Emergency preservation and resuscitation improve survival after 15 minutes of normovolemic cardiac arrest in pigs

OBJECTIVE: Outcome after prolonged normovolemic cardiac arrest is poor, and new resuscitation strategies have to be found. We hypothesized that the induction of deep hypothermia for emergency preservation and resuscitation (EPR) during prolonged cardiac arrest, before the start of reperfusion, will mitigate the deleterious cascades leading to neuronal death and will thus improve outcome. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: Thirteen pigs, Large White breed (27-37 kg). INTERVENTIONS: After 15 mins of ventricular fibrillation, pigs were subjected to 1) EPR (n = 6), 20 mins of hypothermic stasis induced with a cold saline aortic flush; or 2) 20 mins of conventional resuscitation (n = 7). Then cardiopulmonary bypass was initiated in both groups, followed by defibrillation. Controlled ventilation and mild hypothermia were continued for 20 hrs; survival was for 9 days. For neurologic evaluation, neurologic deficit score (100% = brain dead, 0-10% = normal), overall performance category (1 = normal, 5 = dead or brain dead), and brain histologic damage score were used. MEASUREMENTS AND MAIN RESULTS: In the EPR group, brain temperature decreased from 38.5 degrees C +/- 0.2 degrees C to 16.7 degrees C +/- 2.5 degrees C within 235 +/- 27 secs. Five animals achieved restoration of spontaneous circulation and survived to 9 days: two pigs with overall performance category 2 and three pigs with overall performance category 3. Their neurologic deficit score was 45% (interquartile range 35, 50) and histologic damage score was 142 (interquartile range 109, 159). In the control group, four pigs achieved restoration of spontaneous circulation: one survived to 9 days with overall performance category 3, neurologic deficit score 45%, and histologic damage score 226 (restoration of spontaneous circulation, p = .6; survival, p = .03; overall performance category, p = .02). CONCLUSIONS: EPR is feasible in an experimental pig model and improves survival after prolonged cardiac arrest in pigs. Further experimental studies are needed before this concept can be brought into clinical practice.     

The role of Chlamydia pneumoniae in human aortic disease-a hypothesis revisited.

BACKGROUND: The role of Chlamydia pneumoniae in the pathogenesis of aortic aneurysm is controversial. We investigated the presence of C. pneumoniae in tissue samples excised from patients and controls. METHODS: Aortic wall specimens were obtained from 17 patients with acute Stanford type A aortic dissection, 25 patients with thoracic aortic aneurysms (TAA) and 23 patients with abdominal aortic aneurysms (AAA). Eighty-three tissue samples of 73 control patients free of aortic disease were obtained either at surgery or autopsy. The presence of Chlamydia subspecies DNA (sequences specific for all known Chlamydiaceae) and DNA of C. pneumoniae, C. trachomatis and C. psittaci were assessed by a validated highly sensitive and specific real time polymerase chain reaction (PCR) analysis. Atherosclerotic risk factors were assessed in all patients. RESULTS: We failed to detect C. pneumoniae and C. psittaci-DNA in any of the 148 vessel specimens. C. trachomatis-DNA was detected in 1/65 patients and in none of 83 controls (P=0.43). Chlamydia subspecies DNA was found in samples of eight cases and in one control (P=0.01), however, no significant differences were found between the subgroups aortic dissection (P=0.09), TAA (P=0.99) and AAA (P=0.15) and respective controls. CONCLUSIONS: C. pneumoniae does not play a clinically relevant role in acute and chronic aortic disease. The impact of other organisms of the family Chlamydiaceae needs further evaluation.     

