Hypoglycemic hyperemia in retina of newborn pigs. Involvement of adenosine.
OBJECTIVE
To determine whether retinal blood flow increases in response to perinatal hypoglycemia and whether the vasodilator adenosine is involved in mediating the hyperemic response.


METHODS
Retinal fluorescein videoangiography was undertaken in intact eyes of isoflurane-anesthetized piglets using intracarotid injections of sodium fluorescein. Angiograms were recorded to videotape and analyzed off-line by image analysis software to determine stimulus-induced changes in mean arteriovenous transit times, and arteriolar and venular diameters, from which retinal blood flow was calculated. Two groups of animals were rendered hypoglycemic (blood glucose = 19 +/- 1 mg/dl) by insulin (25 IU/kg, intravenously), and angiograms were obtained at 10-minute intervals for 0.5 hour of hypoglycemia. One group (n = 5) served as controls. In the other (n = 5), the nonspecific adenosine receptor antagonist 8-phenyltheophylline (8PT) was administered intravenously approximately 15 minutes before hypoglycemia to examine the role of adenosine in the hemodynamic response to hypoglycemia.


RESULTS
Acute hypoglycemia was associated with an increase in mean retinal blood flow of 94 +/- 18% (P < 0.002). However, in animals pretreated with 8PT, this hyperemic response was severely attenuated, primarily by an effect on arteriovenous transit time. In these latter animals, mean retinal blood flow only increased 19 +/- 10% in response to hypoglycemia (P = 0.13 versus normoglycemic baseline; P = 0.007 versus untreated hypoglycemic animals). All other hemodynamic variables were similar between animal groups.


CONCLUSIONS
Acute hypoglycemia causes a compensatory increase in retinal blood flow in the perinatal period. Because the adenosine receptor antagonist 8PT attenuated this hyperemic response, it is concluded that adenosine is involved in eliciting the increase in retinal blood flow that accompanies hypoglycemia.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Y
Y
Zhu
J M
JM
Gidday
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D005451:Fluorescein Angiography; D006940:Hyperemia / Q000503:physiopathology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D007328:Insulin; D058915:Purinergic P1 Receptor Antagonists; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012171:Retinal Vessels / Q000503:physiopathology*; D013552:Swine; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014741:Video Recording
D001786:Blood Glucose; D007328:Insulin; D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine