Cardiac Autonomic Reflex Research Articles

A cardiac risk score based on sudomotor function to evaluate cardiovascular autonomic neuropathy in asymptomatic Chinese patients with diabetes mellitus.

BackgroundsCardiac autonomic neuropathy is a common but always overlooked. More convenient diagnostic methods are needed.HypothesisCardiac autonomic neuropathy risk score evaluated by SUDOSCAN has a fine diagnostic efficacy detecting cardiac autonomic neuropathy.MethodsThis is a cross-sectional study among patients with diabetes mellitus. Subjects undertook SUDOSCAN tests and cardiac autonomic reflex tests, including heart rate variability due to Valsalva maneuver, heart rate response due to deep breathing and heart rate response due to standing up. Presenting 2 abnormal results was defined as cardiac autonomic neuropathy.ResultsSubjects with cardiac autonomic neuropathy has significantly higher cardiac autonomic neuropathy risk score (32.88±1.60 vs 27.64±1.24,P = 0.010). Cardiac autonomic neuropathy risk score was correlated significantly with the heart rate response due to deep breathing(P = 0.004). Multiple regression analysis including significant variables showed an independent association of cardiac autonomic neuropathy risk score and heart rate response due to deep breathing (P = 0.031) and age (P = 0.000). In receiver operating characteristic curve analysis evaluating the relationship between cardiac autonomic neuropathy risk score and cardiac autonomic neuropathy, The cut-off value was 20.5, with the sensitivity of 90.48%, the specificity of 29.5%, and the positive predictive value of 46.9%. In two-step diagnostic methods, Setting 20.5 as the cut-off value of cardiac autonomic neuropathy risk score and abnormal heart rate response due to standing up as the second diagnostic step’s positive result, and setting 16.5 as the cut-off value of cardiac autonomic neuropathy risk score and abnormal heart rate response due to deep breathing as the second diagnostic step’s positive result, both achieved good diagnostic efficacy.ConclusionCardiac autonomic neuropathy risk score evaluated by SUDOSCAN is a good screening test for cardiac autonomic neuropathy. The two-step diagnostic methods could be considered as surrogate diagnostic methods.

Maternal Heart Rate Variability during the First Stage of Labor.

Labor necessitates continuous adjustments of cardiac autonomic reflexes by alternate activation of the sympathetic and parasympathetic nervous systems. The division of the autonomic nervous system (ANS) that predominates during the first stage of labor is unclear and needs to be further investigated. The study aimed to compare heart rate variability (HRV) in pregnant women in the third trimester with those during the first stage of labor. We conducted a case–control study at Saad Abul Ela Maternity Hospital, Khartoum, Sudan. Forty-five women with singleton, live neonates in the first stage of labor and 45 women in the third trimester (but not in labor) were enrolled as case and control groups, respectively. Data on the medical history, obstetrics history, and clinical examinations that were performed in all of the studied women were obtained using prearranged questionnaires. Cardiac autonomic modulation (CAM) of the heart was examined in both groups based on time and frequency domain HRV indices. There were no significant differences in age, parity, body mass index, and hemoglobin levels between the two groups. Pregnant women in labor had significantly higher LnSDNN, LnRMSSD, LnTP, LnVLF, LnLF, LnHF, LF Norm, and LnLF/HF ratio, but lower HF Norm compared with controls (P < 0.001). These findings remained unchanged when possible confounders were controlled for using regression analysis. Our findings suggest a significant increase in indictors of sympathetic CAM, namely LF Norm and LnLF/HF, during labor. Sympathetic hypertonia associated with labor is unlikely to increase the risk of cardiac events because sympathetic CAM simultaneously increases with global HRV. Increased HRV during labor may be explained by parasympathetic activation as indicated by higher LnHF and LnRMSSD at the time of delivery.

Diagnostic Accuracy of Random ECG in Primary Care for Early, Asymptomatic Cardiac Autonomic Neuropathy.

