Innovative and conventional "conservative" technologies for the treatment of uterine fibroids in Italy: a multidimensional assessment.

BACKGROUND: To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard "conservative" procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE). METHODS: A Health Technology Assessment was conducted, assuming the payer's perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients' clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids' experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy). RESULTS: Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients' perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients' productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of - 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs. CONCLUSIONS: Results suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits.

Could fluorescence-guided surgery be an efficient and sustainable option? A SICE (Italian Society of Endoscopic Surgery) health technology assessment summary.

BACKGROUND: Indocyanine green fluorescence vision is an upcoming technology in surgery. It can be used in three ways: angiographic and biliary tree visualization and lymphatic spreading studies. The present paper shows the most outstanding results from an health technology assessment study design, conducted on fluorescence-guided compared with standard vision surgery. METHODS: A health technology assessment approach was implemented to investigate the economic, social, ethical, and organizational implications related to the adoption of the innovative fluorescence-guided view, with a focus on minimally invasive approach. With the support of a multidisciplinary team, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaires and self-reported interviews, considering the dimensions resulting from the EUnetHTA Core Model. RESULTS: From a systematic search of literature, we retrieved the following studies: 6 on hepatic, 1 on pancreatic, 4 on biliary, 2 on bariatric, 4 on endocrine, 2 on thoracic, 11 on colorectal, 7 on urology, 11 on gynecology, 2 on gastric surgery. Fluorescence guide has shown advantages on the length of hospitalization particularly in colorectal surgery, with a reduction of the rate of leakages and re-do anastomoses, in spite of a slight increase in operating time, and is confirmed to be a safe, efficacious, and sustainable vision technology. Clinical applications are still presenting a low evidence in the literature. CONCLUSION: The present paper, under the patronage of Italian Society of Endoscopic Surgery, based on an HTA approach, sustains the use of fluorescence-guided vision in minimally invasive surgery, in the fields of general, gynecologic, urologic, and thoracic surgery, as an efficient and economically sustainable technology.

An unusual white dwarf star may be a surviving remnant of a subluminous Type Ia supernova.

Subluminous Type Ia supernovae, such as the Type Iax-class prototype SN 2002cx, are described by a variety of models such as the failed detonation and partial deflagration of an accreting carbon-oxygen white dwarf star or the explosion of an accreting, hybrid carbon-oxygen-neon core. These models predict that bound remnants survive such events with, according to some simulations, a high kick velocity. We report the discovery of a high proper motion, low-mass white dwarf (LP 40-365) that travels at a velocity greater than the Galactic escape velocity and whose peculiar atmosphere is dominated by intermediate-mass elements. Strong evidence indicates that this partially burnt remnant was ejected following a subluminous Type Ia supernova event. This supports the viability of single-degenerate supernova progenitors.

Groin Pain Syndrome Italian Consensus Conference on terminology, clinical evaluation and imaging assessment in groin pain in athlete.

The nomenclature and the lack of consensus of clinical evaluation and imaging assessment in groin pain generate significant confusion in this field. The Groin Pain Syndrome Italian Consensus Conference has been organised in order to prepare a consensus document regarding taxonomy, clinical evaluation and imaging assessment for groin pain. A 1-day Consensus Conference was organised on 5 February 2016, in Milan (Italy). 41 Italian experts with different backgrounds participated in the discussion. A consensus document previously drafted was discussed, eventually modified, and finally approved by all members of the Consensus Conference. Unanimous consensus was reached concerning: (1) taxonomy (2) clinical evaluation and (3) imaging assessment. The synthesis of these 3 points is included in this paper. The Groin Pain Syndrome Italian Consensus Conference reached a consensus on three main points concerning the groin pain syndrome assessment, in an attempt to clarify this challenging medical problem.

A Health Technology Assessment: laparoscopy versus colpoceliotomy.

