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Comparison of the Effects of Milrinone, Sodium Nitroprusside, and Nitroglycerine for Induced Hypotension in Elderly Patients Undergoing Spine Surgery: A Randomized Controlled Trial.
Huh, J, Chung, H, Hwang, W
Clinical spine surgery. 2019;(8):E366-E371
Abstract
BACKGROUND The use of induced hypotension is limited because of concerns about hypoperfusion to major organs in elderly patients. The aim of this study was to compare the effects of milrinone with those of other vasodilating hypotensive agents on induced hypotension in elderly patients undergoing spine surgery. METHODS In total, 60 patients older than 60 years who underwent lumbar fusion surgeries were randomized to groups M (milrinone), S (sodium nitroprusside), and N (nitroglycerine). The study drug was infused after perivertebral muscle retraction until complete interbody fusion occurred. The infusion dose was adjusted to achieve a fall of 30% in systolic blood pressure or mean blood pressure to 60 to 65 mm Hg. Intraoperative blood loss, grade of the surgical field, and urine output were recorded. RESULTS Intraoperative blood loss per fused spine level was 288.5±94.4 mL in group M, 399.8±60.3 mL in group S, and 367.0±122.5 mL in group N (P=0.002). The grade of the surgical field was similar among the 3 groups (P=0.439). Hourly urine output was 1.4±0.5 mL in group M, 0.7±0.3 mL in group S, and 0.9±0.4 mL in group N (P<0.001). CONCLUSIONS The use of milrinone for induced hypotension led to less intraoperative blood loss and higher urine output than the use of sodium nitroprusside or nitroglycerine in elderly patients undergoing spine surgery.
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Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction.
Al-Mohammad, A
ESC heart failure. 2019;(4):878-883
Abstract
Hydralazine and nitrate combination was the first treatment that showed improved survival of patients with heart failure with reduced left ventricular ejection fraction (HFREF) in the Vasodilator Heart Failure Trial (V-HeFT trial) in 1986. This showed a 34% reduction of mortality at 2 years of follow-up in patients with advanced heart failure (New York Heart Association Class IV). The angiotensin-converting enzyme inhibitor (ACEi), beta-blockers, mineralocorticoid receptor antagonists, and most recently sacubitril-valsartan have superseded the combination of hydralazine and nitrates. However, the latter combination does have a place bridging the survival gap of Black patients with HFREF when added to their standard therapy. This was demonstrated in the African-American Heart Failure Trial (A-HeFT trial) in 2004 when the risk reduction in the Black patients was 43% compared with that in the placebo. This combination may have a potential use in patients with contraindications to the use of ACEi, angiotensin receptor blockers, and sacubitril-valsartan. This is suggested by both the European Society of Cardiology (ESC) Guidelines and the guidelines of the National Institute for Health and Care Excellence (NICE). In this perspective, the role of the combination of hydralazine and nitrates in the treatment of HFREF is reviewed through a synopsis of the evidence base consisting of three randomized controlled studies, several further analyses of subgroups within those trials, a systemic review, and two large observational studies of registry cohorts. The place of the combination in the treatment cascades proposed by heart failure guidelines of the ESC and NICE is explored. This perspective is to remind us of their appropriate roles, particularly given the findings of underuse of this combination in people of African ancestry in Europe.
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Effects of Nicorandil Versus Nitroglycerin on Arterial Oxygenation During Two-Lung Ventilation and One-Lung Ventilation in Patients With Risk Factors for Myocardial Ischemia: A Prospective, Randomized, Double-Blind Study.
Murakami, C, Kawano, H, Kinoshita, M, Kondo, A, Inoue, M
Journal of cardiothoracic and vascular anesthesia. 2019;(3):702-709
Abstract
OBJECTIVES To compare the effects of nicorandil and nitroglycerin on arterial oxygenation during two-lung ventilation (TLV) and one-lung ventilation (OLV) in patients with risk factors for myocardial ischemia. DESIGN A prospective, randomized, double-blind study. SETTING A tertiary care hospital. PARTICIPANTS Fifty-six patients scheduled for elective video-assisted thoracic surgery were assigned randomly to either the nicorandil group or the nitroglycerin group. INTERVENTIONS Patients in the nicorandil group received a bolus dose of nicorandil, 0.08 mg/kg during induction of anesthesia, followed by a continuous infusion at a rate of 0.08 mg/kg/h. Patients in the nitroglycerin group received a continuous infusion of nitroglycerin at a rate of 1 µg/kg/min from the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Arterial blood gas analysis was performed at the following points: before induction of anesthesia; during TLV; at 5, 10, 20, and 30 minutes after the initiation of OLV. PaO2 at TLV (479.7 ± 57.1 v 408.2 ± 70.9 mmHg, p < 0.001); and at 5 minutes (344.8 ± 85.1 v 282.6 ± 85.8 mmHg, p = 0.012), 20 minutes (215.7 ± 103.0 v 158.2 ± 74.5 mmHg, p = 0.027), and 30 minutes (198.8 ± 103.5 v 147.5 ± 64.1 mmHg, p = 0.039) after OLV was significantly higher in the nicorandil group than in the nitroglycerin group. CONCLUSION This study demonstrated that oxygenation during TLV and OLV was significantly higher in patients receiving nicorandil than in those receiving nitroglycerin.
