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Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography.

OBJECTIVES: The purpose of this investigation was to evaluate the sympathetic nervous system of the heart by positron emission tomographic (PET) imaging in patients with diabetes mellitus with and without diabetic autonomic neuropathy. BACKGROUND: The clinical assessment of cardiac involvement in diabetic autonomic neuropathy has been limited to cardiovascular reflex testing. With the recent introduction of radiolabeled catecholamines such as carbon (C)-11 hydroxyephedrine, the sympathetic innervation of the heart can be specifically visualized with PET imaging. METHODS: Positron emission tomographic imaging was performed with C-11 hydroxyephedrine and rest myocardial blood flow imaging with nitrogen-13 ammonia. Three patient groups were studied, including healthy volunteers as control subjects, diabetic patients with normal autonomic function testing and diabetic patients with varying severity of autonomic neuropathy. Homogeneity of cardiac tracer retention as well as absolute tracer retention was determined by relating myocardial tracer retention to an arterial C-11 activity input function. RESULTS: Abnormal regional C-11 hydroxyephedrine retention was seen in seven of eight patients with autonomic neuropathy. Relative tracer retention was significantly reduced in apical, inferior and lateral segments. The extent of the abnormality correlated with the severity of conventional markers of autonomic dysfunction. Absolute myocardial tracer retention index measurements showed a 45 +/- 21% decrease in distal compared with proximal myocardial segments in autonomic neuropathy (0.069 +/- 0.037 min-1 vs. 0.13 +/- 0.052 min-1, p = 0.02). CONCLUSIONS: This study demonstrates a heterogeneous pattern of neuronal abnormalities in patients with diabetic cardiac neuropathy. The extent of this abnormality correlated with the severity of neuropathy assessed by conventional tests. Future studies in larger groups of patients are required to define the relative sensitivity of this imaging approach in detecting cardiac neuropathy and to determine the clinical significance of these scintigraphic findings in comparison with conventional markers of autonomic innervation.

Adult↗

How does cardiac resynchronization therapy improve exercise capacity in chronic heart failure?

BACKGROUND: Studies have shown that neither ejection fraction nor hemodynamic abnormalities during exercise in chronic heart failure (HF) correlate with symptoms of fatigue and exhaustion. The concept that exercise limitation in patients with chronic HF is due to abnormal hemodynamics during exercise has been revised to acknowledge that the skeletal myopathy of chronic HF contributes significantly to exercise dysfunction in heart failure. Why then does cardiac resynchronization therapy (CRT), a therapy that improves abnormalities of cardiac function, such as cardiac output and ejection fraction, produce a consistent, measurable, irrefutable increase in exercise capacity? METHODS AND RESULTS: In this review I will (1) review the mechanisms of exercise dysfunction in chronic HF, with special attention to the concept of "coordinated adaptation"; (2) analyze the effects of CRT on autonomic dysfunction in HF; and (3) propose a unifying hypothesis to understand how a therapy that improves cardiac function can improve exercise dysfunction attributable to a skeletal myopathy. Specifically, I will review evidence that CRT improves exercise capacity by attenuating the chronic sympathetic activation of HF. CONCLUSION: The decrease in sympathetic activation, and perhaps inflammation, during CRT likely reverses many features of the skeletal myopathy, leading to improved exercise capacity.

Cardiac Pacing, Artificial↗

Analysis of heart rate variability in children with primary nocturnal enuresis.

Although nocturnal enuresis is probably the most common developmental disorder in children, the pathogenesis and management remain unclear. Autonomic dysfunction is one of the proposed mechanisms for nocturnal enuresis in children. The objective of current study was to evaluate autonomic nervous system functions in enuretic children. Twenty-four-hour ambulatory electrocardiographic recordings were obtained, and the time domain variables of HRV were calculated. The results of the present study suggest that sympathetic nervous system hyperactivity is present in enuretic children. This may explain why some enuretic children do not respond to anticholinergic medications. If these conflicting results are confirmed by large-scale clinical studies, Holter ECG examinations may be used for rational approaches in treatment of nocturnal enuresis.

