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Biomedical subjects

J E Heavner

Publications and source records attributed to J E Heavner.

At least 19 recordsLinked to original sources
PubMed1995

Effects of nitric oxide synthesis inhibition with or without nitric oxide inhalation on responses to systemic cocaine administration in rats.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME) i.v. and nitric oxide (NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats. Cocaine (4 mg/kg/min i.v.) produced seizures then isoelectric electrocephalographic (isoEEG) activity as well as an initial increase in systolic blood pressure and heart rate, then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME (2 mg/kg/min i.v.) for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8). Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. No inhalation (80 ppm) did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular system (lower dose for arrhythmias and asystole), but does not affect the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.

Administration, Inhalation↗
PubMed1995

Resuscitation from bupivacaine-induced asystole in rats: comparison of different cardioactive drugs.

The objective of this study was to compare the success of resuscitation attempts with different cardioactive drugs after bupivacaine-induced asystole. Saline, amrinone (1 mg/kg), dopamine (5 micrograms/kg), norepinephrine (2 micrograms/kg), epinephrine (10 micrograms/kg), or isoproterenol (1 microgram/kg) were tested. Sixty rats assigned to six treatment groups (n = 10/group) were lightly anesthetized (0.5% halothane, 70% N2O), paralyzed (doxacurium), and given bupivacaine intravenously at 4 mg.kg-1.min-1 until asystole. Five seconds later up to three treatment drug doses were given at 30-s intervals. Then external cardiac massage was instituted as needed. Spontaneous heartbeat was restored in all animals given norepinephrine or epinephrine. It was not restored in one saline-treated, one dopamine-treated, one isoproterenol-treated, and three amrinone-treated animals. The highest (best) arbitrary scores for overall resuscitation success were achieved with norepinephrine and the lowest with amrinone (P < 0.05). The incidence of ventricular arrhythmias after resuscitation was significantly higher (P < 0.05) in epinephrine- and isoproterenol-treated animals versus other animals. Cardiac rhythm disturbance disappeared within 20 min after successful resuscitation with norepinephrine. Amrinone was no more effective than saline in treating bupivacaine-induced asystole. A drug such as norepinephrine, which has both cardiostimulator (beta 1-receptor agonist) and peripheral vasoconstrictor (alpha 1-receptor agonist) activity, may be the drug of choice for treating asystole induced by bupivacaine.

Amrinone↗
PubMed1995

Dynamic changes in G alpha i-2 levels in rat hearts associated with impaired heart function after myocardial infarction.

The objective of this study was to determine if levels and function of Gs alpha and G alpha i-2 in rat hearts change over time following acute myocardial infarction (MI), and if so, whether the changes in G proteins are associated with changes in heart function. As compared with sham-operated controls, the G alpha i-2 level of MI rats did not change at day 1, increased by 64% at day 3 (P < 0.01) and by 55% at day 9 (P < 0.05) accompanied by reduced adenylyl cyclase activity, and returned to control by day 21. By contrast, the Gs alpha level did not change at any time. Cardiac function in MI animals was markedly impaired at days 1, 3, and 9 as evidenced by substantial elevation in LVEDP and reduction in maximum rates of pressure development and relaxation, and was partially restored at day 21. Increased G alpha i-2 level in MI rats correlated significantly to severity of impaired cardiac function. The results show a three-phase dynamic pattern in G alpha i-2 level following acute MI: a lag phase, an increased expression phase associated with marked impairment of heart function, and a late phase in which the expression returns to control level accompanied by partially restored cardiac function.

Adenylyl Cyclases↗
PubMed1993

Comparison of propofol with thiopentone for treatment of bupivacaine-induced seizures in rats.

Thirty Sprague-Dawley rats were paralysed with pancuronium and their lungs ventilated mechanically with 70% nitrous oxide and 0.5% halothane in oxygen. Bupivacaine 2 mg kg-1 min-1 was infused continuously i.v. until the animals died. At the onset of seizures, animals were given an i.v. bolus of propofol 1 mg kg-1 (n = 10), thiopentone 2 mg kg-1 (n = 10) or lipid vehicle (n = 10). Administration of propofol or thiopentone was repeated each time seizures restarted and lipid vehicle administrations were repeated at 2-min intervals until the electroencephalogram became isoelectric. All animals developed seizures, arrhythmias, isoelectric EEG and asystole. Administration of lipid vehicle induced no obvious changes in ongoing epileptiform activity. The initial doses of thiopentone and of propofol stopped epileptiform activity in all animals, usually within 6 s after administration. The seizure-free period after the initial administration of thiopentone and of propofol lasted, on average, 0.98 min and 1.72 min, respectively. We conclude that propofol may have value in treating seizures induced by bupivacaine.

