Alterations in the baroreceptor reflex control of heart rate in streptozotocin diabetic rats

Baroreflex control of heart rate was studied in conscious diabetic rats at 12, 24 and 48 weeks after the induction of diabetes with streptozotocin. Baseline blood pressure (mean arterial blood pressure) of diabetic rats was significantly lower at 12 weeks after the induction of diabetes when compared to age-matched control rats. However, at 24 and 48 weeks of diabetes, no difference in blood pressure was observed between diabetic and age-matched control rats. In contrast, bradycardia (prolongation of pulse interval) was a consistent feature of diabetic rats at all time points (12, 24, and 48 weeks). To assess parasympathetic control of heart rate, baroreceptor sensitivity was determined by infusing phenylephrine. Baroreflexes in diabetic rats were changed from an increased sensitivity at 12 and 24 weeks to decreased sensitivity at 48 weeks after the induction of diabetes. This suggests that alterations in baroreflex sensitivity might depend upon the length of time the animals were exposed to the diabetes. Insulin treatment in diabetic animals reversed hypotension, bradycardia and altered baroreflex sensitivity observed in 12-week diabetic rats. Non-diabetic rats, in which the development of diabetes was prevented by pretreatment with 3-0-methylglucose before streptozotocin injection, or rats which did not develop diabetes after streptozotocin injection showed a similar baseline blood pressure, heart rate and baroreflex sensitivity to those of age-matched control rats (12, 24 and 48 weeks). This data suggests that changes in blood pressure, heart rate and baroreflex sensitivity are due to the diabetic state, not to streptozotocin toxicity.     

Diabetic neuropathy is a more important determinant of baroreflex sensitivity than carotid elasticity in type 2 diabetes

The object of this study was to evaluate the contribution of carotid distensibilty on baroreflex sensitivity in patients with type 2 diabetes mellitus with at least 2 additional cardiovascular risk factors. Carotid distensibility was measured bilaterally at the common carotid artery in 79 consecutive diabetic patients and 60 matched subjects without diabetes. Spontaneous baroreflex sensitivity assessment was obtained using time and frequency methods. Baroreflex sensitivity was lower in diabetic subjects as compared with nondiabetic control subjects (5.25+/-2.80 ms/mm Hg versus 7.55+/-3.79 ms/mm Hg; P<0.01, respectively). Contrary to nondiabetic subjects, diabetic subjects showed no significant correlation between carotid distensibility and baroreflex sensitivity (r2=0.08, P=0.04 and r2=0.04, P=0.13, respectively). In diabetic subjects, baroreflex sensitivity was significantly lower in subjects with peripheral neuropathy than in those with preserved vibration sensation (4.1+/-0.5 versus 6.1+/-0.4 ms/mm Hg, respectively; P=0.005). Age in nondiabetic subjects, diabetes duration, systolic blood pressure, peripheral or sensitive neuropathy, and carotid distensibility were introduced in a stepwise multivariate analysis to identify the determinants of baroreflex sensitivity. In diabetic patients, neuropathy is a more sensitive determinant of baroreflex sensitivity than the reduced carotid distensibility (stepwise analysis; F ratio=5.1, P=0.028 versus F ratio=1.9, P=0.16, respectively). In diabetic subjects with 2 additional cardiovascular risk factors, spontaneous baroreflex sensitivity is not related to carotid distensibility. Diabetic subjects represent a particular population within the spectrum of cardiovascular risk situations because of the marked neuropathy associated with their metabolic disorder. Therefore, neuropathy is a more significant determinant of baroreflex sensitivity than carotid artery elasticity in patients with type 2 diabetes.     

Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension.