Cardiac autonomic reflex tests (CARTs) are time consuming and require patient cooperation for detecting cardiac autonomic neuropathy (CAN). Heart rate variability (HRV) analysis requires less patient cooperation and is quicker to complete. However the reliability of HRV results as a clinical tool, with respect to length of recording and accuracy of diagnosis is inconclusive. The current study investigated the reproducibility associated with varying length of recording for early CAN (eCAN) assessment. Participants were 68 males, 72 females with average age of 55 for controls and 63 for early CAN. Inclusion criteria were that participants were medication free and presented with no comorbidities. ECGs of control and eCAN were recorded and heart rate changes analyzed with the fast Fourier transform (FFT) and Lomb-Scargle periodogram (LSP). Ten-second to 5-minute recordings were extracted from a 15-minute lead-II ECG and accuracy in assessment of eCAN determined. The eCAN group was older ( P < .001) and systolic blood pressure was higher ( P < .01). HDL-cholesterol was also higher in the eCAN group ( P < .05). HRV analysis showed that both FFT and LSP results were significantly different between eCAN and control down to a 10-second ECG length for low frequency (LSP: P = .013, FFT: P = .024) and high frequency (HF-LSP: P = .002, FFT: P = .002) power. eCAN assessment was optimal down to 90-second recordings with a sensitivity of 100% and specificity of 29.49%. HRV is suitable for clinical practice from ECG recordings of more than 90 seconds with high accuracy and repeatability within a session for each participant.

Heart rate independent QT variability component can detect subclinical cardiac autonomic neuropathy in diabetes.

Cardiac autonomic neuropathy (CAN) may lead to life threatening arrhythmia due to denervation of both the parasympathetic and sympathetic branches of autonomic nervous system innervating the heart. CAN is a frequently under diagnosed complication of diabetes, because a patient can have asymptomatic CAN for several years before it is clinically apparent. However, detection of CAN at the early or subclinical stage leads to more effective treatment outcomes. Cardiac autonomic reflex tests (CART) (i.e. Ewing test battery) are normally used for the detection and staging of CAN. These tests have limitations with the necessity of active participation of the patients for test maneuvers, as a majority of patients will not be able to complete all five tests required due to comorbidities such as frailty, obesity or cardiorespiratory disease. CAN affects both heart rate (measured by RR interval dynamics) and ventricular repolarization function (i.e. QT interval dynamics) of the heart, which can be efficiently analyzed from surface ECG. Therefore, ECG based diagnosis techniques of CAN analysis are becoming popular as they can reduce the limitations of CARTs used traditionally for CAN detection and it complements CART results. In this study, the performance of an ECG based QTV feature derived using a model free approach, which can quantify the QTV component not affected directly by the heart rate (HR) variation, is compared with some other measures of QTV and HRV in subclinical CAN detection in diabetes. Short-term ECGs (i.e. 5 min long) of 60 diabetic subjects without CAN and 50 diabetic subjects detected with early level of CAN determined by CART were analyzed. The proposed measure for quantifying the QTV component independent of HR denoted as QTV~RR stands out to be more discriminatory than other existing variability measures of QTV and HRV in subclinical detection of CAN.

Assessment of the cardiac autonomic neuropathy among the known diabetics and age-matched controls using noninvasive cardiovascular reflex tests in a South-Indian population: A case-control study.

Aim:Diabetes mellitus is a chronic condition characterized by hyperglycemia. The objective of the study was to estimate the prevalence of cardiac autonomic neuropathy in a rural area of South India, among the known diabetics after comparing them with the age-matched healthy controls, utilizing noninvasive cardiac autonomic neuropathy reflex tests.Materials and Methods:A case–control study was conducted for 4 months (October 2014 to January 2015) at an Urban Health and Training Center (UHTC) of a Medical College located in Kancheepuram district, Tamil Nadu. The study was conducted among 126 diagnosed Type 2 diabetes patients and in 152 age- and sex-matched healthy controls to ensure comparability between the cases and controls and, thus, reduce variability due to demographic variables. All the study subjects (cases and controls) were selected from the patients attending UHTC during the study duration, provided they satisfied the inclusion and exclusion criteria. Study participants were subjected to undergo noninvasive cardiac autonomic neuropathy reflex tests. The associations were tested using paired t-test for the continuous (mean ± standard deviation) variables.Results:The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2% (67/126). On further classification, positive (abnormal) results were obtained in 56 (sympathetic – 44.4%) and 51 (parasympathetic – 40.5%) diabetic cases. Overall, heart rate variation during deep breathing was found to be the most sensitive test to detect parasympathetic autonomic neuropathy while the diastolic blood pressure response to sustained handgrip exercise was the most sensitive method to detect sympathetic neuropathy dysfunction.Conclusion:The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2%. Even though cardiac autonomic neuropathy can be detected by various invasive tests, noninvasive tests remain a key tool to detect it in the remote settings in a cost-effective and user-friendly manner without making people visit higher centers.

Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes.

Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac (123)I-metaiodobenzylguanidine scintigraphy was conducted in a subgroup of 29 patients and 14 control subjects and evaluated as the late heart-to-mediastinum ratio and washout rate. Impaired function of all the cardiac autonomic measures (except the washout rate) was associated with reduced CFR. A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate. The late heart-to- mediastinum ratio remained correlated with CFR after further adjustment. In patients with T2DM without cardiovascular disease, we demonstrate an independent association between cardiac autonomic function and CFR. We suggest that a reduced cardiac autonomic function and damage to the adrenergic receptors may contribute to the development of cardiac microvascular dysfunction.

Making sense of a new technology in clinical practice: a qualitative study of patient and physician perspectives.

BackgroundThe number of new technologies for risk assessment available in health care is increasing. These technologies are intended to contribute to both improved care practices and improved patient outcomes. To do so however, there is a need to study how new technologies are understood and interpreted by users in clinical practice. The objective of this study was to explore patient and physician perspectives on the usefulness of a new technology to detect Cardiovascular Autonomic Neuropathy (CAN) in a specialist diabetes clinic. The technology is a handheld device that measures resting heart rate and conducts three cardiac autonomic reflex tests to evaluate heart rate variability.MethodsThe study relied on three sources of data: observations of medical consultations where results of the CAN test were reported (n = 8); interviews with patients who had received the CAN test (n = 19); and interviews with physicians who reported results of the CAN test (n = 9). Data were collected at the specialist diabetes clinic between November 2013 and January 2014. Data were analysed using the concept of technological frames which is used to assess how physicians and patients understand and interpret the new technology.ResultsPhysicians generally found it difficult to communicate test results to patients in terms that patients could understand and to translate results into meaningful implications for the treatment of patients. Results of the study indicate that patients did not recall having done the CAN test nor recall receiving the results. Furthermore, patients were generally unsure about the purpose of the CAN test and the implications of the results.DiscussionInvolving patients and physicians is essential when a new technology is introduced in clinical practice. This particularly includes the interpretation and communication processes related to its use.ConclusionsThe integration of a new risk assessment technology into clinical practice can be accompanied by several challenges. It is suggested that more information about the CAN test be provided to patients and that a dialogue-based approach be used when communicating test results to patients in order to best support the use of the technology in clinical practice.

Inappropriate Sinus Tachycardia

Inappropriate sinus tachycardia (IST) is an uncommon form of arrhythmia characterized by an increased heart rate that is out of proportion to a normal physiologic demand. The etiology of IST remains ill-defined and controversial. Clinical presentation of IST is highly variable, from isolated to sustained palpitations, and can cause deterioration in one's quality of life. IST is usually a diagnosis of exclusion and it is important to rule out other causes of sinus tachycardia before reaching a final diagnosis. Evaluation of cardiac autonomic reflex function is essential to support the diagnosis of IST. The treatment of IST aims to target the multiple mechanisms involved in this disease, and multidisciplinary management, including cardiac rehabilitation, pharmacotherapy, and occasionally radiofrequency modification of the sinus node, should be considered. The prognosis is usually benign, although regular follow-up is required to optimize therapy and prevent the onset of tachycardiomyopathy.

TRPV1 receptor expression in cardiac vagal afferent neurons of infant rats

We examined in infant rats whether cardiac afferent neurons in the nodose ganglia (NG) express transient receptor potential vanilloid 1 (TRPV1) receptors. Anesthetized rats (9–11 days old) were injected with 2 μl of a fluorescent retrograde tracer (Fluoro-Gold, FG) into the ventricular wall through the anterior epicardial surface. After 2 days, the NG were excised under anesthesia for identification of FG-labeled neurons and immunohistochemical analysis. Of 3858 NG neurons, 5% (202 neurons) were labeled with FG. Among the FG-labeled neurons, 180 (89%) were TRPV1 positive, of which 123 co-expressed 200-kDa neurofilaments (NF200), which is specific for myelinated nerve fibers. Among the FG-labeled neurons that expressed both TRPV1 and NF200, 37 had relatively large cell diameters (>26 μm) (range: 12–38 μm). In conclusion, in infant rats, most cardiac afferent neurons (both myelinated and unmyelinated) in the NG may express TRPV1 receptors. Although functional properties such as those related to the arterial baroreflex may vary among the neurons, our results suggest that, in immature animals, TRPV1 receptors help convey cardiac sensations and control autonomic reflexes.

Do specific connection patterns of the ligament of Marshall contribute mechanistically to atrial fibrillation?

Do specific connection patterns of the ligament of Marshall contribute mechanistically to atrial fibrillation?

