Prospects for clinical applications of polymer-coated haemoconcentrator on extracorporeal circuit in cardiopulmonary bypass surgeries.

PURPOSE: Extracorporeal circulation circuits used in cardiopulmonary bypass surgeries are increasingly being coated with polymer materials to reduce the thrombogenicity of extracorporeal devices. However, a haemoconcentrator, which corrects haematocrit and electrolyte imbalances, is not coated with polymers. In this study, we sought to assess the filtration performance of polymer-coated haemoconcentrators in order to obtain insight into their prospects for use in clinical applications. METHODS: In vitro experiments were performed to evaluate the water pressure and flow properties of polymer-coated haemoconcentrators by comparing 3 polymer-coated haemoconcentrators with 3 non-coated haemoconcentrators. The cross-sectional surfaces of both types of haemoconcentrators were observed using a scanning electron microscope (SEM). RESULTS: The slopes of the regression lines for estimating the filtrated fluid flow as a function of the transmembrane pressure were 6.286 ± 0.320 for polymer-coated haemoconcentrators and 3.712 ± 0.170 for non-coated haemoconcentrators. These slopes were found to be significantly different and indicate that the filtration velocity is enhanced in polymer-coated haemoconcentrators over that in non-coated haemoconcentrators. However, the hollow fibre damage observed by SEM was not shown to contribute to higher filtration flow in the polymer-coated haemoconcentrator. Taking these results into consideration, we hypothesise that a polymer coating makes a foreign surface on a hollow fibre slippery, owing to the hydrophobicity of the polymer, thereby enhancing the velocity of the filtration. CONCLUSIONS: The results of this preliminary investigation suggest that a polymer coating can enhance the filtration performance of a haemoconcentrator and that polymer-coated haemoconcentrators might be useful in clinical applications.

Trehalose protects against spinal cord ischemia in rabbits.

OBJECTIVE: This study tested to see if trehalose, a cytoprotective disaccharide, protects against spinal cord ischemia in a rabbit model. METHODS: The infrarenal aorta was mobilized in four groups of 10 rabbits. In groups I, II, and III, it was clamped proximally and distally for 20 minutes. In group I, the clamped aorta was infused at 2.5 L/min for 2 hours with lactated Ringer's (LR) solution. In group II, the clamped aorta was infused with 5% trehalose in LR. LR was administered intravenously (2.0 mL/min) in groups I and II starting 30 minutes before clamping. In group III, 5% trehalose in LR was infused intravenously only. Group IV was a sham-operated control group without aortic clamping. At 8, 24, and 48 hours after reperfusion, hind limb function was scored using the Tarlov score (paralysis = 0, perceptible joint movement = 1, good joint movement but unable to stand = 2, able to walk = 3, normal = 4). Histologic analysis and electron microscopy were performed on anterior horn cells. RESULTS: The Tarlov scores in groups I, II, and III were, respectively, 1.1 ± 1.4, 3.5 ± 0.5, and 2.9 ± 0.9 at 8 hours; 0.8 ± 1.2, 3.9 ± 0.3, and 2.9 ± 0.9 at 24 hours; and 0.6 ± 0.7, 3.9 ± 0.3, and 2.7 ± 0.9 at 48 hours after reperfusion. Group IV scores were normal (4 ± 0) at all assessments. These scores were higher in groups II and III than in group I (P < .01) at all assessments. Scores at 24 and 48 hours were higher in group II than in group III (P < .05). In group III, delayed paraparesis developed in one rabbit at 24 hours and in two more at 48 hours. Histopathologic analysis showed the number of normal neurons was higher in groups II (P < .0001), III (P = .006), and IV (P < .0001) vs group I. Electron microscopy confirmed preserved neuronal cell ultrastructure in rabbits with normal limb function. CONCLUSIONS: Transaortic trehalose infusion was protective against paraplegia, whereas intravenous trehalose reduced spinal cord ischemia. This study was preliminary and further studies are needed.

An extremely large coronary aneurysm associated with a quadricuspid aortic valve in an adult patient.

A 68-year-old woman exhibited an increasingly protruding mass on the left heart border on chest X-ray. Transthoracic echocardiography revealed an echo-free mass in the anterior pericardial space. Transesophageal echocardiography revealed blood flow from the proximal left anterior descending coronary into a large coronary artery aneurysm measuring 61 mm × 51 mm in diameter and a quadricuspid aortic valve with a small cusp between the left and right coronary cusps. Coronary angiography demonstrated the presence of a coronary aneurysm connected to the proximal left coronary anterior descending artery. A giant coronary artery aneurysm and pulmonary artery fistulas extending from the left and right coronary arteries were confirmed by surgeons and successfully treated with surgery.

