Distant effects of nitric oxide inhalation in lavage-induced lung injury in anaesthetised pigs.

BACKGROUND: Inhalation of nitric oxide (INO) exerts both local and distant effects. INO in healthy pigs causes down-regulation of endogenous nitric oxide (NO) production and vasoconstriction in lung regions not reached by INO, especially in hypoxic regions, which augments hypoxic pulmonary vasoconstriction. In contrast, in pigs with endotoxemia-induced lung injury, INO causes increased NO production in lung regions not reached by INO. The aim of this study was to investigate whether INO exerts distant effects in surfactant-depleted lungs. METHODS: Twelve pigs were anaesthetised, and the left lower lobe (LLL) was separately ventilated. Lavage injury was induced in all lung regions, except the LLL. In six pigs, 40 ppm INO was given to the LLL (INO group), and the effects on endogenous NO production and blood flow in the lavage-injured lung regions were studied. Six pigs served as a control group. NO concentration in exhaled air (ENO), NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. RESULTS: The calcium (Ca(2+) )-dependent NOS activity was lower (P < 0.05) in the lavage-injured lung regions in the INO group than in the control group. There were no measurable differences between the groups for Ca(2+) -independent NOS activity, cGMP, ENO, or regional pulmonary blood flow. CONCLUSIONS: Regional INO did not increase endogenous NO production in lavage-injured lung regions not directly reached by INO, but instead down-regulated the constitutive calcium-dependent nitric oxide synthase activity, indicating that NO may inhibit its own synthesis.

Hydatidiform mole with non-metastatic pulmonary complications and a false low level of hCG.

We present a case of hydatidiform mole with non-metastatic pulmonary complications and stress that termination of the pregnancy will cure the patient. The frequent use of sonography in early pregnancy makes it possible to diagnose pathological pregnancies earlier than was possible before. The fact that molar pregnancies are now being terminated at an earlier stage means that some of the complications associated with advanced moles are seldom encountered today. The case also illustrates the so-called 'high dose hook effect' meaning that an extremely high level of hCG may falsely be reported to be very low by the laboratory.

No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in pigs.

AIM: In the severely ill intensive care patients metabolic acidosis and hypoxia often co-exist. We studied the effects of metabolic acidosis on nitric oxide synthase (NOS) dependent and NOS independent nitric oxide (NO) production in hypoxic and hyperoxic lung (HL) regions in a pig model. METHODS: Eighteen healthy anaesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Six pigs received HCl infusion (HCl group), six pigs received the non-specific NOS inhibitor N(ω) -nitro-l-arginine methyl ester (l-NAME) and HCl infusions (l-NAME + HCl group) and six pigs received buffered Ringer's solution (control group). NO concentration in exhaled air (ENO), NOS activity in lung tissue, and regional pulmonary blood flow were measured. RESULTS: Metabolic acidosis, induced by infusion of HCl, decreased the relative perfusion to the hypoxic LLL from 7 (3) [mean (SD)] to 3 (1) % in the HCl group (P < 0.01), and from 4 (1) to 1 (1) % in the l-NAME + HCl group (P < 0.05), without any measurable significant changes in ENO from hypoxic or HL regions There were no significant differences between the HCl and control groups for Ca(2+) -dependent (cNOS) or Ca(2+) -independent NOS (iNOS) activity in hypoxic or HL regions. CONCLUSIONS: Metabolic acidosis augmented the hypoxic pulmonary vasoconstriction, without any changes in pulmonary NOS dependent or NOS independent NO production. When acidosis was induced during ongoing NOS blockade, the perfusion of hypoxic lung regions was almost abolished, indicating acidosis-induced pulmonary vasoconstriction was not NO dependent.

Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg, Sweden.

All newly diagnosed diabetes in Kronoberg during 3 years was registered, with blood samples from 1630/1666 (97.8%) adults. Those positive for GADab and/or ICA and/or C-peptide<0.25nmol/L (0.7%) were classified as type 1 diabetes, the remaining as type 2. Incidence of type 1 in 0-19-year-olds was 37.8(36.1-39.6, 95%CI) and in 20-100 year-olds 27.1(25.6-27.4) per 100 000 and year, it was bimodal with equal peaks in 0-9 year-olds and in 50-80-year-olds. Adults had type 2 incidence 378 (375-380), children 3.1 (2.6-3.6). Among adults 6.9% had type 1 and 93.1% type 2. Among antibodypositive adults (n=101), GADab were present in 90%, ICA in 71%, both GADab and ICA in 61%. Ophthalmology contact as second source was confirmed for 98%. There were no gender differences in type 1 in any age group, small ones in pediatric subgroups. In type 2 men predominated in ages above 40 years. Incidences of type 1 diabetes in both children and adults were very high and as high above age 50 years as in children. Incidence of type 2 was the highest reported from Sweden, to which new diagnostic criteria, a high degree of case-finding, and many elders, may have contributed, but results may also reflect a true increase in incidence of both types of diabetes.

Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS.

To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects.

Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics.

