| 1. |
- Lattuada, Marco, 1974-
(författare)
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Effect of Ventilatory Support on Abdominal Fluid Balance in a Sepsis Model
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In patients affected by acute respiratory failure or acute respiratory distress syndrome (ARDS) the leading cause of death is failure of different vital organs other than the lungs, so called multiple organ dysfunction syndrome (MODS). The abdominal organs have a crucial role in the pathogenesis of this syndrome.There is a lack of knowledge regarding the mechanisms by which mechanical ventilation can affect the abdominal compartment. One hypothesis is that mechanical ventilation can interfere with abdominal fluid balance causing edema and inflammation.We addressed the question whether different levels of ventilatory support (mechanical ventilation with different levels of positive end-expiratory pressure, PEEP, and spontaneous breathing with or without PEEP) can influence abdominal edema and inflammation in both healthy and endotoxin-exposed animals.The effect on lymphatic drainage from the abdomen exerted by different degrees of ventilatory support was evaluated (paper I). We demonstrated that endotoxin increases abdominal lymph production, that PEEP and mechanical ventilation increase lymph production but also impede lymphatic drainage; spontaneous breathing improves lymphatic drainage from the abdomen.By adapting a non-invasive nuclear medicine imaging technique and validating it (paper II), we have been able to evaluate extravascular fluid accumulation (edema formation) in the abdomen over time (paper III) demonstrating that edema increases during endotoxemia, mimicking a sepsis-like condition, and that spontaneous breathing, compared to mechanical ventilation, reduces extravascular fluid. Pro-inflammatory cytokines TNF-α and IL-6 in intestinal biopsies are reduced during spontaneous breathing compared to mechanical ventilation.Abdominal edema results in increased intra-abdominal pressure (IAP): in paper IV we analyzed the effect of increased intra-abdominal pressure on the respiratory system. Pulmonary shunt fraction increased with high IAP both in healthy and LPS animals, resulting in decreased level of oxygenation. These changes are only partially reversible by reducing IAP.In conclusion, mechanical ventilation is a life-saving tool but the possible side effect at the extra-pulmonary level should be considered, and the introduction of some degree of spontaneous breathing when clinically possible is a suggested choice.
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| 2. |
- Nilsson, Manja C. A., 1966-, et al.
(författare)
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Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction in anesthetized pigs, without affecting the endogenous pulmonary nitric oxide production.
- 2012
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 38:3, s. 509-517
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. Methods Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO2) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results There were no differences between the groups for ENO, Ca2+-independent or Ca2+-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q LLL/Q T) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q LLL/Q T increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q LLL/Q T remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO2 (p < 0.01). Conclusions Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.
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| 3. |
- Nilsson, Manja C, et al.
(författare)
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Distant effects of nitric oxide inhalation in endotoxemic pigs
- 2010
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 38:1, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Inhalation of nitric oxide (INO) has distant effects. By a blood- borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO. DESIGN: Prospective, randomized animal study. SETTING: University hospital research laboratory. SUBJECTS: Twenty-two pairs of domestic pigs. INTERVENTIONS: Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group). MEASUREMENTS AND MAIN RESULTS: NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004). CONCLUSIONS: As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.
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| 4. |
- Nilsson, Manja, et al.
(författare)
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Distant effects of nitric oxide inhalation in lavage induced lung injury in anaesthetised pigs
- 2013
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 57:3, s. 326-333
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Tidskriftsartikel (refereegranskat)abstract
- Background Inhalation of nitric oxide (INO) exerts both local and distanteffects. 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 ofthis 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 theeffects on endogenous NO production and blood flow in the lavage-injured lungregions were studied. Six pigs served as a control group. NO concentration inexhaled air (ENO), NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results The calcium (Ca2+)-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 Ca2+-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.
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| 5. |
- Nilsson, Manja
(författare)
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Endogenous Nitric Oxide Production and Pulmonary Blood Flow : during different experimental lung conditions
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the lungs and in other organs, since NO can be transported to remote tissues bound to proteins, or as more stable molecules of nitrite and nitrate. In healthy pigs, INO causes vasoconstriction and down regulation of endogenous NO production in lung regions not reached by INO, and predominantly so in hypoxic lung regions, i.e. augmentation of HPV. In this thesis, distant effects of INO in pigs with endotoxemic- and lavage-induced lung injuries were studied. INO increased the NO production in lung regions not reached by INO in endotoxemic pigs, whereas endogenous NO production was unaffected in pigs with lavage-induced injury. Metabolic and/or hypercapnic acidosis frequently occurs in critically ill patients, but whether acidosis affects the endogenous pulmonary NO production is unclear. The regional NO production and blood flow in hyperoxic and hypoxic lung regions, were studied during metabolic and hypercapnic acidosis. Neither metabolic, nor hypercapnic acidosis changed the endogenous NO production in hyperoxic or hypoxic lung regions. Metabolic acidosis potentiated HPV, whereas hypercapnic acidosis transiently attenuated HPV. In conclusion, the present thesis has demonstrated that INO in experimental sepsis increases the endogenous NO production in lung regions not reached by INO, which may cause increased shunt and poor response to INO. This distant effect is not seen in lavage injuried lungs, an experimental model with less inflammation. Acidosis does not affect the endogenous pulmonary NO production in hyperoxic or hypoxic lung regions. Whereas metabolic acidosis potentiates HPV, hypercapnic acidosis transiently attenuates HPV, due to a combination of hypercapnia-induced increase in cardiac output and a probable vasodilating effect of the CO2-molecule.
