Effects of buffering in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were exposed to extreme hypercapnia (Paco_2-20 kPa) at Fio₂ 0.4 for 480 min, with (n = 6) or without (n = 6) continuous infusion of isotonic buffers (bicarbonate and trometamol). Arterial pH was higher in buffered animals than controls, 7.21 ±0.01 vs 7.01±0.01 (mean ± s.e.mean, P < 0.01). Serum osmolality and Paco₂ did not differ between groups throughout the experiment. The hemodynamic response to hypercapnia was attenuated in the buffered group, who had lower heart rate, 133 ± 6 vs 189±12 min^-1 (P < 0.01), mean arterial pressure (MAP) 109 ± 4 vs 124 ± 4 mmHg (14.5 ± 0.5 vs 16.5 ± 0.5 kPa) (P < 0.05), mean pulmonary arterial pressure 16±1 vs 23 ± 1 mmHg (2.1 ±0.1 vs 3.1 ±0.1 kPa) (P < 0.01), and pulmonary vascular resistance (PVR) 249 ± 21 vs 343 ± 20 dyn s-cm^-5 (2490±210 vs 3430±200 μN-s-cm^-5) (P < 0.01), compared with the control group. Subsequently, both groups were exposed to hypercapnic hypoxemia by stepwise increases in Fio₂ (0.15, 0.10, 0.05) at 30-min intervals, while Fico₂ was kept at 0.2. PVR increased in both groups (P < 0.05) but, except for heart rate, all hemodynamic differences between the groups disappeared during hypoxia. At Fio₂ 0.15, buffered animals had higher arterial oxygen saturation (73 ± 5%) than the controls (55 ± 5%), (P < 0.05). The control animals died after 1–29 min (mean 14 min) at Fio₂ 0.10, while all buffered animals survived Fio₂ 0.10 with stable MAP (122 ± 14 mmHg (16.3 ± 1.9 kPa). The buffered animals died after 4–22 min (mean 15 min) at Fio₂ 0.05. We conclude that buffering to a pH of 7.21 attenuates the observed hemodynamic response in extreme hypercapnia and improves survival in hypercapnic hypoxemia.     

The effect of tolbutamide on cerebral blood flow during hypoxia and hypercapnia in the anaesthetized rat

The increase in blood flow in the cerebral cortex of the anaesthetized rat during hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured using the hydrogen clearance method with acutely implanted platinum electrodes. Hypoxia (PaO₂ 35.3±2.4 Torr) and hypercapnia (PaCO₂ 68.1±5.1 Torr) increased basal CBF from 76.3±9.0 ml/100g/min to 168.1±20.1 ml/100g/min and 162.4±31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia. However, it attenuated the increase of CBF during hypoxia by 66 ±11% (P<0.01). This suggests that opening of tolbutamide-sensitive potassium channels may be involved in the process of hypoxic vasodilation in the rat cerebral cortex.     

Effects of sympathetic stimulation on cerebral and ocular blood flow Modification by hypertension,hypercapnia, acetazolamide,PGI2 and papaverine

The effect of unilateral, electrical stimulatio of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI₂ was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI₂. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12 % blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI₂-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.     

pH and smooth muscle

In this paper, the control of vascular smooth muscle intracellular pH (pH_i) and the mechanisms of importance for the vasodilation to acidosis are reviewed. The three transport pathways of importance for the control of pH_i are a sodium-coupled bicarbonate transport, a Na,H-exchanger and a Cl,HCO₃^?exchange. While the two latter pathways are present in all smooth muscle cells studied, the sodium-coupled bicarbonate transport may be present in two forms which are either coupled to chloride efflux or are independent of chloride. The chloride-independent pathway seems electroneutral, indicating a 1:1 stoichiometry. All three transporters can be activated by vasoactive hormones and the second messengers involved are under intense investigation. With respect to the mechanisms involved in the vasodilation to acidosis, there seems to be a nitric oxide-dependent pathway as well as a direct effect of acidosis on the smooth muscle cells. In some preparations, prostanoids may also be involved. The direct vasodilator effect of acidosis is probably mediated through reduction of extracellular pH and the acidosis is associated with a reduction of the intracellular calcium concentration, which could explain the reduction of smooth muscle tone.     

