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- Fixed-dose combination of losartan and hydrochlorothiazide significantly improves endothelial function in uncontrolled hypertension by low-dose amlodipine: A randomized study. [JOURNAL ARTICLE]
- Anadolu Kardiyol Derg 2014 Oct 23.
Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery are well-known indices for evaluating endothelial function (ECF). The blood pressure-lowering effects of the combination of losartan (ARB) and low-dose hydrochlorothiazide (H: ARB-H; ARB, 50 mg and H, 12.5 mg) are useful. The aim of the present study was to examine whether the combination of losartan and low-dose hydrochlorothiazide could improve ECF.To investigate the effect of ARB-H on ECF in patients with uncontrolled hypertension despite the use of amlodipine (2.5 mg daily), we performed a randomized controlled open-labeled study by using the envelope method and assigned 42 patients to either a control (CTRL) group or an ARB-H combination group, both of which received amlodipine 2.5 mg daily during the treatment period. In addition, both the CTRL (n=21, 69±7 years old) and ARB-H groups (n=21, 69±7 years old) received additional behavioral modification. Before and after 8 weeks of therapy, FMD and NMD were measured in both groups using novel FMD equipment (UNEXEF18G).Although baseline FMD was not different between the two groups, post-therapy FMD increased in the ARB-H group (2.97±1.56 to 3.95±1.86%, p<0.05) but did not change significantly in the CTRL group (2.95±1.43 to 3.11±1.27%, NS). No significant change was seen in NMD when comparing baseline and post-therapy values in either group. No treatment complications were observed.A fixed-dose combination of losartan and hydrochlorothiazide enhances ECF, suggesting that this combination might have both anti-hypertensive and anti-atherosclerotic effects in patients with hypertension.
- [Multiple effect of simvastatin on vascular endothelium of hypercholesterolemia patients]. [English Abstract, Journal Article]
- Beijing Da Xue Xue Bao 2014 Oct 18; 46(5):703-6.
To observe the multiple influence of cholesterol-lowering drug (simvastatin) on ankle brachial index (ABI), flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of brachial artery blood vessel endothelium, and plasma level of monocyte chemotactic protein 1 (MCP-1) of hypercholesterolemia patients without coronary heart disease (CHD).In the study, 51 patients with hypercholesterolemia application were treated with simvastatin (20 mg/d) therapy for 12 weeks. The metabolic index, ankle brachial index (ABI), FMD of brachial artery blood vessel endothelium detected by color doppler ultrasound instrument, the NMD of artery endothelial and the level of MCP 1 were measured before and after therapy respectively. All the results were analyzed and compared with another 30 cases of hypercholesterolemia patients selected without simvastatin treatment.After simvastatin therapy, the TC (total cholesterol) and LDL-C (low density lipoprotein cholesterin) levels were reduced apparently,the values decreased from the original (6.06±1.03) mmol/L and (3.60± 0.82) mmol/L to (4.98±1.34) mmol/L and (3.41±0.10) mmol/L respectively (P<0.01, P< 0.05). Compared with no simvastatin treatment, the bilateral ABI levels were significantly elevated. The right side of ABI (ABIR) elevated from 1.11±0.06 to 1.19±0.07, and the left side of ABI (ABIL) also elevated from 1.12±0.06 to 1.19±0.10 (both sides were P<0.01). The FMD significantly increased from 7.75%±11.30% to 14.20%±15.39% (P < 0.05). The plasma levels of MCP-1 were apparently reduced from (112.0±7.8) ng/L to (108.9±6.2) ng/L (P < 0.05). All these items showed no obvious change within the control group.The API, FMD and plasma levels of MCP-1 of hypercholesterolemia patients without clear coronary heart disease can be improved by simvastatin treatment.
- Different Influences of Extracellular and Intracellular Superoxide on Relaxation through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries. [JOURNAL ARTICLE]
- J Cardiovasc Pharmacol 2014 Oct 17.
