Treatment of massive hemorrhage with liposome encapsulated human hemoglobin (NRC) and hydroxyethyl starch (HES) in beagles.

The efficacy of NRC as a substitute for blood transfusion for treatment of acute, massive hemorrhage was evaluated in this study. Fourteen beagles, anesthetized with a mixture of 50% nitrous oxide, 0.97% sevoflurane and oxygen and ventilated by a respirator, were hemodiluted by withdrawal of 12 ml/kg of blood and infusion of isovolemic HES (hemodilution: HD) four times every 10 min. Then the animals were divided into two groups; an HES group, in which the same HDs were continued and an NRC group, in which the HDs were done with NRC. The hematocrit value decreased to 11% in the HES group after eight HDs and to 13% in the NRC group, which had a 3.9% NRCcrit value during the same period. In the NRC group, Cao2 decreased to 7.9 ml/min, which was significantly higher than the 5.9 ml/dl of the HES group. Oxygen consumption decreased to 56 ml/min in the HES group, but in the NRC group, it dropped to 74 ml/min, which was significantly higher than that of the HES group. Cardiac output increased to 1.2 times that of the control after eight HDs and arterial mean pressure decreased to approximately 60%. The above data indicated that NRC delivered sufficient oxygen to tissues, substituting for circulating red cells and maintained aerobic metabolism. Therefore, it should be possible to use NRC successfully for the treatment of cute, massive hemorrhage.

[Effect of aprotinin on endothelial cell functions during cardiopulmonary bypass].

Fourteen patients undergoing cardiac or great vessel surgery using cardiopulmonary bypass (ECC) were divided into two groups. Group A of 7 patients received 2 x 10(6) units of aprotinin (apr) 15 min before ECC and 0.5 x 10(6) unit immediately after the ECC. Group B of 7 patients received 0.5 x 10(6) unit of aprotinin 15 min before ECC and 2 x 10(6) units immediately after the ECC. Several physiological parameters were measured two hours before ECC, immediately after the cessation of the ECC and 4 hours thereafter. No difference was noted in coagulation time, which remained within normal range, and postoperative hemorrhage between the groups after ECC. Although thrombomodulin, ELAM-1 and ICAM-1 tended to decrease slightly in the two groups immediately after ECC, recovery of the thrombomodulin was much more rapid in the A group than in the B group. On the other hand, blood endothelin level and von Willebrand factor activity were elevated progressively after the ECC. Blood granulocyte-elastase activity and IL-8 increased markedly immediately after the ECC and then tended to decrease. These data indicate that no marked damage would be caused on the endothelial cells during ECC which was carried out using a relatively small dose of apr. However, the protective effect of apr remained to be clarified in the future.

[Hemostatic mechanism associated with aprotinin during and after the extracorporeal circulation for cardiac and great vessel surgery].

It has been reported that aprotinin (apr) is effective for hemostasis during and after the extracorporeal circulation (ECC) for cardiac or great vessel surgery. However its mechanism remains still obscure. In this study, we observed relationships between changes in interleukin-8 (IL-8), endothelial factors, or D-dimer and aprotinin administered before and after the ECC. Fourteen patients in whom cardiac or great vessel surgery was done using ECC were divided randomly into two groups. Seven subjects in Group I (G-I) were infused 10(6) KIU of apr immediately after anesthesia, immediately before and after the ECC, respectively, and 10(6) KIU of apr were also added during the ECC. Seven other subjects (G-II) were infused 10(6) KIU of apr immediately before and at three hours after the ECC, and also 2 x 10(6) KIU of apr immediately after the ECC. No marked hemorrhagic tendency was noted in all subjects and increase in plasma D-dimer was not marked. Immediately after the ECC, granulocyte elastase in plasma increased markedly in both groups but subsequently decreased in the G-II alone while it remained unchanged in the G-I. Similar changes were observed in plasma IL-8 values. During the ECC, intercellular adhesion molecule-1 in plasma decreased in both groups but von Willebrand factor activity decreased in the G-I alone. From the above data, the hemostatic effect of apr may contribute to protect the dysfunction of endothelial cells or to enhance recovering from the dysfunction during the ECC.

[The effects of hypertonic lactated Ringer's solution during transurethral surgery].

