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- Correlation between algogenic effects of calcitonin-gene-related peptide (CGRP) and activation of trigeminal vascular system, in an in vivo experimental model of nitroglycerin-induced sensitization. [JOURNAL ARTICLE]
- Eur J Pharmacol 2014 Jul 3.
The neural mechanism(s) underlying migraine remain poorly defined at present; preclinical and clinical studies shows an involvement of CGRP in this disorder. However current evidence pointed out that CGRP does not exert an algogenic action per se, but it is able to mediate migraine pain only if the trigeminal-vascular system is sensitized. The present study was addressed to investigate CGRP-evoked behavior in nitric oxide (NO) sensitized rats, using an experimental model of nitroglycerin induced sensitization of trigeminal system, looking at neuropeptide release from different cerebral areas after the intra-peritoneal (i.p.) administration of NO-donors. CGRP injected into the rat whisker pad did not induce significant changes in face rubbing behavior compared to controls. On the contrary, CGRP injected in animals pre-treated with 10mg/kg nitroglycerin significantly increased the time spent in face rubbing. Nitroglycerin pre-treated animals did not show any rubbing behavior after locally injected saline. Furthermore, the i.p. treatment with nitroglycerin produced an increase of CGRP levels in brainstem and trigeminal ganglia, but not in the hypothalamus and hippocampus. The absolute amounts of CGRP produced in the brainstem were lower compared to those in the trigeminal ganglion; however, after nitroglycerin stimulation the percentage increase was higher in the brainstem. In conclusion, findings presented in this study suggest that CGRP induces a painful behavior in rats only after sensitization of trigeminal system; thus supporting the concept that a genetic as well as acquired predisposition to trigemino- vascular activation represents the neurobiological basis of CGRP nociceptive effects in migraineurs.
- Intraoperative "Kounis syndrome" that improved electrocardiography changes and hemodynamic situation after administering nitroglycerine. [JOURNAL ARTICLE]
- Braz J Anesthesiol 2014 July - August; 64(4):281-285.
A 58-year-old female without cardiovascular risk factors, was going to be operated to repair the rotator cuff. Induction and interscalene brachial plexus block were uneventful, but after her placement for surgery the patient started with severe bronchospasm, hypotension, cutaneous allergic reaction and ST elevation on the electrocardiogram. An anaphylactic shock was suspected and treated but until the perfusion of nitroglycerina was started no electrocardiographic changes resolved. After necessary diagnostic test the final diagnosis was variant I of Kounis syndrome due to cefazolin and rocuronium. Ephinephrine is the cornerstone of treatment for anaphylaxis but should we use it if the anaphylactic reaction is also accompanied by myocardial ischemia? The answer is that we should not use it because myocardial ischemia in this syndrome is caused by vasospasm, so it would be more useful drugs such as nitroglycerin. But what if we do not know if it is a Kounis syndrome or not? In this article we report our experience that maybe could help you in a similar situation.
- Nitroglycerin-induced myocardial protection and tolerance: role for CGRP. [LETTER]
- Trends Pharmacol Sci 2014 Jul 2.
- Coronary vasodilation by the use of sublingual nitroglycerin using 64-slice dual-source coronary computed tomography angiography. [JOURNAL ARTICLE]
- J Cardiol 2014 Jun 30.
Sublingual nitroglycerin capsules or spray is routinely used to treat anginal attacks and to maximally dilate the epicardial coronary arteries during coronary angiography. These dilated coronary vessels have an advantage, but increased heart rates were disadvantageous for coronary computed tomography angiography (CTA).The influence of applying nitroglycerin was analyzed regarding the coronary diameter, coronary luminal attenuation, evaluable number of coronary segments, heart rate (HR), HR variability, the optimal reconstruction phase, and image scoring of CTA in the same patients using a 64-slice dual-source CT.Fifty-two patients with atypical chest pain underwent coronary CTA before and after the administration of sublingual nitroglycerin without heart rate control. The coronary diameter and luminal attenuation were measured on short-axial images in each coronary segment. The coronary vasodilation ratios (VRs) were calculated from the coronary diameters at the same location before and after the use of nitroglycerin. The local institutional review board approved this study and written informed consent was obtained from all the patients.No significant differences were noted in the HR variability or optimal reconstruction phase, despite an increase in HR after the use of nitroglycerin. Nitroglycerin significantly enlarged the coronary artery diameter, and VRs of each coronary segment ranged from 7.54% to 22.26%. As compared with baseline coronary diameter, VRs of minor segments (16.91%) were significantly larger than those of major segments (11.35%), and the magnitude of VR correlated with the baseline coronary diameter (r=-0.48, p<0.001). Coronary luminal attenuation significantly increased due to additional administration of contrast material after the use of nitroglycerin (p<0.01), but no significant difference was noted in the image quality after the use of nitroglycerin.Sublingual nitroglycerin significantly enlarged the coronary diameters, especially in peripheral small coronary arteries, and increased the evaluable number of coronary segments on coronary CTA.
- Tocolysis for acute preterm labor: does anything work. [JOURNAL ARTICLE]
- J Matern Fetal Neonatal Med 2014 Jul 3.:1-8.
