Needleless connectors substantially reduce flow of crystalloid and red blood cells during rapid infusion.

Although needleless connectors (NC) are frequently used in the perioperative setting, the potential of modern NCs to slow delivery of IV fluids has not been thoroughly studied. We examined flow characteristics of 5 NC models during pressurized delivery of crystalloid and banked red blood cells from a Level 1 warmer through various IV catheters. Crystalloid flow rates were reduced by 29% to 85% from control in catheters >18 gauge, while red blood cell flow reductions ranged from 22% to 76% in these catheters (all P < 0.0050). We suggest that practitioners consider eliminating NCs when large IV catheters are inserted for rapid fluid administration.

Inositol-1,4,5-trisphosphate receptor-mediated Ca2+ waves in pyramidal neuron dendrites propagate through hot spots and cold spots.

We studied inositol-1,4,5-trisphosphate (IP(3)) receptor-dependent intracellular Ca(2+) waves in CA1 hippocampal and layer V medial prefrontal cortical pyramidal neurons using whole-cell patch-clamp recordings and Ca(2+) fluorescence imaging. We observed that Ca(2+) waves propagate in a saltatory manner through dendritic regions where increases in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) were large and fast ('hot spots') separated by regions where increases in [Ca(2+)](i) were comparatively small and slow ('cold spots'). We also observed that Ca(2+) waves typically initiate in hot spots and terminate in cold spots, and that most hot spots, but few cold spots, are located at dendritic branch points. Using immunohistochemistry, we found that IP(3) receptors (IP(3)Rs) are distributed in clusters along pyramidal neuron dendrites and that the distribution of inter-cluster distances is nearly identical to the distribution of inter-hot spot distances. These findings support the hypothesis that the dendritic locations of Ca(2+) wave hot spots in general, and branch points in particular, are specially equipped for regenerative IP(3)R-dependent internal Ca(2+) release. Functionally, the observation that IP(3)R-dependent [Ca(2+)](i) rises are greater at branch points raises the possibility that this novel Ca(2+) signal may be important for the regulation of Ca(2+)-dependent processes in these locations. Futhermore, the observation that Ca(2+) waves tend to fail between hot spots raises the possibility that influences on Ca(2+) wave propagation may determine the degree of functional association between distinct Ca(2+)-sensitive dendritic domains.

Quantification of Postmembrane Gaseous Microembolization During Venoarterial Extracorporeal Membrane Oxygenation.

Prolonged use of venoarterial extracorporeal membrane oxygenation (VA ECMO) may be complicated by end-organ dysfunction. Although gaseous microemboli (GME) are thought to damage end organs during cardiopulmonary bypass, patient exposures to GME have not been well characterized during VA ECMO. We therefore performed an observational study of GME in adult VA ECMO patients, with correlation to clinical events during routine patient care. After institutional review board (IRB) approval, we used two Doppler probes to detect GME noninvasively in extracorporeal membrane oxygenation (ECMO) circuits on four patients for 15 hours total while also recording patient care events. We then conducted in vitro trials to compare Doppler signals with gold-standard measurements using an Emboli Detection and Classification EDAC quantifier (Luna Innnovations, Inc. Roanoke, VA) (Terumo Cardiovascular, Ann Arbor, MI) during simulated clinical interventions. Correlations between Doppler and EDAC data were used to estimate GME counts and volumes represented by clinical Doppler data. A total of 503 groups of Doppler peaks representing GME showers were observed, including 194 statistically larger showers during patient care activities containing 92% of total Doppler peaks. Intravenous injections accounted for an estimated 68% of GME and 88% of GME volume, whereas care involving movement accounted for an estimated 6% of GME and 3% of volume. Overall estimated embolic rates of 24,000 GME totaling 4 µl/hr rivals reported GME rates during cardiopulmonary bypass. Numerous GME are present in the postmembrane circuit during VA ECMO, raising concern for effects on microcirculation and organ dysfunction. Strategies to detect and minimize GME may be warranted to limit embolic exposures experienced by VA ECMO patients.

Minocycline-Induced Hyperpigmentation Mimicking Aortic Dissection.

Minocycline-induced hyperpigmentation of tissues has been documented previously, but extensive cardiovascular involvement is rarely described in literature. We report a case of marked cardiovascular hyperpigmentation resulting from approximately 4 years of minocycline exposure. We will highlight how intraoperative differentiation of minocycline-induced hyperpigmentation from more sinister causes of discoloration led to the appropriate surgical management.