INTRODUCTION: The objective of this paper is the comparison between two different technologies used for the removal of a uterine myoma, a frequent benign tumor: the standard technology currently used, laparoscopy, and an innovative one, colpoceliotomy. It was considered relevant to evaluate the real and the potential effects of the two technologies implementation and, in addition, the consequences that the introduction or exclusion of the innovative technology would have for both the National Health System (NHS) and the entire community. METHODS: The comparison between these two different technologies, the standard and the innovative one, was conducted using a Health Technology Assessment (HTA). In particular, in order to analyse their differences, a multi-dimensional approach was considered: effectiveness, costs and budget impact analysis data were collected, applying different instruments, such as the Activity Based Costing methodology (ABC), the Cost-Effectiveness Analysis (CEA) and the Budget Impact Analysis (BIA). Organisational, equity and social impact were also evaluated. RESULTS: The results showed that the introduction of colpoceliotomy would provide significant economic savings to the Regional and National Health Service; in particular, a saving of € 453.27 for each surgical procedure. DISCUSSION: The introduction of the innovative technology, colpoceliotomy, could be considered a valuable tool; one offering many advantages related to less invasiveness and a shorter surgical procedure than the standard technology currently used (laparoscopy).

A randomized clinical comparison of the Intersurgical i-gel and LMA Unique in non-obese adults during general surgery.

BACKGROUND: The i-gel is a cuffless, single-use supralaryngeal airway device designed to provide a more effective seal than the laryngeal mask airway (LMA). Although the superiority of the i-gel compared to the LMA Classic was determined in a previous study, no studies have been performed that compare it to the disposable LMA Unique. The aim of this study was to compare the Intersurgical i-gelTM against the LMA UniqueTM (uLMA) in terms of ease of placement, time of insertion, and adequacy of placement through a randomized, controlled clinical trial. METHODS: Following Institutional Review Board (IRB) approval and written informed consent, 50 adult patients were recruited for this study. All enrolled patients were ASA 1-2, Mallampati I-II, and scheduled to receive general anesthesia. Patients were randomized to have either the i-gel or the uLMA placed for airway management. After standardized induction techniques, the airway was secured with the assigned device. All patients were interviewed postoperatively for sore throat, hoarseness, and dysphagia. Standard vital signs, end-tidal CO2, tidal volumes, and peak pressures were recorded. Insertion time, leak pressures, and anatomic placement as assessed fiberoptically for the i-gel were recorded. Ease of placement and complications were also recorded. RESULTS: The insertion time was significantly less with the i-gel (21.04±12.6 s vs. 30.04±14.1 s, P=0.02). An inadequate seal was noted in three patients with the i-gel, and it was exchanged for the uLMA in all three cases. There were no significant differences in the ease of insertion, leak pressures, or fiberoptic view. Most of the fiberoptic views, as assessed through the drain tube, demonstrated esophageal mucosa (22/25). Patients receiving the i-gel were significantly more likely to require a second attempt at insertion by the anesthesiologist (OR 8.11, CI 1.1-58.6, P=0.03). Finally, patients receiving the size 5 i-gel were significantly more likely to complain of immediate postoperative symptoms, such as sore throat and dysphagia (OR 29.32, CI 1.4-613.1, P=0.03). CONCLUSION: Although the i-gel had a faster insertion time in comparison to the uLMA, there was a greater need for repeat insertions. The weight criteria established by the manufacturer may need to be readjusted to recommend a larger size device in some patients less than 90 kg because all of the repeat insertions were in patients weighing more than 80 kg. In all other aspects of its use, the i-gel performed similarly to the uLMA.

Loss budget of a setup for measuring mechanical dissipations of silicon wafers between 300 and 4 K.

A setup for measuring mechanical losses of silicon wafers has been fully characterized from room temperature to 4 K in the frequency range between 300 Hz and 4 kHz: it consists of silicon wafers with nodal suspension and capacitive and optical vibration sensors. Major contributions to mechanical losses are investigated and compared with experimental data scanning the full temperature range; in particular, losses due to the thermoelastic effect and to the wafer clamp are modeled via finite element method analysis; surface losses and gas damping are also estimated. The reproducibility of the measurements of total losses is also discussed and the setup capabilities for measuring additive losses contributed by thin films deposited on the wafers or bonding layers. For instance, assuming that additive losses are due to an 80-nm-thick wafer bond layer with Young modulus about ten times smaller than that of silicon, we achieve a sensitivity to bond losses at the level of 5x10(-3) at 4 K and at about 2 kHz.

Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients.

OBJECTIVE: To verify the association of ribosomal anti-P antibodies (anti-P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE). METHODS: Anti-P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions. RESULTS: Serum anti-P were detected in 18/149 patients (12.1%). The anti-P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti-P-positive patients at disease onset was less than 33 yr and, in comparison with the anti-P-negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti-P was also found. However, anti-P were associated with neither neuropsychiatric syndromes nor cognitive impairment. CONCLUSION: This study does not seem to confirm the described association of anti-P with SLE neuropsychiatric manifestations. However, it supports the anti-P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.

