Development of pulmonary hypertension after lung volume reduction surgery

This prospective, longitudinal study was designed to assess the hemodynamic changes occurring in patients who undergo lung volume reduction surgery (LVRS). Patients with emphysema treated with LVRS underwent hemodynamic evaluation before and after surgery. The study group consisted of nine patients with an average age of 64.4 yr. FEV1 rose significantly from 0.64 preoperatively to 0.99 L postoperatively. After surgery, pulmonary artery (PA) systolic pressure rose to 47.9 +/- 12.4 mm Hg, meeting criteria for development of pulmonary hypertension. In six patients, the elevation in PA pressure was attributed to an increase in the pulmonary vascular resistance, but for all nine patients the change was not statistically significant. The pulmonary artery occulsion pressure (PAOP) did not change postoperatively. There was no correlation of PAOP with global left ventricular ejection fraction. While preoperatively there was a negative correlation between symptoms (Mahler dyspnea index) and PA pressure, after surgery the change in PA pressures did not correlate with the change in symptoms (Mahler transitional dyspnea index). We concluded that development of pulmonary hypertension may occur after LVRS in patients whose symptomatic status improves and in whom this condition was not present preoperatively.     

Effect of prolonged heavy exercise on pulmonary gas exchange in horses

During short-term maximal exercise, horses have impaired pulmonary gas exchange, manifested by diffusion limitation and arterial hypoxemia, without marked ventilation-perfusion (VA/Q) inequality. Whether gas exchange deteriorates progressively during prolonged submaximal exercise has not been investigated. Six thoroughbred horses performed treadmill exercise at approximately 60% of maximal oxygen uptake until exhaustion (28-39 min). Multiple inert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained at rest and 5-min intervals during exercise. Oxygen uptake, cardiac output, and alveolar-arterial PO2 gradient were unchanged after the first 5 min of exercise. Alveolar ventilation increased progressively during exercise, from increased tidal volume and respiratory frequency, resulting in an increase in arterial PO2 and decrease in arterial PCO2. At rest there was minimal VA/Q inequality, log SD of the perfusion distribution (log SDQ) = 0.20. This doubled by 5 min of exercise (log SDQ = 0.40) but did not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintain excellent pulmonary gas exchange during exhaustive, submaximal exercise. Although VA/Q inequality is greater than at rest, it is less than observed in most mammals and the effect on gas exchange is minimal.     

Effects of prior arm exercise on pulmonary gas exchange kinetics during high-intensity leg exercise in humans

The activation of MAPKs is controlled by the balance between MAPK kinase and MAPK phosphatase activities. The latter is mediated by a subset of phosphatases with dual specificity (VH-1 family). Here, we describe a new member of this family encoded by the puckered gene of Drosophila. Mutations in this gene lead to cytoskeletal defects that result in a failure in dorsal closure related to those associated with mutations in basket, the Drosophila JNK homolog. We show that puckered mutations result in the hyperactivation of DJNK, and that overexpression of puc mimics basket mutant phenotypes. We also show that puckered expression is itself a consequence of the activity of the JNK pathway and that during dorsal closure, JNK signaling has a dual role: to activate an effector, encoded by decapentaplegic, and an element of negative feedback regulation encoded by puckered.     

Plasma volume expansion with oral fluids in hypohydrated men at rest and during exercise

A case of malignant fibrous histiocytoma (MFH) in a 29-year-old man was reported. CT scans revealed an iso density mass which was homogeneously enhanced by contrast medium. MRI demonstrated that the right frontal tumor showed slight low signal intensity in T1-weighted image, and iso signal intensity in T2-weighted image. Gadolinium-enhanced T1-weighted image showed a homogeneously enhanced multinodular tumor. Right carotid angiogram revealed a tumor stain fed by the precentral artery. On operation, en-bloc resection was performed successfully. Postoperatively, local irradiation of 60Gy was performed. Microscopically, fibroblast-like cells arranged in storiform pattern were observed, and bizarre multinucleated giant cells were also observed. Ki-67 labelling index was 54%. We considered the tumor was a MFH and arose from an intracerebral mesenchymal tissue. We reviewed some literature and briefly discussed clinicopathological features and therapy of intracranial MFH.     