AIMS: Impaired cerebrovascular reactivity and autoregulation has been previously reported in patients with diabetes mellitus. However, the contribution of cardiovascular diabetic autonomic neuropathy and orthostatic hypotension to the pathogenesis of such disturbances is not known. The purpose of this study was to evaluate cerebral blood flow velocity in response to standing in patients with diabetes and cardiovascular autonomic neuropathy with or without orthostatic hypotension. METHODS: We studied 27 patients with diabetes--eight had cardiovascular autonomic neuropathy and orthostatic hypotension (age 46.4 +/- 13.5 years, diabetes duration 25.0 +/- 11.0 years), seven had autonomic neuropathy without hypotension (age 47.3 +/- 12.7 years, diabetes duration 26.4 +/- 12.1 years), and 12 had no evidence of autonomic neuropathy (age 44.1 +/- 13.8 years, diabetes duration 17.1 +/- 10.2 years)-and 12 control subjects (age 42.6 +/- 9.7 years). Flow velocity was recorded in the right middle cerebral artery using transcranial Doppler sonography in the supine position and after active standing. RESULTS: Cerebral flow velocity in the supine position was not different between the groups studied. Active standing resulted in a significant drop of mean and diastolic flow velocities in autonomic neuropathy patients with orthostatic hypotension, while there were no such changes in the other groups. The relative changes in mean flow velocity 1 min after standing up were -22.7 +/- 16.25% in patients with neuropathy and orthostatic hypotension, +0.02 +/- 9.8% in those with neuropathy without hypotension, -2.8 +/- 14.05% in patients without neuropathy, and -9.2 +/- 15.1% in controls. CONCLUSIONS: Patients with diabetes and cardiovascular autonomic neuropathy with orthostatic hypotension show instability in cerebral blood flow upon active standing, which suggests impaired cerebral autoregulation.     

Early detection of orthostatic hypotension by quantitative sudomotor axon reflex test (QSART) in type 2 diabetic patients

OBJECTIVE: Orthostatic hypotension is caused by autonomic nerve dysfunction, mainly by severe sympathetic nerve dysfunction in diabetic patients. Diabetes affects the peripheral nerves in a length-dependent manner. Quantitative sudomotor axon reflex test (QSART) is one of the sensitive tests for detecting sympathetic nerve function. We examined the relation between orthostatic hypotension and QSART at the foot and hand in type 2 diabetic patients. METHODS: Thirty-eight type 2 diabetic patients (age, 48.9 +/- 11.9 years; duration of diabetes, 13.4 +/- 8.6 years) and 13 age-matched non-diabetic controls were evaluated. All subjects aged under 65 years old were recruited. All subjects underwent Schellong tests and quantitative sudomotor axon reflex tests (QSART) at the back of the hand and dorsum of the foot. RESULTS: The sweating volume at the foot dorsum, but not the back of the hand, during the first 10 minutes of QSART was significantly related to the orthostatic hypotension on the Schellong test. In patients with normal, borderline and abnormal blood pressure response to standing, 6 out of 17 (35.3%), 9 out of 12 (75.0%) and 9 out of 9 (100%) had decreased sweating volume of the foot dorsum, respectively. CONCLUSIONS: Our results suggest that orthostatic hypotension may be detected early by QSART at the dorsum of the foot in type 2 diabetic patients.     

Decreased alpha 2-adrenergic receptors on platelet membranes from diabetic patients with autonomic neuropathy and orthostatic hypotension

