Cerebrocortical oxygen supply of sclerotic rats and acute diltiazem therapy.

The therapeutic effects of calcium antagonist diltiazem on cerebrovascular smooth muscle of sclerotic and normal rats has been investigated. Arteriosclerosis was caused by treatment of the rats with a water soluble 1,25-dihydro-cholecalciferol in a dose of 97,000 IU. After 2-4 days, serum urea of the treated animals was increased from 56 +/- 8 to 78 +/- 17 mg/dl. Histological examinations of tissue probes from kidneys, heart, aorta and the major arteries by means of the staining method according to von Kossa clearly showed the picture of the Mönckeberg-type atherosclerosis. The calcified rats (N = 23) and the control group (N = 25) were anesthetized with ketamine/xylazine. Following craniotomy and tracheotomy for artificial ventilation, surface PO2 of the cerebro-cortex and cerebral blood flow via the inhalatory hydrogen clearance technique were measured. Surface PO2 frequency distribution of vitamin D3 treated animals showed a left shift (mean +/- SD = 29 +/- 8 compared with 34 +/- 6 mm Hg for controls) and a CBF decrease (1.36 +/- 0.51 compared to 1.50 +/- 0.60 ml/g.min for the controls). Diltiazem infusion of 2 ml/h corresponding to 5 micrograms/kg bw after 5 minutes caused a slight CBF decrease (1.50 +/- 0.60 to 1.43 +/- 0.78 ml/g.min) in controls and an insignificant CBF reduction in sclerotic rats. Mean arterial blood pressure was lowered by diltiazem infusion. The hypertensive sclerotic rats became almost normal (148 +/- 18 to 91 +/- 15 mm Hg) while the control animals decreased in MAP from 118 to 80 +/- 15 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hypovolemic hypotension on the cerebral oxygen supply of rats with slightly raised or lowered body temperatures.

Combination effects of hypovolemia and body cooling or warming being important for laboratory animals, accident victims, hemorrhagic patients, etc. have been investigated in the anesthetized rat brain. Combined hypovolemic hypotension (MAP +/- SD = 36 +/- 7 mm Hg) and additional cooling (32 degrees) intensified the drop of cerebral cortex PO2 (rPO2) (initial rPO2 +/- SD = 28 +/- 16 mm Hg, hypovolemic rPO2 = 16 +/- 12 mm Hg, N = 15) while slight body warming (39 degrees) improved the cerebral hypoxia (initial rPO2 +/- SD = 41 +/- 20 mm Hg, hypovolemic rPO2 = 32 +/- 21 mm Hg, N = 11) despite arterial saturation of the oxyhemoglobin was normal (N = 11).

The hypoxic response to hypovolemia.

The response of tissue-PO2 to hypovolemic hypotension was determined in the rat brain cortex and liver surface using needle and surface PO2 electrodes. At hypotensive MAP values of 35-40 mm Hg the cerebral cortex is preferentially supplied with blood through sympathico-adrenergic vasoconstriction of the peripheral circulation. This centralization of the blood volume is not sufficient to prevent a significant fall in cerebral PO2 from 34 +/- 18 mm Hg to 24 +/- 16 mm Hg however (n = 27 animals). The decrease in tissue PO2 during hypovolemia is dependent on body temperature and is more pronounced at lower temperatures (32-34 degrees C) than slightly raised temperatures (37.5-39 degrees C). The same degree of hypovolemia gave rise to large anoxic regions on the liver surface which showed signs of irreversible damage after 90 minutes. This was particularly obvious from the values measured after retransfusion of the missing blood with only a mean PO2 of 18 +/- 12 mm Hg compared with 28 +/- 7 mm Hg (n = 29) at the start of the experiment.

Staining PO2 measurement sites in the rat brain cortex and quantitative morphometry of the surrounding capillaries.

The exact positions of microelectrodes used to measure the PO2 in the cerebral cortex of the rat were determined by staining the tissue with Alcian Blue. The measurement sites were subsequently located under a light microscope and correlated with the capillary and cellular arrangement of the cortex. The microelectrodes used for the PO2 measurements were made of gold glass fibers; the Alcian Blue was injected hydrostatically through a micropipette attached to the PO2 microelectrode. The sites where dye had been deposited were seen under a light microscope as green blue spots about 100 micrometers in diameter. The capillaries were visualized by silver nitrate perfusion. Differences between the local PO2 values in the neo- and the archeocortex were found. In the neocortex the mean PO2 was 31 mm Hg, capillary volume 1.6%, capillary surface area 980/mm2, capillary length 13.5/mm; whereas in the archeocortex these values where 21 mm Hg, 0.9%, 820/mm2 and 9.4/mm respectively. These data indicate a relationship between the microcirculatory transport system and the local oxygen tension and provide further evidence that the mean PO2 level tends to decrease when moving from the surface into the archeocortex.