• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.19-27
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• 1975

Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.301-309
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• 2018

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

• Journal of Chest Surgery
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• v.18 no.4
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• pp.692-699
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• 1985

Fifty cases of Open Heart Surgery due to congenital and acquired heart disease were done using the cardiopulmonary bypass in the Department of Thoracic and Cardiovascular surgery, Chosun University Hospital from November, 1980 to June, 1985. 1. The age of the congenital heart disease was from 7 to 29 years, the mean age was 14.5 years. In the acquired heart disease, the age was from 14 to 48 years, and the mean age was 22.3 years. The ratio of male to female was about 1.8:1. 2. The number of congenital cyanotic heart disease were 7 patients, congenital acyanotic heart disease were 17 patients and acquired valvular heart disease were 26 patients. All of the acquired heart disease was one or more valve disease. 3. Preoperative symptoms of the congenital heart disease were exertional dyspnea [cyanotic 100%, acyanotic 70.6%] and palpitation [cyanotic 28.6%, acyanotic 76.1%], and the acquired heart diseases were exertional dyspnea [92.3%], palpitation [34.1 %], and chest discomfort [30.8%]. 4. The method of the myocardial protection during the cardiopulmonary bypass were mild or moderate hypothermia, intermittent coronary perfusion of the cardioplegic solution, topical myocardial hypothermia with 4oC Hartmann`s solution. 5. In the cases of the valve replacement, postoperative oral anticoagulant therapy was started at oral intake of food using the warfarin and persantin, and the prothrombin time was maintained 30-50% of control value during 3-6 months for tissue valve replacement and permanently for metal valve replacement. 6. The postoperative complications were appeared in 24 cases and the complications were wound infection, occipital alopecia, hemorrhage etc. 7. The mortality after open heart surgery was 8 percents and the cause of death was low cardiac output syndrome, right heart failure, DIC, and Left ventricle rupture.

• Journal of Chest Surgery
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• v.18 no.4
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• pp.718-731
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• 1985

Renal dysfunction is a common complication of open-heart surgery: a form of controlled hemorrhagic shock, and successful perioperative management of renal dysfunction depends on recognition of the risk factors and optimal management of factors influencing renal function, including cardiopulmonary bypass, and early detection of renal failure. Changes in renal functional parameters including Ccr, Cosm, CH2O, FENa, and RFI were observed prospectively in forty five patients operated on at Dept. of Thoracic and Cardiovascular Surgery, S.N.U.H., from April to June, 1985. They were 23 males and 22 females with 35 acquired and 10 congenital heart diseases and the mean age and body surface area of them were 38.010.3 years [22-63] and 1.5518 M2[1.151.92] respectively. Followings are the conclusion. 1. The Ccr, representative of renal function, is significantly improved from 90.231.3 ml/min/M2 preoperatively to 101.536.4 ml/min/M2 postoperative and day [P<0.05], and all patients were classified as postoperative renal functional class I of Abel, which representing adequate renal protection during our cardiopulmonary bypass. 2. The Cosm is significantly elevated at immediate postperfusion time and remained high at postoperative one day representing osmotic diuresis at that time, but CH2O shows no significant changes at immediate postperfusion period and is decreased significantly at postoperative one day, representing recovery of renal concentrating ability at that time with decreasing urine flow. 3. The absolute value and changing tendency in FENa and RFI during perioperative period shows no diagnostic reliability on these parameters, but those of CH2O appear to reveal future renal function more accurately than Ccr 4. The depth of hypothermia may be protective upon renal function against the ill effects of prolonged nonpulsatile cardiopulmonary bypass. 5. The depth of the hypothermia, pump time of more than 150 minutes, poor cardiac function, and intraoperative events such as embolism appear to be related with immediate postperfusion renal function. 6. Hemoglobinuria and hemolysis, poor preoperative renal function, history of cardiac surgery, and massive transfusion associated with bleeding appear not to be related with renal dysfunction.

