A combined in vivo/in vitro small animal model for studying pulmonary responses.

A model has been developed which allows an isolated lung to be perfused by a blood-PSS solution continuously processed by an intact animal. This model combines the advantage of control of the isolated perfused lung with a recirculated perfusate that is physiologically maintained. Substances that are generated by the isolated lung are, therefore, removed by metabolism in the intact animal and essential consumables in the perfusate are restored. Studies were performed in rabbits utilizing isolated perfused lung both with and without the intact animal processing the perfusate. The greatest pressor responses to hypoxic ventilation are obtained with a non-processed recirculated perfusate circuit, but the pressor responses decrease with time (12.5 +/- 1.7 cmH2O to 8.2 +/- 1.3 cmH3O) and the baseline pressure is higher initially (18.5 +/- 0.7 mmH2O). With the whole animal in the circuit, the baseline pressure and the initial hypoxic pressor responses are not as large, but are maintained constant (6.8 +/- 0.5 cmH2O to 8.1 +/- 1.0 cmH2O) over the same time period. When the isolated lungs are perfused with either blood-PSS or PSS in a non-processed, non-recirculated system, the hypoxic responses are 8.7 +/- 1.7 cmH2O and 5.7 +/- 1.0 cmH2O at the beginning of the study and decrease with time to 6.5 +/- 1.3 cmH2O and 4.2 +/- 1.0 cmH2O, respectively. The response of the isolated lung is, therefore, more stable with time and shows less individual variability when the whole animal perfusion circuit is employed.

[Inhibition of pulmonary vasoconstriction by inhaled nitric oxide].

We examined effects of inhaled NO gas on pulmonary vasoconstriction induced with hypoxic gas or PGF2 alpha utilizing the isolated perfused rabbit lung. While NO 180 ppm did not change the basal pulmonary artery pressure, the pressure response to hypoxia or PGF2 alpha was completely inhibited by pretreatment with NO inhalation. Inhaled NO during maximal pressor response also depressed the elevated pressure to the basal level. These findings suggest that NO inhaled to the alveoli diffuses directly into the pulmonary vascular smooth muscle and then causes nonspecific vasodilation, and its effect is more potent than that of constitutive type of EDRF/NO.

[A case of crush syndrome resulting from continuous compression of the upper arm by automatically cycled blood pressure cuff].

We report a case of crush syndrome (rhabdomyolysis) resulting from the prolonged compression of the inadvertently inflated blood pressure cuff around her upper arm. A 61-yr-old woman had undergone total gastrectomy, splenectomy and cholecystectomy for gastric cancer. At the end of the surgery lasting for 5 hrs 40 mins, we found the right upper arm extremely swollen with cyanotic petechiae beyond the inflated cuff. Failure of deflation of the automatically cycled blood pressure cuff was strongly suspected as a cause. She complained numbness and ardor on her hand with motor nerve disturbance and plasma CPK level was elevated. Diuretics were given and fluids were infused vigorously to prevent the renal failure, and continuous cervical epidural block was instituted to increase the blood flow to the injured arm. Prostaglandin E1 and ulinastatin (a protease inhibitor) were also effective for recovery from the crush syndrome. One month later she was discharged home accompanied with a slight numbness on the arm. Attention should be paid to deflation of the automatically cycled blood pressure cuff during anesthesia.

[Effects of prostacyclin (PGI2) on the hypoxic pulmonary vasoconstriction in dogs].

