The effects of maternal hypercapnia on foetal oxygenation and uterine blood flow in the pig.

1. The purpose of this investigation was to determine the effects of maternal hyperoxaemia and hypercapnia on the uterine vascular bed and foetal oxygenation in the large white sow at 80-90 days gestation. 2. When maternal hyperoxaemia was induced with 100% oxygen, there was a highly significant rise in the maternal arterial oxygen tension, but no other significant blood gas or vascular changes were observed. 3. When mild maternal hypercapnia was superimposed on maternal hyperoxaemia (oxygen plus 6% carbon dioxide), the oxygen tension and saturation of both the maternal uterine venous and foetal umbilical venous bloods were found when severe hypercapnia was induced (oxygen plus 50% carbon dioxide) but in this case all blood samples showed dramatic changes in PCO2 and pH. These changes were accompanied by an increase in the systemic blood pressure and uterine blood flow, and a decrease in uterine vascular resistance. 4. When mild hypercapnia was induced without hyperoxaemia (air plus 5% carbon dioxide) significant increases were recorded in the oxygen tension and saturation of uterine venous and foetal umbilical venous bloods. Systemic and uterine vascular resistance fell. 5. It was concluded that the increased foetal oxygen tension during maternal hypercapnia was the result of the increased uterine blood flow and greater mass delivery of oxygen to the placenta, so that once the oxygen requirements of the placental tissues themselves were exceeded there would be an increased oxygen gradient at the site of gas exchange. 6. Carbon dioxide concentration in arterial blood plays an important role in determining blood flow through the pregnant uterus in the sow.     

Effects of hypotension induced by adenosine on brain surface oxygen pressure and cortical cerebral blood flow in the pig

Six pigs were anaesthetized with ketamine in combination with fentanyl and droperidol and paralysed with pancuronium. The pigs were tracheotomized and ventilated mechanically. Mean arterial blood pressure, MABP, was lowered from 97 +/- 21 mmHg stepwise to 58 +/- 2, 33 +/- 4 and 22 +/- 4 mmHg by intravenous infusion of adenosine (4-8 mg kg-1 min-1). Regional cerebral blood flow (rCBF) was measured directly onto the cortex of the brain by local atraumatic application of 133xenon. Brain surface oxygen pressure (PtO2) was obtained using a multiwire oxygen surface electrode. At the level of 60 mmHg, rCBF showed a significant increase, while flow values were not changed from initial values with further hypotension. Ten minutes after adenosine was discontinued, rCBF showed a rebound effect with higher values than initially. During normotension mean cortical PtO2 varied between 2.1 KPa and 3.9 kPa. During adenosine infusion PtO2 was increased at MABP-levels of 60 and 30 mmHg, while at 20 mmHg a decrease was seen in all animals. After discontinuation of the adenosine infusion, PtO2 values were higher than those measured at the initial normotension, a similar rebound phenomenon as seen with rCBF. During the experiments all hypotensive levels could be maintained at constant level without progressively increasing infusion rates, indicating no tachyphylaxis during these time periods. After discontinuation of the drug, blood pressure did not fully reach pre-hypotensive level within 10 min. Thus, hypotension induced by adenosine down to a MABP of 30 mmHg in animal experiments does not cause deterioration in either cerebral blood flow or oxygen pressure.     

Effects of histamine on brain capillaries

Summary The effect of histamine administered via the common carotid artery on the transport processes of brain capillaries was investigated in rats. The fine structure of endothelial cells and the glial end-feet system was studied by electron microscopy and the serum albumin was visualized for light microscopy by the peroxidase-antiperoxidase (PAP) immunohistochemical reaction. Sixty microgram per milliliter histamine enhanced the penetration of serum albumin into the capillaries while the number of pinocytotic and coated vesicles significantly increased in the capillary endothelium. Oedematous swelling of the glial end-feet system was also observed. The stimulatory effect of histamine on the transcapillary transport could not be inhibited by a histamine H_1– receptor antagonist, mepyramine. By contrast, metiamide, a histamine H_2–-receptor antagonist prevented both ultrastructural changes and albumin penetration in the brain capillaries to occur.     

Effects of neuropeptides and capsaicin on tracheobronchial blood flow of the pig

Blood flow changes upon systemic i.v. injections in the pig of various neuropeptides, capsaicin, bradykinin and histamine were directly monitored by a Transonic blood flowmeter in the superior laryngeal, bronchial and femoral arteries and indirectly in the larynx and skin using laser Doppler flowmetry. To minimize influence of compensatory reflexes and indirect effects, the pigs were pre-treated with atropine, guanethidine, chlorisondamine and capsaicin. Substance P (SP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), calcitonin gene-related peptide (CGRP), capsaicin, bradykinin and histamine all decreased vascular resistance, suggesting vasodilation in the superior laryngeal and bronchial arteries. All peptides and histamine when given i.v. exerted vasodilatory effects independent of autonomic motor nerves and capsaicin-sensitive afferents. SP was the most potent vasodilator agent tested in both tracheal and bronchial circulation, being about 1000-fold more active than histamine. VIP was about 10-fold more potent than PHI in decreasing vascular resistance and had a preferential action on the SLA compared to CGRP. In the femoral artery capsaicin and also SP in the highest dose increased vascular resistance. Capsaicin increased the laser Doppler signal in both laryngeal mucosa and skin, while i.v. peptides caused variable effects. In conclusion, SP and CGRP mimicked capsaicin-induced vasodilation in the tracheobronchial circulation while VIP had a preferential effect on the tracheal circulation.     

Concerning the influence of the brain cortex on capillaries

Summary Experimental data are presented on the presence of unconditioned and conditioned capillary reflexes to various stimulants, pertaining to the first and second signal system. It has been established that if the left wrist is stimulated, there is reflex constriction of capillaries of the right wrist. It appeared possible to claborate a conditioned reflex of capillaries to pain stimulation with differentiation. Verbal stimulation, such as: I'm pricking, evoked more pronounced reaction of capillaries than unconditioned or conditioned stimuli.Presented by Academician K. M. Bykov     

Segment stroke work and metabolism depend on coronary blood flow in the pig

We determined the mechanical and metabolic effects of graded myocardial ischemia in 23 open-chest, anesthetized pigs. By connecting the midportion of the left anterior descending artery (LAD) to the carotid artery via a constant volume, calibrated pump, we reduced the flow in the LAD to 0, 25, 50, and 75% of control rates for periods of 1 h. Flows of 100% and 150% were also examined. Using pairs of ultrasonic crystals to measure segment dimensions, we calculated segment shortening and thickening, and total and systolic stroke work in the ischemic and normally perfused segments. Blood gases, pH, and lactate and inosine balances were determined from the regional coronary venous blood. At coronary blood flows of 0, 25, 50, and 75% of normal resting flow, total segment work was 8 +/- 8, 25 +/- 4, 51 +/- 5, and 80 +/- 6% of control, respectively, while systolic segment work was -2 +/- 5, -10 +/- 5, 40 +/- 5, and 86 +/- 7% of control, respectively (means +/- SE). Thus, the decrease in total segment stroke work is proportional to the decrease in flow over the range 0-100%. However, no useful work (i.e., systolic work) is done until flow exceeds 25%. Segment shortening and thickening are significantly depressed with flows diminished by only 25%. Segmental inosine production correlates with lactate production and parallels decreased mechanical performance.     

Thermal control of blood flow through capillaries and arteriovenous anastomoses in skin of sheep

Using radioactive microsphere and electromagnetic techniques, hindleg vascular responses were studied in 38 conscious, chronically prepared sheep subjected to either exposure to a warm environment, and/or local warming of the hypothalamus, spinal cord, forelegs or hindlegs. The total proportion of cardiac output passing through AVA's was increased by all treatments. AVA flow in hindleg skin was increased but capillary flow was unchanged by warming the hypothalamus, spinal cord or forelegs. AVA flow was unchanged but capillary flow was increased by warming the ambient air or the hindlegs alone. Equivalent cooling treatments resulted in AVA and capillary flow changes converse to warming.It is concluded that, in sheep, blood flow through cutaneous AVA's is controlled by specific thermoregulatory reflexes, whereas capillary flow is the target of local temperature effects. A significant role for the direction of the thermal gradient across the skin is implicated.     