Platelet adrenergic receptors were studied in normal subjects and diabetic patients with autonomic neuropathy to determine the relationship between adrenoreceptor status and orthostatic hypotension. The binding of [3H]clonidine and [3H]yohimbine to platelet membranes was measured in diabetic patients with autonomic neuropathy and orthostatic hypotension (n = 12) and without orthostatic hypotension (n = 11), diabetic patients without autonomic neuropathy (n = 12), and normal subjects (n = 9). Mean basal and standing plasma norepinephrine levels were not different in the four groups, and there was no relationship between orthostasis and norepinephrine responses. The diabetic patients with orthostatic hypotension had a significantly greater fall in mean blood pressure [31 +/- 2.8 (+/- SE) mm Hg] than any of the other three groups. Diabetic patients with diabetic autonomic neuropathy and orthostatic hypotension had a 30-40% decrease in number of platelet alpha 2-adrenergic receptors, as demonstrated by [3H]clonidine and [3H]yohimbine binding. The maximum number of binding sites for clonidine was 34 +/- 2.8 (+/- SE) fmol/mg protein in normal subjects, 27.4 +/- 3.4 in diabetic patients with neuropathy, 26 +/- 2.5 in diabetic patients with autonomic neuropathy without orthostatic hypotension, and 20.4 +/- 3.8 fmol/mg protein in diabetic patients with autonomic neuropathy with orthostatic hypotension (P less than 0.001). The maximum number of binding sites for yohimbine was 112 +/- 12.6 in normal subjects, 127 +/- 10 in diabetic patients without orthostatic hypotension, and 87 +/- 12.4 fmol/mg protein in patients with diabetic autonomic neuropathy with orthostatic hypotension (P less than 0.001). Reduced platelet alpha 2-receptors are associated with postural hypotension in diabetic autonomic neuropathy. If applicable to the postjunctional alpha 2-adrenergic receptor on sympathetic neurons, reduced vascular responses to changes in posture would be expected despite normal or enhanced norepinephrine secretion.     

Comprehensive study of autonomic function in a population with primary Sjögren's syndrome. No evidence of autonomic involvement

OBJECTIVE: Autonomic neuropathy is associated with increased mortality. Autonomic nervous system disorders have been described in patients with primary Sj?gren's syndrome (SS), but the results in controlled studies have been contradictory, varying from normal to sympathetic or parasympathetic dysfunction. Since the earlier studies employed varying methodologies, which may have led to the discrepancy, we conducted a comprehensive study on autonomic function in patients with primary SS and compared our findings to healthy, carefully matched population based controls. METHODS: A conventional cardiovascular reflex test battery (Valsalva maneuver, deep breathing test, active orthostatic test) and measurements of baroreflex sensitivity with phenylephrine and 24 hour heart rate variability were performed on 30 patients with primary SS and 30 healthy age and sex matched population based controls. RESULTS: There were no significant differences between the SS patients and the healthy controls in any of the tests. CONCLUSIONS: The prevalence of autonomic dysfunction is not increased in patients with primary SS compared to the general population.     

Sensitive detection of hemodynamic failure during orthostatic stress in patients with diabetic polyneuropathy using a mini laser Doppler blood flowmeter

Autonomic dysfunction in diabetes is serious but often underestimated. The purpose of this study was to evaluate hemodynamics within the important initial phase just after standing, which cannot be evaluated by conventional instruments for orthostatic hypotension. Earlobe blood flow (EBF), which indirectly reflects the blood pressure response on standing, was evaluated using a mini laser Doppler flowmeter during standing from the sitting position in 58 healthy controls and 56 diabetic patients categorized as without (11), mild (27), and advanced diabetic polyneuropathy (18). The response area of the EBF waveform within 30 seconds after standing was calculated. An increased response area indicates poor recovery of EBF. Response area increased significantly with the degree of neuropathy (P < .001 for linear trend). Orthostatic hypotension was detected in two patients in the mild neuropathy group. The present approach may be sensitive and practical for detecting autonomic dysfunction not detected with the conventional orthostatic test.     

