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Background Sodium‐glucose cotransporter 2 inhibitors improve cardiovascular outcomes in patients with diabetes with and without heart failure (HF). However, their influence on sympathetic nerve activity (SNA) remains unclear. The purpose of this study was to evaluate the effect of sodium‐glucose cotransporter 2 inhibitors on SNA and compare the responses of SNA to sodium‐glucose cotransporter 2 inhibitors in patients with type 2 diabetes with and without HF. Methods and Results Eighteen patients with type 2 diabetes, 10 with HF (65.4±3.68 years) and 8 without HF (63.3±3.62 years), were included. Muscle SNA (MSNA), heart rate, and blood pressure were recorded before and 12 weeks after administration of dapagliflozin (5 mg/day). Sympathetic and cardiovagal baroreflex sensitivity were simultaneously calculated. Brain natriuretic peptide level increased significantly at baseline in patients with HF than those without HF, while MSNA, blood pressure, and hemoglobin A1c did not differ between the 2 groups. Fasting blood glucose and homeostatic model assessment of insulin resistance did not change in either group after administering dapagliflozin. MSNA decreased significantly in both groups. However, the reduction in MSNA was significantly higher in patients with HF than patients with non‐HF (−20.2±3.46 versus −9.38±3.65 bursts/100 heartbeats; P =0.049), which was concordant with the decrease in brain natriuretic peptide. Conclusions Dapagliflozin significantly decreased MSNA in patients with type 2 diabetes regardless of its blood glucose‐lowering effect. Moreover, the reduction in MSNA was more prominent in patients with HF than in patients with non‐HF. These results indicate that the cardioprotective effects of sodium‐glucose cotransporter 2 inhibitors may, in part, be attributed to improved SNA.

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is associated with augmented sympathetic nerve activity and cardiovascular diseases. However, the interaction between coronary artery plaque characteristics and sympathetic nerve activity remains unclear. The purpose of this study was to clarify the relationships between coronary artery plaque characteristics, sleep parameters and single- and multi-unit muscle sympathetic nerve activity (MSNA) in OSAS patients. Methods and Results: A total of 32 OSAS patients who underwent full-polysomnography participated in this study. The coronary plaque volume was calculated with 320-slice coronary computed tomography (CT). Single- and multi-unit MSNA were obtained during the daytime within 1 week from full-polysomnography. Patients were divided into 2 groups according to their apnea-hypopnea index (AHI) score (mild-moderate group, AHI

Objective We aimed to identify obstructive sleep apnea syndrome (OSAS) severity indices reflecting the anthropometric and metabolic characteristics of patients with OSAS. Methods A total of 76 patients with OSAS underwent nasal continuous positive airway pressure (nCPAP). We also investigated the effects of nCPAP on OSAS-associated muscle sympathetic nerve activity (MSNA), risk for cardiovascular diseases, and insulin secretion and sensitivity. Results Among the OSAS severity indices, HbA1c was significantly correlated with the apnea-hypopnea index, whereas HOMA-beta, HOMA-IR, and hepatic insulin resistance were significantly correlated with % SpO2

Background: Intestinal angina is characterized by recurrent postprandial abdominal pain and anorexia. Commonly, these symptoms are caused by severe stenosis of at least two vessels among the celiac and mesenteric arteries. However, intestinal perfusion is affected not only by the degree of arterial stenosis but also by systemic perfusion. We experienced a unique case of intestinal angina caused by relatively mild stenosis of the abdominal arteries complicated with hypertrophic obstructive cardiomyopathy. Case presentation: We report an 86-year old Japanese man with hypertrophic obstructive cardiomyopathy and advanced atrioventricular block who was diagnosed with intestinal angina. Computed tomography showed mild stenosis of the celiac artery and severe stenosis of the inferior mesenteric artery, and these lesions were relatively mild compared with other reports. A dual-chamber pacemaker with right ventricular apical pacing was implanted to improve the obstruction of the left ventricular outflow tract. After implantation, the patient's abdominal symptoms diminished markedly, and improvement of the left ventricular outflow tract obstruction was observed. Conclusions: Although intestinal angina is generally defined by severe stenosis of at least two vessels among the celiac and mesenteric arteries, the present case suggests that hemodynamic changes can greatly affect intestinal perfusion and induce intestinal angina in the presence of mild stenosis of the celiac and mesenteric arteries. © 2016 The Author(s).

IntroductionFamilial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data—and in particular multicentre data—exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds.Methods and analysisThe Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies.Ethics and disseminationThis study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.Trial registration numberUMIN000038210.

OBJECTIVE Calcium channel blockers (CCBs) are used as antihypertensive agents and have a strong vasodilatory effect; however, the sympathetic activation mediated by baroreflex might cause adverse effects. A recently developed CCB, azelnidipine, decreases the heart rate (HR) while lowering blood pressure (BP), possibly by inhibiting sympathetic nerve activity in animal models. In this study, we evaluated whether azelnidipine inhibited sympathetic nerve activity, compared to amlodipine, in primary hypertensive patients. DESIGN AND METHODS We conducted a prospective, randomized, open-label, and crossover study of 14 patients. We measured the patients' BP, HR and baroreflex sensitivity, and directly recorded muscle sympathetic nerve activity (MSNA), via microneurography, after treatment with either CCB for 8 weeks. RESULTS Although systolic and diastolic BPs did not differ between the azelnidipine and amlodipine groups, the HR in the azelnidipine group significantly decreased compared with that in the amlodipine group. MSNA was significantly reduced in the azelnidipine compared with the amlodipine group (47.7 ± 14.9 vs. 61.5 ± 10.7 bursts per 100 beats, P

Background It has been reported that sympathetic nerve activity (SNA) is associated with fibrinolysis, but the interaction between SNA and the fibrinolytic system with aging has not been elucidated in humans. The purpose of this study was to examine the effect of age-related SNA on the activity of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) using muscle SNA (MSNA). Methods and Results This study included 16 young subjects (mean age 26.1 years) and 10 aged subjects (mean age 56.9 years). Lower body negative pressure (LBNP) was performed at -40 mmHg for 30 min. LBNP significantly increased both tPA and PAI-1 activity (from 5.2±0.5 to 7.3±1.2 IU/ml and from 2.85±0.68 to 4.06±0.73 U/ml, p

It has been shown that cigarette smoking increases blood pressure (BP) and heart rate (HR), and decreases muscle sympathetic nerve activity (MSNA) in healthy young smokers. The decrease in MSNA might be secondary to baroreflex responses to the pressor effect. We tested the hypothesis that cigarette smoking increases MSNA in smokers with impaired baroreflex function. The effects of cigarette smoking on BP, HR, forearm blood flow (FBF), forearm vascular resistance (FVR), and MSNA were examined in 14 patients with stable effort angina (59 ± 3 years, group CAD) and 10 healthy smokers (23 ± 1 years, group C). In group CAD, the arterial baroreflex sensitivity (BRS) was significantly lower than in group C (4.7 ± 0.8 versus 15.1 ± 2.2 msec/mmHg, P < 0.01). In both groups, cigarette smoking increased the plasma concentration of nicotine, systolic and diastolic BP, HR, and FVR significantly (P < 0.01), but decreased FBF significantly (P < 0.01). After smoking, MSNA was decreased significantly in group C (from 35.2 ± 3.5 to 23.5 ± 3.2 bursts/100 beats, P < 0.01), but increased significantly in group CAD (from 48.8 ± 5.4 to 57.3 ± 5.5 bursts/100 beats, P < 0.01). There was significant correlation between BRS and changes in MSNA (r = -0.62, P < 0.01). Cigarette smoking increased MSNA in smokers with impaired baroreflex function. This demonstrates that cigarette smoking stimulates sympathetic nerve activity by both a direct peripheral effect and a centrally mediated effect.

Background The number of the elderly patients with atrial fibrillation (AF) is increasing, but the current status of anticoagulation therapy for elderly patients with AF in Japan is not clear. Methods and Results Among the patients registered in the "Hokuriku Atrial Fibrillation Trial (HAT) 1", 365 AF patients aged ≥65 years were enrolled in this study. Warfarin was used for significantly less patients in the oldest group aged ≥85 years (36%) than in younger populations, but the percentage of antiplatelet use in this oldest population was largest (40%). The elderly group (≥85 years) was compared with a younger group aged between 75 and 84 years. Warfarin was given to 61% of the younger group compared with 36% in the elderly group. In the younger group, the more thromboembolic risks they had according to CHADS2 score, the more warfarin was used, whereas there was no clear trend in the usage of warfarin in the elderly group. Conclusions The number of elderly Japanese patients with AF taking warfarin is currently low, but because the population of elderly AF patients will increase in the future, there is a need for safe and suitable anticoagulation therapy for elderly patients. (Circ J 2008; 72: 2058 - 2061)

