Biomedical subjects

J C Vernon

Publications and source records attributed to J C Vernon.

6 recordsLinked to original sources

PubMed2001

Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.

UNLABELLED: There is no information comparing the ability to reverse the cardiotoxic effects associated with incremental overdosage of bupivacaine (BUP) to levobupivacaine (LBUP), ropivacaine (ROP), or lidocaine (LIDO). Open-chest dogs were randomized to receive incremental escalating infusions of BUP, LBUP, ROP, and LIDO to the point of cardiovascular collapse (mean arterial pressure [MAP] < or = 45 mm Hg). Hypotension and arrhythmias were treated with epinephrine, open-chest massage, and advanced cardiac life support protocols, respectively. Outcomes were defined as the following: successful (stable rhythm and MAP > or = 55 mm Hg for 20 min), successful with continued therapy (stable rhythm and MAP <55 mm Hg after 20 min), or death. Continued therapy was required in 86% of LIDO dogs compared with only 10%-30% of the other dogs (P < 0.002). Mortality from BUP, LBUP, ROP, and LIDO was 50%, 30%, 10%, and 0%, respectively. Myocardial depression was primarily responsible for the profound hypotension, as the occurrence of lethal arrhythmias preceding resuscitation was not different among local anesthetics. Epinephrine-induced ventricular fibrillation occurred more frequently in BUP-intoxicated dogs than in dogs given LIDO or ROP (P < 0.05). The unbound plasma concentrations at collapse were larger for ROP, 19.8 microg/mL (10-39 microg/mL), compared with BUP, 5.7 microg/mL (3-11 microg/mL); whereas the concentrations of LBUP, 9.4 microg/mL (5-18 microg/mL) and BUP were not significantly different from each other. IMPLICATIONS: There were consistent differences among the local anesthetics, the sum of which suggests that larger doses and blood concentrations of ropivacaine (ROP) and lidocaine will be tolerated as compared with bupivacaine (BUP) and levobupivacaine (LBUP). Lidocaine intoxication results in myocardial depression from which resuscitation is consistently successful but will require continuing drug support. After BUP, LBUP, or ROP, resuscitation is not always successful, and the administration of epinephrine may lead to severe arrhythmias. The unbound plasma concentrations at collapse were larger for ROP compared with BUP, whereas the concentrations of LBUP and BUP were not significantly different from each other. Furthermore, larger plasma concentrations of ROP than BUP are present after resuscitation, suggesting a wider margin of safety when large volumes and large concentrations are used to establish upper or lower extremity nerve blocks for surgical anesthesia and during long-term infusions for pain management.

Amides↗

PubMed2000

Ventricular arrhythmias with or without programmed electrical stimulation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine.

UNLABELLED: It is unclear whether the mechanism of death from local anesthetic (LA) intoxication is primarily a consequence of cardiac arrhythmias or myocardial contractile depression, and whether LAs might differ in this susceptibility to these two mechanisms. By using programmable electrical stimulation (PES) protocols in anesthetized, ventilated dogs, we compared the arrhythmogenic potential of bupivacaine (BUP), ropivacaine (ROP), levobupivacaine (LBUP), and lidocaine (LIDO). Open-chest dogs were randomized to receive escalating incremental infusions of the four local anesthetics until cardiovascular collapse. We assumed a concentration relationship of 4:1 for LIDO/BUP, LBUP, and ROP. The effective refractory period did not change significantly until the dose increment corresponding to target concentrations of 8 and 32 microg/mL for BUP, LBUP, ROP, and LIDO, respectively. Thirty percent to 50% increases in effective refractory period occurred in surviving dogs at this dose. The incidence of spontaneous or PES-induced ventricular tachycardia and ventricular fibrillation did not differ among groups. Compared with LIDO, the incidence of PES-induced extrasystoles was more frequent for BUP- and LBUP-treated dogs (P: < 0.05). ROP-treated dogs did not differ from LIDO-treated dogs with respect to PES-induced extrasystoles. At the dose increment preceding cardiovascular collapse, all LAs produced significant increases in heart rate and reductions in blood pressure compared with their respective baseline values. The incidence of programmable electrical stimulation-induced ventricular tachycardia and fibrillation with BUP does not differ from the incidence that occurs with the single S:(-) enantiomers LBUP and ROP, providing further evidence against stereoselective arrhythmogenesis as a primary component of local anesthetic-induced cardiotoxicity. IMPLICATIONS: Progressive bupivacaine intoxication in anesthetized, ventilated dogs does not produce early arrhythmogenic events. The incidence of programmable electrical stimulation-induced ventricular tachycardia and fibrillation with bupivacaine does not differ from the incidence that occurs with the single S:(-) enantiomers levobupivacaine and ropivacaine, providing further evidence against stereoselective arrhythmogenesis as a primary component of local anesthetic-induced cardiotoxicity.

Amides↗

PubMed1999

Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia.

BACKGROUND: Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, noninjurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We hypothesized that IPC of the spinal cord would reduce neurologic injury after experimental aortic occlusion in rats and that this improved neurologic benefit could be induced acutely after a short reperfusion interval separating the IPC and the ischemic insult. METHODS: Forty male Sprague-Dawley rats under general anesthesia were randomly assigned to one of two groups. The IPC group (n = 20) had 3 minutes of aortic occlusion to induce spinal cord ischemia 30 minutes of reperfusion, and 12 minutes of ischemia, whereas the controls (n = 20) had only 12 minutes of ischemia. Neurologic function was evaluated 24 and 48 hours later. Some animals from these groups were perfusion-fixed for hematoxylin and eosin staining of the spinal cord for histologic evaluation. RESULTS: Survival was significantly better at 48 hours in the IPC group. Sensory and motor neurologic function were significantly different between groups at 24 and 48 hours. Histologic evaluation at 48 hours showed severe neurologic damage in rats with poor neurologic test scores. CONCLUSIONS: Ischemic preconditioning reduces neurologic injury and improves survival in a rat model of spinal cord ischemia. The protective benefit of IPC is acutely invoked after a 30-minute reperfusion interval between the preconditioning and the ischemic event.