Autonomic and baroreflex function after captopril in hypertension

Absent reflex tachycardia with captopril therapy suggests blunting of circulatory reflexes, perhaps contributing to antihypertensive efficacy, and angiotensin converting enzyme inhibition may alter sympathetic function. Captopril effects on autonomic function were investigated in five severe hypertensive patients. Mean blood pressure fell in all patients (from 141 +/- 6 to 119 +/- 7 mm Hg, p less than 0.02) without orthostatic blood pressure fall or increase in heart rate (both p greater than 0.1) on captopril. Captopril did not alter baroreflex sensitivity as tested by amyl nitrile hypotension or phenylephrine hypertension (both p greater than 0.1). Comparison of these severely hypertensive patients to age matched normotensive control subjects did reveal markedly blunted baroreflex sensitivity in both the amyl nitrite test (by 89%, p less than 0.01) and the phenylephrine test (by 83%, p less than 0.01), suggesting that baseline blunting of baroreflex function may in part account for absence of reflex tachycardia. Captopril diminished the cardioacceleration after cold stress (from 61 +/- 38 to 23 +/- 43 msec, p less than 0.05) as well as the blood pressure fall after alpha-adrenergic blockade (from 46 +/- 13 to 24 +/- 9 mm Hg, p less than 0.05), suggesting diminished sympathetic stimulation of resistance vessels and decreased sympathetic participation in blood pressure maintenance, possibly at the prejunctional synaptic level. Four biochemical indices of sympathetic activity did not change. Thus captopril-treated patients had blunted reflex tachycardia, commensurate with blunted baroreflex function at baseline, and physiologic and pharmacologic evidence of diminished sympathetic activity was obtained with captopril therapy. Whether diminished sympathetic activity is involved in captopril's antihypertensive effect has not been determined.     

Baroreflex sensitivity and heredity in essential hypertension.

BACKGROUND. Abnormalities in baroreflex control of heart rate may be important in the pathogenesis of essential hypertension. METHODS AND RESULTS. To investigate the influence of heredity on baroreflex function, we measured baroreflex sensitivity in 40 untreated patients with essential hypertension grouped by the presence (FH+) or absence (FH-) of a family history of hypertension and in 24 normotensive counterparts. Baroreflex sensitivity was assessed by both high-pressure (phenylephrine bolus) and low-pressure (amyl nitrite inhalation) stimuli. Subject groups were matched for age, blood pressure, body weight, and race. Baroreflex sensitivity (in milliseconds per millimeter of mercury) assessed by amyl nitrite inhalation was 24.3 +/- 2.8 in FH- normotensives, 12.3 +/- 1.7 in FH+ normotensives, 15.4 +/- 3.3 in FH- hypertensives, and 8.1 +/- 1.2 in FH+ hypertensives. Baroreflex sensitivity assessed by phenylephrine bolus was 28.8 +/- 5.6 in FH- normotensives, 19.3 +/- 2.8 in FH+ normotensives, 19.1 +/- 2.0 in FH- hypertensives, and 13.6 +/- 1.3 in FH+ hypertensives. Two-factor analysis of variance showed significant effects on baroreflex sensitivity for blood pressure status (normotensive versus hypertensive) and for family history of hypertension. After control line (controlling) for the effects of several variables, including age, mean arterial pressure, body weight, and race through multiple linear regression analysis, the effect of family history of hypertension on baroreflex sensitivity was still highly significant. Indeed, of all variables investigated, family history of hypertension was the strongest unique baroreflex sensitivity predictor. CONCLUSIONS. These data suggest that the impairment in baroreflex sensitivity in hypertension is in part genetically determined and may be an important hereditary component in the pathogenesis of essential hypertension.     

Orthostatic blood pressure changes and diabetes duration

To determine the prevalence and the associated clinical characteristics of orthostatic hypotension and orthostatic hypertension in patients with diabetic sensorimotor polyneuropathy (DSP).MethodsA single-center retrospective cross-sectional study was conducted on 200 DSP patients who had 3-minute orthostatic measures as part of the standard clinic evaluation. We measured the heart rate (HR) and blood pressure (BP) supine and again after 3 min of standing.ResultsThe prevalence of orthostatic hypotension was 19.5% and that of orthostatic hypertension was 23%. Subjects with orthostatic hypotension had significantly longer diabetes duration than subjects who were normotensive and those with orthostatic hypertension. Quantitatively, BP changes from supine to standing correlated with diabetes duration (R = 0.306; P = 0.0582) and age (R = 0.434; P = 0.006) in subjects with orthostatic hypotension.ConclusionsOrthostatic hypertension and orthostatic hypotension are frequent in patients with DSP. Orthostatic hypertension is associated with shorter diabetes duration than orthostatic hypotension.     

Reduced baroreflex changes in muscle sympathetic nerve activity during blood pressure elevation in essential hypertension.

To determine whether the baroreflex control of sympathetic nerve activity is altered in patients with essential hypertension, muscle sympathetic nerve activity (MSNA) was recorded microneurographically from the tibial nerves of 23 normotensive subjects and 23 patients with essential hypertension. When phenylephrine (2 micrograms/kg) was injected intravenously, although the pressor response of mean arterial blood pressure (MAP) was significantly enhanced in the hypertensives as compared with the normotensives, the reflex decrease in MSNA was significantly smaller in the hypertensives. Furthermore, the baroreflex slope for MSNA, used as an index of baroreflex sensitivity and calculated by relating the change in MSNA to the change in MAP, was significantly less in the hypertensives. Following the injection of nitroglycerin (2 micrograms/kg), there were no significant differences between the normotensives and hypertensives in the depressor response, the reflex increase in MSNA or the baroreflex slope for MSNA. These observations suggest that the baroreflex change in sympathetic nerve activity is reduced during phenylephrine-induced blood pressure elevation but not during nitroglycerin-induced hypotension in the hypertensives, and that the blunted response of sympathetic nerve activity occurring during hypertension in these hypertensive patients may underlie the maintenance of high blood pressure in essential hypertension.     

Comparative value of 24-hour ECG monitoring and standardized maneuvers in the detection and exploration of cardiac autonomic neuropathy in diabetics

24-hour continuous electrocardiographic ECG monitoring and standardized tests were performed to detect cardiac autonomic neuropathy in diabetic patients. Thirty-eight patients, with a mean duration of diabetes of 10 years, twenty-five IDDM and thirteen NIDDM, and thirty-two controls, with no illness or treatment which could alter the heart rate (HR), were studied. Five standardized tests were performed. Three tests investigated parasympathetic function: variations of HR during Valsalva manoeuvre, deep breathing and standing. The other two tests investigated sympathetic function: detection of orthostatic hypotension and blood pressure response to sustained handgrip. Parasympathetic HR control was impaired in twenty-nine patients, together with impaired sympathetic cardiovascular control in seven. According to the 6 indices studied, 24-hour ECG monitoring detected abnormalities in only eight patients. Mean minimum 24-hour HR and mean sleeping HR were elevated in the group of patients whose five standardized tests were normal and in the group of patients with impairment of both parasympathetic and sympathetic cardiovascular control, but not in the group of patients with only impaired parasympathetic HR control. This study suggests that 24-hour ECG monitoring is a less sensitive test of cardiac autonomic neuropathy than standardized tests. Moreover, it shows HR abnormalities that are not specific to cardiac autonomic neuropathy.     

Baroreflex control of heart rate is impaired in pre-eclampsia

Autonomic nervous dysfunction, such as parasympathetic and sympathetic impairment, has been suggested as possible cause of pre-eclampsia, but the studies are not conclusive. Our purpose was to assess non-invasively if pre-eclampsia is associated with a decreased baroreflex function. Nine women with pre-eclampsia (PE), eight normotensive pregnant women, and seven healthy normotensive non-pregnant women were studied. Continuous finger blood pressure was recorded by a Portapres device in the left lateral recumbent position and active standing. Baroreflex gain was evaluated by cross-spectral analysis of systolic blood pressure and pulse interval. The result was that baroreflex gain at rest was lower in pre-eclamptic women both compared to non-pregnant and healthy pregnant subjects (P<0.05). Moreover, a decrease of the baroreflex sensitivity was present in all pregnant women in the orthostatic position (P<0.05). In conclusion pregnancy per se is associated with a decrease in the baroreflex control of the heart, whereas in pre-eclampsia, the baroreflex sensitivity is impaired further.     

