Elfriede Leniger-Follert

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 μm) and K+ activity was registered with double-barrelled ion-sensitive microelectrodes (tip diameters of 1–3 μm). 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 CO2 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.

Behavior of microflow and localP O 2 of the brain cortex during and after direct electrical stimulation

SummaryMicroflow was continuously recorded at four sites of the brain cortex (cat) during and after direct electrical stimulation of the brain. In some experiments local oxygen partial pressure (Po2) was additionally measured with a new combined element in the same capillary area where microflow was determined. This simultaneous measurement of both microflow and localPo2 in the tissue enabled us to analyze the kinetics of microflow and its dependence on localPo2 during activation. Microflow increased at all sites measured, in most cases within 1–2 s after the beginning of stimulation, reached the maximum of hyperemia after the end of stimulation and then gradually returned to the initial level within 30 s up to several minutes according to the intensity of the stimulation. The reaction pattern of microflow was uniform. As localPo2 normally did not decrease and did not even show an initial decrease after the onset of stimulation, the hyperemia could not be caused by local hypoxia. On the contrary, localPo2 always increased with the increase of microflow. ThisPo2 increase is necessary, because the tissue which consumes more oxygen needs higherPo2 gradients to transport the oxygen to the mitochondria.

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.

Regulation of local tissuePo 2of the brain cortex at different arterial O2 pressures

SummaryLocal tissue oxygen pressure (Po2)was recorded with a platinum multiwire surface electrode at adjacent sites of the cat cortex under steady-state conditions and with different arterial oxygen supply. SimultaneouslyPo2in the sinus sagittalis was continuously recorded through the vascular wall in some experiments. Under normoxic and steady-state conditions localPo2values varied between 0 Torr and almost arterial levels of 90 Torr. This was in accordance with the assumption of a diffusive transport of oxygen in tissue. With increased arterial oxygen supply local tissuePo2reacted quite differently at adjacent sites. Linear increases in local tissuePo2as compared to arterialPo2as well as constant levels, very small increases and even small decreases were recorded. Constancy or small changes, respectively, of localPo2(=localPo2regulation) may be caused by changes in microflow, but changes in oxygen consumption cannot be excluded completely. The regulation of localPo2could be abolished by adding CO2 to the gas mixture or by producing tissue anoxia. With severely reduced arterial oxygen supply local tissuePo2dropped down to hypoxic or anoxic levels at all sites measured.

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 β-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 α-and β-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.

Direct Determination of Local Oxygen Consumption of the Brain Cortex in vivo

SummaryA 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. Then 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.

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 pO 2 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 oygenation 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.

Oxygen Supply and Microcirculation of the Brain Cortex

The actual oxygen supply of the brain is, as in other organs, dependent on the arterial oxygen capacity, the rate of local blood flow, the diffusion conditions within the organ and the oxygen consumption of the tissue. All these parameters may change under different physiological or pathological conditions and thus influence the O2 supply of the brain. In the following minireview I will focus on the following points.

Local Tissue Po2 and Microflow of the Brain Cortex Under Varying Arterial Oxygen Pressure

In the last few years contradictory results of the influence of reduced arterial oxygen supply on the Po2 of the brain cortex have been reported by different authors. As this could be caused by methodological factors, we investigated this problem systematically in a broader range of arterial oxygen supply. We measured local tissue oxygen pressure (Po2) with a platinum multiwire surface electrode simultaneously on up to eight adjacent sites of the cortical surface, and with a platinum needle electrode in the deeper layers of the cortex.

Determination of local myoglobin concentration in the guinea pig heart

SummaryA method is described for calculating local myoglobin concentration in hemoglobin-free perfused guinea-pig heart by measuring the decrease of tissuePo2 during stop of perfusion. The myoglobin concentration in ca. 10 nanogram of tissue varies between 0.106 and 0.676 g-% of the wet weight. The mean value of 0.373 g-% (standard deviation of ±0.138) agrees very well with the values obtained with chemical methods by other authors. The great variation of our values is interpreted as an inhomogeneous distribution of the local myoglobin concentration.