Endothelial progenitor cells in regeneration after acute lung injury: do they play a role?

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common disorders in patients requiring critical care. The clinical management of these disorders is difficult and unrewarding, and thus they are among the most common causes of death in intensive care units. The activation and damage of pulmonary endothelium comprise the hallmark of ALI/ARDS. Therefore, the recruitment of circulating endothelial progenitor cells (EPCs) to these lesions may exert a beneficial effect on the clinical course of ALI/ARDS. Consequently, cell-based therapies using stem cells to regenerate lung tissue have emerged as potential novel treatment strategies. Although initial studies suggested implantations of exogenously administered bone marrow-derived progenitor cells into damaged vessel walls, recent evidence indicates that this is rather a rare occurrence with uncertain physiologic significance. In the past few years, different populations of progenitor cells were identified, with different functional capacities. This review (1) highlights the different populations of EPCs identified or administered in different models of ALI/ARDS, (2) reports on whether beneficial effects of EPCs could be demonstrated, and (3) puts the conflicting results of different studies into perspective.

Influence of the pre-operative time in upright sitting position and the needle type on the incidence of post-dural puncture headache (PDPH) in patients receiving a spinal saddle block for anorectal surgery.

BACKGROUND: A spinal saddle block can be a safe method for anorectal surgery with a low rate of complications when performed with the right technique. A dreaded complication is the post-dural puncture headache (PDPH), which can be decreased by the use of non-cutting spinal needles. Regrettably, cutting Quincke (Q)-type needles are still widely used for economic reasons. Besides size and design of a spinal needle, the pre-operative time in upright sitting position may also influence the incidence of PDPH after spinal saddle block. METHODS: Within 4 months, 363 patients undergoing anorectal surgery in saddle block technique were randomised to receive either a 27-gauge (G) pencil-point (PP) or a 27-G Q spinal needle and were pre-operatively left in upright sitting position for 10 or 30 min, respectively. The incidence of PDPH was assessed 1 week after the operation via a telephone interview. RESULTS: Three hundred sixty three patients (219 males/144 females) were analysed. Fifteen patients (4.1%) developed PDPH. Patients receiving spinal anaesthesia with a Q needle suffered significantly more frequently from PDPH [Q: n = 12 (6.6%) vs. PP: n = 3 (1.7%), p = 0.02], but there was no association between PDPH and pre-operative time in the upright position (p = 0.20). CONCLUSIONS: These data prove that using 27-G PP needles is the method with the fewest side effects caused by spinal saddle block, and suggest that the time spent sitting in the upright position is not clinically relevant.

High incidence of post-dural puncture headache in patients with spinal saddle block induced with Quincke needles for anorectal surgery: a randomised clinical trial.

PURPOSE: Spinal saddle block represents nearly the ideal anaesthesia technique for anorectal surgery. Post-dural puncture headache (PDPH) is a dreaded complication but can be decreased by the use of non-cutting spinal needles to rates less than 1%. Though, cutting Quincke type needles are still widely used for economic reasons, leading to a higher rate of PDPH. We performed this study to demonstrate a reduction of PDPH by the use of very small 29-G compared with commonly used 25-G Quincke type spinal needles. METHODS: Two hundred sixteen adult patients (male/female, 19-83 years, ASA status I-III) were randomised 1:1 to groups, in which either a 25-G or a 29-G Quincke type spinal needle was used for a spinal saddle block. The incidence of PDPH was assessed during 1 week after surgery. RESULTS: Thirty-nine of 216 patients developed PDPH but there was no difference between the two needle sizes (25-G, n = 18/106 vs. 29-G, n = 21/110, p = 0.6870). Women suffered significantly more from PDPH than men (23/86 vs. 16/130, p = 0.0069). Ambulatory patients had a later onset of PDPH than in-patients (24 h [0.5-72] vs. 2 h [0.2-96], p = 0.0002) and the headache was more severe in these patients (NRS 7 [2-10] vs. NRS 3 [1-8], p = 0.0009). CONCLUSIONS: The use of 29-G compared with 25-G Quincke needles led to no reduction of PDPH and is considerably higher compared with data from pencil-point needles. The use of non-cutting or pencil-point spinal needles should become the standard for performing spinal saddle block.

Influence of sedation on patients' perceptions and recovery in patients undergoing minor perianal procedures under spinal saddle block.

OBJECTIVES: Additional intra-operative sedation may help improve acceptability and comfort of anaesthesia in patients undergoing minor anorectal (perianal) procedures under spinal saddle block. This observational study was done to determine which patients request sedatives and to what extent sedatives affect the patients' recovery. SUBJECTS AND METHODS: During a 6-month period, 500 patients undergoing minor perianal procedures received 1.0 ml hyperbaric bupivacaine (0.5%). On request, a light sedation with propofol in bolus application was provided. Patients were evaluated postoperatively using a standardized questionnaire about their perceptions before, during and 48 h after the administration of anaesthesia. RESULTS: More female (91/143, 63.6%) than male (136/259, 52.5%) patients (p = 0.0312) received sedation. Patients with sedation were significantly younger (46.7 +/- 13.8 vs. 50 +/- 13.8 years, p = 0.0171) and had a lower body mass index (BMI; 25.6 +/- 4.3 vs. 27.5 +/- 5.1, p < 0.0001). Time to mobilization and first micturition was significantly longer in patients with sedation (4.8 vs. 4.4 h, p = 0.0194 and 5.8 vs. 5.4 h, p = 0.0188), which was associated with a higher incidence of nausea (7.5 vs. 1.7%, p = 0.0083). CONCLUSIONS: Female gender, younger age, lower body weight and lower BMI were associated with higher subjective requirements for sedation. The use of sedation showed prolongation of time to first mobilization and micturition and a higher incidence of nausea.

