The role of insulin resistance in the association between body fat and autonomic function.

BACKGROUND AND AIM: Excess body fat is associated with altered autonomic function. We investigated whether this association is mediated by insulin resistance. METHODS AND RESULTS: Cross-sectional analysis of a subgroup of the Netherlands Epidemiology of Obesity study with measurements of autonomic function (heart rate variability calculated as mean interbeat interval, standard deviation of all normal intervals (SDNN), low frequency (LF) power and high frequency (HF) power). We measured BMI(kg/m²), total body fat(%) and waist circumference(cm), and calculated the HOMA-index of insulin resistance (HOMA-IR). We examined the association between body fat and heart rate variability with multivariate linear regression analysis. To investigate whether the association was mediated by insulin resistance, we additionally adjusted for HOMA-IR. After exclusion of participants with glucose lowering medication (n = 19), 466 participants were included. Per SD of BMI, the difference in SDNN was -2.7% (95%CI: -5.5, 0.1) in the multivariate model. Additional adjustment for HOMA-IR attenuated this association to -1.2% (95%CI: -4.2, 1.7), suggesting that 55% of the association between BMI and SDNN was mediated by HOMA-IR. All measures of body fat were associated with mean interbeat interval, SDNN and LF power. Depending on the parameter of body fat or heart rate variability, 29-81% of the association was mediated by HOMA-IR. CONCLUSION: In this cross-sectional study, body fat was associated with heart rate variability. This association may at least partially be mediated by insulin resistance. Future studies should investigate whether a reduction in obesity and insulin resistance may prevent the adverse cardiovascular consequences of altered autonomic function.

Novel α-glycosyl compounds from glycosylation of rubusoside.

In this work we investigated mixtures from α-glycosylation of rubusoside with cyclodextrin glycosyltransferases. In addition to the previously known α-1,4 glycosylated derivatives, nine new compounds with rare α-1,3-glycosidic bonds were identified based on nuclear magnetic resonance spectroscopy and mass spectrometric analysis. Furthermore, sensory properties of monoglycosylated rubusoside derivatives were investigated and compared to previously described monoglycosylated compounds. Additionally, digestion with α-amylase from human saliva was investigated for different glycosylated rubusoside derivatives.

A high phosphate diet lowers blood pressure in spontaneously hypertensive rats.

Plasma phosphate values are significantly lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto rats (WKY). In this study, we increased plasma phosphate in SHR by a dietary phosphate intake and followed the effects on blood pressure. Fifteen male WKY and 15 male SHR were housed from 4 weeks of age up to 26 weeks. At 4 weeks of age all SHR manifested a hypophosphatemia compared with age-matched WKY (F = 62, p less than 0.0003). At 5 weeks of age, the rats were divided into three diet groups: a control group, a group receiving 1.41% (wt/vol) KCl in drinking water, and a group receiving 2% (wt/vol) K2HPO4 X KH2PO4 in drinking water. In the control (F = 16.2, p less than 0.02) and KCl groups, (F = 36.3, p less than 0.03), hypophosphatemia persisted throughout the study. The phosphate-supplemented diet normalized plasma phosphate level in SHR but did not change plasma phosphate level in WKY. As a consequence, no difference in plasma phosphate level between WKY and SHR was present in the group receiving additional phosphate from that time on (F = 1.2, p greater than 0.41). The phosphate-supplemented diet significantly decreased systolic blood pressure in both strains. In phosphate-supplemented SHR, a significant decline in systolic blood pressure was observed from 20 weeks of age on (at 20 weeks of age: 222 +/- 3 mm Hg for control SHR vs 198 +/- 5 mm Hg for phosphate-supplemented SHR; p less than 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency dependence of cerebrovascular impedance in preterm neonates: a different view on critical closing pressure.

