Indirect blood pressure determination by Doppler technique in renal hypertensive cats L. R. KLEVANS,
Department
G. HIRKALER,
of Pharmacology,
AND
J. L. KOVACS
Hofhann-La
Roche Inc., Nutley, New Jersey 07110
KLEVANSJ. R., G. HIRKALER, AND J. L. KOVACS. Indirect blood pressure determination by Doppler technique in renal hypertensive cats. Am. J. Physiol. 237(6): H720-H723, 1979 or Am. J. Physiol.: Heart Circ. Physiol. 6(6): H720-H723, 1979.The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in renal hypertensive cats. The accuracy of the method was evaluated by comparing indirect blood pressures from one leg of a cat with direct pressure measurements from the other leg. A linear relationship existed between indirect and direct systolic and diastolic pressures. The consistency of the method was assessed by measuring blood pressure during a 5-h monitoring period in normotensive and renal hypertensive, cats. No significant variation occurred over this period. The sensitivity of the method to blood pressure changes was determined also. A significant reduction in systolic and diastolic pressure induced by hydralazine, 10 mg/kg po, was recorded during a 5-h monitoring period. The development of renovascular hypertension was followed for approximately 70 days. Systolic pressure rose in a logarithmic fashion from 160 to a maximum of 240 mmHg. It was concluded that the Doppler ultrasonic technique is a simple and reliable method for recording indirect blood pressure acutely and chronically in conscious unrestrained cats. ultrasonic sphygmomanometry; teriosonde
renovascular
hypertension;
Ar-
increasingly clear that animal models used for evaluation of antihypertensive drugs do not always predict accurately the clinical efficacy of these agents (6,9). This appears to be particularly true of drugs that must be given chronically before an effect is observed. It is well known, for example, that chronic administration of propranolol lowers blood pressure in humans, but shows variable effects in different hypertensive rat models (6, 9). We have been evaluating the renal hypertensive cat in an effort to establish whether it has utility for predicting the effects of antihypertensive drugs in man. For this model to have utility, a simple and reliable method should be developed for recording blood pressure over long periods of time because chronic effects of antihypertensive drugs would be important in future studies. Therefore our purpose was to assess the validity of the Doppler ultrasonic technique for recording systolic and diastolic pressures indirectly in the renal hypertensive cat. The Doppler technique was chosen for recording blood pressure because it is a simple method and has been used previously in cats (7). IT HAS BECOME
H720
METHODS
Method for producing renal hypertension. Conditioned adult male cats weighing 3.5-4.0 kg were used. A conditioned cat is defined as one that is raised in a closed colony, vaccinated for feline distemper, free from parasites, and free from respiratory infections. Hypertension was induced by cellophane perinephritis. Cats were atropinized (0.02 mg/kg im), anesthetized briefly with ketamine (25 mg/kg im), and intubated with a sterile cuffed endotracheal tube (Murphey eye, 3 mm ID, American Hospital Supply). Anesthesia was maintained with a mixture of halothane and oxygen. Surgery was performed under sterile conditions. The right kidney was exposed through a retroperitoneal incision and removed. The left kidney was wrapped in sterile cellophane. The layers of muscle and skin were sutured together and a topical antibiotic was applied to the incision. Bicillin (300,000 U, Wyeth) was administered both on the day of the surgery and 2 days after the operation. Validation of Doppler ultrasonic method. Dopplershift ultrasonic sphygmomanometry was used to record systolic and diastolic blood pressures indirectly in conscious unrestrained cats. The Doppler signals were recorded with the aid of a Roche 1010 Arteriosonde, a disposable neonatal-size pressure cuff (9624), a Velcrocovered cloth cuff (9618), and a neonatal ultrasonic pressure transducer (8012). The disposable pressure cuff was shortened by 1.5 inches and taped to the cloth cuff. The transducer was attached to the disposable pressure cuff and the transducer cable was wrapped with tape to protect it from possible damage by the animal. The sensitivity of our ultrasonic transducers exceeded 14 mW/cm2; the sensitivity of the commercially available ones range from 5 to 7 mW/cm2. The following procedure was used to record Doppler signals. The medial portion of the right hindlimb of 4.0 -+ 0.5 kg male cats was shaved in the vicinity of the saphenous artery and vein. The transducer was covered liberally with coupling medium (Gelisonde 8098), positioned over the shaved area and secured tightly to the leg by Velcro on the cloth cuff. The cat was held on its right side for a trial pressure recording. The volume adjustment on the Arteriosonde was set to its maximum; then the pressure in the cuff was inflated to 300 mmHg with a Narco Biosystems pump in-line with an aneroid manometer. The deflation rate was set at approximately 2 mmHg/s. If the Doppler sounds were too soft or inaudible during deflation, the transducer was removed and
0363-6135/79/0000-OOOOooo$Ol.25
Copyright
0 1979 the American
Physiological
Society
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on September 14, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
BLOOD
PRESSURE
IN
HYPERTENSIVE
H721
CATS
repositioned on the leg. Once acceptable sounds were obtained, the animal was placed on its right side in a box measuring 12 x 12 x 18 in. Control blood pressures were determined 30-60 min after the trial recording, when the animals were relaxed in the box. After control readings, the animal was removed from the box, placed in a restraining device, and administered a drug. or placebo intragastrically via an infant feeding tube. The pressure cuff and transducer were not removed from the leg during dosing. After dosing, the animal was returned to the box, where systolic and diastolic blood pressures were recorded. Systolic blood pressure was. recorded as the first audible sound (Korotkoff, phase I); as the pressure in the cuff decreased, the intensity of the sound usually increased (phases II and III). Diastolic blood pressure was recorded when the sound intensity abruptly decreased and the sound pitch became “muffled.” Educational tape recordings of Korotkoff sounds were used to train observers tc identify phase I (systolic pressure) and phase IV (diastolic pressure). The accuracy of the Doppler ultrasonic method was evaluated by comparing indirect blood pressures with direct pressure measurements. For this procedure cats were anesthetized with a combination of diallylbarbituric acid (70 mg/kg ip) and urethan (280 mg/kg ip). A polyethylene catheter was inserted into the right femoral artery, and the ultrasonic transducer was placed over the left saphenous artery. Indirect and direct pressures were recorded simultaneously by two observers. Different leveis of systolic and diastolic pressures were achieved by injecting cumulative intravenous doses of clonidine (5-20 ,ug/kg). At least f our different levels of pressure were established in each of four cats. The consistency of the Doppler method was evaluated by measuring systolic and diastolic pressures at hourly intervals over a 5-h period. These experiments were carried out in conscious unrestrained normotensive and renal hypertensive cats. Pressures were measured before and after oral administration of 2 ml of 5% gum arabic. Them sensitivity of the. Doppler method I to a change in. 1 .a * *. . .-m . . * b.lood pressure was evaluated in both acute and chronic experiments. A pressure change induced by hydralazine (10 mg/kg po) was measured over a 5-h period in the acute experiment. The development of hypertension was followed in renal cats over a period of approximately 70 days in the chronic experiments. The initial pressure measurements were taken at least 25 days after surgery. Sta@ical analysis. A linear regression analysis was used to determine the functional relationship between indirect and direct blood pressures, A logarithmic regression analysis was used to determine the relationship between systolic blood pressure and the development of renovascular hypertension. Student’s t test for group or paired data was used to determine the difference between two or more samples of data. P values less than 0.05 were considered to be statistically significant.
paring indirect with direct blood pressure measurements. The indirect systolic and diastolic pressures increased with an increase in the level of the direct pressure (Figs. 1 and 2). All data points were regressed onto a straight line. A high-quality fit was achieved by the regression. The regression coefficient (r) was 0.92 for the systolic line, and 0.96 for the diastolic line. The slopes of both lines (0.97) approached the slope of an ideal line (1.0). Indirect systolic blood pressure tended to underestimate the direct reading because the y-intercept occurred at -7.0 mmHg. Indirect diastolic pressure closely approximated the direct reading. The y-intercept was +l.O mmHg. Indirect diastolic blood pressure could not be recorded as consistently as systolic pressure. Frequently the cuff and transducer had to be repositioned before suitable sounds could be identified. The consistency of the Doppler technique was evaluated by measuring systolic and diastolic pressures at 200 y=-7*39+ r= .92
.97x
*g- -
l CAT 2 *CAT 3 A CAT 4
/
100
200
Direct Systolic (mm Hg 1 FIG.
