscious rats. Microvascular Res, 29, 360-370 (1985). 5. W. Thornton et al., Anthropometric changes and fluid shifts. In Biomedical Results from Skylab (Edited by R. S. Johnston and L. F. Dietlein), pp. 330-338. NASA Scientific and Technical Information Ot~ce (1977). 6. A. Chobanian et al., The metabolic and hemodynamic effects of prolonged bedrest in normal subjects. C&culation 49, 551-559 (1974). 7. V. Popovic, Antiorthostatic hypokinesia and circulation in the rat. The Physiologist 24, S15-16 (1981). 8. W. Thornton et al., Hemodynamic studies of the legs under weightlessness. In The Proceedings of the Skylab Life Sciences Symposium, Vol. II, (coordinated by R. S. Johnston and L. F. Dietlein), pp. 623-625. NASATMX-58154 (1974).
0094-5765/88 $3.00 + 0.00 Pergamon Press plc
CORRELATION OF MACRO A N D MICRO CARDIOVASCULAR FUNCTION D U R I N G WEIGHTLESSNESS A N D SIMULATED WEIGHTLESSNESSt P. M. HUTCHINS, T. H. MARSHBURN, T. L. SMITH, S. W. OSBORNE, C. D. LYNCH and S. J. MOULTSBY Department of Physiology and Pharmacology, Wake Forest University Medical Center, Winston-Salem, NC 27103, U.S.A. (Received 27 May 1987) Abstract--The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermoneutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the preformed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.
I. INTRODUCTION
Understanding biomedical processes in the human during such stresses as weightlessness and heavy g loads is essential for the success of recent manned space flights of increasing frequency and duration. Understanding of hemodynamic processes could result in minimizing discomfort to astronauts, who may experience feelings of fullness in the face, sinus congestion, increased pressure in the eyes and head, and nausea during space flight, as well as reduced tolerance to positive non-zero g-loads upon return to Earth[l]. Better understanding of hemodynamic functioning has economic importance for the space program as well, since cardiovascular changes in the astronaut can adversely effect performance during a mission where maximum return for each flight is at a premium. Most importantly, this knowledge could be used to prevent any loss of function and subsequent catastrophe that could occur during the high stresses placed upon the cardiovascular system during reentry and recovery on Earth. Due to the high cost of space flight and the high demand for time and space on board the Shuttle,
opportunities for physiologic study in a weightless environment are extremely minimal. Ground-based simulations of zero-g conditions are therefore essential. Currently available simulations include lower body positive pressure application, water immersion, and bed rest[2]. Past studies have indicated, however, that antiorthostatic hypokinetic preparations with animal models closely approximate physiologic functioning in a weightless environment and are the easiest of the methods to maintain[3]. This report will describe a unique method of simultaneous observation of the macro- and microcirculation in the unanesthetized rat under antiorhostatic hypokinetic restraint[4]. Measurements of venous and arteriolar diameter have been made with direct monitoring of pulse pressure and heart rate. Parallel observations will be made during space flight aboard the space shuttle. Assessment o f ' t h e relevance of the antiorthostatic hypokinetic restraint model, and a better understanding of the complete hemodynamic functioning of the cardiovascular system during weightlessness, with any role venous neovascularization may play in that functioning, can then be obtained. 2. BACKGROUND
tPaper IAF/IAA-86-391 presented at the 37th Congress of the International Astronautical Federation, Innsbruck, Austria 4-11 October 1986. 253
Only the macroscopic effects of weightlessness and simulated weightlessness on the cardiovascular sys-
254
P.M. HUTCHINSet al. Weightlessness
D
Headward Redistribution of Fluid
Reduced Skeletal
Muscle Activity Increased Venous Return
Decreased Metabolic Demand
Increased
f CardiacOutput | Increased Tissue Volume Receptors
Long-term Autoregulation
Reduced Circulating Blood Volume
Microvascular Changes ~ # Arterioles; t # Venules
TOLERANCE
Fig. 1
tem have been previously studied. A grossly observable effect reported by astronauts during space flight has been a cephalad fluid shift, likely due to loss of gravity-based distending pressure in the vascular beds of the lower extremeties. This response surfaces as edematous swelling of the upper thorax and face during the zero-g period[5]. In studies using antiorhostatic hypokinesia with human subjects to simulate weightlessness, increases in heart rate of 25% over a period of several days have been reported, as well as concomitant increases in cardiac output manifested as a rise in heart rate[3, 6]. Chronic antiorthostatic hypokinetic studies with the rat show a return of cardiac output back to or below normal after several days, with initial decreases in mean arterial pressure returning to normal after two days[7]. Muscle blood flow in the lower extremeties has been shown to be reduced, apparently due to a combination of hypodynamia of antigravity muscles and cephalad fluid shift[8]. There is evidence that fluid normally sequestered in the lower extremities by gravity is translocated to the cardiopulmonary vasculature during space travel. This increase in cardiopulmonary volume manifests as an increase in central venous pressure and subsequently venous return. The elevated venous return then evokes an increase in cardiac output via the Frank-Starling relationship and the Bainbridge reflex. The augmented cardiac output must then produce overperfusion of the microcirculation in some vascular beds (Fig. 1). The resultant imbalance in blood flow supply/demand is known to initiate long-term autoregulatory alterations in microvascular number, lengths and diameters. Recent evidence in rats, exposed to head-down tilt, suggests that mild simulated weightlessness results in an approximate 4 mm Hg increase in central venous