The nonproportional relationship between instantaneous arterial blood pressure (BP) and cerebral blood flow velocity (CBFv) is well explained by the concept of critical closing pressure (CCP). We aimed to determine the frequency response of the neonatal cerebrovascular system, and to establish the exact mathematical relationship between cerebrovascular impedance and CCP under physiologic conditions. In 10 preterm neonates (gestational age, 25-32 weeks; birth weight, 685-1,730 g; age 1-7 days) we Doppler-traced CBFv of the internal carotid artery. Blood pressure was traced simultaneously. Critical closing pressure was graphically determined. Cerebrovascular impedance was calculated as the square root of the ratio of the corresponding peaks in the power spectra of BP and CBFv at zero frequency, and at heart rate (H) and harmonics (xH). Uniformly, the impedance between H and 3H (2 to 6 Hz) was reduced about fivefold, compared with the impedance at zero frequency. The cerebrovascular system behaves like a high-pass filter, leading to a reduction of the DC (direct current) component of CBFv (analogous to current) relative to that of the driving force BP (analogous to voltage). The frequency response of cerebrovascular impedance reflects the ratio of CCP and DC BP. A mathematical derivation of this relationship is given matching the observed results. Thus, both the CCP and the impedance approach are valid.

Chemoreflexsensitivity in chronic heart failure patients.

AIMS: Patients with heart failure are characterised by a disturbed sympathovagal balance, as could be shown by analyses of heart rate variability and baroreflexsensitivity. Furthermore, the modulation of ventilation is disturbed in those patients with an increased ventilation volume following the inhalation of hypoxic gas. This study should evaluate, whether heart failure patients have a decreased hyperoxic chemoreflexsensitivity associated with an increased rate of ventricular arrhythmias. METHODS AND RESULTS: Into this study, 49 consecutive patients were enrolled. Of these, 23 suffered from heart failure; the remaining had no evidence of heart failure and a normal left ventricular ejection fraction. All patients were investigated by analysing the reduction of heart rate following inhalation of pure oxygen. The difference of RR-interval divided by the difference of the venous oxygen partial pressure both before and after oxygen inhalation resulted in the chemoreflexsensitivity. Patients with heart failure showed a significantly decreased chemoreflexsensitivity compared to those without (2.62+/-1.85 vs. 5.80+/-6.37 ms/mmHg, P<0.05). Of patients with heart failure, 69.6% had a decreased chemoreflexsensitivity below 3 ms/mmHg, in contrast to only 38.5% of the control group. Patients with decreased chemoreflexsensitivity showed significantly more non-sustained ventricular tachycardias (46 vs. 4%, P<0.05) during Holter ECG. CONCLUSION: Patients with heart failure show a significantly decreased hyperoxic chemoreflexsensitivity. A decreased chemoreflexsensitivity is associated with an increased rate of non-sustained ventricular tachycardias. This may be related to an increased sympathetic tone in these patients. The chemoreflexsensitivity may be important in arrhythmic risk stratification of patients with heart failure.

Critical closing pressure in preterm neonates: towards a comprehensive model of cerebral autoregulation.

In preterm neonates, intraventricular haemorrhage is linked to the dysfunction of cerebral autoregulation (AR). We aimed at tracing the critical closing pressure (CCP) in order to quantify AR and to reveal its inner workings. In an observational study, 10 preterm neonates (median, range: ga 28 weeks, 25 to 32 weeks; bw 1070, 685 to 1730 g; age 2d, 1 to 7 d) were continuously Doppler traced (a. carotis interna) for > 10 min. Systemic blood pressure (BP, a. umbilicalis, a. radialis, a. temporalis) was recorded simultaneously (> 1200 cardiac cycles each). Systolic BP was on average 11 mmHg above CCP. There was a striking parallel between both variables, even in cases of sudden spontaneous BP fluctuations > 30% (r = 0.72, 0.41 to 0.99), while systolic cerebral blood flow velocity remained largely unaffected (r = -0.15, -0.75 to 0.53), indicating a properly functioning AR. CCP was 28 mmHg, 14 to 38 mmHg. Based on our data, a physiological model of AR is developed, integrating anatomy, metabolic and neuronal pathways with former physiologic findings--including low frequency cycling of cerebral blood flow velocity. Tracing of CCP is thought to have the potential to identify infants with impaired AR. Since this method is noninvasive and independent of angle of insonation (thus rendering it uncritical in probe fixation), it is a promising tool for sustained monitoring of cerebral haemadynamics in the clinical setting.

Mechanical implications of humero-ulnar incongruity--finite element analysis and experiment.