In vitro efficacy of 5 antifungal agents against Candida parapsilosis,Candida orthopsilosis, and Candida metapsilosis as determined by time–kill methodology

Killing activity of amphotericin B, fluconazole, voriconazole, posaconazole, and 5-fluorocytosine was determined against 6 Candida parapsilosis, 3 Candida orthopsilosis, and 4 Candida metapsilosis clinical isolates. After 24 h, 1 of 6 C. parapsilosis, 1 of 3 C. orthopsilosis, and 3 of 4 C. metapsilosis isolates were killed at 1 to 4 μg/mL (1–8× MIC) amphotericin B. The remaining isolates were killed by 2 to 4 μg/mL amphotericin B after 48 h. Fluconazole was fungistatic at ≥1× MIC (0.5–2 μg/mL) against C. parapsilosis and at ≥2× MIC (4–8 μg/mL) against C. orthopsilosis and C. metapsilosis isolates. Voriconazole inhibited C. parapsilosis at ≥1× MIC (0.015–0.12 μg/mL), but the other 2 species were inhibited only at 4 to 8× MIC (0.25–0.5 μg/mL). Against C. orthopsilosis and C. metapsilosis, posaconazole was fungistatic close to the MIC (0.03–0.06 and 0.015–0.03 μg/mL, respectively). Against C. orthopsilosis and C. metapsilosis, fluconazole and voriconazole, but not posaconazole, seem to be less active in vitro than against C. parapsilosis.     

Changes in interleukin-10 mRNA expression are predictive for 9-day survival of pigs in an emergency preservation and resuscitation model

Aim of the study

This study aimed at evaluating (I) the impact of different intra-arrest hypothermia levels on the expression of selected cytokines and (II) their prognostic value for 9-day survival.

Methods

Female Large White pigs (n = 21, 31-38 kg) were subjected to 15 min of ventricular fibrillation, followed by intra-arrest cardiopulmonary bypass cooling for 1, 3, or 5 min achieving brain temperatures (Tbr) of 30.4 ± 1.6, 24.2 ± 4.6 and 18.8 ± 4.0 °C. After 40 min of controlled rewarming, pigs were defibrillated and kept at Tbr of 34.5 °C for 20 h, survival was for 9 days. Plasma samples were analysed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 levels by ELISA. Total RNA out of peripheral blood mononuclear cells was analysed by real-time PCR for IL-1, IL-2, IL-4, IL-10, TNF-α, interferon-γ, inducible NO synthase, and heme oxygenase-1 gene expressions.

Results

Plasma IL-6 and TNF-α levels significantly (p = 0.0001 and 0.0003) increased in all animals within 1 h after resuscitation with no significant differences between groups. Pigs surviving exhibited a decrease in IL-10 expression between baseline and intra-arrest values as compared to non-surviving animals, which showed a slight increase (p = 0.0078). ROC curve analysis revealed that changes in IL-10 expression had a good prognostic power for survival to day 9 (area under the curve = 0.882).

Conclusion

The systemic inflammatory response syndrome after cardiac arrest was reflected by a remarkable increase of plasma IL-6 and TNF-α levels. Intra-arrest hypothermia levels did not influence the expression of selected cytokines. As prognostic marker for survival IL-10 was identified with decreasing mRNA levels during cardiac arrest in survivors.     

Subliminal conditioning of vestibular perception generalizes within otolith organs

Journal of Neurology -     

Co-infection of acyclovir-resistant and acyclovir-sensitive herpes simplex type 2 virus strains in BS-C-1 cells

Co-infection of BS-C-1 cells by the herpes simplex virus type 2 (HSV-2) Curtis strain with its acyclovir (ACV)-resistant mutant (HSV-2-ACV(R)), resulted in a severalfold increase in virus yield, as compared to a single infection. On the other hand, when two viruses (G strain and HSV-2-ACV(R)) belonging to different strains of HSV-2 were involved, their growth was significantly inhibited; the decrease in the titer of the second virus to infect the cells was greater when its infection took place at later times following infection by the first. This inhibition was not due to the shut-off of host cell protein synthesis caused by the first virus, since an HSV-2 mutant which is unable to inhibit the protein synthesis of the host cell was still capable of efficiently inhibiting the growth of the superinfecting virus.