• Korean Circulation Journal
• /
• v.52 no.7
• /
• pp.544-555
• /
• 2022

Background and Objectives: The outcome benefits of β-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of β-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). Methods: A total of 3,075 patients with chronic CAD were included from the Grand Drug-Eluting Stent registry. We analyzed β-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (β-blockers vs. no β-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of β-blockers. Results: During a median (interquartile range) follow-up of 3.1 (3.0-3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, β-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63-1.24), all-cause death (HR, 0.87; 95% CI, 0.60-1.25), and MI (HR, 1.25; 95% CI, 0.49-3.15). In subgroup analysis, β-blockers were associated with a lower risk of all-cause death in patients with previous MI and/or revascularization (HR, 0.38; 95% CI, 0.14-0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of β-blockers. Conclusions: Overall, β-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of β-blockers may exist for patients with previous MI and/or revascularization.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.4
• /
• pp.844-852
• /
• 1997

Background : Recent studies have documented increased release of endothelin(ET) during acute attack of asthma. The purpose of this study is to observe the link between plasma level and urinary excretion of each and changes during acute exacerbation. Method : Plasma and 24 hour urine were collected from sixteen asthmatics during acute exacerbation, twice ; first day of symptomatic exacerbation and two weeks after treatment. Controls were ten healthy normal subjects. All patients were treated with corticosteroid and beta-2 adrenergic agonist on admission. ET was determined by radioimmmunoassay and had 100% cross reactivity with ET-1, 67% with ET-2, 84% with ET-3, and 8% with Big-ET. Results : Plasma ETs were significantly elevated during acute attack of asthma compared with those in remission and controls.,However, there was no significant changes in urine ET concentrations or total ET amounts in 24 hour urine during exacerbation upto two weeks. Those levels of urine ET in asthmatics were still higher than controls. ET concentrations in plasma or urine were not correlated with pulmonary functional parameters and hypoxemia. Conclusion : The findings suggests that increased plasma ETs are related with exaggerated release during acute asthma. Urinary ET excretion is increased in asthma. However, urine ET changes during exacerbation should be observed in a larger and longer scale.

• The Korean Journal of Pharmacology
• /
• v.28 no.1
• /
• pp.61-74
• /
• 1992

Influence of the blockade of the three major pressor systems-sympathetic nervous system (SNS), renin-angiotensin system (RAS) and vasopressin system-on the pressor responsiveness to norepinephrine (NE), angiotensin II (AII), and vasopressin (VP) as well as on basal blood pressure (BP) levels was investigated in urethane-anesthetized rabbits. To block the SNS and RAS, chlorisondamine (CS) and pirenzepine (PZ), sympathetic ganglionic blockers, and enalapril (ENAL), an inhibitor of angiotensin converting enzyme, respectively were used. And for suppressing the VP system bremazocine (BREM), a kappa opiate receptor agonist shown to suppress plasma levels of VP, was employed. Each of CS (0.4 mg/kg), ENAL (2 mg/kg), and BREM (0.25 mg/kg) produced almost same levels of steady hypotensive state. The hypotensive effect of BREM was significantly attenuated by desmopressin, a synthetic VP-like analogue, suggesting the hypotension being at least in part due to suppression of plasma levels of VP. CS, ENAL and BREM elicited further fall of the BP which had been lowered by ENAL or BREM, CS or BREM, and CS or ENAL, respectively. The hypotension produced by both CS and PZ together with either of ENAL or BREM was more marked than that produced by the three drugs other than CS. CS potentiated the pressor response not only to NE but to AII and VP. The pressor effect of AII was increased by ENAL and BREM, too. The pressor response to VP was also enhanced by BREM. Blockade of ${\alpha}-adrenergic$ receptors with phentolamine or phenoxybenzamine potentiated the pressor response to AII and that to VP. The results on basal BP levels indicate that the three major pressor systems are all participating in control of BP, but SNS has the greatest potential for supporting BP. The finding that blockade of one of the pressor systems induced enhanced pressor responsiveness to the pressor hormone of that particular system as well as to the pressor hormone(s) of the other systems(s) provides evidence for important interactions among the three major pressor systems.

• Journal of Yeungnam Medical Science
• /
• v.9 no.2
• /
• pp.382-395
• /
• 1992

GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.