Incidental lung carcinoma detected at CT in patients selected for lung volume reduction surgery to treat severe pulmonary emphysema

OBJECTIVE: Ovarian vein thrombosis (OVT) is a pathologic entity classically considered a postpartum complication and only rarely associated with other disease processes. Before modern imaging methods, diagnosis was primarily made clinically or at exploratory surgery. Our objective was to show that with CT and sonographic imaging, OVT can be detected in atypical clinical situations and that the condition may also be occult. CONCLUSION: Only two of six cases at our institution fit the classic picture of postpartum infection complicated by OVT. The other four cases occurred in conjunction with other pathologic conditions, one of which has not to our knowledge been previously associated with OVT. The diagnosis was not clinically suspected in these four cases. On CT and sonography, OVT was detected incidentally, because clinical symptoms were atypical or absent. Such atypical presentations of OVT pose a clinical dilemma as to appropriate management.     

Video-assisted thoracic surgery for lung volume reduction surgery

Lung volume reduction surgery by video thoracoscopy can result in significant improvement in quality of life and pulmonary function for selected patients suffering from severe emphysema. Clinical trials comparing the use of lasers versus staples, unilateral versus bilateral procedures, and video surgery versus mediansternotomy are summarized. Patient selection and patient care issues are addressed. Information gathered from the selection, evaluation, and study of almost 500 patients treated surgically for emphysema at a single institution is summarized.     

Exercise performance and gas exchange after bilateral video-assisted thoracoscopic lung volume reduction for severe emphysema

BACKGROUND AND PURPOSE: Arm function recovery is notoriously poor in stroke patients. The effect of treatment modalities, particularly those directed at improving upper limb function, has been studied primarily in chronic stroke patients. The purpose of this study was to investigate the effect of a specific therapeutic intervention on arm function in the acute phase after stroke. METHODS: In a single-blind, randomized, controlled multicenter trial, 100 consecutive patients were allocated to either an experimental group that received an additional treatment of sensorimotor stimulation or to a control group. The intervention was applied for 6 weeks. Patients were evaluated for level of impairment (Brunnstr?m-Fugl-Meyer test) and disability (Action Research Arm test, Barthel Index) before, midway, and after the intervention period and at follow-up 6 and 12 months after stroke. RESULTS: Patients in the experimental group performed better on the Brunnstr?m-Fugl-Meyer test than those in the control group throughout the study period, but differences were significant only at follow-up. Results on the Action Research Arm test and Barthel Index revealed no effect at the level of disability. The effect of the therapy was attributed to the repetitive stimulation of muscle activity. The treatment was most effective in patients with a severe motor deficit and hemianopia or hemi-inattention. No adverse effects due to the intervention were found. CONCLUSIONS: Adding a specific intervention during the acute phase after stroke improved motor recovery, which was apparent 1 year later. These results emphasize the potential beneficial effect of therapeutic interventions for the arm.     

Effect of pulmonary hypertension on gas exchange

This paper reviews the effects of pulmonary artery hypertension on gas exchange by exploring three different issues, namely: 1) how does gas exchange behave in diseases characterized by increased vascular tone (primary pulmonary hypertension (PPH), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF)) or decreased vascular tone ("hepatopulmonary syndrome"); 2) how does exercise, as a non-pharmacological tool of increasing pulmonary blood flow, modify gas exchange in these diseases; and 3) how do several drugs that lower (vasodilators) or increase (almitrine) the active component of pulmonary hypertension interact with gas exchange. Available data show that: 1) in PPH a high pulmonary vascular tone enhances gas exchange and when it is lowered, either by oxygen or vasodilators, ventilation perfusion (VA/Q) distributions deteriorate; 2) in COPD a lowered (vasodilators) or augmented (almitrine) active vascular tone is almost invariably paralleled by a deterioration or enhancement of ventilation-perfusion matching, respectively; 3) in IPF an adequate active response of the pulmonary vasculature is essential to maintain gas exchange, both at rest and during exercise; and 4) in patients with liver cirrhosis a low pulmonary vascular tone induces an abnormal VA/Q distribution. In summary, these data show that any situation and/or therapeutic intervention that lowers the active vascular tone deteriorates VA/Q relationships and vice versa. The final effect of pulmonary vascular tone on arterial oxygen tension (PaO2) is less predictable. The reason for this uncertainty is that the actual PaO2 value depends on the interplay of the intra- and extrapulmonary factors that control gas exchange in humans, and not only on the degree of VA/Q mismatching.     

Effect of a new calcium antagonist on hemodynamics at rest and exercise loading in patients with essential hypertension

MPC-1304 ((+-)-methyl 2-oxopropyl 1,4-dihydro 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 86780-90-7), a new calcium antagonist, was orally administered to 10 outpatients with mild essential hypertension. It was observed that MPC-1304 inhibited elevations of blood pressure both at rest and under exercise loading without any adverse hemodynamic effects. The findings obtained indicated that MPC-1304 would be clinically useful in the treatment of hypertensive patients undergoing therapy while continuing normal everyday activities including physical exertion.     

The impact of prostanoids on pulmonary gas exchange during abdominal surgery with mesenteric traction

We investigated the effect of intravenous (iv) ibuprofen on prostanoid release and on pulmonary gas exchange after abdominal mesenteric traction (MT) during either abdominal aortic surgery or pancreas resection. In a prospective, randomized, double-blind study, 400 mg ibuprofen (pancreas n = 13, aorta n = 13) or a placebo (pancreas n = 13, aorta n = 13) was administered iv before skin incision. MT was applied uniformly. The prostanoid plasma concentrations, venous admixture (Q(va)/Q(t)), and PaO2/FIO2 ratio were determined at baseline (before MT) and 5, 15, 45, and 90 min after MT. Patients who underwent aortic surgery were older and exhibited a lower preoperative PaO2 than those who underwent pancreas resection. Placebo-treated patients revealed a 30-fold peak increase in 6-keto-prostaglandin F1alpha (stable metabolite of prostacyclin) levels after intentional MT during aortic as well as pancreatic operations. This response was accompanied by an increase in Q(va)/Q(t) (ibuprofen: pancreas 7% +/- 1%, aorta 14% +/- 2%; placebo: pancreas 16% +/- 3%, aorta 26% +/- 3%/15 min after MT [mean +/- SEM, P < 0.05, placebo vs ibuprofen]), which resulted in decreased PaO2/ FIO2 ratio only in the aortic surgery patients (ibuprofen: 310 +/- 19; placebo: 237 +/- 24 15 min after MT, [mean +/- SEM, P < 0.05]). The authors conclude that ibuprofen-pretreated patients demonstrated almost constant prostanoid levels without changes in pulmonary gas exchange after MT.     

Cardiac output and pulmonary gas exchange at maximal exercise after atrial redirection for complete transposition

AIMS: To assess the determinants of exercise capacity and exercise oxygenation after atrial redirection for complete transposition. METHODS AND RESULTS: At graded bicycle ergometry, including respiratory and arterial blood gas analyses, intra-arterial blood pressure recording, and cardiac output determination (dye-dilution technique), we tested 17 post-Mustard/Senning patients, 8.9-22.0 years old (mean 14.5, SD 4.0). Reference data were obtained by similar methods. At maximal exercise, oxygen uptake (29.6 ml x kg(-1) x min(-1)) and heart rate (167 beats x min(-1)) were low (P<0.001). Right-to-left shunts were detected in five patients. Arterial oxygen partial pressure and saturation fell in all subjects (P<0.0001). In 15/16 (94%) the alveolar-arterial oxygen partial pressure difference was > +2 SD. In 13/15 (87%) stroke volumes fell during exercise. Cardiac output per oxygen uptake was low (P<0.0001), which implies a high arteriovenous oxygen difference and a low mixed venous oxygen content at peak exercise. CONCLUSION: The low exercise capacity was caused by a combination of low maximally attained heart rate and falling stroke volumes. The impaired arterial oxygenation may be caused by a combination of pulmonary ventilation/perfusion mismatch, a low mixed venous content and atrial shunting in some patients.     

Changes in pulmonary physiology after lung volume reduction surgery in a rabbit model of emphysema

BACKGROUND: We administered a specific, nonselective matrix metalloproteinase (MMP) inhibitor (RS-113,456) to examine the effect of MMP inhibition on flow-mediated arterial enlargement in a rodent arteriovenous fistula (AVF) model. METHODS: Four groups of male Sprague-Dawley rats were created: sham (sham operated; n = 10), control (2.0 mm left common femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mL vehicle orally twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113,456 in 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arterial pressure, and body weight were recorded on postoperative days 0, 7, 14, and 21. On day 21, AVF patency was confirmed, the infrarenal aorta and common iliac arteries were exposed, blood flow velocity and external diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired, two-tailed Student t test, one-way analysis of variance, and the Bonferroni/Dunn procedure for post hoc testing. RESULTS: Heat rate, mean arterial pressure, and weight did not vary at any time between groups. Aortic and left iliac diameter was larger in the AVF groups than in sham groups (P < .001), and control and vehicle groups were larger than treatment groups (P < .0001). Changes in aortic and left iliac flow were also significant (AVF was more than sham and control, and vehicle was more than treatment). No difference in aortic and left iliac artery velocity and WSS or right iliac diameter, velocity, flow, or WSS was observed between groups. CONCLUSIONS: MMP inhibition diminishes flow-mediated arterial enlargement in the rat AVF model.     

