Characterization of 5-hydroxytryptamine-induced contraction and acetylcholine-induced relaxation in isolated chicken basilar artery.

The aim of the present study was to clarify the responsiveness of the chicken basilar artery to 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and to characterize the related receptor subtypes in vitro. Basilar arteries were obtained from freshly slaughtered broiler chickens. The 5-HT induced concentration-dependent contraction of the arteries. The concentration-response curves for 5-HT were shifted 30-fold to the right by methiothepin (a 5-HT(1) and 5-HT(2) receptor antagonist) and 3-fold to the right by ketanserin (a 5-HT(2) receptor antagonist). In the presence of ketanserin, the concentration-response curve for 5-HT was shifted 10-fold to the right by methiothepin. The pA(2) value for methiothepin was 8.26. The ACh induced concentration-dependent relaxation under conditions of precontraction by 5-HT. The concentration-response curve for ACh was shifted to the right by atropine [a nonselective muscarinic (M) receptor antagonist] and hexahydro-sila-difenidol hydrochloride, a p-fluoroanalog (pFHHSiD, an M(3) receptor antagonist), but not by pirenzepine (an M(1) receptor antagonist) or methoctramine (an M(2) receptor antagonist). The pA(2) value for pFHHSiD was 7.55. Nω-Nitro-l-arginine (a nitric oxide synthase inhibitor) inhibited ACh-induced relaxation by approximately 50%. These results suggest that 5-HT induces contraction via activation of 5-HT(1) and 5-HT(2) receptors and that ACh induces relaxation via activation of the M(3) receptor. The 5-HT(1) receptor might play a dominant role in 5-HT-induced contraction. One of the factors involved in ACh-induced relaxation is probably nitric oxide released from endothelial cells.

Evaluation of the effects of exercise and a mild hypocaloric diet on cardiovascular risk factors in obese subjects.

A weight reduction program to improve cardiovascular risk factors was implemented in obese subjects. The program consisted of exercise training corresponding to the anaerobic threshold (AT) and a mild hypocaloric diet for 12 weeks. In this program, we evaluated the effects of a combination of exercise training and a diet on cardiovascular risk factors such as obesity, dyslipidemia, and poor exercise performance in obese subjects. In addition, we also evaluated the independent effects of exercise training and dietary modification. For this purpose, we adopted a relative training time and a diet score. A relative training time was calculated as the number of times that the subject performed exercises divided by all of the training sessions scheduled, and the diet score was calculated from information which each subject provided on a self-assessment questionnaire. Twenty three obese subjects (Age: 24-54 years old, 19 men and 4 women, body mass index (BMI) > 26 kg/m2) participated in this study. After the 12-week intervention, the mean reductions in body weight, body mass index and body fat were 4.7 kg, 1.7 kg/m2 and 2.9%, respectively (P < 0.0001). The % change in body weight was significantly associated with the diet score and with the relative training time. The mean reductions in total cholesterol, triglyceride and low density lipoprotein cholesterol were 21 mg/dl (P < 0.002), 34 mg/dl (P < 0.01) and 15.9 mg/dl (P < 0.01), respectively, and the % change in triglyceride was significantly associated with the diet score (P = 0.0056) and tended to correlate with the relative training time (P = 0.0596). Oxygen uptake at AT and at peak exercise were increased from 14.1 +/- 1.6 to 16.0 +/- 3.1 ml/min/kg (P < 0.005) and from 26.3 +/- 4.8 to 28.4 +/- 4.9 ml/min/kg (P < 0.002), respectively. A combination of aerobic exercise and a mild hypocaloric diet significantly contributed not only to weight loss but also to the improvement of dyslipidemia and exercise performance, but either hypocaloric diet or mild exercise independently did less. The diet score and the relative training time were useful for evaluating separately dietary modification and the quantity of exercise.

Effects of a community-based lifestyle-modification program on cardiovascular risk factors in middle-aged women.

We investigate the effectiveness of a community-based lifestyle-modification program for reducing blood pressure and other cardiovascular risk factors in sedentary Japanese middle-aged women. Among an initial cohort of 210 middle-aged sedentary women, 195 subjects completed a community-based 12-week lifestyle-modification program for reducing cardiovascular risk factors. Blood pressure, body weight and the serum lipid profile were measured both at baseline and at the end of the 12-week lifestyle-modification program. The program consisted of mild aerobic exercise and a mild hypocaloric diet. After the 12-week program, both systolic and diastolic blood pressure were significantly reduced, especially in subjects who were hypertensive at baseline. Desirable changes in body weight and the serum lipid profile were also found after the 12-week program. Multiple linear regression analysis revealed that, in obese subjects, the decrease in systolic blood pressure was correlated with both the initial systolic blood pressure and the change in estimated maximum oxygen consumption. In addition, the decrease in diastolic blood pressure was correlated with the initial diastolic blood pressure and the change in body weight. On the other hand, in non-obese subjects, the decrease in blood pressure was correlated with the initial blood pressure and the change in salt intake. A community-based lifestyle-modification program that consisted of mild aerobic exercise and a mild hypocaloric diet was considered to be practically effective for reducing multiple cardiovascular risk factors. Individuals who already have one or more mild cardiovascular risk factors still could be good candidates for a community-based lifestyle-modification program.

