The effects of dexmedetomidine on human internal mammary artery and saphenous vein grafts under hypothermia and normothermia.

OBJECTIVES: The purpose of this study was to determine the effects of hypothermia and normothermia on the isolated human saphenous vein (SV) and internal mammary artery (IMA) responses to dexmedetomidine. METHODS: The response of human IMA and SV strips with (E+) and without (E-) endothelium subjected to cumulative concentrations of (10-9, 0-6 M) dexmedetomidine were recorded at 37 °C and at 28 °C. OnE-way ANOVA was used for analysis. A p < 0.05 was considered significant. RESULTS: At 37˚C dexmedetomidine resulted in similar significant concentration-dependent contractions in both E+ and E- SV strips (p < 0.05). At 37 °C dexmedetomidine resulted in significant concentration-dependent contractions in E+ IMA strips, these contractions were significantly lower at all concentrations of dexmedetomidine in E- compared to E+ IMA strips (p < 0.05). When results between similar groups of SV and IMA strips were compared, the contractions were significantly higher in the IMA strips in E+ and E- at 37 °C and also E- 28 °C groups compared to SV (p < 0.05). CONCLUSION: In conclusion, dexmedetomidine causes in vitro vasoconstriction in human IMA and SV grafts. These contractions are greater in IMA compared to SV grafts. Endothelium-derived pathways are possibly involved in the contractile responses of IMA. Moderate hypothermia augments vasoconstriction in SV grafts (Fig. 3, Ref. 27).

In vitro vasoactive effects of dexmedetomidine on isolated human umbilical arteries.

OBJECTIVE: We aimed to investigate the vasoactive effects of dexmedetomidine on isolated human umbilical arteries and possible mechanisms involved. METHODS: Human umbilical artery strips were suspended in Krebs-Henseleit solution and dose-response curves were obtained for cumulative dexmedetomidine before and after incubation with different agents; propranolol, atropine, yohimbine, prazosin, indomethacin, verapamil. Effects of calcium on cumulative dexmedetomidine-induced contractions were also studied. RESULTS: Cumulative dexmedetomidine resulted in dose dependent contraction responses. Incubation with propranolol (Emax: 93.3 ± 3.26 %), atropine (Emax: 92.0 ± 6.54 %), or indomethacin (Emax: 94.25 ± 2.62 %), did not attenuate dexmedetomidine-elicited contractions (p > 0.05). There were significant decreases in the contraction responses of cumulative dexmedetomidine with yohimbine (Emax: 12.1 ± 11.9 %), prazosin (Emax: 28.8 ± 4.6 %) and verapamil (Emax: 11.2 ± 13.6 %) (p < 0.05). In Ca+2 free medium contraction responses to cumulative dexmedetomidine was insignificant (Emax: 5.20 ± 3.42 %). Addition of cumulative calcium to the Ca+2 free medium resulted in concentration dependent increase in contractions (Emax: 64.83 ± 37.7 %) (p < 0.05). CONCLUSION: Dexmedetomidine induces vasoconstriction in endothelial-free umbilical arteries via both, α1- and α2-adrenergic receptors and also extracellular Ca+2 concentrations play a major role. ß-adrenergic receptors, muscarinic cholinergic receptors, and inhibition of cyclooxygenase enzyme are not involved in this vasoconstriction (Fig. 3, Ref. 36).

The dual effects of leptin on aortic rings with and without endothelium isolated from streptozotocin-induced diabetic rats.