Safety of the paravertebral block in patients ineligible for epidural block undergoing pulmonary resection.

OBJECTIVE: We previously reported the noninferiority of paravertebral block (PVB) to epidural block. In this study, we assessed whether PVB via an intrathoracic approach was also safe for the patients ineligible for epidural block because of, for example, anticoagulation or antiplatelet therapy. METHODS: Patients admitted to our hospital for pulmonary resection between April 2010 and March 2012, and who were ineligible for epidural block for various reasons, were enrolled in this study. A catheter for PVB was inserted in the operative field by the surgeons just before closing the chest. Ropivacaine of 0.2 % was injected at 4 ml/h using an infuser pump for 5 days. Concurrent use of intravenous patient controlled analgesia (IVPCA) for 2 days with PVB was permitted as a post-operative analgesic at the discretion of anesthesiologists. We estimated the post-operative complications in these patients. RESULTS: A total of 35 (15.8 %) consecutive patients were enrolled in this study and successfully completed the study protocol. Thirty-two patients received concurrent IVPCA treatment. Post-operative complications due to PVB were not observed, but other complications included 1 incidence of atrial fibrillation, 1 hypertension, 1 pleural fluid accumulation, 1 respiratory failure requiring mechanical ventilation, and 1 of late chest pain requiring intercostal nerve block. CONCLUSION: This study suggests that PVB is safe in patients ineligible for epidural block and can contribute to their pain relief following pulmonary resection procedure including video-assisted thoracic surgery.

Sodium 4-phenylbutyrate protects against spinal cord ischemia by inhibition of endoplasmic reticulum stress.

OBJECTIVE: Delayed paraplegia after operation on the thoracoabdominal aorta is considered to be related to vulnerability of motor neurons to ischemia. Previous studies have demonstrated the relationship between neuronal vulnerability and endoplasmic reticulum (ER) stress after transient ischemia in the spinal cord. The aim of this study was to investigate whether sodium 4-phenylbutyrate (PBA), a chemical chaperone that reduces the load of mutant or unfolded proteins retained in the ER during cellular stress, can protect against ischemic spinal cord damage. METHODS: Spinal cord ischemia was induced in rabbits by direct aortic cross-clamping (below the renal artery and above the bifurcation) for 15 minutes at normothermia. Group A (n = 6) was a sham operation control group. In group B (n = 6) and group C (n = 6), vehicle or 15 mg/kg/h of sodium 4-PBA was infused intravenously, respectively, from 30 minutes before the induction of ischemia until 30 minutes after reperfusion. Neurologic function was assessed at 8 hours, and 2 and 7 days after reperfusion with a Tarlov score. Histologic changes were studied with hematoxylin-eosin staining. Immunohistochemistry analysis for ER stress-related molecules, including caspase12 and GRP78 were examined. RESULTS: The mean Tarlov scores were 4.0 in every group at 8 hours, but were 4.0, 2.5, and 3.9 at 2 days; and 4.0, 0.7, and 4.0 at 7 days in groups A, B, and C, respectively. The numbers of intact motor neurons at 7 days after reperfusion were 47.4, 21.5, and 44.9 in groups A, B, and C, respectively. There was no significant difference in terms of viable neurons between groups A and C. Caspase12 and GRP78 immunoreactivities were induced in motor neurons in group B, whereas they were not observed in groups A and C. CONCLUSION: Reduction in ER stress-induced spinal cord injury was achieved by the administration of 4-PBA. 4-PBA may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.

Low-dose edaravone injection into the clamped aorta prevents ischemic spinal cord injury.

Previous studies have indicated that high-dose intravenous edaravone (3-10mg/kg) protects against ischemic spinal cord injury. This study examined whether direct injection of low-dose edaravone into the clamped segment of the aorta prevents ischemic spinal cord injury. Spinal cord ischemia was induced in rabbits by aortic clamping below the renal artery and above the aortic bifurcation for 15min at normothermia. In groups A and B, 3 and 1mg/kg of edaravone, respectively, was injected into the clamped segment of the aorta immediately following aortic clamping. In group C, saline was injected. Neurological function was assessed at 8, 24, and 48hr and 7 days after reperfusion with Tarlov criteria. The spinal cord was histologically examined at 7 days with hematoxylin-eosin staining and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The Tarlov score remained grade 4 throughout the period in groups A and B, whereas it dropped to grade 0 or 1 at 7 days in group C, significantly higher in the former two groups. The number of intact motor neurons was significantly greater in groups A and B with less necrotic motor neurons than in group C. There was no significant difference in terms of spinal cord protection between groups A and B. There was no TUNEL-positive neuron in any group, indicating the absence of apoptosis. Low-dose intra-aortic edaravone injection prevents immediate neuronal injury by reducing neuronal cell damage in the early stage as well as delayed neuronal injury at 7 days.

