Response of normal and reperfused livers to glucagon stimulation: NMR detection of blood flow and high-energy phosphates.
The effects of glucagon on blood flow and high-energy phosphates in control and in rat livers damaged by ischemia were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Normal livers and livers which had been made ischemic for 20, 40, and 60 min followed by 60 min of reperfusion were studied. Ischemia led to a loss in adenosine triphosphate (ATP) within 30 min. Reperfusion after 20 min of ischemia led to complete recovery of ATP. 60 min of reperfusion after 40 or 60 min of ischemia led to only a 76% and 48% recovery of ATP, respectively. Glucagon, at doses up to 2.5 mg/kg body weight, caused no changes in the inorganic phosphate (P(i)) to ATP ratio in normal livers as measured by 31P-NMR spectroscopy. In livers which had been made ischemic for 20, 40, or 60 min, glucagon caused an increase in the P(i)/ATP ratio of 18%, 40%, and 40%, respectively. 19F-NMR detection of the washout of trifluoromethane from liver was used to measure blood flow. Glucagon-stimulated flow in the normal liver in a dose-dependent manner, with 2.5 mg glucagon/kg body weight leading to a 95% increase in flow. Ischemia for 20, 40, and 60 min followed by 60 min of reperfusion led to hepatic blood flows which were 63%, 68%, and 58% lower than control liver. In reperfused livers, blood flow after glucagon-stimulation was reduced to 56%, 43%, and 48% of control glucagon-stimulated flow after 20, 40, and 60 min of ischemia. These results indicate that ischemia followed by reperfusion leads to decreases in hepatic blood flow prior to alterations in ATP and the response of the liver to glucagon is altered in the reperfused liver.
Walsh
T R
TR
Pittsburgh NMR Center for Biomedical Research, PA.
Detre
J A
JA
Koretsky
A P
AP
Simplaceanu
E
E
Halow
J M
JM
Rao
P
P
Makowka
L
L
Ho
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005934:Glucagon / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D010710:Phosphates; D000255:Adenosine Triphosphate; D005934:Glucagon