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.

Low-dose atropine attenuates muscle sympathetic nerve activity in healthy humans.

Central muscarinic receptors play an important role in the regulation of cardiac vagal nerve activity. We studied the inhibition of central muscarinic receptors and sympathetic nerve function in humans, since very little information is currently available on this subject. We examined the effects of graded doses of atropine (five doses, range 0.001 to 0.016 mg/kg) on heart rate, arterial pressure, heart rate variability, and muscle sympathetic nerve activity in 13 healthy young volunteers. Atropine caused biphasic effects on heart rate and the high-frequency (HF) power of R-R interval variability. At lower doses (< or =0.002 mg/kg for heart rate, 0.001 mg/kg for HF power), atropine decreased heart rate and increased HF power. In contrast, at higher doses, atropine increased heart rate and decreased HF power. Low-dose atropine significantly attenuated muscle sympathetic nerve activity, burst rate (bursts/min) by -30.5 +/- 6.0% and burst incidence (bursts/100 heart beats) by -23.8 +/- 6.9% at 0.002 mg/kg. Systolic and diastolic arterial pressure did not change with atropine infusion. Low-dose atropine (< or =0.002 mg/kg) did not significantly affect either low frequency (LF) power or LF/HF. These results suggest that central muscarinic receptors may modulate not only cardiac vagal nerve activity but also sympathetic nerve activity in the skeletal muscle vasculature.

Two-dimensional guided M-mode color tissue Doppler echocardiography in artificial preexcitation models.

The purpose of this study was to analyze the left ventricular contraction patterns in artificial preexcitation models by using 2-dimensional guided M-mode color tissue Doppler echocardiography. Three types of preexcitation models were produced in 12 patients by right atrio-mitral annular sequential pacing, carried out at the left ventricular lateral, posterior, and posteroseptal walls. Tissue Doppler M-mode was recorded at anteroseptal, posterior, lateral, and posteroseptal sites in the parasternal short-axis view. The time interval from the onset of the QRS complex during sinus rhythm or from the annular pacing spike during fusion beats to the beginning of systolic motion was measured. During sinus rhythm, the time interval at the anteroseptal wall was shortest. During fusion beats, the time intervals at the mitral annular pacing sites were shortest. In preexcitation models, tissue Doppler M-mode could clearly distinguish the difference of left ventricular contraction patterns and detect the earliest contraction site of the left ventricle.

Influences of bilateral endoscopic transthoracic sympathicotomy on cardiac autonomic nervous activity.

OBJECTIVES: Endoscopic transthoracic sympathicotomy (ETS) is a minimal invasive procedure of thoracic sympathetic blockage. The purpose of this study was to evaluate cardiac autonomic nervous activity after ETS in order to confirm the reliability and safety of ETS. METHODS: A series of electrophysiological studies were performed before and 1 week after bilateral 2nd and 3rd thoracic sympathicotomy in 13 patients with primary palmar hyperhydrosis. Palmar perspiration was measured under sympathetic stress, and body surface mapping was recorded in a supine position. In the head-up tilt test of 0, 30, 60 and 90 degrees, corrected QT interval (QTc) and T wave amplitude (Twa) were assessed. The power spectral analysis of heart rate variability was processed to attain power values of the low-frequency (0.04-0.15 Hz), the high-frequency (0.15-0.40 Hz) and the low/high frequency ratio. RESULTS: In all patients, the perspiration response on the palm to sympathetic stimulation was completely inhibited after ETS. Isointegral mapping revealed that ETS altered electroactivity on the heart. In the head-up tilt study, R-R intervals significantly increased after the surgery in the head-up tilt positions (P < 0.05), although there was no significant difference in the supine position. There is no significant difference in QTc and Twa before and after the surgery, both in the supine and the head-up tilt positions. There was no significant difference in the LF or HF before and after surgery, either in the supine position or the head-up tilt positions. In the LF/HF, there was no significant difference before and after surgery in the supine position. However, the LF/HF in the head-up tilt positions was significantly decreased after surgery (P < 0.05). Sympathetic suppression of ETS was recognized more obviously under the steeper head-up tilt positions. CONCLUSIONS: The influences on the cardiac autonomic nerve system of the ETS of upper thoracic sympathetic nerve were seen to be of a lesser degree at rest. However, the response to sympathetic stimulation was suppressed after the surgery.

Detection of the earliest ventricular contraction site in patients with Wolff-Parkinson-White syndrome using two-dimensional guided M-mode tissue Doppler echocardiography.

