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

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.
Bone Density/*drug effects ; Dexamethasone ; Nitric Oxide Donors/*therapeutic use ; Nitroglycerin/pharmacology ; Nitroglycerin/*therapeutic use ; Osteoporosis/chemically induced ; Osteoporosis/*prevention & control ; Random Allocation ; Rats, Wistar

OBJECTIVE: To investigate the protective effect of combined administration of verapamil and nitroglycerin on the function of canine transplanted lungs. METHODS: Twenty orthotopic left lung transplantations were performed in 40 canines, which were randomly divided into 4 groups. In group I (control), the donor lungs were perfused and preserved with LPD solution, while group II with LPD solution plus verapamil 0.1 g/L, group III with LPD solution plus nitroglycerin 0.1g/L, and group IV with LPD solution plus verapamil 0.1 g/L and nitroglycerin 0.1 g/L. Hemodynamics and graft gas exchange were assessed 0, 2 and 4 h after the operation. The lung grafts were harvested to measure the wet/dry weight ratio, malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity. RESULTS: Compared with group I, II and III, the mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), partial pressure of oxygen in arterial blood (PaO₂), dynamic compliance (Cdyn) and alveolar-arterial oxygen tension volume [P(A- a)O₂] in group IV were improved significantly (P<0.05). No significant difference in the partial pressure of carbondioxide (PaCO₂) and peak inspiratory pressure (PIP) was observed in the 4 groups (P>0.05). In group IV, the wet/dry weight ratio and MDA contents were lower than those in the other 3 groups, and the SOD activity was significantly higher than that of the other 3 groups (P<0.05). CONCLUSION Verapamil and nitroglycerin in LPD solution can protect the respiratory function of canine lung grafts by attenuating pulmonary edema and oxidative stress.
Animals ; Blood Gas Analysis ; Dogs ; Hemodynamics ; Lung ; Lung Transplantation ; Nitroglycerin ; pharmacology ; Organ Preservation ; Protective Agents ; Reperfusion Injury ; Verapamil ; pharmacology

BACKGROUND: Since a change in venous capacitance significantly alters venous return and thus affects cardiac output, it is important to know the effects of vasodilators on venous capacitance. The purpose of this study was to examine the effects of sodium nitroprusside and nitroglycerin on venous capacitance during induced hypotension in halothane anesthetized dogs. METHODS: Fourteen mongrel dogs(SNP group: 7, NTG group: 7), weighing 10~15 kg, were anesthetized with N2O 1.5L/min-O2 1.5L/min-halothane 0.5vol%. Each dog received only one drug. In dogs anesthetized with N2O-O2-halothane, mean arterial pressure(MAP) was decreased by 15%(mild hypotension) and 30%(deep hypotension) of control value by sodium nitroprusside(SNP) and nitroglycerin (NTG), respectively. Venous capacitance was assessed before and during induced hypotension by measuring mean circulatory filling pressure(MCFP). MCFP was measured after arresting the circulation by tightening of superior vena cava and inferior vena cava snares simultaneously. RESULTS: As compared with MCFP before induced hypotension, MCFP was significantly decreased by SNP at deep hypotension and NTG at mild hypotension and deep hypotension. As compared with MCFP at mild hypotension, MCFP at deep hypotension was significantly decreased by NTG and SNP, respectively. CONCLUSIONS: These results suggest that NTG has potent venodilating effect at mild and deep induced hypotension, whereas SNP has venodilating effect only at deep induced hypotension.
Animals ; Cardiac Output ; Dogs* ; Halothane* ; Hypotension* ; Nitroglycerin* ; Nitroprusside* ; Pharmacology ; SNARE Proteins ; Sodium* ; Vasodilator Agents ; Vena Cava, Inferior ; Vena Cava, Superior

OBJECTIVETo evaluate the impact of resveratrol on coronary collateral circulation in pigs suffered from experimental acute coronary occlusion.

METHODSEighteen healthy pigs were randomly divided into 3 groups: resveratrol group, nitroglycerin group and control group. Animal model of acute coronary occlusion was established through PTCA method, and the blood flow spectrum in the left circumflex artery (LCX) was detected using intracoronary Doppler ultrasound.