The aim of this study was to examine the effects of leptin on aortic rings with and without endothelium isolated from streptozotocin (STZ)-induced diabetic and control rats, and also in the presence of an inhibitor of nitric oxide synthase (NOS). Thoracic aortic rings from 5-week STZ-induced diabetic (50 mg/kg i.p.) and age-matched control Sprague-Dawley rats were mounted in isolated tissue baths. Concentration-response curves to leptin (0.1 pM-1 nM) were constructed under basal tone and after precontraction with 1 microM phenylephrine in the presence or absence of Nomega-nitro-L-arginine methyl ester (L-NAME, 10 microM). Leptin caused a concentration-dependent relaxation of precontracted endothelium-intact aortic rings from control and diabetic rats. Responses to leptin in diabetic aorta were significantly increased compared to those of controls (P < 0.05). EC(50) values for leptin were similar for aortic rings from diabetic and control rats (P > 0.05). L-NAME pretreatment caused complete inhibition of the relaxant responses to leptin in the control aortic rings, while it induced a reduction in these responses in the diabetic rings (P < 0.05). Leptin-induced relaxation was eliminated when the endothelium was denuded. Leptin had no effect on the basal tone of endothelium-intact or -denuded aortic rings from control rats. In diabetic rings, leptin elicited concentration-dependent contractions (P < 0.05). Removal of the endothelium significantly increased the contractile effect of leptin on basal tone in diabetic rings (P < 0.05). The results suggest that leptin may induce vasodilatation by endothelial mechanism(s) other than nitric oxide (NO) release from the endothelium in diabetic aortic rings. On the other hand, leptin causes contractile effects on the basal tone in aorta smooth muscle isolated from STZ-induced diabetic rats. The contractile effect of leptin on basal tone may contribute to the development of hypertension in diabetes.

Bupivacaine and ropivacaine: comparative effects on nerve conduction block.

Unlike other drugs which act in the region of the synapse, local anesthetics are agents that reversibly block the generation and conduction of nerve impulses along a nerve fiber. This study aims to investigate the comparative inhibitions of bupivacaine and ropivacaine on the frog sciatic nerve. Isolated nerves were transferred to the nerve chamber which includes Ringer's solution. The nerves were stimulated by standard square wave pulse protocols and the responses were recorded with conventional systems. Bupivacaine (n = 8) and ropivacaine (n = 8) were administered in the nerve chamber bath with cumulative concentrations (10(-9) to 10(-3) M) and the effects were monitored for variable time periods (5, 10 and 15 min). Both bupivacaine and ropivacaine significantly depressed the compound action potential (CAP) parameters in a dose-dependent (p < 0.05) and reversible manner. Difference in the effects of these two drugs was detectable only when the dose (> or =10(-5) M) and exposure time (15 min) were increased. Percent inhibitions in maximum derivatives and latency-period measurements have shown that ropivacaine is not only fast but also much more powerful in conduction block for longer and higher doses. Bupivacaine, on the other hand, is effective in the group of fibers with relatively slower conduction velocity for all the measured doses and time periods. In conclusion, ropivacaine has a sensory specific side of action, when compared with the bupivacaine.

[The effects of sufentanil and remifentanil in the isolated perfused rat kidney]. / Sufentanil ve remifentanilin izole perfüze rat böbregi üzerine etkileri.

In this study, the effects of indomethacin (prostaglandin synthase inhibitor), propranolol (beta adrenergic receptors blocker), tetraethylammonium (TEA) (calcium-dependent potassium channel blocker) and glibenclamide (ATP-sensitive potassium channel blocker), NG nitro-L-arginine (NO synthetase inhibitor) and naloxane (nonselective opioid receptor antagonists) on the responses induced by sufentanil and remifentanil were investigated in the isolated perfused rat kidney. Renal arter was cannulated. Then the kidney was perfused continuously with warmed (37 degrees C) and aerated (95% O2 and 5% CO2). Krebs Henselieit solution by using a peristaltic pump delivering a constant flow (8-10 ml/min). Vascular responses were detected as changes in perfussion pressure, which was monitored continuously with a pressure transuder and recorded on polygraph. After phenilephrine (PE)-induced vasoconstriction had reached a platoe, sufentanil or remifentanil were given. Vasodilatation was recorded. Antagonists or inhibitors were added and responses were recorded. At the end of each experiment; papaverine was used to obtain the maximum dilatation. None of the used antagonists or inhibitors were not effected the submaximum PE construction. The used opioids were not alter in basal perfusion pressure. Antagonists or inhibitors had no effect on papaverine-induced dilatation. Bolus addition of sufentanil and remifentanil produced concentration dependent vasodilation. Indomethacine L-NAME, propranolol, naloxone and glibenclamide did not significantly alter responses of both of the opioids (p > 0.05). But, sufentanil and remifentanil induced dilatation were significantly affected by TEA (p < 0.05). The present results demonstrated that sufentanil and remifentanil decrease perfusion pressure in the isolated rat kidney and such mechanism may involve the calcium active K+ channels activation.

