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Biomedical subjects

G A Petroianu

Publications and source records attributed to G A Petroianu.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: tiapride vs. pyridostigmine.

Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 microMol paraoxon (approximately LD75) groups 2-6 received in addition: G(2)50 microMol tiapride 30 min before paraoxonG(3)50 microMol tiapride 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G41 microMol pyridostigmine 30 min before paraoxon G(5)1 microMol pyridostigmine 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G(6)50 microMol pralidoxime 1 min after paraoxon. Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G3) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G5). Tiapride pretreatment only (G2) is inferior to pyridostigmine pretreatment only (G4). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G4 and G6).

Acute Disease↗
PubMed2006

Tiapride pre-treatment in acute exposure to paraoxon: comparison of effects of administration at different points-in-time in rats.

INTRODUCTION: Accidental and suicidal exposures to organophosphorus compounds (OPC) are frequent. The inhibition of esterases by OPC leads to an endogenous ACh poisoning. Recently, the FDA approved, based on animal experiments, for military combat medical use oral pyridostigmine (PSTG) for pre-exposure treatment of soman; the concept is to block the cholinesterase reversibly using the carbamate pyridostigmine in order to deny access to the active site of the enzyme to the irreversible inhibitor (OPC) on subsequent exposure. We have shown previously that tiapride (TIA) is in vitro a weak inhibitor of AChE. We also have shown recently that in rats coadministration of TIA with the organophosphate paraoxon significantly decreases mortality without having an impact on red blood cell cholinesterase (RBC-AChE) activity. PURPOSE OF THE STUDY: To establish in a prospective, non-blinded study in a rat model of acute high dose OPC (paraoxon; POX) exposure the ideal point in time for TIA pre-treatment administration and to correlate it with measured TIA plasma levels. MATERIAL AND METHODS: There were six groups of rats in each cycle of the experiment and each group contained six rats. The procedure was repeated twelve times (cycles) (n = 72 for each arm; half male and half female). All substances were applied ip. All groups (1-6) received 1 microMol POX ( approximately LD(75)); groups 1-5 also received 50 microMol TIA at different points in time. Group 1 (G(1)): TIA 120 min before POX Group 2 (G(2)): TIA 90 min before POX, Group 3 (G(3)): TIA 60 min before POX, Group 4 (G(4)): TIA 30 min before POX, Group 5 (G(5)): TIA & POX simultaneously, Group 6 (G(6)): POX only. The animals were monitored for 48 hours and mortality/survival times were recorded at 30 min, 1, 2, 3, 4, 24 and 48 h. AChE activities were determined at 30 min, 24 and 48 h in surviving animals. Statistical analysis was performed on the mortality data, cumulative survival times and enzyme activity data. Mortality data was compared using Kaplan-Meier plots. Cumulative survival times and enzyme activites were compared using the Mann-Whitney rank order test. No Bonferroni correction for multiple comparisons was applied and an alpha < or= 0.05 was considered significant. RESULTS: Mortality is statistically significantly reduced by TIA pre-treatment at all points-in-time. Highest protection is achieved if TIA is given 90 to 0 min before OPC exposure. The reduction in mortality is not correlated to TIA plasma levels (C (max) approximately 120 min post ip-administration). TIA pre-treatment is not affecting AChE activity regardless of the timing of administration. CONCLUSION: The lack of correlation between TIA plasma levels and degree of mortality reduction as well as the lack of protective effect on enzyme activity seem to indicate that the site of action of TIA is not the blood. While our hypothesis that TIA would protect AChE in a pyridostigmine-like manner (via protection of the enzyme) could not be confirmed, the reduction in mortality with TIA pre-treatment is nevertheless of potential interest.

Animals↗
PubMed2005

Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p < or = 0.01). The number of catalase positive cells in the clofibrate group is higher than in the moexipril group (p < or = 0.01). High-dose subchronic exposure to the ACE-inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Clonidine increases membrane-associated phospholipase A 2.

BACKGROUND AND OBJECTIVE: An anti-inflammatory effect of alpha2-adrenoreceptor agonists has been suggested. Phospholipase A2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A2 activity in an established in vitro model. METHODS: Human being platelet membranes containing active phospholipase A2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A2 was measured by a radioisotope technique. RESULTS: A massive increase in phospholipase A2 activity was measured after clonidine exposure leading to final values of 92.5 +/- 3.1 pmol mg protein(-1) min(-1) (4.5-fold higher than control values; P < or = 0.01 vs. control). After clonidine exposure the maximal reaction velocity increased, while the Michaelis-Menten constant did not change. The Lineweaver-Burk representation suggested an interaction of clonidine with the phospholipase A2-substrate complex as well as the phospholipase A2 molecule. CONCLUSION: We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A2.

Adjuvants, Anesthesia↗
PubMed2000

The effect of In vitro hemodilution with gelatin, dextran, hydroxyethyl starch, or Ringer's solution on Thrombelastograph.