A weight reduction and weight maintenance program with long-lasting improvement in left ventricular mass and blood pressure.

Obesity is a major risk factor for cardiovascular disease and is associated with hypertension and increased left ventricular mass (LVM). Maintenance of reduced weight has been a matter of recent concerns in the treatment of obese subjects. This study was conducted to confirm the effect of the addition of exercise to diet on maintenance of body weight in a weight reduction program. In addition, this study was conducted to estimate whether LVM changes in parallel with a change in body weight during a long-term follow-up after a weight-reduction program. Twenty-two normotensive (NT) obese subjects and 14 mild hypertensive (HT) obese subjects ranging in age from 22 to 51 years participated in a 12-week supervised weight-reduction program involving mild exercise and a mild hypocaloric diet. After this 12-week intervention, they were advised to maintain their modified lifestyle during a 1-year follow-up period. After the 12-week intervention, the mean reductions in body weight (BW) in the NT and HT groups were 4.1 kg (P < .0001) and 5.8 kg (P < .0001), respectively. LVM in the NT and HT groups was significantly reduced from 154 g to 136 g (P < .005) and from 169 g to 152 g (P < .002), respectively. One year after intervention, the mean gains in BW in the NT and HT groups were 2.3 kg (not significant, NS) and 0.4 kg (NS), respectively. The mean gains in LVM in the NT and HT groups were 8 g (NS) and 7 g (NS), respectively. It was also shown that blood pressures in the HT group were significantly decreased after the 12-week intervention and there was no significant change in blood pressure in the HT group 1 year after intervention. In conclusion, reduced body weight was maintained for 1 year after a 12-week supervised weight-reduction program in both normotensive and mild hypertensive obese subjects. Reduced left ventricular mass was maintained for a long period in both normotensive and mild hypertensive obese subjects and lowered blood pressure was maintained in the mild hypertensive obese subjects.

Effects of mild aerobic exercise and a mild hypocaloric diet on plasma leptin in sedentary women.

1. The present study was conducted to investigate whether mild aerobic exercise and a mild hypocaloric diet, instead of severe restrictions on caloric intake, would affect weight reduction and plasma leptin concentrations. 2. Forty-one middle-aged sedentary women (15 obese and 26 non-obese) participated in a 12 week lifestyle-modification programme to reduce cardiovascular risk factors. Bodyweight, body composition, plasma leptin concentrations, serum lipid profiles, fasting plasma glucose and fasting plasma insulin were measured before and after the 12 week intervention. The intervention consisted of aerobic exercise, corresponding to approximately 50% of maximal oxygen consumption, and personal diet counselling. 3. Bodyweight decreased by (mean +/- SD) 3.9 +/- 3.4 kg in the obese group (P < 0.05) and by 1.7 +/- 1.8 kg in the non-obese group (P < 0.05). The plasma leptin concentration decreased significantly from 14.7 +/- 5.3 to 8.9 +/- 3.6 ng/mL in the obese group (P < 0.001) and from 7.6 +/- 3.9 to 5.6 +/- 2.2 ng/mL in the non-obese group (P < 0.01). 4. Overall, for all subjects, both pre- and postintervention, the plasma leptin concentration was significantly correlated with body mass index (BMI; pre-intervention: r = 0.73, P < 0.0001; postintervention: r = 0.67, P < 0.0001), fat mass (FM; pre-intervention: r = 0.74, P < 0.0001; postintervention: r = 0.63, P < 0.0001) and fasting plasma insulin (pre-intervention: r = 0.66, P < 0.001; postintervention: r = 0.45, P < 0.01). The change in plasma leptin concentration was significantly correlated with the respective changes in BMI (r = 0.64, P < 0.0001), FM (r = 0.48, P < 0.01) and fasting plasma insulin (r = 0.58, P < 0.0001). Interestingly, the ratio of plasma leptin concentration to BMI or FM diminished significantly after intervention. In addition, we found that the plasma leptin concentration decreased in participants whose FM did not decrease. These results suggest that the production of leptin per unit FM decreased after intervention. 5. Mild aerobic exercise and a mild hypocaloric intake decreased body mass and the plasma leptin level in Japanese middle-aged sedentary women. This decrease in plasma leptin levels was likely to be associated with weight reduction plus some unknown factor(s).