Baroreflex and chemoreflex function after bilateral carotid body tumor resection

OBJECTIVE: To investigate whether bilateral carotid body tumor resection invariably and chronically affects arterial baroreflex or peripheral chemoreflex function. METHODS: We studied eight consecutive patients (two men and six women; ages 48.1 +/- 11.8 years), a median time of 3.4 years (range 1.3-20.6 years) after bilateral carotid body tumor resection, and 12 healthy control individuals (eight men and four women; ages 53.7 +/- 10.1 years). Baroreflex sensitivity (phenylephrine), blood pressure and its variability (24 h Spacelabs and 5 h Portapres recordings), responses to standard cardiovascular reflex tests and the ventilatory responses to normocapnic and hypercapnic hypoxia were assessed. RESULTS: Baroreflex sensitivity was lower in patients (6.4 +/- 7.2 ms/mmHg) than in controls (14.7 +/- 6.6 ms/mmHg; P +/- 0.011). Mean office blood pressure and heart rate were normal in patients (123.3 +/- 11.9/79.0 +/- 7.3 mmHg and 67.5 +/- 9.4 beats/min, respectively) and controls (117.8 +/- 10.6/74.0 +/- 6.8 mmHg and 61.1 +/- 9.2 beats/min, respectively). Blood pressure variability was increased during ambulatory measurements. Three patients exhibited orthostatic hypotension. The Valsalva ratio, an index of baroreflex-mediated cardiovagal innervation, was lower in patients (1.4 +/- 0.2) than in controls (1.8 +/- 0.5; P +/- 0.008). The normocapnic ventilatory response to hypoxia was absent in all patients, whereas a small residual response to hypoxia was observed under hypercapnic conditions in two patients. CONCLUSIONS: Bilateral carotid body tumor resection results in heterogeneous expression of arterial baroreflex dysfunction, whereas the normocapnic hypoxic drive is invariably abolished as a result of peripheral chemoreflex failure.     

The orthostatic tachycardia syndrome: evaluation of autonomic function and treatment with octreotide and ergot alkaloids

Orthostatic tachycardia is a poorly understood syndrome in which patients develop dizziness, diaphoresis, or palpitations upon shifting from the supine to the upright posture. The present study was performed to determine whether autonomic neuropathy might be present in these patients, and whether the abnormal hemodynamic response to standing might be the result of failure of reflex vasoconstriction. We measured autonomic function in 9 patients with idiopathic orthostatic tachycardia and 2 patients with orthostatic tachycardia and insulin-dependent diabetes mellitus and compared them to 33 age-matched controls. Although most patients with orthostatic tachycardia had normal vasomotor reflexes and normal surface potential amplitudes, the latency of the autonomic response, a measure of sympathetic nerve conduction velocity, was prolonged in the soles (2.44 +/- 0.08 s in patients with idiopathic orthostatic tachycardia vs. 2.12 +/- 0.04 s in controls; P less than 0.005). In 6 of 9 patients, however, the latencies were within the normal range. Autonomic surface potentials were absent in 1 diabetic patient with orthostatic tachycardia; the latency of the response in the feet was greatly prolonged (2.95 s) in the second patient. We also assessed the response of orthostatic tachycardia patients to octreotide and dihydroergotamine, which are known to have a pressor effect in patients with recognized forms of autonomic neuropathy. These agents, in combination, suppressed orthostatic tachycardia (from 116 +/- 7 to 89 +/- 6 beats/min; P less than 0.001) in patients with this syndrome. In summary, our data indicate that evidence of autonomic dysfunction is present in only a minority of patients with orthostatic tachycardia. Nevertheless, administration of the vasoconstrictor drugs dihydroergotamine and octreotide can prevent the abnormal hemodynamic response to the upright posture shown by patients with this syndrome.     