UNLABELLED: To determine the effects of progressive in vitro hemodilution with various plasma substitutes on whole blood coagulation, blood was obtained from six healthy volunteers. The Thrombelastograph((R)) (TEG; Haemoscope Corp., Morton Grove, IL) variables of reaction time, coagulation time, maximum amplitude, and growth angle were determined. The following plasma substitutes were tested: two gelatin solutions (4% gelatin polysuccinate and 5.5% oxypolygelatin); two dextrans (10% dextran 40 and 6% dextran 60); and five hydroxyethyl starch (HES) preparations (6% HES 70/0.5-0.55, 3% HES 200/0.5, 6% HES 200/0.5, 10% HES 200/0.5, and 6% HES 450/0.7). Ringer's solution was also tested to assist analyzing the intrinsic effect of colloid molecules on blood coagulation. The dilution ratios of citrated blood volume to plasma substitute volume were 10:2, 10:4, and 10:10. Blood coagulation was affected by plasma substitutes when the dilution ratios of citrated blood volume to colloid solution volume were 10:4 and 10:10. TEG variables did not change significantly after in vitro hemodilution with lactated Ringer's solution. The tested gelatin solutions showed less intrinsic effect on blood coagulation than other plasma substitutes. All HES preparations showed similar intrinsic effects as 6% dextran 60. The plasma substitute of 10% dextran 40 had the strongest effect on coagulation. Coagulation time was the most markedly affected TEG variable. Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation, 10% dextran 40 has the strongest effect on coagulation. IMPLICATIONS: Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation than hydroxyethyl starch or dextran, 10% dextran 40 has the strongest effect on coagulation.

Blood Coagulation↗
PubMed1999

Meconium and amniotic fluid embolism: effects on coagulation in pregnant mini-pigs.

OBJECTIVE: A hallmark of amniotic fluid embolism is the induction of coagulation defects. Little is known about the nature of these defects or the causative agent or agents. The purpose of this study was to assess the effects of meconium containing (native) meconium-amniotic-fluid infusion (MAFI) and meconium-free (centrifuged) amniotic-fluid infusion (AFI) on the coagulation system in the mini-pig model. DESIGN: Laboratory study. SETTING: University institute animal laboratory. SUBJECTS: Near-term pregnant Göttingen bred mini-pigs in three groups (control, MAFI, AFI) of six animals each. INTERVENTIONS: After induction of anesthesia, amniotic fluid was collected by cesarean section in all animals. Depending on the group, animals received either Ringer's solution (control), native amniotic fluid (MAFI), or centrifuged amniotic fluid (AFI) via an ear vein. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken from a central vein before infusion (baseline), immediately after infusion, every 10 mins until 90 mins after infusion, and finally, every 20 mins until 150 mins after infusion. The following parameters were measured: Platelets, partial thromboplastin time, prothrombin time, fibrinogen, factors V, VII, VIII, antithrombin III, and protein C. The values relative to baseline in the MAFI and AFI groups were compared with control by rank order test. A p<.05 was considered statistically significant. Compared with the control group, platelets were lower in the MAFI group (p<.005), PTT was prolonged in both the MAFI and AFI groups (p<.005), fibrinogen was lower in both the MAFI and AFI groups (p<.05), prothrombin index was lower (i.e., prothrombin time was prolonged) in the MAFI group (p<.05), and protein C was lower in the MAFI group (p<.005). CONCLUSIONS: Both MAFI and, to a much lesser extent, AFI cause an activation of coagulation in mini-pigs. The changes induced by meconium-free AFI are probably not sufficient to explain the high mortality of the condition.

Amniotic Fluid↗
PubMed1998

Another portable quantitative capnometer.

A new portable quantitative capnometer (Bruker CO2 Module) was tested in an animal lab (mini-pigs) during experiments on air embolism. The end-tidal CO2 values, as measured with this device, showed good agreement with the values of a stationary capnography unit. This device seems suited for quantitative capnometry in the prehospital setting.

Animals↗
PubMed1998

Preliminary observations on the Colibri CO2-indicator.

The performance of a new colorimetric CO2-indicator (Colibri) was assessed in mini-pigs. It performed well during 8-hour procedures. Neither nitrous oxide, nor halothane, nor carbon monoxide, nor intratracheal application of drugs (epinephrine, atropine, lidocaine, and naloxone) interfered with its function. It gave a distinct color change at high ventilation frequencies up to 120/min. The only problem observed was difficulty in matching the colors displayed with the comparison color chart provided. The Colibri's performance seems at least equal to that of the EasyCAP detector, although both devices share some disadvantages (no alarms, semiquantitative, difficult reading in the dark). After initial control of endotracheal tube position by an esophageal detector device, both the Colibri and the EasyCAP seem suited for monitoring of ventilation and circulation if quantitative capnometry is unavailable.