Transcranial motor-evoked potentials following intra-aortic cold blood infusion facilitates detection of critical supplying artery of spinal cord.

OBJECTIVE: In order to determine whether critical intercostal artery is present in the aneurysm during descending thoracic or thoracoabdominal aortic surgery, changes of transcranial motor-evoked potentials (Tc-MEPs) were monitored following infusion of cold blood into the aorta as an adjunct 'on-site assessment'. Accuracy of this method was evaluated. METHODS: Fourteen patients were examined for Tc-MEPs changes following infusion of cold blood (4 degrees C, 300-450 ml) into the aneurysm. The intercostal arteries in the aneurysm were reconstructed when the Tc-MEPs amplitude decreased to below 50% of the baseline within 3 min after cold blood infusion. When the amplitude did not decrease, every intercostal artery in the aneurysm was ligated. RESULTS: The Tc-MEPs amplitude did not decrease in eight cases (57%), while it decreased in six cases (43%). In the former, no case presented with paraplegia despite every intercostal artery being ligated. In the latter, the amplitude recovered after reconstruction in four patients, who had no paraplegia postoperatively. In the remaining two cases, however, the amplitude did not recover: one died of multiple organ failure with postoperative assessment unfeasible; the other developed paraplegia following surgery. Except one case with operative death, both sensitivity and specificity of our criteria with cold blood infusion was 100% in this series. CONCLUSIONS: Cold blood infusion into the clamped segment of aorta accelerates Tc-MEPs changes and can possibly reduce ischemic insults of spinal cord during diagnostic process, while it accurately detects presence of critical intercostal artery in the segment. This method appears to be promising adjunct on-site assessment.

Evoked spinal cord potentials monitored at thoracoabdominal region after trans-intercostal stimulation.

To investigate the feasibility of a novel recording method for trans-intercostal evoked spinal cord potentials (Tic-ESCPs) and the properties of the waveforms, the potentials were recorded and analyzed in an animal model. In two beagle dogs, Tic-ESCPs were recorded at the left twelfth intercostal to fourth lumbar nerves following stimulation at the left eleventh intercostal nerve, either with or without the use of a muscle relaxant. The amplitude and latency of the Tic-ESCP waves were then measured and compared with those of conventional transcranial spinal motor evoked potentials (MEPs). Tic-ESCPs could be obtained at any nerve, with or without the use of a muscle relaxant. The Tic-ESCP waveform was clear and simple, consisting of a small positive (P1) wave and a subsequent large negative (N1) wave. As the site of recording moved farther from the stimulation site, the N1 amplitudes were reduced and the P1 latency was prolonged. Under muscle relaxation, the N1 amplitudes were reduced, and the P1 latencies were shorter. As compared with MEPs, Tic-ESCPs could be evoked by a weaker stimulus, the N1 amplitude was smaller, and the P1 latency was shorter. Tic-ESCP recording was feasible either with or without the use of a muscle relaxant. The Tic-ESCPs showed simple and clear waveforms with smaller stimulations. Therefore, Tic-ESCPs may be useful for intraoperative spinal cord monitoring.

Echo-guided identification of key lumbar arteries supplying the spinal cord in a canine model.

The aim of this study was to anatomically verify echo-guided identification of key lumbar arteries supplying blood to the spinal cord and to examine whether changes in nerve root motion could be used for detecting malperfusion following aortic cross-clamping. In two beagle dogs, nerve root motion was monitored through the intervertebral disc using transesophageal echocardiography. Communications between each lumbar artery and the spinal vasculature were assessed by echogenic signals in the spinal cord following saline injection into each lumbar artery. Nerve root motion immediately disappeared after clamping the aorta and recovered as soon as it was declamped. These changes were induced specifically by clamping the aorta at the first lumbar level. The changes were instantaneous and may be beneficial because of minimal ischemic insult of the spinal cord. In dog #1, the result of the saline injection test was anatomically verified with the presence of a spinal branch. However, in dog #2 echogenic signals appeared in the muscles as well as in the spinal artery. A morphological study showed no spinal branch of the lumbar artery but only an indistinct artery in the intervertebral foramen. These findings probably account for those cases in humans where there is unsuccessful visualization of the Adamkiewicz artery by angiography. Consequently, the above two assessments identified the key artery. Cessation of nerve root motion following segmental clamping of the aorta and echogenic signals in the spinal cord following saline injection into a lumbar artery may represent the key artery with respect to hemodynamics and perfusion, respectively.