Elimination of gaseous microemboli from cardiopulmonary bypass using hypobaric oxygenation.

BACKGROUND: Numerous gaseous microemboli (GME) are delivered into the arterial circulation during cardiopulmonary bypass (CPB). These emboli damage end organs through multiple mechanisms that are thought to contribute to neurocognitive deficits after cardiac surgery. Here, we use hypobaric oxygenation to reduce dissolved gases in blood and greatly reduce GME delivery during CPB. METHODS: Variable subatmospheric pressures were applied to 100% oxygen sweep gas in standard hollow fiber microporous membrane oxygenators to oxygenate and denitrogenate blood. GME were quantified using ultrasound while air embolism from the surgical field was simulated experimentally. We assessed end-organ tissues in swine postoperatively using light microscopy. RESULTS: Variable sweep gas pressures allowed reliable oxygenation independent of carbon dioxide removal while denitrogenating arterial blood. Hypobaric oxygenation produced dose-dependent reductions of Doppler signals produced by bolus and continuous GME loads in vitro. Swine were maintained using hypobaric oxygenation for 4 hours on CPB with no apparent adverse events. Compared with current practice standards of oxygen/air sweep gas, hypobaric oxygenation reduced GME volumes exiting the oxygenator (by 80%), exiting the arterial filter (95%), and arriving at the aortic cannula (∼100%), indicating progressive reabsorption of emboli throughout the CPB circuit in vivo. Analysis of brain tissue suggested decreased microvascular injury under hypobaric conditions. CONCLUSIONS: Hypobaric oxygenation is an effective, low-cost, common sense approach that capitalizes on the simple physical makeup of GME to achieve their near-total elimination during CPB. This technique holds great potential for limiting end-organ damage and improving outcomes in a variety of patients undergoing extracorporeal circulation.

GABAA receptors, anesthetics and anticonvulsants in brain development.

GABA, acting via GABA(A) receptors, is well-accepted as the main inhibitory neurotransmitter of the mature brain, where it dampens neuronal excitability. The receptor's properties have been studied extensively, yielding important information about its structure, pharmacology, and regulation that are summarized in this review. Several GABAergic drugs have been commonly used as anesthetics, sedatives, and anticonvulsants for decades. However, findings that GABA has critical functions in brain development, in particular during the late embryonic and neonatal period, raise worthwhile questions regarding the side effects of GABAergic drugs that may lead to long-term cognitive deficits. Here, we will review some of these drugs in parallel with the control of CNS development that GABA exerts via activation of GABA(A) receptors. This review aims to provide a basic science and clinical perspective on the function of GABA and related pharmaceuticals acting at GABA(A) receptors.

Coincident glutamatergic and cholinergic inputs transiently depress glutamate release at rat schaffer collateral synapses.

The mammalian hippocampus, together with subcortical and cortical areas, is responsible for some forms of learning and memory. Proper hippocampal function depends on the highly dynamic nature of its circuitry, including the ability of synapses to change their strength for brief to long periods of time. In this study, we focused on a transient depression of glutamatergic synaptic transmission at Schaffer collateral synapses in acute hippocampal slices. The depression of evoked excitatory postsynaptic current (EPSC) amplitudes, herein called transient depression, follows brief trains of synaptic stimulation in stratum radiatum of CA1 and lasts for 2-3 min. Depression results from a decrease in presynaptic glutamate release, as NMDA-receptor-mediated EPSCs and composite EPSCs are depressed similarly and depression is accompanied by an increase in the paired-pulse ratio. Transient depression is prevented by blockade of metabotropic glutamate and acetylcholine receptors, presumably located presynaptically. These two receptor types--acting together--cause depression. Blockade of a single receptor type necessitates significantly stronger conditioning trains for triggering depression. Addition of an acetylcholinesterase inhibitor enables depression from previously insufficient conditioning trains. Furthermore, a strong coincident, but not causal, relationship existed between presynaptic depression and postsynaptic internal Ca(2+) release, emphasizing the potential importance of functional interactions between presynaptic and postsynaptic effects of convergent cholinergic and glutamatergic inputs to CA1. These convergent afferents, one intrinsic to the hippocampus and the other likely originating in the medial septum, may regulate CA1 network activity, the induction of long-term synaptic plasticity, and ultimately hippocampal function.