Animals↗
PubMed1993

Comparison of acute central nervous system and cardiovascular toxicity of 2-chloroprocaine and prilocaine in the rat.

In this study, we compared the central nervous system and cardiovascular system toxicity of i.v. administered 0.5% 2-chloroprocaine (N = 10) and 0.5% prilocaine (N = 10) in lightly anaesthetised rats. Arterial blood pressure, ECG and EEG were continuously recorded. Prilocaine produced the predetermined toxic end-points (i.e. seizure activity on EEG, isoelectric EEG, cardiac arrhythmia on ECG, asystole on ECG) at significantly lower doses than 2-chloroprocaine (P < 0.05). The mean dose of prilocaine producing asystole was 166 mg.kg-1 (+/- 45 mg.kg-1, s.d.) vs. 255 mg.kg-1 (+/- 42 mg.kg-1) for 2-chloroprocaine (P < 0.01). The rate of decrease of mean arterial blood pressure during the infusion was significantly faster with prilocaine (P < 0.01). Typically, arrhythmias did not appear until just before asystole, suggesting that neither of the local anaesthetics possessed marker arrhythmogenic properties. It is concluded that prilocaine is slightly more toxic than 2-chloroprocaine in the rat, but that both local anaesthetics have a wide margin of safety. Doses producing seizure activity on the EEG (prilocaine 53 mg.kg-1 and 2-chloroprocaine 70 mg.kg-1, on average) are much higher than those used in clinical practice (usually < 10 mg.kg-1).

Anesthetics, Local↗
PubMed1993

Respiratory frequency and artifact affect the capnographic baseline in infants.

We sought to determine the effect of rebreathing on the capnographic waveform baseline. In anesthetized infants, we studied the effect of respiratory frequency (f) and breathing circuit type (Bain, n = 6, and pediatric circle, n = 4) on capnography of respiratory gas aspirated from the circuit for mass spectrometry (PCO2asp) and flowing through an infrared analyzer (PCO2f-t). As f increased, measured values of PiCO2asp and PiCO2f-t increased in both Bain and circle groups, with the exception of PiCO2f-t values that remained zero in the circle group. PETCO2 decreased as f increased in the circle groups, but remained constant in the Bain groups. These data suggest that artifact, most likely due to parabolic distortion of CO2 plugs traversing long sampling catheters, makes up a significant percentage (8%-36%) of the aspiration capnographic baseline elevation depending on f and breathing circuit type. Despite increases in PiCO2 as f increased, PETCO2 does not increase in Bain circuits due primarily to an increase in minute ventilation (Ve) that offsets the increase in the PiCO2 to provide balance in the CO2 mass relationship (PETCO2 approximately VCO2/Ve+PiCO2). These findings are useful in the correct interpretation of elevated capnographic baseline in infants.

Anesthesia, Closed-Circuit↗
PubMed1993

Sedation and analgesia for gastrointestinal endoscopy.

We compared analgesia and sedation provided by one of four different opioids in combination with midazolam during gastrointestinal endoscopy. Patients were given 1-3 mg midazolam and meperidine 50-100 mg, fentanyl 50-100 micrograms, sufentanil 5-10 micrograms, or alfentanil 150-300 micrograms, plus additional opioid and/or midazolam if needed. No untoward effects (i.e., O2 saturation < 85%, nausea, vomiting, severe bradycardia) occurred. Sedation and analgesia were comparable in the upper gastrointestinal groups. The number of patients with amnesia for the examination was highest in the meperidine group. Recovery time generally was shorter with alfentanil and sufentanil. Recovery time of the lower gastrointestinal patients was significantly longer in the meperidine group than in the other groups; analgesia scores for sufentanil were significantly lower than for meperidine. Sedation scores for these patients were highest in the meperidine group. The number of patients given meperidine who were amnesic was significantly greater than for the other opioids. Meperidine was better than the other opioids with regard to patient comfort and amnesia during colonoscopy.

Adolescent↗
PubMed1992

Severe hypoxia enhances central nervous system and cardiovascular toxicity of bupivacaine in lightly anesthetized pigs.

