Effects of papaverine and carbon dioxide alone or in combination on the blood flow of internal thoracic artery.

OBJECTIVE: The internal thoracic artery is frequently used as an arterial graft for coronary bypass. Spasms of internal thoracic artery may contribute to early myocardial ischemia. To prevent vasospasm and increase the blood flow, some vasodilatory agents (such as carbon dioxide or papaverine) are used. The aim of the study was to evaluate the combined effects of carbon dioxide and papaverine versus either alone on the blood flow of the internal thoracic artery. METHODS: One hundred patients undergoing coronary artery bypass grafting (28 women and 72 men) with similar characteristics were randomly divided into four groups. We used the classic technique without any vasodilatory management before surgery in group 1, papaverine injection into the endothoracic fascia in group 2, and carbodissection technique in groups 3 and 4. Initial free flows of the internal thoracic arteries were measured after cutting of the vessel. After the first measurement, the ITA pedicles were washed with papaverine solution and wrapped with gauze in the first and fourth groups. Blood flow measurements were repeated 15 minutes later in all groups. RESULTS: When vasodilatory management was applied during excision, the blood flows were significantly increased relative to group 1. The mean blood flows reached a significantly higher level in groups 1, 2, 3, and 4 at the second measurements. In groups 2 and 3, the increase at the first measurements compared to the first group's level was continuously high, but no additional increase was observed between the first and second measurements. In groups 1 and 4, regardless of whether a previous vasodilatory management was present, the increases measured at repeated measurements were significant versus each group's first measurements (P < .05). CONCLUSIONS: Vasodilatory management, such as injection of papaverine into endothoracic fascia or carbon dioxide insufflation applied during excision, increased the free blood flows of internal thoracic artery pedicles. Exogenously applied papaverine produces an additional and continuous vasodilatation regardless of whether a vasodilatory intervention was previously applied.

Cardioprotective effect of cold-blood cardioplegia enriched with N-acetylcysteine during coronary artery bypass grafting.

BACKGROUND: Cold-blood cardioplegia is a well-known method in coronary artery bypass graft surgery, and several authors have used various agents in the enrichment of cold-blood cardioplegia to decrease ischemia-reperfusion injury seen during surgery. N-acetylcysteine, which can increase glutathione levels, is one of the agents added to cardioplegic solutions to decrease myocardial injury. This study was planned to assess the efficiency of N-acetylcysteine-enriched cold-blood cardioplegia on early reperfusion injury in patients with ischemic heart disease undergoing coronary artery bypass grafting, using measurements of cardiac troponin I and malondialdehyde release. METHODS: Thirty patients (11 women and 19 men) with left ventricular ejection fraction greater than 0.40 scheduled for coronary artery bypass grafting were randomly divided into two groups. We used cold-blood cardioplegia enriched with N-acetylcysteine (50 mg per kilogram of body weight) in the first group and cold-blood cardioplegia alone in the second group. Hemodynamic variables and clinical properties of the patients were preoperatively and postoperatively evaluated. Enzyme releases were measured in the early hours after the operation. RESULTS: In the N-acetylcysteine-enriched group cardiac troponin I levels were lower than in the N-acetylcysteine-free group, and this difference was statistically significant. Cardiac troponin I levels increased in both groups in the 6th and 12th hours postoperatively, but there was a statistically significant difference between the two groups. Malondialdehyde levels were significantly higher in the N-acetylcysteine-free group after the 6th, 12th, 24th, and 48th hours postoperatively when compared with the N-acetylcysteine-enriched group. CONCLUSIONS: N-acetylcysteine-supplemented cold-blood cardioplegia minimizes myocardial injury in the early hours after and during the cardiac surgery.

The acute alterations in biochemistry, morphology, and contractility of rat-isolated terminal ileum via increased intra-abdominal pressure.

AIM AND SCOPE: To determine the acute effects of increased intra-abdominal pressure (IAP) on the biochemistry, morphology, and contractility of the isolated terminal ileum of rats. BACKGROUND: Laparoscopic procedures are used clinically in diagnostic and treatment modalities and experimentally as a model of ischemia-reperfusion injury induced by the elevation of IAP. Although some clinical and in vivo experimental studies investigate the results of ischemia-reperfusion injury whether induced by elevated IAP or clamping, there is no in vitro study that has investigated the acute effects of high IAP mimicked by a laparoscopic intervention in any of the intra-abdominal organs (like terminal ileum) on the basis of contractility which represents the motility. METHODS: Twenty-four adult with either sex Sprague-Dawley rats were divided into three groups. The control group (Group I) was not subjected to any IAP. In Groups II and III, an IAP of 10 and 20 mmHg, respectively, was established by carbon dioxide pneumoperitoneum for a period of 60 min. Thirty minutes after the desufflation, the terminal ileum was removed for in vitro pharmacological investigation, measurement of malondialdehyde (MDA) values, and histopathological examination. Statistical comparisons among groups were done using the Kruskal-Wallis variance analysis, with post hoc comparison performed with the Mann-Whitney U-test. RESULTS: Tissue MDA value and the damage scores of mucosa and submucosa were significantly increased in both IAP groups. The smooth muscle layer was significantly damaged only in Group III. The contractions obtained by electrical field stimulation (EFS) were inhibited in both IAP groups, and the contractions to acetylcholine were inhibited in Group III when compared to the control group. CONCLUSIONS: In conclusion, we can say that pneumoperitoneum induced IAP may inhibit contractile responses, cause structural alterations which may be related to ischemia-reperfusion injury in rat terminal ileum.