Autonomic nerve antibodies and autonomic nerve function in type 1 and type 2 diabetic patients

Complement-fixing adrenal medulla (CF-ADM), sympathetic ganglion (CF-SG), and vagal (CF-V) nerve antibodies were determined in diabetic patients. Among 74 patients with Type 1 diabetes, CF-ADM was detected in 7 (10%) cases, CF-SG in 14 (19%) cases, and CF-V in 8 (11%) cases. Among 38 patients with Type 2 diabetes, CF-ADM was detected in 5 (13%) cases, CF-SG in 4 (11%) cases, and CF-V in 6 (16%) cases. There were associations between autonomic nerve antibodies and autonomic nerve function. CF-ADM and/or CF-SG were significantly (P less than 0.002) less prevalent in Type 1 diabetic patients with autonomic neuropathy than in those without [5/44 (11%) vs. 14/30 (47%)] and, in agreement with this, the brake index, a sign of parasympathetic and sympathetic autonomic nerve function, was significantly (P less than 0.005) higher (more normal) in these patients (-0.56 +/- 0.13 vs. -1.04 +/- 0.12). In Type 2 diabetic patients, the E/I ratio, an index of parasympathetic nerve function, was significantly (P less than 0.03) lower (more abnormal) in those with CF-V than in those without (-1.81 +/- 0.17 vs. -1.20 +/- 0.11). In conclusion, the frequency of sympathetic nerve antibodies was decreased in Type 1 diabetic patients with autonomic neuropathy, while in Type 2 diabetic patients parasympathetic nerve antibodies were related to severe parasympathetic neuropathy.     

Regulation of QT indices mediated by autonomic nervous function in patients with type 2 diabetes

Both the QT interval and QT dispersion in diabetic patients have been reported to increase with the progression of cardiac autonomic neuropathy and to have a prognostic value. We assessed the cardiac autonomic influences on QT indices using the measurements of baroreflex sensitivity, heart rate variability, and cardiac (123)I-metaiodobenzylguanidine scintigraphic findings in patients with type 2 diabetes mellitus. Forty-two consecutive patients with type 2 diabetes (mean+/-SD: 54+/-10 years, 22 women and 20 men) were studied. Baroreflex sensitivity negatively correlated with the maximum and minimum QTc intervals as well as QT/QTc dispersion. However, the high-frequency power and the ratio of low-frequency power to high-frequency power of heart rate variability did not correlate with any QT indices. The percent washout rate of (123)I-metaiodobenzylguanidine positively correlated with QT/QTc dispersion, but not with maximum and minimum QTc intervals. Our findings suggest that cardiac vagal dysfunction is related to QT interval prolongation while both sympathetic and vagal dysfunctions are related to increased QT dispersion in type 2 diabetic patients. Baroreflex sensitivity and percent washout rate of (123)I-metaiodobenzylguanidine may be useful parameters indicating the abnormalities of the cardiac ventricular repolarization in this population.     

Exercise training restores baroreflex sensitivity in never-treated hypertensive patients

The effects of exercise training on baroreflex control of sympathetic nerve activity in human hypertension are unknown. We hypothesized that exercise training would improve baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in patients with hypertension and that exercise training would reduce MSNA and blood pressure (BP) in hypertensive patients. Twenty never-treated hypertensive patients were randomly divided into 2 groups: exercise-trained (n=11; age: 46+/-2 years) and untrained (n=9; age: 42+/-2 years) patients. An age-matched normotensive exercise-trained group (n=12; age: 42+/-2 years) was also studied. Baroreflex control of MSNA (microneurography) and HR (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium nitroprusside and analyzed by linear regression. BP was monitored on a beat-to-beat basis. Exercise training consisted of three 60-minute exercise sessions per week for 4 months. Under baseline conditions (before training), BP and MSNA were similar between hypertensive groups but significantly increased when compared with the normotensive group. Baroreflex control of MSNA and HR was similar between hypertensive groups but significantly decreased when compared with the normotensive group. In hypertensive patients, exercise training significantly reduced BP (P<0.01) and MSNA (P<0.01) levels and significantly increased baroreflex control of MSNA and HR during increases (P<0.01 and P<0.03, respectively) and decreases (P<0.01 and P<0.03, respectively) in BP. The baseline (preintervention) difference in baroreflex sensitivity between hypertensive patients and normotensive individuals was no longer observed after exercise training. No significant changes were found in untrained hypertensive patients. In conclusion, exercise training restores the baroreflex control of MSNA and HR in hypertensive patients. In addition, exercise training normalizes MSNA and decreases BP levels in these patients.     

