A B S T R AC T Respiratory muscle blood flow and organ blood flow was studied in two groups of dogs with radioactively labeled microspheres to assess the influence of the working respiratory muscles on the regional distribution of blood flow when arterial pressure and cardiac output were lowered by pericardial tamponade. In one group (n = 6), the dogs were paralyzed and mechanically ventilated (Mv), while in the other (n = 6), they were left to breathe spontaneously (Sb). Cardiac output fell to 30% of control values during tamponade in both groups and was maintained constant. None of the dogs was hypoxic. Ventilation in the Sb group peaked after 50 min of hypotension, but remained unchanged in the Mv group. Duplicate measurements of blood flow were made during a control period and after 50 min of tamponade (corresponding to the peak ventilation in Sb). Blood flow to the respiratory muscles increased significantly (P < 0.001) during tamponade in Sb (diaphragmatic flow increased to 361% of control values), while it decreased in Mv. Although the arterial blood pressure and cardiac output were comparable in the two groups, blood flow distribution during tamponade was different. In Sb, the respiratory muscles received 21% of the cardiac output, compared with only 3% in the Mv

In normal subjects and patients with airway obstruction, flows during a forced vital capacity (FVC) manoeuvre are higher after a fast inspiration without an end-inspiratory pause (manoeuvre 1) as compared to a slow inspiration with an end-expiratory pause of ~5 s (manoeuvre 2). In this study, we investigated the influence of these manoeuvres on maximal expiratory volume-time and flow-volume curves in patients with restrictive lung disease.Eleven patients with restrictive lung disease were studied. Their average (±SD) lung function test results were: FVC=55±12% predicted value, forced expiratory volume in one second (FEV1) 52±20% pred, FEV1/FVC 85±6%, total lung capacity 55±8% pred, and carbon monoxide transfer factor 47±18% pred. The patients performed the two FVC manoeuvres in random order. We compared the ensuing spirograms and maximal expiratory flow-volume curves from which peak expiratory flow, FEV1, FEV1/FVC, maximal mid-expiratory flow, and maximal flows were computed.All spirometric indices were significantly higher with manoeuvre 1 than 2. Maximal expiratory flows at the same lung volume were also significantly higher with manoeuvre 1 than 2, in all patients.Routine spirometric indices, obtained during a forced vital capacity manoeuvre depend on the time course of the preceding inspiration in patients with restrictive lung disease. Therefore, the forced vital capacity manoeuvre should be standardized if used in clinical, epidemiological and research studies.

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18028 Background: Lipoplatin is a liposomal formulation of cisplatin, designed to reduce its adverse reactions without reducing efficacy. Its nanoparticles evade immune surveillance and extravasate preferentially into tumors inducing tumor cell apoptosis; lipoplatin may also act as antiangiogenesis factor. This is the initial report of a randomized, multicenter, phase III trial comparing the two drugs. Methods: Eligibility criteria included confirmed diagnosis of inoperable/metastatic NSCLC, no previous chemotherapy, WHO PS 0–1, adequate end-organ function. Patients received Lipoplatin 120 mg/m2 D1,8,15 or cisplatin 100 mg/m2 D1, combined with gemcitabine 1,000 mg/m2 D1,8, in 3-week cycles, with disease evaluation after 3 and 6 cycles. Primary endpoints are overall survival and toxicity, with Response Rates, PFS and QOL also being evaluated. Results: 59 patients have been treated, 33 with lipoplatin and 26 with cisplatin; 17 have completed treatment. 2 lipoplatin patients had a hypersensitivity reaction during the first infusion. There were no grade 4 toxicities. Grade 3 toxicities were observed in <5% of the patients and were comparable for the two groups, except neutropenia (3% for lipoplatin, 15% for cisplatin). Main grade 1–2 toxicities were anemia (93% vs 88%), leucopenia (51% vs 38%), neutropenia (45% vs 30%), thrombocytopenia (58% vs 31%), hepatotoxicity (38% vs 46%), nausea/vomiting (13% vs 35%), asthenia (31% vs 30%) and anorexia (32% vs 34%). Concerning nephrotoxicity, grade 2 was reported in only 6% of lipoplatin patients vs 19% in cisplatin, although lipoplatin was administered without pre-hydration as a 6-hour infusion. Neurotoxicity was also markedly less in lipoplatin. So far, 32 patients have been assessed for response, 16 in each group; 4 partial responses have been reported in each group. However, difference has been observed in stable disease (23% in lipoplatin vs 12% in cisplatin) as well as progressive disease (16% vs 35%). Conclusions: Preliminary results show that lipoplatin may have a better safety and therapeutic profile than cisplatin, when combined with gemcitabine, in advanced NSCLC. Particularly important might be its significantly lower neuro- and nephro-toxicity and its administration on an outpatients basis. No significant financial relationships to disclose.