Effect of vitamin D on endothelial and ventricular function in chronic heart failure patients: A prospective, randomized, placebo-controlled trial.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels are common in patients with chronic heart failure (HF) and are associated with increased mortality risk. This study aimed to establish the safety and efficacy of oral vitamin D3 (cholecalciferol) supplementation and its effect on endothelial and ventricular function in patients with stable HF. METHODS: This study was an investigator-initiated, multicenter, prospective, randomized, placebo-controlled trial. Seventy-three HF patients with 25OHD levels < 75 nmol/L (30 ng/mL) were randomized to receive 4000 IU vitamin D daily or a placebo for 6 months. The primary endpoint was a change in endothelial function between the baseline and after 6 months as assessed using EndoPAT. Secondary endpoints included changes in echocardiographic parameters and differences in quality of life (6-min walking test and New York Heart Association functional status) at 6 months. RESULTS: There were no adverse events in either group during the study period. Vitamin D supplementation did not improve endothelial dysfunction (EndoPAT: baseline, 1.19 ± 0.4 vs 6 months later, 1.22 ± 0.3, P = .65). However, patients' blood pressure, 6-min walking distance, and EQ-5D questionnaire scores improved after vitamin D treatment. In addition, a significant reduction in the left atrial diameter was observed. CONCLUSION: A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Effects of Acupuncture on Cardiac Remodeling in Patients with Persistent Atrial Fibrillation: Results of a Randomized, Placebo-Controlled, Patient- and Assessor-Blinded Pilot Trial and Its Implications for Future Research.

Background and Objectives: In this study, we attempted to determine the effects of acupuncture on cardiac remodeling and atrial fibrillation (AF) recurrence rates in patients with AF after electrical cardioversion (EC). Materials and Methods: We randomly assigned 44 patients with persistent AF to an acupuncture group or a sham acupuncture group. An electroacupuncture treatment session was administered once weekly for 12 weeks at four acupuncture points (left PC5, PC6, ST36, and ST37). Results: Among the 44 recruited participants, 16 (treatment group) and 15 (control group) completed the trial. The three-month AF recurrence rate (primary outcome) was not significantly different between the two groups. Following the completion of treatment, patients who had been treated with acupuncture had a significant reduction in left atrial volume index (42.2 ± 13.9 to 36.1 ± 9.7 mL/m2; p = 0.028), whereas no change in atrial size was observed in the sham acupuncture group. No serious adverse events were observed. The AF recurrence rate and cardiac function did not differ significantly between the two groups. At three months, the acupuncture treatment group showed more favorable atrial structural remodeling compared to the sham acupuncture group. Conclusion: In future research on acupuncture in AF management, it is recommended that the inclusion criteria be amended to include only symptomatic AF, that an appropriate control group is designed, and that the acupuncture treatment frequency is increased to several times per week.

Efficacy and safety of electroacupuncture in acute decompensated heart failure: a study protocol for a randomized, patient- and assessor-blinded, sham controlled trial.

BACKGROUND: The purpose of this trial is to evaluate the effectiveness and safety of electroacupuncture in the treatment of acute decompensated heart failure compared with sham electroacupuncture. METHODS: This protocol is for a randomized, sham controlled, patient- and assessor-blinded, parallel group, single center clinical trial that can overcome the limitations of previous trials examining acupuncture and heart failure. Forty-four acute decompensated heart failure patients admitted to the cardiology ward will be randomly assigned into the electroacupuncture treatment group (n = 22) or the sham electroacupuncture control group (n = 22). Participants will receive electroacupuncture treatment for 5 days of their hospital stay. The primary outcome of this study is the difference in total diuretic dose between the two groups during hospitalization. On the day of discharge, follow-up heart rate variability, routine blood tests, cardiac biomarkers, high-sensitivity C-reactive protein (hs-CRP) level, and N-terminal pro b-type natriuretic peptide (NT-pro BNP) level will be assessed. Four weeks after discharge, hs-CRP, NT-pro BNP, heart failure symptoms, quality of life, and a pattern identification questionnaire will be used for follow-up analysis. Six months after discharge, major cardiac adverse events and cardiac function measured by echocardiography will be assessed. Adverse events will be recorded during every visit. DISCUSSION: The result of this clinical trial will offer evidence of the effectiveness and safety of electroacupuncture for acute decompensated heart failure. TRIAL REGISTRATION: Clinical Research Information Service: KCT0002249 .

Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism: A randomized controlled crossover trial.