Method to create small photo-bleached volumes to monitor blood plasma flow in capillaries

A method has been developed to examine the movement of plasma in capillaries using intravital microscopy. Spatial transients in fluorescence properties are instantaneously induced by laser photo-blaech pulses after which the convective recovery can be monitored. The plasma is tagged with fluorescent dyes coupled to bovine serum albumin, which is injected well before the measurements and circulates with the blood stream. A laser bean from an argon laser source, set to emit light with a wavelength of 488 nm, is focused on the illumination field diaphragm and creates a spot in the object plane of the microscope. At low laser power, the laser spot is aimed at a blood plasma gap between red blood cells in a capillary segment, using a steerable mirror. Light sensors, coupled to photomultipliers in the secondary image plane of the microscope, record the light intensity of the moving plasma/dye while the preparation is continuously illuminated with a xenon epi-illuminating set-up. The laser photo-bleach spot is then used to bleach the dye complex within a 5·4 μm segment of thecapillary for less than 20 ms. The movement of the bleached plasma bolus is tracked by the photo-sensors, placed sequentially along the capillary. Both dye and red blood cell passage can be detected in the photo-multiplier signals, and the relative velocities of the two blood components can be measured. Measurements reveal that the ratio of transit times between blood plasma and red blood cells is 1·23 (SD=0.22, N=18), which is in good agreement with measurements by other techniques.     

Release and vasoconstrictor effects of neuropeptide Y in relation to non-adrenergic sympathetic control of renal blood flow in the pig

The possible involvement of neuropeptide Y (NPY) in sympathetic control of renal blood flow was investigated in the pig in vivo. Exogenous NPY caused renal vasoconstriction with a threshold effect at an arterial plasma concentration of 164 pmol 6(-1). Stimulation of the renal nerves (0.59, 2 and 10 Hz) in control animals evoked rapid and frequency-dependent reduction in renal blood flow and overflow of NPY-like immunoreactivity (NPY-LI) and noradrenaline (NA) from the kidney, suggesting co-release from sympathetic nerves. Following the administration of the alpha- and beta-adrenoceptor antagonists phenoxybenzamine and propranolol, the vasoconstrictor response to exogenous NA was reduced by 98%, whereas that of NPY was unaltered. The response to nerve stimulation with 0.59 Hz was abolished, whereas relatively slowly developing reductions in renal blood flow by 7 and 28% were obtained upon stimulation with 2 and 10 Hz respectively. The nerve stimulation-evoked overflow of NA at 0.59 and 2 Hz, but not at 10 Hz and not that of NPY-LI, was enhanced after adrenoceptor blockade. Twenty-four hours after reserpine treatment (1 mg kg-1 i.v.) the contents of NPY-LI and NA in the renal cortex were reduced by 80 and 98% respectively. Sectioning of the renal nerves largely prevented the reserpine-induced depletion of NPY-LI, but not that of NA. Nerve stimulation of the denervated kidney with 2 and 10 Hz 24 h after reserpine treatment evoked slowly developing and long-lasting reductions in renal blood flow by 6 and 52% respectively. These responses were associated with overflow of NPY-LI, which was similar to and threefold higher than that observed in controls at 2 and 10 Hz respectively, while no detectable overflow of NA occurred. Repeated stimulation with 10 Hz resulted in a progressive fatigue of the vasoconstrictor response and the associated overflow of NPY-LI, giving a high correlation (r = 0.86, P less than 0.001) between the two parameters. It is concluded that NPY is a potent constrictor of the renal vascular bed. Furthermore, although NA is the likely transmitter mediating most of the responses to low to moderate nerve activation under control conditions, the data suggest that NPY may mediate the non-adrenergic reductions in renal blood flow evoked by high-frequency sympathetic nerve stimulation after reserpine treatment.     

