Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (P<0.05). A different response to PC was observed in normal than in HYPO hearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (P<0.05), while in HYPO hearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

Clonidine changes lidocaine free concentrations in rat myocardium without affecting heart function measured by echocardiography.

Lidocaine is a local anaesthetic widely used in regional and epidural anaesthesia. Clonidine a alpha2-adrenergic agonist is an antihypertensive agent, regulating the production of catecholamines (epinephrine and norepinephrine) and added to local anesthetic infusions in order to improve postoperative analgesia. The aim of the study was to investigate the influence of clonidine co-administration on the binding of 14C lidocaine to rat serum and heart tissue protein as well as its pharmacodynamic effects in the heart. Four groups of Wistar rats (n=7) were used; Groups I and II received 4 mg/kg lidocaine i.m. Groups III and IV received lidocaine and 1 microg/kg clonidine i.m. In group I and III fifteen minutes and in groups II and IV thirty minutes after the initial treatment, ultrasound examination of heart function (heart rate, diameter of left ventricle in systole and diastole, ejection fraction) was performed. The animals were then sacrificed in all groups. Lidocaine free fraction in serum and heart was evaluated via ultrafiltration. The kinetics of lidocaine was altered by clonidine co-administration probably by mechanisms related to protein binding alterations. However, the pharmacokinetic interactions were not accompanied by changes of pharmacodynamic parameters including those of heart function as measured by echocardiography.

In vitro binding of lidocaine to liver tissue under the influence of propranolol: another mechanism of interaction?

The co-administration of lidocaine and propranolol leads to significant drug-drug interactions. Beta-blockers decrease liver perfusion and inhibit the activity of hepatic microsomal lidocaine metabolizing enzymes of the P450_2D subfamily. Hence, there is a resulting reduction in the hepatic breakdown of lidocaine and an increase in its serum concentrations. In this study the ability of propranolol to displace lidocaine from its binding sites in liver tissue has been examined through an in vitro model. Rat liver slices were incubated together with propranolol and/or lidocaine in human serum and the percentage of the bound fraction of lidocaine in the experimental mixture was assessed. The present results indicate that propranolol significantly decreases the binding process of lidocaine in liver tissue. This effect develops only when blood is used as incubation medium and the incubation period lasts 60 min. In conclusion, propranolol can displace lidocaine from liver proteins and therefore the co-administration of the two drugs may increase the free fraction of lidocaine excreted by the liver. However, this result arises from an in virro model and thus further investigation is needed.

Decreased vascular reactivity to alpha1 adrenergic stimulation in the presence of hypothyroid state: a part of an adaptive response?

AIM: A hypothyroid state frequently accompanies cardiac illnesses but its physiological significance for the cardiovascular hemodynamics remains largely unknown. Therefore, the present study investigated possible physiological consequences on vascular function in an experimental model of low thyroid hormone state. METHODS: Hypothyroidism was induced in rats by the administration of 6-n-propyl-2-thiouracil in drinking water (final concentration of 0.05%) for 3 weeks, HYPO rats, and untreated rats served as controls (Control). Isolated aortic rings with or without endothelium (E+, E-) were contracted with KCl (10 to 60 mM) and phenylephrine (PE) (10(-10) to 10(-5) M). Maximal tension (Tmax) in g and EC(50) in response to PE and KCl were measured. RESULTS: Tmax was significantly lower while EC(50) was significantly higher in response to PE in HYPO(E+) than in Control(E+). Upon endothelium removal, Tmax was not significantly different between the groups but EC(50) was still significantly higher in HYPO(E-) than in Control(E-). EC(50) in response to KCl was significantly higher in HYPO with or without endothelium and no difference was found in Tmax. CONCLUSIONS: Hypothyroid aortic rings respond less to a1 adrenergic stimulation probably due to the endothelium modulatory effect as well as to intrinsic smooth muscle defect. This seems to be of important clinical relevance.

The influence of premedication and smoking.

The history of smoking and premedication did not influence the proportion of patients who had a cough response to fentanyl when administrated as first agent during induction in anesthesia.

Quinolone levels in serum and maxillofacial tissues under ibuprofen co-administration following surgical trauma.