OBJECTIVE: The purpose of this study was to examine the feasibility of M-mode tissue Doppler imaging for localizing the accessory pathway in patients with Wolff-Parkinson-White (WPW) syndrome. METHODS: Two-dimensional guided tissue Doppler M-mode was recorded at the mitral and tricuspid annular levels in 13 WPW patients. Time intervals were measured from the onset of the delta wave or the R wave to the beginning of the ventricular systolic motion. The earliest contraction site was defined as the site demonstrating the shortest time interval, and compared with the earliest activated site determined by body surface mapping and the successful ablation site. RESULTS: In 6 patients with a left-sided pathway, tissue Doppler localization was identical to the ablation site. In 3 with a left-sided pathway and 3 with a right-sided pathway, localization was judged as an adjacent region of the ablation site. In 1 patient with a right lateral pathway, the pathway location was misdiagnosed. The tissue Doppler diagnosis for the left-sided pathways correlated well with the ablation site, in contrast to the right-sided pathways (p = 0.05). Prediction of the accessory pathway localization by tissue Doppler M-mode was equivalent to localization based on body surface mapping. CONCLUSIONS: In WPW syndrome, tissue Doppler M-mode can detect the earliest contraction sites and seems helpful in localizing the left-sided accessory pathways, but is of limited use for right-sided pathways.

[Evaluation of enzyme-linked immunosorbent assay for antinuclear antibodies].

Antinuclear antibodies (ANAs) are clinically important indicators of collagen diseases. As corresponding antigens for ANAs vary considerably, patients with collagen diseases usually demonstrate several ANAs coincidentally, making difficult to detect the full spectrum of ANAs in each patient's serum. To design an efficient system for measuring ANAs, an enzyme-linked immunosorbent assay (ELISA) which adsorbs eight kinds of recombinant or purified antigens in each well of a multiwell plate was used and results were compared to those obtained with conventional assays by the fluorescent antinuclear antibodies (FANA), and double immunodiffusion (DID) methods. The positivity rates of 106 sera from patients with collagen diseases and 286 sera from healthy subjects were 92.5% and 5.5%, respectively. Sixty-one of 65 positive sera (93.8%) in the corresponding ANAs positive sera by DID or other conventional assay methods were positive by ELISA. Anti-SSA/Ro antibody could be detected with higher sensitivity by this assay method than with the FANA and DID method, but the sensitivities for anti-Scl-70 antibody and anti-centromere antibody were lower. Application of this ELISA method for measuring ANAs along with the FANA test may be beneficial for diagnosis of collagen diseases.

Bilateral coronary artery fistulas with multiple sites of drainage.

A 49-year-old woman presented with bilateral coronary fistulas with multiple sites of drainage. She had been referred to hospital for evaluation of a cardiac murmur, and a coronary arteriogram revealed multiple coronary fistulas. One fistula originated from the proximal part of the left anterior descending coronary artery and connected to the main pulmonary artery. Three coronary artery fistulas arised from a conal branch of the right coronary artery and drained into the main pulmonary artery, the right atrium and the great cardiac vein. This is the first reported case of bilateral coronary fistulas with multiple sites of drainage.

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, peripheral insulin activity [= 10(4)/(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 hyperglycemic 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.

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 Akaike's 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.

[Effect of adriamycin on cell cycle by bromodeoxyuridine-labeling method].

We studied the effect of adriamycin on DNA synthesizing cells from the view point of cell cycle. DNA synthesizing cells were marked by bromodeoxyuridine, which is a known marker for such cells, before administration of adriamycin. Then, the level of this marker was sequentially measured by flow cytometry. At the low concentration (0.01 micrograms/ml), adriamycin caused delay of the shifting time to the S phase 16 hours after administration. The marked cells were accumulated at the G2M phase at a moderate concentration (0.1 micrograms/ml), and blocked at the S phase at the higher concentration (1.0 micrograms/ml).

[Distribution of pancreatic arteries in the human fetus].

Pancreatic arteries were studied in 20 Japanese fetuses (7-8 months). The results were as follows: 1) Pancreatic arteries were originated from the common hepatic artery, the gastroduodenal artery, the splenic artery, and from the superior mesenteric artery. 2) The posterior pancreaticoduodenal arcade was seen in all cases, while the anterior pancreatico-duodenal arcade was not recognized in one case. The inferior pancreatic artery, the great pancreatic artery and the caudal pancreatic artery were found in 17 cases (85%), 14 cases (70%), and in all cases, respectively. 3) The origins of the dorsal pancreatic artery varied. It arose from the splenic artery in 8 cases (40%), the common hepatic artery in 1 case (5%), the superior mesenteric or jejunal artery in 3 cases (15%), and from a bifurcation point of the splenic and common hepatic arteries in 2 cases (10%). In 3 cases (15%), the dorsal pancreatic artery was formed as a communicating branch between the splenic artery and the superior mesenteric artery. 4) The main arterial supply for the pancreatic body and tail was from the celiac artery in 8 cases (40%), and from both the celiac and the superior mesenteric arteries in the other 12 cases (60%).

Intrahepatic territory of the accessory hepatic artery in the human.

The accessory hepatic artery was found in 12 human livers and its intrahepatic territory was investigated. The artery supplies an entire lobe or more without joining the usual hepatic artery in 93% of the cases. The accessory hepatic artery has an important significance for the arterial supply of the liver.