We studied the plasma sodium level and osmolarity when hypertonic lactated Ringer's solution (HLS) with sodium of 213 mEq.l-1 was infused as intraoperative fluid in patients (n = 7) undergoing transurethral resection of the prostate (TUR-P). Regular lactated Ringer's solution was infused in other patients (n = 7) as the control drug. Plasma sodium level and plasma osmolarity decreased significantly in the patients with regular lactated Ringer's solution group. On the other hand, these changes were not observed in the patients of HLS groups. However, three hours after the administration, serum ADH level increased significantly in HLS group while it remained unchanged in control group. It was suspected that the increase in serum sodium concentration might have stimulated secretion of ADH after TUR-P. Our study suggests that the administration of HLS prevents the hyponatremia and hypoosmolarity in patients undergoing TUR-P and that the HLS could be used routinely during this procedure as the essential fluid therapy.

[Metabolic and endocrinological responses to the infusion of a new intraoperative fluid].

A new intraoperative fluid, which is characterized by containing 10 mEq.l-1 of potassium, 140 mEq.l-1 sodium and 1% glucose, was infused into 18 healthy volunteers either at rate of 5, 10 ml.kg-1.h-1 (for 3 hours) or 15 ml.kg-1.h-1 (for 2 hours). Responding to increase in the infusion rate and volume, blood glucose and insulin (IRI) levels increased slightly but remained in the normal range. On the other hand, lipid metabolism was depressed markedly. Although concentrations of both potassium and sodium in serum remained unchanged, sodium and water balance (intake vs. outflow) became absolutely positive. Potassium balance was maintained at zero. Blood renin activity decreased gradually after the infusion was commenced and remained at a lower level for 3 hours after stopping infusion. Blood aldosterone and antidiuretic hormone levels also decreased but more gradually than the decrease of blood renin activity. Noteworthy change was not observed in the variables relating to hepatic and renal functions.

[Changes in the intraoperative hormonal homeostasis following infusion of lactated Ringer's solution with high potassium concentration].

Changes in the concentrations of serum electrolytes and those of water and electrolyte regulating hormones were studied in mongrel dogs undergoing a sham operation (gastrectomy) under general anesthesia. Six dogs (L-group) were infused regular lactated Ringer's solution containing 1% glucose, and other six dogs (KL-group) were infused lactated Ringer's solution containing 1% glucose and potassium 10 mEq.l-1. The serum potassium concentration decreased significantly during the surgery in the L-group, but it remained unchanged in the KL-group. Blood sugar level increased during and after the surgery in the L-group. On the other hand, the blood sugar level changed in a similar way as that of the L-group during the surgery, but it decreased after the surgery in the KL-group. NEFA level also decreased after the surgery in the KL-group. Aldosterone secretion was increased after the surgery in the L-group. On the other hand, the aldosterone secretion increased during the surgery in the KL-group. The differences of the aldosterone secretion between the groups may be due to the direct influence of potassium on the adrenal cortex. Serum concentration of ADH increased in both groups during the surgery. In the L-group, it remained later, but it recovered toward the initial level after the surgery in the KL-group. The above data indicate that no peculiar change occurred in hormonal homeostasis of subjects receiving operations under general anesthesia following the infusion of lactated Ringer's solution with high potassium concentration.

The microcirculation during enflurane and isoflurane anaesthesia in dogs.

The effects of enflurane and isoflurane of 0.75 and 1.5 MAC on capillary blood flow were studied by the microsphere (9 +/- 1 microns in diameter) method in two groups of seven dogs. Simultaneously, changes in the arteriolo-venular shunt were studied by collection of venous blood at a rate of 4.8 ml.min-1 for two minutes. Enflurane anaesthesia at 0.75 MAC decreased capillary blood flow in the thyroid glands (35% of control), left and right ventricular wall (59% and 50%), adrenal gland (59%), liver (63%), spleen (56%), pancreas (35%), omentum (20%), and small intestine (60%) and at 1.5 MAC it decreased further in the thyroid glands (15%), left and right ventricular wall (31% and 32%), adrenal gland (42%), liver (47%), spleen (31%), pancreas (23%), omentum (20%), stomach (45%), and small intestine (54%). No marked changes were noted in the brain, kidney, large intestine or skeletal muscle. The arteriolo-venular shunt was decreased in the kidney from an initial rate of 12.1 to 3.8% at 0.75 MAC and to 2.5% at 1.5 MAC enflurane. In contrast, during isoflurane anaesthesia, capillary blood flow remained unchanged, except for a decrease to the thyroid glands (43%) and right ventricular wall (74%) during 1.5 MAC anaesthesia. However, the arteriolo-venular shunt was increased in the brain from 12.0 to 29.7% and 33.0% during 0.75 and 1.5 MAC isoflurane anaesthesia, respectively. It also increased from 25.0 to 41.0% and 46.3% in the skeletal muscle, and from 8.9 to 19.9% and 17.4% in the whole systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Sevoflurane anaesthesia for one-lung ventilation with PEEP to the dependent lung in sheep: effects on right ventricular function and oxygenation.

