Ex vivo studies demonstrated that a synthetic high-density lipoprotein (HDL) comprised of a complex of recombinant apolipoprotein A-I Milano and 1-palmitoyl-2-oleoyl phosphatidylcholine protects the isolated rabbit heart from reperfusion injury. Therefore, we sought to determine whether a pharmaceutical preparation of this complex, ETC-216 , was cardioprotective in an in vivo model of left anterior descending artery (LAD) occlusion and reperfusion. Initially, ETC-216 (100 mg/kg) was tested in acute (one-treatment) and chronic (two-treatment) i.v. administrations. ETC-216-treated rabbits developed smaller infarcts expressed as percentage of area at risk (p Ͻ 0.01) compared with vehicle treatments. No differences were noted between chronic and acute administration. Therefore, ETC-216 (10, 3, or 1 mg/kg) or equivalent vehicle volumes were acutely infused. Compared with vehicle,
Symptomatic orthostatic hypotension is a serious problem in the elderly because it can precipitate falls and fractures, myocardial infarctions, and strokes. Several disorders may cause symptomatic orthostatic hypotension including age-related changes in physiology, disorders of the autonomic nervous system, drugs, and a decrease in circulating blood volume. Orthostatic hypotension is defined as a fall in systolic pressure of at least 20–30 mm Hg and a fall in diastolic pressure of at least 10–15 mm Hg upon rising, with symptoms of cerebral ischemia. Management includes a search for reversible causes as well as nonpharmacologic and pharmacologic therapies. No single agent has been universally successful in relieving the symptoms of orthostatic hypotension. Trials of single agents or combinations of agents are needed to identify the most appropriate therapy for individual patients.
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