Abstract The central rationale of tocolysis for preterm labor (PTL) is to delay delivery for at least 48 h to allow for transfer of the mother to a tertiary facility and for corticosteroids to induce surfactant production in fetal lungs. Beta-mimetics decrease the number of women in preterm labor giving birth within 48 h without reducing adverse neonatal outcomes. Calcium channel blockers inclusive of nifedipine decrease the adverse neonatal outcomes by significantly delaying delivery. Atosiban has the best maternal and fetal safety profile but does not seem to reduce neonatal complications. Magnesium sulfate is controversial as a tocolytic, but is valuable as a neuroprotective agent and for treatment of eclamptic seizures. Indomethacin may be a reasonable first choice for acute tocolytsis in gestational ages less than 32 weeks' gestation. Prolonged use (>48 h) should be avoided. Transdermal nitroglycerin can reduce neonatal morbidity and mortality as a result of decreased risk of birth before 28 weeks' gestation. Nifedipine may be a reasonable first choice because it is easy to administer and also of limited side effects relative to β2-mimetics. Tocolysis does not appear to significantly lengthen the gestational age beyond seven days.
- Leftward Bulging of Atrial Septum Is Provoked by Nitroglycerin and by Sustained Valsalva Strain. [JOURNAL ARTICLE]
- J Am Soc Echocardiogr 2014 Jun 27.
The motion of the interatrial septum primum (septum) is dependent on the interatrial pressure relation, normally with slightly higher pressure in the left atrium and the septum bulging toward the right atrium. The aim of this study was to explore the physiologic mechanisms that reverse interatrial pressures and provoke leftward bulging of septum (LBA). The hypothesis was that both left ventricular unloading with nitroglycerin and sustained Valsalva strain would independently provoke LBA and that their combination would further intensify the effect.Prospectively collected transesophageal echocardiography recordings from 13 patients with obstructive sleep apnea were retrospectively analyzed for the presence or absence of LBA during resting respiration and during Valsalva strain. In each condition, LBA beats were counted at time points before and after nitroglycerin spray had been administered, which enabled a comparison of the independent effects and the combined effect of the nitroglycerin and the Valsalva maneuver. An LBA beat was defined as a heartbeat displaying any LBA during the cardiac cycle.Nitroglycerin increased the proportion of LBA beats significantly during resting respiration, from 21 ± 27% to 54 ± 43% (P = .008). During Valsalva strain, the proportion increased with nitroglycerin spray from 48 ± 21% to 80 ± 17% (P = .001). After nitroglycerin administration, LBA occurred in at least three beats during strain in all Valsalva periods.Unloading of the left ventricle by nitroglycerin administration and by sustained Valsalva strain independently provoked LBA. The combination of these two interventions further intensified the effect.
- Heparin versus placebo for non-ST elevation acute coronary syndromes. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2014 Jun 27.:CD003462.
Non-ST elevation acute coronary syndromes (NSTEACS) represent a spectrum of disease including unstable angina and non-ST segment myocardial infarction (NSTEMI). Despite treatment with aspirin, beta-blockers and nitroglycerin, unstable angina/NSTEMI is still associated with significant morbidity and mortality. Although evidence suggests that low molecular weight heparin (LMWH) is more efficacious compared to unfractionated heparin (UFH), there is limited data to support the role of heparins as a drug class in the treatment of NSTEACS. This is an update of a review last published in 2008.To determine the effect of heparins (UFH and LMWH) compared with placebo for the treatment of patients with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI).For this update the Cochrane Heart Group Trials Search Co-ordinator searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (2013, Issue 12), MEDLINE (OVID, 1946 to January week 1 2014), EMBASE (OVID, 1947 to 2014 week 02), CINAHL (1937 to 15 January 2014) and LILACS (1982 to 15 January 2014). We applied no language restrictions.Randomized controlled trials of parenteral UFH or LMWH versus placebo in people with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI).Two review authors independently assessed quality of studies and independently extracted data.There were no new included studies for this update. Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (risk ratio (RR) = 0.84, 95% confidence interval (CI) 0.36 to 1.98). Heparins compared with placebo, reduced the occurrence of myocardial infarction in patients with unstable angina and NSTEMI (RR = 0.40, 95% CI 0.25 to 0.63, number needed to benefit (NNTB) = 33). There was a trend towards more major bleeds in the heparin studies compared to control studies (RR = 2.05, 95% CI 0.91 to 4.60). From a limited data set, there appeared to be no difference between patients treated with heparins compared to control in the occurrence of thrombocytopenia (RR = 0.20, 95% CI 0.01 to 4.24). Assessment of overall risk of bias in these studies was limited as most of the studies did not give sufficient detail to allow assessment of potential risk of bias.Compared with placebo, patients treated with heparins had a similar risk of mortality, revascularization, recurrent angina, and thrombocytopenia. However, those treated with heparins had a decreased risk of myocardial infarction and a higher incidence of minor bleeding. Overall, the evidence assessed in this review was classified as low quality according to the GRADE approach. The results presented in this review must therefore be interpreted with caution.