This study was undertaken to examine the effect of sevoflurane on right ventricular function, the safety of sevoflurane for one-lung ventilation and the effects of PEEP (positive end-expiratory pressure) to the dependent lung in this model using 12 open-chest sheep. Haemodynamic variables, including cardiac output, mean arterial blood pressure, right ventricular pressure and pulmonary arterial pressure, and right ventricular segment shortening (sonomicrometry) were measured. First, animals received 2.0, 3.0 or 4.0% sevoflurane for 20 min each, respectively, during two-lung ventilation to measure the dose-dependent haemodynamic effects of sevoflurane. Then one-lung ventilation was performed with a randomized sequence of 0 (ZEEP), 5 and 10 cm H2O PEEP to the dependent lung under 2.0% sevoflurane anaesthesia after one-hour stabilization. A decrease in systolic segment shortening along with increases in both the end-diastolic and end-systolic lengths of the right ventricle were observed at 3.0 and 4.0% sevoflurane, while global right ventricular function remained substantially unchanged during two-lung ventilation. During one-lung ventilation the PaO2 was greater with 5 cm H2O PEEP 198 mmHg (+/- 25 SEM) than with ZEEP 138 mmHg (+/- 22) or with 10 cm H2O PEEP 153 mmHg (+/- 23) (P < 0.05). No differences in haemodynamic variables or segment shortening between ZEEP and PEEPs during one-lung ventilation were observed. We conclude that although sevoflurane causes a dose-dependent depression of right ventricular function, sevoflurane anaesthesia can be safely applied to one-lung ventilation, and that 5 cm H2O PEEP to the dependent lung can improve arterial oxygenation without causing changes in right ventricular function.

Changes in circulating blood volume following isoflurane or sevoflurane anesthesia.

Changes of circulating blood volume (CB volume) measured by the dual indicator dilution method were observed in 33 chronically instrumented mongrel dogs following either alpha-chloralose-urethane (C group), additive isoflurane (I group) or sevoflurane anesthesia (S group). These anesthetic groups were each divided into two subgroups with regard to respiratory care, namely Cp, Ip and Sp for those with intermittent positive pressure ventilation (six animals per subgroups), and Cs, Is and Ss for those with spontaneous breathing (five animals per subgroups). The CB volume under positive pressure ventilation remained unchanged in the Ip and Sp groups at both 0.5 and 1.0 MAC, and in the Cp group. The CB volume remained essentially unchanged in the Cs and Is groups at both 0.5 or 1.0 MAC, but the plasma volume tended to increase slightly in the Is group at 1.0 MAC. In the Ss group under spontaneous breathing, however, the CB volume increased from 84.4 +/- 7.0 to 91.4 +/- 7.7 at 0.5 MAC, and to 91.4 +/- 10.2 ml.kg(-1) at 1.0 MAC (0.01 < P < 0.05). These increases were caused by an increase in the plasma volume. The above data suggests that a concomitant increase in the venous pressure associated with an increase in the intrathoracic pressure produced by positive pressure ventilation would attenuate changes in the CB volume during sevoflurane anesthesia.

Plasma concentrations of lignocaine after obturator nerve block combined with spinal anaesthesia in patients undergoing transurethral resection procedures.

Bilateral obturator nerve block has become a widely accepted technique to avoid adductor contraction during transurethral resection of prostate or bladder tumours. However, little is known about plasma lignocaine concentrations after the block. We conducted this study to assess a safe dose of lignocaine for injection in obturator nerve block. Bilateral obturator nerve block was performed with the aid of a peripheral nerve stimulator in 12 patients after spinal anaesthesia. In group I (n = 6), patients received 2% lignocaine 10 ml (200 mg) for the block; those in group II (n = 6) received 2% lignocaine 15 ml (300 mg). The block was satisfactory and no single adductor contraction was observed in either group during surgery. The peak plasma concentrations of lignocaine were 2.28 (SD 0.29) micrograms ml-1 and 3.75 (0.79) micrograms ml-1 in groups I and II, respectively. The greatest plasma concentration was 5.07 micrograms ml-1 in a patient of group II. There were no symptoms suggesting systemic toxicity. We conclude that bilateral obturator nerve block may be performed safely and effectively with 2% lignocaine 10 ml with the aid of a peripheral nerve stimulator in patients undergoing transurethral resection procedures with spinal anaesthesia.