Diabetes-Related AF. Introduction: Diabetes mellitus is one of the significant independent risk factors for the development of atrial fibrillation (AF). However, the pathophysiological mechanisms of the relationship have not been fully elucidated. Methods and Results: The genetic type II diabetes (GK) rats and their original (Wistar) ones were subjected to electrophysiological (n = 8 per group) and histological (n = 7 per group) studies. At 40 weeks old, when GK rats had significantly (P < 0.01) more increased plasma glucose and HbA 1c values than Wistar rats, atrial electrical stimuli in the isolated-perfused hearts induced significantly greater number of repetitive atrial responses in GK rats than in Wistar rats (47.9 ± 17.5 vs 3.1 ± 1.3 beats, respectively, P < 0.01). GK rats showed significantly longer intra-atrial activation time than Wistar rats (18.3 ± 0.4 ms vs 15.9 ± 0.5 ms, P < 0.01) without any significant difference in the atrial refractoriness. The histological examination revealed significantly increased diffuse fibrotic deposition in GK rats atria compared with Wistar ones (P < 0.01). Conclusion: The present diabetic GK rat showed increased atrial arrhythmogenicity with intra-atrial conduction disturbance, and thus indicated that the structural remodeling of atrium characterized by diffuse interstitial fibrosis would be a major substrate for diabetes-related AF.

Brugada Syndrome and Sodium Channel Blockade. Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel a subunit, which can lead ventricular fibrillation and sudden death. Inattentive use of antiarrhythmic drugs potentially triggers fatal cardiac arrhythmias through further reduction of sodium current (I N a ). We studied the molecular mechanism underlying a case of Brugada syndrome that showed no response to a class Ic antiarrhythmic drug. Molecular genetic studies of a patient with Brugada syndrome identified a novel mutation in SCN5A, which causes substitution of serine for asparagine (N406S) in S6 of domain I (IS6). The provocation test with pilsicainide, a class Ic antiarrhythmic drug, failed to exacerbate ST-segment elevation in this case. Electrophysiological analyses of the N406S-mutant channel expressed together with the β1 subunit in HEK293 cells showed that the voltage dependence of activation was positively shifted by 16 mV and that intermediate inactivation was enhanced. Whereas tonic block by pilsicainide was not changed in the N406S channel, use-dependent block by pilsicainide was almost completely abolished, consistent with the clinical findings of the negative provocation test. In contrast, the N406S channel showed stronger use-dependent block by quinidine than the wild-type channel. We demonstrate a novel Brugada mutation N406S, which is associated with the discordant effects on blocking actions of antiarrhythmic drugs as well as the multiple channel gating defects. We emphasis that an antiarrhythmic drug may exert unpredicted effects in patients with channel mutations.

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.

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 δ 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.

The hypothesis that a coronary vasomotion disorder may exist in the entire coronary artery tree in patients with vasospastic angina was investigated by examining the coronary responses to atrial pacing (130 beats/min) before and after the administration of ergonovine (16 micrograms) into nonspastic coronary arteries. Seven patients with angiographically normal coronary arteries and focal spasm in the right coronary artery and 7 control patients with atypical chest pain and angiographically normal coronary arteries without spasm were studied. Great cardiac vein flow (GCVF) and left anterior descending coronary artery diameters (CDs) were measured by the thermodilution method and quantitative arteriography, respectively. Although the CDs before ergonovine were similar in the 2 groups, the pacing-induced increased in GCVF before ergonovine administration was smaller in patients with vasospastic angina than in control patients (22 +/- 4% vs 49 +/- 11%, respectively; p0.05). After ergonovine administration, pacing both increased GCVF and decreased anterior regional coronary resistance (ACR) to a lesser extent in patients with vasospastic angina than in control patients (GCVF, 16 +/- 4% vs 47 +/- 8%, respectively [p0.01]; ACR, -12 +/- 3% vs -29 +/- 3%, respectively [p0.01]). The decreases in CDs in patients with vasospastic angina observed after ergonovine administration were greater than those in control patients (-18 +/- 2% vs -9 +/- 2%, respectively; p0.05). Thus, not only epicardial, but also resistance coronary arteries are affected by the coronary vasomotion disorder in the nonspastic vascular bed in patients with vasospastic angina.

