• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.463-469
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• 2000

It has been well known that 4-aminopyridine (4-AP) has an excitatory effect on vascular smooth muscle due to causing membrane depolarization by blocking $K^+-channel$. However, we observed that 4-AP had an inhibitory effect on the mesenteric artery of rat. Therefore, we investigated the mechanism of 4-AP-induced vasorelaxation. The mesenteric arcuate artery and its branches were isolated and cut into ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured. 4-AP $(0.1{\sim}10\;mM)$ induced a concentration-dependent relaxation, which was unaffected by NO synthase inhibitor, $N^G-nitro-L-arginine$ methylester $(100\;{\mu}M)$ or soluble guanylate cyclase inhibitor, methylene blue $(100\;{\mu}M).$ Glibenclamide $(100\;{\mu}M)$, ATP-sensitive $K^+$ channel blocker, did not exert any effect on the 4-AP-induced vasorelaxation. 4-AP relaxed the sustained contraction induced by 100 mM $K^+$ or $Ca^{2+}$ ionophore, A23187 $(100\;{\mu}M)$ in a dose-dependent manner. In addition, 4-AP significantly decreased the phasic contractile response to norepinephrine in the absence of extracellular $Ca^{2+}$. However, 4-AP did not block the $^{45}Ca$ influx of rat aorta. From the above results, we suggest that 4-AP may not block the $Ca^{2+}$ influx through $Ca^{2+}-channel,$ but act as a nonspecific vasorelaxant in arterial smooth muscle.

• Biomedical Science Letters
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• v.27 no.4
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• pp.270-276
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• 2021

Physiological agents trigger a signaling process called "inside-out signaling" and activated platelets promote adhesion, granule release, and conformational changes of glycoprotein IIb/IIIa (αIIb/β₃). Activated αIIb/β₃ interacts with fibrinogen and initiates a second signaling step called "external signaling". These two signaling pathways can cause hemostasis or thrombosis, and thrombosis is a possible medical problem in arterial and venous vessels, and platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, modulating platelet activity is important for platelet-mediated thrombosis and cardiovascular disease. Esculetin is a coumarin-based physiologically active 6,7-dihydroxy derivative known to have pharmacological activity against obesity, diabetes, renal failure and CVD. Although some studies have confirmed the effects of esculetin in human platelet activation and experimental mouse models, it is not clear how esculetin has antiplatelet and antithrombotic effects. We confirmed the effect and mechanism of action of escultein on human platelets induced by collagen. As a result, esculetin decreased Ca²⁺ recruitment through upregulation of inositol 1, 4, 5-triphosphate receptor. In addition, esculetin upregulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent pathways and inhibits fibrinogen binding and thrombus contraction. Our results demonstrate the antiplatelet effect and antithrombotic effect of esculetin in human platelets. Therefore, we suggest that esculetin could be a potential phytochemical for the prevention of thrombus-mediated CVD.

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

• Journal of the Korean Society of Food Science and Nutrition
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• v.14 no.3
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• pp.253-258
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• 1985

It was aimed to elucidate the underlying mechanism which is elevated the systemic arterial blood pressure by cadmium(Cd). By using the isolated vas deferens and tail artery from Cd-poisoned rats, it was undertaken to see whether the ${\alpha}-adrenoceptor$ activity and prostaglandins action on the twitch response to electrical stimulation were altered. It was discussed in relation with sympathetic nerve activity. The response to electrical stimulation in vas deferens from Cd-poisoned rats was much enhanced, and frequency 50(Freq.50) was significantly lowered, comparing to control. However, the response of rat tail artery was attenuated by Cd. Inhibitory action of clonidine on the twitch response of vas deferens to electrical stimulation was decreased by Cd-poisoning. However, the increase in response in the presence of methoxamine was not affected. The inhibitory action of prostaglandin $E_2$ on the twitch response in the vas deferens but not in the tail artery was abolished or rather inverted by Cd-poisoning. In the tail artery from Cd-poisoned rats, the maximum contraction to methoxamine or clonidine was significantly decreased, however, $ED_{50}$ of both agonists was not changed. These results suggest that in vas deferens the autoreceptor of presynaptic membrane is inhibited by Cd-poisoning, by which mechanism the sympathetic activity is being enhanced and this alteration may be causally related to the elevation of arterial pressure.

• Journal of Chest Surgery
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• v.37 no.1
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• pp.1-10
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• 2004

Background: Currently, the cardiopulmonary machine with non-pulsatile pumps, which are low in internal circuit pressure and cause little damage to blood cells, is widely used. However, a great number of experimental studies shows that pulsatile perfusions are more useful than non-pulsatile counterparts in many areas, such as homodynamic, metabolism, organ functions, and micro-circulation. Yet, many concerns relating to pulsatile cardiopulmonary machines, such as high internal circuit pressure and blood cell damage, have long hindered the development of pulsatile cardiopulmonary machines. Against this backdrop, this study focuses on the safety and effectiveness of the pulsatile cardiopulmonary machines developed by a domestic research lab. Material and Method: The dual-pulsatile cardiopulmonary bypass experiment with total extracorporeal circulation was conducted on six calves, Extracorporeal circulation was provided between superior/inferior vena cava and aorta. The membrane oxygenator, which was placed between the left and right pumps, was used for blood oxygenation. Circulation took four hours. Arterial blood gas analysis and blood tests were also conducted. Plasma hemoglobin levels were calculated, while pulse pressure and internal circuit pressure were carefully observed. Measurement was taken five times; once before the operation of the cardiopulmonary bypass, and after its operation it was taken every hour for four hours. Result: Through the arterial blood gas analysis, PCO2 and pH remained within normal levels. PO2 in arterial blood showed enough oxygenation of over 100 mmHg. The level of plasma hemoglobin, which had total cardiopulmonary circulation, steadily increased to 15.87 $\pm$ 5.63 after four hours passed, but remained below 20 mg/㎗. There was no obvious abnormal findings in blood test. Systolic blood pressure which was at 97.5$\pm$5.7 mmHg during the pre-circulation contraction period, was maintained over 100 mmHg as time passed. Moreover, diastolic blood pressure was 72.2 $\pm$ 7.7 mmHg during the expansion period and well kept at the appropriate level with time passing by. Average blood pressure which was 83$\pm$9.2 mmHg before circulation, increased as time passed, while pump flow was maintained over 3.3 L/min. Blood pressure fluctuation during total extracorporeal circulation showed a similar level of arterial blood pressure of pre-circulation heart. Conclusion: In the experiment mentioned above, pulsatile cardiopulmonary machines using the doual-pulsatile structure provided effective pulsatile blood flow with little damage in blood cells, showing excellence in the aspects of hematology and hemodynamic. Therefore, it is expected that the pulsatile cardiopulmonary machine, if it becomes a standard cardiopulmonary machine in all heart operations, will provide stable blood flow to end-organs.

• The Korean Nurse
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• v.33 no.4
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• pp.62-85
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• 1994