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes. To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro-oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms. Thirty-two patients (13 females and 19 males; age: 20-69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43-58 years) with GERD only, underwent simultaneous 24-h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full-dosage PPI therapy (esomeprazole 40 mg/day) was prescribed. In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus-heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01). This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

Heart rate turbulence-based predictors of fatal and nonfatal cardiac arrest (The autonomic tone and reflexes after myocardial infarction substudy)

A previous report on heart rate (HR) turbulence showed its value in postinfarction risk stratification. The present study determines the predictive value of HR turbulence in a low-risk population after acute myocardial infarction and provides insight into its pathophysiologic correlates. With use of the database of the The Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, data were obtained from 1,212 survivors with a mean duration of follow-up of 20.3 months. The a priori end point was defined as the combination of fatal cardiac arrest and nonfatal cardiac arrest. HR turbulence characterized by turbulence onset (TO) and turbulence slope (TS) was calculated and correlated with baroreflex sensitivity (BRS) and the SD of the normal-to-normal RR intervals (SDNN). A composite index of cardiac autonomic function was assessed by combining HR turbulence (TO and TS), BRS, and SDNN. Both TO and TS correlated moderately but significantly with BRS and SDNN (r = 0.26 to 0.44, p <0.001 for all correlations). On Cox’s univariate regression analysis, the RRs for abnormal values of TO, TS, and the combination of abnormal TO and TS were 1.86 (95% confidence interval [CI] 0.96 to 3.61, p = 0.065), 4.08 (95% CI 2.11 to 7.89, p <0.0001), and 6.87 (95% CI 3.06 to 15.45, p <0.0001), respectively. The composite autonomic index (combined TO, TS, BRS, and SDNN) was the strongest risk predictor: for all 4 abnormal factors, RR 16.79 (95% CI 6.01 to 46.89, p <0.0001). On multivariate analysis, abnormal TO and TS, and left ventricular ejection fraction remained as independent predictors: RRs 4.07 (95% CI 1.70 to 9.77, p = 0.0017) and 3.53 (95% CI 1.76 to 7.06, p = 0.0004), respectively. In a separate model, the composite autonomic index was the strongest multivariate risk predictor: RR 8.67 (95% CI 2.72 to 7.65, p = 0.0003) for all abnormal factors, and adjusted for left ventricular ejection fraction. Thus, this study confirms the independent value of HR turbulence in predicting fatal cardiac arrest and nonfatal cardiac arrest in a low-risk post-acute myocardial infarction population. By combining HR turbulence, BRS, and SDNN, a comprehensive assessment of cardiac autonomic reflexes and modulation can be obtained.

Prolonged QTc interval and its relationship to autonomic cardiovascular reflexes in patients with cirrhosis

Background / Aims : We have previously shown that an abnormality in cardiac autonomic reflexes (AN) is an independent predictor of mortality in patients with chronic liver disease. Aim of this study was to determine whether there was an association between prolonged QTc interval and cardiac AN. Methods : Cardiac AN and QTc interval were determined in 130 patients (Child A 42, B 53, C 35) with alcoholic and non-alcoholic liver disease. Results : Prolonged QTc (>440 ms) was seen in 58 (Child A 30%, B 46%, C 60%, P=0.04) patients. Autonomic tests were normal in 21%, borderline abnormal in 36% and definitely abnormal in 43%. QTc correlated with albumin ( P<0.001), prothrombin time ( P=0.003) and Child–Pugh score ( P<0.001), but not with Valsalva ratio, heart rate variation with 6 breath/min breathing, tilt table or isometric exercise. By logistic regression analysis, QTc correlated only with Child–Pugh score ( P<0.001). Mean QTc of 34 who died during the follow up was higher than survivors. Cox regression analysis showed that only Child–Pugh score and AN were independent predictors of mortality. Conclusions : Prolonged QTc seen in liver disease is independent of their cardiac autonomic function, but is related to the severity of the liver disease.

A global index of cardiac autonomic status and reflexes Azad Ghuran, Fiona Reid, Irina Savelieva, Maria Teresa La Rovere, Georg Schmidt, J. Thomas Bigger, Jr., A John Camm, Peter J Schwartz, Marek Malik. St. George's Hospital Medical School, London, United Kingdom, Department of Cardiology, Policlinico S. Matteo IRCCS and University of Pavia, Pavia, Italy

A global index of cardiac autonomic status and reflexes Azad Ghuran, Fiona Reid, Irina Savelieva, Maria Teresa La Rovere, Georg Schmidt, J. Thomas Bigger, Jr., A John Camm, Peter J Schwartz, Marek Malik. St. George's Hospital Medical School, London, United Kingdom, Department of Cardiology, Policlinico S. Matteo IRCCS and University of Pavia, Pavia, Italy

Correlates of venous catecholamine concentrations in patients with type 1 diabetes during a cold pressor test.