Toxic systemic reactions to bupivacaine usually involve a number of factors, including hypoxia and acidosis. The objective of this study was to test the hypothesis that cardiovascular and central nervous system responses to bupivacaine overdose are proportional to the severity of hypoxia. The central nervous system and cardiovascular toxicity of bupivacaine was examined in three groups of pigs breathing 30%, 15%, or 10% O2, 70% N2O, and He (FIO2 = 0.15 and 0.1 groups). The 18 2-week-old pigs (6 animals per treatment) were paralyzed with pancuronium and their lungs ventilated mechanically. During the intravenous infusion of bupivacaine 2 mg.kg-1.min-1, four readily identified toxic endpoints (seizures, arrhythmias, isoelectric electroencephalogram, asystole) were observed in all animals, with the exception that 1 pig in the FIO2 = 0.3 group and 1 in the FIO2 = 0.15 group had no arrhythmias. Bupivacaine doses producing seizures, isoelectric EEG, and asystole were significantly less in the FIO2 = 0.1 groups as compared to the other groups. Arrhythmias occurred before seizures in all animals in the FIO2 = 0.1 group but in only 1 of 5 and 2 of 5 animals in the FIO2 = 0.15 and 0.3 groups, respectively. There was no significant difference between the arrhythmic dose of bupivacaine in the FIO2 = 0.3 versus 0.1 animals (8.4 +/- 2.4 vs. 4.0 +/- 1.4 mg.kg-1), but the dose was significantly less in the FIO2 = 0.1 animals than in the FIO2 = 0.15 animals (12.5 +/- 5.6 mg.kg-1). Arterial pH was stable in all three groups during bupivacaine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Acute cardiovascular and central nervous system toxicity of bupivacaine and desbutylbupivacaine in the rat.

Desbutylbupivacaine, a major metabolite of bupivacaine, is known to accumulate during long-term continuous infusion blocks in man. Its acute toxicity in comparison with that of bupivacaine has not been studied. In a lightly anaesthetized rat model, bupivacaine (2 mg/kg/min, N = 10) or desbutylbupivacaine (4 mg/kg/min, N = 10) was infused i.v. until asystole. Arterial blood pressure, ECG and EEG were continuously recorded. The mean doses of bupivacaine producing cardiac toxicity, i.e. arrhythmia (12.4 mg/kg) and asystole (24.0 mg/kg), were approximately half of those of desbutylbupivacaine. Seizure activity on the EEG was observed in only one of the desbutylbupivacaine-infused rats while all rats receiving bupivacaine developed seizures (mean dose 5.2 mg/kg). Desbutylbupivacaine infusion caused a decrease in arterial blood pressure greater than that resulting from bupivacaine infusion. When desbutylbupivacaine 0.67 mg/kg/min was coinfused with bupivacaine 2 mg/kg/min, the cardiovascular toxicity of bupivacaine was clearly potentiated. The EEG parameters were affected in a similar fashion as when bupivacaine alone was infused. In this rat model, desbutylbupivacaine was about half as toxic as bupivacaine judged by cardiac parameters, and clearly less toxic to the central nervous system than bupivacaine.

Animals↗
PubMed1991

End-tidal carbon dioxide pressure in neonates and infants measured by aspiration and flow-through capnography.

In 25 anesthetized, intubated, artificially ventilated, and paralyzed healthy neonates and infants, end-tidal PCO2 (PETCO2) measured by remote multiplexed mass spectrometry was 1.86 +/- 1.58 mm Hg lower than arterial PCO2 (PaCO2). PETCO2 measured by a flow-through cuvette was 1.02 +/- 1.64 mm Hg lower than PaCO2. The difference between the two methods of capnography was not significant. Values for PETCO2 obtained by mass spectrometry changed -0.43 +/- 1.43 mm Hg from baseline after 15 minutes of aspiration at a sample flow rate of 240 ml/min. Values for PETCO2 obtained with flow-through capnography changed -0.17 +/- 2.17 mm Hg from baseline after 15 minutes. In both methods, the changes from baseline in PETCO2 over time were not significant. These results suggest that both methods of capnography studied are reliable and may be used safely in neonates despite high sample flow rates and added apparatus dead space (0.6 ml for tracheal tubes less than or equal to 4.0 mm OD and 4.9 ml for tracheal tubes greater than 4.0 mm OD).

Carbon Dioxide↗
PubMed1991

Effect of different intravenous nutrients on upper gastrointestinal secretion in rats.