OBJECTIVE: Exploring clinically effective methods to reduce ischemia-reperfusion (IR) injury in humans is critical. Several drugs have shown protective effects, but studies using other interventions have been rare. Electroacupuncture (EA) has induced similar protection in several animal studies but no study has investigated how the effects could be translated and reproduced in humans. This study aimed to explore the potential effect and mechanisms of EA in IR-induced endothelial dysfunction in humans. METHODS: This is a prospective, randomized, crossover, sham-controlled trial consisting of two protocols. Protocol 1 was a crossover study to investigate the effect of EA on IR-induced endothelial dysfunction. Twenty healthy volunteers were randomly assigned to EA or sham EA (sham). Flow mediated dilation (FMD) of the brachial artery (BA), nitroglycerin-mediated endothelial independent dilation, blood pressure before and after IR were measured. In protocol 2, seven volunteers were administered COX-2 inhibitor celecoxib (200 mg orally twice daily) for five days. After consumption, volunteers underwent FMD before and after IR identical to protocol 1. RESULTS: In protocol 1, baseline BA diameter, Pre-IR BA diameter and FMD were similar between the two groups (p = NS). After IR, sham group showed significantly blunted FMD (Pre-IR: 11.41 ± 3.10%, Post-IR: 4.49 ± 2.04%, p < 0.001). However, EA protected this blunted FMD (Pre-IR: 10.96 ± 5.30%, Post-IR: 9.47 ± 5.23%, p = NS, p < 0.05 compared with sham EA after IR). In protocol 2, this protective effect was completely abolished by pre-treatment with celecoxib (Pre-IR: 11.05 ± 3.27%; Post-IR: 4.20 ± 1.68%, p = 0.001). CONCLUSION: EA may prevent IR-induced endothelial dysfunction via a COX-2 dependent mechanism.

Close look at the experiences of patients enrolled in a clinical trial of acupuncture treatment for atrial fibrillation in Korea: a qualitative study nested within a randomised controlled trial.

OBJECTIVE: To explore the experiences of patients with atrial fibrillation (AF) in the context of a prospective, two-parallel-armed, participant-blinded and assessor-blinded sham-controlled randomised trial. DESIGN: A nested qualitative study within an ongoing randomised controlled trial to explore acupuncture's antiarrhythmic effects on drug refractory acupuncture in persistent atrial fibrillation (AF) (ACU-AF trial). PARTICIPANTS: Participants were recruited using purposeful sampling and a maximum variation strategy with regard to treatment allocation (treatment or control) and protocol completion (completion or non-completion). SETTING: This was a single-centre in-depth interview qualitative study conducted at a tertiary-level university hospital in Seoul, Republic of Korea. RESULTS: Data saturation was reached after 8 participants. Thematic analysis identified that most patients were not aware of their condition until medical check-up; physician referral was the main reason for trial participation, and patients had high expectations regardless of previous acupuncture experiences. Patients tended to depend on their physicians' opinions because they felt helpless of their condition. No one questioned their assigned treatment groups and generally believed acupuncture treatment was different for cardiovascular diseases. A few patients expressed disappointment in the strict and rigid protocols, in which most practitioners refrained from explaining their acupuncture procedures. CONCLUSIONS: For cardiovascular patients their physician's advice was one of the biggest reasons for enrolling in the acupuncture trial therefore relying on standard recruitment methods may not be effective. Fortunately both real and sham acupuncture groups in our sample were receiving treatment as intended, but in the future, designing a more pragmatic trial (better reflecting clinical settings, expanding the inclusion criteria and using more treatment points) will allow researchers to better explore the comprehensive effects of acupuncture. The findings of this study will allow researchers to improve the currently ongoing ACU-AF trial and to further help interpretation of main trial outcomes once the trial is completed. TRIAL REGISTRATION NUMBER: NCT02110537.

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

OBJECTIVES: Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. METHODS: This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. RESULTS: Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. CONCLUSION: Medium-term administration of OPE an improvement in FMD and circulating EPCs.

Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction.