Influence of nicardipine on post-hypoxic injury in the isolated perfused rat liver.

We investigated microcirculatory changes and hepatocellular injury due to hypoxia/reoxygenation and the effects of nicardipine, a calcium channel blocker, using the isolated perfused rat liver technique. Liver perfusion was carried out in three consecutive phases: 30-min pre-hypoxia perfusion, 120-min hypoxia perfusion and 30-min reoxygenation perfusion in two groups, a control (n = 5) group and a nicardipine group (n = 5). In the nicardipine group, nicardipine (2 x 10(-6) M) was added to the perfusate prior to the hypoxia perfusion. Intrahepatic volumes, sinusoidal volume and extravascular volume accessible to albumin, were assessed by the multiple indicator dilution technique. Though 120-min hypoxia per se caused only a slight increase in the lactate dehydrogenase (LDH) release and no significant alterations in perfusion pressure and intrahepatic volumes, reoxygenation elicited hepatocellular injury assessed by the LDH level in the perfusate along with a substantial increase in perfusion pressure and an increase in extravascular volume. Nicardipine pretreatment attenuated the increase in LDH level, perfusion pressure and intrahepatic volumes after reoxygenation, but there were no difference in liver microcirculation during 120-min hypoxia. The data of the current study emphasized the crucial role of Ca2+ influx in hypoxic/reoxygenation hepatocellular injury and suggested that a direct vasodilating effect of nicardipine on the intrahepatic vasculature during hypoxia is unlikely as the mechanism for its cytoprotective effects.

[Changes in blood sugar levels following infusion of lactated Ringer's solution with various concentrations of potassium and glucose].

Lactated Ringer's solution was prepared, in which concentration of potassium was either 10 or 20 mEq.l-1, and that of glucose was 1.4%. Each preparation was infused into 10 patients who underwent surgical operations under general anesthesia. Effects of this fluid therapy on changes in serum potassium and blood sugar were studied comparing with infusion of lactated Ringer's solution in which concentration of potassium was 10 mEq.l-1, and glucose was 0.7%. Both serum potassium and blood sugar levels were maintained within normal ranges with the lactated Ringer's solution containing 20 mEq.l-1 of potassium and 1.4% of glucose. On the other hand, the former tended to decrease and the latter tended to increase with the lactated Ringer's solution containing potassium 10 mEq.l-1 and glucose 1.4%. We consider that the homeostatic effect with the lactated Ringer's solution containing 20 mEq.l-1 of potassium and 1.4% of glucose would be to lower blood glucose level by concomitant intracellular influx of potassium and glucose. Therefore these high potassium lactated Ringer's solutions balanced adequately with glucose are useful for fluid therapy during surgical procedure under general anesthesia.

[Effect of superimposed high frequency oscillation on pulmonary edema induced by intrapulmonary injection of hydrochloric acid in dogs].

Effect of superimposed high frequency oscillatory ventilation on pulmonary gas exchange was investigated in seven anesthetized and paralyzed dogs with pulmonary edema induced by intrapulmonary injection of hydrochloric acid. Efficacy of the ventilatory modes (HFO:6 Hz and 12 Hz) was evaluated observing changes in ventilation-perfusion mismatch, which was demonstrated by using six inert gas elimination method. The ventilation with 6 Hz HFO had no significant effect on PaO2, true shunt, and perfusion distribution. With 12 Hz HFO, PaO2 showed a tendency to increase from 57 +/- 18 mmHg at IPPV to 144 +/- 117 mmHg (0.05 less than P less than .01), and the true shunt decreased from 42.2 +/- 29.0% at IPPV to 16.6 +/- 25.8% (P less than 0.05). However, no change appeared in the perfusion distribution. During the ventilation with 12 Hz HFO increased mean airway pressure produces a PEEP-like effect, which may improve the pulmonary gas exchange by opening small airways, namely a decrease in the true shunt rather than an improvement in the ventilation-perfusion maldistribution.

Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle.