Respiratory response to CO2 by controlled alveolar hypercapnia

A method of assessing the respiratory response to a hypercapnic stimulus after an increase in alveolar pCO₂ in accordance with an assigned program is suggested. The results are independent of the metabolic level, resistance to respiration, and other factors. Unlike the widely used rebreathing method, this new method enables the ventilatory sensitivity to CO₂ to be compared at rest, during muscular work, when the resistance to respiration is changed, and so on. It can also be used for both clinical and experimental investigations.Respiratory Physiology Group, I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 1, pp. 6–7, January, 1980.     

The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO₂) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg·kg^-1i. v.) reduced CBF to 50% of control without a measurable effect on CMRO₂. During hypercapnia (Pa_CO2 70–80 mmHg) the increase in CBF was reduced by about 80% but CMRO₂ remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg·kg^-1 and maximal effects were obtained with 3–5 mg·kg^-1. Following i. v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1–2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO₂ tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.     

Human spumavirus replication in human cells

It was previously reported that the replication of the human syncytium-forming virus (HSFV), a spumavirus, occurred only in fibroblast-like cell lines (human fetal diploid lung #645 [HFDL]) but not in epithelial-like lines (recovered amnion) [RA]. Factors that may be involved in such a phenomenon were the subject of this investigation. While both permissive (HFDL) and nonpermissive (RA) cell lines supported the replication of several representative animal viruses and adsorbed HSFV equally well, immunofluorescent staining of HSFV antigens revealed markedly fewer fluorescing cells in nonpermissive cultures. Infectious center assays of infected nonpermissive cells indicated the formation of significantly fewer infectious centers. The rate of DNA synthesis was markedly greater in the permissive cell lines. In addition, in the permissive cell line, the amount of proviral DNA revealed by the Hirt procedure and isopycnic banding in CsCl was significantly increased and was infectious as determined by the calcium phosphate-DMSO transfection assay. These results indicate that resistance of HSFV infection in nonpermissive cell cultures is probably an intracellular event.     

小潮气量通气在急性呼吸窘迫综合征中的应用

应用小潮气量通气致容许性高碳酸血症方法对11例急性呼吸窘迫综合征（ARDS）进行临床观察。设定潮气量为6．4±1．1ml／kg,保持动脉血二氧化碳（PaCQ2）为5．97±1．41kPa,血氧分压8．54±3．19kPa。结果7例存活,未发现气压伤。说明小潮气量通气致一定程度高碳酸血症是临床上值得推荐使用的方法。     

慢性低O2高CO2大鼠血管内皮生长因子表达及参一胶囊的影响

目的 :探讨血管内皮生长因子 (VEGF)在低氧性肺动脉高压形成中的意义及参一胶囊对其影响。方法 :采用ELISA法、透射电镜、原位杂交技术等方法 ,观察正常对照组、低O2 高CO2 4周组、低O2 高CO2 4周 参一胶囊组大鼠肺动脉平均压 (mPAP)、右心室重量比 (RV LV S)、血清和肺组织的VEGF的含量、肺细小动脉的超微结构、肺组织VEGFmR NA表达的变化。结果 :低O2 高CO2 组大鼠的mPAP、RV LV S、血清和肺组织的VEGF的含量明显高于正常对照组 (P <0 .0 1)。低O2 高CO2 4周 参一胶囊组大鼠mPAP、RV LV S、血清VEGF显著低于低O2高CO2 组 (P <0 .0 1) ,肺组织的VEGF的含量也低于低O2 高CO2 组 (P <0 .0 5 )。低O2 高CO2 组大鼠肺细小动脉中膜平滑肌细胞明显增生、胶原纤维较正常对照组增多 ,低O2 高CO2 4周 参一胶囊组较低O2 高CO2 组则明显减轻。原位杂交显示低O2 高CO2 组大鼠肺细小动脉VEGFmRNA较正常对照组明显增加 (P <0 .0 1) ,而低O2 高CO2 4周 参一胶囊组与低O2 高CO2 组比较 ,则明显降低(P <0 .0 5 )。结论 :VEGF参与了慢性低氧性肺动脉高压的形成 ,参一胶囊可通过抑制VEGF的作用而有效地降低肺动脉高压