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There is conflicting evidence as to which autonomic receptors mast cells possess and whether the receptors are capable of modulating mediator release. We have studied dog mastocytoma cells because they are available in large numbers in a relatively pure form, unlike normal dog mast cells. Mastocytoma nodules from a dog were excised and disaggregated with collagenase to provide a cell suspension of mastocytoma cells of greater than 92% purity. The presence of autonomic receptors was assessed by both radioligand binding assays and by evaluating pharmacologic modulation of mediator release. In the radioligand binding assays, beta-adrenergic receptors were estimated by [3H]dihydroalprenolol binding, alpha-adrenergic receptors by [3H]prazosin binding and cholinergic receptors by [3H]quinuclidinyl benzilate binding. Nonspecific binding was determined in each case by incubation in the presence of the specific antagonists propranolol, phentolamine, and atropine, respectively. The effect of autonomic agonists on immunologic and nonimmunologic histamine release was examined, using the beta-adrenergic agonists isoproterenol and terbutaline, the alpha-adrenergic agonist phenylephrine with and without propranolol, and the cholinergic agonist acetylcholine. Dose-response curves were constructed both for the autonomic agonists and the histamine-releasing agents. Results from the radioligand binding and the pharmacologic studies were concordant. These dog mastocytoma cells had a high density of beta-receptors (21,500 +/- 3,300; mean +/- SE beta-receptors/cell, n=5) of which the predominant subtype appeared to be beta2. No evidence was found for the presence of alpha-adrenergic or cholinergic receptors either by direct receptor binding or by their actions on histamine release.
Coronary artery disease remains the leading cause of death in the developed world. Over recent years, research has been focused on the development of diagnostic intravascular imaging techniques that enable assessment of plaque composition and morphology, and allow identification of vulnerable, high-risk lesions. Nevertheless recent studies of coronary atherosclerosis have shown that invasive modalities have a limited accuracy in detecting lesions that will progress and cause events, whilst histology-based studies also highlighted the limitations of invasive imaging in assessing plaque characteristics. To overcome these drawbacks, multimodality imaging has been proposed. Although it is apparent that coronary imaging with two or three imaging modalities is time consuming and is associated with a risk of complications, evidence from small clinical studies demonstrated that it provides incremental information about plaque pathology and biology and underscored the need to develop dual-probe hybrid imaging catheters that would enable complete and comprehensive assessment of plaque morphology. This paper reviews the current clinical evidence that supports the use of multimodality intravascular imaging in the study of atherosclerosis, summarizes the key findings of the first invasive imaging studies that utilize hybrid dual-probe catheters, and discusses the limitations of combined intravascular imaging that restrict its broad application in both the clinical and research arena.
The long-term prognostic impact of a composite of periprocedural major adverse events (PMAE) following revascularisation for patients with complex coronary artery disease (CAD) has not yet been established.