1, Dependence
of indirect
systolic
direct systolicpressure.
y=1.25+ r= .96
blood
pressure
on level
of
on level
of
.97x
-0, 100 0 2 .=
2 3 4
RESULTS
Validation of Doppler ultrasonic method. Indirect systolic and diastolic blood pressure was recorded using Doppler-shift sphygmomanometry. The accuracy of this method was evaluated in the anesthetized cat by com-
0
100 Direct
FIG.
direct
2. Dependence diastolic pressure.
of indirect
Diastolic diastolic
(mmHg) blood
pressure
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on September 14, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
H722
KLEVANS,
hourly intervals during a 5-h period (Table 1). These experiments were carried out in conscious, unrestrained, normotensive and renal hypertensive cats. Statistically significant variations did not occur between the first measurement and the following five measurements in the normotensive and renal hypertensive animal groups. Systolic blood pressures in the normotensive animals were less than the pressures in the renal hypertensive cats; pressures ranged from 139 t 8 to 146 t 9 mmHg in the normotensive group and from 158 t 4 to 176 t 11 mmHg in the hypertensive group. The values between groups were significantly different at zero time ( P < O.Ol), 1 h ( P < 0.05), 4 h ( P < O.Ol), and 5 h ( P < 0.01). Diastolic blood pressures in normotensive animals appeared to be slightly less than pressures in hypertensive animals. The sensitivity of the Doppler technique to blood pressure changes was evaluated in conscious, unrestrained, renal hypertensive cats. A blood pressure change induced by hydralazine, 10 mg/kg po, was monitored over a 5-h period (Table 2). Hydralazine significantly decreased both systolic and diastolic blood pressures. The peak effect occurred 1 h after dosing and then gradually returned toward control values. Systolic pressure was significantly lower for 3 h and diastolic pressure was significantly lower for 4 h after dosing. A blood pressure change produced by cellophane perinephritis was followed for approximately 70 days (Fig. 3). Systolic blood pressures were measured between the 20th and 100th day after surgery. The data points were fit to a logarithmic function (r = 0.80). The animals were hypertensive by the 25th day after surgery, as systolic blood pressures exceeded 160 mmHg. Pressure continued to rise in a logarithmic fashion for the next 70 days and reached a maximum of approximately 240 mmHg. DISCUSSION
Doppler ultrasonic sphygmomanometry
can be used to
1. Utilization of Doppler ultrasonic technique to record blood pressure I I
TABLE
Blood I eessure (! ystolic/Diastolic)
Condition
n
Normotensive cats Renal hypertensive cats
5
lh
2h
143+7-t 96t9 176tll 118t16
143t8 95t,7 167t14 106t,8
146t,9 91t9 158k4 t 91tlO
ensive
c it, using
Oh
4
139*8* 104t9 173t,4 107H
Significantly less than renal hyper data: * P < 0.01; t P < 0.05.
4h
3h
I
142&3* 93k5 171t8 105k12
143t,5* 95t,5 169t5 99-+9
t test for grouped
2. Utilization of Doppler ultrasonic technique to record hydralazine-induced blood pressure changes in renal hypertensive cats TABLE
Blood Pressure Oh
180~~5 116&9 * P < 0.001; data.
lh
123t,lO* 74+,8t
(Systolic/Diastolic)
2h
3h
4h
5h
129&10* 79+,7-j-
145+12-j94t,lO
156k8 90+5$
159k2 91+5$
$ P < 0.05;
using
t test
for
paired
HIRKALER,
AND
KOVACS
280 260 F - 240 0 I; 220 -5 a 200 i: : 180 1
51.61 Inx
160
r = 0.80
140 t I 20
I 1 I 40 60 80 TIME After Surgery (days)
FIG. 3. Utilization of Doppler ultrasonic development of perinephritis hypertension pressure.