Two cases are presented in which angina pectoris associated with ST segment elevation occurred during either an ergonovine provocation test or coronary angioplasty, despite the absence of epicardial coronary artery obstruction. In both cases, no epicardial coronary spasm, thromboembolic occlusion, coronary air embolus, vessel dissection, or side-branch occlusion was observed. These findings suggest that transmural myocardial ischemia without epicardial coronary artery obstruction can occur owing to abnormalities of the coronary microcirculation. Microvascular vasoconstriction leading to transmural myocardial ischemia may be induced by ergonovine or by the release of potent vasocon strictors from disrupted coronary lesions during angioplasty.

A 25-year-old woman was admitted because of acute myocarditis. Echocardiogram revealed hypokinesis of the left ventricle with increased wall thickness, but on day 7, the wall motion normalized. Cyclic variation of myocardial integrated backscatter on day 1 was reduced to 1.8 dB (normal range, 2.9-5.3 dB) and normalized to 3.2 dB on day 3. The normalization of the cyclic variation of integrated backscatter in the myocardium preceded the recovery of the left ventricular wall contractility, suggesting the ability of tissue characterization to predict recovery of cardiac function. (Circ J 2002; 66: 416 - 418)

The arterial pressure (AP) response to hemodialysis was studied with echocardiography and strain gauge plethysmography in 17 patients with end-stage renal disease; mean AP was unchanged in seven (group A) and was reduced by more than 10 mm Hg in 10 patients (group B). Following dialysis, body weight decreased and heart rate increased equally in both groups. Ejection fraction did not change in the two groups. Left ventricular end-diastolic volume fell by 13 +/- 10% in group A and by 24 +/- 16% in group B. Cardiac index (CI) fell in group B, but remained unchanged in group A. Systemic vascular resistance (SVR) did not change in both groups. The change in mean AP before and after dialysis was significantly correlated with that in Cl (r = 0.49, p less than 0.05), but not with that in SVR. Calf venous pressure-volume curves were not different between the two groups before dialysis. Hemodialysis shifted the curve toward the volume axis for group B but not for group A. These results suggest that hypotension following dialysis is mainly due to the fall in cardiac output, in which increases in venous distensibility play an important role.

The aim of this study was to: (1) evaluate atrial electromechanical coupling using M-mode Doppler tissue; and (2) test its clinical impact for detecting atrial abnormalities in paroxysmal atrial fibrillation (AF). Using Doppler tissue, the time intervals from the onset of P wave until the backward motions of the right and left atrioventricular rings in the apical 4-chamber view corresponding to the atrial contractions were measured. In paroxysmal AF group, these intervals were significantly longer than in the control group. Using the criteria that an abnormal time interval from the onset of P wave until the backward motion of the left atrioventricular ring is longer than 112 milliseconds, the sensitivity, the specificity, and the positive predictive values for paroxysmal AF are 73%, 93%, and 93%, respectively. This parameter is affected in patients with paroxysmal AF and should be useful for detecting atrial impairment related to paroxysmal AF.

Cardiovascular disease is a major cause of mortality and morbidity in patients with acromegaly. We describe the case of a 43-year-old man with acromegaly who presented with severe congestive heart failure. Treatment with the somatostatin analog octreotide improved cardiac function with an increase in left ventricular ejection fraction (LVEF) from 11% to 27%. LVEF further increased to 43% after trans-sphenoidal surgery. Recovery was uneventful. We emphasize the need for early diagnosis and effective treatment of acromegaly to prevent cardiovascular complications. Octreotide therapy or trans-sphenoidal surgery, if possible, should be considered to control cardiac function even in acromegalic patients with severe congestive heart failure.

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.

A 38-year-old male myotonic dystrophy patient with left hemiblock, bradycardia and ventricular arrhythmias underwent electrophysiologic studies 19 months after he developed dizziness. Rapid and significant progression of binodal disease required implantation of a permanent pacemaker, which responded favorably. We suggest that careful monitoring or electrophysiologic studies are indicated in patients with these findings.

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. (Jpn Circ J 1998; 62: 783 - 784)

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

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

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.

The effects of insulin on vasoconstrictor response were studied in diabetics without autonomic neuropathy. Vasoconstrictor response to phenylephrine was measured before and after insulin injection in 10 diabetics. Mean blood pressure, forearm blood flow, and forearm vascular resistance remained unchanged after insulin administration. But the increase in forearm vascular resistance to phenylephrine decreased significantly and heart rate increased significantly after insulin injection. In 9 diabetics, vasoconstrictor response to tilting was measured before and after insulin injection. Mean blood pressure, cardiac index, and the total peripheral resistance index remained unchanged after insulin administration. However, the increase in the total peripheral resistance index to tilting decreased significantly and heart rate increased significantly after insulin injection. Furthermore, a significant fall in mean blood pressure following tilting was observed only after insulin administration. Although blood glucose levels decreased significantly, no hypoglycemic symptoms occurred. The present study suggests that insulin inhibits vasoconstrictor responses to both alpha agonist and tilting in diabetics.

房室結節二重伝導路を有する45例を対象とし, 心房早期刺激試験 (AEST) により房室結節回帰性頻拍 (AVNRT) の誘発されたA群 (13例) , 単発の房室結節回帰性心房エコー (Ae) の誘発されたB群 (6例) およびAeあるいはAVNRTのいずれも誘発されなかったC群 (26例) に分類した。AESTによりAeあるいはAVNRTが誘発されるためには, 良好な逆行性室房伝導を有する必要があり, A群とB群は全例最短1対1室房伝導周期は460 msec以下であった。一方, 最短1対1室房伝導周期が460 msec以下を示したC群26例中4例においては, AESTによる順行性房室伝導時間の延長が軽度であったためAeは誘発されなかった。頻拍が持続するためには, 良好な逆行性室房伝導能に加えて順行性房室伝導能も良好である必要があり, A群13例は全例最短1対1房室伝導周期は420 msec以下を示した。

心房細動の心室応答におよぼす房室結節二重伝導路 (DAVNP) の影響について検討した。心房早期刺激試験により房室伝導曲線が不連続曲線を示す7例をA群, 連続曲線を示す7例をB群とし, 2群間で房室結節の電気生理学的特性と心房細動時の心室応答様式を比較した。房室結節の有効・機能的不応期および1対1に房室伝導する最短心房刺激周期 (SCL1-1) は, いずれも2群間で差を認めなかった。心房細動時の最短R-R間隔 (SR-R) , 平均心室周期 (MVCL) およびR-R間隔の分布様式は, いずれも2群間で差を認めなかった。SR-RとMVCLは, いずれもSCL1-1との間で有意の正相関を示し, DAVNPの有無にかかわらずいずれも房室結節のfast pathwayの有効・機能的不応期との間で有意の正相関を示した。今回の検討では, 心房細動の心室応答におよぼすDAVNPの特異的な役割を明らかにすることはできなかった。

1. We studied the effects of aging on the variability of blood pressure in mild to moderate essential hypertensive subjects. 2. Cardiac index was greater and total peripheral resistance index was less in patients under 40 years (by an average of 1.06 litres min−1 m−2 and 9.23 mmHg 1−1 min−1 m−2) than in those over 40 respectively (P < 0.001 for each). 3. Pulse pressure/stroke volume was less by an average of 0.345 mmHg/ml in patients under 40 years than that in those over 40 (P < 0.001). Pulse pressure/stroke volume was correlated with age (r = 0.621), average systolic blood pressure (r = 0.623) and inversely with baroreflex sensitivity (r = −0.494). 4. Baroreflex sensitivity was less by an average of 3.1 ms/mmHg in patients over 30 years than in those under 30 (P < 0.025). Baroreflex sensitivity was inversely correlated with age (r = −0.617) and average systolic blood pressure (r = −0.589). 5. Beat by beat variability of systolic blood pressure was correlated with age (r = 0.460), particularly when the data of those in their twenties were excluded (r = 0.618), and significantly with pulse pressure/stroke volume (r = 0.650), average systolic blood pressure (r = 0.618) and inversely with baroreflex sensitivity (r = −0.477). These relationships were not observed for diastolic blood pressure. 6. Maximum difference in systolic blood pressure in a day was correlated with pulse pressure/stroke volume (r = 0.482) and average systolic blood pressure (r = 0.648) but not with baroreflex sensitivity. These relationships were not observed for diastolic blood pressure. 7. Variability of systolic blood pressure in patients over 30 years gradually increased with age. In contrast, those of systolic and diastolic blood pressures in subjects in their twenties were relatively large. This might be related to factors other than aging, presumably those which underlie the hyperdynamic circulatory state.

