Quantitative Evaluation of Cardiac Parasympathetic Activity in Normal and Diabetic Man

Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inversely related to the RR variation (r = 0.89, P < 0.01). Heart rate was increased (P < 0.0001) and RR variation decreased (P < 0.05) during β-adrenergic stimulation with isoproterenol and during parasympathetic blockade with atropine (both P < 0.0001). Hence, the cardiac effects of β-adrenergic stimulation may mimic the effects of diminished parasympathetic function. To evaluate parasympathetic control of RR variation, independently of possible effects of increased sympathetic activities, studies were performed during β-adrenergic blockade with propranolol. RR variation during propranolol was less both in 14 diabetic subjects without clinical symptoms of autonomic neuropathy (P < 0.005) and in 8 diabetics with clinical symptoms of autonomic neuropathy (P < 0.001) when compared with 22 age-comparable normal subjects. The measurement of RR variation was very reproducible with a day-to-day coefficient of variation of 9.7 ± 2.8﹪ (x̄ ± SEM) in diabetic subjects with stable hyperglycemia. It is concluded that supine RR variation during a deep respiratory rate and during β-adrenergic blockade is a sensitive, quantitative, and reproducible method to evaluate parasympathetic nervous activity in normal and diabetic subjects. Furthermore, cardiac parasympathetic activity may be diminished in diabetic subjects before clinical symptoms of autonomic neuropathy are evident.

[1]  E. Hines The significance of vascular hyperreaction as measured by the cold-pressor test , 1940 .

[2]  A. Levin,et al.  A simple test of cardiac function based upon the heart rate changes induced by the Valsalva maneuver. , 1966, The American journal of cardiology.

[3]  P. Nathanielsz,et al.  Abnormal Response to Valsalva Maneuver in Diabetics: Relation to Autonomic Neuropathy , 1967, Diabetes.

[4]  D. Heistad,et al.  Vasoconstrictor response to simulated diving in man. , 1968, Journal of applied physiology.

[5]  Role of the face in the cardiovascular responses to total immersion. , 1970, The Australian journal of experimental biology and medical science.

[6]  N. Shumway,et al.  Hemodynamic performance of the transplanted human heart. , 1971, Surgery.

[7]  P. Watkins,et al.  Cardiac Denervation in Diabetes , 1973, British medical journal.

[8]  S. Taylor,et al.  Different Effects of Adrenergic Beta-receptor Blockade on Heart Rate Response to Mental Stress, Catecholamines, and Exercise , 1973, British medical journal.

[9]  D. Ewing,et al.  Cardiovascular responses to sustained handgrip in normal subjects and in patients with diabetes mellitus: a test of autonomic function. , 1974, Clinical science and molecular medicine.

[10]  P. Watkins,et al.  Defective innervation of heart in diabetic autonomic neuropathy. , 1975, British medical journal.

[11]  P. Low,et al.  The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study. , 1975, Brain : a journal of neurology.

[12]  D. Ewing,et al.  MORTALITY IN DIABETIC AUTONOMIC NEUROPATHY , 1976, The Lancet.

[13]  P. Watkins,et al.  Total Cardiac Denervation in Diabetic Autonomic Neuropathy , 1976, Diabetes.

[14]  D. Eckberg,et al.  Respiratory and baroreceptor reflex interactions in man. , 1977, The Journal of clinical investigation.

[15]  E. Faccio,et al.  Autonomic Neuropathy and Painless Myocardial Infarction in Diabetic Patients: Histologic Evidence of Their Relationship , 1977, Diabetes.

[16]  D. Ewing,et al.  Heart rate response to Valsalva manoeuvre. Reproducibility in normals, and relation to variation in resting heart rate in diabetics. , 1977, British heart journal.

[17]  J. Hampton,et al.  Assessment of vagal control of the heart in diabetes. Measures of R-R interval variation under different conditions. , 1977, British heart journal.

[18]  P. Cryer,et al.  Plasma catecholamines in diabetes. The syndromes of hypoadrenergic and hyperadrenergic postural hypotension. , 1978, The American journal of medicine.

[19]  J R Hampton,et al.  Assessment of Methods for Estimating Autonomic Nervous Control of the Heart in Patients with Diabetes Mellitus , 1978, Diabetes.

[20]  J. Halter,et al.  Glycosylated Hemoglobin in Normal Subjects and Subjects with Maturity-onset Diabetes Evidence for a Saturable System in Man , 1978, Diabetes.

[21]  Autonomic function tests in diabetes mellitus. , 1978, Diabete & metabolisme.

[22]  D. Ewing,et al.  Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes. , 1978, British medical journal.

[23]  D. Ewing Cardiovascular reflexes and autonomic neuropathy. , 1978, Clinical science and molecular medicine.

[24]  D. Janowsky,et al.  Effects of smoking marihuana on left ventricular performance and plasma norepinephrine: studies in normal men. , 1978, Annals of internal medicine.

[25]  P. Watkins,et al.  CARDIORESPIRATORY ARREST AND DIABETIC AUTONOMIC NEUROPATHY , 1978, The Lancet.

[26]  J. Oates,et al.  Comparative Assessment of Stimuli That Release Neuronal and Adrenomedullary Catecholamines in Man , 1979, Circulation.

[27]  D. Ewing,et al.  Non-invasive assessment of left ventricular response to Valsalva manoeuvre in normal and diabetic subjects using praecordial accelerocardiography. , 1979, British heart journal.

[28]  N. Christensen,et al.  Impaired Cardiovascular Responses to Graded Exercise in Diabetic Autonomic Neuropathy , 1979, Diabetes.

[29]  K Koizumi,et al.  Reciprocal and non-reciprocal action of the vagal and sympathetic nerves innervating the heart. , 1979, Journal of the autonomic nervous system.

[30]  J. Halter,et al.  Comparison of a Colorimetric Assay for Glycosylated Hemoglobin with Ion-exchange Chromatography , 1979, Diabetes.

[31]  P. Watkins,et al.  Cardiac denervation in diabetic neuropathy. , 1980, Annals of internal medicine.

[32]  D. Ewing,et al.  Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. , 1980, Annals of internal medicine.

[33]  N. Christensen,et al.  Impaired Responses of Catecholamines, Growth Hormone, and Cortisol to Graded Exercise in Diabetic Autonomic Neuropathy , 1980, Diabetes.

[34]  P. Dyck,et al.  Human diabetic endoneurial sorbitol, fructose, and myo‐inositol related to sural nerve morphometry , 1980, Annals of neurology.