Recently, there has been increasing interest in the alterations in splanchnic and hepatic circulation and preservation of hepatic oxygenation and function during anesthesia and surgery. However, the effects of volatile anesthetics under a condition of marginal hepatic oxygen supply are not well understood. Using a crossover design, we therefore studied the effects of equianesthetic concentrations (1.5 MAC) of halothane, isoflurane, and sevoflurane on hepatic oxygenation and function in nine beagles in which the hepatic artery had been ligated. Portal blood flow was measured by an electro-magnetic flow meter. Hepatic function was assessed by indocyanine green elimination kinetics. While cardiac output and mean arterial pressure were greater during halothane anesthesia than during isoflurane and sevoflurane anesthesia, portal blood flow and hepatic oxygen supply were significantly less during halothane and sevoflurane anesthesia than during isoflurane anesthesia. With regard to hepatic oxygen uptake, there was a significant difference between halothane (2.7 +/- 1.2 ml.min-1 x 100 g-1) and sevoflurane (3.7 +/- 2.0 ml.min-1 x 100 g-1; P less than 0.05). Consequently, the hepatic oxygen supply/uptake ratio and the hemoglobin oxygen saturation and oxygen partial pressure in hepatic venous blood during sevoflurane anesthesia were significantly less than they were with the other anesthetics. Indocyanine green clearance was better preserved during sevoflurane anesthesia (39.7 +/- 12.0 ml.min-1) than during halothane anesthesia (30.9 +/- 8.4 ml.min-1; P less than 0.05). We conclude that sevoflurane is accompanied by a smaller oxygen supply/uptake ratio than is halothane and isoflurane, while it preserves hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Perioperative autotransfusion: haemodilution and red cell salvaging.

We have treated 129 cases of massive haemorrhage during surgery using our combined autotransfusion technique (HAT and SAT). No adverse reactions or complications have been noted and additional homologous blood transfusion has not been required. In addition, circulatory dynamics have been satisfactorily maintained. Although the red cell recycle rate has been maintained at over 85%, the salvaging rate of blood in the operating field has not yet reached 80%. Approximately 30% of the surgical haemorrhage appears to be discarded with surgical sponges or flow out of the operating field. Clearly the cooperation of surgeons is an important factor for success with SAT. Success in autotransfusion may be accomplished by combinations of autotransfusion techniques.

Pulmonary gas exchange and ventilation-perfusion relationships during hypocapnia and thoracotomy in anaesthetized dogs.

The effects of hypocapnia and thoracotomy, both individually and combined, on pulmonary gas exchange and distribution of ventilation-perfusion ratio (Va/Q) were studied in anesthetized and paralyzed mongrel dogs by the six inert gas elimination technique. Normocapnia (PaCO2 35 mmHg) and hypocapnia (PaCO2 20 mmHg) were produced sequentially by varying the inspired CO2 concentration. Thoracotomy was performed at the fourth intercostal space. When ventilation was changed from normocapnia to hypocapnia without thoracotomy, PaO2 decreased from 160 +/- 10 to 147 +/- 11 mmHg and Qs/Qt increased from 0.0 +/- 0.0 to 0.6 +/- 0.7%. However, no change was observed in perfusion distribution following thoracotomy during normocapnia, PaO2 decreased from 160 +/- 10 to 113 +/- 15 mmHg together with a shift of perfusion toward the low Va/Q region. However, no change was observed in Qs/Qt. When ventilation was changed from normocapnia to hypocapnia with thoracotomy, PaO2 decreased from 113 +/- 15 to 98 +/- 12 mmHg and Qs/Qt increased from 0.3 +/- 0.8 to 3.4 +/- 2.0%. After thoracotomy, a shift of perfusion toward the low Va/Q region was observed, which was probably responsible for the decrease in PaO2. The decrease in PaO2 during hypocapnia was due to an increase in the true shunt rather than the development of low Va/Q region. Hypocapnia combined with thoracotomy produced a further reduction of PaO2 and a greater increase in Qs/Qt.

[A simple expression of the intrapulmonary ventilation-perfusion ratio distribution curves].

We propose a method to express the intrapulmonary ventilation-perfusion distribution curves obtained by 6 inert gas elimination technique. A VA/Q distribution curve was obtained by calculating the amount of perfusion distributed in each fraction of the VA/Q as percentage of the cardiac output and then averaging them to obtain a single distribution curve. By this method, it is possible to simplify the representation of the distribution curve, to clarify the serial changes through the experiment, and further to compare different patterns in several experimental groups.