Carotid sinus reflex function alloxan diabetic rabbit
in the
DAVID N. MATISOFF, JOHN C. LEE, AND S. EVANS DOWNING Department of Pathology, Yale University School of Medicine, New Haven,
MATISOFF, DAVID N., JOHN C. LEE, AND S. EVANS DOWNCarotid sinus reflex function in the aLloxan diabetic rabbit. Am. J. Physiol. 236(3): H417-H421, 1979 or Am. J. Physiol.: Heart Circ. Physiol. 5(3): H417-H421, 1979.-Baroreflex function was studied in three groups of adult rabbits. Seven animals were given alloxan (100-200 mg/kg) and became diabetic (group D) with mean blood sugar values of 348 t 30 mg/ dl. Eight animals were given alloxan, but did not develop significant hyperglycemia (135 mg/dl) ( group A). Nine controls ( group C) were also studied (glucose, 101 mg/dl). All animals were anesthetized with pentobarbital (30 mg/kg). Blood pressure (BP) and heart rate (HR) responses to bilateral carotid occlusion (BCO) were measured before and after depressor nerve sectioning (DN,) and sinus nerve sectioning (SN,). Before sectioning, BCO caused a rise in BP of 30 * 4 mmHg in group C, 35 t 3 in group A, and 36 t, 4 in group D. HR increased about 13 beats/min in each group. After DN,, resting BP increased in group C from 97 to 104 mmHg (P < O.OOS), but no change occurred in the other groups. Responses to BCO were significantly but similarly enhanced in all groups after DN,. HR did not increase in group D. Resting BP increased after SN, only in the controls (group C). Differences in BP elevation with BCO before and after SN, (“pure” reflex response) were identical, averaging about 35 mmHg. Thus, no alteration of BP or HR responses to BCO was identified in early alloxan diabetes. However, resting tone in the buffer nerves may have been less. ING.
baroreceptors; heart rate
diabetes;
autonomic
regulation;
blood pressure;
DYSFUNCTION, although clearly evident in both early and late stages of human diabetes mellitus (3, 12, 18) has rarely been studied in experimental models. Eliasson (11) measured conduction velocity in the vagus nerve in adult rats with diabetes of Z-week duration and found no differences from controls. Abnormalities in peripheral nerve conduction have been demonstrated as early as 5-6 days after the onset of experimental diabetes mellitus (11, 14). Both motor and sensory fibers from the hindlimb were similarly affected. Impaired motor nerve conduction velocity is independent of the methods used to produce diabetes: alloxan, streptozotocin, or partial pancreatectomy. In the present study we used adult rabbits made diabetic with alloxan monohydrate as previously described (19). Carotid sinus reflex activity, known to be altered in human subjects with diabetes (5), was assessedand compared with that in normal control animals. Evidence for changes in tonic activity in the carotid sinus and aortic depressor nerves was also sought
AUTONOMIC
0363-6135/79/0000-0000$01.25
Copyright
0
1979 the American
Physiological
Connecticut
by denervation studies. A preliminary findings has appeared (22).
06510
report on the
METHODS
Three groups of adult New Zealand White rabbits of both sexes were studied. To facilitate injections and repeated sampling, indwelling polyethylene catheters were placed in a femoral or jugular vein under local (lidocaine) anesthesia. In some animals, the marginal ear vein was used and samples were withdrawn by direct needle puncture. Fifteen animals received alloxan monohydrate (Eastman Kodak), 100-200 mg/kg body wt (total dose). This was usually given in divided doses of 75, 50, and 25 mg/kg on successive days, with the lower dose repeated if necessary. Seven rabbits became hyperglycemic, with blood sugar values greater than 200 mg/ dl. The remaining eight animals showed an insignificant elevation of blood glucose and were therefore used as the alloxan control group. Nine rabbits not given alloxan served as controls. Blood samples were obtained for pH, glucose (Glucostat, Worthington Biochemical), and hematocrit prior to alloxan administration and daily until studied. Arterial pH, Paz, PCO~(Instrumentation Laboratories), glucose, and hematocrit were measured after anesthesia on the day of the experiment. Intraperitoneal glucose injections were used to maintain blood sugar within the normal range during the hypoglycemic phase following administration of alloxan. The animals were fed Purina rabbit chow and water ad libitum. The nine control animals were similarly studied, but received equivalent volumes of normal saline instead of alloxan. Four were studied immediately. Two were studied at 2 days and three at 4 days after catheter placement. The animals given alloxan, with one exception, were studied 3-5 days after the initial dose. One was studied after 35 days. All rabbits were anesthetized with pentobarbital, 30 mg/kg body wt, iv, and breathed spontaneously during the experiment. The right and left common carotid arteries and accompanying depressor nerves were isolated. A loop-snare technique was used to obtain complete and reversible occlusion without damaging the vessel. The snare was placed well below the carotid bifurcation in each case. Mean arterial pressure and heart rate changes following bilateral occlusion were measured before and after depressor nerve sectioning. The carotid sinus nerves were then sectioned and the occlusion test was repeated. Society
H417
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (129.081.226.078) on January 16, 2019.
H418
MATISOFF,
In each step in this sequence, values were compared with those obtaining immediately prior to carotid occlusion. Pressures were measured in a cannulated femoral artery with Sanborn transducers (267 series) and recorded on a Sanborn 358 oscillograph at chart speeds of 0.5 and 50 mm/s. Mean pressure was obtained by electronic averaging. Heart rate was monitored with a Sanborn cardiotachometer and confirmed by direct countin fast traces. All data were processed and analyzed by standard statistical methods (17) and expressed as means t SE. Differences were considered significant when P < 0.05.
A I” E
0
Corotids
open
LEE,
EEB Carotid
AND
DOWNING
Occlusion
r
VE 180 t
CONTROL
ALLOXAN
DIABETIC
4 Mm221
(N=9)
I80
(Nd5)
;1 ) 160I-
160
5 I
gf 940
t
p
in the
DAVID N. MATISOFF, JOHN C. LEE, AND S. EVANS DOWNING Department of Pathology, Yale University School of Medicine, New Haven,
MATISOFF, DAVID N., JOHN C. LEE, AND S. EVANS DOWNCarotid sinus reflex function in the aLloxan diabetic rabbit. Am. J. Physiol. 236(3): H417-H421, 1979 or Am. J. Physiol.: Heart Circ. Physiol. 5(3): H417-H421, 1979.-Baroreflex function was studied in three groups of adult rabbits. Seven animals were given alloxan (100-200 mg/kg) and became diabetic (group D) with mean blood sugar values of 348 t 30 mg/ dl. Eight animals were given alloxan, but did not develop significant hyperglycemia (135 mg/dl) ( group A). Nine controls ( group C) were also studied (glucose, 101 mg/dl). All animals were anesthetized with pentobarbital (30 mg/kg). Blood pressure (BP) and heart rate (HR) responses to bilateral carotid occlusion (BCO) were measured before and after depressor nerve sectioning (DN,) and sinus nerve sectioning (SN,). Before sectioning, BCO caused a rise in BP of 30 * 4 mmHg in group C, 35 t 3 in group A, and 36 t, 4 in group D. HR increased about 13 beats/min in each group. After DN,, resting BP increased in group C from 97 to 104 mmHg (P < O.OOS), but no change occurred in the other groups. Responses to BCO were significantly but similarly enhanced in all groups after DN,. HR did not increase in group D. Resting BP increased after SN, only in the controls (group C). Differences in BP elevation with BCO before and after SN, (“pure” reflex response) were identical, averaging about 35 mmHg. Thus, no alteration of BP or HR responses to BCO was identified in early alloxan diabetes. However, resting tone in the buffer nerves may have been less. ING.
baroreceptors; heart rate
diabetes;
autonomic
regulation;
blood pressure;
DYSFUNCTION, although clearly evident in both early and late stages of human diabetes mellitus (3, 12, 18) has rarely been studied in experimental models. Eliasson (11) measured conduction velocity in the vagus nerve in adult rats with diabetes of Z-week duration and found no differences from controls. Abnormalities in peripheral nerve conduction have been demonstrated as early as 5-6 days after the onset of experimental diabetes mellitus (11, 14). Both motor and sensory fibers from the hindlimb were similarly affected. Impaired motor nerve conduction velocity is independent of the methods used to produce diabetes: alloxan, streptozotocin, or partial pancreatectomy. In the present study we used adult rabbits made diabetic with alloxan monohydrate as previously described (19). Carotid sinus reflex activity, known to be altered in human subjects with diabetes (5), was assessedand compared with that in normal control animals. Evidence for changes in tonic activity in the carotid sinus and aortic depressor nerves was also sought
AUTONOMIC
0363-6135/79/0000-0000$01.25
Copyright
0
1979 the American
Physiological
Connecticut
by denervation studies. A preliminary findings has appeared (22).
06510
report on the
METHODS
Three groups of adult New Zealand White rabbits of both sexes were studied. To facilitate injections and repeated sampling, indwelling polyethylene catheters were placed in a femoral or jugular vein under local (lidocaine) anesthesia. In some animals, the marginal ear vein was used and samples were withdrawn by direct needle puncture. Fifteen animals received alloxan monohydrate (Eastman Kodak), 100-200 mg/kg body wt (total dose). This was usually given in divided doses of 75, 50, and 25 mg/kg on successive days, with the lower dose repeated if necessary. Seven rabbits became hyperglycemic, with blood sugar values greater than 200 mg/ dl. The remaining eight animals showed an insignificant elevation of blood glucose and were therefore used as the alloxan control group. Nine rabbits not given alloxan served as controls. Blood samples were obtained for pH, glucose (Glucostat, Worthington Biochemical), and hematocrit prior to alloxan administration and daily until studied. Arterial pH, Paz, PCO~(Instrumentation Laboratories), glucose, and hematocrit were measured after anesthesia on the day of the experiment. Intraperitoneal glucose injections were used to maintain blood sugar within the normal range during the hypoglycemic phase following administration of alloxan. The animals were fed Purina rabbit chow and water ad libitum. The nine control animals were similarly studied, but received equivalent volumes of normal saline instead of alloxan. Four were studied immediately. Two were studied at 2 days and three at 4 days after catheter placement. The animals given alloxan, with one exception, were studied 3-5 days after the initial dose. One was studied after 35 days. All rabbits were anesthetized with pentobarbital, 30 mg/kg body wt, iv, and breathed spontaneously during the experiment. The right and left common carotid arteries and accompanying depressor nerves were isolated. A loop-snare technique was used to obtain complete and reversible occlusion without damaging the vessel. The snare was placed well below the carotid bifurcation in each case. Mean arterial pressure and heart rate changes following bilateral occlusion were measured before and after depressor nerve sectioning. The carotid sinus nerves were then sectioned and the occlusion test was repeated. Society
H417
Downloaded from www.physiology.org/journal/ajpheart by ${individualUser.givenNames} ${individualUser.surname} (129.081.226.078) on January 16, 2019.
H418
MATISOFF,
In each step in this sequence, values were compared with those obtaining immediately prior to carotid occlusion. Pressures were measured in a cannulated femoral artery with Sanborn transducers (267 series) and recorded on a Sanborn 358 oscillograph at chart speeds of 0.5 and 50 mm/s. Mean pressure was obtained by electronic averaging. Heart rate was monitored with a Sanborn cardiotachometer and confirmed by direct countin fast traces. All data were processed and analyzed by standard statistical methods (17) and expressed as means t SE. Differences were considered significant when P < 0.05.
A I” E
0
Corotids
open
LEE,
EEB Carotid
AND
DOWNING
Occlusion
r
VE 180 t
CONTROL
ALLOXAN
DIABETIC
4 Mm221
(N=9)
I80
(Nd5)
;1 ) 160I-
160
5 I
gf 940
t
p
