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Z Todorović

Publications and source records attributed to Z Todorović.

At least 19 recordsLinked to original sources
PubMed2003

[Antibiotics in the prevention of the surgical site infection in orthopedic surgery].

Surgical site infection is an actual problem of orthopaedic surgery. Despite considerable efforts that have been done during last several decades (e.g. improvements in surgical techniques, preoperative preparation of the surgical site, infection-control practice, use of preventive antibiotics) surgical site infection still affects about 0.5-2% of patients after closed fracture surgery or insertion of prosthetic devices. They are associated with substantial morbidity and mortality. The adherence to the principles of rationale preventive antibiotic therapy has an important role in the prevention of the surgical infection. In addition, it is well known that inappropriate use of antibiotic promote development of resistance, superinfections and increase the cost of the treatment. This paper focuses on the basic principles of rational use of antibiotics, i.e. appropriate selection of drug, dose, and duration of treatment in the prevention of surgical site infections in orthopaedic surgery.

Antibiotic Prophylaxis↗
PubMed2001

The influence of L-arginine on heart rate and tissue oxygen extraction in haemorrhaged rabbits.

Several studies have already indicated some beneficial effects of L-arginine in haemorrhaged rats. The aim of our study was to assess whether intravenous bolus injection of L-arginine could improve some cardiovascular and metabolic parameters in anaesthetized haemorrhaged rabbits (intermittent bleeding; 40% of the estimated blood volume for 15 min). I.v. bolus injection of L-arginine ( 300 mg kg(-1)--L-Arg(300)) increased heart rate (app. 10%) and decreased venous haemoglobin saturation with oxygen (sO(2)) (app. 23%) 60 min after the cessation of bleeding, without changes in arterial pressure. D-arginine (300 mg kg(-1)i.v. bolus-D-Arg(300)) produced similar, but insignificant haemodynamic and metabolic changes. In addition, no difference was found between the effects of the L- and D-isomers. Accordingly, L-arginine produces beneficial effects on the heart rate and tissue oxygen extraction in haemorrhaged rabbits. However, such changes do not appear to be stereospecific.

Acid-Base Equilibrium↗
PubMed1998

The cardiovascular effects of the administration of L-NAME during the early posthemorrhagic period.

1. The effects of the various doses of NG-nitro-L-arginine methyl ester (L-NAME, 10 and 30 mg/kg) on some cardiovascular and biochemical parameters during the early posthemorrhagic period were studied in anesthetized rabbits subjected to hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced by intermittent bleeding of 40% of the estimated blood volume for 15 min. Blood samples were taken before and after bleeding (0, 15 and 60 min). Simultaneously, the mean arterial pressure (MAP) and the heart rate (HR) were measured. Hemorrhaged rabbits were treated by L-NAME10 or L-NAME30 (10 or 30 mg/kg, i.v. bolus injection, respectively) or the corresponding volumes of saline (0.6 ml, i.v. bolus) immediately after the end of bleeding. 3. The observed cardiovascular parameters (MAP, HR) were significantly reduced after the end of bleeding in all rabbits. 4. The rise of the MAP was significantly more pronounced 30 min after the injection of L-NAME30 in comparison with the corresponding values in the saline (S) group. In contrast, L-NAME10 produced only a small, insignificant increase in the MAP in hemorrhaged rabbits. 5. The L-NAME30-induced rise of the MAP was accompanied by a severe bradycardia, hyperkalemia and an aggravated metabolic acidosis, more severe than the corresponding disturbance of the acid-base status in the S group. The changes in the acid-base parameters were observed both in arterial (pH, excess base) and in venous blood (pH) of hemorrhaged rabbits. 6. In conclusion, the i.v. bolus injection of L-NAME30 (immediately after the end of bleeding) produced a significant increase in the MAP during the first hour after the injury, but the presumable inhibition of the endothelial constitutive nitric oxide synthase during the early posthemorrhagic period resulted in severe cardiovascular and metabolic disturbances.

Animals↗
PubMed1998

Higher environmental temperature potentiates cataleptic effect of fentanyl in rats.

The influence of higher environmental temperature (HET=30/-1 degrees C) on fentanyl-induced behavior was studied in unrestrained rats. Subacute exposure (3 days) of rats to HET significantly (P<0.01) increased the cataleptic effect of fentanyl citrate (0.5 mg/kg), in comparison to the corresponding exposure to normal environmental temperature (NET=22+/-1 degrees C). Also, the hyperthermic response of rats to a low dose of fentanyl citrate (0.2-0.5 mg/kg) was significantly (P<0.01) potentiated, and the hypothermic response to a high dose of fentanyl citrate (1.5 mg/kg) was significantly (P<0.05) attenuated after exposure to HET. Fentanyl-induced hyperexcitability, loss of righting reflex, loss of corneal reflex and analgesia were not significantly affected by HET. This study provides the first evidence on the influence of environmental temperature on drug-induced catalepsy. HET-induced potentiation of the cataleptic response to fentanyl could be the result of an interference with behavioral thermoregulation.

