Diaphragmatic Stripping Research Articles

Tissue contribution to the mechanical features of diaphragmatic initial lymphatics

The role of the mechanical properties of the initial lymphatic wall and of the surrounding tissue in supporting lymph formation and/or progression was studied in six anaesthetized, neuromuscularly blocked and mechanically ventilated rats. After mid-sternal thoracotomy, submesothelial initial lymphatics were identified on the pleural diaphragmatic surface through stereomicroscopy. An 'in vivo' lymphatic segment was prepared by securing two surgical threads around the vessel at a distance of ∼2.5 mm leaving the vessel in place. Two glass micropipettes were inserted into the lumen, one for intraluminar injections of 4.6 nl saline boluses and one for hydraulic pressure (Plymph) recording. The compliance of the vessel wall (Clymph) was calculated as the slope of the plot describing the change in segment volume as a function of the post-injection Plymph changes. Two superficial lymphatic vessel populations with a significantly different Clymph (6.7 ± 1.6 and 1.5 ± 0.4 nl mmHg−1 (mean ± S.E.M.), P < 0.001) were identified. In seven additional rats, the average elastic modulus of diaphragmatic tissue strips was determined by uniaxial tension tests to be 1.7 ± 0.3 MPa. Clymph calculated for an initial lymphatic completely surrounded by isotropic tissue was 0.068 nl mmHg−1, i.e. two orders of magnitude lower than in submesothelial lymphatics. Modelling of stress distribution in the lymphatic wall suggests that compliant vessels may act as reservoirs accommodating large absorbed fluid volumes, while lymphatics with stiffer walls serve to propel fluid through the lumen of the lymphatic vessel by taking advantage of the more efficient mechanical transmission of tissue stresses to the lymphatic lumen.

Upregulation of PPARβ/δ Is Associated with Structural and Functional Changes in the Type I Diabetes Rat Diaphragm

BackgroundDiabetes mellitus is associated with alterations in peripheral striated muscles and cardiomyopathy. We examined diaphragmatic function and fiber composition and identified the role of peroxisome proliferator-activated receptors (PPAR α and β/δ) as a factor involved in diaphragm muscle plasticity in response to type I diabetes.Methodology/Principal FindingsStreptozotocin-treated rats were studied after 8 weeks and compared with their controls. Diaphragmatic strips were stimulated in vitro and mechanical and energetic variables were measured, cross bridge kinetics assessed, and the effects of fatigue and hypoxia evaluated. Morphometry, myosin heavy chain isoforms, PPAR α and β/δ gene and protein expression were also assessed. Diabetes induced a decrease in maximum velocity of shortening (−14%, P<0.05) associated with a decrease in myosin ATPase activity (−49%, P<0.05), and an increase in force (+20%, P<0.05) associated with an increase in the number of cross bridges (+14%, P<0.05). These modifications were in agreement with a shift towards slow myosin heavy chain fibers and were associated with an upregulation of PPARβ/δ (+314% increase in gene and +190% increase in protein expression, P<0.05). In addition, greater resistances to fatigue and hypoxia were observed in diabetic rats.Conclusions/SignificanceType I diabetes induced complex mechanical and energetic changes in the rat diaphragm and was associated with an up-regulation of PPARβ/δ that could improve resistance to fatigue and hypoxia and favour the shift towards slow myosin heavy chain isoforms.

Classification et morbidités des chirurgies de résection dans les cancers de l’ovaire

Postoperative residual disease is a major predicting factor in the treatment of advanced ovarian cancer. The goal of the surgery is now well known. It is to eradicate all macroscopic tumor. So, the most useful way to describe the residual disease is to measure exactly the size of the tumor left after surgery (no gross residual, gross residual <5mm, gross residual <10mm and gross residual >10mm) and to avoid the usual classification (optimal and suboptimal). The goal of no gross residual disease after surgery involves more often extended surgical efforts particulary upper abdominal surgery (diaphragm stripping, splenectomy, etc.). Radical procedures without any macroscopic residual disease have been shown to be safe and potentially beneficial to patients.

In vitro muscle contraction force measurements on isolated and entire rat diaphragms

Inactivity of the diaphragmatic muscles during mechanical ventilation leads to atrophy and contractile dysfunction. Up to now, in vitro force measurements were performed only on single diaphragmatic muscle strips. Our intention was to find out how mechanical and electrical stimulation influences the condition of the diaphragm as a whole organ. To determine the status of the diaphragm, muscle contraction forces were measured on entire rat diaphragms.