Thoracoscopic bilateral lung volume reduction for diffuse pulmonary emphysema

OBJECTIVE: In a prospective study, we investigated the functional results, complications and survival of bilateral video-assisted thoracoscopic (VAT) lung volume reduction (LVR) in a selected group of patients with severe, nonbullous pulmonary emphysema. From January 1994 to September 1996, 42 of 143 candidates (13 female, 29 male, 42-78 years) were operated. They were short of breath on minimal exertion due to severe airflow obstruction and hyperinflation (FEV1 < 30%) pred., TLC > 130% pred., RV > 200% pred.). METHODS: LVR was performed bilaterally by VAT using endoscopic staplers without buttressing the staple lines. Pulmonary function test (PFT), MRC dyspnea score and 12 min walking distance were assessed preoperatively, at 3, 6 and 12 months. In addition lung function was measured at hospital discharge. RESULTS: The patients reported a marked relief of dyspnea, which persisted at all follow-up visits (P<0.001). FEV1 increased from 0.80 +/- 0.24 (L) to 1.14 +/- 0.41 (L) postoperatively, a 43% gain (P < 0.001). A relevant increase of FEV1 persisted for at least 1 year. The residual volume to total lung capacity ratio decreased from 0.64 to 0.56 at hospital discharge. The mean 12 min walking distance increased from 500 +/- 195 (m) to 770 +/- 222 (m) after 1 year (P < 0.001). The mean hospital stay was 13 +/- 5.5 days (median 12.0), drainage time was 9 +/- 4.3 (median 8.0) days. There was no 30 day mortality. Three patients died between 2 and 15 months postoperatively by non surgery related reasons. One patient underwent lung transplantation 5 months after surgical lung volume reduction. CONCLUSIONS: In a selected group of patients with severe, nonbullous pulmonary emphysema, bilateral LVR by VAT results in instantaneous postoperative improvement in pulmonary function and dyspnea. These favorable effects, including an amelioriation in exercise performance, lasted for at least 1 year.     

Alanine and glutamine kinetics at rest and during exercise in humans

PURPOSE: The purpose of this study was to quantify both alanine and glutamine kinetics during exercise of moderate intensity to determine the sum total of alanine and glutamine flux. METHODS: Tracer methods were used to quantify alanine and glutamine rates of appearance (Ra) in plasma at rest and during 180 min of approximately 45% VO2max treadmill exercise in six normal volunteers (25 +/- 2 yr, 68 +/- 2.5 kg, VO2max 43 +/- 2.4 mL.min-1.kg-1; means +/- SE). Bolus injections (N = 3) or primed-constant infusions (N = 3) of 2H5-glutamine and 3-13C-alanine were given at rest on 1 d and 10-15 min after the onset of exercise on a separate day less than 2 wk later. Plasma enrichment decay curves and plateau enrichments were used to estimate alanine and glutamine kinetics. RESULTS: Whereas alanine Ra increased significantly from rest to exercise (5.72 +/- 0.31 vs 13.5 +/- 1.9 mumol.min-1.kg-1, respectively; P < 0.01), glutamine Ra was not significantly altered by exercise (6.11 +/- 0.44 and 6.40 +/- 0.69 mumol.min-1.kg-1 at rest and during exercise, respectively). The total of alanine and glutamine flux increased from 17.93 +/- 0.88 to 25.98 +/- 3.04 (P < 0.05). CONCLUSIONS: Since most muscle amino-N is released as alanine and glutamine, these findings provide strong evidence that amino-N delivery from muscle to the liver is increased during exercise. In addition, it appears that alanine, rather than glutamine, is the predominant N carrier involved in the transfer of N from muscle to the liver during moderate intensity exercise.     