Superoxide production is increased in diseased blood vessels, which is considered to lead to impairment of the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway. To investigate the respective influence of extracellular and intracellular superoxide on vascular function through the NO/sGC/cGMP pathway, mechanical responses of rat external iliac arteries without endothelium were studied under exposure to a superoxide-generating agent, pyrogallol or menadione. Exposure to pyrogallol impaired the relaxation induced by acidified NaNO2 (exogenous NO) but not that by nitroglycerin (organic nitrate), BAY 41-2272 (sGC stimulator), BAY 60-2770 (sGC activator), or 8-Br-cGMP (cGMP analog). Superoxide dismutase (SOD) and tempol restored the impaired relaxation by acidified NaNO2. Superoxide production in the bathing solution, but not in artery segments, was significantly increased by exposure to pyrogallol, which was abolished in the presence of SOD or tempol. On the other hand, exposure to menadione impaired the relaxant response to acidified NaNO2, nitroglycerin, or BAY 41-2272, whereas it augmented that to BAY 60-2770. Also this exposure had no effect on the 8-Br-cGMP-induced vasorelxation. Superoxide production in artery segments was dramatically enhanced by exposure to menadione, whereas that in the bathing solution was not affected. This increase in vascular superoxide production was normalized by tempol, but not by SOD. These findings suggest that extracellular superoxide reacts with NO only outside the cell, whereas intracellular superoxide not only scavenges NO inside the cell but also shifts the sGC redox equilibrium.
- Pain and Anxiety in Rural Acute Coronary Syndrome Patients Awaiting Diagnostic Cardiac Catheterization. [JOURNAL ARTICLE]
- J Cardiovasc Nurs 2014 Oct 16.
In rural areas of Canada, people with acute coronary syndromes (ACS) can wait up to 32 hours for transfer for diagnostic cardiac catheterization (CATH). While awaiting CATH, it is critical that pain and anxiety management be optimal to preserve myocardial muscle and minimize the risk of further deterioration.The aim of this study was to examine the relationship between clinical management, cardiac pain intensity, and state anxiety for rural ACS patients awaiting diagnostic CATH.In a prospective, descriptive-correlational repeated-measures design involving 121 ACS rural patients, we examined the associations of analgesic and nitroglycerin administration with cardiac pain intensity (numeric rating scale) and state anxiety (Spielberger State Anxiety Inventory) and also nurses' pain knowledge and attitudes (Toronto Pain Management Inventory-ACS Version and Knowledge and Attitudes Survey Regarding Pain) using linear mixed models.The mean age of patients was 67.6 ± 13, 50% were men, and 60% had unstable angina and the remainder had non-ST-elevated myocardial infarction. During follow-up, cardiac pain intensity scores remained in the mild range from 1.1 ± 2.2 to 2.4 ± 2.7. State anxiety ranged from 44.0 ± 7.2 to 46.2 ± 6.6. Cumulative analgesic dose was associated with a reduction in cardiac pain by 1.0 points (numeric rating scale, 0-10) (t108 = -2.5; SE, -0.25; confidence interval, -0.45 to -0.06; P = .013). Analgesic administration was not associated with state anxiety. Over the course of follow-up, ACS patients reported consistently high anxiety scores.Whereas cardiac pain declines in most patients in the early hours after admission, many patients experience a persistent anxious state up to 8 hours later, which suggest that development and testing of protocols for anxiety reduction may be needed. More urgently, the development and examination of a treatment intervention, early on in the ACS trajectory, are warranted that targets pain and anxiety for those for whom immediate angioplasty is not possible and who continue to experience cardiac pain and persistent high levels of anxiety. Moreover, a larger prognostic study is required to determine whether high levels of anxiety in rural ACS patients are predictive of major adverse cardiac events.
- Clevidipine: A Review of Its Use for Managing Blood Pressure in Perioperative and Intensive Care Settings. [JOURNAL ARTICLE]
- Drugs 2014 Oct 14.