Total parenteral nutrition has been advocated for nutritional support of patients with proximal small bowel fistula. Data on the direct effects of different nutrients on upper gastrointestinal secretion are controversial. Therefore, we examined the effects of glucose, amino acid, fat and mixed parenteral solutions on gastric juice secretion, hydrochloric acid and pepsin content, duodenal juice secretion, and pancreatic protein, amylase, bilirubin and bicarbonate content in thirty rats with chronic gastric and duodenal fistulas. Gastric secretion was increased by glucose solution (D10W) and by amino acid solution (5% AA) (13% and 12% increase respectively) but not to significant degree by fat emulsion (2% F). Both D10W and 5% AA caused comparable increase in hydrochloric acid secretion (D10W: +34%; 5% AA: +28%) and the pepsin secretion (D10W: +37%). The single infusion of hypertonic glucose, amino acids and fat were associated with decreases in duodenal fistula volume (p less than 0.05) or content output. Mixed nutrients decreased both gastric secretion (volume: -28%; HCl: -19%; pepsin: -65%) and duodenal juice volume (p less than 0.05), protein and amylase content (p less than 0.05). The elevated bilirubin in reduced volume of duodenal juice caused by mixed nutrients may be responsible for bile sludge formation. This study indicates that the use of parenteral nutrition can provide full nutritional support while decreases the fistula output.

Amino Acids↗
PubMed1990

Bupivacaine toxicity in young pigs is age-dependent and is affected by volatile anesthetics.

The influence of age and volatile anesthetic agents on plasma concentrations and toxic effects of bupivacaine were studied in 2-day-old, 2-week-old, and 2-month-old pigs. Bupivacaine was infused at a constant rate while the pigs' ECGs and EEGs were recorded. Six pigs in each age group were lightly anesthetized with 70% N2O/30% O2 during the bupivacaine infusion, and twelve 2-day-old pigs were anesthetized with 70% N2O/30% O2 plus either 0.5 X MAC halothane or isoflurane. Two-day-old pigs were more resistant than older pigs to the toxic effects of bupivacaine despite higher plasma concentrations at all sample times. All pigs given N2O alone or N2O plus halothane had ventricular dysrhythmias, but only one pig in the N2O plus isoflurane group had a ventricular dysrhythmia. Threshold doses of bupivacaine for dysrhythmias in the N2O alone and N2O plus halothane groups did not differ. Seizures occurred in all pigs in the N2O alone group, in none of the N2O plus halothane group, and in two of the N2O plus isoflurane group. The doses required to depress cardiac index and cause asystole were less in the groups receiving halothane and isoflurane. It was concluded that N2O plus halothane and N2O plus isoflurane increase the lethality of bupivacaine while preventing early warning signs of toxicity.

Aging↗
PubMed1990

Alveolar dead space does not affect indirect Fick cardiac output determinations.

We examined the influence of three variables (different breathing circuits, breath selected for analysis, and alveolar dead space ventilation) on the accuracy of noninvasive cardiac output determinations with the Fick CO2 (indirect) equation. We compared noninvasive determinations with invasive thermodilution measurements over a wide range of cardiac outputs in 17 2-mo-old pigs anesthetized with halothane and nitrous oxide and paralyzed with either pancuronium or d-tubocurare. We found that rebreathing and nonrebreathing circuits provide accurate cardiac output determinations and that the optimal breath for analysis with either the rebreathing or nonrebreathing technique appears to depend on the cardiac output. When alveolar dead space was increased by using positional changes and the intracardiac administration of glass beads, there was still a good correlation between noninvasive and invasive cardiac output determinations. We conclude that both rebreathing and nonrebreathing techniques of indirect Fick cardiac output determinations correlate well with thermodilution measures over a wide range of cardiac outputs and alveolar dead space/tidal volume fractions.

Animals↗
PubMed1989

Morphine self-administration in the rat during adjuvant-induced arthritis.

Rats injected with Freund's adjuvant develop a syndrome resembling human rheumatoid arthritis complete with paw swelling, edema and persistent pain. At the onset of pain, arthritic rats and their pain-free littermate controls (vehicle injection) were allowed to self-administer intravenous morphine (5.0 mg/kg/injection) in a 24 hr/day schedule. Self-injected morphine appeared to provide analgesia in arthritic rats as demonstrated by a decreased sensitivity to applied tail pressure. Arthritic rats self-inject significantly less morphine than pain-free animals. Injection of indomethacin, which alleviates the pain and inflammation of the adjuvant-induced disease, reduces, at least initially, morphine self-injection in the arthritic but not pain-free animals. As the adjuvant-induced inflammation and pain dissipated, arthritic rats rapidly began to increase opioid intake. The presence of persistent pain apparently reduces the addictive properties of morphine.

Animals↗