Mechanical and electrophysiological effects of mepivacaine on direct myocardial depression in vitro

The effects of various concentrations (20, 50, and 100 mumol litre-1) of mepivacaine were studied in isolated guinea pig and rat right ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiological parameters. Mepivacaine produced dose-dependent depression of peak force during 0.5 to 3 Hz stimulation rates in guinea pig papillary muscles. Conduction block was frequently noted, especially at higher stimulation rates (2 and 3 Hz) with mepivacaine 50 and 100 mumol litre-1. In rat papillary muscle experiments, about 20% depression of peak force was shown at rested state contraction. Shortening of action potential (AP) duration (APD50: about 10%, APD90: about 10%) and rate-dependent depression of dV/dt max was observed with mepivacaine 100 mumol litre-1. In 26 mmol litre-1 K+ Tyrode's solution, mepivacaine 50 and 100 mumol litre-1 produced a dose-dependent depression of early (50 mumol litre-1: about 20%, 100 mumol litre-1: about 30%) and late (50 mumol litre-1: about 30%, 100 mumol litre-1: about 50%) force development. In slow APs, neither shortening of AP duration nor changes of dV/dt max were shown by mepivacaine 100 mumol litre-1. An approximate 30% depression of contracture induced by rapid cooling after 2 Hz stimulation rates was observed with mepivacaine 100 mumol litre-1. It may be concluded that the direct myocardial depressant effect of mepivacaine is likely to be caused by inhibition of Ca2+ release from the sarcoplasmic reticulum. The Na+ channel blocking action may contribute indirectly to the depression of contractility.ope

Direct myocardial depressant effect of methylmethacrylate monomer

BACKGROUND: The present study explored the mechanism of direct myocardial depression by methylmethacrylate monomer (MMA). METHODS: Isometric contraction of isolated guinea pig right ventricular papillary muscle was measured in modified normal and 26 mm K+ Tyrode solutions at various stimulation rates. Normal and slow action potentials were evaluated by conventional microelectrode technique. MMA effects on various aspects of sarcoplasmic reticulum function were evaluated by its effect on rapid-cooling contractures, rested-state contraction in rat papillary muscle in modified normal Tyrode solution, and in guinea pig papillary muscle under low Na+ (25 mm) Tyrode solution. Whole cell patch clamp techniques were applied to measure the inward Ca2+ currents (I(Ca)). RESULTS: MMA (0.5, 1.5, and 4.7 mm) caused concentration-dependent depression of peak force and maximal rate of force development to approximately 70, 50, and 20% of baseline from rested state to 3 Hz stimulation rates, respectively. Depression of peak force and maximal rate of force development by MMA was dependent on stimulation frequency, with less depression at higher stimulation rates. In low Na+ Tyrode solution, 1.5 mm MMA depressed peak force of rat and guinea pig myocardium by 20-30%. In 26 mm K+ Tyrode solution, 0.5 and 1.5 mm MMA caused selective and marked concentration-dependent depression of late force development (0.5 mm: approximately 60% of baseline, 1.5 mm: approximately 30% of baseline) with no alteration in early force development. MMA (1.5 mm) depressed rapid-cooling contracture to 53 +/- 10% of baseline, accompanied by approximately 63% prolongation of time to peak contracture. In patch clamp studies, MMA reduced I(Ca) in a concentration-dependent manner. CONCLUSIONS: The direct myocardial depressant effect of MMA seems to be caused in part by depression of Ca2+ influx through cardiac membrane, while depolarization-activated sarcoplasmic reticulum Ca2+ release appears modestly depressed.ope

Effects of Desflurane-Induced Preconditioning Following Ischemia-Reperfusion on Modulation of Calcium Homeostasis in Rat Heart

