Thesis--Helsinki. / At head of title: University of Helsinki Central Hospital, Surgical Clinic II. Bibliography: p. [128]-134.

The metabolism of lignocaine to monoethylglycinexylidide has been found useful as an indicator of hepatic function in association with liver transplantation. It has been postulated that this might be due to the common effect of hypoxic damage on liver function and lignocaine metabolism. The aim of this work was to establish whether hepatic lignocaine elimination was impaired by hypoxia and whether lignocaine extraction ratio and clearance could be used as an indicator of hepatic function. This was studied using the isolated pig liver perfused via the hepatic artery and portal vein. To establish whether the pig liver could be used as a possible human model for this investigation and whether lignocaine had any detrimental effects on liver function and blood flow in vivo, hepatic lignocaine elimination and the effects of lignocaine administration on hepatic function and blood flow were studied in the anaesthetized pig, surgically prepared to allow sampling across the liver and direct hepatic blood flow measurement. Hepatic lignocaine elimination was then studied in the isolated perfused liver to determine whether this was similar to that found in vivo. The definitive studies required preliminary investigations not available from the literature to determine the feasibility of comparing in vivo and ex vivo hepatic function using the same liver. In addition, by studying the decay of lignocaine after bolus dose administration the necessary pharmacokinetic parameters to achieve similar constant hepatic affluent lignocaine concentrations in vivo and in the isolated preparation could be determined. The preliminary investigations showed that a sequential experiment using the same liver to compare in vivo and ex vivo function was inappropriate as the energy state of isolated perfused livers previously studied in vivo was significantly different from that in livers perfused immediately. The decay of lignocaine after a bolus dose in vivo and ex vivo could be described by a two-compartment open model and in both preparations the derived pharmacokinetic parameters from this analysis were used to achieve similar constant hepatic affluent concentrations over the study period used to determine hepatic lignocaine elimination. Lignocaine extraction ratio by the in situ pig liver was similar to that reported in man and together with hepatic clearance and intrinsic clearance was similar to that determined in the isolated state when different livers were used for this comparison. There was no detrimental effect of lignocaine administration on hepatic function and blood flow In vivo. Lignocaine extraction ratio and clearance and monoethylglycinexylidide formation were significantly impaired in livers subjected to hypoxia. Lignocaine elimination correlated strongly with hepatic cellular ATP, energy charge and ATP/ ADP ratio as well as with hepatic potassium release but less strongly with aspartate aminotransferase release when this relationship was tested using the combined data from hypoxic and normoxic livers ex vivo. These correlations were positive for hepatic adenine nucleotide status and negative for hepatic potassium and aspartate aminotransferase release. Neither hepatic alanine aminotransferase release nor lactate utilization were significantly affected by hypoxia. Lignocaine extraction ratio, hepatic oxygen consumption, ATP content, bile flow and potassium release were shown to be equivalent, more highly sensitive, and earlier indicators of hypoxic hepatic injury than hepatic aspartate aminotransferase release in the isolated perfused pig liver.

The severely obese patient has varying degrees of intrinsic reduction of expiratory flow rates and lung volumes. Thus, the severely obese patient is predisposed to postoperative atelectasis, ineffective clearing of respiratory secretions, and other pulmonary complications. This study evaluated the effect of bi-level positive airway pressure (Bi-PAP) on pulmonary function in obese patients following open gastric bypass surgery. Patients with a body mass index (BMI) of at least 40 kg/m2 who were undergoing elective gastric bypass were eligible to be randomized to receive either BiPAP during the first 24 h postoperatively or conventional postoperative care. Patients with significant cardiovascular and pulmonary diseases were excluded from the study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), peak expiratory flow rate (PEFR), and percent hemoglobin oxygen saturation (SpO2) were measured preoperatively, and on postoperative days 1, 2, and 3. Twenty-seven patients were entered in the study, 14 received BiPAP and 13 received conventional postoperative care. There was no significant difference preoperatively between the study and control groups in regards to age, BMI, FVC, FEV1.0, PEFR or SpO2. Postoperatively, expiratory flow was decreased in both groups. However, the FVC and FEV1.0 were significantly higher on each of the three consecutive postoperative days in the patients who received BiPAP therapy. The SpO2 was significantly decreased in the control group over the same time period. Prophylactic BiPAP during the first 12--24 h postoperatively resulted in significantly higher measures of pulmonary function in severely obese patients who had undergone elective gastric bypass surgery. These improved measures of pulmonary function, however, did not translate into fewer hospital days or a lower complication rate in our study population of other wise healthy obese patients. Further study is necessary to determine if BiPAP therapy in the first 24 postoperative hours would be of benefit in severely obese patients with comorbid illnesses who have undergone elective gastric bypass.

The possibility that an inadequate response of the pulmonary system might limit high intensity exercise in man has received increasing attention over the past few years. However, very few scientific investigations have focused systematically on pulmonary function during high intensity constant-load exercise. Furthermore, many studies have examined only one part of the pulmonary system during exercise and some have not included blood gas measurements as a measure of the adequacy of pulmonary function. The studies reported in this thesis were designed to investigate the possible failure of the gas exchanging and pump functions of the pulmonary system during high intensity constant-load exercise. In particular, the aim was to determine the extent to which the pulmonary system might be a factor causing fatigue during this form of exercise.

No description available.

There is epidemiological and experimental evidence suggesting that exercise training may reduce the mortality rate from coronary heart disease, in particular the sudden death rate, and that it may improve the peak functional capacity of the heart. This thesis includes experimental work that is relevant to both these questions.

No description available.

No description available.

No description available.

No description available.