Joint Effects of Mexidol and Nitroglycerine on Nitric Oxide Formation in Animal Liver Tissues

This work is investigating Mexidol (2-ethyl-6-methyl-3-hydroxy pyridine succinate) effect on the formation of nitric oxide (NO) in animal liver tissues, which is a regulator of many physiological processes and plays an important role in the vascular relaxation, neurotransmission and immune system functioning. Analyses performed by EPR spectroscopy revealed Hem-NO complex signals from paramagnetic centers in arbitrary units;produced nitrogen oxide amount in liver tissues was determined by method of double integration signals from nitrosyl complexes.

Effects of Nitroglycerine on Erythrocyte Rheology:A Novel Mechanism to Explain the Enhancement of Nutrient Blood Flow to Ischemic Zones

Objectives Nitroglycerine (NTG) enhances coronary blood flow to compromised myocardium is important in relieving ischemia. However, the mechanism for this increase in myocardial blood flow (MBF) is not well defined. In small vessels and capillaries, relative blood viscosity plays a very important role in determining myocardial vascular resistance (MVR). MVR reduce is due partly to the increase in negative charge of erythrocyte surface. We therefore hypothesized that the enhancement of nutrient blood flow to zones of myocardial ischemia during NTG is partly secondary to reduced MVR and blood flow viscosity. The latter is affected by the negative charge of erythrocyte surface. Methods 6 dogs with LAD flow-limiting stenosis (group 1) and 6 dogs with LAD flow-limiting stenosis and LCx occmusion (group 2) were studied. At baseline and during intracoronary infusions of NTG (0.3-0.6 μg·kg-1·min-1), hemodynamics, MBF (mL·min-1·g-1), whole blood viscosity (WBη, mPa. S), elongation index (EI), eletrophoretic mobility of erythocytes (EME, [μ.s-1)/(V.cm-1)]) and percent wall thickening (%WT) were determined. MVR was calculated using driving pressure/MBF. Results As compared to baseline, no changes in hemodynamics were seen during NTG. MBF increased and MVR decreased significantly in normal bed, the central 25% and the entire of stenosed bed (P<0.05), with a decrease in WBη in both group 1 and group 2 dogs (18.6±9.7 % and 19.2±14.5 %, respectively). However, the % decrease in WBη was proportioned to the % increase in MBF or the % decrease in MVR only in the central 25% of stenosed bed (r=0.87, P<0.001), but not in the entire stenosed bed and normal bed. EI did not show statistically significant differences between during NTG and at baseline, but EME did increase. And the % decrease in WBη during NTG was related to the % increase in EME (r=0.83, P=0.01). Conclusions NTG reduced myocardial vascular resistance and blood viscosity due to the change of negative charge of erythrocyte surface may, in part, be the mechanism of the enhancement of nutrient blood flow to zones of myocardial ischemia. These results provide additional insights into the complex anti-ischemic effects of NTG.

Preventive Effects of Nitroglycerine on Glucocorticoid-induced Osteoporosis in Growing Rats

The preventive effects of nitroglycerine （NG） on glucocorticoid-induced osteoporosis in growing rats were studied. Three-month-old female Wistar rats were randomly divided into control group （CON）, dexamethasone group （DXM）, DXM plus a low dose NG group （NG-L）, DXM plus a middle dose NG group （NG-M） and DXM plus a high dose NG group （NG-H）, 8 rats in each group. The rat model of osteoporosis was developed by intramuscular injection of dexamethasone twice a week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment groups every day for 12 weeks. Rats in CON group and DXM group were treated with normal saline of the same amount. After the treatment, the bone mineral density （BMD） and bone metabolism-associated biochemical markers were determined. Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased significantly （P〈0.05 and P〈0.01 respectively）, blood BGP levels and NO levels reduced （both P〈0.01）, and TRAP level increased （P〈0.05）. As compared with DXM group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and NG-M group, but had no significant difference in comparison to CON group. All the markers other than serum NO and TRAP levels had no significant difference between NG-H group and DXM group. It was concluded that low or middle doses of NG could prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG could not. Supplement with NO donor could be considered as a preventive treatment for glucocorticoid-induced osteoporosis in a developing skeleton.

