The rabbit blood shunt subarachnoid haemorrhage model.

The recently introduced rabbit blood shunt subarachnoid haemorrhage model is based on the two standard procedures of subclavian artery cannulation and transcutaneous cisterna magna puncture. An extracorporeal shunt placed in between the arterial system and the subarachnoid space allows examiner-independent SAH in a closed cranium. Despite its straightforwardness, it is worth examining some specific features and characteristics of the model. We outline technical considerations to successfully perform the model with minimal mortality and morbidity. In addition, we discuss outcome measures, advantages and limitations, and the applicability of the model for the study of early brain injury and delayed cerebral vasospasm after SAH.

Longitudinal extension of myelomalacia by intramedullary and subdural hemorrhage in a canine model of spinal cord injury

BACKGROUND CONTEXT In canine intervertebral disc (IVD) extrusion, a spontaneous animal model of spinal cord injury, hemorrhage is a consistent finding. In rodent models, hemorrhage might be involved in secondary tissue destruction by biochemical mechanisms. PURPOSE This study aimed to investigate a causal association between the extents of intramedullary, subdural and epidural hemorrhage and the severity of spinal cord damage following IVD extrusion in dogs. STUDY DESIGN/SETTING A retrospective study using histologic spinal cord sections from 83 dogs euthanized following IVD extrusion was carried out. METHODS The degree of hemorrhage (intramedullary, subdural, epidural), the degree of spinal cord damage in the epicenter (white and gray matter), and the longitudinal extent of myelomalacia were graded. Associations between the extent of hemorrhage and the degree of spinal cord damage were evaluated statistically. RESULTS Intramedullary and subdural hemorrhages were significantly associated with the degree of white (p<.001/ p=.004) and gray (both p<.001) matter damage, and with the longitudinal extension of myelomalacia (p<.001/p=.005). Intriguingly, accumulation of hemorrhagic cord debris inside or dorsal to a distended and ruptured central canal in segments distant to the epicenter of the lesion was observed exhibiting a wave-like pattern on longitudinal assessment. The occurrence of this debris accumulation was associated with high degrees of tissue destruction (all p<.001). CONCLUSIONS Tissue liquefaction and increased intramedullary pressure associated with hemorrhage are involved in the progression of spinal cord destruction in a canine model of spinal cord injury and ascending or descending myelomalacia. Functional and dynamic studies are needed to investigate this concept further.

Off-Hour Admission and Outcomes in Patients with Acute Intracerebral Hemorrhage in the INTERACT2 Trial

BACKGROUND Conflicting data exist of an association between off-hour (weekend, holiday, or night-time) hospital admission and adverse outcome in intracerebral hemorrhage (ICH). We determined the association between off-hour admissions and poor clinical outcome, and of any differential effect of early intensive blood pressure (BP) lowering treatment between off- and on-hour admissions, among participants of the Intensive BP Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS Subsidiary analysis of INTERACT2, a multinational, multicenter, clinical trial of patients with spontaneous ICH with elevated systolic BP, randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Primary outcome was death or major disability (modified Rankin scale of 3-6) at 90 days. Off-hour admission was defined as night-time (4:30 p.m. to 8:30 a.m.) on weekdays, weekends (Saturday and Sunday), and public holidays in each participating country. RESULTS Of 2,794 patients with information on the primary outcome, 1,770 (63%) were admitted to study centers during off-hours. Off-hour admission was not associated with risk of poor outcome at 90 days (53% off-hour vs. 55% on-hour; p = 0.49), even after adjustment for comorbid risk factors (odds ratio 0.92; 95% CI 0.76-1.12). Consistency exists in the effects of intensive BP lowering between off- and on-hour admission (p = 0.85 for homogeneity). CONCLUSIONS Off-hour admission was not associated with increased risks of death or major disability among trial protocol participants with acute ICH. Intensive BP lowering can provide similar treatment effect irrespective of admission hours.

Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage.

BACKGROUND Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. METHODS More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. RESULTS Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Δ at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). CONCLUSIONS Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift.

Misoprostol in addition to routine treatment of postpartum hemorrhage: A hospital-based randomized-controlled trial in Karachi, Pakistan

Background: Postpartum hemorrhage (PPH) remains a major killer of women worldwide. Standard uterotonic treatments used to control postpartum bleeding do not always work and are not always available. Misoprostol's potential as a treatment option for PPH is increasingly known, but its use remains ad hoc and available evidence does not support the safety or efficacy of one particular regimen. This study aimed to determine the adjunct benefit of misoprostol when combined with standard oxytocics for PPH treatment. Methods: A randomized controlled trial was conducted in four Karachi hospitals from December 2005 – April 2007 to assess the benefit of a 600 mcg dose of misoprostol given sublingually in addition to standard oxytocics for postpartum hemorrhage treatment. Consenting women had their blood loss measured after normal vaginal delivery and were enrolled in the study after losing more than 500 ml of blood. Women were randomly assigned to receive either 600 mcg sublingual misoprostol or matching placebo in addition to standard PPH treatment with injectable oxytocics. Both women and providers were blinded to the treatment assignment. Blood loss was collected until active bleeding stopped and for a minimum of one hour after PPH diagnosis. Total blood loss, hemoglobin measures, and treatment outcomes were recorded for all participants. Results: Due to a much lower rate of PPH than expected (1.2%), only sixty-one patients were diagnosed and treated for their PPH in this study, and we were therefore unable to measure statistical significance in any of the primary endpoints. The addition of 600 mcg sublingual misoprostol to standard PPH treatments does, however, suggest a trend in reduced postpartum blood loss, a smaller drop in postpartum hemoglobin, and need for fewer additional interventions. Women who bled less overall had a significantly smaller drop in hemoglobin and received fewer additional interventions. There were no hysterectomies or maternal deaths among study participants. The rate of transient shivering and fever was significantly higher among women receiving misoprostol Conclusion: A 600 mcg dose of misoprostol given sublingually shows promise as an adjunct treatment for PPH and its use should continue to be explored for its life-saving potential in the care of women experiencing PPH. Trial Registration: Clinical trials.gov, Registry No. NCT00116480

