• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.335-344
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• 2024

Diphenyleneiodonium (DPI) has been widely used as an inhibitor of NADPH oxidase (Nox) to discover its function in cardiac myocytes under various stimuli. However, the effects of DPI itself on Ca²⁺ signaling and contraction in cardiac myocytes under control conditions have not been understood. We investigated the effects of DPI on contraction and Ca²⁺ signaling and their underlying mechanisms using video edge detection, confocal imaging, and whole-cell patch clamp technique in isolated rat cardiac myocytes. Application of DPI suppressed cell shortenings in a concentration-dependent manner (IC₅₀ of ≅0.17 µM) with a maximal inhibition of ~70% at ~100 µM. DPI decreased the magnitude of Ca²⁺ transient and sarcoplasmic reticulum Ca²⁺ content by 20%-30% at 3 µM that is usually used to remove the Nox activity, with no effect on fractional release. There was no significant change in the half-decay time of Ca²⁺ transients by DPI. The L-type Ca²⁺ current (I_Ca) was decreased concentration-dependently by DPI (IC₅₀ of ≅40.3 µM) with ≅13.1%-inhibition at 3 µM. The frequency of Ca²⁺ sparks was reduced by 3 µM DPI (by ~25%), which was resistant to a brief removal of external Ca²⁺ and Na⁺. Mitochondrial superoxide level was reduced by DPI at 3-100 µM. Our data suggest that DPI may suppress L-type Ca²⁺ channel and RyR, thereby attenuating Ca²⁺-induced Ca²⁺ release and contractility in cardiac myocytes, and that such DPI effects may be related to mitochondrial metabolic suppression.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.147-162
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• 1992

The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.

• The Korean Journal of Physiology
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• v.18 no.1
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• pp.19-35
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• 1984

Since the first report of Drury and $Szent-Gy{\ddot{o}}rgyi$ in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 $M{\Omega}$. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of $3%\;CO_2-97%\;O_2$ at $35^{\circ}C$. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of $10^{-5}M$ and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of $Ca^{+2}$. Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM $Ca^{+2}$ decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra $Ca^{+2}$ was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at $35^{\circ}C$(mean{\pm}SEM, n=16) was $154{\pm}3.3\;beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), $-73{\pm}1.7\;mV: overshoot(OS), $9{\pm}1.4\;mV: slope of pacemaker potential(SPP), $94{\pm}3.0\;mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}M$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra $Ca^{2+}$ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate $Ca^{2+}$ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing $Ca^{2+}-permeability$ of nodal and atrial cell membranes.

• Journal of Chest Surgery
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• v.39 no.9 s.266
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• pp.674-680
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• 2006

Background: Acute myocardial infarction (MI) is a life-threatening disease and surgical revascularization plays a major role in selected cases. The purpose of this study is to evaluate the left ventricular contractility improvement by examining the wall motion score index (WMSI) and left ventricular ejection fraction (LVEF) in patients who under-went surgical revascularization under diagnosis of acute MI. Material and Method: From January, 2001 to December, 2004, 149 patients who underwent coronary artery bypass surgery within 2 weeks of acute MI were included. We evaluated pre- and postoperative left ventricular contractility by measuring WMSI and LVEF and examined the associating factors. Result: WMSI decreased from $1.54{\pm}4.30\;to\;1.43{\pm}0.40$ (p<0.001) and LVEF increased from $48.1{\pm}12.2%\;to\;49.7{\pm}12.3%$ after surgery (p=0.009). Off-pump technique, non-Q wave, anterior MI, and surgery within 7 days after MI were favorable factors for LVEF improvement (p=0.046, p=0.006, p=0.003, p=0.005, respectively). Conversely, aforementioned factors were irrelevant with WMSI improvement. For triple vessel disease, complete revascularization was favorable factor for WMSI improvement (p<0.001). Conclusion: Coronary artery by-pass surgery can improve WMSI and LVEF in patients with acute MI. In case of anterior MI with non-Q wave, early surgical revascularization within 7 days may be most beneficial in LVEF improvement. Regarding WMSI, complete revascularization may be essential.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.33-40
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• 1978