Fullerene bisadduct stabilizers:The effect of different addition positions on inhibiting the autocatalytic decomposition of nitrocellulose absorbed nitroglycerin

To explore the effect of different positions and number of pyrrolidine bound to the carbon cage on the stabilization effect of fulleropyrrolidine derivatives to nitrocellulose(NC)/nitroglycerine(NG),we synthesized N-(4-methoxy)phenylpyrrolidine-C_(60) and four different of bis(N-(4-methoxy)phenylpyrrolidine)-C_(60) compounds through Prato reaction.Their structures were characterized by UVevis,^(1)H NMR,^(13)C NMR,high-resolution mass spectroscopy,and single-crystal X-ray diffraction.Their stabilization effect to NC/NG were investigated using differential scanning calorimetry,methyl violet,vacuum stabilization effect,weight loss,and accelerating rate calorimeter tests.The results indicated these compounds had excellent stabilization effect to NC/NG.The stabilization effect of the fulleropyrrolidine bisadducts to NC/NG is significantly better than that of fulleropyrrolidine monoadduct and C_(60).Moreover,the position where pyrrolidine binds to fullerene in fulleropyrrolidine bisadducts is different,and its stabilization effect to NC is also different.The stabilization effect order of different bisadduct isomers to nitrocellulose is as follows:e-edge>trans-2>cis-2>trans-3.Electron paramagnetic resonance(EPR)and FT-IR were used to study the stabilization mechanism of fulleropyrrolidine derivatives to NC/NG.The EPR results also show that fulleropyrrolidine bisadducts with different addition sites have different abilities to absorb nitroxide,and their ability is better than that of the monoadduct and C_(60),which is consistent with the results of stabilization effect performance test.

Nitroglycerin reduces augmentation index and central blood pressure independent of effects on cardiac preload

Objective To determine whether reduction in central pressure augmentation and central systolic blood pressure by nitroglycerine (NTG) results from effects on pre-load or is due to arterial dilation. Methods We compared effects of NTG with those of lower body negative pressure (LBNP). Hemodynamic measurements were made at rest,during LBNP (10,20 and 30 mmHg,each for 15 min) and after NTG (10,30 and 100 μg/min,each dose for 15 min) in ten healthy volunteers. Cardiac pre-load,stroke volume and cardiac output were assessed by echocardiography. Central pressure augmentation and central systolic pressure were obtained by radial tonometry using a transfer function. Results LBNP (20 mmHg) and NTG (30 μg/min) reduced pre-load (as measured by the peak velocity of the S wave in the superior vena cava) to a similar degree [by (26.8±3.8)% and (23.9±3.4)%,respectively]. Compared to LBNP,NTG reduced systemic vascular resistance [by (32.9±7.5)%,P<0.01],decreased peripheral and central pressure augmentation [by (20.8±3.4)% units and (12.9±2.9)% units,respectively,each P<0.01]. Conclusion These results suggest that a reduction in pre-load does not explain reduction in pressure augmentation and central systolic blood pressure by NTG and that these effects are mediated through arterial dilation.

“Dermal Nitroglycerin Patch” in Treatment of Preterm Labour

Although preterm birth is the delivery before 37 + 0 weeks of gestation, the majority of prema-turity-related complications occur before 33 + 0 weeks of gestation. The need of today is to select the best agent out of the broad spectrum of available tocolytic agents, for providing maximum benefit to unfortunate sufferers of prematurity. The study aims to assess the role of “Dermal Nitroglycerin Patch” in treatment of preterm labour. Method: Study conducted in Department of Obstetrics & Gynecology, NIMS Medical College & Hospital, Jaipur from July 2014-December 2014. A prospective randomized study of 50 women of preterm labor was enrolled after informed consent. Patients were given dermal nitroglycerin patch as tocolytic agent according to study protocol. Result: 1) Results of NTG PATCH are comparable with other tocolytic drugs in terms of successful tocolysis;2) Maternal and fetal outcome is favourable in cases of NTG PATCH USE in preterm labour;3) Side effect profile was also better with NTG Patch. Conclusion: This randomized prospective study lends support to the proportion that Transdermal Nitroglycerine (NTG Patch) may be promising safe, effective, well tolerated, cost effective and non invasive method of tocolysis.

