Glucagon effect on postischemic recovery of intestinal energy metabolism.
Glucagon is a potent mesenteric vasodilator, inotrope, and stimulant of intestinal metabolism that enhances survival when given during reperfusion after intestinal ischemia. However, the mechanism of improved survival is unclear and may be due to systemic hemodynamic effects rather than intestinal metabolic changes. We examined the effects of glucagon on intestinal energy metabolism during reperfusion after intestinal ischemia. Sprague-Dawley rats were subjected to 50 min intestinal ischemia by clamping the superior mesenteric artery. All received 10 ml/kg.hr 5% glucose in normal saline for 3 hr. One group (n = 17) received 1.6 micrograms/kg.min glucagon for 2 hr beginning at reperfusion. Control rats (n = 10) received only vehicle. Jejunal biopsies preischemia, end ischemia, 10, 20, 45, 80 min, and 24 hr after reperfusion were analyzed for ATP, ADP, and AMP. ATP decreased more than 60% with ischemia and recovered substantially in all animals by 10 min postischemia. ATP recovered steadily in control rats and by 24 hr was not distinguishable from baseline. In contrast, in glucagon-treated rats, ATP decreased at 20 and 45 min during reperfusion, but recovered incompletely by 24 hr after ischemia. Energy charge (EC = ([ATP] + 1/2[ADP]) divided by ([ATP] + [ADP] + [AMP])) decreased during ischemia but recovered immediately after reperfusion in both groups, implying that energy was available, energy metabolic enzyme systems were at least partially intact, and immediate recovery was not limited by available substrate and blood flow. However, energy charge decreased slightly during glucagon infusion, suggesting increased utilization of energy or some derangement of energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Schneider
J R
JR
Section of Vascular Surgery, Veterans Affairs Medical Center, White River Junction, Vermont 05009.
Foker
J E
JE
Macnab
J R
JR
Marquardt
C A
CA
Cronenwett
J L
JL
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005934:Glucagon