Cerebral blood flow in rabbits during hypoperfusion of the brain

Summary Brains of rabbits were perfused by arterial blood via the internal carotids after ligation of vertebral and external carotid arteries. The effect of the reduction of cerebral perfusion volume on cerebral blood flow was studied by recording the clearance of Krypton-85 from the brains.The clearance curves obtained by recording the gamma radiation of the Krypton-85 represented the sum of tissue clearances from the whole brain (about 10 g) and about 45 g of extracerebral tissue and so were not representative of cerebral or cortical blood flow.Using external beta-counting the cortical blood flows calculated from the tissue-clearance curves reached mean values of 87 and 159 ml/100 g/min in perfusions with 12 and 18 ml/min respectively. But during reduced cerebral perfusion (2 ml/min) the clearance curves gave cortical blood flow values of 56 ml/100 g/min on the average and so exceeded the values calculated from the perfusion volume (2 ml/min) and the brain-weight (10 g) two to three times. It is concluded that regions of nonperfusion exceeding 50% of the cerebral tissue coexisted with adequately perfused areas.In hypoperfusion the cortical metabolic state was sufficiently correlated with the perfusion volume, but no correlation existed with the cortical blood flow calculated from the clearance curves.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Effect of low-intensity laser radiation on capillaries in the rat brain

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny Vol. 115, N ^o 2, pp. 219–221, February, 1993     

Impact of acute hypobaric hypoxia on blood flow distribution in brain

Aim: Acute hypobaric hypoxia is well known to alter brain circulation and to cause neuropsychological impairment. However, very few studies have examined the regional changes occurring in the brain during acute exposure to extreme hypoxic conditions. Methods: Regional cerebral blood flow (rCBF) response to hypoxia was investigated in six healthy subjects exposed to either normobaric normoxia or hypobaric hypoxia with ambient pressure/inspired oxygen pressure of 101/21 kPa and 50/11 kPa respectively. After 40 min at the desired pressure they were injected ^99mTc‐HMPAO and subsequently underwent single photon emission computed tomography. Regional cerebral blood flow distribution changes in the whole brain were assessed by Statistical Parametric Mapping, a well established voxel‐based analysis method. Results: Hypobaric hypoxia increased rCBF distribution in sensorymotor and prefrontal cortices and in central structures. PCO₂ correlated positively and SatO₂ negatively with rCBF in several temporal, parahippocampal, parietal and central structures. Conclusions: These findings underscore the specific sensitivity of the frontal lobe to acute hypobaric hypoxia and of limbic and central structures to blood gas changes emphasizing the involvement of these brain areas in acute hypoxia.     

Reaction of the brain capillaries to hypoxia in cats

Using calcium-adenosinetriphosphate histoangiological method of Chilingarian, the morpho-functional characteristics of capillary section of microcirculatory bed were studied in cat's brain and dura mater following experimental hypoxia. Analysis of morphometric data has shown that short-term hypoxia resulted in dilation of brain capillary lumen by 15% in comparison with that in intact animals. Average diameter of dura mater capillaries was found to vary within the limits of control values. Dilation of brain capillaries should be considered as a compensatory-adaptational change aimed at maintenance of metabolic regulation of cerebral circulation.     

Extracellular potassium and blood flow in the post-ischemic rat brain

The concentration of extracellular potassium, [K⁺]_e, was measured in parietal cortex and basal ganglia of rats during and after ten minutes of complete cerebral ischemia. The post-ischemic normalization of [K⁺]_e was considerably delayed in parietal cortex compared to basal ganglia, but in both regions, [K⁺]_e reached its normal concentration within 4 min of the end of the ischemia. Also, in both regions blood flow was elevated at the time of maximal [K⁺]₃ decrease. Our findings suggest that the normalization of [K⁺]_e and cerebrovascular resistance after ischemia are related by positive feed-back, possibly via the stimulation of Na⁺–K⁺-ATPase.Presented in part at the meeting of the Scandinavian Physiological Society, Odense, Denmark, November 1978 (Hansen et al. 1979), and at the Symposium on Cerebral Metabolism and Neural Function, US National Institute of Neurological and Communative Disorders and Stroke, Bethesda, Maryland, May 1979 (Gjedde et al. 1980a)