Anesthetic management of patients undergoing unilateral video-assisted lung reduction for treatment of end-stage emphysema.

OBJECTIVES: Nonanatomic resection of peripheral areas of lung is being performed via sternotomy for the treatment of end-stage emphysema. Recent technologic advances have allowed the resection of lung tissue using video-assisted thoracic surgery (VATS) techniques. The study was performed to document the physiologic changes that occur during unilateral VATS lung reduction in hopes of determining appropriate monitoring and intraoperative management strategies. DESIGN: Prospective trial of unilateral VATS lung reduction. SETTING: Tertiary care university hospital. PARTICIPANTS: Twenty patients with end-stage emphysema. INTERVENTIONS: Participants underwent unilateral VATS lung reduction. MEASUREMENTS AND MAIN RESULTS: Invasive hemodynamic monitoring was performed using radial and pulmonary artery catheters. Hemodynamic and respiratory gas exchange data were collected at four intraoperative points: (1) supine, two-lung ventilation; (2) lateral decubitus, two-lung ventilation; (3) lateral decubitus, one-lung ventilation, and (4) end of surgery, supine, two-lung ventilation. Data were compared with that collected at the first point. Patients tolerated lengthy surgical procedures and remained hemodynamically stable with no episodes of hypoxemia requiring treatment. Extubation was tolerated by 19 of 20 patients at the conclusion of surgery without further requirement of mechanical ventilation. CONCLUSIONS: VATS lung reduction under general anesthesia with one-lung ventilation is well tolerated. Permissive hypercapnia was well tolerated by all patients. Early extubation can be routinely accomplished in these patients.

Protective effect of 2-chloroadenosine on lung ischemia reperfusion injury.

Reperfusion following ischemia yields an inflammatory response characterized by polymorphonuclear leukocyte (PMN) influx, inflammatory mediator release, microvascular permeability alteration, and protein-enriched fluid transudation. Evidence has accumulated suggesting that low-dose adenosine may "down-regulate" the PMN response. This study evaluated the effects of an adenosine analogue, 2-chloroadenosine (2CA), on ischemia-reperfusion (IR) injury in rabbit lungs. In these experiments the left pulmonary hilum was skeletonized, obliterating the bronchial circulation, and the left pulmonary artery and vein were occluded for 1 min for the sham ischemia (SI-V) group or for 1 hr for the ischemia (I-V) and 2CA-treated (I-A) groups. The left lung was inflated with nitrogen during the ischemic period. Saline (SI-V and I-V groups) or 2CA (I-A group) infusions were begun prior to and during the reperfusion period. After 4 hr of reperfusion and restored ventilation, selective left lung physiologic measurements and bronchoalveolar lavage (BAL) were performed. Groups (N = 8/group) were compared using analysis of variance. The I-A group demonstrated a significantly lower mean pulmonary artery pressure and higher cardiac output than the I-V group. Pulmonary vascular resistance was significantly elevated in group I-V compared to group I-A. A significantly greater alveolar WBC influx and protein transudation (BAL/plasma albumin) occurred in the ischemic group compared to the 2CA-treated animals and sham controls. Decreased PaO2 and increased venous admixture were noted in the ischemic group, but did not reach significance when compared to the 2CA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of increased pulmonary microvascular permeability induced by FMLP in isolated rabbit lungs.

We observed that the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L- phenylalanine (FMLP) induced pulmonary edema when polymorphonuclear leukocytes (PMNs) were added to isolated constant-flow buffer-perfused rabbit lungs. This study was designed to test the hypothesis that PMNs activated by FMLP induced lung injury by the modulation of reactive oxygen species (ROS), cyclooxygenase products, or cysteinyl leukotrienes (LTs). Addition of FMLP alone did not increase microvascular permeability (Kf). When PMNs were added to the isolated lung, FMLP caused an 80% increase in Kf. Wet-to-dry weight ratio was also significantly increased with PMNs + FMLP compared with FMLP only. There was a significant positive correlation between total myeloperoxidase activity in lung tissue and Kf values after FMLP (30 min). Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate or ibuprofen, had no effect on the PMN + FMLP-induced increase in Kf. However, the ROS inhibitor catalase and the nonantioxidant LT synthesis blocker MK 886 inhibited the PMN + FMLP increase in Kf. Perfusate levels of LTs (LTC4, -D4, and -E4) were significantly increased from baseline values 30 min after FMLP. Both MK 886 and catalase suppressed the elevation of LTs after PMN + FMLP. These results indicate that FMLP increased a pulmonary microvascular permeability in isolated buffer-perfused rabbit lungs that is PMN dependent and mediated by LT produced possibly by a result of ROS production.

Rapid separation of creatine, phosphocreatine and adenosine metabolites by ion-pair reversed-phase high-performance liquid chromatography in plasma and cardiac tissue.