A case-control study on the etiology of urinary bladder cancer in Istanbul, Turkey.

BACKGROUND: Urinary bladder cancer is the third leading cancer in male in Turkey. The incidence rates of bladder cancer are 13.0 and 2.1/100,000 for males and females, respectively, in Turkey. Smoking and occupation are the main causes of urinary bladder cancer. Our goal was to investigate the etiologic factors of urinary bladder cancer in our region to improve our preventive services. METHODS: We conducted a hospital-based case-control study of patients with bladder cancer and of controls drawn randomly from the acute non-urinary patients of three hospitals in Istanbul. Controls were matched for age, sex, and residence. RESULTS: We interviewed 290 cases and 580 controls. Smoking and occupation were found to be related factors in urinary bladder cancer. CONCLUSION: Preventive measures should be planned regarding smoking and occupational factors for urinary bladder cancer in Turkey.

The contracting and relaxing responses of human internal mammary artery grafts harvested by two different methods.

Perioperative spasm of internal mammary artery is a common experience in coronary artery bypass grafting. Many techniques were described of harvesting the internal mammary artery to prevent vasospasm. We investigated the comparison of the contracting and relaxing responses of human internal mammary artery grafts harvested by two different methods. Patients were divided into two groups depending on the harvesting technique. In the first and second groups arteries were harvested by classical and carbon dioxide insufflation techniques, respectively. In both groups, endothelial function of arteries was assessed by precontracting the rings with phenylephrine (10(-5)M) and dilatating them by cumulative acetylcholine (10(-8) to 10(-5)M) concentrations. Cumulative concentration-response curves for phenylephrine (10(-8) to 10(-4)M), noradrenaline (10(-9) to 10(-4)M), and 5-hydroxytryptamine (10(-9) to 10(-4)M) were obtained in all groups. Endothelial integrity of arteries were histopathologically evaluated. In both groups, acetylcholine caused concentration-dependent relaxations in rings precontracted with phenylephrine (10(-5)M). In arteries harvested by carbon dioxide insufflation technique, acetylcholine caused significantly higher relaxations compared to the rings obtained by classical technique (p<0.05). In all rings of study groups, phenylephrine, noradrenaline and 5-hydroxytryptamine caused concentration-dependent contractions. There was not any significant difference in concentration-dependent responses of these contracting pharmacological agents between the groups. Histopathological evaluation revealed no major arterial damage in both groups. Carbon dioxide insufflation technique does seem not only to protect the integrity of the endothelium and the whole vessel, but also prevent the possible vasospasm of the internal mammary artery segments.

Story of benzene and leukemia: epidemiologic approach of Muzaffer Aksoy.

In 1974, Professor Muzaffer Aksoy established a link to leukemia in humans as a result of occupational exposure to benzene. The aim of this study is to evaluate his epidemiological approach for his investigation on the effects of benzene and to bring attention to the benzene problem in Turkey. Dr. Aksoy observed that a large group of leukemic patients were shoemakers, or they worked in leather manufacturing. In the 1960s, benzene was a popular solvent in the leather industry. Dr. Aksoy conducted a field investigation in Gedikpasa- Istanbul, where the shoemakers worked so that he could draw his key observations from actual environmental conditions. With a gas detector, he found the concentration of benzene in these work places to be 150-210 ppm and up to 650 ppm on rare occasions. He performed an epidemiological study and health education among 28,500 shoe, slipper and handbag workers during the period from 1967 to 1974. He published these data, establishing an association between benzene and leukemia. The incidence of leukemia among the shoe workers was decreased by screening, health education, and legislative actions in Turkey, but it began to increase again because of lack of an occupational health policy and underestimation of the problem. These results suggest the importance of primary prevention of occupational cancers. Dr. Aksoy's epidemiologic approach may highlight the necessity for detailed investigations of the occupational status of patients who need medical aid in order to diagnose the real underlying factor.

Use of polypharmacotherapy in pregnancy: a prospective outcome in a case.