Previous studies show that the humero-ulnar joint is physiologically incongruous [Eckstein et al. (1995a) Anat. Rec. 243, 318-326] and exhibits a bicentric (ventro-dorsal) distribution of subchondral mineralization [Eckstein et al. (1995b) J. Orthop. Res. 13, 286-278]. We therefore asked: (1) Does humero-ulnar incongruity bring about a bicentric distribution of contact pressure? (2) Do tensile stresses occur in the subchondral bone of the trochlear notch that are in the same order of magnitude as the compressive stresses? (3) Do ventral and dorsal maxima of subchondral bone density correlate with a bicentric distribution of strain energy density? To that end, a two-dimensional finite element model was designed. The shape and material properties of the bones were based on CT and the boundary conditions selected to agree with resisted elbow extension at 90 degrees of flexion. The incongruity and contact areas were determined experimentally from casts, and the pressure distribution with Fuji Prescale film. In the model and the experiment contact stresses above 2 MPa were recorded in the ventral and dorsal parts of the joint, and values below 0.5 MPa in the depth of the notch. In the model, tensile stresses of 2.9 MPa were observed in the subchondral bone of the ulna, but not in the humerus. The subchondral strain energy density yielded a bicentric pattern in a model with homogeneous subchondral bone properties. It is shown that humero-ulnar incongruity brings about a bicentric distribution of contact pressure, a tensile stress in the notch that is in the same order of magnitude as the compressive stress, and a distribution of strain energy density that correlates with subchondral density patterns.

A simple method to change geometrical proportions of muscles by means of a tibial lengthening osteotomy in the rat.

A method is designed to change geometrical proportions of muscles in the rat. After a tibial osteotomy, the application of a stainless steel prosthesis resulted in an elongation of about 8% of the tibia. In 23 out of 28 operated rats a correct application of the prosthesis was maintained till the rats were sacrificed. The operation caused hardly any muscle tissue damage. No disuse of the manipulated leg was observed in the operated rats.

The effects of alternative electrical and mechanical stunning methods on hemorrhaging and meat quality of broiler breast and thigh muscles.

Five trials were conducted to determine the effects of various alternative stunning and restraining methods on the quality of chicken broiler meat. The stunning methods used were electrical whole-body and head-only stunning with different voltages (25 vs 100 V) and frequencies (50 vs 200 Hz), and mechanical captive bolt stunning. Before being stunned, the broilers were restrained either by shackling them by the feet, restraining their heads while they were standing, or placing them in a cone. Convulsions during and after stunning were subjectively scored. At 1 d post-mortem, the pH, color, and the intensity and number of hemorrhages, of breast and thigh muscles were measured. Convulsions were, in order of increasing intensity, observed after whole-body stunning using 50 Hz, whole-body stunning using 200 Hz, head-only stunning, and captive bolt stunning. No differences in ultimate pH were measured. A consistent difference in color was observed between whole-body and head-only stunning. Head-only stunning resulted in darker and more red (P < or = 0.01) breast muscles. Head-only and captive bolt stunning resulted in hemorrhages that were located more distal in the breast muscle than those observed after whole-body stunning. Captive bolt stunning (in a cone) resulted in fewer (P < or = 0.01) hemorrhages in breast and thigh muscles than whole-body stunning (100 V, 50 Hz, shackled), and in a similar level of hemorrhaging as electrical head-only stunning (25 V, 200 Hz, in a cone).

The effects of captive bolt and electrical stunning, and restraining methods on broiler meat quality.

The effects of captive bolt stunning using air pressure, compared to electrical water bath stunning, on broiler carcass and meat quality were evaluated. The birds were shackled or placed in a cone. Two trials were conducted using a total of 160 female broilers. The four stunning-restraining treatments were whole-body electrical stunning (10 s, 110 mA, 300 Hz) in a water bath or air pressure stunning (0.5 s, 2 atm) while broilers were shackled by their feet or placed in a cone. Air pressure stunning caused a higher (P < 0.01) degree of convulsions and a lower (P < 0.01) degree of blood loss than electrical stunning, and reduced the prevalence of broken clavicles (P < 0.05) and coracoids (P < 0.01). Blood loss of shackled broilers was slightly higher (P < 0.05) than those restrained in a cone. Air pressure stunning resulted in significantly (P < 0.01) lower pH values and hemorrhaging in filets and thigh muscles than electrical stunning. The incidence of thigh muscle hemorrhaging was significantly (P < 0.01) reduced when broilers were restrained in a cone compared to being shackled. The stunning and restraining treatments did not result in differences in cooking losses. The filets from shackled birds were judged more tender than the filets from cone-restrained birds. With respect to the effect of stunning method, the filets of air pressure stunned birds was judged more tender than the meat from electrically stunned birds. Captive bolt stunning using air pressure has benefits over electrical stunning; however, a suitable stunning and restraining device remains to be developed.

