Tissue pO2 of human brain cortex--method, basic results and effects of pentoxifylline.

A polarographic multiwire surface electrode was used for measurement of local oxygen partial pressure (pO2) on human brain cortex during neurosurgical operations. The two major problems encountered in this application of the electrode involved sterility of the equipment and mounting of the electrode. The described method of sterilization does not alter the electrical properties of the electrode. A special mount was designed to allow free three-dimensional placement of the electrode without exerting pressure on the cortex. Basic results of this technique demonstrated that it is possible to distinguish different pO2 distribution patterns displayed in pO2 histograms for various types of brain tumors and edematous brain tissue. In patients with arteriovenous malformations (AVMs) of the brain, an increase of tissue pO2 in cortical areas adjacent to the AVM was the result of extirpation of the lesion. The effect of intravenously administered pentoxifylline was studied during extraintracranial bypass operations in patients with cerebrovascular disease. In 7 patients a consistent shift of the pO2 histograms to the right, i.e., to higher pO2 values, could be demonstrated. Mean pO2 values increased statistically significantly by 16 +/- 7 mmHg as early as ten minutes after infusion of pentoxifylline. The rapid improvement of tissue oxygenation of human brain cortex is thought to be the result of an improvement of microcirculation, for other parameters influencing tissue pO2 showed no significant alterations if any.

Mechanisms of regulation of cerebral microflow during bicuculline-induced seizures in anaesthetized cats.

Before, during, and after bicuculline-induced seizures, changes in microflow, local tissue PO2, and extracellular H+ and K+ activities were continuously recorded in the suprasylvian gyrus of the cat in parallel with electrical activity. Additionally, the patterns of microflow during seizures after blockade of the beta-adrenergic and cholinergic receptors and after phentolamine application were studied. With the onset of discharges, microflow increased at all sites. The maximum increase was observed when the electrical activity was the strongest. During the period of alternating silent and nonsilent phases, microflow oscillated in parallel with functional activity. When the discharges ceased, microflow decreased to a new steady-state level. Tissue hypoxia was not responsible for the increase in flow because local tissue PO2 increased after the onset of seizures. H+ activity increased after a short delay and also oscillated during the period of oscillating functional activity. After the end of discharges, H+ activity decreased. K+ activity increased immediately with the onset of discharges and mirrored the electrical activity in the further course. The pattern of microflow was not changed by blockade of alpha- and beta-adrenergic and cholinergic receptors. We conclude that besides the increase in systemic blood pressure, K+ and H+ activities could be the main factors responsible for the increase in flow during seizures.

Effect of isovolemic hemodilution on oxygen supply and electrocorticogram in cat brain during focal ischemia and in normal tissue.

The effect of isovolemic hemodilution on local tissue oxygen pressure (pO2) and on the power of the electrocorticogram (ECoG) was investigated in the brain of the cat under normal conditions and during focal ischemia. Ischemia, produced by clamping of the middle cerebral artery (MCA) by a transorbital approach, was performed in two series of cats for 2 h. In one group of animals, isovolemic hemodilution was achieved in the second hour of persisting clamping. Local pO2 was continuously recorded on the median ectosylvian gyrus by a multiwire surface electrode. After MCA clamping, local tissue pO2 markedly decreased and hypoxia occurred in the ischemic area. During isovolemic hemodilution until a hematocrit of 20%, local pO2 in the ischemic area did not decrease any further although arterial oxygen capacity was drastically reduced. The power of the ECoG did also not decrease any further in comparison to the situation of ischemia without hemodilution. In the normal brain isovolemic hemodilution until a hematocrit of 20% did not significantly change mean tissue pO2 and the power of the electrocorticogram. We conclude from these results that during isovolemic hemodilution the decreased arterial oxygen capacity is compensated by an increase in microflow in the normal and ischemic region of the brain.

Oxygen supply of the brain cortex (rat) during severe hypoglycemia.

Oxygen supply of the brain cortex together with changes in the electrocorticogram (ECoG) were investigated during and after insulin induced hypoglycemia in 13 anaesthetized rats. Local oxygen partial pressures (pO2) on the parietal cortex were continuously measured with a multiwire surface electrode of the Clark type. During early hypoglycemia with a mean arterial glucose concentration [G]a of 2.81 (SD +/- 0.40) mmol/l, the local tissue pO2 did not change significantly as compared to the pO2 values recorded during the control period with a normal [G]a of 4.51 (SD +/- 0.70) mmol/l. During severe hypoglycemia at a [G]a of 1.39 (SD +/- 0.2) mmol/l, pO2 began to increase continuously on all 104 measuring sites, independently of changes in arterial blood pressure and ECoG. During a period of 7-18 min of isoelectricity, tissue pO2 remained elevated so long as blood pressure did not decrease. After injection of a 25% glucose solution, pO2 gradually decreased to control values within 30-60 min in most experiments. We conclude from these results that oxygen supply is generally improved during severe hypoglycemia. We assume that the increase in tissue pO2 is mainly caused by an increase in microflow. Thus, the neuronal damage occurring after severe hypoglycemia, as reported in literature, cannot primarily be caused by an oxygen deficiency.

Effect of prostaglandins F2alpha and E1 on local tissue Po2 and microflow of the brain cortex (cat).

