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

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 Nnitro-L-arginine (NNLA; 25 mg/kg), prostaglandin inhibition with indomethacin (INDO, 5 mglkg), 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 (CBFICO) rose significantly during LAB and NNLA (+30%) but fell significantly during INDO (-12%). Similarly, relative cerebral vascular resistance (CVRISVR) 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 (CBFICO) or vascular resistance (CVRISVR). After both NNLA and LAB, as CO fell, CBFICO rose and CVRISVR fell, demonstrating preservation of the "essential" status of the cerebral circulation. In contrast, after INDO as systemic CO fell, CBFICO fell and CVRISVR rose. Prostaglandins,

Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortex

“…Reports on the effects of nitric oxide (NO) on cerebral autoregulation are controversial. In several species systemic administration of NO synthase inhibitors indicated that NO is not involved in the autoregulatory response to marked decreases in MABP (Wang et al 1992; Buchanan & Phillis, 1993; Meadow et al 1994; Saito et al 1994; Thompson et al 1996). Other studies in the adult brain have suggested that NO is at least one of the mediators of vasodilatation near the lower limit of cerebral autoregulation demonstrating a rise in the lower limit of cerebral autoregulation after inhibition of NO synthase in the brain (Kobari et al 1994; Jones et al 1999) or a decrease after infusion of SNP as a NO donator (Stange et al 1991; Tsutsui et al 1995).…”

Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO

“…Indomethacin is widely used at doses up to 5 mg kg −1 in order to test the role of prostaglandins in different processes and organs ( Fabricio et al ., 1998 ; Kato et al ., 1997 ; Meadow et al ., 1994 ; Tamori et al ., 1998 ). In protocol 6 of the present study, cyclo‐oxygenase inhibition via indomethacin (5 mg kg −1 ) altered PIV.…”

Relative Contribution of Endothelium-Derived Relaxation Factor to Vascular Tone in the Systemic, Pulmonary, and Cerebral Circulations of Piglets

“…These observations suggest that the carotid flow probe assessment of CBF may overestimate absolute CBF. Recently, how ever, we in piglets [ 12] and others using differ ent techniques in lambs [29] have shown that the unilateral carotid flow probe methodology provides an excellent estimate of changes in CBF, including under conditions of NO inhi bition.…”

“…The internal carotid artery blood flow (ICBF) tech nique has been described by us previously [12]. Briefly, a modification of the method of Gootman and Klein [13,14] and Scremin et al [15,16] was used.…”