Correlation of flow probe determinations of common carotid artery blood flow and internal carotid artery blood flow with microsphere determinations of cerebral blood flow in piglets.

We investigated whether blood flow determined by a flow probe situated on one common carotid artery provided an accurate estimation of unilateral cerebral blood flow (CBF) in piglets. In eight anesthetized, mechanically ventilated piglets, blood flow determined by an ultrasonic flow probe placed on the right common carotid artery was correlated with CBF determined by microspheres under two experimental conditions: 1) before ligation of the right external carotid artery with both the right external and internal carotid circulations intact [common carotid artery blood flow (CCABF) condition], and 2) after ligation of the right external carotid artery (ipsilateral to the flow probe) with all residual right-sided carotid artery blood flow directed through the right internal carotid artery [internal carotid artery blood flow (ICABF) condition]. The left carotid artery was not manipulated in any way in either protocol. Independent correlations of unilateral CCABF and ICABF with microsphere-determined unilateral CBF were highly significant over a 5-fold range of CBF induced by hypercarbia or hypoxia (r = 0.94 and 0.92, respectively; both p < 0.001). The slope of the correlation of unilateral CCABF versus unilateral CBF was 1.68 +/- 0.19 (SEM), suggesting that CCABF overestimated CBF by 68%. The slope of the correlation of unilateral ICABF versus unilateral CBF did not differ significantly from unity (1.06 +/- 0.15), and the y intercept did not differ significantly from zero [-1.3 +/- 5.2 (SEM) mL]. Consequently, unilateral ICABF determined by flow probe accurately reflected unilateral CBF determined by microspheres under these conditions. Flow probe assessments of CCABF and ICABF in piglets may provide information about dynamic aspects of vascular control in the cerebral circulation that has heretofore been unavailable.

Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.

Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as 5 micrograms kg-1 bolus followed by 0.1 microgram kg-1 min-1 continuous infusion for 105 min in six piglets, while the same treatment was repeated in five animals without preceding HI insult. At third group of six served as sham operated controls. In the HI insult group by 105 min of nimodipine infusion the mean BP dropped by 30% and the cardiac output dropped by 23% of respective baseline. In this group, the renal blood flow dropped between 65% and 77% of baseline and regional cerebral blood flow dropped between 28% and 55% of respective baseline by 45 min and 105 min of nimodipine fashion. In the group with no prior HI insult, 105 min of nimodipine infusion caused no significant changes in these variables. Despite nimodipine infusion, HI insult caused a significant increase in the mean brain water content compared to the two control groups: 89 +/- 3.2% compared to 82.7 +/- 0.5% in the nimodipine control group, and 83.7 +/- 1.7% in the sham group (P < 0.0001). We conclude that while nimodipine therapy without prior asphyxial insult does not cause significant adverse haemodynamic effects, its infusion after even a mild HI insult could cause reduction in renal blood flow and moderate reduction in regional cerebral blood flow, BP, and cardiac output, suggesting a differential effect. A 15 min lag between HI insult and nimodipine therapy may be too long to prevent cerebral oedema.

Renal actions of endothelin-1 in newborn piglets: dose-effect relation and the effects of receptor antagonist (BQ-123) and cyclooxygenase inhibitor (indomethacin).

Although the effects of endothelin-1 (ET-1) on intact or perfused adult kidney are well understood, its effects in the fetus and the newborn have not been well studied. We examined the effects of infusions of 25, 50, and 100 ng/kg of ET-1 per minute on mean blood pressure (MBP), cardiac index (CI), renal blood flow (RBF), glomerular filtration rate (GFR), and urine volume (UV) in 7- to 10-day-old piglets (n = 24). In addition, the effects of pretreatment with a receptor antagonist (BQ-123) and with a cyclooxygenase inhibitor (indomethacin) were studied in 12 separate piglets. ET-1 produced a dose- and level-dependent decrease in CI (60%), RBF (50% to 75%), GFR (66% to 80%) and MBP 15% to 17%. These changes returned to 75% to 80% of baseline 60 minutes after discontinuation of ET-1. Low-dose infusion (25 ng/kg) did not result in any changes in systemic or renal hemodynamics. Plasma half-life of ET-1 in piglets was 2.1 +/- 0.4 minutes. Pretreatment with the specific ETA receptor antagonist BQ-123 completely blocked the ET-1-induced systemic and renal hemodynamic changes. Indomethacin blocked the ET-1-induced rise in MBP but failed to block any renal changes. In fact, indomethacin accentuated the changes induced by ET-1, especially the changes in RBF, RVR, and GFR. Studies of receptor binding in the renal cortex and medulla showed that, in the cortex, the Ki value for ET-1 was 6.32 +/- 1.57, and for ET-3 it was 20.05 +/- 4.38 (p < 0.05); in the medulla, the Ki values were similar for both ET-1 and ET-3. These results indicate that in piglets the renal vascular bed is highly sensitive to ET-1, and its effects are predominantly mediated through ETA receptors.