Influence of intrathecal morphine and buprenorphine on EEG and their analgesic effect

This study was performed on fifty patients undergoing gynecological operations of lower abdomen. Their mean age and body weight were 43 +/- 5yrs and 55 +/- 8kg (mean +/- SD) respectively. All patients were given spinal anesthesia for surgery. Patients were divided into four groups of ten patients at random as follows: Group I (control) received 7.5mg of dibucaine only, Group II received 7.5mg of dibucaine with 0.05mg of buprenorphine (B), Group III received 7.5mg of dibucaine with 0.25mg of morphine (M), Group IV was the same as G-III but received 0.2mg of naloxone after operation. We observed EEG during operation and assessed intrathecal B and M for postoperative analgesic effect and side effects. EEG finding was as follows. In G-I, alpha and beta waves appeared dominantly during operation. In G-II, G-III and G-IV, EEG showed specific beta wave which is characterized with low voltage and rapid activity. This specific EEG change emerged at 10 minutes after the intrathecal injection of M in G-III and G-IV, and at 60 minutes after the intrathecal injection of B in G-II. This finding showed that intrathecal M with less lipid solubility reached more rapidly to CSF in the fourth ventricle than intrathecal B. The result suggests that the earlier respiratory depression may be caused by large doses of intrathecal M. Postoperative analgesic effect was recognized remarkably in G-II, G-III and G-IV (P less than 0.01). The duration for pain relief was 6 hrs in G-II and 12 hrs in G-III and G-IV.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of the nitric oxide donor molsidomine prevent in warm ischemia-reperfusion injury of the rat renal — A functional and histophatological study

Aim of this experimental study is to verify the protective effect of molsidomine on the renal function and structural modifications in the ischemia-reperfusion rat kidney. Sixty-eight male Sprague-Dawley rats, which were right nephrectomized and occluded left renal artery for 60 minutes were used. Group I (n = 10) Sham-Operated animals, which only underwent right nephrectomy. Group II (n = 20) Untreated ischemic rats, which underwent left renal ischemia by occlusion of the renal artery for 60 minutes before blood flow was restored. Group III (n = 18) Molsidomine treated ischemic rats, Group IV (n = 20) L-NAME (N^G-nitro-L-arginine methyl ester) treated ischemic rats. Serum creatinine and blood urea nitrogen (BUN) were measured daily and biopsies were obtained from the remaining left kidneys. At seventh day, 55% and50% of the rats remained alive at the G-II and G-IV respectively. Molsidomine treated rats (G-III) were alive and healthy at day 7. The serum creatinine and BUN levels were significantly higher in G-II and G-IV when compared with the sham-operated group (G-I). G-III rats showed a rapid return to the normal serum creatinine and BUN values on postoperative days 1, 2, 3 and 4. The obtained values in G-III were significantly lower in comparison to the values of G-II and G-IV. The most severe damage (grade3 to 4) was determined in the kidneys of rats from GII or GIV. The degree of renal tubular damage in GIII was evaluated as grade 1 or 2 tubular damage according to Jablonkski's scale. Our findings suggested that the administration of molsidomine may vanquish the pernicious effects of warm ischemia on kidney structure and function. This revised version was published online in June 2006 with corrections to the Cover Date.     

Volume replacement in trauma patients within the first 24 h and its impact on the interpretation of biochemical data

BACKGROUND AND AIMS: Patients of the same and particularly of different trauma studies are primarily incomparable due to different volume replacements. The aim of this prospective study was to analyze the amount of initially administered fluids in trauma patients during the first 24 h and to estimate the impact of dilution on plasma protein concentrations (PPCs) of prostanoids. These substances are vascular endothelium-derived and are thus influenced by blood pressure. PATIENTS/METHODS: Sixty-nine casualties suffering from multiple injuries were enrolled in the study. The amount of any fluid administered was scrutinized during the first 24 h. Patients were divided into subsets according to trauma severity by Injury Severity Score (ISS) (group=G-I: < or = 9; G-II: 10-18; G-III: 19-32; G-IV: >32) and between survivors and non-survivors. At corresponding time points, hemoglobin, hematocrit (Hct) and PPC as well as prostaglandins (PGI, TxA, PGF2a) were evaluated at the site of accident, at hospital admission, and every hour thereafter for the first 24 h. RESULTS: During this period, the total amount of infused fluids ranged between 0.51 (G-I) and >481 (G-IV). The higher the trauma severity, the greater the volume infused (G-III/IV P=0.0003 vs G-I/II). Simultaneously, PPC dropped markedly (P<0.01). Patients who died within 36 h required higher volumes (P<0.003) than survivors. PPC was linearly related (r2=.6685, P<0.001) to Hct. During the first 24 h, the time course of prostanoid concentration was altered when dilution is not taken into account. CONCLUSION: PPC proved a suitable parameter to estimate dilution effects and to adjust plasma concentrations of prostanoids. We recommend that consideration be given to possible dilution effects during the first 24 h when interpreting biochemical data in trauma patients.     