Arterial embolism caused by a peripherally inserted central catheter in a very premature infant:A case report and literature review

BACKGROUND Extremely premature infants have poor vascular conditions.Operators often choose deep veins such as the femoral vein and axillary vein to peripherally insert central catheters,and these vessels are often accompanied by arteries;thus,it is easy to mistakenly enter the artery.CASE SUMMARY The case of an extremely premature infant(born at gestational age 28+3)in whom the left upper extremity artery was accidentally entered during peripheral puncture of the central venous catheter is reported.On the 19th day of hospitalization,the index finger,middle finger and ring finger of the left hand were rosy,the left radial artery and brachial artery pulse were palpable,the recovery was 95%,and the improvement was obvious.At discharge 42 d after admission,there was no abnormality in fingertip activity during the follow-up period.CONCLUSION Arterial embolization in preterm infants requires an individualized treatment strategy combined with local anticoagulation and 2%nitroglycerin ointment for local tissue damage caused by arterial embolism in the upper limb.Continuous visualization of disease changes using image visualization increases the likelihood of a good outcome.

Perioperative Changes of Plasma Endothelin-1 in Patients Undergoing Coronary Artery bypass Grafting and the Effect of Nitroglycerin

Objective To observe the dynamic changes of the plasma ET 1 and the effect of low dose nitroglycerin in patients with coronary artery bypass surgery. Methods\ Forty patients with coronary artery bypass surgery were divided into two group: A and B. Group B received intravenous nitroglycerin 1 μg·kg\+\{ 1\}·min\+\{ 1\} perioperatively. RIA was used to assay the plasma ET 1 level. All the hemodynamic parameters were recorded by the Swan Ganze catheter. Results\ The preoperative plasma ET 1 level in patients with coronary artery disease was significantly higher than the normal level. Five minutes after cardiopulmonary bypass in these patients the plasma ET 1 level was increased significantly until 6 to 8 h after operation. The increasing plasma ET 1 level in group B was less intense than that in group A. There was a positive correlation between the plasma ET 1 level and the mean pulmonary artery pressure in group A 2 and 8 h after operation. Conclusion\ In patients undergoing coronary artery bypass surgery, the increased plasma ET 1 level may be due to the influence of cardiopulmonary bypass partly. Low dose nitroglycerin is beneficial to these patients.

Deterioration in Hemodynamics Reaction, Baroreflex Sensitivity, Sympathetic Nerve Activity and Redox State of Thoracic Aorta in the Experimental Model of Nitrate Tolerance and Its Pharmacological Correction

Continuous treatment with organic nitrates causes nitrate tolerance and provides evidence for a relationship between mitochondrial complex 1 activity and mitochondrial aldehyde dehydrogenase-2 (ALDH-2) with disturbances of the hemodynamics reaction during nitroglycerin (NTG) tolerance (NTGT). The purpose of this study was the evaluation of efficacy of original oxidized form NAD-containing drug, NADCIN®, on hemodynamic reactions, baroreflex sensitivity (BRS) and reflex control of splanchnic sympathetic nerve activity (SSNA), level of redox-potential, activity of ALDH-2 and superoxide anion generation in aortic tissue in rat model of NTGT. Five groups (7 - 9 each) of male Wistar rats, including control, acute i.v. NTG (150 mcg/kg) administration, NTG tolerance NTGT treatment with NADCIN® 8 mg/kg and methylene blue (MB, 2.5 mg/kg) were used. NTGT in rats was accompanied with the greatly attenuation of hemodynamics reaction, BRS, the decreasing of the ability to reflex control of SSNA without pronounce overexpression of endothelin-1 in vessels (aorta). In NTGT rats i.v. NTG along induced less hypotensive reactions and alterations in heart period vs single NTG treated group, more expressively decreased BRS (-34%) and reflex control of SSNA (-18%). NADCIN® significantly inhibits tolerance-inducing properties of the prolonged nitroglycerin infusion (max decrease of blood pressure response to nitroglycerin injection, % of normal controls: NTGT 51.2%, NADCIN® 91.6%, MB 55.8%). NADCIN® in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p < 0,05), reflex control of SSNA (+29.4%, p < 0.05) and reversed the decreasing of NAD/NADH ratio, ALDH-2 activity and decreasing in superoxide generation in thoracic aortic tissue. Thus, course treatment with NADCIN® of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.