Child↗

Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure.

INTRODUCTION: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF-alpha levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.

Aged↗

Impairment of cardiac autonomic function in patients with Duchenne muscular dystrophy: relationship to myocardial and respiratory function.

BACKGROUND: Previous studies reported an impairment of nervous autonomic activity in patients with Duchenne muscular dystrophy (DMD). However, the relationship of the autonomic dysfunction to the impairment of cardiac mechanical function and of respiratory failure is not completely understood. METHODS: We evaluated cardiac autonomic function by time- and frequency-domain heart rate variability (HRV) analysis on 24-hour Holter recordings in 60 patients with DMD (16.8 +/- 4.8 years) and 28 healthy control patients (15.2 +/- 4.6 years, P = not significant). The circadian rhythm of R-R interval, low frequency, high frequency, and low-frequency/high-frequency ratio was also assessed. In all patients, left ventricular ejection fraction was measured by 2D echocardiography; respiratory function was assessed by spirometry. RESULTS: All HRV parameters were lower in patients with DMD than in control subjects, with the percentage of differences between adjacent R-R intervals >50 ms (11.6% +/- 8.5% vs 27.3% +/- 14.1%, P =.00001) and high frequency (23.9 +/- 10.3 ms vs 36.1 +/- 12.2 ms, P =.0001) showing the strongest differences. A significant circadian rhythm of HRV variables was present in both groups, but it was considerably flattened in patients with DMD. There was no correlation between left ventricular ejection fraction and HRV indexes except for a weak correlation with high frequency (r = 0.30, P =.02) and with low-frequency to high-frequency ratio (r = -0.29, P <.03). Similarly modest correlations were found between forced vital capacity and high frequency (r = 0.4, P =.007) and low-frequency/high-frequency ratio (r = -0.32, P =.026). Multiple regression analysis did not show any independent predictive variable for the autonomic impairment. CONCLUSIONS: Our data show a marked impairment of cardiac autonomic function in patients with DMD, which appears to mainly involve the parasympathetic branch and appears to have a multifactorial origin.

Adolescent↗

The neuropathology of septic shock.

The neuropathological correlates of encephalopathy and autonomic dysfunction in septic shock are unclear. We performed post mortem analysis of 5 brain areas susceptible to ischemia and 5 autonomic nuclei (AN) in 23 patients who had died in our intensive care unit (ICU) from septic shock and 8 dying from non-septic shock as well as 5 controls who had died suddenly from extracranial injury. Proinflammatory cytokine (IL1-beta and TNF-alpha) and inducible nitric oxide synthase (iNOS) expression was assessed by immunocytochemistry. Abnormalities in septic shock were: hemorrhages (26%), hypercoagulability syndrome (9%), micro-abscesses (9%), multifocal necrotizing leukoencephalopathy (9%) and ischemia (100%). The incidence of cerebral hemorrhage or hypercoagulability syndrome was not related to clotting disturbances. The intensity of ischemia within susceptible areas was the same in both ICU groups, but more pronounced in the autonomic centers of septic patients (P < 0.0001). Neuronal apoptosis assessed using anti-caspase 3 immunocytochemistry and in situ end labeling was more pronounced in the autonomic nuclei of septic patients. (P < 0.0001). TNF-alpha expression did not differ between groups but vascular iNOS expression assessed by immunocytochemistry was higher in sepsis (P<0.0001) and correlated with autonomic center neuronal apoptosis (P < 0.02). We conclude that septic shock is associated with diffuse cerebral damage and specific autonomic neuronal apoptosis which may be due to circulating factors particularly iNOS.

Adult↗

Improvement of sleep hypopnea by antiparkinsonian drugs in a patient with Parkinson's disease: a polysomnographic study.

