This negative chronotropic effect is synergistic with the direct effect on cardiac pacemaker cells. The arrhythmia itself is not affected, but the pumping function of the heart improves, owing to improved filling. Overall, the heart rate is decreased while stroke volume is increased, resulting in a net increase in blood pressure, leading to increased tissue perfusion. This causes the myocardium to work more efficiently, with optimized hemodynamics and an improved ventricular function curve. Other electrical effects include a brief initial increase in action potential, followed by a decrease as the K+ conductance increases due to increased intracellular amounts of Ca2+ ions. The refractory period of the atria and ventricles is decreased, while it increases in the sinoatrial and AV nodes. A less negative resting membrane potential is made, leading to increased irritability. The conduction velocity increases in the atria, but decreases in the AV node. The effect upon Purkinje fibers and ventricles is negligible. Automaticity is also increased in the atria, AV node, Purkinje fibers, and ventricles.ECG changes seen in people taking digoxin include increased PR interval (due to decreased AV conduction) and a shortened QT interval. Also, the T wave may be inverted and accompanied by ST depression. It may cause AV junctional rhythm and ectopic beats (bigeminy) resulting in ventricular tachycardia and fibrillation. Pharmacokinetics
Digoxin is usually given orally, but can also be given by IV injection in urgent situations (the IV injection should be slow, and heart rhythm should be monitored).
Tympanosclerosis is a condition caused by hyalinization and subsequent calcification of subepithelial connective tissue of the tympanic membrane and middle ear, sometimes resulting in a detrimental effect to hearing. Signs and symptoms
Myringosclerosis rarely causes any symptoms. Tympanosclerosis, on the other hand, can cause significant hearing loss or chalky, white patches on the middle ear or tympanic membrane. Causes
The aetiology for tympanosclerosis is not extensively understood. There are several probable factors which could result in the condition appearing, including:

Long term otitis media (or glue ear)
Insertion of a tympanostomy tube. If aspiration is performed as part of the insertion, the risk of tympanosclerosis occurring increases. Risk also increases if a larger tube is used, or if the procedure is repeated. Atherosclerosis
There is ongoing research as to whether or not cholesteatoma is associated with tympanosclerosis. If there is an association, it is likely that the two conditions co-exist. Pathophysiology
Increased fibroblast activity results in deposition of collagen. Calcium phosphate plaques then form in the lamina propria of the tympanic membrane. Diagnosis
If lesions are typical, non-extensive and with no detriment to hearing, investigation into the condition is rarely required. Audiometry is used to determine the extent of hearing loss, if any. Tympanometry produces tympanograms which can be different when tympanosclerosis is present. Computerised tomography (CT) can be used to determine if disease is present in the middle ear.