Magna Andreen

Central and Splanchnic Hemo dynamics in the Dog during Controlled Hypotension with Adenosine

Central and splanchnic hemodynamic effects during controlled hypotension induced by the administration of the endogenous vasodilator adenosine were studied in ten artificially ventilated dogs under neurolept anesthesia. Adenosine was administered as a continuous infusion in the aorta (n = 3), in the inferior vena cava (n = 3), and after pretreatment with dipyridamole (which inhibits the cellular uptake of adenosine) (n = 4) in a dose sufficient to maintain a mean arterial blood pressure (MABP) level of approximately 50 mmHg. Observations were made before and after 20 min of controlled hypotension. Basal arterial plasma levels of adenosine were in the 10−7 M range (&OV0398; = 0.4 μM). The hemodynamic response was similar in all three settings. Adenosine caused a profound decrease in systemic vascular resistance (SVR) (52%, P < 0.01) and preportal vascular resistance (PPR) (64%, P < 0.01), while hepatic arterial vascular resistance (HAR) increased by 49% (P < 0.05). Cardiac output increased (22%, P < 0.05) through increase of stroke volume (77%, P < 0.01), while heart rate decreased (28%, P < 0.01). Whole-body oxygen uptake decreased (14%, P < 0.01). Portal venous blood flow increased by 28% (P < 0.05), whereas hepatic arterial blood flow decreased by 70% (P < 0.01). In the preportal tissues, oxygen uptake decreased by 21% (P < 0.01). In contrast, hepatic oxygen consumption increased (53%, P < 0.05). Adenosine-induced hypotension was not associated with changes in plasma renin activity or the plasma concentration of norepinephrine. It is concluded that adenosine causes a rapidly induced and easily maintained hypotension and may be a potentially useful agent for controlled hypotension in patients.

The Different Responses of the Hepatic Arterial Bed to Hypovolaemia and to Halothane Anaesthesia

Ten dogs were subjected to a period of hypovolaemia (bleeding volume: 2% of body weight) and to a period of halothane anaesthesia (end‐tidal halothane concentration: 1%). Mean arterial blood pressure decreased to 79% of control value during hypovolaemia and to 58% of control value during halothane anaesthesia. Mean total peripheral and preportal vascular resistances increased during hypovolaemia and were unchanged during halothane. Mean hepatic arterial and portal venous blood flows decreased to 82% and 55% of control values, respectively, during hypovolaemia, and to 41% and 56% of control value, respectively, during exposure to halothane. Mean hepatic arterial resistance was unchanged during hypovolaemia, but increased during halothane. Mean hepatic oxygen consumption did not change significantly during hypovolaemia, but decreased during halothane anaesthesia, in spite of an increased extraction of oxygen from both the hepatic arterial and the portal venous blood. Possible mechanisms which may maintain oxygen supply to the liver by increasing the hepatic arterial fraction of total liver blood flow when portal venous blood flow is reduced are discussed. It is concluded that this mechanism is upset or inhibited during halothane anaesthesia.

Haemodynamics and Oxygen Consumption in the Dog During High Epidural Block with Special Reference to the Splanchnic Region

High epidural block (Th I‐IV) with bupivacaine was carried out in 16 dogs. Mean arterial blood pressure decreased to 52% of control value owing to nearly equal decreases in systemic vascular resistance and cardiac output. Portal venous blood flow decreased from 25.8 ± 8.6 to 16.7 ±7.2 ml/kg b.w. × min‐1 following epidural block, while hepatic arterial blood flow remained unchanged at 9.1 ± 3.1 ml/kg b.w. × min‐1 owing to a reduction in hepatic arterial resistance of 51 %. Hepatic oxygen uptake was maintained during the epidural block through increased oxygen extraction. However, total oxygen uptake decreased by 18 % and, in spite of this, arteriovenous oxygen content difference increased by 25%, indicating circulatory depression.