technique in cats. SBP,
1 100 to document systolic blood
record indirect systolic and diastolic blood pressure in conscious unrestrained cats. The accuracy of this method was established by measuring the indirect pressure as a function of the direct pressure. The data points for these experiments fitted a straight line by a linear regression analysis. The slopes of the lines for systolic and diastolic pressures were close to 1.0, suggesting that the indirect measurement is directly proportional to the true pressure (i.e., direct measurement) throughout the entire range of physiologic blood pressures. The indirect systolic measurement slightly underestimated the direct pressure because the y-intercept for this line was -7 mmHg. The consistency of the Doppler technique was evaluated by measuring blood pressure in normotensive and renal hypertensive cats during a 5-h period. Systolic and diastolic pressures were recorded without significant variation during this time. The sensitivity of the Doppler ultrasonic recording method to changes in blood pressure was determined in both acute and chronic experiments. Hydralazine caused a significant decrease in both systolic and diastolic blood pressure during a 5-h monitoring period in an acute experiment. The development of renovascular hypertension was followed for a period of 70 days in the chronic experiments. Blood pressure rose in a logarithmic fashion. Our studies show, therefore, that the Doppler method has application when studying the acute and chronic effects of antihypertensive drugs in renal hypertensive cats. Doppler ultrasonic instruments have been used to record blood pressure in a variety of species including man (5, ll), monkey (4), dog (Z), and horse (3). We are aware of only one report in which this technique was applied to cats. McLeish (7) recorded Doppler-shift signals from coccygeal, tibia& and ulnar arteries using a Parks Electronic Doppler instrument. We found that Doppler-shift signals also could be detected in the cat using a Roche Arteriosonde coupled to a neonatal-size pressure cuff and transducer. The sensitivity of the transducer must exceed 14 mW/cm2. Clear systolic signals were transmitted consistently when the ultrasonic transducer was placed over the saphenous artery. Clear diastolic signals also could be recorded, but not as consistently as the systolic. Cellophane perinephritis hypertension can be pro-
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on September 14, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
BLOOD
PRESSURE
IN
HYPERTENSIVE
H723
CATS
duced in adult cats by following the methods originally described by Page (8). It was reported previously that cats develop high blood pressure 21-28 days after one kidney is wrapped in cellophane and the contralateral kidney is removed (1, lo), or after both renal arteries are constricted with Goldblatt clamps (12). Blood pressure was measured directly in these studies from a chronic indwelling catheter. The development of renovascular hypertension in cats has not been followed in a longitudinal fashion because of the problems associated with monitoring long-term direct pressure measurements.
These problems were circumvented in our study by use of an indirect method to record blood pressure. In summary, this study indicates that the Doppler ultrasonic technique is-.a simple and reliable procedure for recording indirect blood pressures in conscious unrestrained cats and that the method has application in studying the acute and chronic effects of antihypertensive drugs in cat cellophane perinephritis models of hypertension. Received
26 March
1979; accepted
in final
form
23 July
1979.
REFERENCES 1. FINCH, L. The cardiovascular effects of intraventricular clonidine and BAY 1470 in conscious hypertensive cats. Br. J. Pharmacol. 52: 333-338, 1974. 2. FREUNDLICH, J. J., D. K. DETWEILER, AND H. E. HANCE. Indirect blood pressure determination by Doppler technique in dogs. Curr. Ther. Res. Clin. Exp. 14: 73-80, 1972. 3. HAHN, A. W., H. E. GARNER, J. R. COFFMAN, AND C. W. SANDERS.
Lab. Anim. Sci. 23: 889-893, 1973. 4. HAHN, A. W., AND H. E. GARNER. Indirect measurement of blood pressure in animals. In: Advances in Veterinary Science and Comparative Medicine. New York: Academic, 1977, vol. 21, p. 1-17. 5. LABURTHA, D. R. New instruments for measuring blood pressure. Drugs 11, Suppl. 1: 48-57,1976. 6. LEVY, J. V. Beta-adrenergic blocking drugs in spontaneous hypertension. Am. J. Med. 61: 779-789, 1976. 7. MCLEISH, I. Doppler ultrasonic arterial pressure measurement in the cat. Vet. Rec. 100: 290-291,1977.
8. PAGE, I. H. The production of persistent arterial hypertension by cellophane perinephritis. J. Am. Med. Assoc. 113: 2046-2048, 1939. 9. PFEFFER, M. A., J. M. PFEFFER, A. K. WEISS, AND E. FROHLICH. Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade. Am. J. Physiol. 232: H639-H644, 1977 or Am. J. Physiol.: Heart Circ. Physiol. 1: H639-H644, 1977. 10. POYSER, R. H., J. H. SHORTER, AND R. L. WHITING. The production of hypertension and the effects of some antihypertensive agents in the conscious unrestrained cat. Br. J. Pharmacol. 51: 149P, 1974. 11. STEGALL, H. F., M. B. KARDON, AND W. T. KEMMERER. Indirect measurement of arterial blood pressure by Doppler ultrasonic sphygmomanometry. J. Appl. Physiol. 25: 793-798, 1968. 12. ZANCHETTI, A., M. GUAZZI, AND G. BACCELLI. Influence of sleep on circulation in normal and hypertensive animals. In: Antihypertensiue Therapy. Principles and Practice. Berlin: Springer 1966, p. 74-95.