An 80-year-old man was admitted to our hospital because of bradykinesia, muscle rigidity and respiratory dysfunction during sleep. Concerning bradykinesia and muscle rigidity, we diagnosed him as the early/moderate stage of Parkinson's disease without autonomic dysfunction. Polysomnography (PSG) showed a series of obstructive hypopneas and apneas. After administration of antiparkinsonian drugs, rigidity of the neck and trunk was diminished along with a drastic decrease in hypopnea on PSG. We consider that sleep hypopnea in this patient is caused by involvement of the striated musculature surrounding the upper-airway and/or rigidity in the trunk. These conditions are treatable with antiparkinsonian drugs.

Aged↗

Dopamine and dobutamine have different effects on heart rate variability in patients with congestive heart failure.

BACKGROUND: Autonomic dysfunction plays an important role in the pathogenesis, treatment and prognosis of congestive heart failure (CHF). Sympathomimetic amines have been widely used in the treatment of CHF, but reports on their autonomic effects in CHF are rare. This study was designed to evaluate the effects of dopamine and dobutamine on cardiac autonomic function as assessed by heart rate variability (HRV). METHODS: Twenty patients with symptomatic CHF (systolic dysfunction) were enrolled. After recording one-hour baseline electrocardiographs (ECGs), patients were randomly selected for either dopamine (4 micrograms/kg/minute, Group A) or dobutamine (4 micrograms/kg/minute, Group B) treatment for three days. On the third day, a 24-hour ambulatory ECG was recorded and a tilt-table test was performed. Only furosemide and nitrates were allowed for adjunctive therapy. HRV was measured before and after treatment in both time and frequency domains. Frequency-domain HRV was also measured during head-up tilt. RESULTS: After treatment, all patients improved [New York Heart Association fraction (NYHA Fc) 3.7 to 2.0]. Group A patients had higher post-treatment 24-hour HRV than those in Group B. SDNN (standard deviation of the average normal RR intervals in the entire ECG recording), SDANN (standard deviation of the average normal RR intervals for all five minute segments of an entire ECG recording) and SDNN indices in Group A were significantly higher than in Group B (90 +/- 33 ms vs 41 +/- 12 ms, 78 +/- 32 ms vs 36 +/- 11 ms, and 37 +/- 19 ms vs 16 +/- 7 ms, respectively, all p < 0.05). rMSSD (the square root of the mean of the squared differences between adjacent normal RR intervals over the entire ECG recording) and pNN50 (percentage of differences between adjacent normal RR intervals that are greater than 50 ms computed over the entire ECG recording) were also higher in Group A patients, with borderline significance. All measurements of total frequency and low-frequency and high-frequency components tended to be higher in Group A than Group B, but this was only significant for total frequency amplitude (22.9 +/- 13.4 ms vs 10.9 +/- 6.1 ms, p < 0.05). Dopamine but not dobutamine treatment seems to restore the depressed circadian change in frequency-domain HRV classically seen in patients with CHF. The HRV change during head-up tilting did not differ between the two groups. Three patients in Group B showed non-sustained ventricular tachycardia on ambulatory ECG during the treatment period. CONCLUSIONS: Dopamine and dobutamine have comparable therapeutic effects in patients with CHF, but low-dose dopamine more favorably affects cardiac autonomic function.

Aged↗

Altered ventricular repolarization in central sympathetic dysfunction associated with spinal cord injury.

Complete injury to the cervical spinal cord results in total disruption of central sympathetic outflow. Although ventricular repolarization can be significantly influenced by disorders of autonomic function, the effects of cervical sympathectomy are unknown. Therefore, 40 subjects with complete chronic spinal cord injury were prospectively divided into 2 groups, half with total disruption of central sympathetic outflow (level of injury C5 to C8) known as the high level injury group, and half with nearly intact sympathetic innervation (T10 to L1) serving as controls. The completeness of autonomic dysfunction was verified by the cold pressor response. ST-segment analysis of the resting surface electrocardiogram revealed multilead ST elevation in the high level injury group, with maximum ST height significantly higher than the control group (131 +/- 21 [standard error] vs 47 +/- 8 microV; p = 0.0005). Unlike the control subjects, maximal arm ergometry exercise in the high level injury subjects failed to decrease ST-segment height (delta ST = -3 +/- 6 vs -43 +/- 14 microV in controls; p = 0.02). This difference persisted even after matching for exercise capacity. However, during exogenous stimulation with the sympathomimetic amine isoproterenol, ST-segment height in the high level injury group markedly decreased (mean delta ST = -84 +/- 26 vs -17 +/- 18 microV in controls; p = 0.04). Thus, central sympathetic dysfunction regularly results in multilead ST-segment elevation that decreases to or below isoelectric baseline during low dose isoproterenol infusion. Unlike normal subjects and individuals with normal variant ST-segment elevation, ST height is not altered by exercise. These findings document that ST-segment height in man is greatly influenced by central sympathetic nervous activity both at baseline and during physiologic and pharmacologic stress.