This study evaluated the effects of electroacupuncture (EA) on endothelial function and endothelial progenitor cells (EPC) in patients with cerebral infarction. In a randomized, placebo-controlled, crossover study, 20 patients with cerebral infarction were randomized into two treatment groups: EA or placebo. Before and after each intervention, pulse amplitude tonometry (PAT) was used to assess endothelial function and peripheral blood was analyzed for the number of EPCs. Circulating EPCs were quantified by flow cytometry as CD45(low) CD34(+) KDR2(+) cells. Plasma vascular endothelial growth factor (VEGF) and interleukin (IL)-10 levels were measured. Seven days later, crossover was performed on each group, with each group receiving the other treatment using the same protocol. The PAT hyperemia ratio ranged from 1.57 ± 0.41 to 2.04 ± 0.51 after EA, representing a significant improvement (P = 0.002); however, there was no improvement in the placebo group (P = 0.48). Circulating EPCs, as measured by flow cytometry, increased to 110.6 ± 74.3/100 µL in the EA group (P = 0.001) but did not change in the placebo group (45.9 ± 35.3/100 µL, P = 0.08). The increases in the number of EPCs and the PAT ratio after treatment were correlated (r = 0.78, P < 0.001). Plasma VEGF levels increased with EA compared to baseline (261.2 ± 34.0 vs 334.9 ± 80.5 pg/mL, P = 0.003). The number of circulating EPCs was positively correlated with plasma levels of VEGF (r = 0.50, P = 0.02). In conclusion, EA induced improvement of EPC levels and the PAT ratio in patients with cerebral infarction.

Acupuncture antiarrhythmic effects on drug refractory persistent atrial fibrillation: study protocol for a randomized, controlled trial.

Background. Atrial fibrillation (AF) is the most common form of arrhythmia. Several trials have suggested that acupuncture may prevent AF. However, the efficacy of acupuncture for AF prevention has not been well investigated. Therefore, we designed a prospective, two-parallel-armed, participant and assessor blinded, randomized, sham-controlled clinical trial to investigate acupuncture in persistent AF (ACU-AF). Methods. A total of 80 participants will be randomly assigned to active acupuncture or sham acupuncture groups in a 1 : 1 ratio. Both groups will take the same antiarrhythmic medication during the study period. Patients will receive 10 sessions of acupuncture treatment once a week for 10 weeks. The primary endpoint is AF recurrence rate. Secondary endpoints are left atrium (LA) and left atrial appendage (LAA) changes in function and volume, and inflammatory biomarker changes. Ethics. This study protocol was approved by the institutional review boards (IRBs) of Kyung Hee University Hospital (number 1335-04). This trial is registered with clinicaltrials.gov NCT02110537.

Additional Effects of Back-Shu Electroacupuncture and Moxibustion in Cardioprotection of Rat Ischemia-Reperfusion Injury.

Many preclinical studies show that electroacupuncture (EA) on PC6 and ST36 can reduce infarct size after ischemia-reperfusion (IR) injury. Yet studies to enhance the treatment effect size are limited. The purpose of this study was to explore whether EA has additional myocardial protective effects on an ischemia-reperfusion (IR) injury rat model when back-shu EA and moxibustion are added. SD rats were divided into several groups and treated with either EA only, EA + back-shu EA (B), or EA + B + moxibustion (M) for 5 consecutive days. Transthoracic echocardiography and molecular and immunohistochemical evaluations were performed. It was found that although myocardial infarct areas were significantly lower and cardiac function was also significantly preserved in the three treatment groups compared to the placebo group, there were no additional differences between the three treatment groups. In addition, HSP20 and HSP27 were expressed significantly more in the treatment groups. The results suggest that adding several treatments does not necessarily increase protection. Our study corroborates previous findings that more treatment, such as prolonging EA duration or increasing EA intensity, does not always lead to better results. Other methods of increasing treatment effect size should be explored.

Green tea consumption improves endothelial function but not circulating endothelial progenitor cells in patients with chronic renal failure.

This study was designed to determine the effect of green tea consumption in patients with chronic kidney disease (CKD) on flow-mediated endothelium-dependent vasodilation (FMD) and the number of circulating endothelial progenitor cells (EPCs). Forty patients with CKD requiring chronic dialysis were enrolled. The patients were divided into two groups: the catechin group that consumed green tea (5 g/day for 1 month) and the control group that consumed water. The number of EPCs, inflammatory markers, oxidative stress, and FMD were determined at baseline and 4 weeks after green tea consumption. Clinical characteristics, oxidative stress, inflammatory markers, and circulating EPCs number were not significantly different. FMD was significantly improved after 4 weeks in the catechin group (from 5.68±2.67% to 8.66±3.46%, p=0.002). Short-term green tea consumption induced a rapid improvement in FMD, but did not improve circulating EPC levels in patients with CKD.