Effect of retroviral transduction of canine microvascular endothelial cells on beta(1) integrin subunit expression and cell retention to PTFE grafts

This study evaluated the effect of retroviral transduction on canine microvascular endothelial cell (CMVEC) detachment from fibrin glue coated expanded polytetrafluoroethylene (ePTFE) graft material. CMVEC were isolated from adipose tissue by fluorescent activated cell sorting (FACS). Three treatment groups were evaluated: G-I, transduced CMVEC, selected in antibiotic G418 for 10 days (n=5); G-II, CMVEC selected in G418 and recovered from selection for 4 days (n=5); and G-III, control group of naive CMVEC (n=6). (3)H-thymidine labeled endothelial cells were seeded on fibrin glue coated four-mm diameter PTFE. Grafts were exposed to physiologic shear stresses of 16 dyn/cm(2). Cell detachment was determined by (3)H-thymidine counts in the circuit effluent. beta(1) integrin subunit expression was measured by flow cytometry. After 2 hours of flow exposure, G-I and G-II demonstrated significantly greater cell detachment rates compared with the control seeded grafts. Median peak channel beta(1) integrin subunit value for G-III CMVEC was 2311+/-481.7 vs. 31.5+/-4.51 and 26.3+/-2.0 in the transduced cell groups (p=0.00043). Low beta(1) integrin expression correlated with flow induced high detachment rates of retrovirally-transduced CMVEC.     

Use of different immunosuppressive strategies in recipients of kidneys from nonheart-beating donors

In nonheart-beating donor (NHBD) kidney transplants, immunosuppressive management is difficult mainly because of the high incidence of acute tubular necrosis. This has meant that since the start of our NHBD transplant program, several immunosuppression regimes have been used. The aim of this retrospective study was to evaluate the results obtained over 7 years using different treatment protocols. A total of 172 consecutive NHBD transplants performed between April 1996 and December 2002 were treated as follows: G-I (n = 21), cyclosporine (8 mg/kg/day) plus azathioprine plus steroids; G-II (n = 65), low-dose cyclosporine (5 mg/kg/day) plus mycophenolate plus steroids; G-III (n =17), low-dose tacrolimus (0.1 mg/kg/day) plus mycophenolate plus steroids; and G-IV (n = 69), daclizumab plus low-dose tacrolimus plus mycophenolate plus steroids. Delayed graft function rates were 76.2%, 72.3%, 76.5%, and 42%, respectively, for the four groups (P = 0.000). Rejection-free patient rates were 76.2%, 46.2%, 35.3%, and 71% (P < 0.001). Vascular rejection rates were 19%, 30.8%, 52.9%, and 18.8%, (P = 0.025). Two-year graft survival was 71.4% in group I, 95.4% in group II, 94.1 in group III, and 93.8% in group IV (P =0.004). Patient survival was worse in group I (75.2% in group I, 100% in group II, 100% in group III, and 96.7% in group IV at 2 years; P < 0.001). The use of daclizumab and low-dose tacrolimus could be effective at lowering the incidence of delayed graft function in NHBDT, with no negative repercussions on acute rejection.     

Biochemical Response to Bisphosphonate Therapy in Pagetic Patients with Skull Involvement

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget’s disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, α-α CTX, and β-β CTX) were measured at baseline and 6 months after therapy. The extent of the disease was evaluated using the Coutris’ index. Pagetic patients were classified into three groups: patients with skull involvement (G-I, n = 12), patients without skull involvement (G-II, n = 28), and a subgroup of patients from G-II without skull involvement but with similar disease extent to G-I (G-III, n = 10). At baseline, patients from G-I showed significantly higher values in most markers compared to G-II. α-α CTX was the marker with the highest values in all groups. Moreover, monostotic patients with skull involvement showed higher serum baseline values of TAP per unit of affected area than monostotic patients without skull involvement. After therapy, the percentage of patients with markers within the normal range was lower in G-I than in G-II and G-III. In conclusion, pagetic patients with skull involvement showed a marked increase in bone turnover and a lower response to therapy.     

Heteromorphic grade of renal cell cancer

The present study demonstrates by means of histopathologic analysis that most of the renal adenocarcinomas are microscopically heterogeneous--named by authors as heteromorphic. This heteromorphism means the mixture of different cell types, histological patterns and fields of tumor with different nuclear atypia. 300 surgical specimens of renal cell cancer (RCC) were reclassified retrospectively. The histologic classification was as follows: 1. Nuclear atypia (nuclear grading according to Skinner); 2. Histological structure (compact, tubular, papillary, cystic); 3. Tumor cell types (clear, chromophobe, chromophilic basophilic, chromophilic eosinophilic). Homogeneous tumors consist of the three categories of this basic classifications. Heteromorphic tumors have combinations the three categories: different cell types (clear and granular) and/or histological elements (tubulo-papillary) and/or nuclear structure. Heteromorphism of RCC can be graded as: G-I: homogeneous structure (three patterns, one-one pattern of the three categories; G-II: 3 + 1 patterns.... G-III: 3 + 2 patterns.... G-IV: 3 + 3 or more patterns of the classification given above. This grading system is recommended for the heteromorphism of renal adenocarcinomas.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Should the supplemental vein graft be anastomosed upstream or downstream of the internal thoracic artery (ITA) for ITA hypoperfusion?

BACKGROUND: This study was designed to compare internal thoracic artery (ITA) flow in different settings of supplemental vein grafting for ITA hypoperfusion. METHODS: Fourteen dogs each received two coronary bypass grafts to the circumflex artery (CFX), using left ITA and vein grafts, and then the proximal CFX was ligated. The animals were divided into two groups. G-I dogs receiving the vein graft proximally to the ITA graft and G-II receiving the vein distally. ITA flow was evaluated regarding 1) effects of competition from the vein graft, and 2) pharmacological or physiological effects on the ITA's contribution to distal perfusion. Flow is expressed as a mean (ml/min). RESULTS: ITA flow was 44.2+/-5.9 in G-I, and 45.7+/-6.5 in G-II (p=ns), when the vein graft was occluded. With a vein graft open, ITA flow decreased to 7.5+/-1.6 in G-I, and 6.8+/-1.8 in G-II (p=ns), and ITA's contribution to total perfusion requirements was 18% in G-I and 16% in G-II. Adenosine (0.2 mg/min/kg) increased the ITA flow in both groups, 18.4+/-3.2, and 16.3+/-3.8, respectively (p=ns), and ITA's contribution to distal perfusion was increased to 32% in G-I and 27% in G-II. In contrast, phenylephrine (0.003 mg/min/kg) decreased ITA flow and ITA's contribution to distal flow in both groups (6.1+/-1.1, 11% vs 6.2+/-1.4, 11%, p=ns), but increased vein flow significantly. Cardiac pacing (150 bpm) increased the ITA flow and ITA's contribution to distal perfusion equally in both groups (8.4+/-1.5, 16% vs 7.6+/-2.6, 15%, p=ns). CONCLUSIONS: Supplemental vein grafting, whether it is placed distally or proximally, limits ITA flow and ITA's contribution to distal perfusion both in the resting heart and during the increased myocardial oxygen demand.     

联合应用异博定和还原型谷胱甘肽对兔供肺的保护作用

目的 观察联合应用异博定和还原型谷胱甘肽对兔肺脏保存的影响.方法 健康日本大耳白兔24对,随机分为4组,每组6对.D组用改良型低钾右旋糖酐液(对照组,改良LPD液)行肺灌洗保存,Y组用改良LPD液+异博定(2 mg/kg体重),H组用改良LPD液+还原型谷胱甘肽(3 mmol/L),L组用改良LPD液+异博定(2 mg/kg体重)+还原型谷胱甘肽(3 mmol/L).实验结束时取肺组织测定湿/干比,细胞内钙离子浓度,丙二醛(blDA)含量与超氧化物歧化酶(SOD)活性,并行细胞凋亡测定.结果 L组的肺组织湿/干比、细胞内钙离子浓度、丙二醛(NDA)含量与超氧化物歧化酶(SOD)活性均优于D组(P值均＜0.01),细胞凋亡L组平均灰度值和阳性单位明显好于D组(P＜0.01、P＜0.05).结论 联合应用异博定和还原型谷胱甘肽对于肺缺血再灌注损伤的作用均优于两药单独应用.     