Role of Diaphragmatic Surgery in 69 Patients With Ovarian Carcinoma

Diaphragmatic stripping or coagulation is a technique aiming to optimally cytoreduce ovarian cancer. We investigated the complications, the overall survival, and the relapse rate following this procedure. Records of 69 patients with diaphragmatic involvement who underwent debulking surgery between September 1993 and December 2001 were reviewed. A total of 69 patients underwent diaphragmatic surgery as part of cytoreductive surgery for epithelial ovarian cancer. In 17 cases, the diaphragmatic tumors were stripped from the muscle, in 22 cases coagulated, and in 30 cases stripped and coagulated. Postoperative complications were pleural effusion (41 cases, 3 needed a chest drain, 7 needed a pleural puncture, 1 needed both) and pneumothorax (4 cases, 1 needed a chest drain). In one case of bilateral pleural effusion, the patient developed pneumonia. In one case of pleural effusion on the right side, the patient needed a pleural puncture and developed a partial atelectasis of the middle lobe of the right lung. The median overall survival was 66 months in the stripping group compared with 49 months in the coagulation group. In 56 cases (81%), the patient developed a relapse, and the first site of relapse was the diaphragm in 11 cases (20%). We conclude that diaphragmatic resection is an important part of optimal debulking surgery with an acceptable morbidity.

Pilot Study on Transdiaphragmatic Thoracoscopic-Assisted Pleural Biopsy and Intrathoracic Washing Cytology for Stage IIIc Ovarian Cancer With Diaphragmatic Metastases

The significance of investigations of thoracic cavities as well as pleural biopsy and intrathoracic washing cytology through transdiaphragmatic thoracoscopy for stage IIIc ovarian cancer with diaphragmatic metastases was assessed as a prospective pilot study. Eligibility criteria were established to include patients with stage IIIc ovarian cancer in whom pleural effusions were not detected preoperationally, but prominent diaphragmatic metastases were observed when the abdomen was opened and those who submitted consent. Transdiaphragmatic thoracoscopy was performed after diaphragm stripping. Then, biopsy of the lesion suspected to be disseminated or the plural membrane of the thoracic opening was performed followed by washing cytology using physiological saline. Ten subjects were enrolled. Disseminated lesions were observed on plural membranes, and positive results were obtained in biopsy and washing cytology in 3 subjects. In addition, positive results were seen with biopsy alone in 2 subjects and with washing cytology alone in 2 subjects. Hence, a total of 7 subjects (70.0%) were up-staged to the level of stage IV. Postoperational complications were not observed in any of these cases. It was suggested that stage IIIc ovarian cancer with prominent diaphragmatic metastasis may advance to the level of stage IV from a clinical point of view even if carcinomatous pleural effusions are not detected pre-operationally. Therefore, it is thought that this operational method is useful in the management of progressive ovarian cancer.

Spontaneous rectovaginal fistula during bevacizumab therapy for ovarian cancer: a case report

Recent studies have demonstrated efficacy of bevacizumab for recurrent ovarian cancer, but few data on its use and gastrointestinal potential complications when administered as adjuvant chemotherapy after cytoreductive surgery are available. In this study, we report the first case of a rectovaginal fistula in this indication.

Role of diaphragmatic surgery in 69 patients with ovarian carcinoma

Diaphragmatic stripping or coagulation is a technique aiming to optimally cytoreduce ovarian cancer. We investigated the complications, the overall survival, and the relapse rate following this procedure. Records of 69 patients with diaphragmatic involvement who underwent debulking surgery between September 1993 and December 2001 were reviewed. A total of 69 patients underwent diaphragmatic surgery as part of cytoreductive surgery for epithelial ovarian cancer. In 17 cases, the diaphragmatic tumors were stripped from the muscle, in 22 cases coagulated, and in 30 cases stripped and coagulated. Postoperative complications were pleural effusion (41 cases, 3 needed a chest drain, 7 needed a pleural puncture, 1 needed both) and pneumothorax (4 cases, 1 needed a chest drain). In one case of bilateral pleural effusion, the patient developed pneumonia. In one case of pleural effusion on the right side, the patient needed a pleural puncture and developed a partial atelectasis of the middle lobe of the right lung. The median overall survival was 66 months in the stripping group compared with 49 months in the coagulation group. In 56 cases (81%), the patient developed a relapse, and the first site of relapse was the diaphragm in 11 cases (20%). We conclude that diaphragmatic resection is an important part of optimal debulking surgery with an acceptable morbidity.