Effect of gamma-hydroxybutyric acid on tissue Na+,K- ATPase levels after experimental head trauma.

BACKGROUND: A failure of the Na(+),K(+)-ATPase activity (which is essential for ion flux across the cell membranes) occurs in many pathological conditions and may lead to cell dysfunction or even cell death. By altering the concentration of specific opioid peptides, gamma-hydroxybutyric acid (GHB) may change ion flux across cell membranes and produce the 'channel arrest' which we assumed will inhibit the failure of Na+,K(+)-ATPase activity and therefore lead to energy conservation and cell protection. Therefore we planned this study to see the effects of GHB at two different doses on Na(+),K(+)-ATPase activity in an experimental head trauma model. METHODS: Forty New Zealand rabbits were divided equally into four groups: group I was the sham-operated group, group II (untreated group), group III received head trauma and intravenous (i.v.) 500 mg/kg GHB and group IV received head trauma and i.v. 50 mg/kg GHB. Head trauma was delivered by performing a craniectomy over the right hemisphere and dropping a weight of 10 g from a height of 80 cm. The non-traumatized (left) side was named as 'a' and the traumatized (right) side as 'b'. One hour after the trauma in groups II and III and craniotomy in group I, brain cortices were resected from both sides and in group I only from the right side was the tissue Na-K-ATPase activity determined. RESULTS: The mean +/- SD of Na(+),K(+)-ATPase levels of each group are as follows: group I - 5.97 +/- 0.55; group IIa - 3.90 +/- 1.08; group IIb - 3.58 +/- 0.90; group IIIa - 5.53 +/- 0.60; group IIIb - 5.33 +/- 0.88; group IVa - 5.05 +/- 0.72; group IVb - 4.93 +/- 0.67. The Na(+),K(+)-ATPase levels of group IIa, IIb, IVa and IVb were significantly different from group S (P < 0.05). There were also significant differences between group IIa and groups IIIa and IVa; group IIb and groups IIIb and IVb (P < 0.05). CONCLUSIONS: We conclude that GHB is effective in suppressing the decrease in Na(+),K(+)-ATPase levels in brain tissue at two different dose schedules after head trauma.

Effects of deferoxamine on tissue lactate and malondialdehyde levels in cerebral ischemia.

In the present study, the effects of deferoxamine on tissue lactate and malondialdehyde (MDA) levels after cerebral ischemia in rabbits was studied. Rabbits were divided equally into three groups: group 1: sham-operated group; group 2: cerebral ischemia produced by clamping bilateral common carotid arteries for 60 min; and group 3: deferoxamine 100 mg/kg i.v. administered within 5 min after opening the clamps. EEG recordings were obtained in all groups before clamping and in group 2 and 3 60 min after clamping and 60 min after opening the clamps. One hour after opening the clamps and taking EEG recordings, brain cortices were resected and the concentrations of lactate and MDA were determined using the spectrophotometric enzymatic and thiobarbituric acid methods, respectively. There were significant differences between group 1 and the other groups in MDA and lactate levels (p < 0.05). There were no significant differences in lactate levels between groups 2 and 3. Preischemic EEG grades were the same in all groups. Preischemic and postischemic EEG values were significantly different (p < 0.05), but there were no significant differences between postischemic EEG grades in groups 2 and 3. There was also a correlation between postischemic EEG grades and lactate levels, but no correlation between postischemic EEG grades and MDA levels. These results demonstrate that cerebral ischemia leads to an increase in brain tissue lactate and MDA levels and deferoxamine suppresses the increase of MDA, but not lactate. Deferoxamine treatment caused no significant EEG changes. EEG grades correlated well with lactate levels.

Effects of magnesium sulfate on tissue lactate and malondialdehyde levels after cerebral ischemia.