Chitin synthesis in a gas1 mutant of Saccharomyces cerevisiae.

The existence of a compensatory mechanism in response to cell wall damage has been proposed in yeast cells. The increase of chitin accumulation is part of this response. In order to study the mechanism of the stress-related chitin synthesis, we tested chitin synthase I (CSI), CSII, and CSIII in vitro activities in the cell-wall-defective mutant gas1 delta. CSI activity increased twofold with respect to the control, a finding in agreement with an increase in the expression of the CHS1 gene. However, deletion of the CHS1 gene did not affect the phenotype of the gas1 delta mutant and only slightly reduced the chitin content. Interestingly, in chs1 gas1 double mutants the lysed-bud phenotype, typical of chs1 null mutant, was suppressed, although in gas1 cells there was no reduction in chitinase activity. CHS3 expression was not affected in the gas1 mutant. Deletion of the CHS3 gene severely compromised the phenotype of gas1 cells, despite the fact that CSIII activity, assayed in membrane fractions, did not change. Furthermore, in chs3 gas1 cells the chitin level was about 10% that of gas1 cells. Thus, CSIII is the enzyme responsible for the hyperaccumulation of chitin in response to cell wall stress. However, the level of enzyme or the in vitro CSIII activity does not change. This result suggests that an interaction with a regulatory molecule or a posttranslational modification, which is not preserved during membrane fractionation, could be essential in vivo for the stress-induced synthesis of chitin.

Increase of external osmolarity reduces morphogenetic defects and accumulation of chitin in a gas1 mutant of Saccharomyces cerevisiae.

We have performed a physiological analysis of the effects of high-osmolarity media on gas1Delta cells. The reductions in the duplication time, number of pluribudded cells, hypersensitivity to Calcofluor and sodium dodecyl sulfate, and chitin level indicate a partial suppression of the mutant phenotype. GAS1 deletion was found to be lethal in the absence of the Bck1 and Slt2 (Mpk1) proteins of the cell integrity pathway.

Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVE: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations. METHODS: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never-NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)). RESULTS: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never-NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory. CONCLUSIONS: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

Elective surgery for gastrointestinal tumours in the elderly.

The geriatric population is expanding and clinical decision-making is often complicated by the effects of ageing. Age should not be the only parameter considered when addressing medical problems. Elderly subjects have been denied surgery because of their presumed higher mortality and morbidity. The present review summarises the physiology of the aged and discusses operative risks, mortality and morbidity rates as well as therapeutic results for the different gastrointestinal sites when affected by cancer. Reports on surgical treatments are revisited and compared to the same procedures delivered to younger patients in the context of the ethical issue of offering the best care to every patient. Elective operations by surgical oncologists are found to be safe with the exception of major liver resections. Complication rates and mean hospital stay do not differ between the two age groups provided the procedure is conducted with the best-known technique in expert hands. A drop in operative morbidity has occurred in the past three decades. Several investigators have emphasised the marked increase in morbidity and mortality experienced by elderly patients when undergoing emergency procedures. Associated diseases have to be properly assessed, as the elderly have a frail physiological balance with a reduced capacity for recovery from traumatic events including major surgical procedures. Careful preoperative evaluation, intraoperative conduct and postoperative care are presently achieved in almost every major hospital. Good clinical practice is based on the balance between probability of cure and toxic effects. Treatment of the elderly should no longer be based on untested beliefs and personal opinions. The elderly should be accrued for prospective clinical evaluation and should not be denied optimal surgical treatment.

Determinants of nitric oxide in exhaled gas in the isolated rabbit lung.