A rapid ion-pair reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous detection of creatine, phosphocreatine, hypoxanthine, inosine, adenosine, AMP, ADP, ATP, 8-azaguanine, 2-chloroadenosine, and 2'-O-methyladenosine. This method has proven useful for measuring changes in nucleotide concentrations in both heart tissue and plasma samples. Separation of the compounds of interest is achieved in less than 8 min with re-equilibration in 7 min, making the total run time 15 min. Separation is performed on a 3-microns Ultrasphere ODS column employing tetrabutylammonium phosphate as the ion-pair agent and dipotassium hydrogenphosphate as the counter ion. The accuracy, rapid separation, and re-equilibration time make this method particularly useful for the routine analysis of a large number of samples.

Ibuprofen reduces ethchlorvynol lung injury: possible role of blood flow distribution.

The role of cyclooxygenase products in acute lung injury was determined by pretreatment of dogs with ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only, lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with ibuprofen. The comparison of gravimetric and indicator-dilution measurements of edema fluid indicates that edema fluid could not be reliably detected after treatment with ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of edema, venous admixture was significantly less in the group treated with ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that ibuprofen inhibited cyclooxygenase activity without affecting lipoxygenase activity. These results suggest that in intact dogs ibuprofen has a protective effect on both pulmonary gas transfer and pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.

Hypercarbia during carbon dioxide pneumoperitoneum.

Patients with cardiopulmonary insufficiency undergoing laparoscopic surgery with carbon dioxide (CO2) pneumoperitoneum may retain CO2 resulting in clinically significant respiratory acidosis. A canine model of pulmonary emphysema induced by papain inhalation was utilized to evaluate the respiratory effects of both CO2 and helium pneumoperitoneum. Prior to papain inhalation and 5 and 8 weeks after initial treatment under general anesthesia, mechanical ventilation was adjusted to maintain the end-tidal CO2 (ETCO2) at 40 mm Hg during baseline and pneumoperitoneum physiologic monitoring periods. Utilizing an analysis of variance, hemodynamic and respiratory physiologic parameters were compared. In this canine model, all dogs demonstrated consistent hypercarbia during CO2 pneumoperitoneum prior to papain treatments, but CO2 retention was significantly increased in the emphysematous state. The occurrence of hypercarbia during CO2 pneumoperitoneum may be underestimated by ETCO2 monitoring as was revealed by an increased PaCO2 (arterial carbon dioxide pressure)-ETCO2 gradient with an increasing time interval between papain exposure and period of physiologic monitoring. Irrespective of the pulmonary condition of the dog, helium pneumoperitoneum did not produce any hypercarbic or acidic changes when compared with the concomitant baseline period of dogs prior to the induction of pneumoperitoneum, thus suggesting that helium pneumoperitoneum may be a reasonable alternative in patients at risk for CO2 retention.

Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF.

The objective of this study was to determine whether adenosine (ADO) prevents phorbol myristate acetate- (PMA) induced lung injury by modulating peptidoleukotrienes (LT) and/or tumor necrosis factor (TNF) production. PMA significantly increased pulmonary vascular resistance (PVR, 275 +/- 4 to 447 +/- 30 cmH2O.1-1.min) and microvascular filtration coefficient.(Kf, 0.024 +/- 0.002 to 0.040 +/- 0.006 g.min-1.cmH2O-1) in isolated blood-perfused rabbit lungs. ADO (5 mumol/min) blocked the increases in PVR (257 +/- 9 to 283 +/- 26) and Kf (0.028 +/- 0.005 to 0.018 +/- 0.002). After PMA (30 min), perfusate levels of LTC4 + LTD4 increased by 15.3 +/- 2.1 pg/ml; LTE4 increased by 15.1 +/- 4.1 pg/ml. ADO reduced the increase in LTC4 + LTD4 to 2.7 +/- 6.1 pg/ml, but total LT increased by 31.9 +/- 16.6 pg/ml, implying that ADO enhanced the conversion of LTC4 and LTD4 to LTE4. MK-886 (L663,536), an LT synthesis inhibitor, blocked the increase in total LT (6.1 +/- 13.9 pg/ml) but did not reduce the PMA-induced increase in Kf (0.022 +/- 0.003 to 0.035 +/- 0.005) or PVR (238 +/- 11 to 495 +/- 21). After PMA administration, perfusate TNF levels were not different from the 10-fold increase observed in control experiments and were not reduced by ADO or MK-886. TNF production was independent of perfusate blood components and presumably due to low levels of endotoxin in the perfusate (70-90 ng/ml). These results indicate that ADO does not protect against PMA-induced acute lung injury by altering circulating levels of LT or TNF.

Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy uses carbon dioxide, a highly diffusable gas, for insufflation. With extended periods of insufflation, patient arterial carbon dioxide levels may be adversely altered. Patients were selected for laparoscopic cholecystectomy using the same criteria as for open cholecystectomy. Twenty patients (group 1) had normal preoperative cardiopulmonary status (American Society of Anesthesiologists class I), while 10 patients (group 2) had previously diagnosed cardiac or pulmonary disease (class II or III). Demographic, hemodynamic, arterial blood gas, and ventilatory data were collected before peritoneal insufflation and at intervals during surgery. Patients with preoperative cardiopulmonary disease demonstrated significant increases in arterial carbon dioxide levels and decreases in pH during carbon dioxide insufflation compared with patients without underlying disease. Results of concurrent noninvasive methods of assessing changes in partial arterial pressures of carbon dioxide (end-tidal carbon dioxide measured with mass spectrographic techniques) may be misleading and misinterpreted because changes in partial arterial pressures of carbon dioxide are typically much smaller than changes in arterial blood levels and, unlike arterial gas measurements, do not indicate the true level of arterial hypercarbia. During laparoscopic cholecystectomy, patients with chronic cardiopulmonary disease may require careful intraoperative arterial blood gas monitoring of absorbed carbon dioxide.

Cytoplasmic oestrogen receptor replenishment: oestrogens versus anti-oestrogens.

The effect of the in vivo administration of various triphenylethylene antioestrogens and physiological (0.05 microgram) versus pharmacological (0.5--5 microgram) doses of oestradiol-17 beta (Oe2) on the uterotrophic process in general and the nuclear accumulation and cytoplasmic depletion and replenishment of uterine oestrogen receptor was determined. Regardless of the dose of Oe2 the changes in uterine wet weight, total protein and incorporation of [3H]thymidine into DNA and [14C]leucine into protein were the same at 24 h. The anti-oestrogen receptor was also studied. The net increase, above control, of cytoplasmic oestrogen receptor at 24 h and 48 h after Oe2 injection was approximately 0.35 and 0.77 pmoles/uterus, respectively. The effect of anti-oestrogens (U-11,100A, CI628, en- and zuclomiphene) on the increase in cytoplasmic oestrogen receptor at 24 h and 48 h measured from maximally depleted levels was nearly identical to the Oe2 induced net increase. This suggests that in both cases these particular increases represent newly synthesized receptor and that Oe2 causes some receptor replenishment through a recycling process.

Different nuclear binding sites for antiestrogen and estrogen receptor complexes.

Experiments were performed to determine the in vivo effect of various estrogens and anti-estrogens on the nuclear accumulation and retention of estrogen receptors, the cytoplasmic levels of estrogen receptors, and the formation of salt-resistant and salt-extractable forms of the nuclear estrogen receptor in immature rat uteri. A 5 mug injection of estradiol-17beta (E2) or diethylstilbestrol (DES) resulted in a maximal nuclear translocation of the receptor complexes by 1 h with a subsequent rapid decrease of both the estradiol receptor complex (ERC) and diethylstilbestrol receptor complex (DRC) to levels found in uteri of saline-injected rats by 12 h. However, the antiestrogens U-11,100A, zuclomiphene and enclomphene (100 mug/injection) resulted in a slower nuclear accumulation of receptor complex which continued to increase through 24 h. The cytosol receptor levels with E2 and DES were depleted to 10--20% of control levels within 1 h, but then were replenished so that they were above control levels by 24 h. The clomiphene-type compounds also showed an initial depletion of cytosol estrogen receptor, but the antiestrogens were almost ineffective in receptor replenishment. The estrogen receptor translocated to the nuclear fraction by estrogens demonstrated both salt-extractable (0.3M KCl) and salt-resistant forms at 1--6 h, whereas the clomiphene-type compounds resulted in the formation of only a salt-extractable form of the estrogen receptor at all times. By 12--24 h after injection, the salt-resistant forms of the ERC and DRC were no longer present. The effect of varying the dosage of injected E2 (0.05 mug-5 mug) resulted in the formation of an identical amount of salt-resistant ERC at 1--2 h, whereas the total amount of nuclear ERC (salt-resistant and salt-extractable) varied with the injected dose of E2. However, at 6 h, the amount of salt resistant ERC varied with the injected dose of E2 (0.005-5 mug). These results suggest that the nuclear salt-resistant form (formed by estrogens only) of the estrogen receptor is required for true uterine growth, whereas the nuclear salt-extractable form may be only sufficient for short term estrogenic responses.

Antiestrogen action: differential nuclear retention and extractability of the estrogen receptor.

Since there is a much longer uterine nuclear retention of the U-11, 100A (antiestrogen) receptor complex (UARC) than of the estradiol receptor complex (ERC) at 4-12 hrs after injection, experiments were designed to determine if there is a difference between the relative nuclear affinities for the two RCs as determined by extraction with various ionic strength mediums. Although the UARC was retained longer in the nuclear fraction in vivo, the UARC was completely extractable with 0.3M KCl or 50mM spermine, whereas the ERC demonstrates a salt-resistant form. This suggests that the ERC is more tightly bound to nuclear components through this salt-resistant form of the receptor. In addition, various intercalating agents were used to distinguish the different nuclear chromatin DNA sites where the UARC and ERC may be binding. With actinomycin D (50 uM) more ERC than UARC was retained in the nuclear fraction. However, with ethidium bromide (100uM) less ERC than UARC was retained. Also, the ERC selectively released by ethidium bromide is precisely that fraction not released by salt. These results indicate that the UARC and ERC bind to different chromatin loci.