T. Madsen

Natural Killer Cell Activity and Lymphocyte Function During and After Coronary Artery Bypass Grafting in Relation to the Endocrine Stress Response

The effects of elective coronary artery bypass grafting (CABG) and the associated endocrine stress response on natural killer (NK) cell activity in peripheral blood, the distribution of lymphocyte sub-populations, and the phytohemagglutinin (PHA)-induced lymphocyte transformation were studied in 20 patients anesthetized with cither etomidate-high dose fentanyl (75–125 μg · kg-1) or midazo-lam-low dose fentanyl (<20 μ · kg-1). The endocrine response to surgery was measured as changes in scrum cortisol, plasma epinephrine, and norepinephrine. Compared with control values, a significant increase of NK cell activity was found in both groups prior to induction of anesthesia, followed by a decrease after induction until initiation of cardiopulmonary bypass (CPB) and a gradual increase to levels exceeding controls during CPB. Postoperatively, NK cell activity and the lymphocyte transformation to PHA stimulation were significantly depressed for at least 1–3 days. These changes were accompanied by severe lymphopenia affecting the T-lymphocytes (T3, T4, and T8) and the NK cells (Leu 11). Apart from a delayed cortisol increase in the etomidate group, the endocrine response showed a similar pattern in the two groups. Compared with control values, a significant decrease in the serum cortisol until CPB could be demonstrated, followed by a significant increase persisting for at least 6 days postoperatively. The plasma catecholamines showed a steep rise and, consequently, a significant increase during CPB, followed by a gradual return to control values in the postoperative period. The results indicate that, in patients undergoing CABG, immune surveillance is impaired prior to CPB and during the early postoperative period. The mechanisms underlying the fluctuations in NK cell activity and lymphocyte function arc complex, but the results suggest that the endocrine stress response may be of major importance.

12-Hour Simultaneous Registration of Acid Reflux and Peristaltic Activity in the Oesophagus

Twelve-hour simultaneous registration of acid gastro-oesophageal reflux and peristaltic activity in the oesophagus was carried out on 30 healthy subjects. The intensity of the acid gastro-oesophageal reflux was determined by automatic integration of the pH variation. Acid gastro-oesophageal reflux to pH less than or equal to 4 occurs in normal subjects within a range of 0--2.4% of the total registration period. The intravariation was measured in 10 investigations on 1 subject, and lay within the intervariation. To maintain the pressure-measuring system intact, 3 ml H2O/h were fed to the proximal and distal pressure catheters, respectively; it has been shown that this small quantity of water has no influence on the pH variation. Peristaltic activity for the entire measuring period was recorded and related to the individual reflex episodes. The total activity was found to be dependent on the level of consciousness, with little activity occurring during sleep. A positive correlation was found between the lowest pH during a reflux episode and the peristaltic activity in the oesophagus (p less than 0.001), between the lowest pH during a reflux episode and the duration of the reflux episode (p less than 0.001), and between the peristaltic activity and the duration of the reflux episode (p less than 0.001). During long-term registration of oesophageal pH it appears that pH less than or equal to 4 is a usable parameter for distinguishing between pathological and non-pathological acid gastro-oesophageal reflux. Sudden falls in pH to below 4 release increased peristalsis in the oesophagus.

The Effect of HCl Infusion in the Lower Part of the Oesophagus on the Pharyngo-oesophageal Sphincter Pressure in Normal Subjects

A measuring unit combined with a perfused catheter has been developed for measurement of the pharyngo-oesophageal sphincter pressure. The system is able to register pressure measurements using either intermittent or continuous withdrawal of the catheter, at the same flow rate (0.5 ml/min). Repeated measurements of pharyngo-oesophageal sphincter pressure have been made on eight healthy volunteers. No differences were found in the sphincter pressures measured by the continuous and the intermittent withdrawal techniques (p greater than 0.10); the coefficient of variation was 0.18 for both techniques. The pharyngo-oesophageal sphincter pressure was measured during infusion of 0.1 N HCl (5 ml/min) 5 cm proximally to the gastro-oesophageal sphincter. There was an increase in the pharyngo-oesophageal sphincter pressure after 1 min of infusion (p less than 0.05). Measurements after 5 min and 10 min were no different from the initial value; thus a fall was observed between the first and the fifth minute (p less than 0.05). The observed rise in sphincter pressure may be explained as a response acting to prevent gastro-oesophageal reflux from entering the pharynx.

NEUTROPHIL LYSOSOMAL ENZYME RELEASE AND COMPLEMENT ACTIVATION DURING CARDIOPULMONARY BYPASS

Complement activation and neutrophil degranulation were concomitantly studied during uncomplicated cardiopulmonary bypass (CPB). Plasma concentrations of complement factor C4, complement split product C3d, the neutrophil lysosomal enzyme elastase complexed with alpha 1-proteinase inhibitor (PI) and fibronectin were measured in 12 patients, C3d and elastase/PI increased significantly during CPB (volume-corrected results). The C3d rise was almost linear, whereas elastase/PI showed exponential increase. Mean elastase/PI and mean C3d concentrations at different times during CPB covaried closely. The study showed that during CPB neutrophil lysosomal enzyme release is intimately related to complement activation, although activation of the two systems may be caused by a common third activator within the extracorporeal circuit.

