Hypercapnia and response of cerebral blood flow to hypoxia in newborn lambs.

Individual effects of hypoxic hypoxia and hypercapnia on the cerebral circulation are well described, but data on their combined effects are conflicting. We measured the effect of hypoxic hypoxia on cerebral blood flow (CBF) and cerebral O2 consumption during normocapnia (arterial PCO2 = 33 +/- 2 Torr) and during hypercapnia (60 +/- 2 Torr) in seven pentobarbital-anesthetized lambs. Analysis of variance showed that neither the magnitude of the hypoxic CBF response nor cerebral O2 consumption was significantly related to the level of arterial PCO2. To determine whether hypoxic cerebral vasodilation during hypercapnia was restricted by reflex sympathetic stimulation we studied an additional six hypercapnic anesthetized lambs before and after bilateral removal of the superior cervical ganglion. Sympathectomy had no effect on base-line CBF during hypercapnia or on the CBF response to hypoxic hypoxia. We conclude that the effects of hypoxic hypoxia on CBF and cerebral O2 consumption are not significantly altered by moderate hypercapnia in the anesthetized lamb. Furthermore, we found no evidence that hypercapnia results in a reflex increase in sympathetic tone that interferes with the ability of cerebral vessels to dilate during hypoxic hypoxia.

Relationship of diaphragmatic contractility to diaphragmatic blood flow in newborn lambs.

We determined the relationship of diaphragmatic contraction rate to diaphragmatic blood flow (Qdi), metabolism, and contractility in nine open-chested mechanically ventilated newborn lambs. The diaphragm was paced for 15 min at slow (20/min) and fast (100/min) contraction rates each followed by a 30-min rest period. There was a mild reduction in transdiaphragmatic pressure (Pdi) during the slow contraction period accompanied by a shift to the right of the curve relating stimulation frequency (10-100 Hz) to Pdi. Pdi returned to control at the start of the fast contraction period, but then fell by 30% within 2 min with continued fast contraction rates. The frequency-Pdi curve was significantly shifted to the right. Qdi, O2 transport, and O2 consumption increased during slow contraction and to an even greater extent during fast contraction. Fractional O2 extraction reached an apparent maximum during slow contraction. Lactate efflux from the right phrenic vein during slow contraction remained unchanged from control. During fast contraction lactate efflux rose proportionately more than did O2 consumption. We conclude that the energy demands at fast rates of diaphragmatic contraction in newborn lambs cannot be met by aerobic metabolism alone despite increasing O2 transport to the diaphragm.

Effect of hematocrit on cerebral blood flow with induced polycythemia.

Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.

Base-line O2 extraction influences cerebral blood flow response to hematocrit.

We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS)