Positive end-expiratory pressure aggravates left ventricular diastolic relaxation further in patients with pre-existing relaxation abnormality.

BACKGROUND: Positive end-expiratory pressure (PEEP) has been known to adversely influence cardiac output. Even though left ventricular (LV) diastolic function significantly contributes to LV performance, the effects of PEEP on LV diastolic function remains controversial. We, therefore, aimed to examine the effects of PEEP on LV diastolic function by use of pulsed wave Doppler tissue imaging in patients with pre-existing LV relaxation abnormality. METHODS: Seventeen patients with peak early diastolic velocity of lateral mitral annulus (E') <8.5 cm s(-1) among patients who underwent coronary artery bypass graft surgery were evaluated. Echocardiographic and haemodynamic variables were measured with 0, 5, and 10 cmH2O of PEEP. E' and deceleration time (DT) of peak early transmitral filling velocity (E) were used as echocardiographic indicators of LV diastolic function. RESULTS: Mean arterial blood pressure decreased during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. E' showed a gradual and significant decrease with an incremental increase in PEEP (6.9 ± 0.9, 5.8 ± 0.9, and 5.2 ± 1.2 cm s(-1) during 0, 5, and 10 cmH2O PEEP, respectively), and DT of E was prolonged during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. CONCLUSIONS: Increasing PEEP led to a progressive decline in LV relaxation in patients with pre-existing LV relaxation abnormality.

A laboratory study of the effects of processing blood through a cell salvage device and leucocyte depletion filter on levels of pro-inflammatory cytokines and bradykinin.

We investigated changes in concentrations of interleukin-1ß, interleukin-6, tumour necrosis factor-α and bradykinin in blood during passage through a cell salvage device and a leucocyte depletion filter, with or without application of subatmospheric pressure across the filter. Blood samples from 19 healthy women undergoing scheduled caesarean section showed concentrations of cytokines and bradykinin in blood filtered under gravity flow that were equal to or significantly lower than those of pre-operative venous blood samples. They were also significantly lower than that in postoperative orthopaedic shed blood, which is commonly reinfused after orthopaedic surgery. A minority of samples taken from blood that had been filtered using subatmospheric pressure showed raised interleukin-6 concentrations. We suggest that use of a leucocyte depletion filter for cell-salvaged blood with gravity flow is likely to be safe with regard to concentrations of cytokines and bradykinin. However, this may not hold true for the filter used with subatmospheric pressure. If transfusion of salvaged blood using a leucocyte depletion filter seems to induce hypotension, elevation of interleukin-6 should be suspected.

Impact of intravenous lidocaine on myocardial injury after off-pump coronary artery surgery.

BACKGROUND: Lidocaine has been demonstrated to exert cardioprotective effects against myocardial ischaemia and reperfusion injury. We evaluated whether a continuous i.v. infusion of lidocaine reduced myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). METHODS: In this randomized, double-blinded trial, 99 patients received i.v. lidocaine 2% (i.e. a 1.5 mg kg(-1) bolus at induction of anaesthesia followed by a 2.0 mg kg(-1) h(-1) infusion intraoperatively) or an equal volume of saline. Serum creatine kinase-myocardial band (CK-MB) and troponin I (TnI) concentrations were measured before surgery, upon arrival in the intensive care unit, and at 6, 24, 48, and 72 h after surgery. Cardiac enzymes, other biological markers, and rate of postoperative adverse events were compared between the groups. RESULTS: The median (25-75% inter-quartile range) TnI [0.90 (0.43-1.81) vs 1.71 (0.88-3.02) ng ml(-1), P=0.027] and CK-MB [6.5 (3.9-12.3) vs 9.8 (6.0-18.6) ng ml(-1), P=0.005] concentrations 24 h after surgery were significantly lower in the lidocaine group than in the control group. Moreover, lidocaine infusion reduced the total area under the curve of TnI and CK-MB release after surgery by 42% and 27%, respectively, compared with control. CONCLUSIONS: Continuous i.v. infusion of lidocaine during surgery reduces myocardial injury in patients undergoing OPCAB.

Integrated strain array for cellular mechanobiology studies.