• The Korean Journal of Pharmacology
• /
• v.26 no.1
• /
• pp.13-23
• /
• 1990

Methylene Blue (MeB) and gentian violet $(10^{-6}{\sim}10^{-4}\;M)$ produced contractions in isolated thoracic aortic preparations of rabbits in a dose-dependent fashion, while other dyes, evans blue and eosine yellowish, did not affect the basal tension in the same range of doses. Porcine mesenteric arterial rings also responded to MeB with dose-dependent contractions. Single dose of $10^{-4}$ M MeB produced a biphasic response: contraction followed by relaxation. The contraction developed slowly within $2{\sim}4$ min and peaked in about 20 minutes and then slowly relaxed to the basal level. Tyramine $(10^{-4}\;M)$ also induced contraction but it developed faster and was more persistent than that of MeB. While the tyramine-induced tension was reproducible, the MeB-induced one wat not reiterable until 3 to 5 hours after washing out the MeB. Adding $10^{-4}$ M MeB further potentiated the contraction induced by $10^{-4}$ M tyramine. However, the MeB contraction was not affected by further addition or tyramine. Both tyramine- and MeB-induced tensions were abolished or significantly inhibited by pretreatment with various drugs acting on the sympathetic nervous system. The tyramine-induced tension was more sensitive to guanethidine and 6-hydroxydopamine than the MeB-induced tension, while the latter was more sensitive to $Ca^{2+}-free$ PSS and reserpine. But they have similar sensitivity to prazosin. The MeB-induced tension was significantly inhibited but not abolished by 6-hydroxydopamine pretreatment. However, either tyramine or 6-hydroxydopamine could not affect the basal tension of the ring that MeB once had been tested. These results suggest that MeB-induced contractions of rabbit thoracic aorta and porcine mesenteric artery result from a release of endogenous norepinephrine from adrenergic nerve endings and are dependent in part on extracellular calcium, and that the potency of MeB to release or to deplete norepinephrine is greater than that of either tyramine or 6-hydroxydopamine.

• The Korean Journal of Pharmacology
• /
• v.1 no.1 s.1
• /
• pp.17-36
• /
• 1965

Besides it's all important analgesic action, morphine has, among others, hyperglycemic effect, though not important clinically, which is believed to be resulted from augmented glycogenolysis in the liver and muscles due to the increased liberation of epinephrine from the adrenal medulla upon the stimulation of the posterior part of hypothalamus. It is known that adrenergic blocking agents are acting inhibitory to this sort of hyperglycemia. Much, however, should as yet be studied for the drugs which affect central nervous system and release of endogenous catecholamine as far as their effects on hyperglycemia are concerned. Much is still not known about the effect of ginseng, which has been highly regarded in the Herb Medicine, as far as it's influence on the blood sugar is concerned. Author investigated the effects of chlorpromazine, reserpine and ginseng on epinephrine induced, and morphine-induced hyperglycemiae. Animals used in this experiment were healthy albino rabbits weighing approximately 2.0 kg of body weight and were all fasted for 24 hours, before the experiment undertaken. Blood sugar determination was carried out by Nelson-Somogy method. Results obtained are summarized as follows; 1. The groups of rabbits administered intravenously with epinephrine 0.02 mg/kg, and 0.05 mg/kg, showed marked and transient hyperglycemia within 15 minutes after injection. The maximal rate of elevation in blood sugar to the control level, were 28% and 57% respectively. The blood sugar returned to the control level within 3 hours. Thus, the hyperglycemic responses were paralleled with epinephrine doses. 2. The hyperglycemic responses by morphine were different according to the doses. The groups of rabbits in which 4 mg/kg of morphine was administered, did not show any hyperglycemic effect, but, in which 10 mg/kg of morphine administered, showed severe hyperglycemic effect, resulting in the maximal level within 2 hours after injection. The maximal rate of increasing in blood sugar ,level was 88%. Compared .with epinephrine-injected groups, morphjne-injected groups showed more persistent hyperglycemic effect, but returned to control blood sugar .level in 6 hours after injection. 3. The intravenous injection of chlorpromazine 2 mg/kg and 8 mg/kg evoked a slight, and persistent hyperglycemia. The maximal rate of increasing in blood sugar level were 15% and 23% respectively. These hyperglycemia gradually returned to the normal level in 5 or 6 hours after injection. Thus, the intensity of response was paralleled with the dose of chlorpromazine. 4. The intravenous injection of reserpine 0.2 mg/kg and 0.5mg/kg, showed the most persistent but steady elevation of blood sugar level in this experiments, resulting in the maximal level in 5 hours after injection. The maximal rate of increasing of blood sugar level were 18% and 39% respectively. 5. The blood sugar level from 24 hours to 30 hours after intraperitoneal administration of reserpine 1.0mg/kg, did not show statistically significant difference, compared with control groups. 6. The oral administration of ginseng extract 15 ml/kg did not. show any :change in blood sugar level. 7. The intravenous administration of epinephrine 0.05 mg/kg or morphine 4 mg/kg to the group pretreated with ginseng extract 15 ml/kg $20{\sim}30$ minutes before the experiment, evoked more marked hyperglycemic effect than the non-pretreated group. 8. The intravenous administration of epinephrine 0.02 mg/kg, morphine 4 mg/kg, or morphine 10 mg/kg to the groups pretreated with reserpine 0.2 mg/kg or 0.5 mg/kg $20{\sim}30$ minutes before experiment, produced more marked and persistent hyperglycemic effects than the groups injected with single epinephrine or morphine injection. 9. When epinephrine 0.05 mg/kg or morphine 10 mg/kg administered intravenously to the groups pretreated with the intraperitoneal administration of reserpine 1 mg/kg 24 hours before experiment morphine-induced hyperglycemia was inbibited, but epinephrine-induced hyperglycemia was augmented. 10. When epinephrine 0.05mg/kg or morphine 10 mg/kg administered intravenously to the groups pretreated with chlorpromazine, 2 mg/kg, 4 mg/kg, and 8 mg/kg $20{\sim}30$ minutes before the experiment, morphine-induced hyperglycemia was inbibited, but epinephrine-induced hyperglycemia was more persistent.