PURPOSE: Little is known about the risks associated with prenatal exposure to atypical antipsychotics. Our objective is to present a case of exposure to risperidone and quetiapine in pregnancy, and additionally to some other drugs. CASE: Our case (36-year old) has suffered schizophrenia (DSM-IV) for 5 years and used these drugs (risperidone, quetiapine, mirtazapine, thioridazine, diazepam, hydroxyzine, clomipramine, fluvoxamine, alprazolam, carbamazepine, biperiden, haloperidol, ampicillin+sulbactam, enoxaparin, oxerutine) in her third pregnancy. Because of her psychotic condition, Mrs. N.B. was not aware of her pregnancy until 22nd week and the pregnancy could not be terminated. She had a female infant (3000 g, 50 cm) with APGAR scores of 8-9 at the first and fifth minutes at 37th week with an uncomplicated vaginal delivery. The baby was normal. CONCLUSION: This case may contribute to the existing knowledge regarding use of atypical antipsychotics in pregnancy.

Paroxetine alters KCl- or ATP-induced contractile responses of isolated vas deferens in rats chronically treated with ethanol.

Chronic ethanol administration affects many organ systems, including sexual organs. One of these organs is the vas deferens whose contractility can also be altered by selective serotonin re-uptake inhibitors (SSRIs). The aim of the present study, is to evaluate whether paroxetine (PX), a SSRI, can modify the contractile responses of isolated vas deferens obtained from rats chronically treated with ethanol to the contractile agents, potassium chloride (KCl) and adenosine triphosphate (ATP). For 21 days, alcohol was applied with a modified liquid diet to sexually mature male Sprague-Dawley rats (200-240 g). The vas deferens of the rats were excised at the end of day 21 and suspended in the organ baths by classical pharmacological methods. The responses to contractile agents tested were decreased by chronic ethanol treatment in all groups compared to their untreated matches. PX (10(-7) and 10(-6)M) potentiated the contractions to KCl (20-180 mM) and ATP (10(-6) to 10(-3)M) in epididymal portion but its higher concentrations (10(-5) and 10(-4)M) inhibited the responses, both in the control and chronically ethanol treated rat groups. Prazosin (PR), an alpha adrenergic receptor blocker, could not inhibit PX-induced potentiation in lower concentrations of KCl but could inhibit the potentiation occurred at higher concentrations of KCl in epididymal portion both in the control and chronically ethanol treated rat groups. PR also inhibited PX-induced potentiation on the responses to ATP in epididymal portion both in the control and chronically ethanol treated rat groups. In conclusion, all the results obtained in this study, suggest that chronic ethanol treatment decreased the contractility of vas deferens but did not alter the action pattern of PX on responses to KCl and ATP in rat vas deferens. On the other hand, the potentiation of responses to contractile agents induced by PX can be partially considered as the result of inhibition of noradrenaline re-uptake.

Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model.

The effects of melatonin, a free-radical scavenger and a general antioxidant, on radiation-induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4-wk-old (75-100 g) male Sprague-Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X-irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non-irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 +/- 9.5 and a mean percent overall limb discrepancy of 11.2 +/- 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 +/- 5.8 and 32.2 +/- 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 +/- 1.6 and 8.9 +/- 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01-0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.

The effects of paroxetine on rat isolated vas deferens.

The aim of the present study is to evaluate whether paroxetine (a selective serotonin re-uptake inhibitor) can modify the contractile responses of isolated vas deferens. Some contractile agents, potassium chloride (KCl), adenosine 5'-triphosphate (ATP), noradrenaline (NA), and electrical field stimulation (EFS) caused contractions both in epididymal and prostatic portions of vas deferens. Paroxetine (PX) in concentrations 10(-7) and 10(-6)M potentiated the contractions to KCl and ATP only in epididymal portion but in higher concentrations (10(-5) and 10(-4)M) inhibited the responses in both portions. NA responses were inhibited by PX in all concentrations used, both in prostatic and epididymal portions. Prazosin (PR), an alpha adrenergic receptor blocking agent, inhibited PX-induced potentiation observed for higher concentrations of KCl. PR also inhibited PX-induced potentiation on the responses to ATP in epididymal portion. Pretreatment with PX (10(-7) to 10(-6)M) increased the contractions to EFS but in 10(-5) and 10(-4)M concentrations inhibited them. Even though the preparations were washed out, the inhibited responses of contractile agents could not be restored. After a washout period for PX, when Bay K 8644 (calcium channel activator) was added to the bath medium, the contractile responses to KCl were partially restored. In calcium-free medium, KCl caused contractions in concentrations higher than 80 mM with lower amplitudes which were not affected by PX. Reserpinization did not change the inhibitory pattern of PX's effect on exogenously applied NA in all concentrations tested. In reserpinized rats, the potentiation caused by PX in exogenously applied ATP responses was not observed. In conclusion, we can say that PX has two different effects: inhibition and potentiation of contractions to various agonists. The inhibitory effect of the drug can be explained by a calcium channel blocking activity. The potentiating effect of the drug is mainly related to its presynaptic action, such as NA re-uptake inhibitory effect.