1) The authors studied the effect of increasing age on the contraction and relaxation mechanism in the ureteral smooth muscle of the guinea pig. 2) Two to three week old, three month old, and two to three year old guinea pig ureters were used and the consistent amplitude of contratile responses were induced by using train stimulation. 3) After mounting the specimens in Tyrode's solution containing 2.6mM $Ca^{++}$, the ureter was stimulated, of which amplitude was initial contraction and next continuously superfused with $Ca^{++}$-free Tyrod's solution. When the contractile response stopped by electrical field stimulation, the muscle specimens was superfused with Tyrode's solution 0.25mM $Ca^{++}$ for 15min and stimulated with the same parameters. Thereafter, the contraction of $Ca^{++}$ in the solution was increased step by step up to 2.7mM. 4) The ureters of 2-3 week old guinea pigs needed less $Ca^{++}$ for the recovery of contractile response than those of three month and two to three year old did. In 2.7mM $Ca^{++}$, the ureters of 2-3 week and 3 month old guinea pigs recovered the contractile response of over 90% but those of 2-3 year old recovered the contractility of 77.2%. 5) Isoproterenol inhibited in dose dependent manner from $10^{-7}$ to $10^{-5}\;M$ ureteral contractility of both 2-3 week and 2-3 year old guinea pigs. The inhibition of the old ureter by isoproterenol was significantly less (P<0.025) than that of the younger ureter. However theophylline showed the strong inhibition independent of the function of age. 6) Dibutyryl cyclic AMP showed dose-dependent inhibition of the contraction of ureters of 2-3 week old guinea pigs but there was shown no inhibition in the old ureters. Further, the content of endogenous cyclic AMP in the two week old ureter was higher by 73% than that of 17 month old ureter. Cyclic GMP contents was not much different between two groups. 7) The ureteral smooth muscle of the younger guinea pig had more efficiency than that of the older animals in the mobilization and storage of calcium which concerned itself in the contraction and relaxation mechanism.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.884-892
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• 1998

Background: The gastroepiploic artery is not only an alternative graft but also may be considered an important primary graft for coronary revascularization. However, the long-term patency of the gastroepiploic arterial graft is yet to be determined and the incidence of perioperative spasm and long-term patency of a coronary graft may be affected by the properties of the graft response to certain vasoactive substances. The reactivity of the gastroepiploic artery to vasoactive substances has not been studied extensively and the results of the studies are contradictory. Material and Method: This study was designed to test the reactivity of human gastroepiploic artery to four constrictors and four relaxants. The middle sections of the human gastroepiploic arteries were collected from the patients undergoing gastrectomy and the arterial rings with intact endothelium were suspended in organ baths for isometric tension recording. Result: Epinephrine, norepinephrine, and potassium chloride induced the maximum constriction to higher forces (7.0$\pm$1.1g, 6.6$\pm$0.9g, and 6.5$\pm$1.1g) than 5-hydroxytryptamine did (3.8$\pm$1.7g, p<0.05). Nitroprusside and histamine induced almost full relaxation in the gastroepiploic arteries preconstricted with norepinephrine. There was no significant difference between two relaxants regarding maximum relaxation force. Acetylcholine induced the maximum relaxation to weaker force when compared with nitroprusside and histamine (p<0.05), and isoproterenol was the weakest of the relaxants (p<0.05 compared with acetylcholine). Conclusion: The gastroepiploic artery has a strong capacity of endothelium-dependent relaxation which could have an important influence on long-term patency. The gastroepiploic artery exhibits a potent contractility to catecholamines and the enhanced contractility may facilitate vasospasm in the presence of high circulating levels of catecholamines. Nitroprusside, a potent relaxant in gastroepiploic artery, might be beneficial for the treatment of gastroepiploic arterial graft spasm. The gastroepiploic arterial graft with intact endothelium may respond weakly to beta-adrenoceptor agonist and 5-hydroxytryptamine.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.939-944
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• 1998

