M. D. Jones

Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.

Fetal head compression during normal labor can increase intracranial pressure (ICP). We studied the cerebral and peripheral blood flow responses to ICP elevation in utero in chronically catheterized fetal sheep using the radiolabeled microsphere technique. ICP was elevated, stepwise, in increments of 6±1 mm Hg by infusion of artificial cerebrospinal fluid into a lateral ventricle. When ICP was raised to within 28 mm Hg of baseline mean arterial blood pressure (i.e., ICP above 22 mm Hg), arterial pressure began to increase. Above this ICP level, up to 41 mm Hg, mean cerebral perfusion pressure was maintained by equivalent increases in arterial pressure. Cerebral blood flow and O2 uptake at the highest ICP levels were not different from baseline values. Changes in peripheral organ blood flow were graded according to the level of ICP. At the highest level (ICP=41 nun Hg), renal, gastrointestinal, and skin blood flow decreased by 68percent;, 69percent;, and 65percent;, respectively. Myocardial and adrenal blood flow doubled, whereas heart rate and cardiac output were unchanged. Placenta! blood flow increased in proportion to arterial pressure. Arterial plasma epinephrine, norepinephrine and arginine vasopressin increased by nearly two orders of magnitude. Therefore, as ICP approaches baseline mean arterial pressure, fetal lambs are capable of sustaining cerebral perfusion by initiating profound visceral vasoconstriction without curtailing placental blood flow. Since cerebral O2 uptake was maintained, there is no evidence that stimulation of the peripheral response requires pronounced cerebral ischemia. This highly developed Gushing response may be important for ensuring cerebral viability when the fetal head is compressed during parturition.

Cerebrovascular response to carbon dioxide in lambs receiving extracorporeal membrane oxygenation

ObjectiveTo determine if the institution of extracorporeal membrane oxygenation (ECMO) alters the cerebrovascular response to changes in Paco2. DesignProspective, randomized, controlled animal trial. SubjectsAnesthetized 1− to 7-day-old lambs of mixed breed (n = 16). SettingUniversity research laboratory. InterventionsThe experimental group was placed on ECMO. Both experimental and control groups (n = 8) were exposed to three concentrations of Paco2 (hypocarbia, normocarbia, and hypercarbia) by varying mechanical ventilation and by adding carbon dioxide to the ventilator gases. Measurements and Main ResultsCerebral blood flow was measured by the radiolabeled microsphere method. Arterial blood gases and sagittal sinus blood gases were drawn at the time of cerebral blood flow measurement so that cerebral metabolism, cerebral oxygen transport, and extraction could be calculated. In the control group, as Paco2 increased from 34 ± 2 (SD) to 53 ± 4 torr (4.5 ± 0.3 to 7.1 ± 0.5 kPa), cerebral blood flow increased from 53 ± 12 to 147 ± 50 mL/min/100 g. This increase in cerebral blood flow was not different from that of the ECMO group, where Paco2 increased from 33 ± 2 to 56 ± 3 torr (4.4 ± 0.3 to 7.5 ± 0.4 kPa) and cerebral blood flow increased from 48 ± 17 to 106 ± 38 mL/min/100 g. As Paco2 decreased from 34 ± 2 to 19 ± 2 torr (4.5 ± 0.27 to 2.5 ± 0.27 kPa), cerebral blood flow decreased from 53 ± 12 to 43 ± 8 mL/min/100 g in the control group. This decrease was not different from that of the ECMO group, where cerebral blood flow decreased from 48 ± 17 to 39 ± 10 mL/min/100 g as Paco2 decreased from 33 ± 2 to 22 ± 3 torr (4.4 ± 0.3 to 2.9 ± 0.4 kPa). When regional cerebral blood flow was analyzed, no regional differences in the cerebrovascular responses to Paco2 between ECMO and control groups were found.The cerebral metabolic rate was not different between ECMO and control groups at any level of Paco2, nor was the cerebral metabolic rate affected by changes in Paco2. Oxygen extraction increased with hypocarbia and decreased with hypercarbia in a similar fashion in both ECMO and control groups. ConclusionThe cerebrovascular response to changes in Paco2 was unaffected by ECMO. (Crit Care Med 1994; 22:291–298)