The effects of prostaglandin F2 alpha (PGF2 alpha) and E1 (PGE1) on local tissue Po2 and microflow in the cat's brain surface were studied. Local tissue Po2 was polarographically measured with a multiwire surface electrode, and microflow measured by local hydrogen clearance method. The PGs were investigated by intracarotid (i.c.) infusions, single i.c. and intravenous (i.v.) injections. The i.c. infusions were made with dose of 3, 10 and 30 microgram/kg/min of PGF2 alpha and 0.1, 0.4 and 1.0 microgram/kg/min of PGE1. The i.c. application of PGF2 alpha led to a decrease in local tissue Po2 and tissue microflow. With the use of comparatively low doses (3 and 10 microgram) the effect appeared to be more specific, since SAP did not change significantly. Systemic (i.v.) injections of PGF2 alpha caused a significant drop in arterial pressure and decrease in tissue Po2. Studies with PGE1 always demonstrated a decrease in local tissue Po2 and microflow associated with a significant decrease in the SAP. No evidence for a specific effect was found. Suggestions for possible mechanism of action for these PGs are made.

Simultaneous measurements of microflow and evoked potentials in the somatomotor cortex of the cat brain during specific sensory activation.

The behaviour of both microflow and evoked potentials was investigated in the right somatomotor cortex of the cat (anaesthetized with chloralose) during electrical stimulation of the contralateral left forepaw. Frequency, amplitude, and time of stimulation were varied. Using the local hydrogen clearance method the changes of microflow were continuously monitored in the same cortical area from which the evoked potentials were recorded. The experiments have shown that activation of the somatomotor cortex by somatic stimulation of the contralateral forepaw results in changes of microflow which clearly correlate to the side and amplitude of the primary evoked potentials. An increase in flow as well as in amplitude of the potentials depends on the stimulation parameters. The changes of microflow are limited to a small area of 1--2 mm in diameter. We conclude that a tight coupling of flow to functional activity exists in the microcirculatory range.

Time course of changes of extracellular H+ and K+ activities during and after direct electrical stimulation of the brain cortex.

The kinetics of H+ and K+ activities were recorded during and after direct electrical activation of the brain cortex (cat). H+ activity was measured with H+-sensitive glass microelectrodes (tip diameters of 1--4 micron) and K+ activity was registered with double-barrelled ion-sensitive microelectrodes (tip diameters of 1--3 micron). It could be shown that extracellular H+ activity initially decreased for a few seconds and increased only after the 7.s. Maximum acidosis was always noticed after stimulation ended. Alkalotic as well as acidotic changes were the higher the stronger the stimulation parameters were. K+ activity increased very rapidly after stimulation began, reached its maximum when stimulation ended and then decreased to its initial value with an undershoot. It is concluded that the functional hyperemia of microflow could be triggered by the rapid increase in K+ activity, whereas the initial alkalotic change of extracellular pH means that H+ activity does not play a role in the first phase of this kind of hyperemia. The alkalotic shift is interpreted to be caused by the washout of C02 due to the rapid increase in microflow. In the further course, H+ activity obviously contributes to the maintenance of functional hyperemia. In this later period K+ activity is always below the control value.

The effect of papaverine on local tissue PO2 and microflow in cat brain cortex.

The effect of intracarotid and intravenous administration of papaverine on local tissue PO2 and microflow in the cat's brain surface was studied. Local tissue PO2 was measured with a multiwire surface electrode polarographically, and microflow by local hydrogen clearance method. The intracarotid infusions were made for 1, 2 and 5 min with doses of 0.1, 0.2 and 0.5 mg/kg/min papaverine, and the intravenous ones for 5 min with doses of 0.2, 0.5 and 1 mg/kg/min. The continuous intracarotid infusions showed that papaverine in the doses used distinctly increased local tissue PO2 and microcirculation of the brain surface. With the doses applied, systemic arterial pressure (SAP) changed little. It slightly decreased only during the 5 min infusions containing 0.5 mg/kg/min. The duration of the effect increased with increases in the duration of the infusion and of the dose. The maximum duration was observed with 5 min infusions and lasted for 10--15 min after drug administration was discontinued. During the i.v. infusions, tissue PO2 and microflow rose less than with intracarotid ones. No redistribution of capillary flow was observed.

Direct determination of local oxygen consumption of the brain cortex in vivo.

A method is described to determine local oxygen consumption quantitatively in the brain cortex under in vivo conditions. Local oxygen consumption is calculated from the slope of local tissue PO2 decrease during a few seconds of total ischemia of the brain for each second after the stop of circulation. The decrease of tissue PO2 is recorded simultaneously at several measuring sites. To be independent of oxygen chemically bound to hemoglobin, tissue PO2 values are raised above 100 Torr. The calculation of local oxygen consumption for each second during the short period of ischemia showed that the O2 consumption remains constant only for a few seconds ranging from 5 to maximally 15 s at different locations. The O2 consumption decreases continuously although the tissue PO2 values are still above the full saturation of hemoglobin. The rate of local oxygen consumption varies considerably at different measuring sites of the superficial layers of the brain cortex (cat). The mean value amounts to 3 +/- 1.5 ml O2/100 g tissue and minute.