• The Korean Journal of Physiology
• /
• v.24 no.1
• /
• pp.39-49
• /
• 1990

It has been reported that bombesin induces contraction of the smooth muscle of the gastrointestinal tract. Thus, the present investigation was undertaken to see an influence of bombesin on electrical activity of the gastric smooth muscle, since electrical activity is associated with contractile activity in the smooth muscle of the stomach. Smooth muscle strips $(5\;{\times}\;1.5\;cm)$ that included the corpus and antrum were prepared from the ventral and dorsal portion of the feline stomach along the greater curvature. Circular muscle strips $(1\;{\times}\;0.3\;cm)$ of the corpus were also obtained. Electrical activity of the corpus and antrum of the muscle strip was monophasically recorded by using Ag-AgCl capillary electrodes placed on the circular muscle layer. Contractile activity of the circular muscle strip was also recorded. The recordings were performed in Krebs-Ringer solution that was continuously aerated with $O_{2}$ containing 5% $Co_{2}$, and kept at $36^{\circ}C$. Dose-related responses of electrical activity and contractility to bombesin was studied after frequency of slow waves and contraction of each strip reached to a steady state. An action of $D-leu^{13}-{\psi}\;(CH_{2}NH)-D-leu^{14}-bombesin,\;D-pro^{2}-D-trp^{7,9}-substance\;P$, tetrodotoxin, hexamethonium, atropine, phentolamine or propranolol on the effect of bombesin was also observed. 1) Bombesin increased frequency of slow waves and contractions dose-dependently at concentrations from $10^{-9}\;M\;to\;3\;{\times}\;10^{-8}\;M$. 2) The bombesin analogue at a concentration of $3\;{\times}\;10^{-7}\;M$ antagonized the effect of bombesin on frequency of slow waves. 3) The effect of bombesin on frequency of slow waves was inhibited by tetrodotoxin $(10^{-6}\;M)$ and hexamethonium $(10^{-3}\;M)$ but unaffected by atropine $(10^{-6}\;M)$, phentolamine $(10^{-5}\;M)$ and propranolol $(10^{-5}\;M)$. 4) The effect of bombesin on frequency of slow waves was blocked by the substance P analogue at a concentration of $10^{-5}\;M$. 5) Substance P at a concentration of $10^{-5}\;M$ failed to change frequency of slow waves. It is concluded from the above results that bombesin increases the frequency of slow waves as well as contractions of the smooth muscle strip from the feline stomach, and the effect of bombesin might be mediated by non-cholinergic or non-adrenergic mechanism at neuromuscular junction. However, enteric nerves that have substance P as a neurotransmitter do not appear to participate in the action of bombesin on frequency of slow waves.