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Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study.
Valentini, G, Huscher, D, Riccardi, A, Fasano, S, Irace, R, Messiniti, V, Matucci-Cerinic, M, Guiducci, S, Distler, O, Maurer, B, et al
Annals of the rheumatic diseases. 2019;(11):1576-1582
Abstract
OBJECTIVES To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). METHODS 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. RESULTS During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). CONCLUSIONS The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.
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Effects of mitochondrial ATP-sensitive potassium channel activation (nicorandil) in patients with angina pectoris undergoing elective percutaneous coronary interventions: A meta-analysis of randomized controlled trials.
Zhu, H, Xu, X, Fang, X, Zheng, J, Chen, T, Huang, J
Medicine. 2019;(3):e14165
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Abstract
AIMS: Nicorandil, which is a mitochondrial ATP-sensitive potassium channel opener, is believed to improve perioperative myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI), but recent studies have shown that nicorandil treatment did not improve functional and clinical outcomes in patients with angina pectoris who underwent elective PCI. We performed a meta-analysis to investigate the protective effect of nicorandil on perioperative injury in patients with angina pectoris who underwent elective PCI. METHODS The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials examining the effects of nicorandil. Two investigators independently selected suitable trials, extracted data, and assessed trial quality. RESULTS Seven studies of patients undergoing elective PCI, comprising a total of 979 patients, were included in this review. The results showed that nicorandil did not reduce the levels of markers of myocardial injury (standardized mean difference [SMD] 0.31 [95%CI -0.6, 1.22] for creatine kinase-MB [CK-MB] and 1.29 [95%CI -2.18, 4.76] for troponin I [TNI]), perioperative complications (relative risk [RR] 0.91 [95%CI 0.46-1.81]), target vessel revascularization (RR 0.79 [95%CI 0.50-1.25]) or major adverse cardiac events (MACE) (RR 0.83 [95%CI 0.49-1.43]). Nicorandil did reduce the corrected TIMI frame count (SMD-0.30 [95%CI -0.52, -0.09]). CONCLUSION Although nicorandil did not reduce the overall incidence of perioperative complications and the incidence of major adverse cardiac events (MACE) in patients with angina pectoris who underwent elective PCI, it could still improve no reflow and slow coronary flow.
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An update on current and emerging treatments for pulmonary arterial hypertension in childhood and adolescence.
Wacker, J, Weintraub, R, Beghetti, M
Expert review of respiratory medicine. 2019;(2):205-215
Abstract
Pulmonary hypertension is a severe condition that can develop during childhood due to several different etiologies. During the last two decades, based on a better understanding of the underlying pathobiology leading to pulmonary arterial hypertension, targeted therapies have been developed and have improved the dreadful prognosis of the condition. However, curative therapy remains elusive. Areas covered: In this article, we will review the currently available drugs in pediatric pulmonary arterial hypertension and discuss the recommended management strategies. Expert commentary: Most of the drugtrials in pulmonary hypertension have been performed in adults, with extrapolation of the results to children. Most of the pediatric studies are non-controlled. The rarity of the disease and the lack of identifiable pediatric treatment goals and satisfactory trial end-points could explain the paucity of specific pediatric studies. An evolution has been made in the last few years regarding the treatment strategy of pulmonary arterial hypertension, with evidence that early combination therapy with at least two pulmonary vasodilators was beneficial on the survival. Children with pulmonary hypertension should be referred to experienced centers early, to benefit from a comprehensive initial assessment. Serial clinical and hemodynamic re-evaluation should assess treatment response and guide potential change in therapy.
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Theobromine consumption does not improve fasting and postprandial vascular function in overweight and obese subjects.