The Effects of Etomidate on the Isolated Porcine Coronary Artery / 대한마취과학회지

BACKGROUND: Etomidate produces minimal cardiovascular effects in clinical uses but their effects on the porcine coronary arteries are not well known yet. We studied the direct effects of etomidate on porcine coronary arterial tone and the underlying mechanism of its vascular relaxation. METHODS: Porcine coronary arterial ring segments (3-4 mm) with or without endothelium were suspended in modified Krebs solution (37oC) and preconstricted with K+ 40 mM. Changes in tension were measured following cumulative administrations of etomidate (10(-5), 5 x 10(-5) and 10(-4) M). Relaxation caused by etomidate (10(-4)M) were measured in the presence of either NG-nitro-L-arginine methyl ether (L-NAME 10(-5)M, n = 13), indomethacin (2.8 x 10(-5)M, n = 12), methylene blue (2 x 10(-5)M, n = 12), tetraethylammonium (TEA, KCa2+ blocker, 20 mM, n = 11), glibenclamide (n = 13) 2.5 x 10(-5)M or 4-aminopyridine (4-AP, K+ DR blocker, 10 4 M, n = 12). Effects of etomidate on Ca2+ influx through the voltage operated channel (VOC) of the vascular cells were also evaluated. RESULTS: Arterial reings were relaxed by etomidate in a concentration-dependent manner and these effects were not affected by endothelium. In the etomidate pretreated group, arterial ring in a calcium-free solution showed no contraction with KCl 40 mM, but the contraction after the administration of calcium 2.5 mM less than without etomidate group (47.2 +/- 8.7% vs 97.7 +/- 10.6%). The other group, not pretreated with etomidate, showed the same vascular tone of the control group in a slow upstroke manner with calcium administration. Pretreatment with either L-NAME, indomethacin and methylene blue did not affect etomidate-induced vasorelaxation. The TEA, glibenclamide and 4-AP pretreated groups also did not affect the vascular relaxation. CONCLUSIONS: Etomidate relaxes the porcine coronary artery in a concentration-dependent manner withor without endothelium, via inhibition of Ca2+ influx through the voltage-operated Ca2+ channel.

The Validity of Amsterdam Preoperative Anxiety Information Scale in the Assessment of the Preoperative Anxiety - Compared with hospital anxiety depression scale and visual analogue scale - / 대한마취과학회지

BACKGROUND: There are many objective and subjective methods for measuring the level of preoperative anxiety, but commonly used methods, such as HADS (hospital anxiety depression scale) and VAS (visual analogue scale), are not simple and easily used by patients. APAIS (Amsterdam preoperative anxiety and information scale) is a newly developed preoperative anxiety measuring instrument. The object of this study was to evaluate the ability of APAIS to overcome the limitations of other anxiety measuring instruments. METHODS: 105 adult patients were asked to fill out the questionnaires in APAIS and HADS and also to mark on a 100 mm line in VAS in the range of 0 (calm) to 100 (terrified) how tense they felt at that moment in the evening before surgery. 95 patients responded to the questionnaire. We compared APAIS with the other subjective measurements of anxiety according to patients' sex, ASA class, past history of surgery and level of education, and evaluated the equivalence of the three methods. RESULTS: APAIS has a significant relationship with the other two methods (P < 0.05), but the other two methods have no significant relationship. The data of the APAIS showed a nearly symmetrical distribution as compared with that of HADS and VAS. Women and patients who had had no surgery were significantly anxious as opposed to men and to patients with previous experience of surgery, respectively (P < 0.05). The HADS and APAIS were in good agreement in defining patients as having normal AFFECT or anxiety and there were significant correlations between the three instruments (P < 0.05). CONCLUSIONS: We conclude that the three scales were equivalent in their assessment of anxiety before surgery. Therefore, APAIS will be useful alternative method of measuring subjective preoperative anxiety.