Effects of Enflurane on Haemodynamics and Oxygen Consumption in the Dog with Special Reference- to the Liver and Preportal Tissues

The effects of enflurane anaesthesia on central circulation, total oxygen uptake, splanchnic circulation and splanchnic oxygen uptake were studied in 10 artificially ventilated dogs, basally anaesthetized with thiopental and nitrous oxide. Hepatic arterial, superior mesenteric arterial and portal venous blood flows were measured with electromagnetic flowmetry. Cardiac output was measured by thermodilution. Determinations of oxygen contents were made in arterial, pulmonary arterial, portal venous and hepatic venous blood. The end‐tidal enflurane concentration was kept at about 1 MAC (= 2.2%). Arterial blood pressure diminished to 54% of control value due to decreases of cardiac output to 65% and of total peripheral vascular resistance to 81% of control values. Hepatic arterial, superior mesenteric arterial and portal venous blood flows decreased to 65–70% of control levels and the corresponding vascular resistances all declined to about 80–85% of control values. Total oxygen uptake decreased, but less than cardiac output, leading to an increased arterio‐venous oxygen content difference. Oxygen uptake of the preportal tissues was unchanged and hepatic oxygen uptake was not significantly altered, although there were decreases in hepatic oxygen uptake in some of the individual experiments. It is suggested that the cardiovascular depression following enflurane anaesthesia in the dog was due, to a great extent, to a primary myocardial depression. It is further roncluded that the splanchnic blood flows were relatively well preserved, due to decreases in splanchnic vascular resistancm, and that hepatic and preportal tissue oxygen consumptions were maintained by increased oxygen extraction.

The Elimination of Bupivacaine (Marcain®) after Short Intravenous Infusion in the Dog: with Special Reference to the Role Played by the Liver and Lungs

The elimination of bupivacaine after a short intravenous infusion (1 mg. kg‐1 b.w. for 1 min) was studied in eight dogs. Special interest was focused on the roles played by the liver and lungs. By combining measurements of blood flows and blood concentrations of bupivacaine entering and leaving the liver, it was possible to quantify hepatic elimination of the drug. The concentration time‐curves from pulmonary arterial and aortic blood were similar as regards height and shape and thus did not verify the existence of a pulmonary uptake of bupivacaine of such significance that it dampened the aortic concentration time‐curve. The circulatory changes induced by the infusion were small. The plasma bupivacaine concentration often reached a peak well above 4 μg. ml‐1, but no symptoms of toxicity were registered. The elimination was very fast in comparison with that in man and is probably explained by both a higher hepatic extraction ratio and a greater hepatic blood flow kg‐1 b.w. in the dog. The results support the assumption of a first‐order hepatic hupivacaine elimination. The mean hepatic extraction ratio was constantly about 60% throughout the experiments, and the mean hepatic bupivacaine clearance about 25 ml. kg‐1 min‐1. Cumulative elimination time‐curves were calculated and it was demonstrated that the liver eliminated on average 80% of the given dose during the first hour after the infusion. Finally, it was shown that the mean cumulative elimination time‐curve was not easily linearized, which suggests that the liver eliminated more bupivacaine per time unit during the distribution period than would have been predicted from the usually assumed two or three‐compartment model. It is claimed that distribution volumes calculated by extrapolating the terminal decay slope of the semi‐logarithmic concentration time‐curve to time zero will partly consist of hepatic elimination.

Effects of neurolept anaesthesia (NLA) on haemodynamics and oxygen consumption in the dog with special reference to the liver and preportal tissues.

The etrects of neurolept anaesthesia (NLA) on central circulation, total oxygen uptake and splanchnic cirrulation and oxygen uptake were studied in 12 artificially ventilated dogs, basally anaesthetized with thiopental and nitrous oxide. Hepatic arterial, superior mesenteric arterial and portal venous blood flows were measured with electromagnetic flowmetry. Cardiac output was measured by thermodilution. Determinations of oxygen contents were made in arterial, pulmonary arterial, portal venous and hepatic venous blood. NLA was induced with droperidol 0.5 mg kg‐1 b.w. and fentanyl 0.01 mg kg‐1 b.w. Arterial blood pressure decreased to 63% of control value due to reductions of cardiac output to 78% and of total peripheral vascular resistance to 81% of control values. Hepatic arterial, superior mesenteric arterial and portal venous blood flows all diminished to 75% of control values. Hepatic arterial, superior mesenteric arterial and preportal tissue vascular resistances all decreased. Total oxygen uptake declined to the same extent as cardiac output, leaving the arterio‐venous oxygen difference unchanged. Oxygen uptake of the preportal tissues was unaffected and hepatic oxygen uptake was not significantly reduced, although there were decreases of hepatic oxygen uptake in some of the individual dogs. It is suggested that the cardiovascular depression following NLA was due to adaptation to a lowered total oxygen uptake. It is further concluded that splanchnic circulation was well preserved due to decreases in splanchnic vascular resistances, and that splanchnic oxygen consumption was maintained by means of increased oxygen extraction.

