Near-infrared spectrophotometry determined brain oxygenation during fainting

During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50° head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10° head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA v_mean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (ΔHbO₂) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (ΔCytO₂). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78–103) to 68 (57–79) mmHg; median and range), heart rate (96 (72–111) to 65 (50–107) beats min^?1), MCA v_mean (59 (51–82) to 41 (29–56) cm s^?1), ΔHbO₂ (by ?5.3 (?3.0 to ?14.8) μmol l^?1) and ΔCytO₂ were reduced (by ?0.2 (?0.1 to ?0.4) μmol l^?1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and ΔHbO₂ increased to 2.2 (?0.9–12.0) mmol L^?1 above the resting value and also ΔCytO₂ recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA v_mean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.     

Oxygen-dependent mechanisms in cerebral autoregulation

Autoregulatory adjustments in the caliber of cerebral arterioles were studied in anesthetized cats equipped with cranial windows for the direct observation of the pial microcirculation. Increased venous pressure caused slight, but consistent, arteriolar dilation, at normal and at reduced arterial blood pressure and irrespective of whether or not intracranial pressure was kept constant or allowed to increase. Arterial hypotension caused arteriolar dilation which was inhibited partially by perfusion of the space under the cranial window with artificial CSF equilibrated with high concentrations of oxygen. This vasodilation was inhibited to a greater extent by perfusion of the space under the cranial window with fluorocarbon FC-80, equilibrated with high concentrations of oxygen. CSF or fluorocarbon equilibrated with nitrogen did not influence the vasodilation in response to arterial hypotension. The response to increased venous pressure was converted to vasoconstriction when fluorocarbon equilibrated with high concentrations of oxygen was flowing under the cranial window. The vasodilation in response to arterial hypotension was inhibited by topical application of adenosine deaminase. The results show that both metabolic and myogenic mechanisms play a role in cerebral arteriolar autoregulation. Under normal conditions, the metabolic mechanisms predominate. The presence of the myogenic mechanisms may be unmasked by preventing the operation of the metabolic mechanisms. The major metabolic mechanism seems to be dependent on changes in PO₂ within the brain with secondary release of adenosine.     

Hyperglycemic and Hyperosmolar Responses to Graded Hemorrhage

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levels and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8, 20, and 25 mOsm/kg H₂O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. — Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.     

Effect of Transmural Pressure on Constrictor Reactions of Caudal Artery in Hypotensive and Hypertensive Rats

Clipping of the abdominal aorta distally to the renal arteries produces a persistent decrease in blood pressure in hindquarter vessels by 35-40%. On week 6-7 postoperation, the reactions of the caudal artery perfused in vitro under constant pressure to norepinephrine were studied. At transmural pressure of 150 mm Hg, the vascular responses in hypotensive rats were reduced compared to those in normotensive control. By contrast, the responses of hypertensive vessels were more pronounced at 75 mm Hg even after deendothelization.     

Venodilator effects of adenosine triphosphate and sodium nitroprusside; Comparisons during controlled hypotension

Adenosine triphosphate as well as sodium nitroprusside has been used for hypotensive anesthesia. The purpose of this study was to examine the possibility that two hypotensive drugs may exert different effects on venous capacitance during controlled hypotension. In rats anesthetized with ketamine, mean arterial pressure was lowered to 50mmHg by intravenous infusion of adenosine triphosphate or sodium nitroprusside. Venous capacitance was assessed before and during induced hypotension by measuring the mean circulatory filling pressure (MCFP). MCFP was measured after briefly arresting the circulation by inflating an indwelling balloon in the right atrium. MCFP was lower during adenosine triphosphate-induced as well as sodium nitroprusside-induced hypotension as compared with the respective value at control (P < 0.01 for adenosine triphosphate and sodium nitroprusside). However, the decrease in MCFP by adenosine triphosphate (0.8 ± 0.1mmHg) was less (P < 0.01) than that by sodium nitroprusside (2.3 ± 0.3mmHg). These results suggest that at a comparable level of arterial hypotension venodilator effect of adenosine triphosphate was less than that of sodium nitroprusside. Less venodilatation during adenosine triphosphate-induced hypotension may contribute to the maintenance of cardiac output during hypotensive anesthesia.(Hoka S, Takeshita A, Aishima K et al.: Venodilator effects of adenosine triphosphate and sodium nitroprusside; comparisons during controlled hypotension. J Anesth 1: 144–147, 1987)     

前部增生性玻璃体视网膜病变引起慢性低眼压房水生成率的测定

目的：探讨前部增生性玻璃体视网膜病变（anterior prolieferative vitreoretinopathy,aPVR)低眼压状态下房水生成率变化,从房水动力学的角度揭示aPVR引起慢性低眼压的发病机制。方法：利用培养的同种兔皮肤成纤维细胞制作aPVR引起慢性低眼的动物模型。于术前及术后不同时间点分别观测眼压、术后14d,28d,56d分别以高效液相色谱仪测量房水荧光素清除率,进一步计算房水生成率。结果：术后2周、4周、8周实验组平均眼压、房水生成率明显低于对照组（P＜0．05或P＜0．01）。结论：在aPVR病理状态下,低眼压的形成与房水生成率下降有关。     

