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Atrial natriuretic peptide (CDD/ANP-99-126) has been identified as a bronchodilator in various species including humans. We investigated the effect of urodilatin (CDD/ANP-95-126) in 18 clinically stable asthmatics showing an increase of the FEV1 by > or = 15% after salbutamol inhalation. Prior to the study inhaled beta 2-agonists were withheld for 8 h. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure, and heart rate in intravenous infusion of 20, 40 or 60 ng kg-1 min-1 urodilatin was administered for 40 min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of 1.25 mg salbutamol. Forty and 60 ng kg-1 min-1 urodilatin showed a significant effect on the central (FEV1, PEF, MEF75) and peripheral airways (MEF50, MEF25) after 10 min infusion (P < 0.05). A bronchodilation not significantly different from 1.25 mg salbutamol was induced by 40 ng kg-1 min-1 in the central airways only, while 60 ng kg-1 min-1 led to a similar effect at all levels of the bronchial tree. Lung function parameters returned to baseline within 30 min after cessation of the urodilatin infusion. Heart rate showed a tendency to increase after 40 min infusion (P < 0.05), but blood pressure did not change significantly. In conclusion, the maximal bronchodilating effect of intravenous urodilatin in clinically stable asthmatics was comparable to 1.25 mg salbutamol.

The protective effect of 11.4, 22.8 or 45.6 pmol/kg/min cardiodilatin/atrial natriuretic peptide (CDD/ANP-(99–126)), urodilatin (CDD/ANP-(95–126)) or vehicle intravenously against acetylcholine-induced bronchoconstriction was compared in spontaneously breathing, halothane-anesthetized Wistar rats. The inhalation of acetylcholine induced significant alterations of the spontaneous breathing parameters evaluated by whole-body plethysmography without significant differences between the treatment groups. Forced parameters detect airflow changes with a greater sensitivity and were measured in hyperventilation-induced temporary apnoea after the challenge. The forced expiratory volume in 0.1 s revealed a significant protective effect of 11.4 pmol/kg/min urodilatin compared to the controls whereas the parameters of the forced expiratory flow-volume curve were significantly preserved by 11.4 and 22.8 pmol/kg/min urodilatin (P < 0.05). Urodilatin showed protective effects against an acetylcholine challenge whereas CDD/ANP-(99–126) was without significant influence.

Pulmonary rejection and infection are the most important complications after lung transplantation. To evaluate the diagnostic value of pulmonary function testing for early detection and discrimination of these complications, seven heart-lung recipients were examined. The diagnosis of each complication was confirmed by clinical and laboratory findings including transbronchial biopsies and bronchoalveolar lavage. Eight episodes of rejection, ten episodes of viral infection and six episodes of bacterial pneumonia were analyzed. Pulmonary rejection was associated with a significant fall in the FEV 1 /IVC% and the FEF50%. In viral infection, the most impressive finding was a reduction in the Dco, whereas no obstructive or restrictive airway dynamics were observed. During bacterial pneumonia, pulmonary function measurement revealed a decrease in IVC without signs of obstructive airway dynamics. Adequate treatment resulted in reconstitution of pretreatment values. Assessment of lung function provides valuable information for the diagnosis of pulmonary complications following HLTx.

The effects of acute stress during a parachute jump on hormonal responses were studied in 12 experienced and 11 inexperienced military parachutists. Each subject performed two jumps. Prior to and immediately after each jump blood samples were drawn and analysed for plasma levels of cortisol, prolactin, thyrotropin (TSH), somatotropin (STH), and luteinizing hormone (LH). While there was a significant increase in cortisol, prolactin and TSH levels after both jumps, no alterations could be observed in STH and LH levels. Stress-induced hormonal responses were not affected by jump experience. There was also no association between the endocrine variables and anxiety scores.

Despite omental wrap and avoidance of prophylactic administration of corticosteroids in the early postoperative phase, ischemic bronchial complications still represent an important source of early morbidity and mortality following lung transplantation. In a retrospective analysis, the effect of pharmacological enhancement of pulmonary collateral flow on bronchial healing was investigated. Thirty-nine consecutive unilateral or bilateral transplant procedures (Tx) were analyzed. Immunosuppression consisted of rabbit antithymocyte globulin (RATG), cyclosporine A, and azathioprine. In group 1 (10 Tx, 12 anastomoses) routine immunosuppression was employed and the anastomoses wrapped with an omental or pericardial pedicle. In group 2 (29 Tx, 41 anastomoses) PGI2 (4 ng/kg per min x 48 h), heparin (200 U/kg per day), and prednisolone (0.5 mg/kg per day) were added to the therapeutic regimen. The 2 groups were comparable with respect to age and sex of the patients, primary diagnosis, type of transplant, intraoperative use of extracorporeal circulation, graft ischemia, duration of mechanical ventilation, and mortality. Bronchoscopic evidence of a significant bronchial ischemia (extending more than 1 cartilaginous ring beyond the anastomosis) was seen in 8 of 12 anastomoses in group 1 vs 14 of 53 anastomoses in group 2 (P = NS). In group 1, significant bronchial stenosis required implantation of an endobronchial silicone stent in 6 of 12 anastomoses, whereas in group 2, no significant bronchial stenosis occurred (P less than 0.01). No negative effects possibly related to the prophylactic administration of corticosteroids could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