Does coronary stenting following balloon angioplasty improve myocardial fractional flow reserve?

PURPOSE: Suboptimal distal coronary flow reserve after successful balloon angioplasty has been attributed to angiographically unrecognized inadequate lumen expansion, and adjunct coronary stenting has been shown to improve coronary flow reserve. The aim of this study was to investigate whether myocardial fractional flow reserve (FFRmyo) would increase further after coronary stenting compared with balloon angioplasty alone in the same patient group. METHODS: FFRmyo and quantitative coronary angiography were obtained before and after pre-stent balloon dilation, and again after stent placement in 11 patients (7 left anterior descending artery, 3 right coronary artery and 1 left circumflex artery). FFRmyo was calculated as the ratio of Pd/Pa during intracoronary adenosine 5'-triphosphate (50 micrograms and 20 micrograms in the left and right coronary arteries, respectively)-induced maximum hyperemia, where Pd represents mean distal coronary pressure measured by a 2.1 Fr infusion catheter and Pa represents mean aortic pressure measured by the guiding catheter. RESULTS: Percent diameter stenosis significantly decreased after balloon angioplasty (74% +/- 15% vs 37% +/- 17%, p < 0.001), and decreased further after stent placement (18% +/- 10%, p < 0.001 vs baseline and balloon angioplasty). FFRmyo after coronary stenting (0.85 +/- 0.09) was significantly higher than that at baseline (0.51 +/- 0.16, p < 0.001) and after balloon angioplasty (0.77 +/- 0.11, p < 0.05). There was a significant correlation between angiographic variables and FFRmyo. The increase in lumen dimensions after coronary stenting was followed by a further significant improvement of FFRmyo. CONCLUSION: These results suggest that coronary stenting may provide a more favorable functional status and lumen geometry of residual coronary stenosis compared with balloon angioplasty alone.

Can aggressive lipid lowering using low-density lipoprotein apheresis prevent restenosis after percutaneous transluminal coronary angioplasty in patients with normocholesterolemia?

We examined whether aggressive lipid lowering using low-density lipoprotein (LDL) apheresis could prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). Fifteen patients with 17 lesions underwent LDL apheresis once within a week before and after PTCA and thereafter every 2 or 3 weeks (apheresis group) for about 4 months. The control group consisted of 17 patients with 17 lesions. No patients received additional lipid lowering drugs after PTCA. In the apheresis group, the time interval means of the total and LDL cholesterol levels were significantly lower than those in the control group whereas no significant differences were found between the 2 groups regarding the mean percent diameter stenosis or minimal lumen diameter before and after PTCA and at follow-up. The restenosis rate was 29.4% in the apheresis group and 47.1% in the control group. The restenosis rate tended to be slightly lower in the apheresis group. The overall results, however, indicated that aggressive lipid lowering does not prevent restenosis.

Measurement of myocardial fractional flow reserve during coronary angioplasty in patients with old myocardial infarction.

Although myocardial fractional flow reserve (FFRmyo) has been demonstrated to be a useful index for determining functional significance of coronary stenosis, the data in previous studies was derived from a highly selected group of patients. The aim of this study was to investigate the value of FFRmyo in a more clinically relevant group of patients, especially in patients who also had resistance vessel dysfunction. We measured FFRmyo in 20 consecutive patients who had undergone elective coronary angioplasty. FFRmyo was calculated by the ratio of Pc/Pa during intracoronary adenosine 5'-triphosphate (ATP; 50 micrograms in the left coronary and 20 micrograms in the right coronary artery) induced maximal hyperemia, where Pa represents mean aortic pressure obtained by the guiding catheter and Pc represents mean distal coronary pressure measured by a 2.1 F infusion catheter. In total, 21 vessels were dilated and 14 of them were infarct-related arteries. The percent diameter stenosis significantly decreased from 80 +/- 14% to 27 +/- 17%, and the FFRmyo increased significantly from 0.46 +/- 0.18 to 0.77 +/- 0.15 after angioplasty. There was no significant differences in the FFRmyo between vessels with previous myocardial infarction and those without, after angioplasty (0.78 +/- 0.18 vs. 0.76 +/- 0.08). There was a significant correlation between the percent diameter stenosis and FFRmyo before (r = 0.83, P < 0.001) and after (r = 0.64, P < 0.01) angioplasty. In conclusion, FFRmyo significantly improved immediately after angioplasty in vessels with myocardial infarction as well as those without. These results led us to suggest the usefulness of FFRmyo in patients who had both epicardial stenosis and resistance vessel dysfunction. The significant correlation between FFRmyo and quantitative coronary arterial diameter stenosis would further support the more widespread use of FFRmyo in the clinical setting.

Coronary angioplasty of a severe coronary stenosis at the site of a myocardial bridge.

We report the case of a patient who underwent coronary angioplasty for a severe stenosis at the site of a myocardial bridge. Although favorable angiographic results and the disappearance of myocardial ischemia were obtained, a significant pressure gradient across the lesion and abnormal myocardial fractional flow reserve remained immediately following angioplasty. These results suggest that pressure measurements may be of limited value in this subset of patients.

Comparative effects of dobutamine and amrinone on coronary blood flow in patients with idiopathic dilated cardiomyopathy.

Although amrinone has favorable hemodynamic effects in patients with congestive heart failure, little is known about its effects on coronary blood flow (CBF). We compared the effects of intravenous low-dose dobutamine and amrinone on CBF in 10 patients with dilated cardiomyopathy using a Doppler guidewire. We infused dobutamine at a dose of 5 and 10 microg/kg/min for 5 min. After the end of each stage, coronary flow velocity (CFV) and coronary arterial diameter (CAD) in the proximal left anterior descending coronary artery, and hemodynamic variables were obtained. After the CFV and hemodynamics returned to baseline, we infused 1 mg/kg of amrinone over 5 min, and obtained these variables at 5 and 10 min after the cessation of the infusion. CAD did not increase with dobutamine, but significantly increased after amrinone (% increase: 10 +/- 7%; P < 0.001 vs. baseline). CFV progressively increased with dobutamine (5 microg/kg/min: 21 +/- 26%; P < 0.05 vs. baseline; 10 microg/kg/min: 53 +/- 42%; P < 0.005 vs. baseline and 5 microg/kg/min), but slightly decreased after amrinone (-4 +/- 17%; P = not significant vs. baseline). CBF increased during dobutamine (5 microg/kg/min: 25 +/- 29%; P < 0.05; 10 microg/kg/min: 66 +/- 55%; P < 0.005) and after amrinone (19 +/- 22%; P < 0.05) compared to that at baseline. Although there was a significant correlation between the percent increase in CFV and that in dP/dt during dobutamine infusion (r = 0.82, P < 0.001), this correlation was not observed after amrinone (r = 0.23). In conclusion, although both agents significantly increased CBF in patients with dilated cardiomyopathy, they do so by different mechanisms. Amrinone mainly increases CBF by causing dilatation of epicardial coronary arteries. These results suggest that amrinone has beneficial effects on coronary flow dynamics in dilated cardiomyopathy.

Weight reduction regresses left ventricular mass regardless of blood pressure level in obese subjects.

The effects of weight reduction on left ventricular mass in obese normotensive and hypertensive subjects were investigated. Previous studies have shown that weight reduction in hypertensive (HT) obese patients is associated with decreased left ventricular mass (LVM) and decreased blood pressure (BP). This study was performed to examine whether weight reduction would also regress LVM in normotensive (NT) obese subjects and to clarify the mechanisms of these effects if they occurred. A weight-reduction program consisted of mild exercise and mild hypocaloric intake. M-mode echocardiography was performed to estimate the LVM. After the 12-week intervention, the mean reductions in body weight (BW) in the NT (n = 11) and HT (n = 11) groups were 4.9 kg (p < 0.005) and 4.6 kg (p < 0.0005), respectively. Systolic, diastolic, and mean BP were significantly reduced by 13, 9, and 11 mm Hg, respectively, in the HT group. By contrast, no significant changes in systolic, diastolic, or mean BP were observed in the NT group. LVM was significantly reduced from 176 +/- 26 gm to 159 +/- 26 gm (p < 0.05) in the HT group and from 167 +/- 33 gm to 145 +/- 34 gm (p < 0.02) in the NT group. These results suggest that weight reduction in obese subjects by mild exercise and mild hypocaloric intake can lead to a reduction in LVM, regardless of whether the subjects have normal or high blood pressure.

[Psychosomatic effect of a health program on obese employees].