Prevalence and characteristics of myocardial bridging in coronary angiogram data from consecutive 5525 patients

Background Large discrepancy of the incidence of myocardial bridging （MB） has been reported either among the postmortem studies or among the studies with coronary angiogram. This study was to investigate the prevalence of MB in large number of coronary angiograms and the angiographic characteristics of MB.Methods A total of 5525 consecutive patients who underwent first diagnostic coronary angiography from January 2003 to March 2006 in Zhongshan Hospital were enrolled in this study. MB was diagnosed when the angiographical ＂milking effect＂, defined as the systolic compression and complete or partly release of the compression in diastole, was seen in the epicardial coronary arteries. Angiography was routinely repeated after intracoronary injection of 200 pg nitroglycerin. The systolic compression and length of MB were compared before and after the administration of nitroglycerin and also before and after stent implantation in patients with significant stenosis in segment proximal to the MB.Results Among 5525 patients, MBs were found in a total of 888 patients angiographically with the prevalence of 16.1%. Atherosclerotic lesions were found more often in the segment proximal to the MB with 344/854 （40.3%） patients than in the segment distal to the MB with 47/854 （5.5%） （P 〈0.01）. The systolic compression （（43.3±13.7）% at baseline vs （54.2±14.0）% after nitroglycerine） and the average length （（20.9±7.5） mm at baseline vs （22.7±8.0） mm after nitroglycerine） of the MB segment were increased after intracoronary injection of nitroglycerin （both P 〈0.01）. Stent implantation was performed in 88 patients with significant stenosis in the segment proximal to the MB. The systolic compression and the length of the MB segment were increased after stenting compared with those before stenting （systolic compression, （49.4±14.6）% at baseline vs （57.3±12.3）% after stenting, and length of MB, （19.5±6.1） mm at baseline vs （21.8±6.3） mm after stenting, P 〈0.01）.Conclusions MB was a frequent finding in coronary angiogram with an incidence of 16.1%. Intracoronary administration of nitroglycerin and stent implantation in the segment proximal to the MB could enhance the systolic compression and the length of the MB angiographically.

Effect of inhalation of nebulized NO donor substance on acute hypoxic lung injury in newborn piglets

Background Birth asphyxia may result in multiple organ dysfunction such as lung injury. Inhalation of nebulized nitric oxide precursor can selectively reduce pulmonary hypertension. However, it is unknown whether such precursors can alleviate lung injury induced by hypoxia. We evaluated the effect of inhalation of nebulized nitroglycerine and sodium nitroprusside on acute hypoxic lung injury in newborn piglets. Methods Acute hypoxic lung injury was induced by inspiring 10% 02 for 1 hour. Twenty-four anaesthetized and mechanically ventilated piglets （5-7 days old） were randomly divided into four groups： （1） group S, not hypoxic; （2） group C, nebulized saline after hypoxia; （3） group NTG, nebulized nitroglycerine after hypoxia; （4） group SNP, nebulized sodium nitroprusside after hypoxia, Respiratory dynamic compliance and resistance of respiratory system were recorded at baseline, 0.5 hour and 1 hour of hypoxia; then 0.5 hour, 1 hour, 3 hours and 5 hours following hypoxia. After nebulization, arterial blood was collected for measuring methaemoglobin and nitrate/nitrite levels. Right lung tissue, wet-dry ratio and myeloperoxidase level were determined. White blood cell count （WBC）, total surfactant phospholipids （TPL） and disaturated phosphatidyl choline （DSPC） of the bronchoalveolar lavage fluid （BALF） were calculated. Left lungs were used for examining pathological changes. Results No significant difference was observed in respiratory dynamic compliance, resistance of respiratory system, wet-dry ratio, levels of methaemoglobin and nitrate/nitrite after nebulization, TPL or DSPC/TPL among four groups. WBC in BALF in groups NTG and SNP significantly decreased as compared with group C： similarly for myeloperoxidase level in lung tissue. Lung histological findings showed infiltration of neutrophils in groups NTG and SNP decreased significantly as compared with group C. Conclusion Inhalation of nebulized nitroglycerine or sodium nitroprusside can alleviate the infiltration of neutrophils, while it affects neither the metabolism of phospholipids nor water content in the lungs.

Effect of Aldehyde Dehydrogenase 2 Gene Polymorphism on Hemodynamics After Nitroglycerin Intervention in Northern Chinese Han Population