Administration of antibiotics is considered to be an important factor, during or after operational procedures in the maxillofacial area, in order to avoid post-surgical complications. Furthermore, administration of anti-inflammatory drugs is often prescribed for control of the post-operative pain. The aim of this study was to determine the levels of quinolones in serum and tissues (parotid gland, tongue, mandible), during traumatic injury in the oral cavity, with or without co-administration of ibuprofen, a non-steroidal anti-inflammatory drug. Four groups of Wistar rats, (A, B control), (C, D experimental) were used. In the experimental group, traumatic injury was performed through the whole length of the cheek. Groups B and D received ibuprofen. The quinolone levels in serum and tissues were estimated by the inhibition zone of B. subtilis. Free fatty acid (FFA) levels and the adrenal weight, considered as a stress index, were increased in trauma groups. Quinolone concentrations in serum and in most of the tissues were significantly higher in the experimental groups compared to the controls. However, the co-administration of ibuprofen caused a higher increase of the quinolone levels in the control animals than in the experimental groups.

Interaction between nandrolone decanoate and calcitonin in bone formation markers (osteocalcin and bone specific alkaline phosphatase) and IGF-I in rats.

Bone tissue has been shown to contain numerous cell-to-cell signaling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling, due to their potent effects on bone cell metabolism. Our investigation was intended to assess the effect of nandrolone decanoate and calcitonin treatment on biochemical markers of bone formation (bone alkaline phosphatase - osteocalcin) and insulin-like growth factor-I in rats. We studied 48 adult male rats. The animals were divided into four groups. Group (A) served as control. Animals in Group (B) were injected with 4 mg/kg/day nandrolone decanoate. Animals in Group (C) were injected with 400mU/rat/day calcitonin and Group (D) received combined therapy for seven days. Nandrolone decanoate and calcitonin have a mild but significant effect on insulin-like growth factor-I without affecting osteocalcin levels, while calcitonin alone decreases the BALP levels. The coadministration of two agents caused notable elevation on insulin-like growth factor-I, followed by a significant increase of osteocalcin and bone alkaline phosphatase.

Morphological changes of parotid glands following adjuvant arthritis and ibuprofen treatment in rats.

Drug administration and numerous systemic diseases may cause morphological changes of the parotid gland. The aim of this study was to investigate the possible relationship between experimental adjuvant arthritis following ibuprofen treatment and morphological alterations of the parotid glands in rats. Freud's adjuvant was injected intradermally into the plantar surface of the hind paw of the animals to induce experimental arthritis. Ibuprofen was administrated per os (17 mg/kg/day). Both adrenals and parotid glands were isolated and their absolute and relative weights were evaluated. A full histological examination of parotid glands took place. The diameter of the foot as well as the serum levels of rheumatoid factor was measured. In conclusion, both experimental adjuvant arthritis and ibuprofen treatment induce morphological changes of the parotid tissues, which are related to macro- and micro-structure of the gland.

Masseteric hypertrophy associated with administration of anabolic steroids and unilateral mastication: a case report.

In this report we present a patient with unilateral masseteric hypertrophy who used anabolic steroids and was chewing entirely unilaterally for 1 month. Computed tomography and histologic examination were used to confirm the diagnosis. The combined action of unilateral mastication and anabolic steroid use is probably responsible for the rapid development of unilateral masseteric hypertrophy.

Stress-induced lidocaine modification in serum and tissues.

The aim of this study is to examine the influence of acute (trauma) and chronic (cold swimming and adjuvant rheumatoid arthritis) stress on lidocaine concentrations in plasma. Forty male Wistar rats were used. The animals were divided into four groups. Group A served as control. Group B underwent mandible osteotomy. Group C was submitted to swimming stress in cold water 4 degrees C for ten minutes daily for 15 minutes, while group D underwent experimental arthritis with Freud's adjuvant. All groups received lidocaine i.m (2.5 mg/kg). Blood samples were collected and FFA (free fatty acid), unbound-lidocaine, albumin and a1-acid glycoprotein concentrations were estimated. Furthermore, the adrenals, heart and liver were isolated. The adrenals' relative weight (adrenal weight/body weight) was assessed, while lidocaine concentrations in the heart and the liver incubation medium were measured by intertechnic a-counter. Lidocaine and FFA levels in serum as well as the adrenal weights demonstrated a significant elevation in stress-groups as compared to the control group. Furthermore, in the stress-groups, lidocaine concentrations in heart tissue were significantly increased, whereas in the liver they were significantly reduced as compared to the control group. Our results indicate that stress can alter lidocaine levels in plasma and tissues, suggesting that stress should be considered an important factor when determining the dosage of lidocaine in clinical application.