Prevention and Management of Postpartum Hemorrhage

Este video de formación clínica ofrece orientación sobre el manejo activo de la tercera etapa del parto, el tratamiento de la hemorragia posparto y la hemorragia excesiva

Detection and Differentiation of Intraretinal Hemorrhage in Spectral Domain Optical Coherence Tomography.

PURPOSE The purpose of this study was to classify and detect intraretinal hemorrhage (IRH) in spectral domain optical coherence tomography (SD-OCT). METHODS Initially the presentation of IRH in BRVO-patients in SD-OCT was described by one reader comparing color-fundus (CF) and SD-OCT using dedicated software. Based on these established characteristics, the presence and the severity of IRH in SD-OCT and CF were assessed by two other masked readers and the inter-device and the inter-observer agreement were evaluated. Further the area of IRH was compared. RESULTS About 895 single B-scans of 24 eyes were analyzed. About 61% of SD-OCT scans and 46% of the CF-images were graded for the presence of IRH (concordance: 73%, inter-device agreement: k = 0.5). However, subdivided into previously established severity levels of dense (CF: 21.3% versus SD-OCT: 34.7%, k = 0.2), flame-like (CF: 15.5% versus SD-OCT: 45.5%, k = 0.3), and dot-like (CF: 32% versus SD-OCT: 24.4%, k = 0.2) IRH, the inter-device agreement was weak. The inter-observer agreement was strong with k = 0.9 for SD-OCT and k = 0.8 for CF. The mean area of IRH detected on SD-OCT was significantly greater than on CF (SD-OCT: 11.5 ± 4.3 mm(2) versus CF: 8.1 ± 5.5 mm(2), p = 0.008). CONCLUSIONS IRH seems to be detectable on SD-OCT; however, the previously established severity grading agreed weakly with that assessed by CF.

Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice

Deficiency of blood coagulation factor V or tissue factor causes the death of mouse embryos by 10.5 days of gestation, suggesting that part of the blood coagulation system is necessary for development. This function is proposed to require either generation of the serine protease thrombin and cell signaling through protease-activated receptors or an activity of tissue factor that is distinct from blood clotting. We find that murine deficiency of prothrombin clotting factor 2 (Cf2) was associated with the death of approximately 50% of Cf2−/− embryos by embryonic day 10.5 (E10.5), and surviving embryos had characteristic defects in yolk sac vasculature. Most of the remaining Cf2−/− embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare Cf2−/− neonates died of hemorrhage on the first postnatal day. These studies suggest that a part of the blood coagulation system is adapted to perform a developmental function. Other mouse models show that the absence of platelets or of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in development may be independent of its effects on blood coagulation and instead may involve signal transduction on cells other than platelets.

Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189

The vascular endothelial growth factor (VEGF) has been shown to be a significant mediator of angiogenesis during a variety of normal and pathological processes, including tumor development. Human U87MG glioblastoma cells express the three VEGF isoforms: VEGF121, VEGF165, and VEGF189. Here, we have investigated whether these three isoforms have distinct roles in glioblastoma angiogenesis. Clones that overexpressed each isoform were derived and inoculated into mouse brains. Mice that received VEGF121- and VEGF165-overexpressing cells developed intracerebral hemorrhages after 60–90 hr. In contrast, mice implanted with VEGF189-overexpressing cells had only slightly larger tumors than those caused by parental cells and little evidence of hemorrhage at these early times after implantation, whereas, after longer periods of growth, enhanced angiogenicity and tumorigenicity were apparent. There was rapid blood vessel growth and breakdown around the tumors caused by cells overexpressing VEGF121 and VEGF165, whereas there was similar vascularization but no eruption in the vicinity of those tumors caused by cells overexpressing VEGF189, and none on the border of the tumors caused by the parental cells. Thus, by introducing VEGF-overexpressing glioblastoma cells into the brain, we have established a reproducible and predictable in vivo model of tumor-associated intracerebral hemorrhage caused by the enhanced expression of single molecular species. Such a model should be useful for uncovering the role of VEGF isoforms in the mechanisms of angiogenesis and for investigating intracerebral hemorrhage due to ischemic stroke or congenital malformations.