pressure and a 20% increase in cardiac output. The length of time required to adapt to head-down tilt depends in large part to the degree of tilt. We have shown that this level of increase in cardiac output and the resultant overperfusion of the microcirculation is associated with a doubling of the number of postcapillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. Since it is known that blood volume is contracted during space travel, then the increased venous capacity and reduced blood volume may contribute greatly to post-flight orthostatic intolerance (Fig. 1). Hence a thorough knowledge of the anatomical and physiological alterations in the microcirculation during weightlessness is crucial to a correct understanding of cardiovascular function during space flight. Cardiovascular alterations exert a controlling effect on the microcirculation and capillary fluid balance. Capillary hydrostatic pressure is most closely associated with the level of central venous pressure, capillary flow and post-capillary resistance. The pressure in the capillary (Pc) may be expressed as: P,. = F*
Roost + CVP,
where F, is capillary flow, Rpost is post-capillary resistance and CVP is central venous pressure. F, is determined by: F< = (P. - CVP)/Rore + Rp.... where Pa is arterial pressure and Rpre is pre-capillary resistance. Substituting the second expression into the first yields: P, = (R*P~ + CVP)/(I + R),
Cardiovascular function in weightlessness
~ \
BLOOD PRESSURE TRANSDUCER AMPLIFIERS - IEXCI a°° TATION
8 t)It T ~ DIGITAL
255
~OAESSSANYO MC I ROCOMPUTER WCC~L• Weesso
Fig. 2. Schematic of blood pressure monitoring system.
where R is the post- to pre-capillary resistance ratio. Since P~ is the primary regulator of capillary filtration and reabsorption in non-pathological conditions, then capillary fluid balance is determined by the arterial and venous pressures and the ratio of postto pre-capillary resistances. Arterial pressure is the multiplicative product of cardiac output (CO) and the total peripheral resistance (TPR), which is the sum of the pre-capillary and post-capillary resistances. Vascular resistance is determined by the length, number and diameter of the individual blood vessels, and the viscosity of blood. This laboratory has developed techniques for observing macro- and microcirculatory changes in the unanesthetized rat during weightlessness and simulated weightlessness. Quantitative measurements of vessel (arteriolar and venular) length, diameter and number, vascular patterns, branching ratios, vasomotion amplitude and frequency will be made to determine the microvascular response to weightlessness in an attempt to explain gross cardiovascular phenomena during spaceflight. 3. METHODS
The microcirculatory preparation consists of a lightweight, lexan chamber implanted around an intact, single layer of skeletal muscle on the back of the rat. The preformed microvasculature of the muscle cutaneous maximus (or m. cutaneous trunci) may be observed in the conscious, unanesthetized animal. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and direct arterial and venous pressures allows for the correlation of macroand microcirculatory changes at the same time and in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, rate-pressure product, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total carciovascular function may be obtained in the same animal without the complicating influence of anesthetics. AA
17 2
H
For some experiments, arterial pressure was the only large-scale hemodynamic variable monitored. In these experiments, pressure was obtained using a catheter inserted into the caudal artery to the level of the aorta. The caudal artery surgical procedures are performed under aseptic conditions. Animals are anesthetized using a 1:! mixture of Rompun (20 mg/ml) and Ketamine hydrochloride (100 mg/ml) at a dose of 0.1 cc/100g body wt. Prior to surgery, the hair of the proximal part of the tail is clipped and a small part of the skin covering the ventral tail artery and tail vein shaven. This area is cleaned with Phisohex and swabbed with Betadine solution. A midline incision is made on the ventral side of the tail and the ventral tail artery exposed. The artery is then ligated, cut, and a PE 10 catheter inserted and advanced 8-9 cm. The catheter is secured in the artery with a 5-0 silk thread ligature. The catheter is checked for viability (i.e. does blood flow back into it.9). A small amount of penicillin is applied into the wound to prevent infection. The wound is then closed using Vetafil. A protective cuff is placed around the tail so that the wound is covered. Care is given not to compress the tail. The catheter is connected to a flow-through swivel and to a pressure transducer (MS20-AA21 AKS, Electromedics) and amplifier that will continuously monitor pressure (Fig. 2). The analog-to-digital converter and microcomputer allow sampling of each pressure waveform 2400 times each minute and the real-time calculation of mean systolic and diastolic pressure, mean arterial pressure, heart rate, rate-pressure product and physiologic baroreceptor index. The data are computed and stored each 10 s. Ground-based studies also included testing of the Animal Enclosure Module (AEM) and observations of acute and chronic exposure of rats to antiorthostatic hypokinesia. The acute preparation involved video recording and photographing of the dorsal backflap of the eight rats as described above during a control period and then at 10, 20 and 30 min intervals during a head down tilt of fifteen degrees. The photomicrographs were used to measure diameters of the most distinct venules and arterioles in the preparations (50-200 microns), using the methods
256
P.M. HUTCHINSet al.