3兄弟の筋強直性ジストロフィー症について電気生理学的検討を行った。症例K.K., 42歳, 男性。動悸発作を主訴として当科受診。洞調律時心電図では1度房室ブロック, 心室内伝導障害がみられ, 頻拍発作時心電図では左脚ブロック型の心室頻拍を示した。His束心電図ではA-H時間130msec, H-V時間70msecであった。症例T.K., 41歳, 女性。心電図では右軸偏位, Wenckebach型2度房室ブロック, 心室内伝導障害, 心室性期外収縮がみられ, His束心電図ではA-H時間210msec, H-V時間80msecであった。症例S.K., 38歳, 男性。心電図では左軸偏位, 1度房室ブロック, 心室内伝導障害を示し, His束心電図では, A-H時間140msec, H-V時間75msecであった。以上より, 本症ではHis-Purkinje線維系のみならず房室結節内での伝導障害の存在が示唆され, 時に頻拍性不整脈の発生の可能性も考えられた。

洞不全症候群8例についてaprindine (MS-5075) 100mg (以下A) 静注前後で電気生理学的検査を施行した。洞周期と最大洞結節回復時間は, A静注前後で有意な変化はみられなかった。洞房伝導時間は, A静注後有意に延長した。1例においてA静注後2対1洞房ブロックを, 他の1例で著明な洞停止をA静注後一過性に認めた。静注前に洞結節回復時間の延長している例においてはA静注後さらに延長する症例がみられた。房室伝導機能は静注前後で有意な変化はみられなかった。以上より, 洞不全症候群においては同剤の使用は慎重に行うべきであると考えられた。

His-Purkinje系を介するリエントリー (Re-HPS) に及ぼす心周期の影響について検討した。心周期の短縮によりRe-HPSを生じるエコー帯の幅は縮少ないし消失する傾向を示した。その際, 最小2乗法により求めた心周期と不応期との関係直線の平均勾配は, His-Purkinje系の機能的不応期+0.227±0.03 (P

Baroreflex control of heart rate, pressor responses to alpha agonist (phenylephrine) and isometric exercise before and during salt loading were compared between 13 normotensive subjects with hypertensive relatives (group A) and 9 normotensive subjects with no family history of hypertension (group B). Baroreflex slope was significantly lower in group A than in group B (9.6 +/- 1.6 vs 17.6 +/- 1.9 msec/mmHg; p less than 0.01), although blood pressure, heart rate and aortic distensibility were not different between two groups. Pressor responses to phenylephrine and isometric exercise were identical for both groups. During salt loading, pressor responses to phenylephrine and isometric exercise were significantly greater in group A than in group B. Baroreflex slope was not affected by salt loading in the two groups. These results suggest that baroreflex control of heart rate is impaired in normotensive young subjects with hypertensive relatives and this defect may be inherited rather than the result of elevated arterial pressure and decreased aortic distensibility. Pressor responses to alpha agonist and isometric exercise during high-sodium diet were augmented in subjects with a family history of hypertension.

To determine whether insulin has a vasodilator action on the artery and vein, the effects of insulin at varying concentrations (120 microU/ml, 1.2 mU/ml, 12 mU/ml, and 120 mU/ml) on vasoconstriction by norepinephrine (NE) and angiotensin II (ANG II) were studied in the isolated rabbit femoral artery and vein. Helical strips were suspended in an organ bath filled with modified Krebs solution (pH 7.4), were gassed with 95% O2/5% CO2 at 36 degrees C, and isotonic contractions were measured. Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10(-8) M for the artery and 10(-7) M for the vein) at greater than or equal to 1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 x 10(-10) M for the artery and 3 x 10(-9) M for the vein) at greater than or equal to 1.2 mU/ml for the artery and greater than or equal to 12 mU/ml for the vein. The results indicate that insulin has an inhibitory effect on NE- and ANG II-induced contraction in both the artery and vein, and this appeared to be a contributory factor in the hypotensive effect observed in diabetic patients treated with insulin.