Behavioral responses of broilers to different gaseous atmospheres.

This study was conducted to determine the differences in behavioral response of broilers when they come into contact for the first time with gas mixtures that can be used for stunning. The six test groups were divided into four experimental groups that were exposed to gas mixtures used for stunning and two control groups that were exposed to atmospheric air. The different gas mixtures and their concentrations were a) air, no flow (control-); b) circulating air, flowing (control+); c) >90% Ar in air; d) 60% CO2 in air; e) 40% CO2 and 30% O2 in air; and f) 70% Ar and 30% CO2 in air. The behavior of the broilers before entering the gas tunnel, the number of birds that moved into the gas mixture, and the behavior in the gas mixture were recorded on video and analyzed afterward. No differences among the groups were observed in the number of broilers that walked into the gas tunnel or in the number of birds that tried to return to the cage. Exposure of broilers to the 70% Ar and 30% CO2 mixture resulted in the fastest loss of posture. The number of broilers exhibiting headshaking and gasping was least in the >90% Ar in air mixture. Convulsions were rarely seen in the 40% CO2 and 30% O2 mixture; the other gas mixtures resulted in severe convulsions. The experiment did not indicate that broilers could detect or avoid increased CO2 or decreased O2 levels when they come into contact with such atmospheres for the first time.

Autonomic function is not associated with the incidence of type 2 diabetes in a high-risk population: the Hoorn study.

AIM: Impaired autonomic function is a complication of type 2 diabetes mellitus (DM2), but may also be involved in its development. For this reason, this study looked at the association of autonomic function with the incidence of DM2 in a homogeneous Caucasian population. METHODS: This Hoorn study was a prospective population-based study of individuals aged 50-75 years. For the 631 participants, the standard deviation of all normal-to-normal intervals (SDNN) and eight other parameters of autonomic function were calculated at baseline. Fasting and 2-h glucose were measured during follow-up by oral glucose tolerance test (OGTT). DM2 at baseline and follow-up was ascertained by questionnaire and OGTT. After excluding participants with DM2 at baseline, the association of parameters of autonomic function with incident diabetes was examined using logistic-regression analysis while adjusting for possible confounders. RESULTS: After excluding those with known (n=67) or newly diagnosed (n=126) DM2 at baseline and those missing follow-up data (n=140), 298 participants were eligible for the study (182 with normal glucose tolerance, 19 with impaired fasting glucose and 97 with impaired glucose tolerance). During a median follow-up of 9.2 (range 4.5-11.1) years, 94 incident cases of DM2 were observed. After adjusting for confounding variables, the DM2 odds ratio was 1.12 (95% CI: 0.77, 1.64) per SDNN increase. Results for other parameters of autonomic function were similar. CONCLUSION: The present study found no evidence of an association between autonomic function and DM2 incidence in a population at high risk of diabetes. This implies that previously observed associations between autonomic function and glucose metabolism in cross-sectional settings may reflect reverse causation.

Morphomechanics of the humero-ulnar joint: I. Joint space width and contact areas as a function of load and flexion angle.

BACKGROUND: Previous studies have shown that the trochlear notch is deeper than necessary for an exact fit with the humerus. However, humero-ulnar joint space width and contact areas have so far not been quantified for variations in the load and angle of flexion. METHODS: Six fresh cadaveric specimens were investigated at 30 degrees, 60 degrees, 90 degrees, and 120 degrees of flexion and at loads of 25 and 500 N, simulating resisted elbow extension. The joint space width and contact were determined, using polyether casting material. RESULTS: At 25 N all joints made contact in the ventral and dorsal aspects of the articular surfaces, whereas in the depth of the trochlear notch the joint space was on average between 0.3 and 2.8 mm wide, with some variation between individuals. At 500 N the joint space width was considerably reduced and the contract areas expanded towards the depth of the notch. The size of the dorsal contact areas was significantly smaller at 30 degrees and that of the ventral ones at 120 degrees, their ventro-dorsal ratio decreasing considerably from 30 degrees to 120 degrees (p < 0.01). CONCLUSION: These results indicate that the size of the contact areas depends to a slight extent on the joint position, but that at all loads and flexion angles a bicentric contact and an important central joint space width emerge because of the concave incongruity of the joint. These data may be used for numerical calculations, analysing the effects of incongruity on the joint stress and on the functional adaptation of the subarticular tissues.