Smolders, L, Mensink, RP, van den Driessche, JJ, Joris, PJ, Plat, J
European journal of nutrition. 2019;(3):981-987
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BACKGOUND Theobromine, a component of cocoa, may favorably affect conventional lipid-related cardiovascular risk markers, but effects on flow-mediated dilation (FMD) and other vascular function markers are not known. OBJECTIVE To evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial vascular function markers. DESIGN In a randomized, double-blind crossover study, 44 apparently healthy overweight (N = 30) and obese (N = 14) men and women with low HDL-C concentrations, consumed daily 500 mg theobromine or placebo for 4 weeks. After 4 weeks, FMD, peripheral arterial tonometry (PAT), augmentation index (AIx), pulse wave velocity (PWV), blood pressure (BP) and retinal microvasculature measurements were performed. These measurements were carried out under fasting conditions and 2.5 h after a high-fat mixed meal challenge. RESULTS 4-week theobromine consumption did not change fasting vascular function markers, except for a decrease in central AIx (cAIx, - 1.7 pp, P = 0.037) and a trend towards smaller venular calibers (- 2 µm, P = 0.074). Consuming a high-fat mixed meal decreased FMD (0.89 pp, P = 0.002), reactive hyperemia index (RHI, - 0.30, P < 0.001), peripheral systolic BP (SBP, - 3 mmHg, P ≤ 0.001), peripheral diastolic BP (DBP, - 2 mmHg, P ≤ 0.001), central SBP (- 6 mmHg, P ≤ 0.001) and central DBP (- 2 mmHg, P ≤ 0.001), but increased heart rate (HR, 2 bpm, P < 0.001). Theobromine did not modify these postprandial effects, but increased postprandially the brachial artery diameter (0.03 cm, P = 0.015), and decreased the cAIx corrected for a HR of 75 (cAIx75, - 5.0 pp, P = 0.004) and peripheral AIx (pAIx, - 6.3 pp, P = 0.017). CONCLUSION Theobromine consumption did not improve fasting and postprandial endothelial function, but increased postprandial peripheral arterial diameters and decreased the AIx. These findings do not suggest that theobromine alone contributes to the proposed cardioprotective effects of cocoa. This trial was registered on clinicaltrials.gov under study number NCT02209025.
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Extracranial activation of ATP-sensitive potassium channels induces vasodilation without nociceptive effects.
Al-Karagholi, MA, Ghanizada, H, Hansen, JM, Aghazadeh, S, Skovgaard, LT, Olesen, J, Ashina, M
Cephalalgia : an international journal of headache. 2019;(14):1789-1797
Abstract
INTRODUCTION Levcromakalim opens ATP-sensitive potassium channels (KATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. KATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans. METHODS To assess the local effect of KATP channel opening in trigeminal and extra-trigeminal regions, we performed a crossover, double-blind, placebo-controlled study in healthy volunteers. Participants received intradermal and intramuscular injections of levcromakalim and placebo in the forehead and the forearms. RESULTS Intradermal and intramuscular injections of levcromakalim did not evoke more pain compared to placebo in the forehead (p > 0.05) and the forearms (p > 0.05). Intradermal injection of levcromakalim caused more flare (p < 0.001), skin temperature increase (p < 0.001), and skin blood flow increase (p < 0.001) compared to placebo in the forehead and the forearms. CONCLUSION These findings suggest that it is unlikely that levcromakalim induces head pain by direct activation of peripheral neurons.
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Anti-anginal drugs: Systematic review and clinical implications.
Pavasini, R, Camici, PG, Crea, F, Danchin, N, Fox, K, Manolis, AJ, Marzilli, M, Rosano, GMC, Lopez-Sendon, JL, Pinto, F, et al
International journal of cardiology. 2019;:55-63
Abstract
BACKGROUND The cornerstone of the treatment of patients affected by stable angina is based on drugs administration classified as first (beta-blockers, calcium channel blockers, short acting nitrates) or second line treatment (long-acting nitrates, ivabradine, nicorandil, ranolazine and trimetazidine). However, few data on comparison between different classes of drugs justify that one class of drugs is superior to another. METHODS We performed a systematic review of the literature following PRISMA guidelines. INCLUSION CRITERIA i) paper published in English; ii) diagnosis of stable coronary disease; iii) randomized clinical trial; iv) comparison of two anti-angina drugs; v) a sample size >100 patients; vi) a follow-up lasting at least 2 weeks; vii) paper published after 1999, when a meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina of Heidenreich et al. was published. OUTCOME to establish whether the categorization in first and second line antianginal treatment is scientifically supported. RESULTS Eleven trials fulfilled inclusion criteria. The results show that there is a paucity of data comparing the efficacy of antianginal agents. The little data available show that there are not compounds superior to others in terms of improvement in exercise test duration, frequency of anginal attacks, need for sub-lingual nitroglycerin. CONCLUSION The categorization of antianginal drug in first and second line is not confirmed.
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Pharmacologic Management of Portal Hypertension.
Bunchorntavakul, C, Reddy, KR
Clinics in liver disease. 2019;(4):713-736
Abstract
Terlipressin, somatostatin, or octreotide are recommended as pharmacologic treatment of acute variceal hemorrhage. Nonselective β-blockers decrease the risk of variceal hemorrhage and hepatic decompensation, particularly in those 30% to 40% of patients with good hemodynamic response. Carvedilol, statins, and anticoagulants are promising agents in the management of portal hypertension. Recent advances in the pharmacologic treatment of portal hypertension have mainly focused on modifying an increased intrahepatic resistance through nitric oxide and/or modulation of vasoactive substances. Several novel pharmacologic agents for portal hypertension are being evaluated in humans.