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on September 14, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
Department
G. HIRKALER,
of Pharmacology,
AND
J. L. KOVACS
Hofhann-La
Roche Inc., Nutley, New Jersey 07110
KLEVANSJ. R., G. HIRKALER, AND J. L. KOVACS. Indirect blood pressure determination by Doppler technique in renal hypertensive cats. Am. J. Physiol. 237(6): H720-H723, 1979 or Am. J. Physiol.: Heart Circ. Physiol. 6(6): H720-H723, 1979.The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in renal hypertensive cats. The accuracy of the method was evaluated by comparing indirect blood pressures from one leg of a cat with direct pressure measurements from the other leg. A linear relationship existed between indirect and direct systolic and diastolic pressures. The consistency of the method was assessed by measuring blood pressure during a 5-h monitoring period in normotensive and renal hypertensive, cats. No significant variation occurred over this period. The sensitivity of the method to blood pressure changes was determined also. A significant reduction in systolic and diastolic pressure induced by hydralazine, 10 mg/kg po, was recorded during a 5-h monitoring period. The development of renovascular hypertension was followed for approximately 70 days. Systolic pressure rose in a logarithmic fashion from 160 to a maximum of 240 mmHg. It was concluded that the Doppler ultrasonic technique is a simple and reliable method for recording indirect blood pressure acutely and chronically in conscious unrestrained cats. ultrasonic sphygmomanometry; teriosonde
renovascular
hypertension;
Ar-
increasingly clear that animal models used for evaluation of antihypertensive drugs do not always predict accurately the clinical efficacy of these agents (6,9). This appears to be particularly true of drugs that must be given chronically before an effect is observed. It is well known, for example, that chronic administration of propranolol lowers blood pressure in humans, but shows variable effects in different hypertensive rat models (6, 9). We have been evaluating the renal hypertensive cat in an effort to establish whether it has utility for predicting the effects of antihypertensive drugs in man. For this model to have utility, a simple and reliable method should be developed for recording blood pressure over long periods of time because chronic effects of antihypertensive drugs would be important in future studies. Therefore our purpose was to assess the validity of the Doppler ultrasonic technique for recording systolic and diastolic pressures indirectly in the renal hypertensive cat. The Doppler technique was chosen for recording blood pressure because it is a simple method and has been used previously in cats (7). IT HAS BECOME
H720
METHODS
Method for producing renal hypertension. Conditioned adult male cats weighing 3.5-4.0 kg were used. A conditioned cat is defined as one that is raised in a closed colony, vaccinated for feline distemper, free from parasites, and free from respiratory infections. Hypertension was induced by cellophane perinephritis. Cats were atropinized (0.02 mg/kg im), anesthetized briefly with ketamine (25 mg/kg im), and intubated with a sterile cuffed endotracheal tube (Murphey eye, 3 mm ID, American Hospital Supply). Anesthesia was maintained with a mixture of halothane and oxygen. Surgery was performed under sterile conditions. The right kidney was exposed through a retroperitoneal incision and removed. The left kidney was wrapped in sterile cellophane. The layers of muscle and skin were sutured together and a topical antibiotic was applied to the incision. Bicillin (300,000 U, Wyeth) was administered both on the day of the surgery and 2 days after the operation. Validation of Doppler ultrasonic method. Dopplershift ultrasonic sphygmomanometry was used to record systolic and diastolic blood pressures indirectly in conscious unrestrained cats. The Doppler signals were recorded with the aid of a Roche 1010 Arteriosonde, a disposable neonatal-size pressure cuff (9624), a Velcrocovered cloth cuff (9618), and a neonatal ultrasonic pressure transducer (8012). The disposable pressure cuff was shortened by 1.5 inches and taped to the cloth cuff. The transducer was attached to the disposable pressure cuff and the transducer cable was wrapped with tape to protect it from possible damage by the animal. The sensitivity of our ultrasonic transducers exceeded 14 mW/cm2; the sensitivity of the commercially available ones range from 5 to 7 mW/cm2. The following procedure was used to record Doppler signals. The medial portion of the right hindlimb of 4.0 -+ 0.5 kg male cats was shaved in the vicinity of the saphenous artery and vein. The transducer was covered liberally with coupling medium (Gelisonde 8098), positioned over the shaved area and secured tightly to the leg by Velcro on the cloth cuff. The cat was held on its right side for a trial pressure recording. The volume adjustment on the Arteriosonde was set to its maximum; then the pressure in the cuff was inflated to 300 mmHg with a Narco Biosystems pump in-line with an aneroid manometer. The deflation rate was set at approximately 2 mmHg/s. If the Doppler sounds were too soft or inaudible during deflation, the transducer was removed and