Animals↗

PubMed1999

Thoracic epidural anesthesia reduces infarct size in a canine model of myocardial ischemia and reperfusion injury.

OBJECTIVE: To determine the effects of thoracic epidural anesthesia on myocardial infarct size, regional myocardial blood flow (RMBF), and plasma norepinephrine in an anesthetized canine model of ischemia reperfusion injury with infarction. DESIGN: Blinded, randomized, placebo-controlled animal study. SETTING: Experiments were performed in the cardiothoracic research laboratory at Wake Forest University Baptist Medical Center. PARTICIPANTS: Anesthetized, open-chest mongrel dogs were used in these studies. METHODS: Dogs were instrumented for measurement of aortic pressure (AP) and left ventricular systolic pressure (LVSP), dP/dt, and RMBF Epidural catheters were inserted at thoracic segment T5. Three groups received epidural 0.5% bupivacaine: low-dose (n = 7; 0.3 mg/kg bolus, 0.15 mg/kg/ h), mid-dose (n = 7; 0.6 mg/kg bolus, 0.3 mg/kg/h), high-dose (n = 7; 1.2 mg/kg bolus, 0.6 mg/kg/h). The vehicle (VEH) group received epidural saline. Bolus followed by maintenance infusions began 30 minutes before the onset of ischemia (60 min) and continued through reperfusion (180 min). RESULTS: Myocardial infarct size was significantly reduced in the high-dose group versus the VEH and low-dose groups (p < 0.05). After initiation of the mid and high dose, AP, LVSP, and dP/dt decreased 7% to 16% (high vVEH; p < 0.05). VEH dogs showed a 130% increase from control in early postischemic RMBF. There was a dose-dependent attenuation in this reflow response: 72%, 31%, and 6% increase in RMBF in the low, mid, and high groups, relative to controls (p < 0.05 high v VEH). Although there was no significant difference in plasma norepinephrine, fewer surges occurred in the high-dose group. CONCLUSIONS: Thoracic epidural anesthesia reduces infarct size and postischemic hyperemia in a model of ischemia reperfusion injury.

Anesthesia, Epidural↗

PubMed1998

Cloricromene reduces infarct size and alters postischaemic blood flow defects in dog myocardium.

1. The aim of the present investigation was to evaluate the effect of cloricromene on myocardial infarct size, regional myocardial blood flow and neutrophil accumulation in a canine model of ischaemia-reperfusion. 2. Dogs were instrumented to measure blood pressure, left anterior descending (LAD) coronary flow (flow probe) and regional myocardial blood flow (coloured microspheres). Two groups were studied: (i) CLO (n = 8) received an infusion of cloricromene (15 micrograms/kg per min); and (ii) VEH (n = 8) received saline. Infusions began at the onset of ischaemia (60 min) and continued through reperfusion (180 min). 3. Haemodynamic responses were not different between groups. Cloricromene reduced the area of necrosis expressed as a percentage of the area at risk from 35 +/- 3% in the VEH group to 23 +/- 4% in the CLO group (P < 0.05). Regional myocardial blood flow in the ischaemic region was different between groups; VEH dogs showed an early reperfusion hyperaemia followed by a progressive reduction in flow, while CLO dogs exhibited a gradual increase in reflow in the absence of an early hyperaemic response (P < 0.05). Left anterior descending flow was enhanced during the reperfusion period in the CLO group compared with VEH (P < 0.05). Cloricromene reduced polymorphonuclear neutrophil (PMN) infiltration (myeloperuxidase activity) in all myocardial regions when compared with VEH (non-ischaemic zone, 0.34 +/- 0.54 vs 0.05 +/- 0.01 IU/100 mg; ischaemic zone, 2.03 +/- 0.80 vs 0.24 +/- 0.08 IU/100 mg; and necrotic zone, 0.56 +/- 0.04 vs 3.59 +/- 1.09 IU/100 mg for VEH vs CLO groups, respectively; P < 0.01). In a separate in vitro preparation, cloricromene reduced adherence of platelet-activating factor (PAF)-stimulated PMN to canine coronary endothelium. Stimulation of PMN by 100 nmol/L PAF resulted in adherence of 176 +/- 36 compared with 48 +/- 12 cells/mm2 in PAF-stimulated PMN treated with 100 mumol cloricromene (P < 0.001). 4. These data indicate that cloricromene reduces myocardial infarct size in a canine model of ischaemia-reperfusion injury. Postischaemic blood flow patterns are significantly different in cloricromene-treated dogs. Cloricromene-mediated reductions in infarct size, neutrophil accumulation and adherence may play a role in this effect.

Animals↗

PubMed1976

Prompts to increase attendance in a community mental-health center.

The effect of a brief appointment reminder for mental-health center applicants is reported. A standardized phone message was delivered by an administrative staff member one to three days before the appointment and a sequential experimental design alternating baseline and phone message conditions was used to assess the effects of the procedure. The no-show rate averages were 32%, 11%, 25%, and 14% respectively. The cost of the procedure was $162.00, which was totally recovered when only six appointments were kept. Since over 1000 patients were involved in the study, the return on the investment of +162.00 is considerable. Implications for this procedure are discussed for other community mental-health centers and for other community care-giving agencies.

Appointments and Schedules↗