In the present study, the effects of magnesium sulfate on tissue lactate and malondialdehyde (MDA) levels after cerebral ischemia in rabbits were studied. The rabbits were divided equally into three groups. Group 1 (n = 8) was the sham-operated control group, in group 2 (n = 8) only cerebral ischemia was induced by clamping bilaterally the common carotid arteries for 60 min, and in group 3 (n = 8) magnesium sulfate was administered at a dose of 100 mg/kg i.v. within 5 min after opening the clamps. In group 1 EEG recordings were obtained immediately and 60 and 120 min after craniectomy. In groups 2 and 3 EEG recordings were obtained immediately after craniectomy but before clamping and 60 min after clamping. One hour after opening the clamps and taking EEG recordings, brain cortices were resected, and the concentrations of lactate and MDA were determined using spectrophotometric/enzymatic and thiobarbituric acid methods, respectively. In all groups, there were significant differences between MDA and lactate levels (p < 0.05). There were no significant differences in lactate levels between groups 2 and 3 (p > 0.05), and also the preischemic EEG grades were the same in all groups. Preischemic and postischemic EEG values were significantly different (p < 0.05), and there were also significant differences between postischemic EEG grades in groups 2 and 3 (p < 0.05). There was a correlation between postischemic EEG grades and MDA and lactate levels. These results demonstrate that cerebral ischemia-reperfusion injury leads to an increase in brain tissue lactate and MDA levels, that magnesium sulfate suppresses the increase of MDA and lactate concentrations, and that magnesium sulfate treatment improves the EEG changes. The EEG grades correlated well with MDA and lactate levels.

Effects of bupivacaine and ropivacaine on the isolated human umbilical artery.

In this in vitro study on the human umbilical artery, the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME), indomethacin, prazosin, yohimbine and propranolol on the responses induced by bupivacaine and ropivacaine were investigated. Arteries isolated from umbilical cords from women who did not exhibit systemic diseases, who were not on medication and who had normal full-term deliveries, were cut into spiral strips 12 x 3 mm. Strips were mounted in organ baths at 37 degrees C continuously gassed with 5% CO(2) in oxygen. The responses to the drugs were recorded isometrically on a polygraph. In the bupivacaine study, when we administered cumulative concentrations of bupivacaine (10(-9) - 10(-4) M; n = 6) on basal tonus, there was no relaxation or contraction response on the tissue. Strips were precontracted with serotonin (10(-6)M 5-HT) then bupivacaine (10(-9) - 10(-4) M) was directly administered cumulatively. In the ropivacaine group, when cumulative concentrations of ropivacaine (10(-9) - 10(-4) M; n = 6) were administered on the tissue, preconstricted with 5-HT, ropivacaine did not alter the contraction response. Ropivacaine (10(-9) - 10(-4) M) was directly administered to the bath. Though bupivacaine produced relaxation, ropivacaine produced contraction (P < 0.05). Indomethacin, prazosin, yohimbine and propranolol did not significantly alter these responses. In addition, it was demonstrated that L-NAME did not affect the relaxation responses induced by bupivacaine. Thus adrenergic receptors, nitric oxide syntenaze and prostaglandins do not appear to affect the responses induced by these two local anesthetics.

Effects of bupivacaine and ropivacaine on hemodynamic parameters in rabbits.

In the present study the toxic effects of ropivacaine and bupivacaine on the cardiovascular and respiratory systems of rabbits were studied. Both drugs were administered intravenously at doses of 0.5, 1, 2.5, 5 and 10 mumol/kg. The effects of the two drugs on blood pressure, ECG and respiration rate were evaluated by considering the changes occurring 30 sec after intravenous bolus injection. High doses (5 and 10 mumol/kg) of bupivacaine and ropivacaine significantly reduced the heart rate and systolic pressure (p < 0.05). Five and 10 mumol/kg of bupivacaine significantly reduced diastolic pressure (p < 0.05), but only the 10 mumol/kg dose of ropivacaine had the same effect. Low doses of bupivacaine and high doses of ropivacaine significantly increased the PR interval, QRS duration and QT interval (p < 0.05). The 5 mumol/kg dose of bupivacaine caused ventricular tachycardia in 3 of 6 rabbits, whereas ropivacaine caused tachycardia in 1 of 5 rabbits. Neither drug had a significant effect on respiration rate or blood gas values (p > 0.05). The results indicate that ropivacaine is less cardiodepressive and arrhythmogenic than bupivacaine.