A first-time parachute jump was chosen as a model to evaluate the endocrine response to acute psychological stress. In 43 inexperienced tandem parachutists, blood was drawn continuously from 2 h before to 1 h after the jump and analyzed at 10-min intervals for plasma concentrations of epinephrine (E), norepinephrine (NE), cortisol, GH, PRL, and TSH. In addition, heart rate was recorded throughout the experiment. There was a significant increase in heart rate and E concentrations during the jump itself. NE, cortisol, GH, PRL, and TSH peaked with a latency of 10-20 min. Apart from cortisol and TSH concentrations, which were still elevated 1 h after the stress event, plasma levels of the other endocrine variables normalized within 1 h following the jump. Statistically significant cross-correlations could be observed between E and NE (r = 0.60, no time lag) and between E and PRL (r = 0.58, 10-min time lag) only. Even in a very homogenous group of subjects and under well-controlled conditions, endocrine responses to acute psychological stress show considerable variations.

In animal studies, the bronchial effects of urodilatin (URO, CDD/ANP-95-126, INN: ularitide) were superior to those of cardiodilatin/atrial natriuretic peptide (CDD, CDD/ANP-99-126). We compared the bronchodilating properties of intravenous URO and CDD in 36 clinically stable asthmatics showing a β 2 -agonist-induced increase of the FEV 1 by ≥ 15%. Any aerosol medication was discontinued for at least 8 h prior to the study. After baseline measurements of lung function parameters (FEV 1 , VC, PEF, MEF 75 , MEF 50 , MEF 25 ) an intravenous infusion of 5.7, 11.4 or 17.1 pmol/kg/min URO or CDD was administered for 40 min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of 1.25 mg salbutamol (SALB). Both peptides had significant effects. While 11.4 pmol/kg/min URO dilated the central airways (FEV 1 , PEF, MEF 75 ) slightly more potently than the peripheral bronchioles (MEF 50 , MEF 25 ), 17.1 pmol/kg/min URO was as effective as SALB at all levels of the tracheobronchial tree. CDD reached only 50% of the SALB effect without a predominant localization of its action. The cardiovascular parameters revealed a significantly stronger vasorelaxant activity of CDD. In conclusion, the dose-dependent bronchodilating properties of intravenous URO were significantly superior to those of CDD.

The role of neuropeptides in the psychoneuroendocrinological stress response is largely unknown. In this study the effect of acute psychological stress on beta-endorphin and substance-P plasma concentrations was investigated and further the effect of different anxiety levels or control attributions on beta-endorphin or substance-P levels were determined. Blood samples were obtained from 47 inexperienced tandem-parachutists 2 h before, immediately after, and 1 h after a parachute jump and plasma concentrations of beta-endorphin and substance-P were analysed. Anxiety levels and control attributions were assessed by psychometric scales. Whereas substance-P concentrations seemed to be unaffected by the jump stress, there was a transient but significant increase in beta-endorphin levels immediately after jumping. However, subjects higher in state-anxiety at the point of jumping (exit) displayed higher substance-P values at all three time points compared to the "low-anxiety" jumpers. In addition, stress-induced beta-endorphin secretion was dependent on subjective control attributions.

Stress has been suggested for a long time to be associated with a decrease in natural killer (NK) activity. There is also accumulating evidence from psychoneuroimmunological research1 that stress situations such as examination2,3 or bereavement4 may alter a wide range of immunological functions, especially NK cell function. Moreover, increased incidence of viral infections or cancer have been reported in stressed populations5,6.

The occurrence of severe graft failure after lung transplantation which appears refractory to conventional treatment represents a difficult situation with regard to the therapeutic strategies available. Of 17 patients undergoing single lung transplantation at our center, 2 developed early graft failure. In both, temporary artificial cardiopulmonary support by means of extracorporeal membrane oxygenation became necessary as a bridge to retransplantation. Both patients were successfully retransplanted after 8 h and 232 h, respectively, of extra-corporeal support. Postoperatively, there was a variety of complications. The first patient completely recovered from temporary severe cerebral dysfunction diagnosed as "locked-in syndrome". She was discharged from hospital on the 93rd postoperative day and remains alive and well 10 months after her operation. The other patient recovered well early after retransplantation. Later, however, airway problems developed, requiring the implantation of endotracheal stents. Cachexia and several episodes of viral pneumonia contributed to the progressive deterioration of her clinical status. She finally died after being hospitalized for 5 months after the original operation. These two cases illustrate the feasibility of using extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.