described above+ Frequency and amplitude measurements of the vasodilation of a selected arteriole in each rat were also made using the video records. For the chronic measurements, rats were suspended by the tail at the same 15 deg angle. Control photomicrographs and videorecordings were made on the first day of the head down tilt, and once daily thereafter. The preparation was discontinued after three days. 4. R E S U L T S
For the acute and chronic exposures to antiorthostatic hypokinesia, results were determined by averaging the percent of controls of each vessel diameter for each rat during each of the 10, 20 and 30 min periods in the acute preparation, and once daily for two days after the control period in the chronic preparation. Arterioles and venules were treated separately. Using the Student t-test, the arterioles showed a significant increase (P < 0.05) in vessel diameter of 10% during the 3 0 m i n period following initiation of the head down tilt. The venules showed no significant changes in diameter. A percent of control for the frequency and amplitude of vasomotion for the selected arteriole was also determined for each rat in the acute preparation. No significant variation of either parameter was observed after subjecting the data to a two-way analysis of variance. In the chronic preparation, a 20% increase in venular diameter was observed 1 day after the control period (P < 0.001), and a 2% increase after 2 days (P < 0.01). The arterioles exhibited a significant increase in diameter 1 day after the control (P < 0.05), but not after 2 days. Heart rate and mean arterial blood pressure increased slightly ( < 10%) during the first hour after head down tilt, however both were returned to control by the second hour (Fig. 3). Heart rate-pulse pressure product increased 68% during the first hour but was returned to control by the third hour. The baro-receptor reflex index was reduced to approximately 50% of control for the first two hours and rebounded to almost 3 times control by the third hour. This indicates that although gross hemodynamic measurements are changed relatively little, cardiovascular function is altered significantly during the acute phase of head down tilting.
300 A I' /
250
I
/ 200
I
X
I' 15o
~"
/
Xx
I'
"'"
\
100
50
0
~°~
I ....i
I
I
I
I
1
2
3
4
I
Hours a f t e r t i l t
Fig. 3. Cardiovascular alterations due to 15 deg head-down tilt. Mean arterial pressure ( ); heart rate ( - - - ) ; ratepressure product (. . . . ); baroreceptor index ( . . . . ).
Acknowledgements--Supported in part by NAS 2-10523, NIH HL-13936, HL-31151 and HL-7304.
REFERENCES
1. G. Gibson, Skylab 4 crew observations. In Biomedical Results from Skylab (Edited by R. S. Johnston and L. F. Dietlein), pp. 23-24. NASA Scientific and Technical Information Otfice (1977). 2. H. Sandier, Low-g simulation in mammalian research. The Physiologist 22, S19-22 (1979). 3. L. I. Kakurin et al., Antiorthostatic hypokinesia as a method of weightlessness simulation. Aviat. Space Environ. Med. 47, 1083-1086 (1976). 4. T. Smith et al., Long-term micro- and macrocirculatory measurements in conscious rats. Microvascular Res, 29, 360-370 (1985). 5. W. Thornton et al., Anthropometric changes and fluid shifts. In Biomedical Results from Skylab (Edited by R. S. Johnston and L. F. Dietlein), pp. 330-338. NASA Scientific and Technical Information Ot~ce (1977). 6. A. Chobanian et al., The metabolic and hemodynamic effects of prolonged bedrest in normal subjects. C&culation 49, 551-559 (1974). 7. V. Popovic, Antiorthostatic hypokinesia and circulation in the rat. The Physiologist 24, S15-16 (1981). 8. W. Thornton et al., Hemodynamic studies of the legs under weightlessness. In The Proceedings of the Skylab Life Sciences Symposium, Vol. II, (coordinated by R. S. Johnston and L. F. Dietlein), pp. 623-625. NASATMX-58154 (1974).