Wednesday, May 18, 2016

What is rotating inotrope therapy ? A lifesaving regimen for decompensated heart failure of both adult and pediatric population!

The catecholamine neurotransmitters  mediate their physiological responses through the family of adrenergic receptors. Three types or subfamilies of adrenergic receptors have been identified: the alpha-1, alpha-2 and beta. Within each of these subfamilies are receptor subtypes, including the subtypes of alpha-2 adrenergic receptors: alpha-2A, -2B and -2C (Bylund et al., 1994).

The expression of these receptors is not static and can change with disease, aging or therapeutic treatment. Alteration of receptor density can occur at any of the steps from gene transcription to degradation of the receptor protein itself. Continued agonist stimulation of a receptor population often causes a rapid reduction in response to the agonist, a phenomenon known as desensitization. Short-term desensitization is characterized as a rapid (minutes) and reversible uncoupling of the receptor-G protein complex mediated by receptor phosphorylation. This is followed by sequestration and internalization of receptors from the cell surface. Receptors are not lost during short-term desensitization because removal of agonist rapidly restores receptor function. Downregulation, on the other hand, is defined as a decrease in receptor density and displays a much longer time course (hours) which is thought to result from an actual loss of receptors. Removal of agonist will allow recovery of receptor density, but this recovery takes longer, requiring synthesis of new receptors in most cases (Hein and Kobilka, 1995; Toews et al., 1991).


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