Autonomic Nervous System Diseases↗

Dopamine-beta-hydroxylase in patients with cystic fibrosis.

The enzymatic activity of plasma dopamine-beta-hydroxylase (DBH) was determined in 92 children/adolescents with cystic fibrosis, in 25 parents (heterozygotes) of these patients and in 68 healthy controls. Statistically significant (P less than 0.01) lower DBH levels were found in cystic fibrosis patients (17.9 +/- 1.4 mumol/min per 1, SEM) compared to the controls (25.5 +/- 2.1 mumol/min per 1). In 37 patients plasma norepinephrine and dopamine levels were compared to the enzymatic activity, no significant correlation between these variables being shown (r = -0.134 for norepinephrine; r = 0.159 for dopamine). However, due to the large variability of DBH within the groups and due to the lack of relationship of this enzymatic activity to plasma catecholamines, it is concluded that these differences may neither account for the observed elevation of plasma dopamine in cystic fibrosis patients (0.94-6.73 nmol/l vs. 0.01-0.986 nmol/l for controls) nor for their putative autonomic dysfunction.

Adolescent↗

Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy.

Dysfunction of the autonomic nervous system is a recognized complication of diabetes. Neuroaxonal dystrophy (NAD), a distinctive axonopathy involving distal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in human and several insulinopenic experimental rodent models. Recent studies have suggested that loss of the neurotrophic effects of insulin and/or IGF-I on sympathetic neurons and not hyperglycemia per se, may underlie the development of sympathetic NAD. The streptozotocin (STZ)-diabetic and BB/W rat, the most commonly used experimental rodent models, develop marked hyperglycemia and concomitant deficiency in both circulating insulin and IGF-I. These animals reproducibly develop NAD in nerve terminals in the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. The Zucker Diabetic Fatty (ZDF) rat, an animal model of type 2 diabetes, also develops severe hyperglycemia comparable to that in the STZ- and BB/W-diabetic rat models, although in the presence of hyperinsulinemia. In our study, ZDF rats maintained for 6 to 7 months in a severely diabetic state, as assessed by plasma glucose and glycated hemoglobin levels, maintained significant hyperinsulinemia and normal levels of plasma IGF-I at sacrifice. NAD did not develop in diabetic ZDF rat sympathetic ganglia and ileal mesenteric nerves as assessed by quantitative ultrastructural techniques, which is in dramatic contrast to neuropathologic findings in comparably hyperglycemic 6-month STZ-diabetic insulinopenic rats. These data combined with our previous results argue very strongly that hyperglycemia is not the critical and sufficient element in the pathogenesis of diabetes-induced NAD, rather that it is the loss of trophic support, most likely of IGF-I or insulin, that causes NAD.

Adrenergic Fibers↗

Cardiac autonomic dysregulation in patients with acute hepatitis.

BACKGROUND: Autonomic dysfunction is common in patients with chronic liver disease, but it is still unclear whether acute hepatitis coincides with alterations in autonomic functions. METHODS: We evaluated the heart rate variability (HRV) of 10 patients with acute hepatitis (6 males, 4 females; mean age, 44.0 y; range, 20-69 y). Frequency-domain analysis of short-term and stationary R-R intervals was performed on the first day of admission to detect low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF in normalized units (LF%). The same measurement was repeated on the 7th day of admission. RESULTS: We found that there was a significant increase of HF as well as variance of the R-R interval on the 7th day after admission (P < 0.05). There was a significant negative correlation between HF and the change of total bilirubin (P < 0.05). CONCLUSIONS: The study demonstrates a change in cardiac vagal tone associated with acute hepatitis by analysis of HRV, and such alteration is less pronounced later during the clinical course of acute hepatitis.