Background: The sugical results of the Cox-Maze procedure (CMP) for lone atrial fibrillation(AF) have proven to be exellent. However, those for AF associated with mitral valve(MV) disease have been reported to be a little inferior. Materials and methods: To assess the efficacy and safety of the CMP as a combined procedure with MV operation, we studied retrospectively our experiences. Between April 1994 and October 1997, we experienced 70 (23 males, 47 females) cases of CMP concomitantly with MV operation. Results: The etiologies of MV disease were rheumatic in 67 and degenerative in 3 cases. The mean duration of AF before sugery was 66$\pm$70 months. Fifteen patients had the past medical history of thromboembolic complications, and left atrial thrombi were identified at operation in 24 patients. Twelve cases were reoperations. Aortic cross clamp (ACC) time was mean 151$\pm$44 minutes, and cardiopulmonary bypass (CPB) time was mean 246$\pm$65 minutes. Concomitant procedures were mitral valve replacement (MVR) in 19, MVR and aortic valve replacement (AVR) in 14, MVR and tricupid annuloplasty (TAP) in 8, MVR with AV repair in 3, MV repair in 11, MVR and coronary artery bypass grafting (CABG) in 2, MVR and AVR and CABG in 1, redo-MVR in 10, redo-MVR and redo-AVR in 2 patients. The rate of hospital mortality was 1.4%(1/70). Perioperative recurrence of AF was seen in 44(62.9%), and atrial tachyarrhythmias in 10(14.3%), low cardiac output syndrome in 4(5.7%), postoperative bleeding that required mediastinal exploration in 4(5.7%) patients. Other complications were acute renal failure in 2, aggravation of preoperative hemiplegia in 1, and transient delirium in 1 patient. We followed up all the survivors for 16.4 months(3-44months) on an average. Sinus rhythm has been restored in 65(94.2%) patients. AF has been controlled by operation alone in 73.9% and operation plus medication in 20.3%. Two patients needed permanent pacemaker implantation; one with sick sinus syndrome, and the other with tachycardia- bradycardia syndrome. Only two patients remained in AF. We followed up our patients with transthoracic echocardiography to assess the atrial contractilities and other cardiac functions. Right atrial contractility could be demonstrated in 92% and left atrial contractility in 53%.We compared our non-redo cases with redo cases. Although the duration of AF was significantly longer in redo cases, there was no differences in ACC time, CPB time, postoperative bleeding amount and sinus conversion rate. Conclusions: In conclusion, the CMP concomitant with MV operation demonstrated a high sinus conversion rate under the acceptable operative risk even in case of reoperation.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.224-236
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• 1999

Background: To evaluate the short-term effect of dynamic cardiomyoplasty on circulatory function and detect the related factors that can affect it, experimental cardiomyoplasties were performed under the state of normal cardiac function and heart failure. Material and Method: A total of 10 mongrel dogs weighing 20 to 30kg were divided arbitrarily into two groups. Five dogs of group A underwent cardiomyoplasty with latissimus dorsi(LD) muscle mobilization followed by a 2-week vascular delay and 6-week muscle training. Then, hemodynamic studies were conducted. In group B, doxorubicin was given to 5 dogs in an IV dose of 1 mg/kg once a week for 8 weeks to induce chronic heart failure, and simultaneous muscle training was given for preconditioning during this period. Then, cardiomyoplasties were performed and hemodynamic studies were conducted immediately after these cardiomyoplasties in group B. Result: In group A, under the state of normal cardiac function, only mean right atrial pressure significantly increased with the pacer-on(p<0.05) and the left ventricular hemodynamic parameters did not change significantly. However, with pacer-on in group B, cardiac output(CO), rate of left ventricular pressure development(dp/dt), stroke volume(SV), and left ventricular stroke work(SW) increased by 16.7${\pm}$7.2%, 9.3${\pm}$3.2%, 16.8${\pm}$8.6%, and 23.1${\pm}$9.7%, respectively, whereas left ventricular end-diastole pressure(LVEDP) and mean pulmonary capillary wedge pressure(mPCWP) decreased by 32.1${\pm}$4.6% and 17.7${\pm}$9.1%, respectively(p<0.05). In group A, imipramine was infused at the rate of 7.5mg/kg/hour for 34${\pm}$2.6 minutes to induce acute heart failure, which resulted in the reduction of cardiac output by 17.5${\pm}$2.7%, systolic left ventricular pressure by 15.8${\pm}$2.5% and the elevation of left ventricular end-diastole pressure by 54.3${\pm}$15.2%(p<0.05). With pacer-on under this state of acute heart failu e, CO, dp/dt, SV, and SW increased by 4.5${\pm}$1.8% and 3.1${\pm}$1.1%, 5.7${\pm}$3.6%, and 6.9${\pm}$4.4%, respectively, whereas LVEDP decreased by 11.7${\pm}$4.7%(p<0.05). Comparing CO, dp/dt, SV, SW and LVEDP that changed significantly with pacer-on, both under the state of acute and chronic heart failure, augmentation widths of these left ventricular hemodynamic parameters were significantly larger under the state of chronic heart failure(group B) than acute heart failure(group A)(p<0.05). On gross inspection, variable degrees of adhesion and inflammation were present in all 5 dogs of group A, including 2 dogs that showed no muscle contraction. No adhesion and inflammation were, however, present in all 5 dogs of group B, which showed vivid muscle contractions. Considering these differences in gross findings along with the following premise that the acute heart failure state was not statistically different from the chronic one in terms of left ventricular parameters(p>0.05), the larger augmentation effect seen in group B is presumed to be mainly attributed to the viability and contractility of the LD muscle. Conclusion: These results indicate that the positive circulatory augmentation effect of cardiomyoplasty is apparent only under the state of heart failure and the preservation of muscle contractility is important to maximize this effect.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.425-430
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• 2014

