Atsuhiro Shimakura

Spectral analysis of heart rate, arterial pressure, and muscle sympathetic nerve activity in normal humans

We investigated the frequency components of fluctuations in heart rate, arterial pressure, respiration, and muscle sympathetic nerve activity (MSNA) in 11 healthy women using an autoregressive model and examined the relation among variables using Akaikes relative power contribution analysis with multivariate autoregressive model fitting. Power spectral analysis of MSNA revealed two peaks, with low-frequency (LF) and high-frequency (HF) components. The LF component of MSNA was a major determinant of the LF component of arterial pressure and R-R interval variability (0.70 +/- 0.07 and 0.18 +/- 0.05, respectively). The effect of the LF component of MSNA on arterial pressure showed no change in response to propranolol but was diminished (0.35 +/- 0.08) by phentolamine (P < 0.02). The effect of the LF component of MSNA on R-R interval was not altered by pharmacological sympathetic nerve blockade. The HF component of MSNA did not influence other variables but was influenced by R-R interval, arterial pressure, and respiration. These findings indicate that the LF component of MSNA reflects autonomic oscillations, whereas the HF component is passive and influenced by other cardiovascular variables.

Primary Antiphospholipid Syndrome and Pulmonary Hypertension with Prolonged Survival A Case Report

The outcome of patients with pulmonary hypertension (PHT) and antiphospholipid syndrome (APS) is usually fatal. The authors report the rare case of a patient with primary APS and nonthrombotic PHT who has survived for twenty years after the onset of PHT. In this case, the patients PHT resembled the primary idiopathic variety with clear lung fields and normal perfusion on the lung scan, and the combination therapy with nitrate, digoxin, and diuretics had been performed. During her clinical course over twenty years, she had not experienced any critical pulmonary thrombosis that influenced the progression of nonthrombotic PHT or any other severe systemic involvement of APS.

Compensatory Enlargement of Angiographically Normal Coronary Segments in Patients with Coronary Artery Disease In Vivo Documentation Using Intravascular Ultrasound

Intravascular ultrasound (IVUS) frequently reveals plaque formation at sites with a normal angiographic appearance. However, whether angiographically normal coronary arteries undergo adaptive expansion in vivo remains uncertain. The authors studied 12 patients (11 men, 1 woman; mean age fifty-three ± ten years [mean ± SD]) with focal coronary stenosis. Sixty IVUS images from angiographically normal coronary segments were analyzed (14 left main, 44 left anterior descending, and 2 left circumflex coronary arteries). The mean percent area stenosis was 36 ± 5% and the circular shape factor of the lumen cross section averaged 0.97 ± 0.02. Both total arterial area and internal elastic lamina area increased as the plaque area expanded (y = 2.13x + 8.07, r = 0.87, P = 0.0001; y = 2.06x + 4.57, r = 0.87, P = 0.0001, respectively), suggesting that for every 1 mm2 increase in plaque area, the total arterial area increased by approximately 2.13 mm2 and the internal elastic lamina area increased by approximately 2.06 mm2. The lumen area also increased as the plaque area expanded (y = 1.06x + 4.57, r = 0.68, P = 0.0001), suggesting that for every 1 mm2 increase in plaque area, the lumen area increased by approximately 1.06 mm2. The medial area did not correlate with the plaque area (r = 0.15, P = 0.26). Thus, compensatory enlargement precedes development of angiographically detectable coronary atherosclerosis. Furthermore, in early stages of atherosclerosis, arterial enlargement may overcompensate for plaque area. The reduction of the total medial mass does not appear to contribute to the mechanism of compen satory enlargement.

Percutaneous transluminal mitral valvuloplasty improves cardiopulmonary baroreflex sensitivity in patients with mitral stenosis

Patients with heart failure frequently have increased sympathetic tone, which could result in part from impairment of the inhibitory influence of cardiopulmonary baroreflexes. Percutaneous transluminal mitral valvuloplasty (PTMV) provides a unique model for evaluating functional changes in cardiopulmonary baroreflexes without open-heart surgical manipulation. We examined the effects of PTMV on cardiopulmonary baroreflexes and sympathetic nerve activity in 10 patients with mitral stenosis. We measured muscle sympathetic nerve activity using microneurography. Cardiopulmonary baroreflex provocation was performed by applying a lower body negative pressure of -10 mm Hg, and its sensitivity was determined by dividing the percent change in muscle sympathetic nerve activity by the change in central venous pressure. Response to isometric exercise was assessed by handgrip at 30% of maximal voluntary contraction for 3 min. PTMV significantly increased mitral valve area and cardiac index and decreased mean left atrial pressure. PTMV significantly decreased burst rate from 25.1+/-2.5 to 15.6+/-2.6 bursts/min (p < 0.01) and burst incidence from 37.1+/-3.7 to 23.6+/-3.3 bursts/100 heart beats (p < 0.01). After PTMV, cardiopulmonary baroreflex sensitivities measured using burst rate and burst incidence were -39.9+/-4.9%/mm Hg and -38.7+/-6.2%/mm Hg, respectively, which were significantly steeper than those before PTMV (-9.2+/-1.1%/mm Hg and -8.4+/-1.1%/mm Hg; p < 0.01). There were significant correlations between muscle sympathetic nerve activity at rest and cardiopulmonary baroreflex sensitivity. PTMV did not affect muscle sympathetic responses to handgrip exercise. These results suggest that patients with mitral stenosis have baseline sympathetic nerve activation, which could result in part from impaired cardiopulmonary baroreflexes.

