Effects of the prilocaine and of the association of prilocaine with different vasoconstrictors on the isolated hearts of rats.

This study aimed to observe the effects of prilocaine chloridate (P) and the associations of P with felypressin (P+F), and epinephrine (P+E) on the heart rate and force of contraction on the isolated hearts of rats. The hearts were perfused according to Langendorff's method. The experiments were performed with the following substances: prilocaine (P), felypressin (F), and epinephrine (E). P was used in doses of 1.25, 2.5, and 5.0 mg. The same doses of F and P (1.0, 1.5 and 3.0 microg) were used in association with the P, respectively. Right after the application of the three doses of P, a reduction in the force of contraction was observed, with higher intensity at a higher dose, which led to cardiac arrest. A similar result was obtained with the administration of the three associations of P+F. Also the application of the three associations P+E resulted in a reduction of the force of contraction, that was, however, less intense with the associations of 1.25 mg P + 1.0 microg E and 2.5 mg P+1.5 microg E, as compared to the same doses of P alone and P+F. The two higher doses of P and P+F on the heart rate elicited a significant reduction in relation to the control, but with the associations of P+E no alterations were observed, with any one of the doses used. The results obtained in the present study suggest that an association of P and E must be used in local anesthesia, since epinephrine may well protect the heart from the depressive effects of the anesthetic salts.

Effects of vasoconstrictors used in local anesthesia upon isolated rat heart.

Some reports have demonstrated that the vasoconstrictor effect of catecholamines may be amplified by felypressin. Thus, the association of felypressin and epinephrine with local anesthetics may be indicated to achieve more effective vasoconstrictor actions with fewer collateral effects from both the anesthetic and the vasoconstrictor. This study aimed to characterize the effects of felypressin and associations of felypressin and epinephrine upon the contraction force and the cardiac rate of the isolated rat heart (n=20) perfused by Langendorff's method. The following solutions were utilized: epinephrine, 4.5nmol; felypressin at doses of 0.5, 1.6 and 5.5IU and associations of felypressin at the same doses with 4.5nmol epinephrine. Contraction force and cardiac rate were recorded at 15, 30, 60 and 120s after the administration of each solution, and before the administration, a control measurement (time 0) was taken. Felypressin at a dose of 0.5IU did not have any effect upon the heart, but the doses of 1.6 and 5.5IU decreases the cardiac rate and the contraction force, respectively. Epinephrine and all of the felypressin and epinephrine associations produced increases in these parameters. The association of 0.5IU felypressin and 4.5nmol epinephrine promoted a similar effect to that of epinephrine (4.5nmol) alone up to 120s. The association of 1.6IU felypressin and 4.5nmol epinephrine increases the contraction force up to 60s. After the administration of the association of 5.5IU felypressin and 4.5nmol epinephrine this increase was observed up to just 30s. The cardiac rate values obtained after the administration of the associations of 1.6 and 5.5IU felypressin with 4.5nmol epinephrine were lower than those seen after the use of 4.5nmol epinephrine alone. In this study it was observed that the association of felypressin with epinephrine decreased the effects of epinephrine which increases the cardiac rate and the contraction force in the isolated rat heart.

Verification of protector effect of the norepinephrine and felypressin upon the cardiovascular system under action of the lidocaine hydrochloride and prilocaine hydrochloride in anesthetized rats.