0363-6135/79/0000-OOOOooo$Ol.25
Copyright
0 1979 the American
Physiological
Society
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on September 14, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
BLOOD
PRESSURE
IN
HYPERTENSIVE
H721
CATS
repositioned on the leg. Once acceptable sounds were obtained, the animal was placed on its right side in a box measuring 12 x 12 x 18 in. Control blood pressures were determined 30-60 min after the trial recording, when the animals were relaxed in the box. After control readings, the animal was removed from the box, placed in a restraining device, and administered a drug. or placebo intragastrically via an infant feeding tube. The pressure cuff and transducer were not removed from the leg during dosing. After dosing, the animal was returned to the box, where systolic and diastolic blood pressures were recorded. Systolic blood pressure was. recorded as the first audible sound (Korotkoff, phase I); as the pressure in the cuff decreased, the intensity of the sound usually increased (phases II and III). Diastolic blood pressure was recorded when the sound intensity abruptly decreased and the sound pitch became “muffled.” Educational tape recordings of Korotkoff sounds were used to train observers tc identify phase I (systolic pressure) and phase IV (diastolic pressure). The accuracy of the Doppler ultrasonic method was evaluated by comparing indirect blood pressures with direct pressure measurements. For this procedure cats were anesthetized with a combination of diallylbarbituric acid (70 mg/kg ip) and urethan (280 mg/kg ip). A polyethylene catheter was inserted into the right femoral artery, and the ultrasonic transducer was placed over the left saphenous artery. Indirect and direct pressures were recorded simultaneously by two observers. Different leveis of systolic and diastolic pressures were achieved by injecting cumulative intravenous doses of clonidine (5-20 ,ug/kg). At least f our different levels of pressure were established in each of four cats. The consistency of the Doppler method was evaluated by measuring systolic and diastolic pressures at hourly intervals over a 5-h period. These experiments were carried out in conscious unrestrained normotensive and renal hypertensive cats. Pressures were measured before and after oral administration of 2 ml of 5% gum arabic. Them sensitivity of the. Doppler method I to a change in. 1 .a * *. . .-m . . * b.lood pressure was evaluated in both acute and chronic experiments. A pressure change induced by hydralazine (10 mg/kg po) was measured over a 5-h period in the acute experiment. The development of hypertension was followed in renal cats over a period of approximately 70 days in the chronic experiments. The initial pressure measurements were taken at least 25 days after surgery. Sta@ical analysis. A linear regression analysis was used to determine the functional relationship between indirect and direct blood pressures, A logarithmic regression analysis was used to determine the relationship between systolic blood pressure and the development of renovascular hypertension. Student’s t test for group or paired data was used to determine the difference between two or more samples of data. P values less than 0.05 were considered to be statistically significant.
paring indirect with direct blood pressure measurements. The indirect systolic and diastolic pressures increased with an increase in the level of the direct pressure (Figs. 1 and 2). All data points were regressed onto a straight line. A high-quality fit was achieved by the regression. The regression coefficient (r) was 0.92 for the systolic line, and 0.96 for the diastolic line. The slopes of both lines (0.97) approached the slope of an ideal line (1.0). Indirect systolic blood pressure tended to underestimate the direct reading because the y-intercept occurred at -7.0 mmHg. Indirect diastolic pressure closely approximated the direct reading. The y-intercept was +l.O mmHg. Indirect diastolic blood pressure could not be recorded as consistently as systolic pressure. Frequently the cuff and transducer had to be repositioned before suitable sounds could be identified. The consistency of the Doppler technique was evaluated by measuring systolic and diastolic pressures at 200 y=-7*39+ r= .92
.97x
*g- -
l CAT 2 *CAT 3 A CAT 4
/
100
200
Direct Systolic (mm Hg 1 FIG.