Relationship between glycemic control and orthostatic hypotension in type 2 diabetes mellitus--a survey by the Fukuoka Diabetes Clinic Group

We examined the prevalence of orthostatic hypotension and its association with glycemic control, as assessed by hemoglobin A1 (HbA1) concentration, in type 2 diabetic patients. The prevalence of orthostatic hypotension in 886 diabetics who were referred to our study and in 587 diabetics who were not given any antihypertensive drugs was 7% and 6%, respectively. The relationship between orthostatic hypotension and HbA1 levels was evaluated only in subjects not receiving antihypertensive drugs, since antihypertensive agents might induce orthostatic hypotension. HbA1 levels were 11.0 +/- 2.1% in the diabetic patients with orthostatic hypotension, which was significantly higher than the HbA1 levels of 9.9 +/- 2.2% in the diabetic patients without orthostatic hypotension. Multivariate analysis also revealed that the association remained significant after adjustment for the treatment and duration of diabetes, age, sex and body mass index. These findings suggest that glycemic control contributes to the development of orthostatic hypotension in type 2 diabetic patients.     

Baroreflex control of muscle sympathetic nerve activity after carotid body tumor resection

Bilateral carotid body tumor resection causes a permanent attenuation of vagal baroreflex sensitivity. We retrospectively examined the effects of bilateral carotid body tumor resection on the baroreflex control of sympathetic nerve traffic. Muscle sympathetic nerve activity was recorded in 5 patients after bilateral carotid body tumor resection (1 man and 4 women, 51+/-11 years) and 6 healthy control subjects (2 men and 4 women, 50+/-7 years). Baroreflex sensitivity was calculated from changes in R-R interval and muscle sympathetic nerve activity in response to bolus injections of phenylephrine and nitroprusside. In addition, sympathetic responses to the Valsalva maneuver and cold pressor test were measured. The integrated neurogram of patients and control subjects contained a similar pattern of pulse synchronous burst of nerve activity. Baroreflex control of both heart rate and sympathetic nerve activity were attenuated in patients as compared with control subjects [heart rate baroreflex sensitivity: 3.68+/-0.93 versus 11.61+/-4.72 ms/mm Hg (phenylephrine, P=0.011) and 2.53+/-1.36 versus 5.82+/-1.94 ms/mm Hg (nitroprusside, P=0.05); sympathetic baroreflex sensitivity: 3.70+/-2.90 versus 7.53+/-4.12 activity/100 beats/mm Hg (phenylephrine, P=0.10) and 3.93+/-4.43 versus 15.27+/-10.03 activity/100 beats/mm Hg (nitroprusside, P=0.028)]. The Valsalva maneuver elicited normal reflex changes in muscle sympathetic nerve activity, whereas heart rate responses were blunted in the patients with bilateral carotid body tumor resection. Maximal sympathetic responses to the cold pressor test did not differ between the two groups. Denervation of carotid sinus baroreceptors as the result of bilateral carotid body tumor resection produces chronic impairment of baroreflex control of both heart rate and sympathetic nerve activity. During the Valsalva maneuver, loss of carotid baroreflex control of heart rate is less well compensated for by the extra carotid baroreceptors than the control of muscle sympathetic nerve activity.