Uptake of Bupivacaine (Marcaine®) in Liver and Lung after Intramuscular Administration in the Dog

The uptake of bupivacaine in the liver and lung of the dog was studied 10, 20, 30 and 60 min after intramuscular injection of the drug. It was possible to quantify this uptake by combining measurements of concentrations and flows. The administration of bupivacaine (0.75 mg/kg b.w.) did not result in any significant circulatory changes. Arterial bupivacaine concentrations showed major variations, indicating interindividual differences in absorption rate. Lung uptake after 10 min was high in two dogs with initially high blood concentrations of bupivacaine, but low after 20 min or longer. The other dogs showed little or no uptake. Mean hepatic bupivacaine uptake was about 50% of the total dose during the first hour after injection; this indicates the central role of the liver in eliminating bupivacaine even during the initial period following administration. The hepatic extraction ratio showed interindividual variations, but the mean value of about 55% was constant throughout the observation period. This is in agreement with earlier findings indicating a first‐order elimination of bupivacaine.

Effects of Enflurane on Splanchnic Circulation

A brief summary of the anatomy and physiology of the splanchnic circulation is presented. The influence of 1 MAC enflurane anaesthesia on splanchnic circulation and oxygenation was studied in 10 dogs. Superior mesenteric arterial, portal venous and hepatic arterial blood flows decreased less than mean arterial blood pressure, due to reductions in superior mesenteric arterial, preportal vascular and hepatic arterial resistances. It is suggested that these reactions within the splanchnic circiilarion are mainly dependent on normal autoregulative responses elicited by the fall in blood pressure. Oxygen consumption of the preportal tissues and the liver was unchanged as a result of increased extraction of oxygen.

Hepatic Release of Fluoride from Halothane under Hypoxic and Non‐Hypoxic Conditions in the Dog

Six dogs were subjected to halothane anaesthesia under hypoxic and non‐hypoxic conditions. Plasma fluoride levels in hepatic venous and arterial blood, as well as blood flow to the liver, were measured during anaesthesia. The amount of fluoride released by the liver could thus be calculated. Release of fluoride took place in all animals during non‐hypoxic halothane anaesthesia. The amount released varied between the individual animals and in three of them it rose further during hypoxic anaesthesia. The occurrence of defluorination of halothane, even under non‐hypoxic conditions, may indicate a reductive metabolism in at least some parts of the liver. The significance of this hypothesis is discussed.

Effects of Prenalterol and Volume Loading with Dextran on Haemodynamics and Oxygen Consumption in Dogs During High Epidural Block with Special Reference to the Splanchnic Region

High lumbar epidural block was induced in seven dogs, causing a fall in mean arterial blood pressure (AP) from 24.5 ⋅ 2.9 to 12.0 ⋅ 3.1 kPa owing to reductions in cardiac output (QT) and systemic vascular resistance (SVR) to 67% and 68% of the pre‐epidural values. Volume loading with dextran 10 ml ⋅ kg‐1 b. w. increased QT nearly to the pre‐epidural value. SVR decreased further to 61% of the pre‐epidural value and AP was only slightly increased to 14.9 ⋅ 2.7 kPa. Subsequent administration of prenalterol 20 μg ⋅ kg‐1 b. w. caused a further increase in QT to 17% above the pre‐epidural value due to an increase in heart rate of 51 beats/min. AP did not change since SVR decreased further to 49% of the pre‐epidural value. The hepatic arterial blood flow (QHA) was essentially unchanged during epidural block as well as during volume loading, while the portal venous blood flow (QPV) was changed concurrently with (QT). In spite of the decrease in SVR, the preportal and hepatic arterial vascular resistances were not diminished following prenalterol. The increase in QT must therefore have favoured other vascular beds. Hepatic and pre‐portal tissue oxygen uptakes were unchanged during the experimental procedure, while whole‐body oxygen uptake decreased by 20% following the epidural block and increased nearly to the pre‐epidural level following volume loading in combination with prenalterol.