Morbidity and survival of 32 recurrent ovarian cancer patients treated with aggressive cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion

16078 Background: Cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion (CS/IPHC) has shown increased survival for patients with recurrent and persistent GI malignancies with peritoneal dissemination. We present our preliminary experience with CS/IPHC as palliative therapy for recurrent ovarian cancer treated at a single institution. Methods: A retrospective review of CS/IPHC for women with recurrent or persistent epithelial ovarian carcinoma previously treated with platinum/taxane chemotherapy at a single institution from 2002–2006 was performed. Each patient had an attempted optimal surgical debulking (volume of residual disease &lt;1 cm) prior to chemoperfusion. IPHC was performed on all patients for 100 minutes at temperatures between 40–42°C with either mitomycin C (40 mg/m2) or cisplatin (100 mg/m2). Post-surgical complications were evaluated. End points analyzed included morbidity, progression free survival, and over all survival. Results: Thirty-two patients were identified, with optimal cytoreductive surgery obtained in 26 (81.3%). Procedures required for cytoreduction included omentectomy (n=16), splenectomy (n=14), colonic resection (n=14), small bowel resection (n=13), ileostomy (n=9), hepatic resection (n=5), partial gastrectomy (n=5), and diaphragmatic stripping (n=3). Over-all morbidity was 65.6%, with major morbidity of 9.4%. There were three mortalities within sixty days of operation. Common morbidities included neutropenia (n=5), ileus (n=5), pleural effusions (n=4), and sepsis (n=4). Median length of stay was 11 days (6 to 47). Nineteen patients had a documented recurrence with a median progression free survival of 8 months (1 to 22). Median survival was 13 months (1 to 54) for these patients with recurrent end stage ovarian cancer. Conclusions: CS/IPHC is associated with high morbidity, but acceptable mortality. In a subset of patients, survival is improved compared to historical controls for recurrent ovarian cancer. A randomized phase II study is planned based on this data. No significant financial relationships to disclose.

Splenectomy in the context of primary cytoreductive operations for advanced epithelial ovarian cancer

Objective. To determine if the need to perform splenectomy due to metastatic disease in the context of complete primary cytoreduction for ovarian cancer diminishes the prognosis for survival. Methods. Between 1990 and 2004, 356 stage IIIC epithelial ovarian cancer patients underwent resection of all visible disease before systemic platinum-based combination chemotherapy. Forty-nine (13.8%) required a splenectomy due to metastatic disease. Survival was analyzed (log rank) on the basis of whether splenectomy was necessary. The frequency of performing other procedures, operative time, blood loss, transfusion rate, and hospitalization, was compared (Chi-square test; discrete and binomial data, t test; continuous data) on the basis of whether a splenectomy was required. Results. Survival was not influenced (log rank) by the requirement of splenectomy (required; median 56.4 months, estimated 5-year survival of 48% vs. not required; median 76.8 months, estimated 5-year survival of 58% P = 0.4). The splenectomy subgroup more commonly required en-bloc resection of reproductive organs with rectosigmoid (89.8% vs. 55.7%, P < 0.001), diaphragm stripping (63.3% vs. 33.6%, < 0.001)), full-thickness diaphragm resection (28.6% vs. 9.4%, P < 0.001), and resection of grossly positive retroperitoneal nodes (67.3% vs. 46.3%, P = 0.006). The splenectomy group had a longer operative time (238 min vs. 192 min, P = 0.004), estimated blood loss (1663 ml vs. 1167 ml, P = 0.001), transfusion rate (5.3 units prbc vs. 3.2 units prbc, P = 0.002), and hospitalization (16.1 vs. 12.2 days P = 0.001). Conclusions. The need for splenectomy to achieve complete cytoreduction is a reflection of advanced disease but is not a manifestation of tumor biology precluding long-term survival.

