Primary angioplasty for any patient with ST-elevation myocardial infarction? Guideline-adherent feasibility and impact on mortality in a rural infarction network.

AIMS: The aim of this study was to assess the guideline-adherent feasibility of area-wide primary angioplasty in rural German surroundings and its impact on reperfusion and outcome in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: All consecutive patients with acute STEMI (n = 347) admitted to any of the hospitals (5 non invasive and 1 invasive with established 24 h/7 days primary angioplasty service) in a 350.000 inhabitant rural area during the year 2002 (n = 184) and 2005 (n = 163) were included in this registry. In 2002, emergency medical services transferred acute STEMI patients to the nearest emergency room, where reperfusion therapy (fibrinolysis or primary angioplasty) was organised. In 2005, all patients were transferred directly to the cathlab bypassing any emergency room when possible. Primary angioplasty increased from 53 to 89% (p < 0.01), fibrinolysis decreased from 27 to 2% (p < 0.01) and the no revascularisation rate from 21 to 9% (p < 0.01). Onset of pain to balloon time in primary angioplasty was reduced from median 339 to 191 min (p < 0.01), median first medical contact to balloon time in 2005 was 101 min. Overall, 6-month mortality decreased from 19 to 10% (p = 0.03). CONCLUSIONS: After transition to a uniform primary angioplasty concept, an increase in overall reperfusion rates and a decrease in time delays could be observed in a rural German infarction network.

Intratidal compliance-volume curve as an alternative basis to adjust positive end-expiratory pressure: a study in isolated perfused rabbit lungs.

OBJECTIVE: Repeated collapse and reopening of alveoli have been shown to aggravate lung injury, which could be prevented by positive end-expiratory pressure (PEEP). Yet, how to adjust optimum PEEP is a matter of debate. We suggest a new strategy to adjust PEEP, which is based on the analysis of the intratidal compliance-volume curve. This approach was compared with a strategy based on the static pressure-volume curve. Furthermore, two other ventilator settings were investigated. One served as a negative control likely to provoke atelectasis, and the other was expected to induce overdistension. DESIGN: Prospective, randomized block design. SETTING: Laboratory. SUBJECTS: Isolated, perfused, and ventilated rabbit lungs. INTERVENTIONS: Tidal volumes of 8 mL/kg of body weight were used throughout. After stabilization, the lungs were randomized to one of four protocols (lasting 120 mins; n = 6 per group). Group 1 was ventilated at zero end-expiratory pressure. In group 2, PEEP was set above the lower inflection point of the static pressure-volume curve. In group 3, adjustment of PEEP was based on the intratidal compliance-volume curve, as determined by the slice method. In group 4, increasing PEEP levels ensured a plateau airway pressure of 20-25 cm H2O likely to provoke overdistension. MEASUREMENTS AND MAIN RESULTS: The ventilation/perfusion (VA/Q) distribution was analyzed by the multiple inert gas elimination technique. Alveolar derecruitment was indicated by shunt and low VA/Q areas as observed in group 1. In groups 2 and 3, VA/Q data initially indicated full recruitment. In contrast to group 3, shunt increased in group 2 near completion of the experiments. Group 4 showed complete recruitment, but the VA/Q distribution included high VA/Q areas. CONCLUSIONS: The intratidal compliance-volume curve represents a rational basis for adjusting PEEP in the isolated lung model. Because this strategy does not require invasive measures and facilitates continuous assessment of ventilator settings, it may be of clinical interest.

Different strategies to keep the lung open: a study in isolated perfused rabbit lungs.

OBJECTIVE: Atelectatic alveoli can be recruited or kept open either by sustained inflation maneuvers or by positive end-expiratory pressure (PEEP). Little is known about potential interactions between both approaches. Especially, it is not known whether the recruiting effect of sustained inflation maneuvers is maintained in combination with a low PEEP, as suggested recently. In an attempt to answer this question, we combined sustained inflation maneuvers with either high or low PEEP. Both approaches were compared with a strategy likely to result in alveolar atelectasis and with another ensuring adequate alveolar recruitment by adjustment of PEEP alone. DESIGN: Randomized block design. SETTING: Laboratory. SUBJECTS: Isolated perfused rabbit lungs (n = 28). INTERVENTIONS: The lungs were ventilated with a tidal volume of 8 mL/kg. After stabilization, the lungs were randomized to one of four ventilatory strategies, which then were followed for 120 mins: a) PEEP 1 cm H2O (PEEP1, negative control); b) PEEP 1 cm H2O and 30 sec-sustained inflations (20 cm H2O) every 30 mins (SI-1); c) PEEP 3 cm H2O combined with sustained inflations (SI-3); and d) PEEP repeatedly adjusted following a previously established strategy ensuring full alveolar recruitment (DYN, positive control). MEASUREMENTS AND MAIN RESULTS: Distribution of ventilation and perfusion (Va/Q distribution) was analyzed by the multiple inert gas elimination technique. Volume-dependent compliance within the tidal volume was determined by using the slice method. Shunt and Va/Q mismatch significantly differed between SI-1 and SI-3, indicating full alveolar recruitment only in the latter. Data of SI-1 did not differ substantially from those of PEEP1, and data obtained in SI-3 were similar to those of DYN. CONCLUSIONS: First, enduring alveolar recruitment by sustained inflation maneuvers is only possible when the alveoli are stabilized thereafter by sufficient PEEP. Second, a ventilation strategy that uses repeated sustained inflations on a comparably high PEEP may not be superior to adequate adjustment of PEEP alone.

Thiopental inhibits the activation of nuclear factor kappaB.

BACKGROUND: Thiopental is frequently used for the treatment of intracranial hypertension after severe head injury. Its long-term administration increases the incidence of nosocomial infections, which contributes to the high mortality rate of these patients. However, the mechanism of its immunosuppressing effect remains unknown. METHODS: The effect of thiopental (200-1000 microg/ml) on the activation of the nuclear transcription factor kappaB (NF-kappaB; electrophoretic mobility shift assays), on NF-kappaB-driven reporter gene activity (transient transfection assays), on the expression of NF-kappaB target genes (enzyme-linked immunoassays), on T-cell activation (flow cytometric analyses of CD69 expression), and on the content of the NF-kappaB inhibitor IkappaB-alpha (Western blotting) was studied in human T lymphocytes in vitro. RESULTS: Thiopental inhibited the activation of the transcription factor NF-kappaB but did not alter the activity of the cyclic adenosine monophosphate response element binding protein. Other barbiturates (methohexital), anesthetics (etomidate, propofol, ketamine), or opioids (fentanyl, morphine) did not affect NF-kappaB activation. Thiopental-mediated suppression of NF-kappaB could be observed in Jurkat cells and in primary CD3+ lymphocytes from healthy volunteers, was time- and concentration-dependent, occurred at concentrations that are clinically achieved, and persisted for hours after the incubation. It was associated with an inhibition of NF-kappaB-driven reporter gene activity, of the expression of interleukin-2, -6, and -8, and interferon gamma, and of the activation of CD3+ lymphocytes. Suppression of NF-kappaB appeared to involve reduced degradation of IkappaB-alpha. CONCLUSION: The results demonstrate that thiopental inhibits the activation of NF-kappaB and may thus provide a molecular mechanism for some of the immunosuppressing effects associated with thiopental therapy.