Acute Disease↗

Carotid artery elasticity and baroreflex sensitivity in patients with glaucoma.

PURPOSE: To investigate non-invasively the elasticity of common carotid artery and the arterial baroreflex function in patients with chronic open-angle glaucoma. PATIENTS AND METHODS: Data were obtained from patients with chronic open-angle glaucoma (n = 16) [primary open angle- and juvenile open-angle glaucoma] and from age- and sex-matched healthy control subjects (n = 18). End diastolic diameter and pulsatile distension of the common carotid artery were measured with a high-precision, automated ultrasound wall-tracking system (WTS). Spontaneous fluctuation in cardiac interval and systolic pressure were used to determine baroreflex sensitivity. RESULTS: There was no difference in heart rate and pulse pressure between patients with glaucoma and the control subjects. In the glaucoma patients both distensibility coefficient of common carotid artery and baroreflex sensitivity were reduced (two-way factorial ANOVA; P < 0.002). Stiffness (characterizing the rigidity of vessel wall) was higher in the glaucoma patients than in the controls (P = 0.002). CONCLUSIONS: Our results suggest that in patients with chronic open-angle glaucoma the arterial rigidity is significantly increased and therefore the baroreflex function is significantly decreased. These findings may have relevance in the understanding of the autonomic dysfunction and vascular dysregulation in glaucoma.

Adult↗

Parainfectious myelitis: three distinct clinico-imagiological patterns with prognostic implications.

Seventeen parainfectious myelitis patients were studied for site, extent and severity of lesions. Three patterns were observed each having distinct clinical, electrophysiological and MRI features: 1) focal segmental myelitis--focal cord lesion with long tract signs and good prognosis; 2) ascending myelitis--continuous lesion from conus to mid-cord with upper and lower motor neuron signs (not necessarily spinal shock), dysautonomia and poor outcome; 3) disseminated myelitis--discrete lesions scattered throughout the cord with subtle signs in spinal segmental distribution, above and below the transverse level and moderate outcome. Severe autonomic dysfunction, denervation of paraspinal muscles, "dense" lesion on imaging and often (but not always) the absent somatosensory evoked potentials carried poor outcome. In conclusion "parainfectious myelitis" is a better term to describe transverse myelitis, as the lesion extends to a large vertical extent. Further classification into 3 subgroups may improve understanding of anatomical and physiological dysfunction and prediction of outcome.

Adolescent↗

A case report of postulated 'Barré Liéou syndrome'.

The case history presented is of a 32 year old woman suffering with severe occipital and bilateral temporal pain together with autonomic disturbances affecting her vision, balance and breathing, symptoms which have been postulated as 'Barré Liéou syndrome'. She complained of pain referred to the left arm and associated circulatory and sensory disturbance in keeping with the diagnosis of complex regional pain syndrome type I. Traditional Chinese and Western trigger point acupuncture techniques were used in order to treat her pain and autonomic dysfunction. Acupuncture was successful in reducing, but not totally alleviating, her pain, and was particularly effective in reducing the majority of autonomic symptoms.

Acupuncture Points↗

Autonomic nervous system reactivity in irritable bowel syndrome.

