P.-F. Migeotte is with the Department of Cardiology, Universite Libre de Bruxelles 1050, Brussels, Belgium (e-mail: Pierre-Francois.Migeotte@ulb.ac.be).K.-S. Park is with the Department of Biomedical Engineering, Seoul National University, Seoul 110-799, Korea (e-mail: kspark@bmsil.snu.ac.kr).M. Etemadi is with the Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA 94143 USA (e-mail: mozziyar.etemadi@ucsf.edu).K. Tavakolian is with the Department of Electrical Engineering, University of North Dakota, Grand Forks, ND 58202 USA (e-mail: kouhyart@gmail.com).R. Casanella is with the Instrumentation, Sensors, and Interfaces Group, Universitat Politecnica de Catalunya, 08034 Barcelona, Spain (e-mail: ramon. casanella@upc.edu).J. Zanetti is with Acceleron Medical Systems, Arkansaw, WI 54721 USA (e-mail: jmzsenior@gmail.com).J. Tank is with the Klinsche Pharmakologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany (e-mail: Tank.Jens@mh-hannover.de).I. Funtova is with the

No abstract

Diabetic autonomic dysfunction, even when not yet manifest, is associated with a high risk of mortality [1±11] which makes its early identification clinically important. In the early eighties Ewing and co-workers [1,12] validated a battery of laboratory tests for identification of autonomic abnormalities in patients with diabetes mellitus. These tests consist in the measurement of the heart rate changes induced by manouvers such as deep breathing, Valsalva and standing which engage reflexes that alter vagal and sympathetic modulation of the heart [13±17]. They further consist in the measurement of the blood pressure responses to standing, cold pressure test and hand-grip exercise which allow assessment of sympathetic modulation of systemic vascular resistance [15±19].Although useful for the identification of a diabetic-dependent damage of autonomic cardiovascular Diabetologia (1997) Summary Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age ± SD 41.9 ± 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (±71.3 % and ±60.2 % respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (±57.0 % and ±43.5 %, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i. e. under conditions suitable for routine outpatient evaluation. [Diabetologia (1997

Blood pressure (BP) and heart rate (HR) continuously fluctuate over time (18), under the influence of control mechanisms aimed at maintaining cardiovascular homeostasis. This term, from the Greek homeo (similar) and stasis (steady), indicates a condition that dynamically aims at achieving stability, without entirely reaching it. Indeed, daily life BP fluctuations are generated by external perturbations and by neural control mechanisms opposing their effects in the attempt to bring BP back towards a reference "set point" (24). As a result of these complex interactions, cardiovascular (CV) variability (V), rather than being "undesirable noise", reflects the activity of cardiovascular control mechanisms, representing a rich source of information on their performance in health and disease. The methods used to analyze this phoenomenon include several approaches, respectively aimed at estimating BP or HR variance, their spectral powers (1) and coherence, HR turbulence (3), entropy, self-similarity and symbolic logic (11; 31), or BP-HR interactions to quantify the baroreflex sensitivity on HR (BRS) (15).Evidence that CVV does represent an index of autonomic control of circulation, comes from three types of studies: 1) animal studies showing univocal changes in BPV or HRV following blockade, Downloaded from 2 amplification or selective interference with autonomic cardiovascular regulation; 2) human studies in which manipulation of autonomic cardiovascular control through drug administration or laboratory stimulations induced consequent changes in BPV or HRV; and 3) studies focussing on changes in BPV and/or HRV in patients affected by diseases where the autonomic nervous system was primarily or indirectly affected. The former include pure autonomic failure or spinal lesions, while examples of the latter are diabetes mellitus, congestive heart failure, acute myocardial infarction, obstructive sleep apnea and arterial hypertension. The link between autonomic function and CVV can be better appreciated by separately focussing on HRV, BPV as well on their mutual interaction as a means to quantify BRS (22; 24). HR variability. Vagal and sympathetic cardiac controls operate on HR in different frequency bands. Electrical stimulation of the vagus nerve and left stellate ganglion in dogs showed that vagal regulation has a relatively high cut-off frequency, modulating HR up to 1.0 Hz, while sympathetic cardiac control operates only below 0.15 Hz (4; 24; 29). In dogs and humans, parasympathetic blockade by atropine eliminates most HR fluctuations above 0.15 Hz (high frequency, HF), while only partly reducing those below 0.15 Hz; conversely, cardiac sympathetic blockade with propranolol reduced HR fluctuations below 0.15 Hz only, leaving those at HF largely unaffected (4; 29). After combined sympathetic and parasympathetic blockade, and after cardiac transplantation, a small HF HRV persists, probably due to mechanical modulation of sinus node by respiration (5). Low frequency (LF, 0.04-0.14 Hz) fluctuations in HR are affected by elec...