1.Nitroglycerine promotes myocardial oxygen metabolism and regional cardiac function in vivo.
Jian-ping BIN ; D Elizabeth LE ; Shao-min CHEN ; Dao-gang ZHA ; Yi-li LIU ; Sanjiv KAUL
Journal of Southern Medical University 2007;27(4):423-426
OBJECTIVETo investigate the effects of nitroglycerine (NTG) on myocardial oxygen metabolism and regional cardiac function in canine hearts with a stable systemic hemodynamics in situ.
METHODSEight anesthetized open-chest dogs with flow-limited left anterior descending branch of the coronary artery or left circumflex artery (LCx) stenosis were studied. The percentage of ventricular wall thickening (%WT) was measured with quantitative two-dimensional echocardiography (2DE), myocardial blood flow (MBF) with radiolabeled microspheres and tissue oxygen pressure (tPO(2).) with oxygen-dependent quenching of phosphorescence. 2DE was performed and radiolabeled microspheres and Pd-porphyrin injected in the dogs at rest during intracoronary infusion of 0.3-0.6 mg x kg(-1) x min(-1) of NTG. Myocardial oxygen consumption (MVO(2), ml x min(-1) x 100 g(-1)) was calculated as the multiplication product between the arterio-venous oxygen content difference and MBF, and myocardial O(2) delivery as the product between arterial oxygen content and MBF.
RESULTSAs compared with the baseline, NTG increased %WT and MBF significantly in both normal and ischemic beds (P<0.05). There was a significant increase in MVO(2) during NTG infusion in the ischemic bed (P<0.05) in comparison with that measured at rest. NTG, however, significantly increased the ability of myocardial O(2) delivery in both normal and ischemic beds (P<0.05), therefore tPO(2) was still higher in the ischemic bed during NTG infusion than that at rest (P<0.05). The percentage increment in tPO(2) was significantly greater in the ischemic bed than percentage MBF increment.
CONCLUSIONSNTG enhances myocardial oxygen concentration in normal and ischemic myocardium and may increase oxygen release to the ischemic myocardium in vivo. NTG may have a positive inotropic effect on regional cardiac function. In addition to direct effect on vascular tone, NTG plays important roles in the cardiovascular system by modulating myocardial oxygen metabolism and contractile function.
Animals ; Dogs ; Echocardiography ; Hemodynamics ; Myocardium ; metabolism ; Nitroglycerin ; pharmacology ; Oxygen Consumption ; drug effects
2.The Metabolism and Liver Toxicity of N,N-dimethylformamide in the Isolated Perfused Rat Liver.
Sang Baek KOH ; Bong Suk CHA ; Jong Ku PARK ; Soung Hoon CHANG ; Sei Jin CHANG
Yonsei Medical Journal 2002;43(4):491-499
N,N-dimethylformamide (DMF) is metabolized by the microsomal cytochrome p-450 into mainly N-hydroxymethyl- N-methylformamide (HMMF), which further breaks down to N-methyformamide (NMF). However, the detailed mechanism of its toxicity remains unclear. We investigated the metabolism and the toxicity of DMF using the isolated perfused liver model. DMF was added to the recirculating perfusate of the isolated perfused rat liver at concentrations of 0, 10 and 25 mM. Samples were collected from the inferior vena cava at 0, 30, 45, 60, 75, and 90 minutes following addition of the DMF. The metabolites of DMF were analyzed using Gas-chromatography (GC). The changes in the rate of oxygen consumption by the DMF were monitored during perfusion. The enzyme activities (aspartic aminotransferase:AST, alanine aminotransferase:ALT, and lactic dehydrogenase:LDH)) in the perfusate were monitored to see if DMF caused hepatotoxicity. As the perfusion progressed, the DMF concentration in the perfusate decreased, but the level of NMF increased to a maximum of 1.16 mM. The rate of oxygen consumption increased at DMF concentrations of 10 mM and 25 mM. However, when a known inhibitor of cytochrome p-450, SKF 525A (300 micro M), was used to pretreat the perfusate prior to the addition of the DMF, the rate of oxygen consumption was significantly inhibited, indicating the cytochrome p-450 system was responsible for the conversion of DMF to NMF. On addition of the DMF, the activities of the enzymes AST, ALT and LDH were significantly increased a time and dose dependent manner. However, following pretreatment with SKF 525A, their releases were inhibited.
Animal
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Dimethylformamide/*metabolism/*toxicity
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Liver/drug effects/*metabolism
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Male
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Oxygen Consumption/drug effects
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Perfusion
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Rats
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Rats, Sprague-Dawley
3.Effect of nitrogen supply on biomass accumulating and root respiration dynamic changing of Glycyrrhiza uralensis.
Pei-Jun GUO ; Guo-Feng WU ; Wen-Lan LIU ; Yu-Ling FAN ; Guang-Li NIU ; Guang-Ming WU ; Zhi-Rong SUN
China Journal of Chinese Materia Medica 2014;39(9):1584-1588
This paper aimed to study the effect nitrogen supplying on biomass accumulation and root respiration dynamic change of Glycyrrhiza uralensis and reveal the metabolic pathway of root respiration impact the biomass accumulating of G. uralensis. Six groups of one-year-old G. uralensis were fertilized with total nutrition containing various nitrogen concentration (0, 0.5, 1, 2, 4, 8 mmol x L(-1)) every week. At the end of every month, from June to October, the volume respiration rate and biomass of different classes of root samples were determined, and the correlation between root respiration and biomass was analyzed. The results indicated a negative correlation between volume respiration rate and biomass, nitrogen supply significantly affected both root respiration and biomass of G. uralensis by reducing root respiration and increasing root biomass. Under 8 mmol x L(-1) nitrogen supplying, there existed the optimal inhibition of root respiration, which has increased biomass of G. uralensis.
Biomass
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Dose-Response Relationship, Drug
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Glycyrrhiza uralensis
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drug effects
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growth & development
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metabolism
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Kinetics
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Nitrogen
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pharmacology
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Oxygen Consumption
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drug effects
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Plant Roots
;
drug effects
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metabolism
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Seasons
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Time Factors
4.Lack of integrative control of body temperature after capsaicin administration.
Tai Hee LEE ; Jae Woo LEE ; Toshimasa OSAKA ; Akiko KOBAYASHI ; Yoshio NAMBA ; Shuji INOUE ; Shuichi KIMURA
The Korean Journal of Internal Medicine 2000;15(2):103-108
BACKGROUND: Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin, the pungent ingredient of hot peppers, facilitated heat production and heat loss simultaneously in rats. We recently found that the capsaicin-induced heat loss and heat production occur simultaneously and that the biphasic change in body temperature is a sum of transient heat loss and long-lasting heat production. Moreover, suppression of the heat loss response did not affect capsaicin-induced heat production and suppression of heat production did not affect capsaicin-induced heat loss. These observations suggest the independent peripheral mechanisms of capsaicin-induced thermal responses. Thus, the capsaicin-induced thermal responses apparently lack an integrated control. METHODS: Male Wistar rats were maintained at an ambient temperature of 24 1 degrees C on a 12 h on-off lighting schedule at least for two weeks before the experiments. They were anesthetized with urethane (1.5 g/kg, i.p.) and placed on a heating pad, which was kept between 29 and 30 degrees C. Skin temperature(Ts) was measured with a small thermistor, which was taped to the dorsal surface of the rat's tail, to assess vasoactive changes indirectly. Colonic temperature(Tc) was measured with another thermistor inserted about 60 mm into the anus. O2 consumption was measured by the open-circuit method, and values were corrected for metabolic body size (kg0.75). Capsaicin (Sigma) was dissolved in a solution comprising 80+ACU- saline, 10+ACU- Tween 80, and 10+ACU- ethanol, and injected subcutaneously at a dose of 5 mg/kg. Each rat received a single injection of capsaicin because repeated administration of capsaicin renders an animal insensitive to the subsequent administration of capsaicin. Laminectomy was performed at the level of the first and second cervical vertebrae to expose the cervical spinal cord for sectioning. The brain was transected at 4-mm rostral from the interaural line with an L-shaped knife. RESULTS: After administration of capsaicin, O2 consumption increased from 13.5 0.4 mL/min/kg0.75 at 0 min to a peak of 15.9 0.4 mL/min/kg0.75 at 71 min and gradually declined but remained higher than the basal value until the end of the 4-h observation period. Ts also immediately increased from 27.7 0.2 degrees C to 31.9 0.3 degrees C at 39 min, and it returned to the baseline level within 90 min after the capsaicin administration. Tc initially decreased from 37.1 0.1 degrees C to 36.8 0.2 degrees C at 43 min and then gradually increased over the baseline level and remained at 37.6 0.2 degrees C until the end of the experiment. In spinalized rats, the capsaicin-induced increases in O2 consumption was largely attenuated, while the basal O2 consumption was similar to that of control rats. The basal Ts of spinalized rats was 32.4 0.3 degrees C, which was higher than that of control rats. Capsaicin increased Ts by less than 1 degree C, and Tc did not change after the capsaicin administration. O2 consumption of decerebrated rats was statistically higher than that of control rats after the injection of capsaicin. However, capsaicin did not increase Ts, showing a lack of a vasodilatory response. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss but not the heat production response. CONCLUSION: These results show that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and suggest that the body temperature regulation is performed without an integrative center.
