Leigh A Ladd

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The risk of accidental intravascular injection and consequent acute toxicity is ever-present with most neural blockade techniques. The severity of cardiovascular and central nervous system (respectively, CVS and CNS) toxicity is directly related to the local anesthetic potency, dose, and rate of administration. Nonetheless, although the anesthetic potency(More)
AIMS Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. METHODS A(More)
1. The racemic local anaesthetic agent bupivacaine is widely used clinically for its long duration of action. Levobupivacaine and ropivacaine are bupivacaine enantiopure congeners, developed to improve upon the clinical safety of bupivacaine, especially the risk of fatal arrhythmogenesis. 2. In previous preclinical studies of the safety of these drugs with(More)
BACKGROUND Previous preclinical safety studies in ewes have found intravenous levobupivacaine and ropivacaine to be less potent toward causing central nervous system (CNS) and cardiac toxicity than bupivacaine. Analogous cardiotoxicity has been demonstrated directly in various cardiac preparations ex vivo. Moreover, drug-related arrhythmogenicity has been(More)
UNLABELLED In preclinical pharmacological studies of levobupivacaine (S-bupivacaine), we determined its tolerability, cardiovascular actions, and pharmacokinetics, and we estimated its margin of safety compared with bupivacaine in conscious sheep. Levobupivacaine HCl. H(2)O was infused IV for 3 min into 10 previously instrumented ewes (approximately 50 kg).(More)
Cell therapies have been used to regenerate the heart by direct myocardial delivery, by coronary infusion and by surface attached scaffolds. Multipotent mesenchymal stem cells (MSC) with capacity to differentiate into cardiomyocytes and other cell lines have been predominantly trialled in rodents. However, large animal models are increasingly needed to(More)
BACKGROUND The liver is the most frequently injured abdominal organ after blunt injury; sometimes it may be very difficult to achieve haemostasis. In this study we examined the use of InLine radiofrequency ablation (RFA) for the coagulation and haemostasis of simulated liver injury. MATERIALS AND METHODS Six pigs were tested in this study. We created two(More)
OBJECTIVES The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. MATERIALS AND METHODS We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating(More)
BACKGROUND Local anesthetic toxicity is often studied experimentally in anesthetized subjects, but clinical toxicity usually occurs in conscious patients. In this study, we determined the influence of general anesthesia on the pharmacokinetics of six local anesthetics administered i.v. at approximately the highest recommended doses. METHODS Chronically(More)