Cross-spectral analysis of cerebral autoregulation dynamics in high risk preterm infants during the perinatal period.

In preterm infants intraventricular hemorrhage occurs predominantly within the perinatal period, which may be due to a "lost autoregulation" of cerebral blood flow (CBF). In this study, perinatal autoregulation dynamics were investigated in high risk preterm infants by cross-spectral analysis (CSA), which is a statistical tool in the analysis of time series. In 15 ventilated preterm infants of 25-32 gestational weeks, a total number of 30 records were made between 24 and 96 h of life. Doppler-derived CBF velocity (CBFv), used as a quantitative measure for CBF, and direct mean arterial blood pressure (MABP) were measured continuously for 10 min. The spectral power of low frequency (LF, 0.02-0.2 Hz) oscillations in CBFv and MABP was quantified by spectral analysis. From the results of CSA, a LF phase-shift between the CBFv and MABP LF oscillations was calculated in each record. Within the study group, the LF spectral power of CBFv and MABP was initially low and increased significantly until 96 h of life. The LF phase-shift was about 0 degrees at 24 h and increased significantly to 55 degrees at 96 h of life. The initially low LF spectral power of CBFv and MABP may indicate a perinatal depression of autonomic nervous centers, which are thought to control LF oscillations of vital parameters. In the light of a high pass filter model for autoregulation, the initially low LF phase-shift may indicate an initially impaired autoregulation, which supports the "lost autoregulation" hypothesis.

Changes in the somatosensory evoked potentials and spontaneous electroencephalogram of broiler chickens during exposure to gas mixtures.

1. Six week-old broiler chickens implanted with electroencephalogram (EEG) recording and somatosensory stimulating electrodes were exposed to either 90% argon in air, a mixture of 30% carbon dioxide and 60% argon in air or a mixture of 30% oxygen and 40% carbon dioxide (balance nitrogen) for 2 min, to determine the times to onset of changes in spontaneous EEG and the loss of somatosensory evoked potentials (SEPs) and thus unequivocal loss of consciousness. 2. In addition, after a 2 min exposure to the carbon dioxide-oxygen mixture, some broilers were allowed to recover in air and their EEGs and SEPs were continuously recorded until the return of normal EEG and SEPs. During this period, the time to return of response to comb pinching was also determined in 10 broilers. 3. All broilers exposed to either argon or the carbon dioxide-argon mixture died within 2 min, whereas, only 3 out of 17 broilers died during the 2 min exposure to the carbon dioxide-oxygen mixture. 4. During exposure to argon, unlike the other 2 gas mixtures, the majority of broilers showed high amplitude, low frequency electrical activity in the EEG on average at 10 s. The mean times to onset of EEG suppression were 17, 19 and 40 s after exposure to argon, the carbon dioxide-argon mixture and the carbon dioxide-oxygen mixture, respectively. An isoelectric EEG occurred on average at 58 and 41 s after exposure to argon and the carbon dioxide-argon mixture, respectively. An isoelectric EEG did not occur in broilers which were exposed to the carbon dioxide-oxygen mixture. 5. The SEPs were abolished in broilers on average 32 and 24 s after exposure to argon and the carbon dioxide-argon mixture, respectively. During exposure of broilers to the carbon dioxide-oxygen mixture the SEPs were abolished in the majority of birds on average at 47 s, however, 2 out of 14 birds retained their SEPs for the entire period of 2 min exposure to this gas mixture. 6. During the recovery after exposure to the carbon dioxide oxygen mixture, response to comb pinching and SEPs returned either at the time of, or soon after, the onset of high frequency electrical activity in the suppressed EEG of broilers. The mean times to return of response to comb pinching and SEPs were 52 and 43 s, respectively. 7. Based on the time to onset of EEG suppression or loss of SEPs, exposure of broilers to either 90% argon in air, or a mixture of 30% carbon dioxide and 60% argon in air, resulted in quicker loss of consciousness than during exposure to a mixture of 40% carbon dioxide, 30% oxygen and 30% nitrogen. The time to return of consciousness after a 2 min exposure to the carbon dioxide-oxygen mixture was also found to be rapid.