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| 6. |
- Nilsson, Manja, et al.
(författare)
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No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in pigs
- 2011
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 202:1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- 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 omega-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 Ca2+-dependent (cNOS) or Ca2+-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.
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| 7. |
- Strang, Christof M., et al.
(författare)
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Improved ventilation-perfusion matching with increasing abdominal pressure during CO(2)-pneumoperitoneum in pigs
- 2011
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 55:7, s. 887-896
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Tidskriftsartikel (refereegranskat)abstract
- Background: CO(2)-pneumoperitoneum (PP) is performed at varying abdominal pressures. We studied in an animal preparation the effect of increasing abdominal pressures on gas exchange during PP. Methods: Eighteen anaesthetized pigs were studied. Three abdominal pressures (8, 12 and 16mmHg) were randomly selected in each animal. In six pigs, single-photon emission computed tomography (SPECT) was used for the analysis of V / Q distributions; in another six pigs, multiple inert gas elimination technique (MIGET) was used for assessing V / Q matching. In further six pigs, computed tomography (CT) was performed for the analysis of regional aeration. MIGET, CT and central haemodynamics and pulmonary gas exchange were recorded during anaesthesia and after 60min on each of the three abdominal pressures. SPECT was performed three times, corresponding to each PP level. Results: Atelectasis, as assessed by CT, increased during PP and in proportion to abdominal pressure [from 9 +/- 2% (mean +/- standard deviation) at 8mmHg to 15 +/- 2% at 16mmHg, P <0.05]. SPECT during increasing abdominal CO(2) pressures showed a shift of blood flow towards better ventilated areas. V / Q analysis by MIGET showed no change in shunt during 8 mmHg PP (9 +/- 1.9% compared with baseline 9 +/- 1.2%) but a decrease during 12mmHg PP (7 +/- 0.9%, P <0.05) and 16mmHg PP (5 +/- 1%, P <0.01). PaO(2) increased from 39 +/- 10 to 52 +/- 9 kPa (baseline to 16 mmHg PP, P <0.01). Arterial carbon dioxide (PCO(2)) increased during PP and increased further with increasing abdominal pressures. Conclusion: With increasing abdominal pressure during PP perfusion was redistributed more than ventilation away from dorsal, collapsed lung regions. This resulted in a better V / Q match. A possible mechanism is enhanced hypoxic pulmonary vasoconstriction mediated by increasing PCO(2).
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| 8. |
- Strang, Christof M., et al.
(författare)
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Ventilation-perfusion distributions and gas exchange during carbon dioxide-pneumoperitoneum in a porcine model
- 2010
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 105:5, s. 691-697
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: /st> Carbon dioxide (CO(2))-pneumoperitoneum (PP) of 12 mm Hg increases arterial oxygenation, but it also promotes collapse of dependent lung regions. This seeming paradox prompted the present animal study on the effects of PP on ventilation-perfusion distribution (V/Q) and gas exchange. METHODS: /st> Fourteen anaesthetized pigs were studied. In seven pigs, single photon emission computed tomography (SPECT) was used for spatial analysis of ventilation and perfusion distributions, and in another seven pigs, multiple inert gas elimination technique (MIGET) was used for detailed analysis of V/Q matching. SPECT/MIGET and central haemodynamics and pulmonary gas exchange were recorded during anaesthesia before and 60 min after induction of PP. RESULTS: /st> SPECT during PP showed no or only poorly ventilated regions in the dependent lung compared with the ventilation distribution during anaesthesia before PP. PP was accompanied by redistribution of blood flow away from the non- or poorly ventilated regions. V/Q analysis by MIGET showed decreased shunt from 9 (sd 2) to 7 (2)% after induction of PP (P<0.05). No regions of low V/Q were seen either before or during PP. Almost no regions of high V/Q developed during PP (1% of total ventilation). Pa(o(2)) increased from 33 (1.2) to 35.7 (3.2) kPa (P<0.01) and arterial to end-tidal Pco(2) gradient (Pae'(co(2))) increased from 0.3 (0.1) to 0.6 (0.2) kPa (P<0.05). CONCLUSIONS: /st> Perfusion was redistributed away from dorsal, collapsed lung regions when PP was established. This resulted in a better V/Q match. A possible mechanism is enhanced hypoxic pulmonary vasoconstriction.
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