Effects of carazolol on electrocadiographic and trace element status in sheeps

Carazolol is a non-specifi c β-adrenargic reseptor blocking agent. It ıs structurally analogous to catecholamins, in that, when administered, it forms reversible bonds with β-adrenergic, however, induce adrenergic effects, and it inhibits the actions of the catecholamins in times of stres by saturing their sites of operation. The purpose of the research was to investigate the effects of carazolol on some serum enzymes, trace elements and cardiovascular status in sheep. Seven sheeps (age 6 months, 35 ± 10 kg) were used in this study. Carazolol administered by the intramuscular route at the dose of 0.01 mg/kg. Serum levels of urea, creatinin, ALT, AST, G-GT, LDH, T. protein, Ca, P, Mg, Cu, Fe, Zn, Se were investigated. Although all serum enzymes did not show any difference, serum Fe and Zn levels were decreased. Important results were obtained in electrocardiography (abnormal T wave and ST segment depression). These results suggest that carazolol may increase incidence rate of myocardiyal ischemia risk in sheeps and it investigated by new researches. Research Article Effects of carazolol on electrocadiographic and trace element status in sheeps Remzi Gonul1, Lora Koenhemsı1, Handan Aydın Vural2*, Tevfi k Gulyasar3, Hasret Demırcan Yardıbı4, Erman OR1 and Bora Barutcu5 1Istanbul University, Faculty of Veterinary Medicine, Department of Internal Medicine, Turkey 2Istanbul University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Turkey 3Trakya University, Medical School, Department of Biophysic, Turkey 4Istanbul University, Faculty of Veterinary Medicine, Department of Biochemistry, Turkey 5Istanbul University, Cerrahpasa Medical School, Department of Biophysic, Turkey *Address for Correspondence: Handan Aydın Vural, Istanbul University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Turkey, Email: haydin@istanbul.edu.tr Submitted: 27 March 2018 Approved: 06 April 2018 Published: 09 April 2018 Copyright: 2018 Gonul R, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction β-adrenargic receptor blockers have been used in the treatment of cardiovascular diseases such as arterial hypertension, coronary heart disease, supraventricular and ventricular tachyarrhytmias. Currently, there are many β-adrenargic receptor blockers for clinical use that differ with respect to pharmacokinetic and pharmacodynamic properties [1].
One of these, Carazolol, is a non-speci ic β-adrenargic receptor blocker agent having 1-(carbazol-4-yloxy)-3-isopropylamino-2-propanolol chemical structure [2]. It is a strong analogous of catecholamine (adrenalin-noradrenalin). It can bind to β receptors irreversibly. It is binding to β-adrenoreceptors are inhibited by the endogenous catecholamine secretion in stressed conditions [3]. Consequently, carazolol is used in the treatment of circulatory disorders caused by stress in many animals species including particulary pigs, also against neonatal mortality caused by weak uterine contractions, to reduce neonatal deaths by shortening the parturition time, milk withdrawal, semen collection in males, arti icial insemination of females, in the treatment and preventation of retentio secundinarium caused by dystocia and in the treatment of endometritis in combination with other drugs in cattles [2].
However there is lack of studies performed for the acute effects of carazolol in the organism. Therefore, in this study we planned to investigate the effects of carazolol on electrocardiography, tension, oxygen saturation and some biochemical parameters in acute period in sheeps.

Material and Method
The study was carried on 7 Kivircik sheeps that were between 25-45 kg, nonpregnant, determined to be healthy after clinical examination, obtained from İ.Ü. Research and Application Farm. For this study, 0.01 mg/kg Carazolol was injected intramuscularly to each sheep. ECG, SpO2 ve blood pressure changes were investigated before and ½ hours after the administration of drug and changes on blood parameters and trace element levels were investigated after 2 hours.
10cc blood without anticoagulant was taken from V. Jugularis for the serum blood analysis of sheeps. Biochemical blood parameters (ALT, ALP, GGT, Urea, Creatinin, LDH, T. Protein, Ca and P) were determined spectrophotometrically. Trace element calculations were made with atomic absorbtion device (Shimadzu AA-6800). Se calculations were performed with graphite furnace (Shimadzu Graphite Furnace Atomizer GFA-EX7).
Electrocardiographic records were taken as appropirate to technique with PETAŞ Kardiyopet 300 device. Blood pressure and oxygen saturation was measured with EDAN M9B bed-side monitor. For this purpose, non invasive blood pressure (diastolic, sistolic and mean) was taken from femoral or metatarsal artery depending on the size of animal. Oxygen saturation (SpO2), was determined from ear tip arterial blood of animals by measuring the hemoglobin oxygen saturation in arterial blood with plethysmogram by the device.
The mean values, standard deviations and statistical differences were performed by Student t test.

Results
No clinical difference was determined in the general conditions of animals 2 hours after the administration of drug.
No statistical difference was determined in biochemical parameters in blood analysis performed 2 hours after carazolol injection. The decrease in Fe and Zn was found statistically signi icant at p<0.05 level (Table 1).
SpO2 and blood pressure measurements performed 1/2 hour after the carazolol injection were found to increase, however these changes were not found statistically signi icant (Table 2). Although no signi icant differences were observed in the measurements carried on electrocardiographic traces of ECG records obtained ½hours after injection (Table 3), abnormal T wave and ST segment depression changes were observed in two animals ( Figure 1).  T Period (mm/sn) 0,04±0,008 0,05±0,01

Discussion
In veterinary medicine, carazolol has been used to decrease cardiovascular responses arising from catecholamine usage, in stress related disorders, in the area of veterinary arti icial insemination and gynecology [3].
No studies were found regarding to side effects however the drug has been used widely recently. In our study, urea, creatinin, ALT, ALP, GGT, LDH, Ca, P, T.Protein, Mg, Cu levels in blood serum parameters were found to be in normal level however statistical decrease in p<0.5 level on serum Fe, Zn levels was determined after Carazolol injection.Moreover, all other values were reported to be within referance values. Some behavioural,physiological, haemotologic and neurohormonal changes can occur in animal body depending on the stress [4][5][6][7][8]. Most of the trace elements were known to be function as a part of enzym, hormon and vitamins [4,9]. For this reason, we think that stress factors must be taken into consideration in the evaluation of changes observed in sheeps after carazolol injection and new studies should be done relating to this subject.
Researchers [5,7,9] have also reported that several hormons that play role in stress cause elevation in cardiac rhythm and blood pressure, increase in plasma catecholamine and behavioral changes. In our study, elevation in systolic, mean and diastolic arterial blood pressure were not found statistically signi icant after carazolol injection to sheeps. Nevertheless, this condition is thought to be result of stress that was created during administration as well as the detection of changes in the second controls after injection suggesting the stress and side effects of drug.
When the acute effects of drug to the heart were evaluated no indings were observed except abnormal T wave and depression in ST segment formed in two animals. We have observed that the drug may cause some biochemical and cardiovascular effects, although the drug has been used more recently. We think that these should also be taken into consideration when using the drug and the side effects of the drug must be further investigated.