The data were analyzed by using an S. P. S. S. computerized program for mean, standard deviation, percentage and paired t-test. The results of this study were as follows: 1. The increase in $PaO_2$ after hyperoxygenation and hyperinflation was highly statistically significant(p=0.041), and the increase in $PaO_2$ immediately after suctioning was not significant (p=0.752). The time of lowest $PaO_2$ was 30 seconds after the endotracheal suction. 2. The occurrance of cardiac arrhythmia after the endotracheal suction included sinus tachycardia, sinus arrhythmia, sinus bradycardia, premature atrial contraction (PAC), and premature ventricular contraction (PVC). The most frequent cardiac arrhythmia was sinus tachycardia (a subjects). Sinus arrhythmia was observed in 5 subjects and continued till 10 minutes after suctioning in two of these. Sinus bradycardia occurred in only 3 subjects and among them, 1 subjects shows sinus arrythmia till 10 minutes after suctioning along. PAC was observed in only one subject and continued till five minutes after suctining along with sinus arrhythmia. PVC was observed in three subjects: it lasted for only 30 seconds after suctioning in two subjects. but continued for 10 minutes after suctioning in the third. 6 subjects manifested two kinds of Cardiac arrhythmia Three of them showed sinus tachycardia with PVC, another 2 showed sinus bradycardia with sinus arrhythmia, and the other subject showed sinus arrhythmia with PAC. 3. The increases in heart rate during the endotracheal suction immediately after and at 30 seconds after suctioning were statistically significant (p=0.005). The increase in heart rate at one minute after suctioning was also significant (p=0.023). The increase in heart rate continued until 10 minutes after the endotracheal suction, but was not statistically significant In this study, endotracheal suctioning with hyperoxygenation and hyperinflation was effective in preventing a decrease in $PaO_2$ after suctioning, but not in preventing cardiac arrhythmias. Nurses should be aware of the complications of endotracheal suctioning and do effective hyperoxygenation and hyperinflation before and after suctioning. Further research is needed to develop a efficient endotracheal suction method which will minimize complications. This study needs to be replicated with different population of patients intubatted or having a tracheostomy, specifically, patients who cardiac or pulmonary desease. The data were analyzed by using an S. P. S. S. computerized program for mean, standard deviation, percentage and paired t-test. The results of this study were as follows: 1. The increase in $PaO_2$ after hyperoxygenation and hyperinflation was highly statistically significant(p=0.041), and the increase in $PaO_2$ immediately after suctioning was not significant (p=0.752). The time of lowest $PaO_2$ was 30 seconds after the endotracheal suction. 2. The occurrance of cardiac arrhythmia after the endotracheal suction included sinus tachycardia, sinus arrhythmia, sinus bradycardia, premature atrial contraction (PAC), and premature ventricular contraction (PVC). The most frequent cardiac arrhythmia was sinus tachycardia (a subjects). Sinus arrhythmia was observed in 5 subjects and continued till 10 minutes after suctioning in two of these. Sinus bradycardia occurred in only 3 subjects and among them, 1 subjects shows sinus arrythmia till 10 minutes after suctioning along. PAC was observed in only one subject and continued till five minutes after suctining along with sinus arrhythmia. PVC was observed in three subjects: it lasted for only 30 seconds after suctioning in two subjects. but continued for 10 minutes after suctioning in the third. 6 subjects manifested two kinds of Cardiac arrhythmia Three of them showed sinus tachycardia with PVC, another 2 showed sinus bradycardia with sinus arrhythmia, and the other subject showed sinus arrhythmia with PAC. 3. The increases in heart rate during the endotracheal suction immediately after and at 30 seconds after suctioning were statistically significant (p=0.005). The increase in heart rate at one minute after suctioning was also significant (p=0.023). The increase in heart rate continued until 10 minutes after the endotracheal suction, but was not statistically significant In this study, endotracheal suctioning with hyperoxygenation and hyperinflation was effective in preventing a decrease in $PaO_2$ after suctioning, but not in preventing cardiac arrhythmias. Nurses should be aware of the complications of endotracheal suctioning and do effective hyperoxygenation and hyperinflation before and after suctioning. Further research is needed to develop a efficient endotracheal suction method which will minimize complications. This study needs to be replicated with different population of patients intubatted or having a tracheostomy, specifically, patients who cardiac or pulmonary desease.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.463-468
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• 2013

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated $K^+$ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane $A_2$ ($TXA_2$) and hypoxia-activated nonselective cation channel ($I_{NSC}$) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and $TXA_2$-activated $I_{NSC}$ was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased $I_{NSC}$ might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.4
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• pp.225-233
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• 2002

