After total ischemia occurs, the myocardium switches immediately from aerobic glycolysis to anaerobic glycolysis resulting in the reduced ability to produce high energy phosphates such as ATP and Creatinine Phosphate. At this point, the lack of the energy and lactate accumulation results in cessation of contraction within 60 seconds of ischemia (i.e. Vessel Occlusion). Subsequent to this is a period of "myocardial stunning," in which reversible ischemic damage is taking place. At approximately 30 minutes after the onset of total ischemia the damage becomes irreversible, thereby ending the phase of myocardial stunning. The generation of oxygen-derived [free radicals] during the initial period of reperfusion after ischemia is believed to contribute to the pathogenesis of myocardial stunning.Some evidence suggests that brief, repetitive episodes of myocardial ischemia may result in chronic myocardial stunning and ventricular contractile impairment. Diagnosis
Imaging techniques such as echocardiography, ventriculography, and nuclear imaging can be used to detect a contractile dysfunction following reperfusion after an episode of ischemia. The area of dysfunction should also maintain normal perfusion, detected via Positron Emission Tomography, echocardiography with contrast, and/or thallium scintigraphy in order for a diagnosis of myocardial stunning to be considered. However, there are many practical challenges to diagnosing myocardial stunning using these methods. Accurate detection of regional myocardial blood flow and contraction function abnormalities must be detected at levels of high sensitivity. The diagnosis of myocardial stunning must also be differentiated from other conditions such as hibernating myocardium and persistent (silent) subendocardial ischemia, which can also co-exist with superimposed stunning.
Aminoglycoside-induced production of reactive oxygen species may also injure cells of the cochlea. Once-daily dosing and co-administration of N-acetylcysteine may protect against aminoglycoside-induced ototoxicity. The anti-bacterial activity of aminoglycoside compounds is due to inhibition of ribosome function and these compounds similarly inhibit protein synthesis by mitochondrial ribosomes because mitochondria evolved from a bacterial ancestor. Consequently, aminoglycoside effects on production of reactive oxygen species as well as dysregulation of cellular calcium ion homeostasis may result from disruption of mitochondrial function. Ototoxicity of gentamicin can be exploited to treat some individuals with Ménières disease by destroying the inner ear,  which stops the vertigo attacks but causes permanent deafness. Due to the effects on mitochondria, certain inherited mitochondrial disorders result in increased sensitivity to the toxic effects of aminoglycosides. Macrolide antibiotics, including erythromycin, are associated with reversible ototoxic effects. The underlying mechanism of ototoxicity may be impairment of ion transport in the stria vascularis. Predisposing factors include renal impairment, hepatic impairment, and recent organ transplantation. Loop diuretics
Certain types of diuretics are associated with varying levels of risk for ototoxicity. Loop and thiazide diuretics carry this side effect. The loop diuretic furosemide is associated with ototoxicity, particularly when doses exceed 240 mg per hour. The related compound ethacrynic acid has a higher association with ototoxicity, and is therefore used only in patients with sulfa allergies. Diuretics are thought to alter the ionic gradient within the stria vascularis. Bumetanide confers a decreased risk of ototoxicity compared to furosemide.