RESULTSThe average peak velocity (APV) in infarction correlation artery (IRA) was significantly decreased immediately after coronary occlusion [(0.85 ± 0.25) cm/s vs. (24.83 ± 3.43) cm/s, P < 0.05]. The APV remained unchanged during 0, 30 and 60 minutes after the occlusion. Reversed or bidirectional blood flow was observed and the APV increased significantly [(9.22 ± 0.80) cm/s vs. (0.84 ± 0.21) cm/s, (8.93 ± 1.28) cm/s vs. (0.86 ± 0.26) cm/s respectively, P < 0.05] after the coronary injection of resveratrol (2 mg) or nitroglycerin (0.3 mg). There was no significant difference in peak APV between the resveratrol and nitroglycerin groups. The duration of increased APV was significantly longer in resveratrol group than that in nitroglycerin group [(58.83 ± 6.15) min vs. (21.80 ± 5.79) min, P < 0.05].

CONCLUSIONSThe collateral circulation after acute coronary occlusion was obviously insufficient in pigs. Resveratrol could significantly improve the blood flow in coronary collateral circulation after acute occlusion in this model.

Animals ; Antioxidants ; pharmacology ; Collateral Circulation ; Coronary Circulation ; drug effects ; Coronary Occlusion ; drug therapy ; Coronary Vessels ; Disease Models, Animal ; Heart ; Hemodynamics ; Nitroglycerin ; Stilbenes ; pharmacology ; Swine

In patients with variant angina, previous data have been inconclusive as to whether basal coronary artery tone is elevated at the spastic and non-spastic sites. Thus, the purpose of this study was to assess the basa coronary artery tone and the responsiveness to acetylcholine (Ach) and ergonovine (Erg) in patients with variant angina. We compared the basal coronary artery tone and the constrictive responses to Ach and Erg between 31 patients (Group 1) with variant angina in whom spasm was provoked by the low doses of Ach (intracoronary 20 micrograms) or Erg(intravenous 50 micrograms) and 35 patients (Group 2) provoked by higher doses of Ach (intracoronary 100 micrograms) or Erg (intravenous cumulative dose of 350 micrograms), and 26 control subjects. Patients with variant angina in whom spasm was provoked by low doses of Ach or Erg, had a higher incidence of mixed disease, multi-vessel spasm and higher disease activity. The basal coronary artery tone at the spastic and nonspastic sites of spasm related artery was significantly more elevated in Group 1 than that in Group 2 (44+/- 17 vs 14 +/- 11% and 26 +/- 14 vs 16 +/- 10% respectively, P< 0.05), but not in the nonspasm related artery, The magnitudes of vasoconstrictive responses to Ach and Erg at the nonspastic sites were also greater in Group 1 than those in Group 2 and the control groups (Ach; 40 +/- 20 vs 26+/- 11, 27 +/- 12%: Erg; 37 +/- 18 vs 12 +/- 8, 13 +/- 10% respectively, P< 0.05). However, the basal coronary artery tone was not elevated at the spastic and nonspastic sites in Group 2 compared to the in control subjects. These findings suggest that the basal coronary artery tone is increased in patients with variant angina with higher disease activity at the spastic sites and nonspastic sites of the spasm-related artery, and this may be related to the occurrence of coronary artery spasm.
Acetylcholine/pharmacology ; Angina Pectoris, Variant/physiopathology ; Coronary Vessels/*drug effects/physiopathology ; Dose-Response Relationship, Drug ; Ergonovine/*pharmacology ; Female ; Human ; Male ; Middle Age ; Nitroglycerin/pharmacology ; Spasm/chemically induced/physiopathology ; Vasoconstriction/drug effects/physiology ; Vasoconstrictor Agents/*pharmacology ; Vasodilator Agents/pharmacology

OBJECTIVETo compare the relief effect of diltiazem, papaverine and nitroglycerin on radial artery spasm in elderly patients with coronary atherosclerotic heart disease.

METHODSSixty patients aged beyond 70 years underwent coronary artery bypass grafting (CABG) with autologous radial artery from July 2009 to March 2010. Redundant radial artery was collected and the relief function of different drugs was evaluated through "organ bath" technique in vitro. All the patients were randomly divided into 3 groups based on different antispasmodic drugs: diltiazem, papaverine and nitroglycerin. Thirty seconds free blood flow of radial artery and hemodynamic parameters (heart rate, mean arterial pressure and central venous pressure) were assessed before and after intra-radial administration of diltiazem, papaverine and nitroglycerin in vivo.