Animal
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Body Temperature Regulation/drug effects+ACo-
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Brain/physiology
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Brain/drug effects
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Capsaicin/pharmacology+ACo-
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Decerebrate State
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Male
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Oxygen Consumption/drug effects
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Rats
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Rats, Wistar
5.Effects of feixianping on serum interleukin-6 and oxygen partial pressure in pulmonary fibrosis rats.
Shu-chen WANG ; Yan-ping ZHANG ; Mao-rong FAN ; Qing MIAO ; Wei WANG ; Wen-jiang ZHANG ; Yuan-yuan ZHANG ; Jia-yang LIN
Chinese Journal of Integrated Traditional and Western Medicine 2005;25(2):147-149
OBJECTIVETo study the effects of feixianping (FXP) in improving hypoxemia and on serum interleukin-6 (IL-6) in experimental rats with pulmonary fibrosis (PF).
METHODSTwo hundred and forty healthy male SD rats were randomly divided into 5 groups, 48 in each group, i.e. the normal control group (A), the model group (B), the prednisone group (C) and the two FXP groups of high (21.6 mg x kg(-1)) and low (10.8 mg x kg(-1)) dosage (D and E). PF model rats were established by intratracheal instillation of bleomycin, excepting those in Group A, to which normal saline was administered. The corresponding treatment to various groups started from the 1st day after modeling. Rats were sacrificed in batch at 4 time points, i.e., the 7th, 14th, 21st and 28th day, their arterial blood was collected for determination of blood partial pressure of oxygen (PaO2) and serum IL-6 content.
RESULTSSerum IL-6 content in Group B at all the time points was higher than that in other groups at the same time points (P<0.01). In the FXP treated groups (D and E), levels of IL-6 at the 7th, 14th and 28th day showed no significant difference from those in Group A and C. Since the 14th day, FXP showed its effect in improving hypoxemia in experimental rats which could basically keep in accordance with the effect of prednisone.
CONCLUSIONFXP can ameliorate hypoxemia and reduce the level of serum IL-6 in experimental PF rats.
Animals ; Blood Gas Monitoring, Transcutaneous ; Drugs, Chinese Herbal ; pharmacology ; Interleukin-6 ; blood ; Male ; Oxygen Consumption ; drug effects ; Pulmonary Fibrosis ; blood ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley
6.Effect of 3, 4-dihydroxyacetophenone on Na+, K+ -ATPase activity of injured mitochondria and the oxygen consumption of brain cells of rat.
Acta Pharmaceutica Sinica 2005;40(1):13-16
AIMTo investigate the effect of 3,4-dihydroxyacetophenone (alpha-DHAP) on Na+, K+ -ATPase activity of injured brain mitochondria induced by ascorbate-FeSO4 and the oxygen consumption of rat brain cells stimulated by ADP.
METHODSNa+, K+ -ATPase activity was determined according to the method of inorganic phosphate. Swelling of the brain mitochondria was detected with the method of spectrophotometer. Lipid peroxidation was detected according to the thiobarbituric acid method of spectrophotometer. Oxygen consumption was measured by oxygen electrode method.
RESULTSThe decrease of Na+, K+ -ATPase activity, mitochondria swelling and formation of lipid peroxidation were shown in rat brain mitochondria and cells induced by ascorbate-FeSO4. alpha-DHAP was shown to increase the activity of Na+, K+ -ATPase, decrease the mitochondria swelling and inhibit the production of lipid peroxidation of brain mitochondria and cells induced by ascorbate and FeSO4. alpha-DHAP can also reduce the oxygen consumption of brain cells stimulated by ADP.
CONCLUSIONalpha-DHAP can protect the structure and the function of brain mitochondria and cells by scavenging the free radical and resisting the reaction of lipid peroxidation.
Acetophenones ; pharmacology ; Adenosine Diphosphate ; pharmacology ; Animals ; Brain ; cytology ; metabolism ; Free Radical Scavengers ; pharmacology ; Lipid Peroxidation ; drug effects ; Male ; Mitochondria ; drug effects ; metabolism ; Mitochondrial Swelling ; drug effects ; Oxygen Consumption ; drug effects ; Rats ; Rats, Wistar ; Sodium-Potassium-Exchanging ATPase ; metabolism
7.Use of Tadalafil for Treating Pulmonary Arterial Hypertension Secondary to Chronic Obstructive Pulmonary Disease.
Hyun Sook KIM ; Jae Hyeong PARK ; Seoung Ju PARK ; Jong Kwan PARK ; Heung Bum LEE
The Korean Journal of Internal Medicine 2007;22(1):37-39
Pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD) is incurable and it has an unpredictable survival rate. Two men who suffered from COPD presented with progressive dyspnea and edema, respectively. PAH, as estimated by the peak velocity of tricuspidal regurgitation, and the depressed myocardial performance index (MPI) of the right ventricle (RV) were noted on echocardiography. In addition to the baseline therapy for their depressed ventilatory function, we prescribed tadalafil 10 mg orally every other day for 2 weeks and then we doubled the dosage. They well tolerated the medication without any notable side effects. After 4 weeks of tadalafil treatment, the patients' pulmonary arterial pressure was decreased and the MPI of the RV was improved in both. The exercise capacity, as measured by the respiratory oxygen uptake, also improved from 10.9 mL/kg/min to 13.8 mL/kg/min in one patient. We report here on 2 patients with PAH secondary to COPD, and they showed notable improvement of their pulmonary hemodynamics and exercise capacity with the administration of tadalafil.