Elevated Brain Water During Urease-Induced Hyperammonemia in Dogs

Liver dysfunction often results in elevated levels of plasma ammonium (hyperammonemia), which is thought to be one of several major factors contributing to hepatic encephalopathy. Either hyperammonemia alone or liver dysfunction cause pathological changes marked by astrocytic swelling (Gibson et al. 1974; Laursen 1982), and biochemical changes marked by glutamine accumulation in brain tissue (Bachmann and Colombo 1983; Mans et al. 1982). One major mechanism for ammonia detoxification in brain is glutamine formation from glutamate and ammonia by the enzyme glutamine synthetase (Cooper et al. 1979). Because this enzyme is localized in astrocytes, we speculated that brain swelling might be linked to glutamine accumulation as a biochemical marker of brain ammonia toxicity (Brusilow and Traystman 1986).

Peripheral Organ Blood Flow Distribution During Raised Intracranial Pressure in Young Lambs

Elevation of intracranial pressure (ICP) is capable of producing a rise in arterial blood pressure as a component of the classic Cushing response. The end-organ response responsible for the rise of arterial blood pressure is thought to involve sympathetically-mediated peripheral vasoconstriction and increased cardiac output. Studies by Brashear and Ross (1970) have shown that beta adrenergic blockage prevents a rise in cardiac output when ICP is raised, and that after alpha adrenergic blockade, increasing ICP produces a fall in systemic vascular resistance.

Importance of Cerebral O2 Extraction Reserve During Elevated Intracranial Pressure in Young Lambs

The cerebral vascular bed autoregulates its blood flow in the face of elevated intracranial pressure (ICP) (Haggendal et al. 1970). With severe increases in ICP sufficient to reduce cerebral perfusion pressure below approximately 50 mm Hg, cerebral blood flow falls. However, it has been shown that cerebral oxygen consumption is maintained in dogs and rhesus monkeys in spite of a fall in cerebral flow (Grubb et al. 1975, Haggendal et al. 1970). This suggests that the brain has an oxygen extraction reserve which plays an important role in maintaining cerebral O2 uptake. Using the sheep as an experimental animal, we evaluated the importance of the oxygen extraction reserve during elevated ICP. We studied both newborn lambs and older lambs, for two reasons. First, it is not known how well cerebral blood flow is autoregulated and how cerebral O2 consumption is affected in the newborn when ICP is elevated. Second, the brain of the newborn lamb normally extracts a smaller fraction of oxygen than the adult sheep (Jones et al. 1982); thus, the newborn may have a greater O2 extraction reserve because it has a lower fractional O2 extraction under normal conditions.

Possible Physiological Role of the Cushing Response During Parturition

The Cushing response to elevated intracranial pressure (ICP) is often regarded as a defence mechanism of last resort when other mechanisms fail to maintain cerebral perfusion pressure. However, one physiological stress in which ICP may be commonly elevated is parturition. The fetus ordinarily is buoyed in amniotic fluid and uterine contractions produce equivalent increases in arterial pressure and ICP. However, once the head is engaged in the birth canal and begins to dilate the cervix, pressure on the skull is considerable. In the human fetus with its large, compliant skull, pressure on the equator of the skull may exceed amniotic fluid pressure by 50mm Hg or more (Lindgren 1960), and this pressure appears to be nearly fully transmitted intracranially (Schwarcz et al. 1969). Because fetal arterial pressure is only 40–50mm Hg greater than amniotic fluid pressure, cerebral ischemia might occur during intense labor. Even in non-human species with smaller skulls or closed fontanelles, the bone sutures usually are not fused and transient periods of elevated ICP are likely.

Oxygen Delivery to the Brain Before and After Birth

We studied the relationship between cerebral oxygen consumption and cerebral oxygen delivery (cerebral blood flow x arterial oxygen content) in fetal, newborn, and adult sheep, Relative to the amount of oxygen consumed, cerebral oxygen delivery in the fetus exceeds that in the lamb and adult by 70 percent. This may represent a protective advantage for the fetus or simply a necessary adaptation to the low arterial oxygen pressure in the intrauterine environment.