Circulation stabilizing therapy and pulmonary high-resolution computed tomography in a porcine brain-dead model.

BACKGROUND: Currently 80% of donor lungs are not accepted for transplantation, often due to fluid overload. Our aim was to investigate if forced fluid infusion may be replaced by a new pharmacological therapy to stabilize circulation after brain death in an animal model, and to assess therapy effects on lung function and morphology trough blood gas parameters and state-of-the-art High-resolution CT (HRCT). METHODS: Brain death was caused by surgical decapitation. To maintain mean aortic pressure > 60 mmHg, pigs were treated with forced electrolyte solution infusion (GI; n = 6) or the pharmacological therapy (GII; n = 11). GIII (n = 11) were non-decapitated controls. Lung function was investigated with blood gases and lung morphology with HRCT. RESULTS: GI pigs became circulatory instable 4-6 h after brain death in spite of forced fluid infusion, five pigs showed moderate to severe pulmonary edema on HRCT and median final PaO2 /FiO2 was 29 kPa (Q1; Q3; range 26; 40; 17-76). GII and GIII were circulatory stable (mean aortic pressure > 80 mmHg) and median final PaO2 /FiO2 after 24 h was 72 kPa (Q1; Q3; range 64; 76; 53-91) (GII) and 66 kPa (55; 78; 43-90) (GIII). On HRCT, only two pigs in GII had mild pulmonary edema and none in GIII. More than 50% of HRCT exams revealed unexpected lung disease even in spite of PaO2 /FiO2 > 40 kPa. CONCLUSION: Pharmacological therapy but not forced fluid infusion prevented circulatory collapse and extensive HRCT verified pulmonary edema after acute brain death. HRCT was useful to evaluate lung morphology and revealed substantial occult parenchymal changes justifying efforts toward a more intense use of HRCT in the pre-transplant evaluation.

Pharmacological normalization of circulation after acute brain death.

BACKGROUND: Circulatory instability is a serious problem after brain death in organ donors. The hypotension is often counteracted with infusion of large amounts of crystalloid solutions, which may impair lung function leading to rejection of the lungs as donor organs. The aim was to show that the circulation can be normalized pharmacologically for 24 h in pigs after total removal of the brain and brainstem by decapitation (between C2 and C3). METHODS: Twenty-four 40-kg pigs (n = 8 × 3) were included: non-decapitated, decapitated, and decapitated with pharmacological treatment. All animals got the same basal fluid supply and ventilation. The pharmacological treatment consisted of the neuronal monoamine reuptake blocker cocaine and low doses of noradrenaline and adrenaline. Desmopressin, triiodothyroxine, thyroxine and cortisol were also given. RESULTS: After decapitation, a catecholamine storm occurred, with an increase of noradrenaline and adrenaline by a factor of 79 and 298, respectively. Thirty minutes later, the pigs were hypotensive. The median time to the aortic pressure that was less than 40 mmHg was 9:09 h (range 5:50 to 22:01). After 6 h, the concentration of thyroid hormones and cortisol was significantly reduced. With pharmacological treatment of decapitated animals, the aortic pressure, renal blood flow, creatinine, urine production, liver function and blood gases did not differ significantly from the non-decapitated control animals. CONCLUSION: Pharmacological substitution of pituitary gland function, blockade of peripheral catecholamine neuronal reuptake and low doses of catecholamines normalize circulation in decapitated pigs throughout a 24-h observation period, whereas untreated decapitated pigs all develop severe circulatory collapse within 12 h.

Increased alveolar nitric oxide in early systemic sclerosis.

OBJECTIVES: Assessment of inflammatory activity in interstitial lung disease of systemic sclerosis (SSc) is difficult. Nitric oxide (NO) has gained attention in the pathogenesis of SSc. The aim of the study was to investigate alveolar NO concentration (CA(NO)) in SSc patients with short disease duration and to relate CA(NO) to radiologic findings. METHODS: In a prospective study, 34 consecutive patients with disease duration of less than 2 years from onset of first non-Raynaud symptom and 26 healthy controls were enrolled. Exhaled NO was measured and CA(NO) was calculated. CA(NO) levels were related to the radiologic extent of pulmonary fibrosis measured as the extent of traction bronchiectasis within areas of ground glass opacities and reticulations. RESULTS: CA(NO) levels were increased in patients with early SSc compared to healthy controls (3.52 (2.94-4.09) versus 2.08 (1.6-2.6); p<0.001). Both SSc patients with SSc-ILD (3.56 (3.04-4.73), p<0.001) and SSc patients without SSc-ILD (2.98 (2.68-3.98), p<0.01) had higher CA(NO) levels compared with healthy controls (2.08 (1.6-2.6)). CA(NO) levels did not differ between SSc patients without SSc-ILD and SSc patients with SSC-ILD. CA(NO) levels did not correlate to the extent of pulmonary fibrosis but were associated with the extent of ground glass opacities (rs=0.37, p<0.05) and reticulations (rs=0.37, p<0.05) on HRCT. CA(NO) levels were not correlated to lung function tests. CONCLUSIONS: In patients with early SSc, alveolar NO is increased and may precede radiological changes of SSc-ILD. CA(NO) may therefore be a marker of early lung involvement.