The ultrashort-acting dihydropyridine calcium channel antagonist clevidipine (Cleviprex(®)) has a rapid onset and offset of effect and reduces blood pressure (BP) by decreasing arteriolar resistance without affecting venous capacitance vessels. This article reviews the clinical efficacy and tolerability of intravenous clevidipine when used to manage BP in perioperative and intensive care settings, as well as summarizing its pharmacological properties. Intravenous clevidipine effectively treated preoperative and postoperative hypertension in patients undergoing cardiac surgery, according to the results of the randomized, multicentre, double-blind, phase III ESCAPE-1 and ESCAPE-2 trials. The randomized, open-label, multicentre, phase III ECLIPSE trials indicated that in terms of keeping systolic BP within the target range, clevidipine was more effective than nitroglycerin or sodium nitroprusside perioperatively and had similar efficacy to nicardipine postoperatively in cardiac surgery patients. In small, double-blind trials in patients undergoing coronary artery bypass graft surgery, perioperative clevidipine was noninferior to nitroglycerin, and postoperative clevidipine had similar efficacy to sodium nitroprusside. Noncomparative studies demonstrated that clevidipine provided rapid BP control in patients with acute neurological injuries (including intracerebral haemorrhage, subarachnoid haemorrhage and acute ischaemic stroke), and was not associated with 'overshoot' in the vast majority of patients. Intravenous clevidipine was generally well tolerated and was usually associated with no reflex tachycardia or only very modest increases in heart rate. In conclusion, intravenous clevidipine is a valuable agent for the management of BP in perioperative and intensive care settings.
- Pre-Hospital Glyceryl Trinitrate: Potential for Use in Intracerebral Hemorrhage. [JOURNAL ARTICLE]
- J Neurol Disord 2013 Nov 14; 2(1)
Intracerebral hemorrhage is associated with poor clinical outcome and high mortality. Research and treatment modalities have focused on the expansion of the primary hematoma through blood pressure control and activation of coagulation factors. However, clinical trials have failed to show decreased rates of death or disability in intracerebral hemorrhage following hospital initiation of blood pressure control. However, as clinical deterioration often occurs immediately after onset, pre-hospital initiation of blood pressure control may be more ideal.Relevant terms in the National Library of Medicine PubMed database and selected research including basic science, translational reports, meta-analyses, and clinical studies were searched.Trends indicating improved clinical outcome in intracerebral hemorrhage after hospital-initiated intensive systolic blood pressure control (goal<140 mmHg) have been demonstrated. Statistical significance may not have been obtained because of late treatment times of blood pressure control that approached median 4-6 hours after clinical onset. One trial utilizing glyceryl trinitrate in the pre-hospital setting has been shown to significantly decrease blood pressure within fifteen minutes and improve 90-day clinical outcome.Glyceryl trinitrate represents an ideal pre-hospital blood pressure medication because it can be delivered via sublingual or transdermal routes, has a quick and graded onset of action, has neuroprotective effects, maintains cerebral perfusion, and has an established record of safety. As intracerebral hemorrhage requires prompt action to prevent clinical deterioration, more emphasis on pre-hospital therapies for blood pressure reduction will become essential in future therapies.
- Evaluation of the Advantageous Anesthetic Properties of Dexmedetomidine Used as Hypotensive Agent Compared With Nitroglycerin in Orthognathic Surgery. [JOURNAL ARTICLE]
- J Oral Maxillofac Surg 2014 Jul 30.
To evaluate the advantageous anesthetic properties, such as the decrease of intraoperative analgesic requirement, time to extubation and recovery, and early postoperative pain, of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery.The authors implemented a prospective, single-blinded, randomized clinical trial. The sample was composed of healthy patients who were admitted for bimaxillary osteotomies and were assigned to 1 of 2 groups by a computer-generated random number and blinded to the group. Dexmedetomidine or nitroglycerin was used as the hypotensive drug for each group. All patients underwent hypotensive anesthesia and surgery according to standard protocol. Intraoperative amount of fentanyl, time to eye opening, time to follow basic verbal commands, time to extubation, early postoperative pain scores, and analgesics were recorded. Compared means were analyzed using the unpaired Student t test. A 2-sided statistical test was used. A P value less than .05 was considered significant.The sample was composed of 40 participants. The intraoperative fentanyl requirement was significantly lower in the dexmedetomidine group than in the nitroglycerin group (168.75 ± 56.29 and 222.50 ± 96.12 μg, respectively; P = .037). Times to eye opening and following commands were considerably longer in the dexmedetomidine group, but the time to extubation showed no meaningful difference. Early postoperative pain after 30 and 60 minutes and the requirement for meperidine were not meaningfully different between the 2 groups.Dexmedetomidine, used as a hypotensive drug, has anesthetic benefits compared with nitroglycerin. Dexmedetomidine decreases the intraoperative fentanyl requirement and does not meaningfully change the time to extubation, early postoperative pain, and analgesic drug requirement.