Effects of exercise on fluid exchange and body composition in man during 14-day bed rest

To determine the cause of the body weight loss during bed rest (BR), fluid balance and anthropometric measurements were taken from seven men (19-21 yr) during three 2-wk BR periods which were separated by 3-wk ambulatory recovery periods. Caloric intake was 3,073 +/- 155 (SD) kcal/day. During two of the three BR periods they performed supine isotonic exercise at 68% of VO2max on the ergometer for 1 h/day; or supine isometric exercise at 21% of maximal leg extension force for 1 min followed by a 1-min rest for 1 h/day. No prescribed exercise was given during the other BR period. During BR, body weight decreased slightly with no exercise (-0.43 kg, NS), but decreased significantly (P less than 0.05) by -0.91 kg with isometric and by -1.77 kg with isotonic exercise. About one-third of the weight reduction with isotonic exercise was due to fat loss (-0.69 kg) and, the remainder, to loss of lean body mass (-0.98 kg). It is concluded that the reduction in body weight during bed rest has two major components: First, a loss of lean body mass caused by assumption of the horizontal body position that is independent of the metabolic rate. Second, a loss of body fat content that is proportional to the metabolic rate.     

Changes in lung volume and volume of emphysema after unilateral lung reduction surgery: analysis with CT lung densitometry

PURPOSE: To evaluate changes in volume of the lungs and volume of emphysema after unilateral lung reduction surgery (ULRS) by using computed tomographic (CT) lung densitometry. MATERIALS AND METHODS: Twenty-eight patients underwent CT before and 3 months after ULRS. With use of a density mask software program and a three-dimensional graphics workstation, CT scans were analyzed to define the volume of the lungs and the volume of emphysema. Pre- and postoperative mean CT numbers were determined. RESULTS: After ULRS, the surgically reduced lung volume decreased 22%, and the intact opposite lung volume increased 4%. Emphysema in the surgically reduced lung decreased 14% and was unchanged in the intact opposite lung. Mean CT numbers in the surgically reduced lung increased 26 HU but were unchanged in the intact opposite lung. CONCLUSION: The effects of ULRS on each lung can be evaluated by using CT lung densitometry and a three-dimensional graphics workstation. ULRS reduces emphysema and lung volume in the surgically reduced lung without statistically significant worsening of contralateral emphysema at 3 months.     

Hypervolemia in men from fluid ingestion at rest and during exercise

BACKGROUND: Plasma osmolality (Osm) is important for controlling and maintaining plasma volume (PV) and body water. The effect of oral rehydration fluids for ameliorating dehydration is well-established; but optimal composition and Osm of fluids for hyperhydrating normally hydrated subjects is less clear. METHODS: Six treatments were used without and with oral fluids of varying ionic and constituent concentrations for hyperhydrating six previously euhydrated men (30 +/- SD 8 yr, 76.84 +/- 16.19 kg, 73 +/- 12 ml.kg-1 PV, 40 +/- 10 ml.min-1.kg-1 peak VO2) sitting at rest for 90 min (VO2 = 0.39 +/- SE 0.02 L.min-1) and during subsequent 70 min of submaximal exercise (VO2 = 2.08 +/- SE 0.33 L.min-1, 70 +/- 7% peak VO2). The hypothesis was that the fluid composition is more important than plasma Osm for increasing PV in euhydrated subjects at rest and maintaining it during exercise. Drink formulation compositions, given at 10 ml.kg-1 body wt, (mean = 768 ml), for the sitting period were: Performance 1 (P1; 55 mEq Na+, 365 mOsm.kg H2O-1), P2 (97 mEq Na+, 791 mOsm.kg-1), P2G (113 mEq Na+, 4% glycerol, 1382 mOsm.kg-1), AstroAde (AA; 164 mEq Na+, 253 mOsm.kg-1), and 01 and 02 (no drinking). The exercise drink (10 ml.kg-1, 768 ml) was P1 for all treatments except 02 (no drinking); thus, drink designations were: P1/P1, P2/P1, P2G/P1, AA/P1, 0/P1, and 0/0. RESULTS: PV at rest increased (p < 0.05) by 4.7% with P1 and by 7.9% with AA. Percent change in PV during exercise was +1% to +3% (NS) with AA/P1; -6% to 0% (NS) with P1/P1, P2/P1, P2G/P1, and 0/P1; and -8% to -5% (p < 0.05) with 0/0. AA, with the lowest Osm of 253 mOsm.kg-1, increased PV at rest (as did P1) and maintained it during exercise, whereas the other drinks with lower Na+ and higher Osm of 365-1382 mOsm.kg-1 did not. CONCLUSION: Drink composition appears to be more important than its Osm for increasing PV at rest and for maintaining it during exercise in previously euhydrated subjects.