颅脑手术中应用硝酸甘油或复合艾司洛尔调控血压效果的比较

目的：比较艾司洛尔复合硝酸甘油（NTG）降压与单纯硝酸甘油降压效果。方法：36例ASA Ⅰ-Ⅱ级颅外择期手术病人分为两组：艾司洛尔复合NTG组18例,单纯NTG组18例,观察并比较两组控制性降压时血气,血液动力学的变化。结果：艾司洛尔能明显加快NTG起效速率,NTG用量减少55．7％,并能抑制单纯NTG控制性降压时反射性心率增快;停止降压后血压平衡上升,RPP值下降;PaO2,BE仅轻度下降,与单纯NTG组比较有显著差异。结论：艾司洛尔复合NTG控制性降压有明显的协同作用。无反跳现象,对动脉血气影响小。     

尼卡地平和硝普钠用于颅内血管术中控制性降压的比较观察

目的：探寻颅脑术中控制性降压的理想药物。方法：选用20例22－52岁颅内动脉瘤及动静脉畸形手术病人,随机分为尼卡地平（N）组和硝普钠（S）组。观察两组降压前和降压10、20、30min及停药10、20min时的平均动脉压（MAP）,心率（HR）,颅内压（ICP）,中心静脉压（CVP）的变化,同步监测动脉及颅内静脉血气值,计算动脉氧含量（CaO2)与颈内静脉氧含量（CjO2)的差,即动静脉氧含量差值（AJDO2）和收缩压与心率乘积（RPP）。结果：两组降压均有效,与降压前比较,MAP明显下降。在控制性降压及复压过程中,N组血压变化平稳,HR、ICP和JADO2无显著变化,RPP明显下降（P＜0．01）。S组有一过性心动过速（P＜0．05）,ICP和AJDO2明显升高（P＜0．01或P＜0．05）,停药后,血压反跳（P＜0．01或P＜0．05）。结论：尼卡地平用于颅脑术中控制性降压安全有效,其临床价值优于硝普钠。     

Effects of FR173657, a non-peptide B2 antagonist,on kinin-induced hypotension,visceral and peripheral oedema formation and bronchoconstriction

1. Kinins are believed to play a key role in many inflammatory conditions. Therefore, bradykinin antagonists are being developed for potential therapeutic applications. In the present investigation we describe the pharmacology, in vivo, of (E)-3-(6- acetamido- 3-pyridyl)- N-[N- [2,4- dichloro- 3-[(2- methyl-8- quinolinyl)oxymethyl]phenyl]- N-methylaminocarbonylmethyl]acrylamide ({"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657), a novel, non-peptide bradykinin antagonist.
2. The hypotensive effects of i.v. injections of bradykinin (50 pmol) in captopril-pre-treated anaesthetized rats were significantly inhibited by 100 nmol kg⁻¹ {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 s.c., and completely abolished by 300 nmol kg⁻¹. The full inhibitory effect developed within 60 min and remained unchanged for at least 4 h. However, the effect was reversible, since 24 h after an injection of 300 nmol kg⁻¹ {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 no inhibitory effect could be observed.
3. The plasma protein extravasation into the pancreas and duodenum induced by an i.v. infusion of bradykinin (11 nmol kg⁻¹ within 20 min) in captopril-treated anaesthetized rats was completely abolished by {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 at doses of 30 nmol kg⁻¹ s.c. and above, given 60 min before bradykinin. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 3 nmol kg⁻¹ was ineffective, while a dose of 10 nmol kg⁻¹ produced an intermediate effect.
4. The paw oedema induced by the subplantar injection of bradykinin (30 nmol) in anaesthetized rats was inhibited slightly by s.c. injection of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 0.3 μmol kg⁻¹, whereas 1 and 3 μmol kg⁻¹ produced significant inhibition of the bradykinin-induced oedema. The maximum inhibition amounted to about 50% and could not be increased even when the dose of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 was increased to 30 μmol kg⁻¹. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 did not effect the oedema caused by histamine or 5-hydroxytryptamine.
5. Bradykinin (20 nmol kg⁻¹, i.v.) caused increases in pulmonary inflation pressure by 300–600 Pa in anaesthetized, respirated guinea-pigs. The effect was reduced to 58±9% of the initial value 60 min after the s.c. injection of {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 1 μmol kg⁻¹, whereas only 9±7% remained after 10 μmol kg⁻¹. The bronchoconstrictor actions of histamine remained unaffected by {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657.
6. In summary, {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657 is a highly potent and selective bradykinin antagonist. The inhibitory action in vivo lasts for longer than 4 h but is fully reversible. {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657, or similar compounds, will be a useful tool for the pharmacological investigation of pathophysiological states and may possess a therapeutic potential in diseases involving the endogenous release of kinins.