RESULTSAll three drugs could relieve radial artery spasm in different levels and the eventual relief rate was over 80%. Only nitroglycerin could relax radial artery completely, the relief capacity of nitroglycerin, diltiazem and papaverine decreased in order. There was no significant difference in the hemodynamic parameters before and after the injection. Blood flow of radial artery increased in nitroglycerin group [(42 ± 10) ml/30 s vs. (28 ± 7) ml/30 s, P < 0.05] while there was no significant difference in diltiazem [(23 ± 10) ml/30 s vs. (25 ± 8) ml/30 s, P > 0.05] and papaverine group [(25 ± 10) ml/30 s vs. (24 ± 9), P > 0.05].

CONCLUSIONSNitroglycerin could relieve vasospasm of radial artery effectively and increased blood flow. Nitroglycerin is the suitable antispasmodic drug for radial artery in the elderly patients with coronary atherosclerotic heart disease compare with diltiazem and papaverine.

Aged ; Aged, 80 and over ; Coronary Artery Bypass ; Coronary Artery Disease ; physiopathology ; surgery ; Diltiazem ; pharmacology ; Female ; Follow-Up Studies ; Humans ; Male ; Nitroglycerin ; pharmacology ; Papaverine ; pharmacology ; Parasympatholytics ; pharmacology ; Radial Artery ; drug effects ; physiology ; transplantation

OBJECTIVETo investigate the influence of nitroglycerin tolerance (NT) on arterial ischemia (90 min) and reperfusion (120 min).

METHODSMale Sprague-Dawley rats were infused with nitroglycerin (GTN) or saline for 12 h and ascending aorta was rapidly isolated. The isolated aorta was subjected to one of the following treatments: stimulative ischemia/reperfusion, stimulative ischemia/reperfusion (I/R) plus glutathione (GSH, 0.1 mmol/L) during reperfusion, or control solution (Kreb's solution for 3.5 h).

RESULTSCompared with I/R group, contractile function, vasorelaxation responses to Ach, NO production were significantly decreased and CK, LDH activity as well as nitrotyrosine formation in reperfusion solution were significantly increased in I/R + NT group and these effects could be prevented with addition of GSH in I/R + NT aortas.

CONCLUSIONSOur results demonstrated that NT could aggravate arterial I/R injury by increasing the production of ONOO- and GSH may play a cardioprotective role against NT-induced myocardial injury by attenuating the formation of ONOO-.

Animals ; Aorta ; drug effects ; Drug Tolerance ; Glutathione ; metabolism ; In Vitro Techniques ; Male ; Nitroglycerin ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology ; physiopathology ; Vasoconstriction

BACKGROUNDNitroglycerin (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 of ALDH2 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.

METHODSThis 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.

RESULTSBoth 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 ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR 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).

CONCLUSIONALDH2 (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.

Aged ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Asian Continental Ancestry Group ; Female ; Hemodynamics ; drug effects ; genetics ; physiology ; Humans ; Male ; Middle Aged ; Nitroglycerin ; pharmacology ; Polymorphism, Genetic ; genetics

OBJECTIVETo study the clinical value and safety of the head-up tilt table test (HUTT) in children under 6 years old.

METHODSThe HUTT results between September 2000 and August 2011 of 144 2 to 6-year-old children (81 boys and 63 girls) with syncope and dizziness of unknown causes were retrospectively studied.

RESULTSEight children completed the based tilt table test and 136 cases completed the sublingual nitroglycerin tilt table test. No serious side effects were found in these children. Thirty-two (22.2%) of the 144 children had a positive result of HUTT, including 18 boys and 14 girls (P>0.05). When HUTT-induced syncope met positive standards, ECG record and blood pressure recovered to normal levels within 5 minutes by changing the position of the test bed, keeping the airway open, nasal oxygen inhalation and oral milk.

CONCLUSIONSThe HUTT is valuable, safe and compliant in children under 6 years old.

Age Factors ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Dizziness ; diagnosis ; physiopathology ; Electrocardiography ; drug effects ; Female ; Humans ; Male ; Nitroglycerin ; pharmacology ; Retrospective Studies ; Syncope ; diagnosis ; physiopathology ; Tilt-Table Test