Effects of exogenous PGI2 on the hypoxic pulmonary vasoconstriction (HPV) were investigated by measuring %QLLL and the ratio of the left lower lobe blood flow (QLLL) to the total pulmonary blood flow (QT), in separately ventilated canine in vivo model. With PGI2 infusion, %QLLL, that had decreased from 20.7 +/- 1.9% to 4.1 +/- 1.1% by the hypoxic gas ventilation, gradually increased to 16.4 +/- 3.2% at the maximum dose (1.0 micrograms kg-1. min-1). Simultaneously both pulmonary artery pressure and PaO2 decreased significantly. Systemic blood pressure dropped markedly but cardiac output remained at the initial level. These results suggest that exogenous PGI2 improves the pulmonary circulation by reducing pulmonary hypertension induced with HPV, while PGI2 induces hypoxia by inhibiting HPV response and systemic hypotension by dilating the peripheral resistance vessels. Therefore, we have to consider these two opposite effects of PGI2 on its clinical application.

[Evaluation of inhibitory effect of isoflurane on the hypoxic pulmonary vasoconstriction response in dogs].

The effect of isoflurane on hypoxic pulmonary vasoconstriction (HPV) was examined using the separately ventilated left lower lobe lung model in dogs. When the HPV was induced with anoxic gas ventilation of the left lower lobe, the magnitude of HPV inhibition by isoflurane of 2 MAC was predominant, as assessed by the index of pressure-flow curve which is a novel indicator of pulmonary vascular tone in the left lower lobe. However, isoflurane 2 MAC attenuated the HPV by only 16%, as assessed by indices of the changes in left lower lobe blood flow rate and PaO2. This weak HPV inhibition, as shown by the latter parameters, may result from the net effect of isoflurane-induced HPV inhibition and secondary HPV enhancement due to decreases in cardiac output and pulmonary arterial pressure by isoflurane. However, none of the parameters showed inhibition of HPV when the HPV was induced by collapse of the left lower lobe. This discrepancy in the results may be caused by a lack of isoflurane reaching the hypoxic lobe when the HPV is induced with atelectasis. These results show that potency of HPV inhibition with isoflurane depends on the method of induction or evaluation of HPV, and that inhibition of HPV response with isoflurane at clinical concentrations is negligible in an atelectasis-induced HPV, in which no isoflurane is directly reaching the hypoxic lobe.

[Evaluation of halothane induced HPV inhibition with analysis of pressure-flow curve].

We investigated the effect of halothane on the hypoxic pulmonary vasoconstriction using in vivo measurement of the pressure-flow curve of the left lower lobe in the dog. With hypoxic ventilation of the left lower lobe, the pressure-flow curve shifted to the right and the slope of the curve became flatter. Although inhalation of 1 MAC halothane by the left lower lobe during hypoxic ventilation had no effect on the pressure-flow curve configuration, inhalation of 3, 5 MAC made the slope steeper. We analyzed these changes by the distensibility model proposed by W. Mitzner et al, and our data support the hypothesis that hypoxic ventilation decreases the small pulmonary vessels of 1-4 orders and also increases the compliance of the orders of vessel where the constriction has occurred, and halothane antagonizes the HPV response by further increasing the compliance of the constricted vessels. The inhibitory effect of halothane on HPV was weaker in in vivo preparation compared with the effect in in vitro preparation. Some humoral factors in the perfusate could contribute to this effect.

[Efficacy of simultaneous bolus injection of lidocaine with propofol on pain caused by propofol injection].

To investigate the effect of simultaneous bolus injection of 2% lidocaine 2 ml on preventing the pain on propofol injection, 80 patients were randomly assigned to one of four study groups; Group I received simultaneous bolus injection of 2% lidocaine 2 ml with infusion of propofol; Group II received bolus injection of saline 2 ml, 10 s before the start of infusion of propofol-lidocaine mixture; Groups III and IV received bolus injections of lidocaine and saline, separately 10 s before starting propofol infusion. Incidence of propofol-induced pain was significantly more frequent (P < 0.001) in Group IV (70%) than in the other groups (20% each). Number of patients who were satisfied with this anesthetic induction and requested for the same induction method in the next anesthesia was significantly larger in the groups receiving lidocaine (P < 0.05). Simultaneous bolus injection of lidocaine with propofol showed a similar clinical efficacy compared with both preadministration and premixing of lidocaine in preventing the propofol-induced pain.