Ca2+ overload induced by ischemia-reperfusion alters Ca2+ homeostasis, which plays an important role in myocardial cell injury. Although desflurane has been commonly used in anesthesia, little is known about its cardioprotective effect associated with Ca2+ homeostasis in ischemia-reperfused rat heart. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Rats were randomly assigned to one of three groups; Sham, I/R only, desflurane preconditioning group. In the present study, desflurane reduced infarct size (43.6±5.5% vs. 19.1±1.9% for I/R and desflurane, respectively, p<0.01). In desflurane-treated rat heart, we observed a consistent decrease in the expression of pro-apoptotic protein Bax leading to a decrease in cytochrome c release. We also found that desflurane enhanced expression of anti-apoptotic protein Bcl-2, activated ERK concerned with survival, and significantly attenuated abnormal changes of sarcoplasmic reticulum genes and proteins in ischemia-reperfused rat heart. These results suggest that desflurane prevents myocardial injury in response to ischemia-reperfusion by modulating sarcoplasmic reticulum function.ope

Changes of Serum ADH Level during Matoidectomy under General Anesthesia

BACKGROUND: Markedly reduced urine have been commonly observed during mastoidectomy under general anesthesia. The aim of study was to evaluate the surgery-related mechanism of reduced urine during mastoidectomy. METHODS: 11 patients undergoing mastoidectomy were studied. Blood samples were drawn from CVP line inserted through right internal jugular vein just before drilling (Pre-D); at 15 min after drilling (D-15); at the time closest to the inner ear (CHP-1); at 15 min (CHP-2) and 30 min (CHP-3) after CHP-1 and just before emergence (End). MAP, HR, temperature, CVP, and urine output (UO) were recorded at each period. 0.9% normal saline with room temperature was used to irrigate surgical field. Serum ADH, and the osmolalities (serum and urine) were measured. In 6 patients, serum TSH and FSH were measured, simultaneously. RESULTS: There were no significant hemodynamic changes during procedure. UO was decreased in 50% during and after the drilling. No differences showed in UO between before and after the drilling of CHP. Plasma ADH level after the CHP was increased 2-3 fold than before. Serum osmolality was unchanged throughout the periods, while the urine osmolality was significantly increased after the period of CHP. FSH was not changed during the periods and TSH was decreased slightly than in Pre-D. CONCLUSIONS: The reduced urine output during mastoidectomy may be influenced by the drilling-related vibration, which may affect the supraoptico-hypophyseal tract, resulting in ADH release. The irrigated isotonic saline with higher osmolality (308 mOsm/kgH2O) than plasma osmolality may partly contributed to the increased ADH.ope

Effect of Thiopental on Transient Outward Current (Ito) and Inwardly Rectifying K+ Current (Ik1) in Rat Ventricular Myocytes

BACKGROUND: Patients with the long QT syndrome, either congenital or acquired, have an increased development of serious ventricular arrhythmia, Torsade de Pointes. Thiopental (5 mg/kg) has been reported to prolong the QTc interval in patients undergoing surgery with normal repolarization. Recent studies have indicated that the clinical concentration of thiopental prolonged the action potential duration (APD), which was attributed to inhibition of the delayed rectifier (Ik) and/or the inward rectifier (Ik1) at various animal myocardial preparations. The rat ventricular cells were used to study the contribution of transient outward current (Ito) and Ik1 because they possess a variety of K+channel subtypes including Ito and Ik1 with little or no Ik, similar to those of human ventricular myocytes. The effect on Ca2+ current (ICa,L), which can alter the K+ conductance, was also observed. METHODS: With approval of the animal research committee in Yonsei University Medical College, isolated ventricular cells were obtained from enzymatically treated rat hearts. The ICa,L was elicited from a holding potential of -40 mV to + 60 mV under the modified Tyrode solution. Ik1 was obtained from a holding potential of -40 mV before their membrane potential was changed from -130 to + 50 mV. Ito was recorded during depolarizing steps from -80 mV followed by inactivation of Na+current by short pulses to -40 mV and then depolarized with 10 mV increments to test potentials up to + 60 mV. ICa,L was blocked by adding 0.5 mM CdCl2 during measurement of Ito. Normal action potential was measured using conventional microelectrode technique. RESULTS: At membrane potential of +60 mV, 50microM thiopental caused modest depression of Ito to 82 ± 1% of control. From the dose-response curve from 1 to 1000microM, the IC50 of thiopental was 163microM. While 50microM thiopental caused modest depression of Ik1 of 87 ± 2% of control at a test potential of -130 mV, no depression was observed from -110 mV to + 50 mV. ICa,L was significantly reduced to 57 ± 5% of control. The APD90 was prolonged by 76% following application of 50microM thiopental. CONCLUSIONS: Prolongation of APD induced by thiopental was associated with reduction of Ito. Considering the high current density of Ito in rat ventricular myocytes, inhibition of Ito seems to play a major role in thiopental-induced APD prolongation.ope

