A review of guidelines for antibiotic prophylaxis before invasive dental treatments

Bacteraemia associated with invasive dental treatments can propagate infective endocarditis in high-risk cardiac patients. Over the past decade, antibiotic prophylaxis before dental treatment has been questioned. This review aims to compare the variations between the UK, European and American antibiotic prophylaxis guidelines before dental treatments. Antibiotic prophylaxis guidelines by the National Institute for Health and Care Excellence (NICE)—Clinical Guideline 64, Scottish Dental Clinical Effectiveness Programme (SDCEP), American Heart Association (AHA), European Society of Cardiology (ESC), European Society of Endodontology (ESE) and Belgian Health Care Knowledge Centre (KCE) position statements were compared regarding the indications, high-risk patients and prophylaxis regimens before dental treatments. In the United Kingdom, the NICE—Clinical Guideline 64 and SDCEP—Implementation Advice do not advise the prescription of prophylactic antibiotics for the majority of high-risk cardiac patients undergoing routine dental treatments. On the contrary, the AHA, ESC and KEC recommend the prescription of antibiotics prior to invasive dental procedures in high-risk cardiac individuals. The ESE also indicates prophylaxis before endodontic procedures for patients with other conditions, including impaired immunologic function, prosthetic joint replacement, high-dose jaw irradiation and intravenous bisphosphonates. Among these guidelines, there are variations in antibiotic prophylaxis regimens. There are variations regarding the indications and antibiotic prophylaxis regimens before invasive dental treatments among these available guidelines

Blood Pressure in Healthy Humans is Regulated by Neuronal NO Synthase

NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown. We undertook the first human study to assess the physiological effects of systemic nNOS inhibition on basal hemodynamics. Seventeen healthy normotensive men aged 24±4 years received acute intravenous infusions of an nNOS-selective inhibitor, S-methyl-l-thiocitrulline, and placebo on separate occasions. An initial dose-escalation study showed that S-methyl-l-thiocitrulline (0.1–3.0 µmol/kg) induced dose-dependent changes in systemic hemodynamics. The highest dose of S-methyl-l-thiocitrulline (3.0 µmol/kg over 10 minutes) significantly increased systemic vascular resistance (+42±6%) and diastolic blood pressure (67±1 to 77±3 mm Hg) when compared with placebo (both P<0.01). There were significant decreases in heart rate (60±4 to 51±3 bpm; P<0.01) and left ventricular stroke volume (59±6 to 51±6 mL; P<0.01) but ejection fraction was unaltered. S-methyl-l-thiocitrulline had no effect on radial artery flow-mediated dilatation, an index of endothelial NOS activity. These results suggest that nNOS-derived NO has an important role in the physiological regulation of basal systemic vascular resistance and blood pressure in healthy humans

Impaired Neuronal Nitric Oxide Synthase-Mediated Vasodilator Responses to Mental Stress in Essential Hypertension

Neuronal NO synthase (nNOS) regulates blood flow in resistance vasculature at rest and during mental stress. To investigate whether nNOS signaling is dysfunctional in essential hypertension, forearm blood flow responses to mental stress were examined in 88 subjects: 48 with essential hypertension (42±14 years; blood pressure, 141±17/85±15 mm Hg; mean±SD) and 40 normotensive controls (38±14 years; 117±13/74±9 mm Hg). A subsample of 34 subjects (17 hypertensive) participated in a single blind 2-phase crossover study, in which placebo or sildenafil 50 mg PO was administered before an intrabrachial artery infusion of the selective nNOS inhibitor S-methyl- l -thiocitrulline (SMTC, 0.05, 0.1, and 0.2 μmol/min) at rest and during mental stress. In a further subsample (n=21) with an impaired blood flow response to mental stress, responses were measured in the presence and absence of the α-adrenergic antagonist phentolamine. The blood flow response to mental stress was impaired in hypertensive compared with normotensive subjects (37±7% versus 70±8% increase over baseline; P &lt;0.001). SMTC blunted responses to mental stress in normotensive but not in hypertensive subjects (reduction of 40±11% versus 3.0±14%, respectively, P =0.01, between groups). Sildenafil reduced the blood flow response to stress in normotensive subjects from 89±14% to 43±14% ( P &lt;0.03) but had no significant effect in hypertensive subjects. Phentolamine augmented impaired blood flow responses to mental stress from 39±8% to 67±13% ( P &lt;0.02). Essential hypertension is associated with impaired mental stress–induced nNOS-mediated vasodilator responses; this may relate to increased sympathetic outflow in hypertension. nNOS dysfunction may impair vascular homeostasis in essential hypertension and contribute to stress-induced cardiovascular events. </jats:p

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P &lt; 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P &lt; 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW &amp; NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/ . </jats:p