The biological activities [15] of the phenylpropanoids and their role as antimicrobial agents [16,17] is well recognised, as well as their properties as antiallergic and anti-inflammatory agents through lipoxygenase inhibition [18] and their antimutagenic actions [19,20].In this study we have examined the antioxidant properties of the hydroxycinnamic acids in terms of their abilities to increase the resistance of low density lipoproteins (LDL) to cholesterol oxidation, lipid peroxidation and oxidative modification of the apoprotein B,j 0. The results show that the sequence of the effectiveness against lipid peroxyl radicals generated in the lipophilic phase of LDL and in protecting LDL cholesterol from oxidation is: chlorogenic = caffeic > ferulic > p-coumaric acid.

Myocardial perfusion imaging with single-photon emission computed tomography has poor concordance with FFR and tends to underestimate or overestimate the functional importance of coronary stenosis seen at angiography in comparison with FFR in patients with multivessel disease. These findings might have important consequences in using MPI to determine the optimal revascularization strategy in patients with multivessel coronary disease.

Background-Nitric oxide (NO)-mediated local regulation of vascular tone is considered to involve endothelial NO synthase (eNOS). However, we recently reported that human forearm basal microvascular tone in vivo is tonically regulated by neuronal NO synthase (nNOS), in contrast to an acetylcholine-stimulated reduction in tone, which is eNOS dependent. Here, we investigated the in vivo effects of an nNOS-selective inhibitor, S-methyl-L-thiocitrulline (SMTC), on the human coronary circulation and on flow-mediated dilatation in the forearm. Methods and Results-In patients with angiographically normal coronary arteries, intracoronary infusion of SMTC (0.625 mol/min) reduced basal coronary blood flow by 34.1Ϯ5.2% (nϭ10; PϽ0.01) and epicardial coronary diameter by 3.6Ϯ1.2% (Pϭ0.02) but had no effect on increases in flow evoked by intracoronary substance P (20 pmol/min). The nonselective NOS inhibitor N G -monomethyl-L-arginine (25 mol/min) also reduced basal coronary flow (by 22.3Ϯ5.3%; nϭ8; PϽ0.01) but, in contrast to SMTC, inhibited substance P-induced increases in flow (PϽ0.01). In healthy volunteers, local infusion of SMTC (0.2 mol/min) reduced radial artery blood flow by 36.0Ϯ6.4% (nϭ10; Pϭ0.03) but did not affect flow-mediated dilatation (Pϭ0.55). In contrast, N G -monomethyl-L-arginine (2 mol/min) infusion reduced radial blood flow to a similar degree (by 39.7Ϯ11.8%; Pϭ0.02) but also inhibited flow-mediated dilatation by Ϸ80% (PϽ0.01). Conclusions-These data indicate that local nNOS-derived NO regulates basal blood flow in the human coronary vascular bed, whereas substance P-stimulated vasodilatation is eNOS mediated. Thus, nNOS and eNOS have distinct local roles in the physiological regulation of human coronary vascular tone in vivo.

Vascular blood flow and its distribution among different vascular beds are regulated by changes in microvascular tone. Nitric oxide (NO) plays a key role in the local paracrine regulation of vessel tone both under resting conditions and when blood flow increases in response to agonist stimulation or increased shear stress. The conventional notion that endothelial NO synthase (eNOS)-derived NO is largely responsible for both effects has been challenged by first-in-human studies with a selective inhibitor of neuronal NOS (nNOS), S-methyl-l-thiocitrulline (SMTC). These studies reveal that SMTC causes a reduction in basal blood flow in the normal human forearm and coronary circulations (that is reversed by l-arginine), without affecting the eNOS-mediated vasodilatation elicited by acetylcholine, substance P, or increased shear stress. S-methyl-l-thiocitrulline also inhibits mental stress-induced vasodilatation. These results are consistent with a significant body of experimental studies suggesting that nNOS plays an important role in the local regulation of vessel tone in other species, independent of the effects of nNOS-derived NO in the central nervous system. These emerging data suggest that eNOS and nNOS have distinct roles in the physiologic local regulation of human microvascular tone in vivo and pave the way for further detailed investigation of the relative contribution of nNOS and eNOS in vascular regulation in human disease.

Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions.

Summary Background Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI. Methods Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure. Findings Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82–89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2–4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55–0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48–0·93). Interpretation The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older. Funding NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.

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Background-There is evidence that endothelial coverage of drug-eluting stents might be delayed or absent, a risk factor for late thrombotic events. We studied the effects of different drug-polymer-device iterations on endothelium-dependent coronary vasomotion. Systemic markers of endothelial inflammation were correlated with coronary vasomotor changes. Methods and Results-Patients with paclitaxel-eluting stents (nϭ11), sirolimus-eluting stents (nϭ21), biolimus A9-eluting stents (nϭ28), zotarolimus-eluting stents (nϭ10), and bare-metal stents (nϭ13) were studied 10, 9, 9, 9, and 12 months after implantation, respectively. Endothelium-dependent coronary vasomotion was tested proximally and distally to the stent and at a reference vessel segment during atrial pacing at increasing heart rates by quantitative coronary angiography. Indexes of platelet-monocyte binding and other biomarkers were studied in a subgroup of 19 patients. The baseline characteristics and hemodynamics of the patients in the different stent groups were comparable. Significant differences were observed across the 5 stent groups, concerning the vasomotion of segments proximal (Pϭ0.006) and distal (Pϭ0.003) to the stent. Normal vasomotion (vasodilatation) was maintained in the biolimus A9-eluting stent, zotarolimus-eluting stent, and bare-metal stent groups, whereas vasoconstriction was observed in the sirolimus-eluting stent and paclitaxel-eluting stent groups. Platelet-monocyte binding in whole blood showed a significant inverse correlation with vasomotion in reference but not in segments adjacent to the stent (rϭϪ0.57; Pϭ0.01). Conclusions-Paclitaxel-eluting stents and sirolimus-eluting stents seem to cause endothelial dysfunction of the implanted vessel, whereas biolimus A9-eluting stents and zotarolimus-eluting stents behave more closely to bare-metal stents, with preserved endothelial vasomotor response. Coronary vasoconstriction was not associated with detectable systemic endothelial activation.