Muscarinic receptor subtypes in the airways appear to subserve different physiological functions. M1-receptors facilitate neurotransmission through parasympathetic ganglia and enhance cholinergic reflexes, but are also localized to alveolar walls. M2-receptors act as autoreceptors on post-ganglionic cholinergic nerves and inhibit acetylcholine release. There is some evidence that they may be defective in asthma (as a consequence of airway inflammation?) and this may enhance cholinergic reflexes and account for beta-blocker-induced asthma. M2-receptors in airway smooth muscle may also counteract the bronchodilator action of beta-agonists. M3-receptors mediate contractile responses in airway smooth muscle via phosphoinositide hydrolysis, and are the predominant receptors on submucosal glands and airway vascular endothelium. M4- and M5-receptors have not been identified in human airways, but in rabbit lung M4-receptors are expressed on alveolar walls and smooth muscle. Anticholinergic drugs which selectively block M3 and M1-receptors may have an advantage over currently used non-selective antagonists in the treatment of airway obstruction.
The bronchial epithelium has a number of mechanical functions including mucociliary clearance and protection against noxious agents. However, there is increasing evidence that it is a metabolically active tissue that may modulate the function of the underlying smooth muscle by metabolism and regulation of mediators and the production of relaxant, constrictor, or chemotactic factors. It is therefore possible that the epithelial abnormalities observed in asthmatics may lead, via several different mechanisms, to increased bronchial hyperresponsiveness (figure 2), which is a fundamental feature of asthma. However, it may not be necessary to invoke structural damage to explain derangement of epithelial function. It is possible that functional biochemical abnormalities may be present in epithelial cells, thereby producing bronchial hyperresponsiveness in the absence of histologic abnormalities. Further studies with bronchial epithelium, similar to those with vascular endothelium, are needed to clarify its role in the pathogenesis of asthma.
Of 19,994 percutaneous transluminal coronary angioplasty procedures performed in The Netherlands between April 1980 and January 1989, the long-term follow-up of 454 patients who underwent angioplasty of ≥1 saphenous vein bypass graft was reviewed. In 46% of patients single graft angioplasty was attempted, and in 54% of patients sequential graft angioplasty was attempted. The clinical primary success rate was 90%. In-hospital mortality was 0.7%, 2.8% of patients sustained a procedural myocardial infarction, and 1.3% of patients underwent emergency bypass surgery. After a follow-up period of 5 years, 74% of patients were alive, and 26% were alive and event-free (no myocardial infarction, no repeat bypass surgery or repeat angioplasty). In patients in whom the initial angioplasty attempt was unsuccessful, only 3% were event-free at 5 years, versus 27% of successfully dilated patients. The time interval between the angioplasty attempt and previous surgery was a significant predictor for 5-year event-free survival. The event-free survival rates for patients who had bypass surgery 1 year before, between 1 and 5 years, and 5 years before angioplasty, were 45, 25 and 19%, respectively. Less than one-third of patients with previous bypass surgery who had angioplasty of the graft remained event-free after 5 years. In patients needing angioplasty within 1 year after bypass surgery, better long-term results were achieved.