Practicability and patients' subjective experiences of low-dose spinal anaesthesia using hyperbaric bupivacaine for transanal surgery.

PURPOSE: The safety, effectiveness and long lasting post-operative analgesia make spinal anaesthesia in saddle block technique an "ideal" method for transanal surgery. To improve patient satisfaction and offer reliable operation conditions to surgeons, this study quantifies practicability and patients' subjective experiences with this technique. METHODS: Within a 5-month period, 400 consecutive patients undergoing transanal surgery in saddle block technique were evaluated by a standardised questionnaire. RESULTS: The success rate of spinal anaesthesia was 99.5%. Side effects occurred far less frequently as mentioned in the literature. The duration of the sensory block was about twice as long as the time until first mobilisation and micturition. Despite some negative experiences during the procedure, 92% of the investigated patients would choose a saddle block again. CONCLUSIONS: Both from reasons of practicability and from patients' view, spinal anaesthesia in saddle block technique can be thoroughly recommended for transanal surgery. Patients undergoing a stapler haemorrhoidectomy should receive additional opioids.

Hypothermic injury: the mitochondrial calcium, ATP and ROS love-hate triangle out of balance.

BACKGROUND/AIMS: Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine. METHODS: Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species and reduced thio-group measurement, intracellular calcium measurement and mitochondrial calcium staining were performed in the study. RESULTS: Intracellular ATP was almost completely depleted within 12 hrs of hypothermic preservation in untreated human umbilical vein endothelial cells (HUVEC), while dopamine pre-treatment significantly delayed ATP depletion. 4 hrs after hypothermia a redox imbalance was observed in untreated cells, which increased with the duration of hypothermia. The redox imbalance was primarily caused by depletion of SH reduction equivalents and was significantly inhibited by dopamine. In addition, hypothermia-induced Ca(2+) influx and mitochondrial Ca(2+) accumulation were both prevented by dopamine. The protective effect of dopamine was abrogated by ionomycin and sodium azide and partly by oligomycin and CCCP. CONCLUSIONS: Our data demonstrated that loss of intracellular ATP, generation of a redox imbalance and accumulation of intracellular Ca(2+) underlie cold preservation injury. Dopamine improves the redox balance, prevents intracellular Ca(2+) accumulation and delays ATP depletion.

Donor dopamine treatment limits pulmonary oedema and inflammation in lung allografts subjected to prolonged hypothermia.

BACKGROUND: Endothelial barrier dysfunction severely compromises organ function after reperfusion. Because dopamine pretreatment improves hypothermia mediated barrier dysfunction, we tested the hypothesis that dopamine treatment of lung allografts positively affects tissue damage associated with hypothermic preservation and reperfusion. METHODS: Rats were treated for 1 hr with dopamine (5 microg/min/kg) or vehicle (NaCl). Thereafter lungs were explanted, flushed with Perfadex solution and stored at 4 degrees C for different time periods. Peak inspiratory pressure (PIP), pulmonary arterial pressure (PAP), and lung weight were measured online during reperfusion. Inflammatory mediators in the perfusate and the expression of adhesion molecules in situ were measured after perfusion. RESULTS: Lungs could tolerate a cold ischemia time of up to 6 hr with stable PIP, PAP, and no edema formation upon reperfusion. Cold ischemia time above 6 hr significantly increased PIP, PAP, and pulmonary edema in untreated but not in dopamine treated lungs (P< or =0.001 dopamine treated vs. untreated). Perfusion and ventilation alone induced a strong up-regulation of cytokine-induced neutrophil chemoattractant-1 and adhesion molecules in untreated lungs, whereas in dopamine treated lungs significantly lower levels were found. Dopamine treatment also inhibited tissue damage associated with hypothermic preservation as measured by nicotinamide adenine dinucleotide staining. CONCLUSION: Our study suggests that donor dopamine treatment is a highly effective modality to maintain organ quality of lung allograft. These findings are of high clinical relevance because prevention of tissue damage might reduce complications associated with lung transplantation and hence improve graft survival in lung transplant recipients.

Hypothermia-induced loss of endothelial barrier function is restored after dopamine pretreatment: role of p42/p44 activation.

BACKGROUND: Donor dopamine usage is associated with improved immediate graft function after renal transplantation. Although prolonged cold preservation results in an increased vascular permeability, the present study was conducted to examine in vitro and in vivo if dopamine pretreatment influences endothelial barrier function under such conditions. METHODS: To assess cold preservation injury in vitro and in vivo, cultured human umbilical vein endothelial cells (HUVEC) and Lewis donor rats were pretreated with dopamine or isotonic saline prior to cold storage. Injury was determined by lactate dehydrogenase (LDH) release, histology, and functional analysis. RESULTS: In vitro cold storage resulted in intercellular gap formation in both untreated and dopamine pretreated HUVEC. In the latter monolayer integrity was completely restored upon rewarming and paracellular transport of fluorescein isothiocyanate-dextran was significantly reduced. In dopamine treated HUVEC, intercellular gap formation was independent of cell death and was associated with redistribution of junctional proteins and condensation of cytoskeleton proteins. In untreated HUVEC proteolysis and cell death were clearly evident after hypothermia. Closing of intercellular gaps was dependent on p42/p44 activation. Regeneration of adenosine triphosphate was only observed in dopamine pretreated cells. Only in dopamine treated Lewis renal allografts subjected to cold storage, activation of p42/p44 occurred upon rewarming. These grafts had a better renal function and displayed less inflammatory cells five days after transplantation. CONCLUSION: Our study demonstrates beneficial effects of dopamine treatment on cold storage induced endothelial barrier disturbances. This may contribute to the positive effects of catecholamines on immediate graft function of renal allografts in men.