Analysis of cardiac adrenergic mechanisms in hypoxic lambs

Abstract

Adrenergically mediated inotropic and chronotropic responses to hypoxemia were studied in 12 neonatal lambs ranging from 1 to 10 days of age. Six lambs were adrenalectomized (Adnx) and six were sham operated. Inotropic changes were assessed from measurements of left ventricular dP/dtmax under controlled hemodynamic conditions. Atropine (1 mg) was given and hypoxia produced by adding N2 to the respirator. In the sham-operated lambs, dP/dtmax increased as a function of the level of hypoxemia. With a mean arterial O2 partial pressure (PaO2) of 21.7 +/- 2.0 Torr, dP/dtmax averaged 17 X 10(2) mmHg/s above control values. Adnx did not reduce resting dP/dtmax, but comparable levels of hypoxemia elicited a much smaller increase (5 X 10(2) mmHg/s) in this group (P less than 0.02). In the sham-operated lambs, ganglionic blockade with tetraethylammonium chloride (TEAC, 100 mg) reduced the hypoxic response to similar values (6.5 X 10(2) mmHg/s). These residual inotropic responses were completely abolished by beta-adrenergic blockade with practolol (4 mg/kg). Chronotropic changes were identical in both groups (18.7 beats/min) and abolished by TEAC alone. It is concluded that the major fraction of adrenergic inotropic stimulation during hypoxemia is derived from the adrenal glands and that autonomic neural function is essential to the release process. Heart rate responses are independent of adrenal integrity. A residual source of inotropic stimulation, blocked by practolol, is derived from unidentified sources.