Systemic and myocardial effects of ATP and adenosine during hypoxic pulmonary hypertension in lambs.
The systemic and myocardial effects of adenosine and ATP were investigated in 12 newborn lambs, instrumented at 5-7 d of age with catheters in the aorta, pulmonary artery, coronary sinus, and right and left atria and flow transducers around the main pulmonary artery and left circumflex coronary artery. Studies were done 3-7 d after recovery from surgery. Pulmonary hypertension was induced by exposure to alveolar hypoxia (10% O2, 5% CO2, and 85% N2), which was maintained throughout the experiment. Adenosine, ATP, or an equal volume of saline (control) was infused into the right atrial line in doses of 0.04 to 2.5 mumol/kg/min during hypoxia. Alveolar hypoxia caused significant increases in pulmonary artery pressure, pulmonary vascular resistance, left circumflex flow, left ventricular O2 consumption, and systemic and myocardial O2 extraction and a decrease in systemic O2 transport. ATP and adenosine caused selective decreases in pulmonary artery pressure and pulmonary vascular resistance at doses of 0.04 to 0.30 mumol/kg/min and decreases in both pulmonary and systemic pressures and resistances at 0.60 to 2.5 mumol/kg/min. ATP and adenosine caused increases in systemic O2 transport, left circumflex flow, left ventricular O2 transport, and left ventricular O2 consumption and decreases in systemic O2 extraction and left ventricular O2 extraction at 0.3 to 2.5 mumol/kg/min. Systemic O2 consumption did not change during the study. arterial and coronary sinus blood lactate levels increased during hypoxia and decreased from hypoxia at 2.5-mumol/kg/min infusion rates of adenosine and ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
Konduri
G G
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Department of Pediatrics, Children's Hospital of Michigan, University School of Medicine, Detroit 48201.
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D010100:Oxygen / Q000493:pharmacokinetics*; D010101:Oxygen Consumption / Q000187:drug effects*; D010547:Persistent Fetal Circulation Syndrome / Q000188:drug therapy* / Q000378:metabolism; D012756:Sheep
D000255:Adenosine Triphosphate; D000241:Adenosine; D010100:Oxygen