Vasoconstrictor substances, as norepinephrine and epinephrine, were mixtured to local anesthetics to decrease their toxic effects and to prolong the depth of the anesthesia. However, these catecholamines produce systolic and diastolic hypertension. The effects of felypressin, a synthetic vasoconstrictor, upon arterial blood pressure and heart are lesser than those of norepinephrine or epinephrine, but due to its effects like oxytocin these catecholamines are yet the most used vasoconstrictors in association with lidocaine or another anesthetic salt. These vasoconstrictors are contraindicated for some physician, mainly for cardiac patients. But, are the catecholamines or is the salt the most dangerous components of the local anesthetic? The effects of the salt and catecholamines are opposite, but which of these exercises their effects first when inside blood vessel? Singi et al. [Pharmacol. Res. 44 (2001)] demonstrated that the first effect is always of the salt and that norepinephrine promotes protector effects upon guinea-pig isolated heart against lidocaine action. But, is this true for in vivo animals? The present study was performed with the aiming to answer this question and to verify if felypressin can induce the same effect of the norepinephrine. Fourteen Rattus norvegicus albinus, weighing 350g on average, were used. After being anesthetized with sodic thiopental, they were tracheostomizeds and one jugular and one carotid were cannuled for application of substances and to record the blood arterial pressure, respectively. The ECG was gotten through electrodes located in the front and back paws of the animals. The animals were separated in two groups, each one with seven rats. The lidocaine hydrochloride 2% in the doses of 600 microg and 3% in the doses of 900 microg acted on the cardiovascular system reducing the arterial pressure and modifying the electrocardiogram, while the prilocaine hydrochloride, in the same doses, also reduced the arterial pressure, but did not modify the electrocardiogram. When norepinephrine was associated to lidocaine 3% hydrochloride, it was possible to observe that this salt always exercised its effect first and a protective effect against the fall of pressure produced for the lidocaine. The same protective effect did not occur when felypressin was associated with prilocaine hydrochloride 3%.

Norepinephrine prevents the adverse effects of lidocaine upon the heart. An experimental study in isolated guinea-pig hearts.

The adverse effects of local anesthetics associated with catecholamines upon the cardiovascular system, such as arterial pressure alterations and cardiac arrhythmias, have been highly discussed in pharmacological literature. When present in the blood circulation, the anesthetic salt promotes depressing effects at the cardiovascular system level, whilst the catecholaminic vasoconstrictors promote opposite effects upon the cardiovascular system. This paper aimed to verify which component is responsible for the initial effect upon the isolated heart of the guinea-pig by comparing the same anesthetic with and without vasoconstrictor. Guinea-pig hearts perfused using the Langendorff method received separate injections of lidocaine hydrochloride, without vasoconstrictor (LC), and with the vasoconstrictor norepinephrine at 1 : 50,000 (LCN) in doses of 3, 4 and 5 mg. LC was seen to significantly reduce the contraction force (CF) and the cardiac rate (CR) at all injected doses and at all times registered. LCN, though, significantly reduced CF in all doses only at 15 s after administration. At 30 and 60 s, LCN elevated CF to values close to those of the control. LCN in its 3 mg dose significantly increased CR at 30 and 60 s; with the 4 mg dose, significant alterations did not occur in CR and with the 5 mg dose CR was reduced significantly at 15 and 30 s, returning to values close to those of the control at 60 s. The electrocardiographic traces with LCN were similar to those with LC with a reduction occurring in the automatism of the sinus node, prolongation of the PR interval and widening of QRS, with all doses utilized at 15 s. Soon after the administration of LC and LCN ventricular asystole occurred, having a larger duration with LC. This duration was also increased when higher doses of anesthetics were used. The authors concluded that the initial cardio-depression effect of local anesthetics, with the vasoconstrictor norepinephrine, in the isolated guinea-pig heart is due to the anesthetic salt and that the vasoconstrictor exerts a protecting action against this effect.

Plasma testosterone and 11-ketotestosterone levels of male pacu Piaractus mesopotamicus (Cypriniformes, Characidae)

The levels of testosterone (T) and 11-ketotestosterone (11-KT) of the South American pacu Piaractus mesopotamicus were determined by radioimmunoassay during two stages of the reproductive cycle, i.e., resting and maturation, and the gonadosomatic index (GSI) was calculated. The highest levels of T and 11-KT were reached during the maturation stage (T= 2400 + 56 pg/ml; 11-KT= 2300 + 60 pg/ml) and lower levels were maintained during the resting period. The rise in androgen levels occurred with the appearance of spermatozoa in the maturation stage, when GSI was highest.

Primary structure of three forms of gonadotropin-releasing hormone (GnRH) from the pacu brain.