We have developed an integrated strain array for cell culture enabling high-throughput mechano-transduction studies. Biocompatible cell culture chambers were integrated with an acrylic pneumatic compartment and microprocessor-based control system. Each element of the array consists of a deformable membrane supported by a cylindrical pillar within a well. For user-prescribed waveforms, the annular region of the deformable membrane is pulled into the well around the pillar under vacuum, causing the pillar-supported region with cultured cells to be stretched biaxially. The optically clear device and pillar-based mechanism of operation enables imaging on standard laboratory microscopes. Straightforward fabrication utilizes off-the-shelf components, soft lithography techniques in polydimethylsiloxane, and laser ablation of acrylic sheets. Proof of compatibility with basic biological assays and standard imaging equipment were accomplished by straining C2C12 skeletal myoblast cells on the device for 6 hours. At higher strains, cells and actin stress fibers realign with a circumferential preference.

YH12852, a potent and highly selective 5-HT4 receptor agonist, significantly improves both upper and lower gastrointestinal motility in a guinea pig model of postoperative ileus.

BACKGROUND: Postoperative ileus (POI) is a transient gastrointestinal (GI) dysmotility that commonly develops after abdominal surgery. YH12852, a novel, potent and highly selective 5-hydroxytryptamine 4 (5-HT4 ) receptor agonist, has been shown to improve both upper and lower GI motility in various animal studies and may have applications for the treatment of POI. Here, we investigated the effects and mechanism of action of YH12852 in a guinea pig model of POI to explore its therapeutic potential. METHODS: The guinea pig model of POI was created by laparotomy, evisceration, and gentle manipulation of the cecum for 60 seconds, followed by closure with sutures under anesthesia. Group 1 received an oral administration of vehicle or YH12852 (1, 3, 10 or 30 mg/kg) only, while POI Group 2 was intraperitoneally pretreated with vehicle or 5-HT4 receptor antagonist GR113808 (10 mg/kg) prior to oral dosing of vehicle or YH12852 (3 or 10 mg/kg). Upper GI transit was evaluated by assessing the migration of a charcoal mixture in the small intestine, while lower GI transit was assessed via measurement of fecal pellet output (FPO). KEY RESULTS: YH12852 significantly accelerated upper and lower GI transit at the doses of 3, 10, and 30 mg/kg and reached its maximal effect at 10 mg/kg. These effects were significantly blocked by pretreatment of GR113808 10 mg/kg. CONCLUSION AND INFERENCES: Oral administration of YH12852 significantly accelerates and restores delayed upper and lower GI transit in a guinea pig model of POI. This drug may serve as a useful candidate for the treatment of postoperative ileus.

Conduction block by clonidine is not mediated by alpha2-adrenergic receptors in rat sciatic nerve fibers.

BACKGROUND AND OBJECTIVES: Clonidine, an alpha(2)-adrenergic agonist, has been shown to prolong local anesthesia. It appears that clonidine by itself produces conduction block by acting on peripheral nerves. However, whether clonidine-induced conduction block is mediated through alpha(2)-adrenergic receptors remains unclear. The purpose of this study was to see if clonidine's nerve-blocking action was through alpha(2)-adrenergic receptors by examining clonidine's action in the presence of alpha(2)-adrenergic antagonists. METHODS: The compound action potentials (CAPs) evoked by electrical stimuli were recorded from the isolated rat sciatic nerve in a recording chamber. Conduction block was examined by analyzing CAPs with regard to peak amplitude and time-to-peak in the presence of clonidine alone or clonidine plus alpha(2)-adrenergic antagonist yohimbine or idazoxan. RESULTS: Both clonidine and yohimbine produced concentration-dependent, reversible, conduction block. Based on concentration-response relationships, the 50% of effective concentration (EC(50)) were estimated to be 1.61 +/- 0.51 mmol/L (mean +/- SD) for clonidine and 51.4 +/- 27.2 micromol/L for yohimbine. A mixture of equal volumes of 2.07 mmol/L clonidine and 55.6 micromol/L yohimbine produced conduction block to a level close to the mean value between conduction blocks induced by 2.07 mmol/L clonidine alone and 55.6 micromol/L yohimbine alone. Addition of idazoxan, a more specific alpha(2)-adrenergic antagonist than yohimbine, to clonidine was without effect on clonidine-induced conduction block. CONCLUSIONS: The results indicated that the mixture of clonidine and yohimbine, in which either drug inhibited impulse conduction, produced conduction block in an additive manner, and that clonidine-induced conduction block was not reversed by coapplication with a specific alpha(2)-adrenergic antagonist idazoxan. These data suggest that clonidine's effects likely depend on mechanisms not mediated by alpha(2)-adrenergic receptors.