In some patients with type 1 diabetes, various physiologic reactions during a cold pressor test (CPT) are impaired. Whether this is caused by diabetic autonomic neuropathy, disturbed secretion of catecholamines, or disturbed blood glucose control is unknown. The authors, therefore, performed CPTs in patients with type 1 diabetes and in control subjects. They measured blood glucose concentrations, insulin concentrations, cardiac autonomic reflexes, and (before and after the CPT) venous catecholamine concentrations and analyzed correlations between these variables. Twenty-two patients with type 1 diabetes (17 men, 5 women; mean age +/- SD, 26.6 +/- 6.5 y; diabetes duration, 7.6 +/- 0.7 y; glycosylated hemoglobin concentration, 7.7 +/- 2.4%) and 35 control subjects with comparable age and gender distributions were studied. Venous catecholamines were measured before and at the end of a 5-minute CPT. In patients with diabetes, only noradrenaline concentrations increased during the CPT, whereas adrenaline concentrations that were already increased at rest did not change. Adrenaline concentrations correlated inversely with insulin concentrations. In control subjects, both adrenaline and noradrenaline increased significantly during the CPT. In both groups, the magnitude of the individual change in catecholamine concentrations was inversely correlated with the respective resting concentration. Changes in catecholamines, cardiovascular reflex tests, and blood glucose concentrations did not correlate with blood pressure changes. The authors conclude that, in patients with diabetes, resting adrenaline concentrations are related to insulin concentrations. Contrary to control subjects, in patients with diabetes, only noradrenaline increased during CPTs. In both groups, changes in catecholamine concentrations after the CPT were inversely related to the respective resting concentrations.

Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus.

C ardiac sympathetic signals play an important role in the regulation of myocardial perfusion. We hypothesized that sympathetically mediated myocardial blood flow would be impaired in diabetics with autonomic neuropathy. We studied 28 diabetics (43+/-7 years old) and 11 age-matched healthy volunteers. PET was used to delineate cardiac sympathetic innervation with [(11)C]hydroxyephedrine ([(11)C]HED) and to measure myocardial blood flow at rest, during hyperemia, and in response to sympathetic stimulation by cold pressor testing. The response to cardiac autonomic reflex tests was also evaluated. Using ultrasonography, we also measured brachial artery reactivity during reactive hyperemia (endothelium-dependent dilation) and after sublingual nitroglycerin (endothelium-independent dilation). Based on [(11)C]HED PET, 13 of 28 diabetics had sympathetic-nerve dysfunction (SND). Basal flow was regionally homogeneous and similar in the diabetic and normal subjects. During hyperemia, the increase in flow was greater in the normal subjects (284+/-88%) than in the diabetics with SND (187+/-80%, P=0.084) and without SND (177+/-72%, P=0.028). However, the increase in flow in response to cold was lower in the diabetics with SND (14+/-10%) than in those without SND (31+/-12%) (P=0.015) and the normal subjects (48+/-24%) (P<0.001). The flow response to cold was related to the myocardial uptake of [(11)C]HED (P<0.001). Flow-mediated brachial artery dilation was impaired in the diabetics compared with the normal subjects, but it was similar in the diabetics with and without SND. Diabetic autonomic neuropathy is associated with an impaired vasodilator response of coronary resistance vessels to increased sympathetic stimulation, which is related to the degree of SND.

Exogenous NPY modulation of cardiac autonomic reflexes and its pressor effect in the conscious rabbit.