Background：Nitroglycerin （NTG） is one of the few immediate treatments for acute angina.Aldehyde dehydrogenase 2 （ALDH2） is a key enzyme in the human body that facilitates the biological metabolism of NTG.The biological mechanism of NTG serves an important function in NTG efficacy.Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different.However,data on NTG measurement by pain relief are subjective.This study aimed to investigate the influence ofALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output （CO） and systemic vascular resistance （SVR） in Northern Chinese Han population.Methods：This study selected 559 patients from the Affiliated Hospital of Qingdao University.A total of 203 patients presented with coronary heart disease （CHD） and 356 had non-CHD （NCHD） cases.All patient ALDH2 genotypes （G504A） were detected and divided into two types：Wild （GG） and mutant （GA/AA）.Among the CHD group,103 were wild-type cases,and 100 were mutant-type cases.Moreover,196 cases were wild-type,and 160 cases were mutant type among the NCHD volunteers.A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0,5,and 15 minute time points after medication with 0.5 mg sublingual NTG.Two CO and SVR indicators were used for a comparative analysis of all case genotypes.Results：Both CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD （F =16.460,15.003,P =0.000,0.000） and CHD groups （F =194.482,60.582,P =0.000,0.000）.All CO values in the wild-type case of both NCHD and CHD groups increased,whereas those in the mutant type decreased.The CO and △CO differences were statistically significant （P 〈 0.05; P 〈 0.05）.The SVR and △SVR changed between the wild-and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences （P 〈 0.05; P 〈 0.05）.Conclusion：ALDH2 （G504A） gene polymorphism is associated with changes in noninvasive hemodynamic parameters （i.e.CO and SVR） after intervention with sublingual NTG.This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

Effect of intravenous nitroglycerin on hemodynamics in infants and children with congestive heart failure

Objective To understand the effect of intravenous nitroglycerin (NTG) on hemodynamics in infants and small children with congestive heart failure secondary to congenital cardiac defect of left to right shunt Methods Heart rate, blood pressure and total peripheral resistance were monitored continuously Echocardiography was used to measure ejection fraction, fractional shortening, end diastolic volume index of left ventricle, pulmonary capillary wedge pressure, pulmonary artery mean pressure and left ventricular wall stress before uhe use and during 0 5, 1 0, 1 5, 2 5, and 5 0?μg·kg 1 ·min 1 dosages of nitroglycerin (NTG) Results There was no significant difference in the indexes of heart rate, blood pressure, ejection fraction and fractional shortening of left ventricle, stroke volume index, cardiac output index, end diastolic volume index before the use and after the use of NTG Pulmonary capillary wedge pressure decreased from 15 5±2 3?mm?Hg before the use of NTG to 14 3±2 2?mm?Hg after the use of 0 5?μg·kg 1 ·min 1 NTG ( P <0 05), minimum to 12 3±2 4?mm?Hg; left ventricular wall stress Ⅰ, Ⅱ and Ⅲ decreased from 407±65? dyn·cm 2 ·10 3, 166±48?dyn·cm 2 ·10 3, 255±52? dyn·cm 2 ·10 3 to 357±75?dyn·cm 2 ·10 3, 136±48? dyn·cm 2 ·10 3, 218±52?dyn·cm 2 ·10 3 ( P <0 05), minimum to 321±50?dyn·cm 2 ·10 3, 114±42? dyn·cm 2 ·10 3, 187±42?dyn·cm 2 ·10 3, respectively Total peripheral resistance and pulmonary artery mean pressure were decreased when the dosage of intravenous NTG was increased to above 2 5?μg·kg 1 ·min 1 ( P <0 05) There was no statistical difference in the above indexes of the different dosages Conclusion Congestive heart failure secondary to congenital cardiac defect of left to right shunt in infants and small children is the indication of using intravenous NTG which could improve hemodynamics There was different selectivity in dosage between arterial and venous vasodilatation, and the change in hemodynamics was independent of dosage The dosages of 0 5-1 0?μg·kg 1 ·min 1 NTG are recommended when the decrease of cardiac preload is the main point of therapy of heart failure

Clinical Study on Composite Salvia Miltiorrhizae Injection (复方丹参注射液) in Preventing Nitroglycerin Controlled Hypotension for Lowering Arterial Partial Pressure of Oxygen Induced by Hypotension

Objective: To observe the effects of Salvia miltiorrhizae composita (SMC) on blood gas variations of nitroglycerin (NTG) controlled hypotension. Methods: Sixteen patients who were arranged to undergo operation under general anesthesia in controlled hypotension condition were randomly divided into the control group (n=8) and the SMC group ( n=8). NTG was used to create controlled hypotension in both groups and blood pressure decreased by about 30% compared with the control values. Patients in the SMC group were administered intravenously with SMC (16 ml) before the utilization of NTG. Results: Significant PaO 2 decrease and Pa etCO 2 increase were observed in the control group during the controlled hypotension period. However, blood gas values in the SMC group did not obviously change. Conclusion: SMC can prevent the side effects of NTG on blood gas.