EFFECTS OF ADENOSINE ON CARDIOPULMONARY FUNCTIONS AND OXYGEN-DERIVED VARIABLES DURING ENDOTOXEMIA

Objectives: To determine the effects of a prophylactic intravenous inf usion of adenosine on cardiopulmonary functions and oxygen derived var iables in a porcine model of endotoxemia. Design: Prospective, randomi zed, placebo-controlled, unblinded study. Setting: University research laboratory. Subjects: Thirty country bred pigs, aged 6 to 7 wks, weig hing 24.9 +/- 0.65 (SEM) kg body weight. Interventions: Pigs were anes thetized by iv pentobarbital and fentanyl, intratracheally intubated, and mechanically normoventilated with a gas mixture of nitrous oxide/o xygen = 1:1. Intravascular catheters were inserted to allow for determ ination of arterial, central venous blood pressure, pulmonary artery o cclusion pressure, cardiac output, and sampling of blood for gas analy ses. Group 1 (n = 10) received a 330-min intravenous infusion of Salmo nella abortus equi endotoxin (5 mu g/kg body weight x hr). Group 2 (n = 10) received an additional intravenous infusion of adenosine (150 mu g/kg body weight x min), started 30 mins before the infusion of endot oxin. Control groups 3 and 4 (n = 5 for both groups) received adenosin e or physiologic saline, respectively. Measurements and Main Results: Parameters of cardiopulmonary nary function and oxygen derived variabl es were calculated from pulmonary artery catheter measurements and blo od gas analyses using standard formula. Plasma concentrations of purin e compounds (adenosine, inosine, hypoxanthine) were determined by high performance liquid chromatography. Since tumor necrosis factor-alpha plays a central role in the development of endotoxic shock, concentrat ions of this cytokine were determined in serum by enzyme-linked immuno sorbent assay. Infusion of adenosine before the beginning of the infus ion of endotoxin increased plasma concentrations of the nucleoside fro m 193 +/- 72 to 553 +/- 65 nmol/L and decreased the systemic vascular resistance by 50%. Although acting as a potent vasodilator under contr ol conditions, adenosine did not aggravate the arterial hypotension el icited by endotoxemia but significantly increased cardiac output by a comparably small decrease in systemic vascular resistance, prevention of pulmonary vasoconstriction, and improvement of left ventricular per formance. Despite significant pulmonary vasodilation, gas exchange was not worsened but slightly improved by adenosine. With the increase in cardiac output and arterial oxygenation, systemic oxygen delivery alm ost doubled. This adenosine induced oxygen flux was not a surplus but was most likely utilized by tissues, as suggested by the much earlier beginning of the increase in the systemic oxygen consumption and the a ttenuation of the decrease in the gastric mucosal pH(i). No effects of adenosine were observed on the endotoxin-induced increase in serum co ncentrations of tumor necrosis factor alpha. Conclusions: Infusion of adenosine might be useful to improve flow-dependent oxygen delivery an d tissue oxygenation during endotoxic shock without the induction of a dverse cardiopulmonary side effects. The beneficial hemodynamic effect s of adenosine appear not to be mediated by the inhibition of the rele ase of tumor necrosis factor-alpha.