OCT imaging has the potential to elucidate structural and functional aspects of the pathogenesis and the dynamics of cardiovascular events. These unique capabilities might help the development of preventive strategies for the leading cause of morbidity and mortality in Western countries. We hope this book will stimulate interest in this fascinating optical imaging technology and encourage further research.
Muscarinic receptors are present on several different cells in lung and are predominantly involved in bronchoconstriction and mucus secretion. Muscarinic receptor activation leads to breakdown of phosphoinositides in airway smooth muscle cell membranes, which leads to intracellular calcium release and contraction. Muscarinic receptor subtypes are now recognised, and muscarinic receptors on cholinergic nerves which inhibit acetylcholine release (auto-receptors) may differ from those on airway smooth muscle. There is evidence that muscarinic receptor density is less in peripheral airways, so that cholinergic drugs may be less effective against small airway obstruction. The possibility that muscarinic receptors function abnormally in airway disease has been considered but is unlikely since the airways are hyperresponsive to several different stimuli, in addition to cholinergic agonists.
beta 2-Adrenergic receptors (beta 2R) are widely distributed and mediate a wide range of cellular responses in lung. Because glucocorticosteroids increase expression of beta 2R in cell lines, we have investigated the effects of glucocorticoids on the beta 2R mRNA level and the number of beta 2R in human peripheral lung in vitro. Incubation of lung tissues with dexamethasone (Dex) elevated both beta 2R mRNA level (as measured by Northern blot analysis) and beta 2R number (as measured by [125I]iodocyanopindolol binding). The increased accumulation of beta 2R mRNA could be detected at 15 min (1.27 +/- 0.1-fold) and the maximal accumulation occurred at 2 h (2.73 +/- 0.5-fold). The Dex-induced increase in beta 2R mRNA returned to the control level by 17 h. The increase in beta 2R number (1.58 +/- 0.2-fold) was slower, reaching a maximum between 17 and 24 h. Dex increased beta 2R mRNA in a time- and concentration-dependent manner that was abolished by the steroid receptor antagonist mifepristone (RU-38486 or RU-486). The stability of beta 2R mRNA was unchanged by Dex, and a nuclear run-on assay revealed that Dex approximately doubled the transcriptional rate of the beta 2R gene. These observations suggest that glucocorticoids act on steroid receptors to increase beta 2R expression by increasing the rate of beta 2R gene transcription.
Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries.
