Abstract
ABSTRACT: The brain is considered an “essential” organ, defined as one whose blood supply is preferentially maintained vis-a-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 (~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. Cerebral vascular regulation can be considered along two complementary dimensions. Vascular regulation within the cerebral circulation itself (cerebral autoregulation) is expressed as CBF versus CPP. CBF was unchanged as CPP fell during LAB and as CPP rose after NNLA in piglets. In contrast, after INDO, CBF fell as CPP rose. Vascular regulation of the cerebral circulation vis-a-vis the rest of the body (referred to here as cerebral-specific vascular regulation) can be expressed either in terms of blood flow (CBF/CO) or vascular resistance (CVR/SVR). After both NNLA and LAB, as CO fell, CBF/CO rose and CVR/SVR fell, demonstrating preservation of the “essential” status of the cerebral circulation. In contrast, after INDO as systemic CO fell, CBF/CO fell and CVR/SVR rose. Prostaglandins, but not endothelium-derived relaxation factor seem critical both for cerebral autoregulation and for preservation of the essential hemodynamic status of the brain vis-a-vis the rest of the body in piglets.
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Meadow, W., Rudinsky, B., Bell, A. et al. The Role of Prostaglandins and Endothehum-Derived Relaxation Factor in the Regulation of Cerebral Blood Flow and Cerebral Oxygen Utilization in the Piglet: Operationalizing the Concept of an Essential Circulation. Pediatr Res 35, 649–656 (1994). https://doi.org/10.1203/00006450-199406000-00006
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DOI: https://doi.org/10.1203/00006450-199406000-00006
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