• Journal of Chest Surgery
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• v.41 no.4
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• pp.405-416
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• 2008

Background: Spinal cord ischemic injury during thoracic and thoracoabdominal aortic surgeries remains a potentially devastating outcome despite using various methods of protection. Neuronal voltage-dependent sodium channel antagonists are known to provide neuroprotection in cerebral ischemic models. This study was designed to compare the neuroprotective effects of phenytoin with those of hypothermia in a rabbit model of spinal cord ischemia. Material and Method: Spinal cord ischemia was induced in New Zealand white rabbits by means of infrarenal aortic cross clamping for 25 minutes. Four groups of 8 animals each were studied. The control group and the hypothermia group received retrograde infusion of saline only ($22^{\circ}C$, 2 mL/min); the normothermic phenytoin group and the hypothermicphenytoin group received retrograde infusion of 100 mg of phenytoin at different rectal temperatures ($39^{\circ}C$ and $37^{\circ}C$, respectively) during the ischemic period. The neurologic function was assessed at 24 and 72 hours after the operation with using the modified Tarlov criteria. The spinal cords were harvested after the final neurologic examination for histopathological examination to objectively quantify the amount of neuronal damage. Result: No major adverse effects were observed with the retrograde phenytoin infusion during the aortic ischemic period. All the control rabbits became severely paraplegic, Both the phenytoin group and the hypothermia group had a better neurological status than did the control group (p < 0.05). The typical morphological changes that are characteristic of neuronal necrosis in the gray matter of the control animals were demonstrated by means of the histopathological examination, whereas phenytoin or hypothermia prevented or attenuated these necrotic phenomena (p < 0.05). The number of motor neuron cells positive for TUNEL staining was significantly reduced, to a similar extent, in the rabbits treated with phenytoin or hypothermia. Phenytoin and hypothermia had some additive neuroprotective effect, but there was no statistical significance between the two on the neurological and histopathological analysis. Conclusion: The neurological and histopathological analysis consistently demonstrated that both phenytoin and hypothermia may afford significant spinal cord protection to a similar extent during spinal cord ischemia in rabbits, although no significant additive effects were noticed.

• Journal of Chest Surgery
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• v.26 no.7
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• pp.513-520
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• 1993

Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch still poses one of the most complicated technical and tactical challenges in surgery. The use of total circulatory arrest[TCA] with profound hypothermia in the surgical treatment of aneurysmal dissection involving the ascending aorta and aortic arch has been reported as popular surgical methods. However, the safe period of prolonged circulatory arrest with hypothermia remains controversial and ischemic damage to the central nervous system and uncontrollable perioperative bleeding have been the major problem. We have found profound hypothermic circulatory arrest with retrograde cerebral perfusion via the superior vena cava to achieve cerebral protection. We experiment the aortic anastomosis in 7 adult mongrel dogs, using profound hypothermic circulatory arrest with continuous retrograde cerebral perfusion[RGCP] via superior vena cava. We also studied the extent of cerebral protection using above surgical methods, by gas analysis of retrograde cerebral perfusion blood and returned blood of aortic arch, preoperative, intraoperative and postoperative electroencephalography and microscopic findings of brain tissue. The results were as follows: 1. The cooling time ranged from 15 minutes to 24 minutes[19.71$\pm$ 3.20 minutes] ; Aorta cross clamp time ranged from 70 minutes to 89 minutes[79.86 $\pm$ 7.54 minutes] ; Rewarming time ranged from 35 minutes to 47 minutes[42.86$\pm$ 4.30 minutes] ; The extracorporeal circulation time ranged from 118 minutes to 140 minutes[128.43$\pm$ 8.98 minutes] [Table 2]. 2. The oxygen content in the oxygenated blood after RGCP was 12.66$\pm$ 1.25 ml/dl. At 5 minutes after the initiation of RGCP, the oxygen content of returnedlood was 7.58$\pm$ 0.21 ml/dl, and at 15 minutes 7.35$\pm$ 0.17 ml/dl, at 30 minutes 7.20$\pm$ 0.19 ml/dl, at 60 minutes 6.63$\pm$ 0.14 ml/dl [Table 3]. 3. Intraoperative electroencephalographic finding revealed low amplitude potential during hypothermia, and no electrical impulse throughout the period of circulatory arrest and RGCP. Electrical activity appeared after reperfusion, and the electroencephalographic reading also recovered rapidly as body temperature returned to normal [Fig. 2]. 4. The microscopic finding of brain tissue showed widening of the interfibrillar spaces. But there was no evidence of tissue necrosis or hemorrhage [Fig. 3]. We concluded the retrograde cerebral perfusion during hypothermic circulatory arrest is a simplified technique that may have a excellent brain protection.