Analgesics, Opioid↗
PubMed1997

Physostigmine and modulators of nitric oxide system on the mean arterial pressure of the spontaneously hypertensive rat.

1. A slow intravenous infusion of L-arginine (3 mg kg-1) lasting one hr produced significant hypotension in urethane-anaesthetized spontaneously hypertensive rats (SHRs). 2. A slow intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) (3 mg kg-1 h-1) did not produce any significant change in the mean arterial pressure during infusion. After stopping infusion of L-NAME, a slowly developing increase of the mean arterial pressure was observed during the following 40 min. 3. The pressor response to physostigmine (20, 40 and 80 micrograms kg-1, IV), injected during a slow intravenous infusion of either L-arginine or L-NAME, was not changed. 4. L-arginine and L-NAME depressed the pressor responses to physostigmine, if physostigmine was injected after the end of a 1-hr infusion. 5. Acute pretreatment with increasing doses of physostigmine markedly affected the blood pressure response to L-arginine (i.e., L-arginine-caused hypotension was more pronounced), but only slightly that to L-NAME. 6. In conclusion, L-arginine, as a donor of NO, produced hypotension by itself and also decreased, but not significantly, the central cholinergically-mediated hypertension (CCMH) produced by physostigmine. It is quite possible that the peripheral NO released by L-arginine antagonized the increased adrenergic activity in the CCMH. This does happen in normotensive rats, but to a lesser degree than in SHRs, as shown in the current experiments. 7. Also, our results show that inhibition of endogenous NO biosynthesis using L-NAME does not necessarily lead to pressor response in vivo, at least in SHRs. It is concluded that L-arginine-nitric oxide pathways operate in SHRs, as well as in normotensive Wistar rats, but their role in modulating cholinergically-mediated regulation of the mean arterial pressure is less pronounced in SHRs than in normotensive animals.

Animals↗
PubMed1995

The effect of physostigmine on acid-base status in arterial and venous blood of anaesthetized rabbits following hypovolemic shock.

1. The effects of physostigmine (70 micrograms kg-1, intravenously) on acid-base status in arterial and venous blood were studied in anaesthetized rabbits subjected to hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced using intermittent bleeding of 50% of the estimated blood volume, during 30 min. Experimental group was treated with physostigmine (70 micrograms kg-1 body mass, intravenously) and the control group with the same volume (0.1 ml) of saline, immediately after bleeding. Blood samples were taken before and after bleeding (0, 15 and 60 min). 3. It was found that physostigmine increased the mean arterial blood pressure, did not change the heart rate, and improved survival of the animals. 4. These effects of physostigmine were associated with significant decrease in venous pH, produced mainly by increased PCO2. This can partly be explained in terms of additional vasoconstriction due to physostigmine action. 5. In arterial blood decreased pH, decreased standard bicarbonate, negative values of excess base and decreased PCO2 were observed both in physostigmine-treated and the control group of animals, indicating partly respiratory compensated metabolic acidosis. These findings indicate that the hypertensive effect of physostigmine in shock was not accompanied by more severe disturbance in arterial acid-base status than was observed in hypovolemic shock alone.

Acid-Base Equilibrium↗
PubMed1995

The effect of nickel chloride on the isolated hemidiaphragm of the rat.

1. NiCl2 (cumulative concentrations of 0.56-1.91 mmol 1(-1)) produced concentration-dependent depression of tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of isometric contraction of the isolated rat hemidiaphragm, during direct subtetanic (DST) electrical stimulation, only. EC50 values for NiCl2-induced depression of Td and Dt/dt max were 0.88 +/- 0.06 and 0.83 +/- 0.13 mmol 1(-1), respectively. NiCl2 did not significantly change either parameter of the isometric contraction during direct single-pulse (DSP) electrical stimulation. 2. Maximal depression of Td and dT/dt max, produced by a single concentration of NiCl2 (1 mmol 1(-1)) during DST electrical stimulation was obtained 20 min after addition of the drug in the bathing medium. 3. In the normal Tyrode solution, addition of CaCl2 (final concentration of 5.86 mmol 1(-1)) almost completely antagonized the depressant effect of NiCl2 (1 mmol 1(-1)) on Td and dT/dt max during DST electrical stimulation. In the calcium-free solution, the depression both of Td and dT/dt max produced by NiCl2 (1 mmol 1(-1)) was significantly more pronounced in comparison with the effect of NiCl2 in the normal Tyrode solution. 4. L-calcium channel activator, Bay K 8644 (25 mumol 1(-1)), significantly potentiated both Td and dT/dt max during DST electrical stimulation, but NiCl2 (1 mmol 1(-1)) decreased both parameters of the isometric contraction even in the presence of this concentration of Bay K 8644. On the other hand Bay K 8644 (25 mumol 1(-1)) did not antagonize NiCl2-induced depression of Td and dT/dt max. 5. Verapamil (2.5 mumol 1(-1); 45 min of incubation) and lidocaine (0.10 mmol 1(-1); 30 min of incubation) significantly potentiated the depression of Td and dT/dt max, produced by NiCl2 (1 mmol 1(-1), during DST electrical stimulation. The addition of CaCl2 (final concentration of 7.20 mmol 1(-1)) in the bathing medium only partially antagonized the depressant synergistic action of both verapamil or lidocaine and NiCl2 on Td and dT/dt max. 6. Forskolin (cumulative concentrations of 2.60-44.20 mumol 1(-1)) fully antagonized NiCl2-induced depression of both Td and dT/dt max; propranolol (1 mumol 1(-1)) did not abolish this antagonizing action of forskolin. Also, NiCl2 (cumulative concentrations of 0.56 -1.54 mmol 1(-1)) did not change potentiating effect of forskolin (23.4 mumol 1(-1)).(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Some new evidence on antifatigue action of aminophylline on the isolated hemidiaphragm of the rat.