Pulmonary Disease, Chronic Obstructive/*complications
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Pulmonary Artery/drug effects/*pathology
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Phosphodiesterase Inhibitors/*therapeutic use
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Oxygen Consumption/drug effects
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Middle Aged
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Male
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Hypertension, Pulmonary/*drug therapy/etiology
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Humans
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Exercise Tolerance/drug effects
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Carbolines/*therapeutic use
8.Dietary supplement with a combination of Rhodiola crenulata and Ginkgo biloba enhances the endurance performance in healthy volunteers.
Zhang-jin ZHANG ; Yao TONG ; Jun ZOU ; Pei-jie CHEN ; Ding-hai YU
Chinese journal of integrative medicine 2009;15(3):177-183
OBJECTIVETo determine whether the ingestion of a herbal supplement called Rhodiola-Gingko Capsule (RGC) would enhance the endurance performance of healthy volunteers and change relevant hormones in a favorable manner.
METHODSSeventy healthy male volunteers (age ranges from 18 to 22 years old) were randomly assigned to RGC group (35 cases, each capsule containing 270 mg herbal extracts, 4 capsules per day) or placebo group (35 cases, equivalent placebo preparation) for 7 weeks using computer produced digital random method. The endurance performance, serum testosterone and cortisol levels were measured at the baseline and the endpoint.
RESULTSSixty-seven subjects (34 in the RGC group and 33 in the placebo group) completed a 7-week treatment. The RGC group displayed a significantly greater baseline-to endpoint increase in maximal oxygen uptake (VO(2max)) than placebo group in both absolute (P=0.020) and relative values (P=0.023). At the endpoint, the serum cortisol level was unchanged in the RGC group compared with the baseline, but it was significantly elevated in the placebo group (P<0.05). The endpoint ratio of testosterone to cortisol, a surrogate for overtraining and fatigue in endurance exercises, was also indifferent compared with the baseline in the RGC group, but significantly decreased in the placebo group (P<0.05).
CONCLUSIONThe combined herbal supplement of Rhodiola and Gingko could improve the endurance performance by increasing oxygen consumption and protecting against fatigue.
Adolescent ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Fatigue ; drug therapy ; Ginkgo biloba ; Humans ; Hydrocortisone ; blood ; Integrative Medicine ; Male ; Oxygen Consumption ; drug effects ; Physical Endurance ; drug effects ; Placebos ; Rhodiola ; Testosterone ; blood ; Young Adult
9.Experimental study on the Sanxiansinli capsule against fatigue and viability of mice.
Zai-ling SUN ; Da-wen WEI ; Jun-mei ZHAO ; Xiao-jun SHEN
China Journal of Chinese Materia Medica 2006;31(5):416-418
OBJECTIVETo investigate the effect of the Sanxianxinli capsule against fatigue and viability of mice.
METHODThe mouse shinning, burden swimming, heat-resistant, cold resistant and tolerating anoxia were detected by experiment.
RESULTThe results showed that the Sanxansinli capsule have function of improveing the stamina, cold resistant, heat-resistant and tolerating anoxia,and prolonging were the survival time in cold, high temperature and anoxia.
CONCLUSIONThe Sanxianxinli capsule have function against fatigue and can also improve the resistibility of body.
Animals ; Capsules ; Cold Temperature ; Curculigo ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Epimedium ; chemistry ; Fatigue ; physiopathology ; Hot Temperature ; Hypoxia, Brain ; physiopathology ; Male ; Mice ; Oxygen Consumption ; drug effects ; Physical Endurance ; drug effects ; Plants, Medicinal ; chemistry
10.Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1.
Woochul CHANG ; Chang Youn LEE ; Jun Hee PARK ; Moon Seo PARK ; Lee So MAENG ; Chee Soon YOON ; Min Young LEE ; Ki Chul HWANG ; Yong An CHUNG
Journal of Veterinary Science 2013;14(1):69-76
The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1alpha activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1alpha. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1alpha expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1alpha was important for MSC survival under hypoxic conditions.
Cell Survival
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Cobalt
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Gene Expression Regulation/*physiology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
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Mesenchymal Stromal Cells/drug effects/metabolism/*physiology
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MicroRNAs/*metabolism
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Oxygen/pharmacology
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*Oxygen Consumption
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RNA, Small Interfering/metabolism