Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

Blood platelets from 10 normal human subjects have been examined with a sensitive differential interference contrast (DIC) microscope . The entire transformation process during adhesion to glass is clearly visible and has been recorded cinematographically, including the disk to sphere change of shape, the formation of sessile protuberances, the extension and retraction of pseudopodia, and the spreading, ruffling, and occasional regression of the hyalomere . The exocytosis of intact dense bodies can be observed either by DIC microscopy, or by epifluorescence microscopy in platelets stained with mepacrine . Details offluorescent flashes indicate that the dense bodies usually release their contents extracellularly, but may do so intracytoplasmically under the influence of strong, short wavelength light on some preparations of mepacrine-stained platelets . The release of one or more dense bodies leaves a crater of variable size on the upper surface of the granulomere . Such craters represent the surface component of the open canalicular system and their formation and disappearance can be directly observed . Because these techniques permit quantitation of several parameters of motility which are not readily observable by other techniques, it is suggested that high extinction DIC microscope examination may become a rapid and useful method of studying congenital and acquired platelet disorders . Many features of platelet transformation have been confirmed and extended by scanning electron micrographs . These can in turn be interpreted by reference to time-lapse films of living platelets.KEY WORDS platelets " transformation release reaction -exocytosis pseudopodia motility -DIC microscopy scanning electron microscopy It has been known since the last century that platelets (thrombocytes) undergo a change of shape (transformation) as part of their role in hemostasis (for reviews, see references 19, 20, 22, 51, 60, 66, and 67) . Light microscope observation established that platelets formed spiky protuberances and gradually spread on glass surfaces in imitation of their spreading on damaged vascular endothelia (9) . However, the resolution and sen-J . CELL BIOLOGY C The Rockefeller University Press "

1. Sealey JE, Laragh JH. Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness.

The use of antiplatelet agents, specifically the thienopyridines, has become a standard of care in the approach to the patient presenting with an acute coronary syndrome. These drugs irreversibly inhibit the platelet by permanently binding to the surface P2Y12 receptor and blocking the downstream fibrinogen cross-linking between platelets, which leads to aggregation and thrombus. However, currently available therapeutic choices are limited by potential interaction with other medications, slow hepatic conversion to active metabolite, genetic resistance, and narrow therapeutic safety margin. In order to overcome these disadvantages, there has been an interest in developing alternatives to thienopyridines. Recent investigations have included ticagrelor, a reversible inhibitor of the P2Y12 platelet receptor, which appears to have overcome several drawbacks of the current thienopyridines. Its unique pharmacokinetic and pharmacodynamic profiles result in an inhibition of platelet aggregation that is rapid, high, consistent, and less susceptible to interpatient variability than currently available P2Y12 inhibitors. In addition, ticagrelor offers a potential mortality advantage not apparent with current agents. Although questions regarding the nature, magnitude, and clinical significance of several observed adverse effects (dyspnea and ventricular pauses) remain unanswered, it appears that ticagrelor may represent a significant advancement over currently available oral antiplatelet agents.

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