• The Korean Journal of Pharmacology
• /
• v.21 no.2
• /
• pp.119-127
• /
• 1985

The renal function is under regulatory influence of the central nervous system, mainly through activation of sympathetic nerve to the kidney, and it was recently reported that clonidine, an agonist to ${\alpha}_2$-adrenoceptors, induces diuresis and natriuresis when injected directly into a lateral ventricle of the rabbit brain (i.c.v.). This study was undertaken, therefore, to obtain further information as to the role of the central ${\alpha}_2$-adrenoceptors in regulating renal function, by observing the effects of i.c.v. yohimbine, a specific antagonist of adrenoceptors of ${\alpha}_2$-type, on the rabbit renal function, and to elucidate the mechanism involved in it. With 10 ${\mu}g/kg$ i.c.v. of yohimbine sodium excretion transiently increased along with increasing tendency of urine flow, renal plasma flow and glomerular filtration rate. These responses decreased with increasing doses. With 100 and 300 ${\mu}g/kg$ i.c.v. marked antidiuresis and antinatriuresis as well as profound decreases of renal perfusion and glomerular filtration were noted. Systemic blood pressure transiently increased. In reserpinized rabbits, 100 ${\mu}g/kg$ yohimbine i.c.v. did not produce any significant changes in urine flow, sodium excretion as well as in renal hemodynamics. The pressor response was also abolished. In preparations in which one kidney was denervated and the other left intact as control, i.c.v. yohimbine elicited typical antidiuretic antinatriuretic response in the innervated control kidney, whereas the denervated experimental kidney responded with marked diuresis and increases in excretory rates of sodium and potassium and in osmolar clearance in spite of absence of increased filtration and perfusion . Systemic blood pressure responded as in the normal rabbits. These observations indicate that i.c.v. yohimbine affects renal function in dual ways in opposite directions, the first being the antidiuretic antinatriuretic effects which results from decreased renal perfusion and glomerular filtration due to sympathetic activation and which is predominantly expressed in the normal rabbits, and the second less apparent effect being the diuretic and natriuretic action which is not mediated by nerve pathway but brought about by some humoral mechanism and which is effected by decreased sodium reabsorption in the tubules, possibly of the proximal portion.

• Journal of Chest Surgery
• /
• v.29 no.2
• /
• pp.191-198
• /
• 1996

Amrinone is a non-glycosidic, non-adrenergic positive inotropic agent with peripheral and coronary vasodilator effect. It inhibits phosphodiesterase F-III, the cardiac cyclic-AMP specific phosphodiesterase, selectively and potently. In this study, the effects of IV administered amrinone and dopamine were compared in 40 patients who had open heart surgery. Amrinone was administered as a bolus of 1 5~2mglkg for several minutes, followed by continuous infusion at 5~1 Oug/kg/min. The hemodynamic measurements including heart rate, systolic and diastolic pressure, cardiac index, pulmonary wedge pressure, and systemic vascular resistance were recorded immediately for 12~24 hours awl 7th day following operation. In amrinone group, cardiac index increased from 3.73$\pm$1.39 L/min/m2 to 5.44$\pm$2.65 L/min/m2 at the time of posterative 48 hours (n=20, p< 0.05). The decrease in systemic vascular resistance from 1237.5 $\pm$ 637.7 dyne/sec/cm2 to 1000.8 $\pm$ 608.5 dyne/sec/cm2(p<0.05). In Dopamine group, the heart rate increased from 92.1 $\pm$ 13.0/min to 101.0 $\pm$ 13.1/min and the cardiac index decreased from 3.40 $\pm$ 0.50 L/min/m2 to 2.53 $\pm$ 1.15 L/min/m2 at the time of postoperative 12 hours(p<0.05). Systemic vascular resistance increased from 1058.5 $\pm$ 234.6 dyne/sec/cm2 to 1979.7 $\pm$ 759.2 dynelsec/cm2 The comparison of the hemodynamic effects of amrinone and dopamine, both drugs improved cardiac performance. But the administration of amrinone results in a higher cardiac index, diastolic blood pressure and lower systemic vascular resistance than those achieved with dopamine (p<0.05). The uniqueness of the action of amrinone on the heart and its sustained hemodynamic effect suggest it has clinical promise, pos operative care of cardiac surgery

• Journal of Life Science
• /
• v.18 no.3
• /
• pp.291-297
• /
• 2008

We investigated whether 1) the combined capsaicin (75 mg), sesamin (30 mg), and L-carnitine (900 mg) (CCSC) ingestion enhances autonomic nervous system (ANS) activities including thermogenic sympathetic activity as energy metabolic modulator, 2) ${\beta}_3-AR$ polymorphism of each subject influences with ANS activity. Seven healthy males $(22.0{\pm}0.5\;yr)$ volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis were continuously measured during 5 min every 30 min for total 120 min resting condition with CCSC or placebo oral administration chosen at random. The results indicated that, there are not $Arp/Arg^{64}$ variants of the ${\beta}_3-AR$ genotypes in our subjects. There were not also significant differences in heart rate during rest between both trials. The difference of ANS activity did not reach the statistical significance between both trials. However, the significant improvement showed TOTAL power, HF component, and the indices of SNS and PNS activities before and at 30 min after CCSC ingestion (p<0.05, respectively). In conclusions, although each component of combined CCSC is associated with lipolysis and/or fat oxidation, the combined CCSC consumption is not influenced in stimulation of thermogenic sympathetic activity as modulator of energy metabolism. In rather, our results suggested that CCSC ingestion improves the balance of both SNS and PNS activities. Therefore, it will be considered many combined nutrient components for ergogenic and/or lipolysis effects as well as genetic variants affecting ANS activity in further studies.