Perchlike fish are a vast group of advanced teleosts. The species examined to date have three forms of gonadotropin-releasing hormone (GnRH) within a single species, but the origin of the third GnRH peptide is unknown. In this study, the primary structure of three GnRH peptides is determined from the brain of the pacu, Piaractus mesopotamicus, an example of a teleost that is less advanced than the perchlike fish. The GnRH was purified from pacu brain extracts using high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The three forms identified by chemical sequencing and mass spectrometry are sea bream GnRH (pGlu-His-Trip-Ser-Tyr-Gly-Leu-Ser -Pro-Gly-NH2, 1113.4 Da); chicken GnRH-II (pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2, 1236.6 Da); and salmon GnRH (pGlu-His-Trp-Ser-Tyr-Gly-Trp-Leu-Pro-Gly-NH2, 1212.3 Da). In addition the number of forms of GnRH in the brains of male and female fish was determined separately. The same three forms of GnRH were present in the brains of both sexes as determined by antisera cross-reactivity and elution position from the HPLC column. The results indicate that the pacu brain has the identical forms of GnRH identified in perchlike fish and hence, the origin of three forms occurred earlier in evolution than previously thought.

Plasma testosterone and 11-ketotestosterone levels of male pacu Piaractus mesopotamicus (Cypriniformes, Characidae).

The levels of testosterone (T) and 11-ketotestosterone (11-KT) of the South American pacu Piaractus mesopotamicus were determined by radioimmunoassay during two stages of the reproductive cycle, i.e., resting and maturation, and the gonadosomatic index (GSI) was calculated. The highest levels of T and 11-KT were reached during the maturation stage (T = 2400 +/- 56 pg/ml; 11-KT = 2300 +/- 60 pg/ml) and lower levels were maintained during the resting period. The rise in androgen levels occurred with the appearance of spermatozoa in the maturation stage, when GSI was highest.

Plasma steroid and corticosteroid levels in female pacu Piaractus mesopotamicus, Teleostei-Characidae.

We report the plasma levels of estradiol-17 beta (E2), testosterone (T), 17 alpha-20 beta-dihydroxy-4-pregnen-3-one (17-20P), and cortisol (F) in female pacu during the reproductive cycle (N = 44) and in females induced to ovulate with an analogue of luteinizing hormone releasing hormone (LHRHa; 10 micrograms/kg) (N = 24). The plasma hormone levels were determined by validated radioimmunoassays. Females sampled during the reproductive cycle were grouped into 4 gonadal stages: resting, early maturation, advanced maturation and regression. The calculated gonadosomatic index varied from 0.5 +/- 0.1% in resting stage to 8.1 +/- 0.6% in advanced maturation stage. The E2 and T values were highest during the early maturation stage (E2 = 2172 +/- 7.1 pg/ml; T = 412 +/- 58 pg/ml) and the F values were highest during the advanced maturation stage (132 +/- 5 ng/ml). Females induced to ovulate by LHRHa injection were sampled at 0.6, and 12 h after injection of LHRHa. Two additional groups were sampled at ovulation and 24 h after ovulation. The E2 values were highest at 6 h (2917 +/- 65 pg/ml). The T and F values were highest at ovulation (T = 3498 +/- 77 pg/ml; F = 387 +/- 16 ng/ml) and 17-20P was detected only at ovulation (2163 +/- 80 pg/ml).

Plasma steroid and corticosteroid levels in female pacu Piaractus mesopotamicus, Teleostei-Characidae

We report the plasma levels of estradiol-l7Beta (E2), testosterone (T), 17(alpha-2Obeta-dihydroxy-4-pregnen-3-one (l7-2OP), and cortisol (F) in female pacu during the reproductive cycle (N = 44) and in females induced to ovulate with an analogue of luteinizing hormone releasing hormone (LHRHa; 10 mug/kg) (N = 24). The plasma hormone levels were determined by validated radioimmunoassays. Females sampled during the reproductive cycle were grouped into 4 gonadal stages: resting, early maturation, advanced maturation and regression. The calculated gonadosomatic index varied from 0.5 ñ 0.1 per cent in resting stage to 8.1 ñ 0.6 per cent in advanced maturation stage. The E2 and T values were highest during the early maturation stage (E2 = 2172 ñ 7.1 pg/ml; T = 412 ñ 58 pg/ml) and the F values were highest during the advanced maturation stage (l32 ñ 5 ng/ml). Females induced to ovulate by LHRHa injection were sampled at 0, 6, and 12 h after injection of LHRHa. Two additional groups were sampled at ovulation and 24 h after ovulation. The E2 values were highest at 6 h (2917 + 65 pg/ml). The T and F values were highest at ovulation (T = 3498 + 77 pg/ml; F = 387 ñ 16 ng/ml) and 17-20P was detected only at vulation (2163 ñ 80 pg/ml).