The Development of an Inspiratory Time Adjustable Transtracheal Jet Ventilator and Evaluation in a Human Adult Trachea-Lung Model

Background: Transtracheal jet ventilation (TTJV) has been used for 'Cannot Ventilate/Cannot Intubate' situation, lefe-saving situations, by simply introducing an IV catheter (angiocatheter) through the cricothyroid membrane. To decrease the occurrence of barotrauma caused by a continuous high pressure oxygen supply while applying TTJV, it would be ideal to have a TTJV system equipped with an inspiration time adjustable function which any currently commercially available TTJV does not have. Methods: Recently, we made a prototype of an inspiration time adjustable TTJV and measured the corresponding injection volumes and peak inflation pressures according to the changes of oxygen supply pressure and inspiration time using catheters ranging from 14 to 20 G in a simulated human adult trachea-lung model. Results: A 16 G angiocatheter provided 465 ⁑ 5 ml of injected volume with a peak inflation pressure of 25 cmH2O under a 50 psi oxygen supply at 1 second of inspiration, which would be adequate for an adult tidal volume. When a 14 G catheter was used under the same conditions as above, the injected volume was 1128 ⁑ 9 ml. All injected volumes were under 310 ml when 18 and 20 G angiocathers were used at various driving pressures (10⁣50 psi) and inspiration time (0.5, 0.75, and 1 s). Conclusions: An inspiration time adjustable TTJV can easily provide enough tidal volume to maintain oxygenation, and could be expected to prevent or reduce barotraumatic complications such as pneumothorax.ope

Effects of Head and Neck Position on Nasotracheal Tube Intracuff Pressure: A Prospective Observational Study

To prevent endotracheal tube-related barotrauma or leakage, the intracuff pressure should be adjusted to 20–30 cm H2O. However, changes in the nasotracheal tube intracuff pressure relative to neck posture are unclear. In this study, we investigated the effect of head and neck positioning on nasotracheal tube intracuff pressure. Fifty adult patients with nasotracheal tubes who were scheduled for surgery under general anesthesia were enrolled. Following intubation, intracuff pressure was measured by connecting the pilot balloon to a device that continuously monitors the intracuff pressure. Subsequently, the intracuff pressure was set to 24.48 cm H2O (=18 mmHg) for the neutral position. We recorded the intracuff pressures based on the patients’ position during head flexion, extension, and rotation. The initial intracuff pressure was 42.2 cm H2O [29.6–73.1] in the neutral position. After pressure adjustment in the neutral position, the intracuff pressure was significantly different from the neutral to flexed (p 30 cm H2O occurred in 12% of patients. Therefore, it is necessary to adjust the intracuff pressure after tracheal intubation and each positional change.ope

Electrophysiologic Mechanisms of Sevoflurane on Prolongation of the QT Interval: K+ Currents in Rat Ventricular Myocytes