BACKGROUND: Autonomic dysfunction has been implicated as one of the factors involved in the pathogenesis of irritable bowel syndrome (IBS). AIM: To evaluate autonomic function in patients with IBS. METHODS: Thirty-five patients with IBS and thirty healthy controls were evaluated by standard cardiovascular reflex tests. Parasympathetic function was assessed by measuring heart rate responses to deep and slow breathing (E:I ratio), Valsalva maneuver (Valsalva ratio) and head-up tilt tests (30:15 ratio). Sympathetic adrenergic function was assessed by measuring diastolic blood pressure responses to handgrip test at 4 min and cold pressor test at 1 min and also by change in systolic blood pressure in response to head-up tilt. Autonomic functions were tested twice, keeping at least a one-week interval, to find out stability over time. Anxiety status of the subjects was assessed by evaluating responses to a questionnaire. RESULTS: Parasympathetic reactivity was significantly increased in IBS patients as compared to controls during visit 1 (E:I 1.7 [SD 0.2] vs 1.4 [0.1], p < 0.001; Valsalva ratio 2.0 [0.3] vs 1.5 [0.1], p < 0.001; 30:15 ratio 1.2 [0.1] vs 1.1 [0.01], p < 0.001). Similar results were obtained in visit 2. The diastolic blood pressure responses during handgrip and cold pressor tests were not different in comparison to controls during both the visits. However, tilting resulted in less marked rise in diastolic blood pressure (9.1 [4.1] vs 12.1 [6.8] mmHg, p < 0.01) at 0.5 min and less rise in heart rate (6.0 [2.5] vs 10.3 [6.3] per min, p < 0.01) at 1 min in IBS patients during visit 1. The anxiety score of IBS patients was significantly higher (46.2 [3.2] vs 21.6 [1.7], p < 0.001). CONCLUSION: IBS patients have increased parasympathetic reactivity and a high level of anxiety trait.

Adult↗

Sympathetic skin response in scleroderma.

Examination of the sympathetic skin response (SSR) was performed in 32 patients with systemic sclerosis, morphea and mixed connective tissue disease displaying scleroderma-like features. The control group consisted of 26 healthy subjects and 12 patients with other skin diseases and asymmetrical cutaneous changes. Right and left median and tibial nerves were stimulated successively and the responses were recorded from the palms and soles simultaneously. SSR abnormalities (delayed latency, decrease and/or asymmetry of amplitude, absent response) were observed in 68.8% of the patients, most frequently in linear scleroderma. An amplitude asymmetry of the responses from upper extremities was the most characteristic pattern of abnormalities. There was no correlation between the SSR and the localization, degree and character (inclurated oedema, atrophy, sclerosis) of skin changes, the duration of the disease, symptoms of the disorder of the autonomic nervous system symptoms (vasomotor and/or sudomotor) and the changes in capillaroscopy. All patients with slow motor conduction and sensor conduction velocities (MCV and SCV) had lower SSR amplitude and the patients with prolonged skin sensory chronaxy had more often delayed latency. The results revealed presence of disturbances of the autonomic nervous system in all varieties of scleroderma, both systemic and localized forms, even without any other signs of autonomic dysfunction.

Adolescent↗

The heart in diabetes.

Since the introduction of insulin, heart disease has become a major impediment to survival in persons with diabetes mellitus. Coronary disease has increased severity and accelerated development in diabetic persons compared with an age- and sex-matched nondiabetic population. A peculiar vulnerability of women to the influence of diabetes with loss of premenopausal coronary disease protection has been found. The symptomatology of coronary events may differ and coronary care data show a higher incidence of sudden death in diabetic patients who have a myocardial infarction than in their non-diabetic counterparts. Insulin may play a role in the myocardial adjustment to an ischemic insult by enhancing glucose intake and suppressing lipolysis and ketogenesis. Carbohydrate intolerance in dogs, rhesus monkeys and humans appears associated with similar histologic and compositional changes in the myocardium. Abnormalities in diastolic ventricular function not attributable to large- or small-vessel coronary disease have been found in the diabetic subjects of each species. Studies in humans who have diabetes have assessed single pressure-volume relationships and more exacting measures of ventricular compliance are needed. Abnormalities of myocardial function in patients with diabetes have been found using echo and radionuclide techniques. Many of these findings need to be correlated with invasive data or confirmed in larger populations. Autonomic dysfunction is common in diabetic persons and may imply an associated poor prognosis. Reflex abnormalities in parasympathetic function are most prevalent and occur before sympathetic dysfunction.

Adult↗