Nitric oxide concentrations in the exhaled gas (NOe) increases during various inflammatory conditions in humans and animals. Little is known about the sources and factors that influence NOe. NOe at end expiration was measured by chemiluminescence in an isolated, blood-perfused rabbit lung. The average end-expiratory concentration over 10 breaths was used. The effect of positive end-expiratory pressure (PEEP), flow rate, pH, hypoxia, venous pressure, and flow pulsatility on NOe were determined. At constant blood flow, increasing PEEP from 1 to 5 cm H2O elicited a reproducible increase in NOe from 49 +/- 7 to 53 +/- 8 parts per billion (ppb) (p < 0.05). When blood pH was increased from 7.40 to 7.74 by breathing low CO2 gas, NOe rose from 45 +/- 7 to 55 +/- 7 ppb (p < 0.001). Hypoxia caused a dose-dependent decrease in NOe from 37 +/- 3 during baseline to 23 +/- 2 during ventilation with 0% O2 (p < 0.01). Venous pressure elevation from 0 to 5 and 10 mm Hg decreased NOe from 32 +/- 5, to 26 +/- 5 and 24 +/- 5 ppb, respectively (p < 0.05). Switching from steady to pulsatile flow (same man flow) resulted in a small, albeit significant reduction in NOe; 30 +/- 4 to 28 +/- 4 ppb (p < 0.05). Changes in flow rate between 200 and 20 ml/min were associated with small changes in NOe; however, when flow was stopped, NOe rose substantially to 56 +/- 6 ppb (p < 0.05). The changes in NOe were rapid (1 to 2 min) and reversible. The results suggest that NOe is influenced by ventilatory and hemodynamic variables, pH, and hypoxia. We suggest that caution must be taken when interpreting changes in exhaled NO in humans or experimental animals. Changes in total and regional blood flow, capillary blood volume, ventilation, hypoxia, and pH should not be overlooked.

Segmental pulmonary vascular responses to ATP in rat lungs: role of nitric oxide.

ATP exhibits vascular pressor and depressor responses in a dose- and tone-dependent manner. The vascular site of ATP-induced contraction or dilation has not previously been characterized. Using the vascular occlusion technique, we investigated the effects of ATP in isolated rat lungs perfused with autologous blood (hematocrit = 20%) and described its action during resting and elevated tone in terms of changes in resistances of the small and large arteries and veins. During resting tone, ATP (10(-5) M) caused contraction primarily in the small arteries and, to some extent, in the small veins, suggesting that P2x purinoceptors are present in these small vessels. During hypoxia, ATP caused dilation primarily in the small arteries, suggesting that P2y purinoceptors are predominant in small arteries. During U-46619-induced contraction, which occurred evenly throughout the four segments, ATP caused dilation in the large arteries and veins but not in the small arteries and veins. After treatment with N omega-nitro-L-arginine to inhibit nitric oxide synthesis, ATP-induced contraction was potentiated, and its dilatory effects during hypoxia were attenuated. The action of ATP was independent of prostanoids, because its constrictor and dilatory responses were not affected significantly by indomethacin. In conclusion, the results indicate that the effects of ATP on the pulmonary vasculature are primarily due to P2x and P2y purinoceptors in the small arteries. Contribution of these purinoceptors in other vessels to changes in total vascular resistance in rat lung was minor.

Analysis of the double occlusion which provides four pressure gradients.

The arterial, double and venous occlusions are used to partition pulmonary vascular resistance into four segments. In this study, we tested whether the same can be accomplished from one double occlusion. In an isolated canine lung left lower lobe perfused with blood (flow rate = 500 mL.min-1), the pulmonary arterial and venous pressures (Pa and Pv, respectively) were measured directly. Arterial, double, and venous occlusions were performed and analysed as usual (Method 1) to measure pressures in small arteries and small veins (Pa' and Pv', respectively) and capillary pressure (Pc). Alternatively, one double occlusion was analysed (Method 2), not only for Pa, Pv and Pc, but also as independent arterial and venous occlusions to measure Pa' and Pv'. Method 1 yielded Pa, Pa', Pc, Pv', and Pv (Baseline) of 14.2 +/- 1.7, 10.8 +/- 1.6, 8.9 +/- 1.9, 7.3 +/- 1.5 and 1.3 +/- 0.6 mmHg, respectively (1 mmHg = 0.133 kPa). Method 2 yielded values for the same five pressures equal to 14.7 +/- 2.1, 11.0 +/- 2.2, 8.9 +/- 1.9, 7.3 +/- 1.3 and 1.3 +/- 0.6 mmHg, respectively. There was no significant difference in the pressure profile obtained using the two methods, nor were there differences during hypoxia and angiotensin infusion. These results suggest that a more thorough analysis of the double occlusion can provide the same information about distribution of vascular resistance as provided by a combination of the three occlusions. The advantage of the new approach is that fewer occlusions are needed and resistance distribution can be assessed during a transient response. Because all pressures are derived from one occlusion, the pressures would be more accurate relative to each other.

Effects of heat and moisture exchangers on minute ventilation, ventilatory drive, and work of breathing during pressure-support ventilation in acute respiratory failure.