- Impact of Intravenous Nitroglycerin in the Management of Acute Decompensated Heart Failure. [JOURNAL ARTICLE]
- Curr Heart Fail Rep 2014 Oct 10.
Intravenous nitroglycerin is a well-known, but underused, treatment for acute decompensated heart failure. Nitroglycerin has a rapid onset of action and short half-life and there is a clear dose-response curve on both global hemodynamics and peripheral circulation. IV nitroglycerin reduces LV and RV filling pressures and afterload. In the case of acute decompensated heart failure, there is a typical decreased bioavailability of nitric oxide (NO), which needs to be supplemented by exogenous nitrates. Additionally, there is benefit on clinical endpoints, such as fast optimization of arterial oxygenation, lower rates of mechanical ventilation, and improved survival. Drawbacks of therapy include not only side effects such as headache, resistance, and development of tolerability to nitrates but also free radical production. However, nitrates in combination with diuretics remain the cornerstone of acute decompensated heart failure treatment. We propose a more aggressive use of nitrates and a more limited use of inotropes (due to ischemic demand and pro-arrhythmogenic characteristics) in normo- or hypertensive patients with acute heart failure.
- Pregabalin alleviates the nitroglycerin-induced hyperalgesia in rats. [JOURNAL ARTICLE]
- Neuroscience 2014 Oct 5.
The association between the clinical use of nitroglycerin (NTG) and migraine suggests NTG as an animal model trigger for migraine. NTG-induced hyperalgesia in rats has been extensively used as a migraine model for pre-clinical research. Pregabalin is an anti-epileptic drug and may play a role in the preventive treatment of migraine; however, the mechanism of this action remains to be clarified. Herein, we performed the present study to investigate the effect of pregabalin on the NTG-induced hyperalgesia in rats. Sixty male Sprague-Dawley rats were divided equally into six groups. Thirty minutes before NTG injection, the rats were pretreated with pregabalin. von Frey hair testing was employed to evaluate tactile sensitivity. Enzyme-linked immunosorbent assay was used to analyze plasma calcitonin gene-related peptide (CGRP) levels in the jugular vein. Immunohistochemistry was applied to detect c-Fos-immunoreactive neurons and western blot was performed to detect c-Fos protein expression in trigeminal nucleus caudalis (TNC). We found that pregabalin pretreatment alleviated the NTG-induced hyperalgesia. Moreover, pregabalin suppressed peripheral CGRP release, c-Fos-immunoreactive neurons and the protein expression of c-Fos in TNC as well. These data suggest that pregabalin could alleviate the NTG-induced hyperalgesia. Further studies are required to determine the mechanisms of action for this effect.
- High levels of mannose-binding lectin are associated with lower pulse wave velocity in uraemic patients. [JOURNAL ARTICLE]
- BMC Nephrol 2014 Oct 4; 15(1):162.
Uraemia is associated with a highly increased risk of cardiovascular disease. Mannose-binding lectin (MBL) has been shown to be involved in cardiovascular pathophysiology and a protective effect of MBL is suggested. The purpose of the present study was to evaluate a potential impact of MBL on vascular parameters in uraemic patients.A cohort of 98 patients with end stage renal disease (ESRD) awaiting kidney transplantation had pulse wave velocity (PWV) and augmentation index (AIX) examined by tonometry and endothelial dependent flow-mediated (FMD) and endothelial independent nitroglycerin-induced (NID) dilatory capacities of the brachial artery measured by ultrasound. An oral glucose tolerance test (OGTT) was performed and serum levels of MBL were measured using Luminex xMAP bead array technology.The cohort was divided in two groups according to MBL-concentration below or above the median concentration. These groups were comparable regarding age, BMI, and duration of ESRD. PWV was significantly lower in the group with high MBL levels compared to the group with low MBL levels and trends toward better AIX and higher insulin sensitivity (ISI) was also seen in the group with high MBL levels. No difference was seen in FMD and NID.High levels of MBL are associated with lower PWV and the use of antihypertensive drugs in a cohort of patients with ESRD awaiting kidney transplantation suggesting a beneficial role of high levels of MBL on arterial stiffness in uraemia.