- The Valsalva Maneuver Can Misdiagnose 'Normal' as 'Pseudonormal': A Word of Caution for an Echocardiographic Evaluation of Diastolic Function. [JOURNAL ARTICLE]
- Cardiology 2014 Jun 19; 128(4):355-362.
Objectives: To identify differences in cardiac hemodynamic changes between the Valsalva maneuver and nitroglycerin (NTG) administration. Methods: Fifty-three subjects (37 men, 43 ± 12 years) with normal cardiac function [left ventricular ejection fraction ≥55%, early to late mitral inflow velocity ratio (E/A) ≥1, left atrial volume index ≤34 ml/m(2) and early diastolic mitral annulus velocity (E') ≥8 cm/s] were enrolled. Doppler parameters were determined at rest, during the Valsalva maneuver and after NTG administration. Results: Decreased E, A and E/A were observed both during the Valsalva maneuver and after NTG administration (p < 0.0001 for all). However, the reduction in E (ΔEValsalva: -30 ± 16 cm/s vs. ΔENTG: -17 ± 17 cm/s) and E/A (ΔE/AValsalva: -0.37 ± 0.28 vs. ΔE/ANTG: -0.19 ± 0.25) and the prolongation of the deceleration time (DT) of E (ΔDTValsalva: 105 ± 74 ms vs. ΔDTNTG: 83 ± 63 ms) were more prominent during the Valsalva maneuver than with NTG administration (p < 0.0001 for all). Particularly, a greater decrease in E' was observed during the Valsalva maneuver (ΔE'Valsalva: -3 ± 2 cm/s vs. ΔE'NTG: -2 ± 2 cm/s, p < 0.0001). Eighteen subjects (34%) showed ΔE/A ≥0.5 during the Valsalva maneuver; thus, they were mislabeled as 'pseudonormal', while only 3 subjects (6%) showed ΔE/A ≥0.5 after NTG administration. Conclusions: The Valsalva maneuver not only decreases preload but also affects myocardial performance, thus, its use can result in the mislabeling of normal subjects as pseudonormal. © 2014 S. Karger AG, Basel.
- Drug efficacy in treating stable angina pectoris: a protocol for network meta-analysis of randomised controlled trials. [Journal Article]
- BMJ Open 2014; 4(6):e005453.
There were 11 pairwise meta-analysis on the efficacy of β-blockers (including atenolol, propranolol, bisoprolol, metoprolol and nadolol), calcium channel blockers (including amlodipine, diltiazem, felodipine, nifedipine and verapamil), and nitrates (including isosorbide dinitrate, isosorbide mononitrate and nitroglycerin) in treating stable angina pectoris. No network meta-analytic study has been published to evaluate the efficacies of these antianginal drugs. Current clinical guidelines (eg, National Institute of Health and Care Excellence (NICE) clinical guideline 126) are only based on the findings of limited clinical trials and pairwise meta-analysis. This study aims to fill this gap of research by conducting a Bayesian network meta-analysis to compare all these antianginal drugs.Randomised controlled trials (RCT) on the drug therapy of stable angina pectoris with multiple outcome measures, selected from symptomatic relief, ECG tests, exercise tests, heart rates and blood pressures, etc, will be included. Overall effect sizes will be represented as mean differences with 95% credible intervals (CrI) for continuous outcome data and as ORs with 95% CrI for dichotomous outcome data. Bayesian network meta-analysis by WinBUGS will be conducted to compare the efficacies of these drugs. Sensitivity analysis on the quality of RCTs and subgroup analysis on the category of included drugs will be performed.Ethical approval is not required because this study includes no confidential personal data and interventions on the patients. Network meta-analysis is based on the RCT reports of eligible drugs in treating stable angina pectoris. The results of this study will be disseminated by an open access and peer-reviewed publication.PROSPERO CRD42014007113.
- Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock. [JOURNAL ARTICLE]
- Crit Care 2014 Jun 19; 18(3):R126.
Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients.This interventional study recruited patients with circulatory shock who persisted with abnormal peripheral perfusion, despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/h and doubled stepwise (4 mg/h, 8 mg/h and 16 mg/h) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI) and tissue O2 saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose and after cessation of nitroglycerin infusion. Data were analyzed using linear model for repeated measurements and are show as mean (SE).Of the 15 patients included, 4 patients (27%) responded with a nitroglycerin initial dose of 2 mg/h. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff and PI towards normal at the maximum dose of nitroglycerin: from 9.4 (0.6) to 4.8 (0.3) sec (P <0.05), from 3.3 (0.7) to 0.7 (0.6) [degree sign]C (P <0.05), and from [log] -0.5 (0.2) to 0.7 (0.1)% (P <0.05), respectively. Similar changes in StO2 and RincStO2 were also observed: from 75 (3.4) to 84 (2.7)% (P <0.05) and 1.9 (0.08) to 2.8 (0.05)%/s (P <0.05), respectively. The magnitude of changes in StO2 was more pronounced for StO2 < 75%: 11% versus 4%, respectively (P < 0.05).Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients. Simple and fast physical examination of peripheral circulation at bedside can be used to titrate nitroglycerin infusion.