BACKGROUND: Whereas sevoflurane (SEVO) has been reported to prolong the QT interval, little has been known on the electrophysiologic effects of SEVO which contributes to the prolongation of action potential (AP) duration. METHODS: The ventricular myocytes were obtained from enzymatically treated rat hearts. The standard whole cell voltage-clamp methods were used. The AP was measured using current clamp technique. As a repolarizing K+ current, the transient outward K+ current (Ito), the sustained outward K+ current (Isus), and the inwardly rectifying K+ current (IkI) were measured. The L-type Ca2+ current (ICa, L) was also obtained. After the baseline measurements, the myocytes were exposed to 1.7 and 3.4% SEVO. SEVO concentrations in Tyrode superfusate at room temperature were 0.35 and 0.7 mM for 1.7 and 3.4% SEVO, respectively. Results are mean ± SEM. RESULTS: SEVO prolonged the AP duration, while the amplitude and the resting membrane potential remained unchanged. At membrane potential of +60 mV, peak Ito was significantly reduced by 18 ± 2 and 24 ± 2% by 0.35 and 0.7 mM SEVO, respectively. 0.7 mM SEVO did not shift the steady-state inactivation curve. Isus was unaffected by 0.7 mM SEVO. The IkI at -130 mV was little altered by 0.7 mM SEVO. ICa, L was significantly reduced by 28 ± 3 and 33 ± 1% by 0.35 and 0.7 mM SEVO, respectively. CONCLUSIONS: Prolongation of AP duration by SEVO in rat ventricular myocytes is likely to be caused by a reduction of Ito. Resting membrane potential was unaffected by SEVO, which seems to be related to no alteration of IkI).ope

Neuroprotection From Excitotoxic Injury by Local Administration of Lipid Emulsion Into the Brain of Rats

Lipid emulsion was recently shown to attenuate cell death caused by excitotoxic conditions in the heart. There are key similarities between neurons and cardiomyocytes, such as excitability and conductibility, which yield vulnerability to excitotoxic conditions. However, systematic investigations on the protective effects of lipid emulsion in the central nervous system are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of kainic acid-induced excitotoxicity through intrahippocampal microinjections. Kainic acid and/or lipid emulsion-injected rats were subjected to the passive avoidance test and elevated plus maze for behavioral assessment. Rats were sacrificed at 24 h and 72 h after kainic acid injections for molecular study, including immunoblotting and qPCR. Brains were also cryosectioned for morphological analysis through cresyl violet staining and Fluorojade-C staining. Anxiety and memory functions were significantly preserved in 1% lipid emulsion-treated rats. Lipid emulsion was dose-dependent on the protein expression of β-catenin and the phosphorylation of GSK3-β and Akt. Wnt1 mRNA expression was elevated in lipid emulsion-treated rats compared to the vehicle. Neurodegeneration was significantly reduced mainly in the CA1 region with increased cell survival. Our results suggest that lipid emulsion has neuroprotective effects against excitotoxic conditions in the brain and may provide new insight into its potential therapeutic utility.ope

Ionic mechanisms of desflurane on prolongation of action potential duration in rat ventricular myocytes

PURPOSE: Despite the fact that desflurane prolongs the QTC interval in humans, little is known about the mechanisms that underlie these actions. We investigated the effects of desflurane on action potential (AP) duration and underlying electrophysiological mechanisms in rat ventricular myocytes. MATERIALS AND METHODS: Rat ventricular myocytes were enzymatically isolated and studied at room temperature. AP was measured using a current clamp technique. The effects of 6% (0.78 mM) and 12% (1.23 mM) desflurane on transient outward K⁺ current (I(to)), sustained outward current (I(sus)), inward rectifier K⁺ current (I(KI)), and L-type Ca²⁺ current were determined using a whole cell voltage clamp. RESULTS: Desflurane prolonged AP duration, while the amplitude and resting membrane potential remained unchanged. Desflurane at 0.78 mM and 1.23 mM significantly reduced the peak I(to) by 20 ± 8% and 32 ± 7%, respectively, at +60 mV. Desflurane (1.23 mM) shifted the steady-state inactivation curve in a hyperpolarizing direction and accelerated inactivation of the current. While desflurane (1.23 mM) had no effects on I(sus) and I(KI), it reduced the L-type Ca²⁺ current by 40 ± 6% (p<0.05). CONCLUSION: Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing I(to) in rat ventricular myocytes.ope