1. Aminophylline (cumulative concentrations of 0.036-3.60 mmol/l) produced a concentration-dependent increase in both tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of the isolated hemidiaphragm of the rat both during direct single-pulse and subtetanic stimulation. 2. The repeated series of additions of aminophylline into the bathing medium (the second and the third series) produced even further, more pronounced potentiation of both Td and dT/dt max during subtetanic stimulation only, the potentiation being the strongest after the third series of additions of the drug ("antifatigue effect"). The antifatigue effect of aminophylline was much more pronounced than the antifatigue effect of the equimolar concentrations of caffeine. 3. The presence of intact beta 1-adrenergic receptors seems to be essential for the antifatigue action of aminophylline under our experimental conditions. 4. The antifatigue effect of aminophylline was not affected by reserpine or 6-OHDA pretreatment of rats. 5. In a Ca(2+)-free medium the stimulatory effect of aminophylline on Td and dT/dt max was abolished or depressed (single-pulse and subtetanic stimulation, respectively). After returning the muscle into the medium containing Ca2+, the effect of aminophylline was significantly potentiated during both types of the stimulation. 6. The antifatigue action of aminophylline was preserved even in the presence of nicardipine or its solvent in the bathing medium. 7. In the presence of heparin (which produced a significant depression of both Td and dT/dt max by itself during direct subtetanic stimulation) the stimulatory effects of aminophylline on Td and dT/dt max (the second and third series of additions) were significantly potentiated in comparison with the effects of the first series of additions of aminophylline (with no heparin in the bathing medium). 8. The dose-response curves for the effects of aminophylline in the presence of Ni2+ on Td and dT/dt max during direct single-pulse stimulation were significantly shifted to the right. Ni2+ by itself produced significant and dose-related depression of both Td and dT/dt max during single-pulse and subtetanic stimulation, the subtetanic stimulation being much more sensitive. The antifatigue effect of aminophylline during subtetanic stimulation was preserved in the presence of Ni2+. 9. Our results indicate the important role of the extracellular calcium and the involvement of intact beta 1-adrenergic receptors in the antifatigue action of aminophylline. Also, the potentiating effect of heparin on the antifatigue action of aminophylline is presumably due to the influx of extracellular calcium through L-type Ca2+ channels during subtetanic stimulation. Our results indicate the possibility of the presence of T-type calcium channels (which can be blocked by Ni2+) in the isolated hemidiaphragm of the rat, but they do not seem to be involved in the antifatigue action of aminophylline.

Adrenergic beta-Antagonists↗
PubMed1991

The potentiation of cardiodepressant and hypotensive effects of bradykinin by enalapril and captopril both in vitro and in vivo.

1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.

Anesthesia↗
PubMedDate not supplied

The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the mean arterial pressure of the rat.

The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in urethane-anaesthetized rats. The drugs were chosen because physostigmine has been known to produce an increase in peripheral adrenergic activity, whereas L-arginine and L-NAME have been known to modulate nitric oxide (NO) production. Slow infusion of L-arginine produced significant hypotension, but only in animals pretreated by physostigmine. L-NAME applied in the same way produced a slow developing increase in blood pressure, but not in animals pretreated by physostigmine. The pressor responses to physostigmine were potentiated if the drug was injected during infusion of L-NAME, and depressed if the drug was injected after stopping L-NAME infusion (in rats not pretreated with physostigmine). It is concluded that L-arginine-NO pathways act in vivo to oppose peripheral vasoconstrictor influences coupled with central cholinergically mediated activation of the adrenergic system, as produced by physostigmine. In this way, NO is part of a general mechanism for blood pressure regulation.

Animals↗