The Validity of Amsterdam Preoperative Anxiety Information Scale in the Assessment of the Preoperative Anxiety - Compared with hospital anxiety depression scale and visual analogue scale - / 대한마취과학회지

BACKGROUND: There are many objective and subjective methods for measuring the level of preoperative anxiety, but commonly used methods, such as HADS (hospital anxiety depression scale) and VAS (visual analogue scale), are not simple and easily used by patients. APAIS (Amsterdam preoperative anxiety and information scale) is a newly developed preoperative anxiety measuring instrument. The object of this study was to evaluate the ability of APAIS to overcome the limitations of other anxiety measuring instruments. METHODS: 105 adult patients were asked to fill out the questionnaires in APAIS and HADS and also to mark on a 100 mm line in VAS in the range of 0 (calm) to 100 (terrified) how tense they felt at that moment in the evening before surgery. 95 patients responded to the questionnaire. We compared APAIS with the other subjective measurements of anxiety according to patients' sex, ASA class, past history of surgery and level of education, and evaluated the equivalence of the three methods. RESULTS: APAIS has a significant relationship with the other two methods (P < 0.05), but the other two methods have no significant relationship. The data of the APAIS showed a nearly symmetrical distribution as compared with that of HADS and VAS. Women and patients who had had no surgery were significantly anxious as opposed to men and to patients with previous experience of surgery, respectively (P < 0.05). The HADS and APAIS were in good agreement in defining patients as having normal AFFECT or anxiety and there were significant correlations between the three instruments (P < 0.05). CONCLUSIONS: We conclude that the three scales were equivalent in their assessment of anxiety before surgery. Therefore, APAIS will be useful alternative method of measuring subjective preoperative anxiety.

Effects of Amrinone on the Vascular Tension of the Isolated Rabbit Pulmonary Artery / 대한마취과학회지

BACKGROUND: Amrinone is a noncatecholamine, nonglycoside compound, which is known to possess both cardiac inotropic and vasodilatory actions. This drugs has been increasingly used in clinical practice for the management of low cardiac output syndrome during anesthesia, particularly for patients associated with right heart failure and pulmonary hypertension. The aim of this study was to explore the direct vasoactive effect of amrinone and its action mechanisms in the isolated rabbit pulmonary artery. METHODS: The rabbits' pulmonary arteries were dissected free and cut into rings (3 4 mm) and mounted for isometric tension in a tissue chamber. The effects of amrinone (5 10 6 5 10 4 M) on the vascular tension were assessed in the by KCl (40 mM)- or norepinephrine (NE, 10 6 M)- precontracted pulmonary arterial rings with or without endothelium. Also effects of K channel blockers (tetraethyl ammonium 20 mM, glybenclamide 2.5 10 5 M, 4-aminopyridine (4-AP) 5 10 4 M), protein kinase A & G inhibitor (H8), L-NAME, methylene blue and indomethacin on the amrinone- induced vascular responses were investigated. Also studied was effects of amrinone on the Ca2 influx through voltage operated channel (VOC) and receptor operated channel (ROC) of the vascular cells. RESULTS: Amrinone produced vasorelaxation of KCl- or NE-precontracted pulmonary artery in a dose-dependent fashion. The amrinone-induced vasorelaxation was not affected by the denudation of the endothelium. Pretreatment with L-NAME and methylene blue did not affect the vasodilatory effect of amrinone, suggesting that nitric oxide is not involved. Following pretreatment with indomethacin (a cyclooxygenase inhibitor) or K channel blockers, the amrinone-induced vasorelaxation was not altered. After exposure to Ca2 free solution, amrinone attenuated the KCl- or NE-induced contraction even in the presence of Ca2 , implying that VOC and ROC are blocked by amrinone. On the other hand, protein kinase A blocker (H8) completely abolished the amrinone-induced relaxation in the KCl-precontracted pulmonary artery. CONCLUSIONS: These findings suggest that the amrinone-induced vasorelaxations result from inhibition of VOC and ROC as well as from the activation of protein kinase A in the isolated rabbit pulmonary artery.

Effects of Ketamine on the Ca(2+) Channel and K(+) Channel of the Porcine Coronary Artery / 대한마취과학회지