[A modified technique for insertion of the laryngeal mask airway in children].

We modified the technique for laryngeal mask airway (LMA) insertion in children. This modification involves inserting a two-thirds inflated LMA with its lumen facing laterally toward left and then rotating it 90 degrees clockwise as it passes downwards into position behind the larynx. Then the cuff is inflated fully. We conducted a survey on the use of LMA in ten consecutive children for minor superficial surgery. After slow induction, anesthesia was maintained with 3.0% of end-tidal sevoflurane concentration in 100% oxygen for 5 minutes before insertion of LMA. No muscle relaxant was used. Successful insertion was judged by the clinical integrity of the airway. The standard LMA insertion technique or another airway device was applied when three trials had failed. Traumatic insertion was observed by the attachment of blood clots to the surface of the removed LMA. A satisfactory airway was achieved in all of the children who participated in the survey. There were no significant differences in vital signs between pre- and post-insertion. Only one child was found to have attachment of blood clots on the surface of the removed LMA. We conclude that our technique would be one recommended method in pediatric practice.

[Two cases of advanced and metastatic breast cancers treated by docetaxel in combination with intra-arterial infusion of adriamycin].

Two cases of advanced and metastatic breast cancers were treated by docetaxel (TXT) in combination with intra-arterial infusion of adriamycin (ADM). Patients received 60 mg/body TXT i.v. and 30 mg/body ADM ia (AT therapy) bi-weekly. Clinical responses were observed in these two patients and the durations of responses were over 20 weeks. Critical toxicities of grade 2 leukopenia and alopecia were observed but grade 4 severe toxicities were not. Thus AT therapy can be easily and safely performed with outpatients. This therapy can improve the response rate and time to progression; therefore phase I or phase I/II clinical trials of AT therapy in Japan are recommended.

[Studies on phosphorylation of estrogen receptor from porcine uterus].

Estrogen receptor (ER) complex with estrogen interacts with estrogen responsive element (ERE) in target gene promoters and modulates transcription. ER phosphorylation process might be involved in the transcription regulation. To investigate the ER phosphorylation, the author have purified ER from porcine uterine cytosol through heparin-Sepharose column chromatography followed by immunoprecipitation with monoclonal anti ER antibody and protein A-Sepharose. The ER was phosphorylated with [gamma-32P] ATP without any protein kinase, showing that ER has autophosphorylation activity. 63kDa and 120kDa proteins were mainly detected by SDS-PAGE analysis following autoradiography. ER became phosphorylated in the presence of divalent cation such as Mg2+ or Ca2+ in a time-dependent manner and an ATP concentration-dependent manner. Phosphoamino acid analysis showed phosphorylation of serine residue. Phosphorylation was stimulated by estrogen (E2), and phosphorylated receptor was bound to DNA fragment that contained EREs. It is suggested that ER phosphorylation process might participate in transcription regulation.

[A clinical study of pulmonary edema on paraquat poisoning by double indicator dilution method using heat and sodium].

We studied the formation of pulmonary edema on 9 patients with paraquat poisoning using thermal-sodium double indicator dilution method for the measurement of lung water. In survivors group (n = 4) extravascular thermal volume (EVTV) was not almost changes. In non-survivors group (n = 5) EVTV increased about three times as much as that in survivors group on 32 hours after admission. EVTV was correlated with PCP-PCOP in both survivors group and non-survivors group (n = 64, r = 0.665, p less than 0.01). But EVTV in non-survivors group was higher than that in survivors group within same PCP-PCOP. In non-survivors group delta EVTV/delta (PCP-PCOP) in 24 hours after admission was correlated with initial PCP-PCOP (r = 0.984, p less than 0.01). We propose that the formation of pulmonary edema on paraquat poisoning is mainly due to the increased capillary permeability, influenced by the increased pressure gradient of capillary barrier.