SUMMARY 1 To clarify whether acute changes in the properties of baroreflexes can occur in man, we evaluated the time course of baroreflex control of heart rate and cardiopulmonary baroreflex control of forearm vascular resistance (FVR) over 240 min after intravenous administration of propranolol (0.2 mg/kg) in 13 healthy young men. 2 Systolic and diastolic blood pressure remained unchanged after propranolol. Propranolol significantly decreased cardiac index and heart rate, and significantly increased total peripheral resistance. These effects remained unchanged for 240 min after propranolol. 3 Baroreflex control of heart rate was significantly augmented immediately after, and at 30, 60 min after propranolol, but partly reverted to the initial level afterwards. Cardiopulmonary baroreflex control of FVR was reduced immediately after, and at 30, 60 min after propranolol, but partly reverted to the initial level afterwards. Pressor responses to phenylephrine was reduced immediately after propranolol, but no significant differences were observed after 30 min. 4 These results suggest that acute changes in the properties of baroreflexes occur in man after propranolol.

1. We have monitored intra-arterial pressure continuously throughout the day and analysed every beat by computer. 2. Baroreflex sensitivity (ms/mmHg) was measured four times a day (07.00, 12.00, 17.00 and 20.00 hours) in seven patients and three times a day (07.00, 12.00 and 17.00 hours) in 23 patients. The diurnal variation of baroreflex sensitivity in individual patients was 0–5.3 ms/mmHg and was not consistent. Mean baroreflex sensitivity was reduced in hypertensive patients compared with normotensive subjects. 3. A negative correlation was seen between baroreflex sensitivity and the variability of systolic blood pressure. 4. Baroreflex sensitivity was well correlated with the variability of heart rate.

Peripheral circulatory effects of insulin were studied in the diabetic patients with and without autonomic neuropathy. Forearm blood flow, calf venous vol ume and calf venous distensibility were measured by strain gauge plethysmo graphy. In the diabetic patients with autonomic neuropathy, mean blood pres sure fell from 96±5 to 88±5 mmHg after an intravenous injection of 4 U of monocomponent insulin (p < 0.001). Forearm vascular resistance decreased from 53.99±8.29 to 45.88±7.76 mmHg•ml -1•100ml-1•min-1 after insulin (p < 0.01). Insulin increased calf venous volume from 1.20±0.19 to 2.23±0.44 ml/100ml (p < 0.05) and calf venous distensibility from 0.039±0.004 to 0.082±0.016 ml/mmHg (p < 0.05). In contrast, in the diabetic patients without autonomic neuropathy, there were no significant changes in the mean blood pressure, forearm vascular resistance, calf venous volume and calf venous dis tensibility. Symptoms of hypoglycaemia did not occur in any patient. These results suggest that insulin has a vasodilator action on both resistance and capacitance vessels, which may be one of the main factors in insulin-in duced hypotension.

To determine whether cholinergic mechanisms contribute to blood pressure regulation, we examined the effects of atropine on pressor responses to phenylephrine and vasoconstrictor responses to the cold pressor test (CPT) and lower body negative pressure (LBNP) in 16 healthy subjects. Heart rate, blood pressure and cardiac index were significantly increased, and central venous pressure (CVP) was significantly decreased after atropine (0.04mg/kg). After atropine, pressor responses to phenylephrine at doses of 20, 40 and 80 micrograms were significantly increased by 101, 112 and 93% (p less than 0.001); however, atropine attenuated pressor responses to CPT (p less than 0.001) and forearm vasoconstrictor responses to LBNP. In 6 propranolol-treated subjects, atropine also augmented pressor responses to phenylephrine but attenuated pressor responses to CPT. These results suggest that atropine augments the pressor response to an alpha-agonist, which may be partly explained by inhibition of compensatory vascular responses mediated by cholinergic mechanisms.

The effects of insulin on pressor responsiveness to alpha agonist (phenylephrine) and angiotensin II, and baroreflex function were studied in fifteen diabetic patients without autonomic neuropathy. The dose of phenylephrine required to increase systolic pressure by 25 mmHg (PD25) was significantly increased from 38 +/- 7 to 62 +/- 9 micrograms (p less than 0.05) after IV injection of 4 U of Actrapid monocomponent insulin. The dose of angiotensin II required to increase systolic pressure by 30 mmHg (AD30) was also increased from 0.29 +/- 0.07 to 0.48 +/- 0.10 micrograms (p less than 0.01). Following insulin administration, the dose-response curves for phenylephrine and angiotensin II were shifted to the right. The baroreflex sensitivity was not affected by insulin. In contrast, there was no significant change in PD25, AD30 or baroreflex sensitivity after the injection of saline. These results suggest that insulin attenuates the pressor responsiveness to alpha agonist and angiotensin II, which may be one of the significant mechanisms in insulin-induced vasodilation.