• Journal of Chest Surgery
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• v.18 no.4
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• pp.732-739
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• 1985

This study was experimentally undertaken to evaluate the effect of the coronary vasodilator-mixed cardioplegic solution on myocardial protection during prolonged aortic cross-clamping. The dogs were divided into two groups: control group A[received hypothermic cardioplegic solution without any additive coronary vasodilator], and comparing group 8[received hypothermic cardioplegic solution, mixed with various coronary vasodilators and Inderal]. Group A further was divided into two subgroups: subgroup A-1[ischemic time, 90 minutes], and subgroup A-2 [ischemic time, 240 minutes]. Group B further was divided into five subgroups: subgroup B-1 [received papaverine mixed hypothermic cardioplegic solution], subgroup B-2[received nitroglycerin mixed hypothermic cardioplegic solution], subgroup B-3 [received nitroprusside mixed hypothermic cardioplegic solution, subgroup B-4[received hydralazine mixed hypothermic cardioplegic solution], and subgroup B-5 [received inderal mixed hypothermic cardioplegic solution]. The specimens from all of the subgroups were studied by electron microscopic examination. The specimens of subgroups [B-l, B-2 8-3, and B-4], received coronary vasodilators mixed hypothermic cardioplegic solutions, were also compared by methylene blue induced staining of the myocardium and coronary vessels. The results obtained were as followings: l. On electron microscopic examination, all of the specimens, including subgroup A-2, showed no irreversible change of the myocardium. But the best result was obtained from the subgroup B-l, treated by papaverine mixed hypothermic cardioplegic solution. The subgroup B-2, treated by nitroglycerin, was next. And the subgroup B-5, treated by Inderal, was agreeable, comparing the electron microscopic finding with control group in the effect of myocardial protection. 2. The distribution in the myocardium of cardioplegic solution was demonstrated with the aid of methylene blue staining in the subgroups of B-l, B-2, B-3, and B-4, and they were the groups treated by papaverine, nitroglycerin, nitroprusside, and hydralazine in their grouping order. The best result was obtained from the subgroup B-1 [papaverine]. The subgroup B-2 [nitroglycerin] was next. The subgroup B-3 [nitroprusside] was moderate in finding of the colorization. The subgroup B-4 [hydralazine] was the poorest in the distribution of the cardioplegic solution in the myocardium. From these results, it appeared that myocardial protection during ischemic arrest for open heart surgery could be enhanced considerably when coronary dilatation was assured.

• Journal of Chest Surgery
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• v.30 no.9
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• pp.847-853
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• 1997

Although the effects of adenosine on the heart, including the clinical suppression of cardiac arrhythmias, have been recognized for more than half a century, it is only in the last decade that the therapeutic potential of adenosine has been recognized. The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. We used to modified Langendonf system to evaluate myocardial protective effect. Isolated rat hearts were subjected to 90 minutes of deep hypothermic arrest(15$^{\circ}C$) with modified St. Thomas'Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution. Two groups of hearts w re studied: (1) control group(n=10) cardioplegia alone; (2) adenosine group(n=10) adenosine(0.75mg/kg/min) added to the cardioplegic solution. Significantly better percent recovery(p<0.01) in hemodynamics(except heart rate) at 60 minutes after reperfusion was evident compared to baseline values in the adenosine group. (systolic no란ic pressure : 78.5$\pm$3.6% vs 66.6$\pm$5.9%, airtic overflow volume : 61.7$\pm$ 11.6% vs 37.2$\pm$ 15.4%, coronary flow volume 77.1$\pm$7.5% vs 57.2$\pm$ 11.1%, and cardiac output : 65.6$\pm$ 11.5% vs 44.2$\pm$ 12.4%). Heart rate was similar in two groups(94.4$\pm$4.8% vs 95.3 $\pm$ 6.8%). Adenosine groups resulted in significantly rapid recovery time of heart beat after reperEusion(p<0.01) (24.5$\pm$7.6 sec. vs 179.0$\pm$ 131.1sec.). In biochemical study, CPK levels(0.1 $\pm$0.3U/L vs 1.4$\pm$0.8U/L) and lactic acid levels(0.08$\pm$0.Immol/L vs 0.34$\pm$0.2 mmol/L) were significantly low in adenosine groups(p<0.01). We concluded that adenosine included cardioplegia have better recovery effects after r perfusion in myocardial ischemia compared to adenosine free cardioplegia.