Surgery for Ovarian Cancer: Rationale and Guidelines

Ovarian cancer is the second most common gynecologic cancer in women and the leading cause of death caused by gynecologic malignancy. Surgery plays a fundamental role in treating this challenging disease. Goals of primary surgery for ovarian cancer are to establish diagnosis, proper staging, determination of prognosis, and optimal cytoreduction of gross disease before chemotherapy for improved outcome. In addition to standard removal of the ovaries, uterus, omentum, and pelvic and para-aortic lymph nodes for early disease, extended surgical techniques used to debulk advanced disease include bowel resection, splenectomy, partial liver resection, peritoneal or diaphragmatic stripping, and use of laser or ultrasound (CUSA). Secondary surgery is used in a variety of situations. Second-look procedures were performed historically to determine response to chemotherapy to delineate duration of treatment, but now are best used in a research setting with the advent of improved chemotherapeutic agents. As a high percentage of patients have a gynecologic malignancy recurrence after primary treatment, many practitioners perform secondary cytoreductive procedures for recurrent disease. Additionally, in the recurrent setting, surgery may be necessary for relief of bowel obstruction and palliation of symptoms. Surgical management of ovarian cancer must be performed by surgeons, such as gynecologic oncologists, who have a firm understanding of the disease process, display good clinical judgment, and are adequately trained to perform the complex surgery that commonly is required for appropriate care.

Procedures Required to Accomplish Complete Cytoreduction of Ovarian Cancer: Is There a Correlation with “Biological Aggressiveness” and Survival?

Objective. The aim of this study was to determine if the necessity of using specific procedures to attain complete cytoreduction in ovarian cancer correlates with innate biologic aggressiveness and independently influences survival.Methods. Between 1990 and 2000, 213 patients with Stage IIIC epithelial ovarian cancer underwent complete cytoreduction before initiation of systemic platinum-based combination chemotherapy. Survival was stratified and analyzed (log rank and Cox regression) on the basis of whether extrapelvic bowel resection, diaphragm stripping, full-thickness diaphragm resection, modified posterior pelvic exenteration, peritoneal implant ablation and/or aspiration, and excision of grossly involved retroperitoneal lymph nodes were necessary to attain a visibly disease-free cytoreductive outcome.Results. The median and estimated 5-year survival for the cohort were 75.8 months and 54%, respectively. Survival was influenced (log rank) by the requirement of diaphragm stripping (required, median 42 months vs not required, median 79 months; P = 0.03) and the extent of mesenteric and serosal implants that required removal (none, median not reached, vs 1–50 implants, median not reached, vs >50 implants, median 40 months; P = 0.002). Survival was independently influenced (Cox regression) only by the extent of peritoneal metastatic implants that required removal (P = 0.01). The other investigated procedures and type of chemotherapy used did not influence survival.Conclusions. The need to remove a large number of peritoneal implants correlates with biological aggressiveness and diminished survival, but not significantly enough to preclude long-term survival or justify abbreviation of the operative effort. The need to use the other investigated procedures had minimal or no observed influence on survival.

Reversal of impaired calcium homeostasis in the rat diaphragm subjected to Monocrotaline–induced pulmonary hypertension

Monocrotaline (MCT) pneumotoxicity is known to alter the structure of pulmonary vascular wall and impairs endothelial cell function resulting in pulmonary hypertension. Its effect on the diaphragm muscle has not yet been elucidated. This study examines the effect of MCT pneumotoxicity on calcium transport in the rat diaphragm. Pulmonary hypertension induced by MCT pneumotoxicity caused a significant increase ( P<0.001) in calcium accumulation in strips isolated from rat diaphragms. Treatment of rats having received MCT with Indapamide reduced calcium uptake by diaphragmatic strips to levels that are not significantly different from the control ( P>0.05). Treatment with Indapamide alone did not elicit any change in calcium accumulation in the diaphragmatic strips. Treatment of the animals with MCT, Indapamide or both did not produce any significant change ( P>0.05) in the cell volume of the diaphragmatic strips. Pulmonary hypertension increased calcium uptake by the muscle cells in the rat diaphragm which may alter diaphragmatic contractility; an effect that was prevented by Indapamide.

