Motohisa Osaka

Potentiated Sympathetic Nervous and Renin-Angiotensin Systems Reduce Nonlinear Correlation Between Sympathetic Activity and Blood Pressure in Conscious Spontaneously Hypertensive Rats

Background—Patients with a reduced nonlinear component of heart rate regulation have a poorer outcome. Methods and Results—We investigated whether a nonlinear correlation between renal sympathetic nerve activity (RSNA) and blood pressure or renal blood flow is reduced in conscious, spontaneously hypertensive rats (SHR) by comparing them with normotensive Wistar-Kyoto rats (WKY). We also determined the linearity and nonlinearity of the correlation in SHR who were given an angiotensin II receptor blocker, candesartan, orally for 2 weeks. The RSNA value was higher in SHR than in WKY, and coherence peaks of transfer function were found at 0.05 and 0.80 Hz (ie, below respiratory- and cardiac-related fluctuations). The coherence (linearity) of the transfer function was significantly higher and gain was smaller in SHR than in WKY. Because mutual information values (linear and nonlinear correlation) were similar in both strains, we found the nonlinear correlation to be lower in SHR than in WKY. Time delay values calculated by the mutual information method demonstrated that RSNA preceded blood pressure and renal blood flow by 0.5 to 1.0 s. In SHR given candesartan, the RSNA value was lower, and the linearity was lower and nonlinearity higher than SHR given vehicle. Conclusions—Linear correlation between RSNA and blood pressure or renal blood flow was higher in SHR than in WKY, whereas the nonlinear correlation was lower. Oral treatment with candesartan increased the nonlinearity and reduced the linearity in SHR. Increased RSNA and the renin-angiotensin system may be responsible for the lower nonlinearity and higher linearity in hypertension.

Mutual information discloses relationship between hemodynamic variables in artificial heart-implanted dogs

A mutual information (MI) method for assessment of the relationship between hemodynamic variables was proposed and applied to the analysis of heart rate (HR), arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) in artificial heart-implanted dogs to quantify correlation between these parameters. MI measures the nonlinear as well as linear dependence of two variables. Simulation studies revealed that this MI technique furnishes mathematical features well suited to the investigation of nonlinear dynamics such as the cardiovascular system and can quantify a relationship between two parameters. To constitute a model free of the natural heart, two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses in acute canine experiments. RSNA was detected with the use of bipolar electrodes attached to the renal sympathetic nerve. Analysis of data during control revealed that correlation between HR and RSNA was higher than that between HR and BP and that between RSNA and BP ( P < 0.05). Although RSNA seemed to fluctuate noncorrelatedly with BP in higher pacing rates, the MI values between them disclosed their strong correlation. Surprisingly, correlation between RSNA and BP was stronger during a pacing rate of 60 beats/min than during higher pacing rates and control ( P < 0.05). It is suggested that the baroreflex system may be susceptible to pacing rates during the total artificial heart state. We calculated the time delay between HR and RSNA, between RSNA and BP, and between HR and BP by regarding a time delay at which the maximum MI value between each pair of parameters was given as a physiological delay. Our results indicate that RSNA leads BP, BP leads HR, and RSNA leads HR during control ( P < 0.05). We conclude that this method could provide a powerful means for measuring correlation of physiological variables.A mutual information (MI) method for assessment of the relationship between hemodynamic variables was proposed and applied to the analysis of heart rate (HR), arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) in artificial heart-implanted dogs to quantify correlation between these parameters. MI measures the nonlinear as well as linear dependence of two variables. Simulation studies revealed that this MI technique furnishes mathematical features well suited to the investigation of nonlinear dynamics such as the cardiovascular system and can quantify a relationship between two parameters. To constitute a model free of the natural heart, two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses in acute canine experiments. RSNA was detected with the use of bipolar electrodes attached to the renal sympathetic nerve. Analysis of data during control revealed that correlation between HR and RSNA was higher than that between HR and BP and that between RSNA and BP (P < 0.05). Although RSNA seemed to fluctuate noncorrelatedly with BP in higher pacing rates, the MI values between them disclosed their strong correlation. Surprisingly, correlation between RSNA and BP was stronger during a pacing rate of 60 beats/min than during higher pacing rates and control (P < 0. 05). It is suggested that the baroreflex system may be susceptible to pacing rates during the total artificial heart state. We calculated the time delay between HR and RSNA, between RSNA and BP, and between HR and BP by regarding a time delay at which the maximum MI value between each pair of parameters was given as a physiological delay. Our results indicate that RSNA leads BP, BP leads HR, and RSNA leads HR during control (P < 0.05). We conclude that this method could provide a powerful means for measuring correlation of physiological variables.

Primary biliary cirrhosis with fibrosing alveolitis

SummaryA 65-year-old case diagnosed as primary biliary cirrhosis without definite signs of Sjögren’s syndrome at age 62 developed interstitial lung disease, which was clinically, histologically, radiographically, and scintigraphically compatible with fibrosing alveolitis. Analysis of the cells in bronchoalveolar lavage fluid revealed, however, increased proportions of not only neutrophils but also lymphocytic cells, which were predominant. This case should focus attention on the association of primary biliary cirrhosis and fibrosing alveolitis.