• Journal of Chest Surgery
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• v.25 no.3
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• pp.211-219
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• 1992

Hypothermic cardioplegia is a well established method to optimize myocardial preservation during ischemic arrest, and it has been demonstrated that oxygenation of crystalloid cardioplegic solutions markedly enhances myocardial protection, The addition of a small amount of red blood cells to a crystalloid cardioplegic solutions improves capillary perfusion. Considering these results, we changed our cardioplegic solution from cold oxygenated crystalloid[Group 2] to cold oxygenated diluted blood[Group 1]. In this investigation, we examined the effects of two hypothermic potassium cardioplegic solutions on myocardial preservation in 50 patients[30 of Group 1 and 20 of Group 2] of child age group. Factors considered preoperatively included age, sex, body weight, preoperative diagnosis, and they showed no statistical differences, Intraoperative factors considered included duration of cardiopulmonary bypass, duration of aortic occlusion, operative mortality, which also revealed no statistically significant differences, We measured the serum levels of GOT[glutamate oxaloacetate transaminase] and CPK [creatine phosphokinase] during the first two days postoperatively, which, in both groups, showed significantly higher values until postoperative 1 day, and decreasing tendancy thereafter, however we failed to find any significant difference between two groups regarding the serum levels of those enzymes each day. Time for extubation and use of inotropics also revealed no significant differences. Defibrillation was needed less in Group 1 than in Group 2[p<0.05], and one case of supraventricular tachyarrhythmia occured in Group l. We conclude that cold oxygenated diluted blood cardioplegia provides no less preservation than does an oxygenated crystalloid cardioplegic solution in child age group.

• Journal of Chest Surgery
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• v.33 no.6
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• pp.502-506
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• 2000

Background: Anticoagulant therapy can be required during pregnancy with prosthetic heart valves. Warfarin and heparin provide real protection against thromboembolic phenomena, but they also carry serious risks for the fetus and the mother. In an attempt to identify the best treatment for pregnant women with cardiac valve prostheses who are receiving anticoagulant, we studied 19 pregnancies, the warfarin was discontinued and heparin was administered every 12 hours by subcutaneous injection in doses adjusted to keep the midinterval aPTT in the therapeutic range(at least 2-2.5 control) from the conception to the 12th week of gestation and oral antiocagulant was then administered until the middle of the third trimester in the therapeutic range(at least 2 INR), and heparin therapy was restared until delivery. Also in order to avoid an anticoagulant effect during delivery, it has been our practice to instruct women to either discontinue their heparin injections with the onset of labur or to stop heparin injections 12 hours prior to the elective induction of labour. Result: The outcome of 19 pregnancies managed with above protocol was spontaneous abortion in 3 cases, voluntary termination in 2 cases, premature delivery at 35 weeks in 1 case and delivery at full-term in 14 cases. There was no maternal morbidity and moratality and fetopathy. Conclusion: We conclude that in the second and third trimester of pregnancy, warfarin provide effective protection against thromboembolism, Oral antiocagulant therapy should be avoided in 2 weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. However, the substitution of heparin at first trimester and 2 weeks before delivery reduce the incidence of complications.