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, $K^+$ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, $N^G$-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the $H_2$ receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through $H_2$ receptor and NO/sGC pathways.

• The Korean Journal of Physiology
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• v.15 no.1
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• pp.61-66
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• 1981

In 1944 Cavallito and Bailey first extracted an essential oil, a powerful antibacterial principle, from the garlic and named it allicin. Later Stoll and Seeback elucidated that allicin was produced from alliin by the enzymatic action of arinase. Damaru observed the depressor responses following intraperitoneal administration of garlic juice in cats. And Thiersch presented evidence that garlic had a protective action against experimental arterosclerosis in cholesterol-fed animals. On the other hand it was also reported that anemias were caused by long-term ingestion of garlic as a result of reduction in hemoglobin and RBC. From the experiment in which the effect of garlic on the blood sugar level was studied, Lee insisted garlic elevated blood sugar level. However, August and Jain claimed that hypoglycemia was induced by garlic administration. Recently Bordia and Bansal suggested that essential oils extracted from onion and garlic have a strong preventive effect on hyperlipemia and prolonged coagulation time resulted from fat-feeding. Furthermore Bordia et al indicated that garlic exerted a strong fibrinolytic activity. In early 1920 s Sugihara reported that essential oil of garlic not only decreased arterial blood pressure but also had a paralytic effect on the isolated heart and intestinal strip of animals. The present study was proposed to investigate the effect of garlic juice and the mechanism of its action on the motility of the isolated rabbit duodenum. The motility of the isolated duodenum was recorded on polygraph by means of force transducer connected with Magnus apparatus. And the isolated duodenum was separtely pretreated with $acetylcholine(5{\times}10^{-7}\;gm/ml)$, $pilocarpine(2.5{\times}10^{-6}\;gm/ml)$, $histamine(5{\times}10^{-6}\;gm/ml)$ and barium $chloride(2.5{\times}10^{-5}\;gm/ml)$ in order to find out interations of these drugs with ASJ. The results obtained were as follows; At concentrations of 0.25%, 0.5% and 1.0% ASJ markedly inhibited contractions of isolated duodenum while tonus as well as contractility of the isolated intestine were decreased also with 0.5% and 1.0% ASJ. Since ASJ markedly abolished augmented motility of isolated intestine by histamine and partly reduced that by $BaCl_2$, it is strongly suggested that inhibitory action of ASJ on the intestinal motility is caused mainly by its antihistamine effect and partly by its direct action on the intestinal smooth muscle.