Influence of hemodynamic changes on neuroendocrine response in acute heart failure

We studied 15 patients with acute deterioration of chronic left ventricular heart failure. We compared the influence of reduction of ventricular filling pressures with glyceryl trinitrate versus reduction of ventricular filling pressures with diuretics on plasma concentration of epinephrine, norepinephrine, aldosterone and renin activity. Reduction of ventricular filling pressures with glyceryl trinitrate had no influence on plasma concentrations of epinephrine, norepinephrine, aldosterone and renin activity. After reduction of ventricular filling pressures with diuretics plasma concentrations of epinephrine, norepinephrine and aldosterone decreased, while plasma renin activity did not change. We conclude that there is a difference in the influence of reduction of ventricular filling pressures with glyceryl trinitrate versus reduction of ventricular filling pressures with diuretics, on neuroendocrine response in patients with acute deterioration of left ventricular heart failure. Thus some of the neuroendocrine effects of glyceryl trinitrate are likely to be different from those of diuretics, though that they both produce a reduction in left ventricular filling pressure.     

Ambulatory blood pressure,left ventricular mass,and conduit artery function late after successful repair of coarctation of the aorta

OBJECTIVES: We sought to evaluate the determinants of hypertension during daily life and left ventricular (LV) hypertrophy in patients with successfully repaired coarctation of the aorta (CoA), as well as their relationship to abnormalities of arterial function. BACKGROUND: Arterial hypertension may recur late after repair of CoA, which is related to a more adverse outcome. Furthermore, patients with normal resting blood pressure (BP) may have hypertension during daily life and LV hypertrophy. The determinants of these two adverse prognostic factors have not been investigated. METHODS: We studied 72 patients (9 to 58 years of age) who underwent coarctation repair at age 0.1 to 480 months (42 [60%] at <1 year) and had been followed up for 155 +/- 76 months. They underwent ambulatory BP monitoring, echocardiography for LV mass, studies of brachial artery responses to flow (i.e., flow-mediated dilation [FMD]) and glyceryl trinitrate (GTN), and determination of pulse wave velocity (PWV) and measures of arterial reactivity and stiffness. Findings were compared with those of 53 healthy volunteers. RESULTS: Patients had higher 24-h systolic BP and LV mass than controls. Both endothelium-dependent FMD and the response to the smooth muscle dilator GTN were reduced, and PWV was increased. There was a negative independent correlation between GTN response and 24-h systolic BP in both patients and control subjects. Systolic BP at 24 h was an independent predictor of LV mass, having an accentuated impact in coarctation subjects as compared with controls. CONCLUSIONS: In patients with repaired coarctation, reduced vascular reactivity is associated with hypertension during daily life and with increased LV mass, both of which are important predictors for late morbidity and mortality.     

Impaired endothelium-dependent and independent vasodilation in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. N^G monomethyl-l-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p<0.01 for all doses). N^G monomethyl-l-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p<0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p<0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications.     

Usefulness and safety of shortened head-up tilt testing potentiated with sublingual glyceryl trinitrate in older patients with recurrent unexplained syncope

OBJECTIVES: To evaluate the sensitivity and tolerability of shortened, glyceryl trinitrate (GTN)-potentiated, head-up tilt test (HUT) in patients older and younger than 65 with unexplained syncope and to compare the specificity of GTN-potentiated HUT (GTN-HUT) in older and younger controls. DESIGN: Methodological study. SETTING: Syncope units in secondary and tertiary hospitals. PARTICIPANTS: Three hundred twenty-four consecutive patients with unexplained syncope (100 aged > or =65 (mean age +/- standard deviation 73 +/- 6; 35 men) and 224 aged <65 (41 +/- 15; 111 men)) and 64 controls (29 aged > or =65 (73 +/- 6; 13 men) and 35 aged <65 (42 +/- 13; 16 men)). INTERVENTION: Patients and controls were tilted upright to 60 degrees for 20 minutes. If syncope did not occur, sublingual GTN (400 microg) was administered and 60 degrees HUT was continued for 15 minutes. Responses were classified as positive, negative, or exaggerated (slow decrease in blood pressure with a slight decrease in heart rate after GTN). MEASUREMENTS: Electrocardiogram and arterial pressure were monitored continuously. RESULTS: GTN-HUT was positive in 60% and 66% (NS), negative in 29% and 33% (NS), and exaggerated in 11% and 1% (P <.001) of older and younger patients, respectively. In older and younger controls, the GTN-HUT was negative in 70% and 86% and exaggerated in 28% and 9% of cases, respectively, (P <.05). The overall specificity (considering as negative also the exaggerated responses) was 97% in older and 94% in younger subjects. No patient or control experienced serious side effects. CONCLUSION: The shortened GTN-HUT provides satisfactory positivity rate and specificity in older patients. This test may be considered as a diagnostic tool in assessing recurrent unexplained syncope in older patients.     