1. Neuropeptide Y (NPY) may inhibit sympathetic and vagal transmission via presynaptic Y2 receptors and cause vasoconstriction via postsynaptic Y1 receptors. We examined the effects of NPY and related peptides on cardiovascular parameters and autonomic reflexes in the conscious rabbit. Further, the postjunctional effects of NPY and related peptides were assessed on acetylcholine (ACh) and isoprenaline agonist dose-chronotropic response curves. 2. In conscious rabbits the cardiac baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch like and nasopharyngeal reflexes were assessed in control, propranolol-treated or methscopolamine-treated (baroreflex only) groups, before and 30 min after i.v. administration of NPY (10 microg kg[-1] + 5 microg kg[-1] min[-1]) or vehicle (saline, 10 ml h[-1]). The effects of equivalent pressor doses of [Leu31, Pro34]NPY or methoxamine on the baroreflex were also examined. In separate animals, dose-heart rate (HR) response curves to isoprenaline or ACh were constructed before and 15 min after administration of NPY, [Leu31,Pro34]NPY (ACh only) or [Leu31,Pro34]NpY + sodium nitroprusside (ACh only). 3. Administration of NPY-receptor agonists caused sustained bradycardia (in the absence of methscopolamine) and rightward shifts of the barocurves in all 3 groups. The range of sympathetically-mediated tachycardia was significantly decreased by NPY or [Leu31,Pro34]NPY in the methscopolamine-treated group. However, these changes in the baroreflex were no different from those elicted by equipressor doses of methoxamine. There was no vagal inhibition by any NPY-receptor agonist in all three autonomic reflexes examined. ACh or isoprenaline dose-HR response curves were not affected by NPY peptide administration. 4. We conclude that in the conscious rabbit, at a single dose that elicits a significant pressor response, exogenous NPY has no direct effect on modulation of cardiac and autonomic reflexes. Non-specific effects of exogenous NPY on the baroreflex may be fully explained by its pressor action. There was no effect of NPY on postjunctional ACh or isoprenaline agonist dose-response curves. Therefore, it is unlikely that endogenous NPY has a functional role in directly modulating cardiac autonomic neurotransmission in the rabbit.

Acute cardiovascular effects of the concurrent administration of enalapril, prazosin or amlodipine in healthy Nigerians

The acute circulatory effects of the combination of prazosin 1 mg, enalapril 10 mg or amlodipine 5 mg were evaluated and compared in placebo controlled, randomised, double blind, latin-square, cross-over study in 8 normotensive healthy Nigerians. Supine and erect blood pressure were reduced by the active treatment combinations ( F = 8.8, P = 0.0006, analysis of variance). In all, the onset of blood pressure fall was within 2 h, with a peak reduction at 4–6 h and persisting for at least 12 h. The combination of converting enzyme inhibitor and alpha blocker, however, caused a significantly greater hypotensive action than the other combinations ( P < 0.05, analysis of variance). There was a modest reflex tachycardia in the erect position on all treatments ( P = 0.008). Cardiac autonomic reflexes or left ventricular echocardiographic indices were unaffected by the drug combinations. The haemodynamic effect of enalapril plus prazosin combination, which separately cause little hypotensive effect in Africans, may reflect an important pharmacodynamic interaction between α 1 and angiotensin II vascular receptors. All combinations lower blood pressure and warrant further study in Nigerian hypertensives. However, the enalapril plus prazosin combination caused the greatest blood pressure fall, and caution is indicated during their concurrent use, owing to enhanced first dose hypotension.

Effect of disease duration on cardiac autonomic reflexes in young patients with insulin-dependent diabetes mellitus

The association of disease duration with deterioration of cardiovascular autonomic reflexes was studied in two groups of young patients with insulin-dependent diabetes mellitus (IDDM). The mean age of the patients in both groups was 31 years and the mean duration of the disease was 3 ( n = 18) and 16 ( n = 22) years. No significant difference in group means was seen in the test parameters of autonomic nerve function. However, five patients with long-term disease, but none with short-term disease, had test scores indicating cardiac autonomic neuropathy. It was concluded that (1) the duration of the disease has no overall effect on autonomic nerve function in young patients with IDDM, but (2) a few individuals with IDDM may have some precipitating factors leading to autonomic neuropathy in the course of the disease.

Autonomic and sensory nerve function in diabetic foot ulceration

Peripheral sensory and autonomic nerve dysfunction are thought to be crucial factors in the pathogenesis of diabetic foot ulceration. However, their relative importance is not known. In this study we have compared peripheral sensory nerve function and cardiac autonomic reflexes in 51 diabetics with a history of foot ulceration and 480 diabetic control subjects. In the diabetics with ulceration ankle reflexes were absent or impaired and vibration perception threshold reduced in 96.1% and 82.4%, respectively, compared with 40.8% and 25.8%, respectively, in control subjects (P less than 0.001). Cardiac autonomic tests were abnormal more frequently in the diabetics with ulceration and an autonomic score derived from four tests was abnormal in 62.8% of those with ulceration compared with 13.5% of those without ulceration (P less than 0.001). Discriminant analysis of the two groups of diabetes showed that an abnormal autonomic score was the best predictor of foot ulceration in diabetic patients.