Animals↗
PubMed1998

[Bellows or bag? Testing 10 ventilators and some medical history comments].

We compared a new bellows ventilator (Kendall Cardiovent) with two other bellows (Dräger Resutator 63, Tagg Breathsaver) and seven bag or ball ventilators (Aerodyne Hope, Ambu Mark 3, Ambu Silicon, Dräger Resutator 2000, Laerdal Resu, Mercury CPR, Weinmann Combibag). Tidal volumes were measured with two Laerdal Recording Resusci Annies, one lying on the floor, one in a bed. Twelve participants performed mask ventilation with all ten devices on both manikins for two minutes, trying to achieve tidal volumes of between 0.8 and 1.21 as recommended by the AHA. The last ten ventilations each on the graphic strips were analysed for volume. The participants scored handling of the devices on a 6-point scale (1 = very good, 6 = insufficient). The results of the Cardiovent were compared to those of the other devices by rank sum test (percentage of correct ventilations) and sign test (subjective handling). The Cardiovent provided exact ventilation with 95% of ventilations) on the floor and 78% of ventilations in bed in the recommended range. However, the percentage of correct ventilations with the Cardiovent was not significantly different to the other devices except for a lower percentage of correct ventilations with the Combibag in the in bed setting. Concerning subjective handling, the Cardiovent was significantly superior to several ball ventilators.

Equipment Design↗
PubMed1997

[Stress free anesthesia induction ZESTRANI (ZEro STRess ANesthesia Induction) in Göttingen minipigs. An experimental method].

The Göttingen Mini-pig is a popular laboratory animal, that is used i.a. in experimental surgery and anaesthesia. For ethical and scientific reasons it is mandatory to minimize the stress the laboratory animals are exposed to. The presented stress-free experimental anaesthesia induction (ZESTRANI) is based on innovative means to achieve adequate analgesia using different substances appropriate for the animal's state of consciousness. Markedly lower heart rates and mean arterial pressures are seen when the ZESTRANI-method is used as compared retrospectively to the previously used "conventional" anaesthesia induction. With the ZESTRANI method no "fight or flight"-reactions are seen.

Anesthesia, General↗
PubMed1996

A portable quantitative capnometer in test.

A new hand-held quantitative capnometer (BCI Capnocheck) was tested in the animal lab setting. The end-tidal CO2 values, as measured with this device, showed good agreement with arterial (Paco2) values. This device seems suited for quantitative capnometry in the prehospital setting. It must be noted, however, that this device has no alarms.

Animals↗
PubMed1996

Oximetry for amniotic fluid embolism detection in mini-pigs: tail or snout?

The continuous, non-invasive real-time monitoring of arterial oxygenation (pulse oximetry) has become a standard of care in both human and veterinary medicine. It allows reliable, simple and inexpensive assessment of the arterial oxygenation status. In pigs, commonly used sites for oximetry-probe placement are the ear, snout or tongue, while more recently the 'pig-tail oximetry' has been suggested. In a study regarding the coagulation system during amniotic fluid embolism (AFE) in mini-pigs, we compared tail and snout for oximetry-probe placement and compared them with the 'gold standard': blood-gas analysis (BGA). In both the AFE group and the control group, the tail measurements were slightly lower and the snout measurements were slightly higher than the BGA results. In the experimental model used, both tail and snout measurements were able to detect a temporary desaturation immediately after amniotic fluid embolism (AFE). Blood-gas analysis (BGA) performed on blood drawn from a large artery missed the event. Clinically, there is no significant difference between snout and tail as oximetry-probe placement sites: both are reliable oximetry sites in mini-pigs.

Animals↗
PubMedDate not supplied

Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): in vitro effect of ranitidine.

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP is a weak and reversible inhibitor of cholinesterases. We have shown that MCP has a cholinesterase protective effect against inhibition by organophosphates. The putative mode of protective action of MCP is competition for the active site of the enzyme with the more potent organophosphate. In the present paper we present our results using another weak inhibitor of cholinesterases: ranitidine (RAN). The purpose of the study was to quantify in vitro the extent of RAN-conferred protection, using paraoxon (POX) as an inhibitor. Paraoxon is a non-neuropathic organophosphate responsible for a large number of accidental or suicidal exposures. Red blood cell (RBC) acetylcholinesterase (AChE) activities in whole blood and butyrylcholinesterase (BChE) activities in human plasma were measured photometrically in the presence of different POX and RAN concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing RAN concentrations. The IC50 shift induced by the presence of RAN increases with the RAN concentration in a linear manner. The shift was more pronounced with RBC-AChE. The protective effect of RAN on cholinesterase could be of practical relevance in the treatment of POX poisoning. We conclude that in vivo testing of RAN as an organophosphate protective agent is warranted.

Acetylcholinesterase↗