Enhanced nitric oxide release during cortical spreading depression following infusion of glyceryl trinitrate in the anaesthetized cat

Intravenous infusion of glyceryl trinitrate (GTN) into migraineurs induces an immediate headache followed by migraine. We studied the effect of GTN 10.25 g kg¹ min ¹) on local cerebrovascular laser Doppler flux (rCBF_LDF), artery diameter and NO concentration (selective NO microelectrode) in the pial middle cerebral artery perfusion territory of the anaesthetized cat, at rest and during cortical spreading depression (SD). GTN infusion induced a significant increase in pial artery diameter, rCBF_LDF, and NO concentration. Following termination of infusion, NO concentrations remained significantly elevated above controls for 60 min, other parameters returned to baseliae within 10 min ( p 0.05, ANOVA, post hoc Dunnett's multiple comparison procedure). Two hours after termination of infusion KCl-evoked SD was initiated. GTN-treated animals exhibited significantly ( p 0.05, Kruskal-Wallis) elevated SD-induced NO release compared to controls. All other parameters remained unaffected. Our results demonstrate that GTN induces a prolonged increase in local NO concentrations and enhances SD-induced NO release.     

The protective effects of silymarin nanoemulsion on 5-fluorouracil-induced gastrointestinal toxicity in rats

5-Fluorouracil (5FUra) is the third most popular chemotherapeutic component employed to treat solid tumors. In the present study, we aimed to appraise the silymarin (SM) and silymarin nanoemulsion (SMN) effect on 5FUra-induced gastrointestinal toxicity in adult male rats. A total of 30 male Wistar rats were divided into 6 groups including the control (Crl) group, and groups treated with SMN (5 mg.kg⁻¹), SM (5 mg.kg⁻¹), 5FUra + SMN (5 mg.kg⁻¹), and 5FUra + SM (5 mg.kg⁻¹) by IP injection for 14 days. And gastrointestinal toxicity was induced by a single intraperitoneal (IP) injection of 5FUra (100 mg.kg⁻¹) for the last group in the study. Treating rats with SM and SMN diminished elevating malondialdehyde (MDA) levels, and improved total antioxidant capacity (TAC) levels. Also, the intensity of mRNA expression of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) caused by 5FUra in the gastrointestinal tissue tract, and macroscopic oral ulcerations decreased, ass well as weight loss was prevented, particularly in the SMN group. Moreover, in the microscopic scope, there were significant improvements in the levels of hyperemia, hyaline, and inflammatory cell infiltration in the tongue, esophagus, and intestinal tissues in the FUra + SMN and FUra + SM groups compared to 5FUra. Hence, treatment with SM and SMN reduced oxidative stress, histopathological degeneration, and gene expression of inflammatory markers in the gastrointestinal tract. According to the results, treatment with SM and SMN markedly decreases the gastrointestinal toxicity caused by 5FUra.     

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial

Aim

Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF.

Method

Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis.

Results

A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes.

Conclusion

While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.     

Emergency protocol in the dental clinic: Assessing medical emergency training requirements and guidelines for dentists

BackgroundMedical emergencies are an unavoidable reality affecting dental practices. This review synthesizes and examines the guidelines offered by governmental and professional organizations.Types of Studies ReviewedLicensing agencies and professional associations were chosen as organizations of focus based on legal authority, high professional regard, or both. International and interprofessional organizational counterparts were chosen as points of comparison. In total, 11 organizations were examined. Guidelines reported were compiled by examination of documents published on official agency websites and in associated peer-reviewed journals.ResultsGuidelines for the handling of medical emergencies in the dental clinic vary in level of detail and scope among sources. Licensing agencies provide basic requirements for training, encouraging oral health care providers to develop and integrate their own emergency response plans. Professional associations provide extensive detail on instruction in medical emergency management. Both licensing agencies and professional associations provide lists of emergency medications and equipment, with varying levels of instruction on drug maintenance and organization. Professional associations emphasize regular review of training and office emergency drills.ConclusionOral health care professionals are provided with basic and required elements of medical emergency training by licensing agencies. They may seek out recommended, but not required, instruction from professional associations. Although guidance is provided, literature on protocol instituted in dental practices is limited. Further research is necessary to determine the oral health care community’s approach to emergency management.Practical ImplicationsProviders must be prepared to handle medical emergencies that they encounter. Accessible and understandable guidelines are crucial to safe dental practice.