Modifications of clonidine binding to rabbit liver protein under the influence of non-steroid-anti-inflammatory drugs in vitro.

This study was designed to investigate the binding of clonidine to liver protein as well as the possible interactions with non-steroid anti-inflammatory drugs (NSAIDs) during the binding process in the rabbit. The binding of clonidine to slices (S) and homogenized slices (H) was estimated by a radioisotopic method following incubation with a mixture of cold and 3H-labelled clonidine in Ringer solution at 37 degrees C for 360 min. The binding of clonidine was assessed in the absence and presence of the following NSAIDs: flurbiprofen, ketoprofen, ibuprofen and acetylsalicylic acid. The results showed that the percentage of clonidine binding did not differ between intact and homogenized slices. The addition of all NSAIDs but ibuprofen, significantly decreased the protein binding of clonidine both in intact and homogenized liver slices. This finding could be attributed to the different affinity of ibuprofen for liver protein compared to the remaining NSAID's which may arise from a number of chemical properties including its dual Pka values.

Lipid kinetics in obese patients undergoing laparoscopy. The impact of cortisol inhibition by etomidate.

The aim of this study was to investigate the response of cortisol, insulin and lipid parameters [serum Lipoprotein Lipase activity, choleseryl-ester transfer protein, triglycerides, total Cholesterol, High Density Lipoprotein, Free Fatty Acids] during the perioperative period in obese patients undergoing laparoscopic cholecystectomy. Twenty obese patients were included and divided in two groups. In group A (n=10) patients were anaesthetized with propofol and group B (n=10) with etomidate. Blood samples were collected before induction in anaesthesia, just after the end of the operation and at one, two and three hours postoperatively. According to our results, in both groups serum LPL activity showed a significant decrease whereas serum Free Fatty Acids a potent increase over time. Likewise, both groups did not demonstrate significant changes over time in choleseryl-ester transfer protein activity, total cholesterol, triglycerides, High Density Lipoprotein or insulin concentrations in serum. Furthermore, cortisol release was significantly inhibited in the etomidate group while substantially enhanced in propofol group. Additionally, apart of triglycerides, no difference was found between the two groups in all the lipid parameters and insulin concentrations. In conclusion, serum Free Fatty Acids levels and Lipoprotein Lipase activity demonstrated significant alterations in obese patients underwent laparoscopic cholecystectomy and this result did not seem to be related with the anaesthetic agent used for induction in anaesthesia.

Ultrasound-guided combined intermediate and deep cervical plexus nerve block for regional anaesthesia in oral and maxillofacial surgery.

OBJECTIVES: We examined the application of an ultrasound-guided combined intermediate and deep cervical plexus nerve block for regional anaesthesia in patients undergoing oral and maxillofacial surgery. METHODS: A total of 19 patients receiving ultrasound-guided combined intermediate and deep cervical plexus anaesthesia followed by neck surgery were examined prospectively. The sternocleidomastoid and the levator of the scapula muscles as well as the cervical transverse processes were used as easily depicted ultrasound landmarks for the injection of local anaesthetics. Under ultrasound guidance, a needle was advanced in the fascial band between the sternocleidomastoid and the levator of the scapula muscles and 15 ml of ropivacaine 0.75% was injected. Afterwards, the needle was advanced between the levator of the scapula and the hyperechoic contour of the cervical transverse processes and a further 15 ml of ropivacaine 0.75% was injected. The sensory block of the cervical nerve plexus, the analgesic efficacy of the block within 24 h after injection and potential block-related complications were assessed. RESULTS: All patients showed a complete cervical plexus nerve block. No patient required analgesics within the first 24 h after anaesthesia. Two cases of blood aspiration were recorded. No further cervical plexus block-related complications were observed. CONCLUSIONS: Ultrasound-guided combined intermediate and deep cervical plexus block is a feasible, effective and safe method for oral and maxillofacial surgical procedures.