Enhanced insulin response to oral glucose load in patients with angina pectoris associated with ST segment elevation in the absence of epicardial coronary arterial obstruction.

The authors treated 10 patients with microvascular angina (MVA) manifesting angina pectoris, ST segment elevation suggestive of transmural myocardial ischemia, and no epicardial arterial obstruction. Since such patients frequently showed abnormal responses to oral glucose loading, the authors investigated the glucose and insulin responses to glucose loading in 10 MVA patients, 25 patients with vasospastic angina (VAP), 25 patients with effort angina (EAP), and 25 control subjects. Insulinogenic index, periph eral insulin activity [=104/(peak glucose x insulin at glucose peak)], glucose area, and insulin area were calculated. The MVA group included two patients with impaired glucose tolerance and two newly diagnosed diabetic patients. These proportions were similar to those in the VAP and EAP groups. Glucose levels at 30 to 180 min and insulin levels at 90 to 120 min in the MVA group were higher than in the control group. Peak glucose, glucose area, peak insulin, and insulin area were higher in the MVA group than in the control group (p<0.01).Those in the VAP and EAP groups were also higher. Insulin/glucose ratio at 120 min was higher, peripheral insulin activity, lower, in the disease groups than in the control group (p<0.05).The MVA patients showed a hyper glycemic and hyperinsulinemic response to oral glucose loading, as did the patients with EAP and VAP. Enhanced insulin response to oral glucose loading may also contribute to the pathogenesis of MVA.

Non-Invasive Measurement of Arterial Stiffness Using the Analysis ofOscillometric Waveform during Cuff-Inflation

Background We developed the new method which is measured arterial stiffness simultaneously with blood pressure by oscillometry during cuff inflation, and evaluated usefulness of the index as a marker of cardiovascular disease. Methods The cuff pressure pulse waves during linear cuff inflation were extracted by blood pressure measurement device in 97 outpatients with hypertension. The paired values of the cumulatively added cuff oscillation amplitudes and the corresponding cuff pressures are stored in the device during the measurement. Each of the cumulative addition value was exchanged to the ratio of total addition, and the cuff pressures, P0 and P1, corresponding to the ratios, R0 and R1, respectively, were used for calculation of the Cuff-Oscillometric Stiffness Parameter (CSP) which was defined as ln (P1/P0) / (R1/R0-1). Furthermore, we calculated the Modified Cuff-Oscillometric Stiffness Parameter (MCSP) using CSP, age, height and weight. We also measured Cardio-Ankle Vascular Stiffness Index (CAVI), the carotid Intima-Media Thickness (IMT), blood chemistry, and Framingham Risk Score (FRS) for coronary heart disease. Results CSP was significantly correlated with CAVI(r= 0.608, p <0.0001). There were significant correlated with IMT, FRS. MCSP was closely correlated with CAVI(r= 0.803, p <0.0001). In addition, CSP, MCSP, and CAVI were associated with blood components as markers of diabetes. Conclusions These results suggest that our new method is useful for the screening arteriosclerosis-related disease, and helpful for health care management in home because of easy to use, low cost, and short time measuring.

Effect of pimobendan on cardiopulmonary baroreflex control of sympathetic nerve activity in healthy young men.

In order to determine the effect of pimobendan on sympathetic nerve activity and cardiopulmonary baroreflex (CPB), electrocardiogram, direct arterial pressure, central venous pressure (CVP) and cardiac output were recorded along with muscle sympathetic nerve activity (MSNA) in 8 healthy young men. CPB function was evaluated before and 60 min after oral administration of 5 mg pimobendan using the response of MSNA to lower body negative pressure (LBNP) of -5 and -10 mm Hg. The same protocol also was performed during handgrip exercise. Cardiac index, MSNA increased and CVP decreased significantly (p<0.01, respectively), but arterial pressure and heart rate unchanged after pimobendan administration. During LBNP, CVP decreased and MSNA increased significantly. CPB sensitivity was augmented from 5.53+/-0.75 to 8.59+/-0.78 burst incidence/mm Hg after pimobendan administration (p<0.01). Pimobendan did not alter the percentage increase of MSNA during handgrip exercise. In conclusion, pimobendan induces an increase in basal sympathetic nerve activity by decreasing CVP and augmenting CPB sensitivity without changing arterial pressure in healthy young men.