In Vivo Fatiguing Contraction of Rat Diaphragm Produces Hydroxyl Radicals

It is suggested that free radical generation is a cause of muscle fatigue from in vitro studies. We examined whether hydroxyl radical would be generated in an in vivo fatiguing contraction of the diaphragm. Diaphragmatic fatigue was induced in rats by the in vivo rhythmic electrical stimulation of the diaphragm under mechanical ventilation for 30 min. The force-frequency relationship of a diaphragmatic muscle strip was assessed, and the production of hydroxyl radical in muscle strip was evaluated by measuring the metabolites of a reaction of salicylate with hydroxyl radical (2,3- and 2,5-dihydroxybenzoate [DHBA]). After fatiguing contraction, the contractile force of the diaphragm was decreased by approximately 58% at all stimulating frequencies (P < 0.01). There was more 2,3-DHBA in the fatigued muscles compared with the control muscles (219 ± 22 ng/g tissue versus 109 ± 17, respectively, P < 0.01) and 2,5-DHBA (198 ± 23 ng/g tissue versus 84 ± 14, respectively, P < 0.01). There was a significant relationship between contractile force and the sum of 2,3- and 2,5-DHBA (r = −0.71, P < 0.01). These results suggest that the development of fatigue in the diaphragm is related to the generation of hydroxyl radical. Copyright © 1996 Elsevier Science Inc.

Oxidative stress in clinical situations - fact or fiction?

Oxidative stress in clinical situations - fact or fiction?

Failure of vasodilator administration to increase blood flow to the fatiguing diaphragm.

Recent studies have suggested that coronary and limb muscle vessels do not maximally vasodilate under conditions in which cardiac and limb muscle contractile function is dependent on the level of blood flow but, rather, maintain a "vasodilator reserve." If a vasodilator reserve is also present in the fatiguing diaphragm, it may be possible to augment flow to this muscle with vasodilator administration, improving muscle function. The purpose of the present study was therefore to examine the effect of administration of a potent vasodilator, nitroprusside, on the blood flow and contractile function of the fatiguing diaphragm. Studies were performed using an in situ canine diaphragmatic strip preparation that permitted direct measurement of force and blood flow; cardiac output was monitored with a thermodilution catheter. The effects of nitroprusside were examined with the diaphragm rhythmically contracting in response to both subfatiguing and fatiguing stimulation paradigms. For both contraction paradigms, nitroprusside infusions elicited appreciable increases in cardiac output. Nitroprusside infusions also produced significant increases in diaphragmatic blood flow during subfatiguing diaphragmatic contractions but had no effect on flow during fatiguing contractions. Nitroprusside also had no effect on the rate of diaphragmatic fatigue. These data suggest that, under the conditions examined, the diaphragm exhausts its vasodilator reserve during the development of fatigue and vasodilator administration has no appreciable effect on diaphragm blood flow and function. Moreover, although vasodilator drugs with actions similar to nitroprusside are used clinically to augment flow to vital organs, our data would indicate that these drugs have no functionally significant effect on blood flow to the fatiguing diaphragm.

Force-frequency relationships of in vivo human and in vitro rat diaphragm using paired stimuli

Supramaximal stimuli, with time intervals of 100 ms (10 Hz) to 10 ms (100 Hz), were delivered in pairs to the phrenic nerves, bilaterally, in five seated normal subjects, while transdiaphragmatic pressure swings (Pdi,s) were recorded at relaxed end-expiratory lung volume with airways closed. In fresh diaphragms, Pdi,s increased between 10-20 Hz and reached a plateau between 20-30 Hz. Diaphragmatic fatigue decreased Pdi,s at all frequencies. Pdi,s was assumed to be the sum of two successive responses (T1+T2), T1 being constant at any frequency and equal to a single twitch, T2 being obtained by subtraction. We found that T2 amplitude, which was significantly reduced after fatigue, was fully returned to normal after 15 min rest at high, not at low, stimulation frequencies. The ratio of T2 at 10 Hz over 100 Hz (T2(10/100)) thus decreased from 1.33 +/- 0.05 before fatigue to 0.97 +/- 0.12 after fatigue, and to 0.81 +/- 0.06 after 15 min rest. Similar results were obtained in isolated rat diaphragmatic strips stimulated and fatigued in vitro, from which we found a highly linear relationship (r = 0.94, p < 0.001) between the ratio of T2(10/100) and that of tetanic force at 10 Hz over 100 Hz (P10/100). We conclude that phrenic nerve paired twitches provide similar information when obtained from phrenic tetanic stimulation in terms of diaphragmatic contractility, and the decrease in T2(10/100) ratio indicates diaphragm low frequency fatigue.

Effects produced by infusion of a free radical-generating solution into the diaphragm.