OBJECTIVES: To evaluate the effect of two commonly used heat and moisture exchangers on respiratory function and gas exchange in patients with acute respiratory failure during pressure-support ventilation. DESIGN: Prospective, randomized trial. SETTING: Intensive care unit of a university hospital. PATIENTS: Fourteen patients with moderate acute respiratory failure, receiving pressure-support ventilation. INTERVENTIONS: Patients were assigned randomly to two treatment groups, in which two different heat and moisture exchangers were used: Hygroster (DAR S.p.A., Mirandola, Italy) with higher deadspace and lower resistance (group 1, n = 7), and Hygrobac-S (DAR S.p.A.) with lower deadspace and higher resistance (group 2, n = 7). Patients were assessed at three pressure-support levels: a) baseline (10.3 +/- 2.4 cm H2O for group 1, 9.3 +/- 1.3 cm H2O for group 2); b) 5 cm H2O above baseline; and c) 5 cm H2O below baseline. Measurements obtained with the heat and moisture exchangers were compared with those values obtained using the standard heated hot water humidifier. MEASUREMENTS AND MAIN RESULTS: At baseline pressure-support ventilation, the insertion of both heat and moisture exchangers induced in all patients a significant increase in the following parameters: minute ventilation (12.4 +/- 3.2 to 15.0 +/- 2.6 L/min for group 1, and 11.8 +/- 3.6 to 14.2 +/- 3.5 L/min for group 2); static intrinsic positive end-expiratory pressure (2.9 +/- 2.0 to 5.1 +/- 3.2 cm H2O for group 1, and 2.9 +/- 1.7 to 5.5 +/- 3.0 cm H2O for group 2); ventilatory drive, expressed as P41 (2.7 +/- 2.0 to 5.2 +/- 4.0 cm H2O for group 1, and 3.3 +/- 2.0 to 5.3 +/- 3.0 cm H2O for group 2); and work of breathing, expressed as either power (8.8 +/- 9.4 to 14.5 +/- 10.3 joule/ min for group 1, and 10.5 +/- 7.4 to 16.6 +/- 11.0 joule/min for group 2) or work per liter of ventilation (0.6 +/- 0.6 to 1.0 +/- 0.7 joule/L for group 1, and 0.8 +/- 0.4 to 1.1 +/- 0.5 joule/L. for group 2). These increases also occurred when pressure-support ventilation was both above and below the baseline level, although at high pressure support the increase in work of breathing with heat and moisture exchangers was less evident. Gas exchange was unaffected by heat and moisture exchangers, as minute ventilation increased to compensate for the higher deadspace produced in the circuit by the insertion of heat and moisture exchangers. CONCLUSIONS: The tested heat and moisture exchangers should be used carefully in patients with acute respiratory failure during pressure-support ventilation, since these devices substantially increase minute ventilation, ventilatory drive, and work of breathing. However, an increase in pressure-support ventilation (5 to 10 cm H2O) may compensate for the increased work of breathing.

Site of action of endogenous nitric oxide on pulmonary vasculature in rats.

The effect of endogenous nitric oxide (NO) on the pulmonary hypoxic vasoconstriction was studied in isolated and blood perfused rat lungs. By applying the occlusion technique we partitioned the total pulmonary vascular resistance (PVR) into four segments: (1) large arteries (Ra), (2) small arteries (Ra'), (3) small veins (Rv'), and (4) large veins (Rv). The resistances were evaluated under baseline (BL) conditions and during; hypoxic vasoconstriction and acetylcholine (Ach) which was injected during hypoxic vasoconstriction. After recovery from hypoxia and Ach, Nomega-nitro-L-arginine (L-NA) was added to the reservoir and the responses to hypoxia and Ach were reevaluated. Before L-NA, hypoxia caused significant increase in the resistances of all segments (P < 0.05), with the largest being in Ra and Ra'. Ach-induced relaxation during hypoxia occurred in Ra, Ra' and Rv' (P < 0.05). L-NA did not change the basal tone of the pulmonary vasculature significantly. However, after L-NA, hypoxic vasoconstriction was markedly enhanced in Ra, Ra', and Rv' (P < 0.01) compared with the hypoxic response before L-NA. Ach-induced relaxation was abolished after L-NA. We conclude that, in rat lungs, inhibition of NO production during hypoxia enhances the response in the small arteries and veins as well as in the large arteries. The results suggest that hypoxic vasoconstriction in the large pulmonary arteries and small vessels is attenuated by NO release.