Alan Bernjak

Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk.

Recent trials of intensive glycemic control suggest a possible link between hypoglycemia and excess cardiovascular mortality in patients with type 2 diabetes. Hypoglycemia might cause arrhythmias through effects on cardiac repolarization and changes in cardiac autonomic activity. Our aim was to study the risk of arrhythmias during spontaneous hypoglycemia in type 2 diabetic patients with cardiovascular risk. Twenty-five insulin-treated patients with type 2 diabetes and a history of cardiovascular disease or two or more risk factors underwent simultaneous continuous interstitial glucose and ambulatory electrocardiogram monitoring. Frequency of arrhythmias, heart rate variability, and markers of cardiac repolarization were compared between hypoglycemia and euglycemia and between hyperglycemia and euglycemia matched for time of day. There were 134 h of recording at hypoglycemia, 65 h at hyperglycemia, and 1,258 h at euglycemia. Bradycardia and atrial and ventricular ectopic counts were significantly higher during nocturnal hypoglycemia compared with euglycemia. Arrhythmias were more frequent during nocturnal versus daytime hypoglycemia. Excessive compensatory vagal activation after the counterregulatory phase may account for bradycardia and associated arrhythmias. QT intervals, corrected for heart rate, >500 ms and abnormal T-wave morphology were observed during hypoglycemia in some participants. Hypoglycemia, frequently asymptomatic and prolonged, may increase the risk of arrhythmias in patients with type 2 diabetes and high cardiovascular risk. This is a plausible mechanism that could contribute to increased cardiovascular mortality during intensive glycemic therapy.

Wavelet Phase Coherence Analysis: Application to Skin Temperature and Blood Flow

The technique of wavelet phase coherence analysis is introduced and used to explore relationships between oscillations on blood flow and temperature in the skin of 10 healthy subjects. Their skin temperature and blood flow were continuously recorded: under basal conditions for 30 min; during local cooling of the skin with an ice-pack for 20 min: and 30 min thereafter. The group mean basal skin temperature of 33.4°C was decreased to 29.2°C during the cooling period, and had recovered to 32.1°C by the end of the recording. The wavelet transform was used to obtain the time–frequency content of the two signals, and their coherence. It is shown that cooling increases coherence to a statistically significant extent in two frequency intervals, around 0.007 and 0.1 Hz, suggesting that these oscillatory components are involved in the regulation of skin temperature when cold is applied as a stress.

The Effects of General Anesthesia on Human Skin Microcirculation Evaluated by Wavelet Transform

BACKGROUND:Time-frequency analysis of the laser Doppler flowmetry signal, using wavelet transform, shows periodic oscillations at five characteristic frequencies related to the heart (0.6–2 Hz), respiration (0.15–0.6 Hz), myogenic activity in the vessel wall (0.052–0.15 Hz), sympathetic activity (0.021–0.052 Hz), and very slow oscillations (0.0095–0.021), which can be modulated by the endothelium-dependent vasodilator acetylcholine. We hypothesized that wavelet transform of laser Doppler flowmetry signals could detect changes in the microcirculation induced by general anesthesia, such as alterations in vasomotion and sympathetic activity. METHODS:Eleven patients undergoing faciomaxillary surgery were included. Skin microcirculation was measured on the lower forearm with laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside before and during general anesthesia with propofol, fentanyl, and midazolam. The laser Doppler flowmetry signals were analyzed using wavelet transform. RESULTS:There were significant reductions in spectral amplitudes in the 0.0095–0.021 (P < 0.01), the 0.021–0.052 (P < 0.001), and the 0.052–0.15 Hz frequency interval (P < 0.01) and a significant increase in the 0.15–0.6 Hz frequency interval. General anesthesia had no effect on the difference between acetylcholine and sodium nitroprusside on relative amplitudes in the 0.0095–0.021 Hz frequency interval (P < 0.001). CONCLUSION:General anesthesia reduces the oscillatory components of the perfusion signal related to sympathetic, myogenic activity and the component modulated by the endothelium. However, the iontophoretic data did not reveal a specific effect on the endothelium. The increase in the 0.15–0.6 Hz interval is related to the effect of mechanical ventilation.

Skin Blood Flow in the Upper and Lower Extremities of Diabetic Patients with and without Autonomic Neuropathy

Background: Microvascular blood flow in the human skin is subject to rhythmic variations reflecting the influence of heartbeat, respiration, intrinsic myogenic activity, neurogenic factors and endothelial activity. The aim of our study was to test the hypothesis that basal skin blood flow (BSBF) and its dynamic components differ (1) among diabetic patients without autonomic neuropathy and with it and healthy control subjects, and (2) among the upper and lower extremities. Patients and Methods: BSBF at four recording sites with predominantly nutritive capillary circulation (right and left caput ulnae, right and left medial malleolus) was measured by laser Doppler flowmetry in 25 diabetic patients without cardiovascular autonomic neuropathy (D), 18 neuropathic diabetic patients (DAN) and 36 healthy controls (C). Wavelet transform was applied to the laser Doppler signal. Results: In absolute terms, mean flow, mean amplitude of the total spectrum and mean amplitudes at all frequency intervals were highest in C, followed by DAN and lowest in D. However, these differences were statistically significant only in the left arm. Within all three groups, mean flow and spectral amplitudes were significantly higher in the arms than in the legs, besides there was a significant difference between the two arms in D. Conclusion: We have confirmed the differences in BSBF among D, DAN and C, and demonstrated differences among the four recording sites which have not been previously described. The latter indicates an uneven progression of autonomic neuropathy and allows for speculation that the left arm is the latest to be affected.