1, Dependence
of indirect
systolic
direct systolicpressure.
y=1.25+ r= .96
blood
pressure
on level
of
on level
of
.97x
-0, 100 0 2 .=
2 3 4
RESULTS
Validation of Doppler ultrasonic method. Indirect systolic and diastolic blood pressure was recorded using Doppler-shift sphygmomanometry. The accuracy of this method was evaluated in the anesthetized cat by com-
0
100 Direct
FIG.
direct
2. Dependence diastolic pressure.
of indirect
Diastolic diastolic
(mmHg) blood
pressure
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on September 14, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
H722
KLEVANS,
hourly intervals during a 5-h period (Table 1). These experiments were carried out in conscious, unrestrained, normotensive and renal hypertensive cats. Statistically significant variations did not occur between the first measurement and the following five measurements in the normotensive and renal hypertensive animal groups. Systolic blood pressures in the normotensive animals were less than the pressures in the renal hypertensive cats; pressures ranged from 139 t 8 to 146 t 9 mmHg in the normotensive group and from 158 t 4 to 176 t 11 mmHg in the hypertensive group. The values between groups were significantly different at zero time ( P < O.Ol), 1 h ( P < 0.05), 4 h ( P < O.Ol), and 5 h ( P < 0.01). Diastolic blood pressures in normotensive animals appeared to be slightly less than pressures in hypertensive animals. The sensitivity of the Doppler technique to blood pressure changes was evaluated in conscious, unrestrained, renal hypertensive cats. A blood pressure change induced by hydralazine, 10 mg/kg po, was monitored over a 5-h period (Table 2). Hydralazine significantly decreased both systolic and diastolic blood pressures. The peak effect occurred 1 h after dosing and then gradually returned toward control values. Systolic pressure was significantly lower for 3 h and diastolic pressure was significantly lower for 4 h after dosing. A blood pressure change produced by cellophane perinephritis was followed for approximately 70 days (Fig. 3). Systolic blood pressures were measured between the 20th and 100th day after surgery. The data points were fit to a logarithmic function (r = 0.80). The animals were hypertensive by the 25th day after surgery, as systolic blood pressures exceeded 160 mmHg. Pressure continued to rise in a logarithmic fashion for the next 70 days and reached a maximum of approximately 240 mmHg. DISCUSSION
Doppler ultrasonic sphygmomanometry
can be used to
1. Utilization of Doppler ultrasonic technique to record blood pressure I I
TABLE
Blood I eessure (! ystolic/Diastolic)
Condition
n
Normotensive cats Renal hypertensive cats
5
lh
2h
143+7-t 96t9 176tll 118t16
143t8 95t,7 167t14 106t,8
146t,9 91t9 158k4 t 91tlO
ensive
c it, using
Oh
4
139*8* 104t9 173t,4 107H
Significantly less than renal hyper data: * P < 0.01; t P < 0.05.
4h
3h
I
142&3* 93k5 171t8 105k12
143t,5* 95t,5 169t5 99-+9
t test for grouped
2. Utilization of Doppler ultrasonic technique to record hydralazine-induced blood pressure changes in renal hypertensive cats TABLE
Blood Pressure Oh
180~~5 116&9 * P < 0.001; data.
lh
123t,lO* 74+,8t
(Systolic/Diastolic)
2h
3h
4h
5h
129&10* 79+,7-j-
145+12-j94t,lO
156k8 90+5$
159k2 91+5$
$ P < 0.05;
using
t test
for
paired
HIRKALER,
AND
KOVACS
280 260 F - 240 0 I; 220 -5 a 200 i: : 180 1
51.61 Inx
160
r = 0.80
140 t I 20
I 1 I 40 60 80 TIME After Surgery (days)
FIG. 3. Utilization of Doppler ultrasonic development of perinephritis hypertension pressure.