[Chemoreflex and baroreflex sensitivity in patients with survived sudden cardiac death]. / Chemoreflex- und Baroreflexsensitivität bei Patienten mit überlebtem plötzlichem Herztod.

INTRODUCTION: To evaluate patients with an increased risk of sudden cardiac death the analysis of ventricular late potentials, heart rate variability and baroreflexsensitivity is helpful. However, the prediction of malignant arrhythmic events cannot be performed with sufficient accuracy. For a better identification of high risk patients other methods are necessary. In this study the impact of the chemoreflexsensitivity for the prediction of ventricular tachyarrhythmias was investigated. METHODS: Out of 44 patients included in the study, 23 were survivors of sudden cardiac death (SCD). Seven patients suffered from sustained monomorphic ventricular tachycardias, 14 had no arrhythmic events in their prior history. For the investigation of the baroreflexsensitivity (BRS) systolic blood pressure was augmented by Norfenefrin (Novadral) and the resulting increase of RR-intervals was measured in the surface-ECG. For determination of the chemoreflexsensitivity (ChRS) the ratio of the RR-interval-shift and the blood pressure shift during a 5-min inhalation of oxygen with a nose mask was formed. RESULTS: Patients with aborted SCD showed significantly decreased values for the ChRS compared to those patients without an arrhythmic event in their prior history (2.49 +/- 1.86 vs. 6.75 +/- 6.79 mm Hg, p < 0.001). In contrast, for the BRS no significant differences could be found (5.23 +/- 3.95 vs. 5.34 +/- 3.10 mm Hg, p = n.s.). Patients with aborted sudden cardiac death and inducible tachyarrhythmias during the electrophysiologic study showed significantly lower values of BRS and ChRS compared to patients without inducibility. CONCLUSION: As a new method for identification of patients with an increased risk of sudden cardiac death the analysis of chemoreflexsensitivity seems feasible and indicates an increased arrhythmic risk with a high sensitivity. The predictive impact has to be corroborated in larger patient collectives by prospect studies.

Chemoreflexsensitivity in patients with survived sudden cardiac arrest and prior myocardial infarction.

For evaluation of patients with an increased risk of sudden cardiac death, the analyses of ventricular late potentials, heart rate variability, and baroreflexsensitivity are helpful. But so far, the prediction of a malignant arrhythmic event is not possible with sufficient accuracy. For a better risk stratification other methods are necessary. In this study the importance of the ChRS for the identification of patients at risk for ventricular tachyarrhythmic events should be investigated. Of 41 patients included in the study, 26 were survivors of sudden cardiac arrest. Fifteen patients were not resuscitated, of whom 6 patients had documented monomorphic ventricular tachycardia and 9 had no ventricular tachyarrhythmias in their prior history. All patients had a history of an old myocardial infarction (> 1 year ago). For determination of the ChRS the ratio between the difference of the RR intervals in the ECG and the venous pO2 before and after a 5-minute oxygen inhalation via a nose mask was measured (ms/mmHg). The 26 patients with survived sudden cardiac death showed a significantly decreased ChRS compared to those patients without a tachyarrhythmic event (1.74 +/- 1.02 vs 6.97 +/- 7.14 ms/mmHg, P < 0.0001). The sensitivity concerning a survived sudden cardiac death amounted to 88% for a ChRS below 3.0 ms/mmHg. During a 12-month follow-up period, the ChRS was significantly different between patients with and without an arrhythmic event (1.64 +/- 1.06 vs 4.82 +/- 5.83 ms/mmHg, P < 0.01). As a further method for evaluation of patients with increased risk of sudden cardiac death after myocardial infarction the analysis of ChRS seems to be suitable and predicts arrhythmias possibly more sensitive than other tests of neurovegetative imbalance. The predictive importance has to be examined by prospective investigations in larger patient populations.