Human skin microcirculation after brachial plexus block evaluated by wavelet transform of the laser Doppler flowmetry signal.

Background:The skin microcirculation may be evaluated noninvasively by laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside. Wavelet transform of the perfusion signal shows periodic oscillations of five characteristic frequencies in the interval 0.0095–1.6 Hz. The aim of the current study was to investigate alterations in skin microcirculation induced by brachial plexus block, with emphasis on the periodic oscillations. Methods:Healthy nonsmokers undergoing hand surgery (n = 13) were anesthetized with brachial plexus block, using bupivacaine, lidocaine, and epinephrine. Skin microcirculation was evaluated by laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside before and after brachial plexus block. Wavelet transform of the perfusion signal was performed. As a control group, 10 healthy nonsmokers were included. Results:In the anesthetized arm, skin perfusion after brachial plexus block increased from 19 (12–30) to 24 (14–39) arbitrary units (P < 0.01). A significant increase was also seen in the contralateral arm from 17 (14–32) to 20 (14–42) arbitrary units (P < 0.01). After brachial plexus block, spectral analysis revealed a significant reduction in relative amplitude of the oscillatory components within the 0.0095- to 0.021- (P < 0.001) and 0.021- to 0.052-Hz (P < 0.001) intervals in the anesthetized arm. Conclusion:Alterations in skin microcirculation induced by brachial plexus block can be evaluated by wavelet transform of the laser Doppler flowmetry signal. Brachial plexus block reduces the oscillatory components within the 0.0095- to 0.021- and 0.021- to 0.052-Hz intervals of the perfusion signal. These alterations are related to inhibition of sympathetic activity and a possible impairment of endothelial function.

Evolution of cardiorespiratory interactions with age

We describe an analysis of cardiac and respiratory time series recorded from 189 subjects of both genders aged 16–90. By application of the synchrosqueezed wavelet transform, we extract the respiratory and cardiac frequencies and phases with better time resolution than is possible with the marked events procedure. By treating the heart and respiration as coupled oscillators, we then apply a method based on Bayesian inference to find the underlying coupling parameters and their time dependence, deriving from them measures such as synchronization, coupling directionality and the relative contributions of different mechanisms. We report a detailed analysis of the reconstructed cardiorespiratory coupling function, its time evolution and age dependence. We show that the direct and indirect respiratory modulations of the heart rate both decrease with age, and that the cardiorespiratory coupling becomes less stable and more time-variable.

COHERENCE BETWEEN FLUCTUATIONS IN BLOOD FLOW AND OXYGEN SATURATION

We have determined the wavelet phase coherence between simultaneously recorded microvascular blood flow and oxygen saturation signals from 88 healthy subjects, thus enabling us to study their common fluctuations. Measurements were taken for 30 min from the arm and leg, at two depths. In the skin, blood flow and oxygen saturation were found to be coherent both at the cardiac frequency and below 0.1 Hz down to about 0.01 Hz. Coherence in the arm extends to lower frequencies than that in the leg. From the deeper recordings, no coherence was found on either limb. The existence of coherence between skin blood flow and oxygen saturation demonstrates causal connections between them within certain frequency ranges. The method has yielded the first detailed insight into the dynamics of blood oxygenation.

Human sympathetic outflows to skin and muscle target organs fluctuate concordantly over a wide range of time‐varying frequencies

Non‐technical summary  Traffic carried over two branches of the sympathetic nervous system can be recorded in cooperative human subjects, with fine needles inserted directly into leg nerves. We made simultaneous recordings of sympathetic activity with two needles inserted into nerve tracts supplying skin and muscles, and used a mathematical method, wavelet phase coherence, to obtain insights into how the brain regulates neural oscillations. Our results document continuously varying and coherently coupled human skin and muscle sympathetic nerve oscillations over time (suggesting that they are driven by other central frequency generators).

Incipient cardiovascular autonomic imbalance revealed by wavelet analysis of heart rate variability in type 2 diabetic patients

Aim  Incipient cardiovascular autonomic imbalance is not readily diagnosed by conventional methods. Spectral analysis of heart rate variability (HRV) by wavelet transform (WT) was used to measure cardiovascular autonomic function in patients with Type 2 diabetes.

Skin Blood Flow and Its Oscillatory Components in Patients with Acute Myocardial Infarction

Background/Aims: Laser Doppler flowmetry (LDF) was used to determine the influence of acute myocardial infarction (AMI) and of successful reperfusion treatment on basal skin blood flow and its oscillatory components. Methods: Skin LDF was performed on all extremities in 58 patients 4–9 days after AMI (Killip class I), and in 71 healthy age- and sex-matched controls. Wavelet analysis was applied to evaluate oscillatory components within the interval 0.005–2 Hz. Results: AMI patients had reduced mean flow (p < 0.01) and oscillatory components (p < 0.04) in all extremities. Reperfused (n = 40), compared to nonreperfused (n = 18), patients had higher mean flow and total spectral amplitude at all recording points. The difference was statistically significant only in legs (group median LDF in the left leg was 9.68 AU for reperfused and 5.71 AU for nonreperfused patients, p < 0.04, and 11.47 and 4.24 AU in the right leg, p < 0.01). Reperfused patients had significantly higher total spectral amplitude in both legs (p < 0.04). Conclusions: In AMI patients, reduced skin blood flow and its oscillatory components may reflect ongoing neurohumoral activation despite absence of clinically apparent heart failure. The reduction of blood flow and its oscillatory components was larger in nonreperfused AMI patients, although they had a comparable left ventricular function.