technique in cats. SBP,
1 100 to document systolic blood
record indirect systolic and diastolic blood pressure in conscious unrestrained cats. The accuracy of this method was established by measuring the indirect pressure as a function of the direct pressure. The data points for these experiments fitted a straight line by a linear regression analysis. The slopes of the lines for systolic and diastolic pressures were close to 1.0, suggesting that the indirect measurement is directly proportional to the true pressure (i.e., direct measurement) throughout the entire range of physiologic blood pressures. The indirect systolic measurement slightly underestimated the direct pressure because the y-intercept for this line was -7 mmHg. The consistency of the Doppler technique was evaluated by measuring blood pressure in normotensive and renal hypertensive cats during a 5-h period. Systolic and diastolic pressures were recorded without significant variation during this time. The sensitivity of the Doppler ultrasonic recording method to changes in blood pressure was determined in both acute and chronic experiments. Hydralazine caused a significant decrease in both systolic and diastolic blood pressure during a 5-h monitoring period in an acute experiment. The development of renovascular hypertension was followed for a period of 70 days in the chronic experiments. Blood pressure rose in a logarithmic fashion. Our studies show, therefore, that the Doppler method has application when studying the acute and chronic effects of antihypertensive drugs in renal hypertensive cats. Doppler ultrasonic instruments have been used to record blood pressure in a variety of species including man (5, ll), monkey (4), dog (Z), and horse (3). We are aware of only one report in which this technique was applied to cats. McLeish (7) recorded Doppler-shift signals from coccygeal, tibia& and ulnar arteries using a Parks Electronic Doppler instrument. We found that Doppler-shift signals also could be detected in the cat using a Roche Arteriosonde coupled to a neonatal-size pressure cuff and transducer. The sensitivity of the transducer must exceed 14 mW/cm2. Clear systolic signals were transmitted consistently when the ultrasonic transducer was placed over the saphenous artery. Clear diastolic signals also could be recorded, but not as consistently as the systolic. Cellophane perinephritis hypertension can be pro-
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BLOOD
PRESSURE
IN
HYPERTENSIVE
H723
CATS
duced in adult cats by following the methods originally described by Page (8). It was reported previously that cats develop high blood pressure 21-28 days after one kidney is wrapped in cellophane and the contralateral kidney is removed (1, lo), or after both renal arteries are constricted with Goldblatt clamps (12). Blood pressure was measured directly in these studies from a chronic indwelling catheter. The development of renovascular hypertension in cats has not been followed in a longitudinal fashion because of the problems associated with monitoring long-term direct pressure measurements.
These problems were circumvented in our study by use of an indirect method to record blood pressure. In summary, this study indicates that the Doppler ultrasonic technique is-.a simple and reliable procedure for recording indirect blood pressures in conscious unrestrained cats and that the method has application in studying the acute and chronic effects of antihypertensive drugs in cat cellophane perinephritis models of hypertension. Received
26 March
1979; accepted
in final
form
23 July
1979.
REFERENCES 1. FINCH, L. The cardiovascular effects of intraventricular clonidine and BAY 1470 in conscious hypertensive cats. Br. J. Pharmacol. 52: 333-338, 1974. 2. FREUNDLICH, J. J., D. K. DETWEILER, AND H. E. HANCE. Indirect blood pressure determination by Doppler technique in dogs. Curr. Ther. Res. Clin. Exp. 14: 73-80, 1972. 3. HAHN, A. W., H. E. GARNER, J. R. COFFMAN, AND C. W. SANDERS.
Lab. Anim. Sci. 23: 889-893, 1973. 4. HAHN, A. W., AND H. E. GARNER. Indirect measurement of blood pressure in animals. In: Advances in Veterinary Science and Comparative Medicine. New York: Academic, 1977, vol. 21, p. 1-17. 5. LABURTHA, D. R. New instruments for measuring blood pressure. Drugs 11, Suppl. 1: 48-57,1976. 6. LEVY, J. V. Beta-adrenergic blocking drugs in spontaneous hypertension. Am. J. Med. 61: 779-789, 1976. 7. MCLEISH, I. Doppler ultrasonic arterial pressure measurement in the cat. Vet. Rec. 100: 290-291,1977.
8. PAGE, I. H. The production of persistent arterial hypertension by cellophane perinephritis. J. Am. Med. Assoc. 113: 2046-2048, 1939. 9. PFEFFER, M. A., J. M. PFEFFER, A. K. WEISS, AND E. FROHLICH. Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade. Am. J. Physiol. 232: H639-H644, 1977 or Am. J. Physiol.: Heart Circ. Physiol. 1: H639-H644, 1977. 10. POYSER, R. H., J. H. SHORTER, AND R. L. WHITING. The production of hypertension and the effects of some antihypertensive agents in the conscious unrestrained cat. Br. J. Pharmacol. 51: 149P, 1974. 11. STEGALL, H. F., M. B. KARDON, AND W. T. KEMMERER. Indirect measurement of arterial blood pressure by Doppler ultrasonic sphygmomanometry. J. Appl. Physiol. 25: 793-798, 1968. 12. ZANCHETTI, A., M. GUAZZI, AND G. BACCELLI. Influence of sleep on circulation in normal and hypertensive animals. In: Antihypertensiue Therapy. Principles and Practice. Berlin: Springer 1966, p. 74-95.
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