A 12-week training period including exercise and diet was undertaken to determine the effects of a newly developed health program on the physical and phychological parameters in 24 obese employees of a certain company. The association between a number of somatic parameters and psychological variables, including the attitude toward better health, and the level of mental health (General Health Questionnaire) were analysed before, immediately or 1 year after the program. After the program, significant overall improvements were found in several physical parameters. Those who had higher initial levels of attitudes toward better health showed greater exercising/dieting achievements during the program. Furthermore, these considerable health-related attitudes seemed to be concerned with higher HDL levels preceding the program, and minor improvements in diastolic blood pressure due to the program. The GHQ scores tended to increase in proportion to decreased exercising/ dieting achievements during the program and undesirable lifestyle that ignored any form of exercising.

Increased susceptibility of angiographically smooth left anterior descending coronary artery to an impairment of vasoresponse to acetylcholine, and the relation between impaired vasoresponse and low-density lipoprotein cholesterol level.

In the present study, we demonstrated that the angiographically smooth LAD is more susceptible than the LC to an impairment of vasoresponse to acetylcholine, suggesting the more severe endothelial dysfunction in the LAD. We also showed that levels of LDL play a partial but important role on endothelial dysfunction.

Effect of sustained release diltiazem (Diltiazem-R) in patients with stable effort angina.

Ca++-antagonist is effective not only for variant angina but also for effort angina. The effects of sustained release diltiazem (diltiazem-R) and beta 1-blocker (atenolol) on exercise tolerance were studied in seven patients with stable effort angina in a cross over trial. Diltiazem-R (100mg) or atenolol (50mg) was given once a day, each treatment period lasting for two weeks after a two-week control period. The treadmill exercise test was performed on the last day of each protocol. Both diltiazem-R and atenolol decreased heart rate at rest and the decrease with atenolol was greater than that with diltiazem-R. The systolic blood pressure was unchanged at rest by both drugs. At maximal work levels, atenolol decreased the heart rate and pressure rate product significantly but diltiazem-R did not. Both diltiazem-R and atenolol significantly prolonged the exercise time (average 137 and 165 seconds respectively), time to onset of 1mm ST depression (240 and 288 seconds respectively). There was no significant difference in exercise tolerance between diltiazem-R and atenolol. These findings suggest that diltiazem-R, a sustained release Ca++-antagonist, provides beneficial effects in patients with stable effort angina.

[Health and exercise: effects of exercise on high blood pressure].

Many factors, such as genetic, psychological, environmental, and socioeconomical factors, influence the health of individuals. Recently behavioral risks which cause preventable chronic diseases or premature death have been increasing. These risk factors are mainly due to living habits, such as over-eating, less exercise and psychological stress. Physical activity or fitness is reported to be inversely associated with morbidity and mortality from chronic diseases, such as cardiovascular diseases diabetes mellitus, cancer and so on. Hypertension has also been reported to be associated with low physical fitness in cross-sectional studies. We have so far reported a significant blood pressure reduction in mild hypertensive patients who completed mild intensity exercise training in well controlled studies. Exercise seemed to modify the multiple factors that might participate in raising and maintaining high blood pressure. The mechanisms of lowering blood pressure by exercise training are mainly due to a depletion of blood volume or the reduction of both cardiac output and the sympathetic tone. They were supported by the evidence of increased levels of prostaglandin E, dopamine, taurine, and decreased levels of plasma norepinephrine and endogenous ouavain-like substance. In this article, we have reviewed the physiological and biochemical roles of exercise, the effects of exercise on high blood pressure, and the hypotensive mechanism of mild aerobic exercise hypertensive patients.

[Comparison of the casual serum triglyceride levels at health check-up with the values during fasting].

Since higher levels of serum triglycerides were frequently found during the UOEH physical check-up for employees and students in 1989, we analysed subjects with higher triglyceride levels and discussed ways of handling them. Blood sampling to determine serum lipids was done between 13:00-15:00. Of the total (males 1257, females 1267), 272 had higher serum triglyceride levels (over 200 mg/dl) (males 246, females 26) (1st TG). One hundred and twenty-one of the group with higher TG levels in the 1st examination were reevaluated by blood sampling the morning after overnight fasting (2nd TG). There was a significant positive correlationship between the TG levels from the 1st examination and those from the 2nd examination (r = 0.62, n = 121, P < 0.0001). The predictive value calculated from the equation between the TG in the first and second measurements was 341.7 mg/dl. There was a 14.9% rate of false negatives in subjects under 341.7 mg/dl on the first TG measurement. However, there were only 6.3% false negatives in the subjects under 250 mg/dl on the first TG measurement. Age, body mass index and serum cholesterol level were significantly higher in the group with the higher TG level on reevaluation (more than 160 mg/dl) than those in the group with the lower TG level on reevaluation (less than 160 mg/dl). We concluded from these results that the casual serum TG levels above 250 mg/dl might be a suitable cut off level in physical check-ups.