The role of prostaglandins and endothelium-derived relaxation factor in the regulation of cerebral blood flow and cerebral oxygen utilization in the piglet: operationalizing the concept of an essential circulation.
The brain is considered an "essential" organ, defined as one whose blood supply is preferentially maintained vis-à-vis other less-essential circulations during periods of reduced systemic cardiac output (CO). We asked whether the actions of either prostaglandins or endothelium-derived relaxation factor might underlie the essential qualities of the cerebral circulation; that is, would the absence of one or the other impair the ability of the brain to preferentially redirect systemic blood flow during a period of reduced systemic CO. We compared hemodynamics in the cerebral and systemic circulations in 33 anesthetized piglets under three conditions that reduced systemic CO equivalently: endothelium-derived relaxation factor inhibition with the substituted L-arginine analog N-nitro-L-arginine (NNLA; 25 mg/kg), prostaglandin inhibition with indomethacin (INDO; 5 mg/kg), and inflation of a left atrial balloon (LAB) catheter. NNLA, INDO, and LAB each reduced CO to an equivalent value (approximately 30% from baseline). NNLA and INDO, but not LAB elevated systemic blood pressure, cerebral perfusion pressure (CPP), systemic vascular resistance (SVR), and cerebral vascular resistance (CVR). Cerebral blood flow (CBF) was preserved after NNLA and LAB but fell after INDO (-35%). Despite the equivalent reduction in CO noted during the three experimental protocols, the proportion of systemic blood flow directed toward the brain (CBF/CO) rose significantly during LAB and NNLA (+30%) but fell significantly during INDO (-12%). Similarly, relative cerebral vascular resistance (CVR/SVR) fell significantly during LAB and NNLA but rose during INDO.(ABSTRACT TRUNCATED AT 250 WORDS)
Meadow
W
W
Department of Pediatrics, University of Chicago, Illinois 60637.
Rudinsky
B
B
Bell
A
A
Lozon
M
M
Randle
C
C
Hipps
R
R
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002302:Cardiac Output; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D010101:Oxygen Consumption / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology*; D013552:Swine
D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin