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ABSTRACT: Lipid emulsion (20%) is advocated as a rescue drug for local anesthetic toxicity. No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels.
We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before infusion (baseline) and at 5-minute intervals during the infusion for measurement of blood gases and free, bound, and total serum ropivacaine concentrations via high-performance liquid chromatography. Five swine received ropivacaine only, and 6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1 mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine infusions were terminated at asystole and no resuscitation was initiated. Total ropivacaine dose and time to death were recorded. The swine were cooled (mean temperature, 25.5°C ± 0.8°C at 6 hours postmortem) to reflect morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours postmortem for analysis. Additionally, a craniotomy and laparotomy were performed at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and muscle for analysis.
Analysis of the postmortem serum ropivacaine concentrations in the control and the lipid-treated animals indicated that both the total (bound and not bound to proteins) and free (not bound to proteins) ropivacaine concentrations were significantly higher in the lipid-treated animals (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095). The lipid group had a statistically significant earlier onset of death (asystole) compared with the control group (P = 0.0274). Tissue analysis indicated that the ropivacaine concentration significantly decreased postmortem in the lung, kidney, and brain tissues of the lipid-treated animals (P = 0.0168, P = 0.0073, and P = 0.0018, respectively). Tissue drug concentrations in the control animals remained unchanged after death.
Our data show that postmortem blood samples in swine that experience local anesthetic cardiovascular collapse and are treated with lipid emulsions will result in measurements that cannot be directly extrapolated to premortem drug concentrations.
Anesthesia and analgesia 08/2011; 114(4):894-900. · 3.08 Impact Factor
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ABSTRACT: The mechanisms of fluoroquinolone-induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. An in vitro contracture test used to investigate cellular processes in malignant hyperthermia (MH) can be applied to study the effects of fluoroquinolones.
With approval of the local ethics committee, muscle biopsies of 18 MH susceptible (MHS) and 12 MHS non-susceptible (MHN) pigs were performed. Individual bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After equilibration they were exposed to ciprofloxacin or levofloxacin. The measured baseline tension was analyzed (Wilcoxon test: P < 0.05).
There were no differences in weight, length, or predrug tension between the groups. Both levofloxacin an ciprofloxacin induced significant contractures in MHS muscle bundles but not in MHN.
Fluoroquinolones appear to have a pathological influence on intracellular calcium handling. A pre-existing impairment of the calcium homeostasis, however, seems to be necessary for this behavior.
Muscle & Nerve 02/2011; 44(2):208-12. · 2.37 Impact Factor
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ABSTRACT: Malignant hyperthermia susceptibility (MHS) is diagnosed by an invasive in vitro caffeine-halothane contracture test (CHCT) carried out on biopsied skeletal muscle tissue. We are presenting a novel blood test approach for malignant hyperthermia testing in a swine model. Our main aim was to determine whether adenosine production from lymphocytes after 4-chloro-m-cresol (4CmC) stimulation distinguishes homozygous swine carrying the Arg615Cys mutation in the ryanodine receptor type 1 (RyR1) gene (MHS swine) from normal swine.
Lymphocytes were isolated from arterial blood (40 ml) obtained from MHS (n = 7) and normal (n = 7) swine. Cells were suspended in Hank's balanced salt solution and treated with 4CmC (0-10 mm) at 37°C in the presence of adenosine deaminase inhibitor. After termination and purification of samples, aliquots (50 μl) were assayed for adenosine content using high performance liquid chromatography.
Baseline adenosine levels before stimulating lymphocytes with 4CmC were 0.025 ± 0.004 and 0.041 ± 0.006 μm (mean ± SEM) in lymphocytes from normal and MHS swine, respectively (P = 0.125). Maximum responses were achieved at 1 mm 4CmC for both cell-line groups. Adenosine levels after stimulation with 4CmC (1 mm) were 0.185 ± 0.009 and 0.397 ± 0.038 μm in lymphocytes from normal and MHS swine, respectively (P = 0.0035). There was no overlap between adenosine levels in stimulated lymphocytes from MHS and normal swine.
4CmC stimulation of porcine lymphocytes induces increased adenosine formation in MHS cells relative to those from normal swine; evaluation of adenosine formation in response to RyR1 agonists in human lymphocytes is needed.
Anesthesiology 10/2010; 113(4):917-24. · 5.36 Impact Factor
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ABSTRACT: Previous studies have shown that the liver is the first organ to display signs of injury during hemorrhagic shock. We examined the mechanism by which pyruvate can prevent liver damage during hemorrhagic shock in swine anesthetized with halothane. Thirty minutes after the induction of a 240-min controlled arterial hemorrhage targeted at 40 mmHg, hypertonic sodium pyruvate (0.5 g. kg(-1). h(-1)) was infused to achieve an arterial concentration of 5 mM. The volume and osmolality effects of pyruvate were matched with 10% saline (HTS) and 0.9% saline (NS). Although the peak hemorrhage volume increased significantly in both the pyruvate and HTS group, only the pyruvate treatment was effective in delaying cardiovascular decompensation. In addition, pyruvate effectively maintained the NADH/NAD redox state, as evidenced by increased microdialysate pyruvate levels and a significantly lower lactate-to-pyruvate ratio. Pyruvate also prevented the loss of intracellular antioxidants (GSH) and a reduction in the GSH-to-GSSG ratio. These beneficial effects on the redox environment decreased hepatic cellular death by apoptosis. Pyruvate significantly increased the ratio of Bcl-Xl (antiapoptotic molecule)/Bax (proapoptotic molecule), prevented the release of cytochrome c from mitochondria, and decreased the fragmentation of caspase 3 and poly(ADP ribose) polymerase (DNA repair enzyme). These beneficial findings indicate that pyruvate infused 30 min after the onset of severe hemorrhagic shock is effective in maintaining the redox environment, preventing the loss of the key antioxidant GSH, and decreasing early apoptosis indicators.
AJP Heart and Circulatory Physiology 11/2002; 283(4):H1634-44. · 3.71 Impact Factor
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Current Sports Medicine Reports 7(2):74-80. · 1.14 Impact Factor