BACKGROUND: Ketamine produces increasing in heart rate and arterial blood pressure, in vivo. However, the direct effects of ketamine itself on the porcine coronary arteries are not well determined. In this study, the direct effects of ketamine on the porcine coronary artery responses to vasoactive agents that operate through Ca2+ channel, K+ channels and endothelium related mechanisms were investigated, in vitro. METHODS: Adult porcine hearts(n=12) were obtained from a slaughter house. Coronary arteries were perfused and dissected with 4oC Krebs solution, and were cut into vessel rings and prepared with and without the endothelium(3~4mm in length). The ring segments were suspended in tissue bath(5ml) filled with Krebs solution at 37oC and bubbled with 95% O2-5% CO2 gas mixture. The effect of ketamine(5 10 5, 10 4, 2 10 4M) on vascular smooth muscle tone caused by Ca2+[voltage operated channel(VOC), receptor operated channel(ROC)] and K+channels(Ca2+activated K+ currents, ATP-sensitive K+ currents) regulation were studied with Ca2+ free solution and K+channel blocker. RESULTS: Ketamine induced vasorelaxation of porcine coronary rings that were precontracted by KCl(50 mM) or acetylcholine(3 10 7M). The changes of vascular tone in endothelium intact and removed group did not show statistical significance. In ketamine pretreated group(Ca2+ free solution), after ketamine pretreatment, the last vascular tone was same as that relaxed by ketamine. The other group that without pretreatment of ketamine, the last vascular tone was same as that precontracted with KCl or acetylcholine. In the TEA pretreated group, the porcine coronary artery relaxation was reversed. However, pretreatment with glybenclamide, the porcine coronary artery relaxation was not reversed. CONCLUSIONS: Ketamine induced vasorelaxation of the porcine coronary artery as concentration relating manner, in vitro. The vasorelaxation induced by ketamine was not associated with endothelium. Furthermore, an antagonism of Ca2+ channels(VOC, ROC) and activation of Ca2+ activated K+ channels may be responsible for the porcine coronary arterial relaxing effect of ketamine.

The Divided Doses of Neostigmine for the Rapid Recovery at Profound Muscle Relaxation of Pancuronium in Rabbits / 대한마취과학회지

BACKGROUND: The reversal of neuromuscular blocker might be accelerated if the anticholinesterase was administered in divided doses. This study has been conducted to evaluate the correct ratio of divided doses of neostigmine for the rapid recovery in the rabbits after pancuronium when the profound relaxation(PTC=0) was confirmed. METHODS: Rabbits(n=60) were randomly allocated to 6 groups. After pancuronium 0.2 mg/kg intravenously, spontaneous recovery was evaluated in group 1. When the profound relaxation(PTC=O) was confirmed at 5 min. after pancuronium, neostigmine 50 ug/kg was injected as a bolus in group 2. At that time, neostigmine was given at 10 ug/kg followed by 40 ug/kg 3 min. later in group 3. At that time, neostigmine was given at 20 ug/kg followed by 30 ug/kg 3 min. later in group 4. At that time, neostigmine was given at 30 ug/kg followed by 20 ug/kg 3 min. later in group 5. At that time, neostigmine was given at 40 ug/kg followed by 10 ug/kg 3 min. later in group 6. RESULTS: The mean time from injection of pancuronium to 95% recovery was 99.3 min. in group 1, 59.8 min. in group 2, 53.2 min. in group 3, 51.5 min. in group 4, 50.8 min. in group 5 and 41.1 min. in group 6. The recovery index was significantly reduced in group 6(p<0.05). CONCLUSIONS: We conclude that the recovery time is reduced when neostigmine is administered in divided doses: a larger priming dose followed by a smaller bolus at profound relaxation.

The Effect of Thiopental on the Isolated Rabbit Abdominal Aorta / 대한마취과학회지

The characteristics of an ideal intravenous anesthetic agent include stability in solution, rapid onset of action, minimal effect on the cardiovascular and respiratory systems, short elimination half life, and minimal side effects. Using this criteria, the ultra-short acting barbiturate, thiopental has long been considered the gold standard of intravenous agents used for induction of anesthesia. In normovolemic subjects, thiopental produces a transient decrease in blood pressure, and increase in heart rate. In practice, thiopental is administered high dose(30 mg/kg IV) for brain protection, rarely. We tried to confirm the direct vascular effects of thiopental and its mechanism on the rabbit abdominal aorta in vitro. The rabbit abdominal aorta were precontracted with norepinephrine(10(-7) M) in 5 ml tissue bath and 10(-5), 10(-4), and 10(-3) M thiopental was administrated in cumulative manner. Ten minutes later, changes of the vascular tones were obtained. For confirming the relaxing mechanism induced by thiopental, experiment was performed by indomethacin, methylene blue and LNAME pretreatment, and endothelium removed, respectively. The results were as follows 1) Thiopental at 10(-5), and 10(-4) M produced no signifcant changes, and at 10(-3) M produced signifcant relaxation. 2) There were no significalnt difference in their vascular tones between intact and denuded endothelium group. 3) The vascular tones were not affected by LNAME, methylene blue, and indomethacin pretreatment. These results suggest that thiopental induce vasorelaxation in rabbit abdominal aorta at high concentration(10(-3) M). The vasorelaxation mechanism is not correlated with NO, cyclic GMP, prostacyclin and endothelium.