Although studies have examined the susceptibility and pattern of injury induced by infusion of free radical-generating solutions into a number of vital organs, no such investigation has been performed for the diaphragm. The purpose of the present study was to examine the susceptibility of the diaphragm to damage by a free radical-generating solution (iron-ADP complexes). Studies were performed using an in situ canine diaphragmatic strip preparation in which the phrenic artery supplying the strip was cannulated and perfused with blood from the ipsilateral femoral artery. Four groups of studies were performed: (1) a group in which saline was infused into the arterial supply of the diaphragm for 15 min; (2) a group in which a solution of iron-ADP was infused; (3) a group in which both iron-ADP and superoxide dismutase (SOD), a free radical scavenger, were infused; and (4) a group given iron-ADP and denatured SOD. Strip tension and blood flow were monitored during electrically induced diaphragmatic contractions for 15 min before intraphrenic infusions, during the period of infusions, and for 90 min after cessation of infusions. We found that diaphragm tension did not change over time in saline-treated control animals but fell significantly in animals in which iron-ADP was infused. The effects of iron-ADP were largely prevented by concomitant administration of active SOD, but not by denatured SOD. On average, at 90 min after cessation of infusions, tension had fallen to 82 +/- 6, 41 +/- 8, 63 +/- 4, and 28 +/- 9% of its initial value in saline, iron-ADP, iron-ADP/SOD, and iron-ADP/denatured SOD groups, respectively (p < 0.001 for comparison of the four groups, with saline and iron-ADP/SOD groups different from the other two groups). Diaphragm blood flow did not change significantly in any group. These data suggest that free radical-mediated diaphragmatic injury can result in a marked reduction in diaphragm contractility.

Role of extracellular Ca2+ in diaphragmatic contraction: effects of ouabain, monensin, and ryanodine.

The effects of zero extracellular Ca2+ on the contractility of rat diaphragmatic strips in vitro were studied in conjunction with various pharmacological agents known to influence the intracellular Ca2+ concentration: the Na+ ionophore, monensin, and the Na(+)-K+ pump inhibitor, ouabain, which enhance [Ca2+]i, caffeine, which induces Ca2+ release from the sarcoplasmic reticulum (SR), and ryanodine, which prevents Ca2+ retention by the SR. The effect of increasing [Ca2+]i on diaphragmatic contraction was assessed by comparing contractions induced by 120 mM K+ in the small muscle strips before and after the addition of ouabain or monensin. Monensin (20 microM) and ouabain (1-100 microM) augmented contractions up to threefold. Treatment of diaphragm strips with 3 nM ryanodine increased baseline tension 360% above the original resting tension but only if the diaphragm was electrically stimulated concurrently; 100 microM ryanodine induced contracture in quiescent tissue. High K+ contractures were of greater magnitude in the presence of ryanodine compared with control, and relaxation time was prolonged by greater than 200%. Ca(2+)-free conditions ameliorated these actions of ryanodine. Ryanodine reduced contractions induced by 10 mM caffeine and nearly abolished them in Ca(2+)-free solution. The data demonstrate that extracellular Ca2+ is important in certain types of contractile responses of the diaphragm and suggest that the processes necessary to utilize extracellular Ca2+ are present in the diaphragm.

Effects of Steroids on Diaphragmatic Function in Rats

The present study was undertaken to determine the effects of 8 days of corticosteroid administration on diaphragmatic atrophy and contractile properties. One hundred sixty rats were divided into a pair-fed (PF) group (n = 80) and a steroid-treated (ST) group (n = 80). The treated rats received a single injection of Kenacort 80 retard (0.1 mg/kg intramuscularly). The experimental period was 8 days. Steroid treatment resulted in a 30% decrease in body weight in the ST group when compared with the PF group. Diaphragmatic mass in the ST group decreased in proportion to body weight (30%) as did the weight of the extensor digitorum longus (EDL). The soleus muscle was unaffected. The diaphragmatic atrophy was associated with a significant decrease (p less than 0.001) in normalized tetanic force as assessed both in vivo and in vitro. Diaphragmatic strength was determined in vivo by measuring transdiaphragmatic pressure (Pdi) during bilateral electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 1000 Hz). The force-frequency relationship was also studied in vitro using direct stimulation of costal diaphragmatic strips. In both preparations, twitch and low-frequency force were unaffected, whereas normalized tetanic force in the ST group was markedly reduced compared with that in the PF group (p less than 0.001). Soleus and EDL muscles were also studied in vitro. Although steroid treatment had no effect on the soleus, in the EDL, a slight (11%) decrease in normalized tetanic tension was observed.(ABSTRACT TRUNCATED AT 250 WORDS)