Ahlquist (1948) postulated that sympathetic receptor sites were of two types, which he called a and ,B, and this concept has been supported by other workers. Most of the sympathetic excitatory effects depend on a-receptors, and the inhibitory effects on f-receptors. One important exception is the heart, where stimulation is a P-adrenergic action. The older adrenergic-blocking drugs are known to inhibit only the a-receptors, and this explains their failure to influence sympathetic control of the myocardium. The first drug capable of ,B-adrenergic blockade was dichloroisoprenaline (D.C.I.) (Powell and Slater, 1958), but this was by no means free of sympathomimetic action of its own (Furchgott, 1959;Dresel, 1960;Black and Stephenson, 1962). Pronethalol is a similar agent, with little sympathomimetic activity. It was originally described under the provisional official name of nethalide by Black and Stephenson (1962). Like D.C.I. it bears a structural resemblance to isoprenaline (Fig. 1).The drug has been used in the present study to investigate the effects of sympathetic blockade of the heart on the heemodynamics of exercise. SUBJECTS AND METHODTen normal volunteer medical students, 9 men and 1 woman, were studied; their ages ranged from 20 to 27 years. Observations of cardiac output, heart rate, and blood pressure were made at rest and on treadmill exercise on two separate occasions: once without medication, and once after the administration of pronethalol. Before the tests, each student was made familiar with the cardiac laboratory and with the techniques used. The order in which the experiments were performed was alternated so that with five subjects the observations after pronethalol were made first.The cardiac output estimations were made using a dye-dilution technique with the Cambridge earpiece and mark-2 recorder. Nylon catheters of 1'02 mm. internal diameter were introduced percutaneously over a Seldinger guide wire into antecubital veins, one in each arm, and passed about 18 in. (46 cm.) to bring them near the origin of the superior vena cava. One was used for injections of 2 per cent Coomassie blue, and the other, with multiple side-holes near the tip, for obtaining samples of venous blood. Blank and tail specimens were obtained for each curve because, when using an earpiece, calibration does not remain constant with changes in posture or on exercise. Arterial sampling was found to be unnecessary provided adequate time was allowed for complete mixing. Good baselines during exercise could be obtained by careful attention to stability of the earpiece on the ear: this was achieved by fitting a pad of polyester foam around the earpiece, and securing the pad with a crepe bandage. Adequate earthing of both the patient and the recorder was also important. There was often a slight phasic respiratory artefact of the baseline, especially during exercise, but not enough to affect the validity of the calculations. In several subjects it was necessary to administer oxygen to prevent variations in arterial saturation ...

Summary:Catheter balloon valvuloplasty of stenotic aortic valves has met with generally poor short-and longtemi clinical results. Part of this problem resides with the lack of recognition of various etiologies of aortic stenosis. Part I of this review discusses the various etiologies of aortic stenosis and provides an anatomic basis for successful valve dilation. Results of an in vitro study indicate stenotic aortic valves are dilated by various mechanisms (cracking, stretching) based in part upon the etiology of the aortic valve stenosis.Key words: aortic stenosis, aortic balloon valvuloplasty, bicuspid aortic valve, rheumatic disease, degenerative aortic stenosis percutaneous balloon aortic valvuloplasty may improve some symptoms, the high incidence of recurrence of clinical symptoms within several weeks and the high mortality within 8 months of the dilation limits the procedure to selected patients.The results of aortic balloon valvuloplasty described above represent no clinical or morphologic attempt to separate patients (aortic valves) into subgroups of specific aortic valve etiology. Specific morphologic selection of stenotic aortic valves for balloon dilation may greatly improve these initial dismal clinical results of dilation. Part 1 of this review provides an anatomic basis for aortic balloon valvuloplasty and indicates mechanisms of successful balloon dilation for various causes of aortic valve stenosis.

Summary:This two-part article examines the histologic and morphologic basis for stenotic and purely regurgitant aortic valves. Part I discussed stenotic aortic valves and Part II discusses causes of purely regurgitant aortic valves. In over 95% of stenotic aortic valves, the etiology is one of three types: congenital (primarily bicuspid), degenerative, and rheumatic. Other rare causes included active infective endocarditis, homozygous type 11 hyperlipoproteinemia, and systemic lupus erythematosis. The causes of pure aortic regurgitation are multiple but can be separated into diseases affecting the valve (normal aorta) (infective endocarditis, congenital bicuspid, rheumatic, floppy), diseases affecting the walls of aorta (normal valve) (syphilis, Marfan's, dissection), disease affecting both aorta and valve (abnormal aorta, abnormal valve) (ankylosing spondylitis), and disease affecting neither aorta nor valve (normal aorta, normal valve) (ventricular septal defect, systemic hypertension). Diseases affecting the aortic valve alone are the most common subgroup of conditions producing purely regurgitant aortic valves.

This two-part article examines the histologic and morphologic basis for stenotic and purely regurgitant mitral valves. In Part I, conditions producing mitral valve stenosis were reviewed. In over 99% of stenotic mitral valves, the etiology is rheumatic disease. Other rare causes of mitral stenosis include congenitally malformed valves, active infective endocarditis, massive annular calcium, and metabolic or enzymatic abnormalities. In Part II, conditions producing pure mitral regurgitation are discussed. In contrast to the few causes of mitral stenosis, the causes of pure (no element of stenosis) mitral regurgitation are multiple. Some of the conditions producing pure regurgitation include floppy mitral valves, infective endocarditis, papillary muscle dysfunction, rheumatic disease, and ruptured chordae tendineae.

Summary: This three-part article examines the histologic and morphologic basis for stenotic and purely regurgitant tricuspid valves. In Part III, morphometric analysis of tricuspid valve annular circumference, leaflet area, and the product of annular circumference and leaflet area are shown to be useful in establishing etiology for the purely regurgitant tricuspid valves and in assessing the anatomic basis of pure tricuspid regurgitation in the presence of mitral stenosis.