Effect of Cisapride on the Gastro-Oesophageal Function in Normal Human Subjects

The aim of this study was to investigate oesophageal peristalsis and gastro-oesophageal function in normal subjects after 4 days of cisapride 10 mg p.o. 3 times/day and 10 mg 1.5 h before the investigation. The study was carried out in a double-blind cross-over design with coded cisapride or placebo tablets. Basal sphincter pressure increased after cisapride (p less than 0.002). The peristaltic pressure amplitude in the oesophageal body as well as the duration and velocity of the peristaltic pressure wave were measured after wet swallows. No changes were found. Intragastric pH was unchanged after cisapride. No effect was found on the result of a standard acid clearing test. Plasma concentration of cisapride did not correlate with any of the other variables. Oral cisapride increases fasting gastro-oesophageal sphincter pressure, but does not influence oesophageal peristalsis, acid clearing or intragastric pH in normal subjects.

Oesophageal Peristalsis in Normal Subjects: Influence of pH and Volume during Imitated Gastro-oesophageal Reflux

Acid gastro-oesphageal reflux in normal human subjects is followed by oesphageal peristalsis. The aim of the present study was to investigate the influence of pH and volume during imitated reflux on oesophageal peristalsis. Fluid volumes of 2.5, 5, 10, and 15 ml (pH 1.0, 4.0, or 7.0) were instilled randomly in the lower end of the oesophagus in eight healthy subjects. Further, repeated instillations were carried out in one subject. Oesophageal pressures were measured 5, 10, and 15 cm oral to the gastro-oesophageal sphincter and in the pharynx, and pH 5 cm oral to the sphincter. Peristalsis confined to the oesophagus was found to be related to the volume of the instilled fluid, whereas pharynx-mediated peristalsis seemed to be related to the acidity of the fluid. It is concluded that peristalsis after imitated gastro-oesophageal reflux is influenced by both the volume and the acidity of the instilled fluid. Volume seems to initiate a local clearing mechanism, whereas low pH initiates pharynx-mediated peristalsis.

Acid Gastro-Oesophageal Reflux and Oesophageal Pressure Activity during Postprandial and Nocturnal Periods: A Study in Subjects with and without Pathologic Acid Gastro-Oesophageal Reflux

The aim of the investigation was to evaluate the relative quantity of acid gastrooesophageal reflux during different time periods in subjects with and without pathologic reflux. Twenty duodenal ulcer patients, 10 with and 10 without pathologic acid gastro-oesophageal reflux, and 26 asymptomatic volunteers were subjected to 12 h of simultaneous monitoring of pH and pressure activity in the oesophagus. The monitoring period was divided into a 3-h postprandial period, a night period of 6 h, and a 3-h period in the morning. The highest reflux frequency and the longest duration of oesophageal acid exposure were found in the postprandial hours (p less than 0.001). Thereafter, all groups had an even reduction in reflux rate. A greater absolute reduction in the duration of oesophageal acid exposure could be measured in patients with pathologic reflux as compared with the other groups (p less than 0.001). In spite of this, both reflux frequency and time with acid in the oesophagus were increased during the night in patients with pathologic reflux (p less than 0.001). Pathologic refluxers had in total 11 times as much reflux as normal subjects, and in addition 37.9% of the reflux took place during the 6 night hours. In contrast, only 5.4% of the reflux recorded in normal subjects occurred during this period. The pressure activity during periods with a normal intraoesophageal pH was reduced in all three groups during the night (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Oesophageal peristalsis. A simple system for the recording of oesophageal peristalsis, and the influence of bolus volume on peak peristaltic pressure amplitude.

Peak oesophageal peristaltic pressure amplitude was recorded in 8 healthy subjects at points 5 and 15 cm proximal to the gastro-oesophageal sphincter, by using an in situ tip-transducer simultaneously with a continuous flush (Intraflo) perfused catheter system with external pressure transducer. Dry swallows and wet swallows of 2.5, 5 and 10ml, respectively, were made in random succession. In all cases the pressures recorded by either system correlated well. In all cases the peristaltic pressure amplitude was significantly higher after the wet swallows. The catheter and flow system used in this study is simple and makes recording of peristaltic pressures independent of the shape of the in situ transducer, and its therefore well suited for measuring the amplitude of oesophageal contractions.

Intraluminal oesophageal manometry. Influence of pressure probe diameter.

The influence of the pressure-probe diameter on the values of gastro-oesophageal sphincter pressure, pharyngo-oesophageal sphincter pressure, and peak peristaltic pressure in the oesophageal body was investigated in eight healthy subjects. A low-compliance perfused pressure-measuring unit was used for the recordings. Three different probes were made with external diameters of 1.5 mm, 3.5 mm, and 4.5 mm. Sphincter pressures were measured in the resting state, and peristaltic pressures were measured during wet swallows. The pressure in the sphincter regions was found to depend on the diameter of the probe, whereas the peak peristaltic pressure amplitudes were independent of the probes used. The need for standardization of manometry equipment is emphasized.

Sympathetic Influence on the Normal Eustachian Tube: An Experimental Study in the Rat

A new variant of the inflation test of the Eustachian tube is presented; a constant air flow generator was constructed with minimal sensitivity to counterpressure, and variations in air pressure were measured, reflecting variations in Eustachian tube patency. By means of this test the effect of Otrivin (alpha 2-receptor stimulation) and Timacar (beta-receptor blocking) on the Eustachian tube was investigated with saline serving as reference. The following results were obtained: Otrivin lowers the opening pressure and the steady state pressure, and reduces the pressure drop during active opening. Timacar alone has no statistically significant effect on the Eustachian tube, but the combined effect of the two drugs is a more pronounced decrease in steady state pressure than the decrease seen following alpha 2-adrenergic stimulation alone. An explanation could be an alpha 2-receptor modulation by the beta-blocking agent. Consequently, autonomous regulation should be further studied in the search for a better understanding of Eustachian tube physiology.