Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome (HPS).METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placementat the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were considered.RESULTS: TIPS patency was confirmed by hemodynamic evaluation. No changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo later.CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

Sustained low diffusing capacity in hepatopulmonary syndrome after liver transplantation

AIM: To study the presence of sustained low diffusing capacity (DLCO) after liver transplantation (LT) in patients with hepatopulmonary syndrome (HPS).METHODS: Six patients with mild-to-severe HPS and 24 without HPS who underwent LT were prospectively followed before and after LT at mid-term (median, 15 mo). HPS patients were also assessed at long-tem (median, 86 mo).RESULTS: Before LT, HPS patients showed lower PaO2 (71 ± 8 mmHg), higher AaPO2 (43 ± 10 mmHg) and lower DLCO (54% ± 9% predicted), due to a combination of moderate-to-severe ventilation-perfusion (VA/Q) imbalance, mild shunt and diffusion limitation, than non-HPS patients (94 ± 4 mmHg and 19 ± 3 mmHg, and 85% ± 3% predicted, respectively) (P < 0.05 each). Seven non-HPS patients had also reduced DLCO (70% ± 4% predicted).At mid- and long-term after LT, compared to pre-LT, HPS patients normalized PaO2 (91 ± 3 mmHg and 87 ± 5 mmHg), AaPO2 (14 ± 3 mmHg and 23 ± 5 mmHg) and all VA/Q descriptors (P < 0.05 each) without changes in DLCO (53% ± 8% and 56% ± 7% predicted, respectively). Post-LT DLCO in non-HPS patients with pre-LT low DLCO was unchanged (75% ± 6% predicted).CONCLUSION: While complete VA/Q resolution in HPS indicates a reversible functional disturbance, sustained low DLCO after LT also present in some non-HPS patients, points to persistence of sub-clinical liver-induced pulmonary vascular changes.

肝肺综合征时直立位低氧血症的气体交换机制

The mechanism of orthodeoxia (OD), or decreased partial pressure of arterial o xygen (PaO2) from supine to upright, a characteristic feature of hepatopulmonary syndrome (HPS), has never been comprehensively elucidated. We therefore investi gated the intrapulmonary (shunt and ventilation-perfusion <<VA/Q>> mismatching) a nd extrapulmonary factors governing PaO2 in 20 patients with mild to severe HPS (14 males, 6 females; 50 ±3 years old SE) at upright and supine, in random orde r. We set out a cutoff value for OD, namely a PaO2 decrease ≥5%or ≥4mmHg (are a under the receiver operating characteristic curve, 0.96 each). Compared to sup ine, 5 patients stowed OD (PaO2 change, -11%±2%, -7 ±1 mm Hg, P < .05) wit h further VA/Q worsening (shunt +low VA/Q mode increased from 19%±7%to 21% ±7%of cardiac output <<QT>>, P < .05), as opposed to 15 patients who did not (+ 2%±2%, +1 ±1 mm Hg) with VA/Q improvement (from 20%±4%to 16%±4%of QT, P < .01). Cardiac output was significantly lower in OD patients in both positio ns. Changes in extrapulmonary factors at upright, such as increased minute venti lation and decreased QT, were of similar magnitude in both subsets of patients. In conclusion, our data suggest that gas exchange response to OD in HPS points t o a more altered pulmonary vascular tone inducing heterogeneous blood flow redis tribution to lung zones with prominent intrapulmonary vascular dilatations.

L-NAME喷雾剂在肝肺综合征中的应用效果

Enhanced pulmonary production of nitric oxide (NO) has been implicated in the pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with NG-nitro-L-arginine methyl ester (L-NAME) in both animals and humans with HPS has improved arterial hypoxemia. We assessed the role of enhanced NO production in the pathobiology of arterial deoxygenation in HPS and the potential therapeutic efficacy of selective pulmonary NO inhibition. We investigated the effects of nebulized L-NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS (60 ±7 [SD] yr; alveolar-arterial oxygen gradient, range 19-76 mmHg; arterial oxygen tension, range 37-89 mmHg). Nebulized L-NAME maximally decreased exhaled NO (by -55%; P < .001), mixed venous nitrite/nitrate (by -12%; P= .02), and cardiac output (by -11%; P= .002) while increased systemic vascular resistance (by 11%; P = .008) and pulmonary vascular resistance (by 25%; P = .03). In contrast, ventilation-perfusion mismatching, intrapulmonary shunt and, in turn, arterial deoxygenation remained unchanged. In conclusion, gas exchange disturbances in HPS may be related to pulmonary vascular remodeling rather than to an ongoing vasodilator effect of enhanced NO production.

Membrane and Subcellular Muscle Injury Are Induced by Single or Multiple Exposure to Cigarette Smoke

Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD). Diaphragm injury is observed in patients with COPD. However, the potential role of smoking in triggering or perpetuating muscle injury is unknown. The present study was aimed at evaluating the potential role of commercial tobacco smoke as a direct cause of skeletal muscle injury in experimental conditions. Seventy Wistar rats (170 - 250 g) were assigned to smoking (n = 49) or non-smoking (n = 21) groups. The smoking groups were submitted to a single or multiple (i.e., five or thirty) daily sessions of cigarette smoking in an inhalatory chamber (time length: 2 h each session). The level of exposure was constant and assessed by CO concentrations (50 ppm) and serum cotinine analysis. Animals submitted to a single smoke exposure and the corresponding controls were euthanized in groups at 0 h, 2 h, 4 h, 24 h or 48 h after completing the exposure. Animals submitted to multiple exposures were euthanized at 0 h after smoking. Samples from vastus lateralis muscle were obtained and processed for assessing cell injury and selected protein expression. Monoclonal anti-albumin antibodies were used to identify muscle fibers with sarcolemmal (membrane) injury. Subcellular muscle injury was assessed using transmission electron microscopy (EM). MyoD, myogenin and α-tubulin were immunodetected using western blot techniques. Exposure to cigarette smoke associated with significant membrane damage (mean relative difference (MRD) with controls: +181%, p = 0.004) and sarcomere disruptions (MRD: +226%, p = 0.001). Expression of MyoD and myogenin (normalized to α-tubulin) were significantly increased at 4 h and remained increased at 48 h post-exposure. We conclude that not only a single but also consecutive exposure to tobacco smoke have acute deleterious effects on peripheral muscle structure. A rapid induction of subrogate markers of skeletal muscle stress and repair processes associates to sarcolemmal and sarcomere damage.