Age-adjusted level of circulating elastin as a cardiovascular risk factor in medical check-up individuals

Aims The level of circulating soluble elastin (CSE) is reported to increase proportionally with the degree of clinical atherosclerosis; however, its diagnostic use is limited because CSE also increases with age. We aimed to investigate whether alterations in CSE concentrations are implicated in potential cardiovascular dysfunctions (indicated by standard physiological parameters) in medical check-up individuals, taking age into consideration. Methods In a total of 531 individuals (age 20–89 years), CSE levels were correlated most significantly with age. The groups of male and female individuals were each further divided into two subgroups: those with higher and those with lower CSE levels than the reference values determined by polynomial regression. Results Male participants with lower CSE levels (n = 128) than the age-adjusted reference baseline levels showed higher serum glucose (P < 0.008), uric acid (P < 0.008) and triglyceride (P < 0.02) levels than those with higher CSE levels (n = 126). However, most of the parameters tested in female participants with lower CSE levels (n = 140) were statistically comparable to those with higher CSE levels (n = 137). The ratio of CSE level to the age-adjusted reference level was calculated in each of the male participants, and declines in the ratio were significantly correlated with increases of serum glucose, uric acid and triglyceride levels (P < 0.005, P < 0.02 and P < 0.006, respectively). Conclusion The decrease in age-adjusted CSE levels is a potential indicator of eventual cardiovascular dysfunction in medical check-up individuals, as predicted by the risk factors dyslipidemia, hyperuricemia or diabetes.

Symbolic strings and spatial 1/ f spectra

Abstract Some string dynamics which are expected to show non-trivial correlations are proposed and studied. It is because we were motivated by the observation that some DNA sequences show spatial 1 f correlation. Our model is based on a rule by which one string is split into two parts in the middle and another string is inserted between them when the strings are made longer. The basic model shows long-range correlations with a structure characteristic of cyclic patterns on the log-log plot of the spectrum. The effects of string cross-over and point-mutation are also studied. The cross-over destroys the structures appearing in the basic model and makes 1 f - like correlation clear. The point-mutation makes the power spectrum flat as is expected from the white-noise nature. The analogy of the cross-over model with real DNA evolution dynamics is suggested.

A MODIFIED CHUA CIRCUIT SIMULATES 1/f-LIKE FLUCTUATION OF HEARTBEAT INTERVALS

The low-frequency portion of the power spectrum of human heartbeat intervals exhibits a 1/f-like scaling behavior. Despite its clinical significance, the mechanism remains unknown. By recording heartbeat intervals, renal sympathetic nerve activity (SNA), and blood pressure (BP) in conscious rats with normal or high BP, we reported that the scaling slope of heartbeat intervals is steeper in the rats with high BP, and that SNA leads to heartbeat interval and BP changes, and also the dynamics of these three variables, heartbeat intervals, BP, and SNA, results from a low-dimensional chaos. This hemodynamics is modeled excellently by modification of a known chaotic electrical circuit, Chua circuit. Increasing the resistive element between SNA and BP in the circuit increases the scaling slope and abolishes the low-dimensional chaos. Therefore, sensitivity of BP to sympathetic control is likely to determine the scaling slopes of heartbeat intervals in health and disease.

LOCAL BOX-COUNTING TO DETERMINE FRACTAL DIMENSION OF HIGH-ORDER CHAOS

To determine the attractor dimension of chaotic dynamics, the box-counting method has the difficulty in getting accurate estimates because the boxes are not weighted by their relative probabilities. We present a new method to minimize this difficulty. The local box-counting method can be quite effective in determining the attractor dimension of high-order chaos as well as low-order chaos.

A MODIFIED CHUA CIRCUIT SIMULATES A V-SHAPED TROUGH IN AUTONOMIC ACTIVITY AS A PRECURSOR OF SUDDEN CARDIAC DEATH

Recently we have reported that a previously unidentified V-trough of sympathetic nerve activity (SNA) is a potential precursor of lethal cardiac events by examining 24-hour ambulatory electrocardiograms in which such an event was recorded by chance. The V-trough was marked by three consecutive compartments: a small variation lasting two hours, an abrupt descent lasting 30 min and a sharp ascent for 40 min. We reported that the hemodynamics consisting of heart rate, SNA and blood pressure (BP) is modeled excellently by the modification of a known chaotic electrical circuit, Chua circuit. A V-trough of SNA appears by increasing the resistive element between SNA and BP in the circuit, which corresponds to the impaired regulation of BP by SNA. This finding is consistent with an acknowledged finding that the depressed baroreflex (reflex of BP by SNA) may trigger a lethal arrhythmia.

Reliability of Heart Rate Variability Analysis by Using Electrocardiogram Recorded Unrestrainedly from an Automobile Steering‐Wheel

Some cases of traffic accidents are assumed to be due to the occurrences of cardiac events during driving, which are thought to be induced by imbalance of autonomic nervous activities. These can be measured by analyzing heart rate variability. Therefore, we developed a new system of steering‐wheel electrocardiogram with a soft‐ware to remove noises. We compared the trends of sympathetic and parasympathetic nerve activities measured from the steering‐wheel electrocardiograms with those recorded simultaneously from chest leads. For each parameter of instantaneous heart rate, low‐ or high‐frequency component of heart rate variability in all the cases, the trend from the steering‐wheel electrocardiogram resembled that from the chest‐lead electrocardiogram. In 3 of 7 subjects, the trend of LF/HF showed a strong relationship between the steering‐wheel electrocardiogram and the chest‐lead electrocardiogram. Our system will open doors to a new strategy to keep a driver out of a risk by notifying it while driving.