Kanagawa hemolysin (KH), an exotoxin produced from Kanagawa phenomenon-positive Vibrio parahemolyticus, has been shown to possess various biological activities including hemolysis, enterotoxicity, cytotoxicity, and cardiotoxicity. The aim of this study was to investigate the effect of KH on the cardiovascular system and its mechanism, employing in vivo and in vitro experiments of the rat. Intracerebroventricular (icv) administration of 100 mHU KH produced a marked and continuous pressor effect (icv KH-pressor effect), and the icv pressor effect was not repeatable. However, intravenous (iv) injection of the same dose of KH induced a prominent depressor effect (iv KH-depressor effect). The icv KH-pressor effect was inhibited by acid-denaturation, while the iv KH-depressor effect was not. Simultaneous icv administration of the three agents (ouabain, diltiazem, or bumetanide: $10{\mu}g/kg$ each) significantly reduced the pressor effect. The icv KH-pressor effect was inhibited by treatment with iv phentolamine or chlorisondamine, but was not affected by iv candesartan. The iv KH-depressor effect was repeatable and was attenuated by treatment with iv NAME or methylene blue. In vitro experiments using isolated thoracic aorta, $10^{-6}$ M phenylephrine (PE) and 50 mM KCl produced a sustained contraction. In rings contracted with either agents, KH showed relaxant responses in a concentration- dependent fashion and the relaxation (KH-vasorelaxation) was not dependent on the existence of the endothelium. The KH-vasorelaxation in the endothelium-intact rings contracted by PE was abolished by methylene blue treatment. In summary, the present findings suggest that in the icv KH-pressor effect the cation leak-inducing action of KH is implicated, which leads to the increased central sympathetic tone, that the iv KH-depressor effect results from the vasorelaxation via NO-guanylate cyclase system, and that the KH-vasorelaxation is independent of the endothelium and the guanylate cyclase system is involved in it. In conclusion, the mechanism of KH producing the icv pressor effect may not be identical to that of KH producing the iv depressor effect.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.115-121
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• 1990

The interaction between a calcium channel blocker nifedipine and atrial natriuretic peptide (ANP) was examined in normotensive and renal hypertensive rats. The infusion of either ANP or nifedipine produced a significant decrease in mean arterial pressure (MAP). The combined infusion of ANP with nifedipine resulted in a greater fall of MAP than did the infusion of each drug alone. ANP significantly increased urinary volume and excretion of sodium, while nifedipine was without effects. The diuretic/natriuretic effects of ANP were potentiated by the combined infusion with nifedipine. The vasodepressor and renal effects of ANP or nifedipine were qualitatively similar between the normotensive and hypertensive rats. Nifedipine caused an upward and leftward shift of the ANP dose-relaxation curve of the phenylephrine-precontracted thoracic aortic rings isolated from the normotensive rats , suggesting that the vasodilation sensitivity to ANP is increased in the presence of nifedipine. These results indicate that nifedipine enhances the vasodepressor effect of ANP, the likely mechanisms being attributable to a contraction of effective intravascular volume as a consequence of potentiated renal excretion and a greater peripheral vasodilation.

• Archives of Reconstructive Microsurgery
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• v.17 no.2
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• pp.120-125
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• 2008

Purpose: Heat therapy by heat lamp after microvascular surgery is being used for preventing blood vessels's contraction and blood-flow's disturbance. As usually, incandescent lamp has been used. But there have been several problems and need for improvement in the existing heat lamp treatment. So we would like to introduce improved heat lamp to keep an appropriate temperature and intensity of illumination. Methods: The existing heat lamps are the ones of general light stands covered with newspaper, having 60 watt light bulb of incandescence and lampshade made of aluminum. We have tried to improve shortcomings of the existing heat lamps by enlarging the size of aluminum lampshade and attaching a curtain that can block heat and light. We conducted a comparative study between the existing and improved heat lamps. Under the assumption that there are several affected parts, we have also measured the distance from heat lamp to patients' eye region and then intensity of illumination. Result: The target temperature of surface was realized in 11 minutes with the maximum temperature reaching at 36.6 degrees C in 28 minutes at the existing heat lamp while the target temperature reached in 7 minutes with the maximum temperature reaching at 39.0 degrees C in 17 minutes at the improved heat lamp. The existing and improved heat lamp showed 38 lx and 0.1 lx of intensity of lumination, respectively. Conclusion: Using improved heat lamps, we can keep an appropriate temperature and we think we can make contribution to patients' treatment by making them and their neighbors able to sleep with minimized disturbance thanks to low intensity of illumination secured by blocking light.