In order to estimate the incidence and significance of aspiration during anaesthesia, a study of cases in which this complication had occurred was made at the Karolinska Hospital. With the aid of the anaesthetic recordkeeping system of the Department of Anaesthesia and the computer-based register of diagnoses of in-patients at the hospital, all cases in which aspiration was recorded were retrieved. Eighty-three cases of aspiration were retrieved from the file of anaesthetic records and four from the in-patient register. This constitutes an incidence of 4.7 aspirations in 10 000 anaesthetics, or 1 in 2131. The patients most often affected were children and the elderly. In 83% of the cases there were one or more preoperative factors indicating an increased risk for aspiration, such as emergency operation (38 cases, 43%), upper abdominal or emergency abdominal surgery (14 cases, 16%), a history indicating delayed gastric emptying (e.g. peptic ulcer/gastritis, pregnancy, obesity, unusual stress or pain, elevated intracranial pressure, 54 cases, 61%). In 29 cases (33%) there was a history indicating an increased risk of regurgitation, e.g. nasogastric tube, oesophageal disease or pregnancy. In 15 cases of elective surgery, no history of increased risk for aspiration could be found. In 67% of those cases the aspiration was preceded by difficulties involving the airways or intubation. The incidence of aspiration was more than sixfold higher during the night than during regular daytime working hours. In 41 cases (47%) the aspiration led to aspiration pneumonitis confirmed by x-ray. Fifteen patients (17%) needed mechanical ventilation, and four died.(ABSTRACT TRUNCATED AT 250 WORDS)

Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric oxide.

We hypothesized that the diversion of blood away from a hypoxic lung to the opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the oxygenated lung. We measured individual lung blood flow when 50 ppm NO was selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia. Twenty two patients with healthy lungs were studied during intravenous anaesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas elimination technique. Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05) of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05). Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow if the opposite lung is hypoxic.

Nitric oxide increases dramatically in air exhaled from lung regions with occluded vessels.

BACKGROUND: We observed dramatic changes in exhaled nitric oxide concentration (DeltaNOE) during wedge measurements, and hypothesised that occlusion and redistribution of pulmonary blood flow affects NOE. METHODS: We inflated the balloon of the pulmonary artery catheter and measured NOE and central hemodynamics in closed chest anesthetised pigs (n = 11) ventilated with hyperoxic gas (fraction of inspired oxygen [FIO2] = 0.5), before and during lung injury, and in open chest anesthetised pigs (n = 17) before and during left lower lobar (LLL) hypoxia (FIO2 0.05), and during hyperoxic (FIO2 0.8) ventilation of the other lung regions (HL). RESULTS: In the closed chest pigs NOE increased from 2.0 (0.9) to 3.4 (2.0) p.p.b. (P < 0.001) during wedge, and returned to 2.0 (1.0) p.p.b. when the balloon was deflated. The increase in mean pulmonary artery pressure (MPaP) during wedge was small and insignificant (P > 0.07). When the balloon was inflated in the right pulmonary artery in the open chest pigs, the perfusion of the HL decreased from 2.57 (0.58) to 2.34 (0.55) l min(-1) (P < 0.001), and NOEHL increased from 2.5 (0.9) to 6.2 (3.2) p.p.b. (P < 0.001). The perfusion of the LLL increased from 0.33 (0.26) to 0.54 (0.34) l min(-1) (P < 0.001), and NOELLL decreased from 1.7 (0.6) to 1.5 (0.5) p.p.b. (P < 0.001). Neither lung injury nor LLL hypoxia had any influence on DeltaNOE (P > 0.07) during wedge. The correlation coefficient (R2) was 0.66 between changes in regional blood flow and DeltaNOE, and 0.37 between changes in MPaP and DeltaNOE. CONCLUSIONS: Nitric oxide concentration increases dramatically from lung regions with occluded vessels, whereas changes in MPaP have minor effects on NOE. This is an important fact to consider when comparing NOE within or between studies, and indicates a possible marker of diseases with occluded lung vessels.

Hypoxic pulmonary vasoconstriction in human lungs. A stimulus-response study.

BACKGROUND: A stimulus-response relation between alveolar oxygen tension and pulmonary vascular resistance has been observed in animals. This study investigated this relation in healthy human lungs. The distribution of pulmonary blood flow was measured during unilateral (1) graded hypoxia (fractional concentration of oxygen in inspired gas [FIO2] = 0.12, 0.08, and 0.05) and contralateral hyperoxia (FIO2 = 1.0; n = 6); (2) single-step hypoxia (FIO2 = 0.05) and contralateral hyperoxia (n = 5); and (3) normobaric hyperoxia and contralateral normoxia (FIO2 = 0.25; n = 6). METHODS: Seventeen patients with healthy lungs were studied during intravenous anesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas (sulfurhexafluoride) elimination technique. RESULTS: (1) Unilateral graded hypoxia reduced the perfusion of the hypoxic lung from a mean (+/-SD) of 52 (2)% of cardiac output (Q) during bilateral hyperoxia, to 47 (5)% (P > 0.05) 40 (3)% (P < 0.01), and 30 (8)% (P < 0.001) of Q, respectively. These progressive reductions in the perfusion of the hypoxic lung were all significantly different from each other. (2) Unilateral single-step hypoxia caused a blood flow diversion of the same magnitude as when the lung was previously ventilated with FiO2 of 0.12 and 0.08. The perfusion of the hypoxic lung was reduced from 46 (9)% of Q (bilateral hyperoxia) to 26 (4)% of Q (P < 0.01). (3) Unilateral hyperoxia did not significantly change the relative blood flow distribution between the two lungs or the pulmonary artery pressure. CONCLUSIONS: A stimulus-response relation between graded hypoxia and blood flow diversion defines hypoxic pulmonary vasoconstriction in the normal human lung. Hyperoxia has no significant effect on vascular resistance in the normal human lung.

Pulmonary vasoconstriction during regional nitric oxide inhalation: evidence of a blood-borne regulator of nitric oxide synthase activity.

BACKGROUND: Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. METHODS: Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. RESULTS: Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions. CONCLUSIONS: Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.