Theophylline improves functional recovery of isolated rat lungs after hypothermic preservation

BACKGROUND: Raising intracellular cyclic adenosine monophosphate levels protects lungs from ischemia-reperfusion injury. We hypothesized that the phosphodiesterase inhibitor theophylline would protect lungs during storage. METHODS: Rat lungs were perfused with modified bicarbonate buffer mixed with rat blood (4:1 vol/vol) (37 degrees C) and ventilated (80 breaths/min). After 20 minutes of perfusion during which vascular resistance and airway compliance were measured, lungs were flushed with and then immersed in bicarbonate buffer (4 degrees C) alone or containing theophylline (30 to 1,000 micromol/L). After 6 hours of storage, lung function was reassessed during 40 minutes of reperfusion. RESULTS: Lungs stored in the presence of theophylline had improved lung function on reperfusion. After 40 minutes of reperfusion, pulmonary compliance was 0.008+/-0.004 mL/cm H2O, 0.022+/-0.010, 0.037+/-0.007, 0.044+/-0.006, and 0.073+/-0.003 mL/cm H2O, and vascular resistance was 3.84+/-0.40 cm H2O x min x mL(-1), 3.64+/-0.78, 2.12+/-0.35, 2.22+/-0.25, and 1.90+/-0.38 cm H2O x min x mL(-1) in lungs stored in the presence of 0, 30, 100, 300, or 1,000 micromol/L theophylline, respectively. Similar improvements were obtained for wet to dry weight ratio and gas exchange. CONCLUSIONS: Theophylline merits investigation as a potentially beneficial addition to solutions for the flushing and storage of human lungs for transplantation.     

Statins and vitamin D: a friendly association in pre-dialysis patients

The increased mortality rate observed in patients with chronic kidney disease is related to the high prevalence of cardiovascular disease in this population. Recently, it has been shown that interventional therapy with statins and/or vitamin D could improve the outcomes of these patients. The aim of this study was to identify the risk factors for mortality in a group of patients with chronic kidney disease (stages 4 and 5—pre-dialysis) and verify whether vitamin D and statins could change the outcome. We included 95 patients (mean age—69.4) with stages 4 and 5 (pre-dialysis) of our “low-clearance” outpatient clinic, with an average eGFR of 16.9 ml/min and a mean follow-up of 24.1 months. Several biological, nutritional, laboratory and inflammatory parameters were analysed at baseline. Our population was divided into three groups: G-I, patients not medicated with either vitamin D or statins; G-II, patients medicated with either vitamin D or statins; and G-III, patients medicated with vitamin D and statins. We found (ANOVA) that the serum levels of pre-albumin (P = 0.018) and PTH (P = 0.03) were lower in G-I. Concerning the inflammatory parameters, G-I showed higher levels of hsCRP (P = 0.014) and a trend to higher IL-6 levels (P = 0.077). We found the actuarial survival at 30 months (Kaplan–Meier), to be 56.4% in G-I, 82.3% in G-II and 100% in G-III (log rank = 13.08 P = 0.0014). Using the Cox proportional hazards model, we found that the existence of coronary artery disease (P = 0.0001) and the absence of medication with vitamin D and/or statins (P = 0.005) independently influenced the mortality of our patients. In conclusion, we found, in our study, that patients under vitamin D and statins (with a synergistic effect) were less inflamed and showed a lower mortality rate.     

Evaluation of sequential perfusion with Euro-Collins and Belzer solutions for pancreas preservation in rats

OBJECTIVE: To investigate the effect of Euro-Collins and Belzer solutions in a sequential preservation of the pancreas. METHODS: Forty-five Wistar-EPM rats were divided into four groups, according to the solution used during preservation: (1) saline solution (SF): animals perfused and preserved with saline solution; (2) Euro-Collins group (C): animals perfused and preserved with Euro-Collins solution; (3) Belzer group (B): animals perfused and preserved with Belzer solution; (4) Euro-Collins/Belzer group (CB): animals perfused with equal parts of Euro-Collins and Belzer solutions sequentially and preserved with Belzer solution. After perfusion, the animals underwent pancreas resection and preservation with the respective substance at 4 degrees C. Amylase was measured in the preservation solution after 12, 24, 36, or 48 hours. Finally, the pancreas was analyzed histologically, and a statistical analysis was performed. RESULTS: Groups SF and C showed the highest amylase levels in the preservation solution during all periods. The levels were higher than in groups C and CB (P = .05). Amylase levels were similar in groups B and CB to 24 hours (P = .05). Histological analysis was significant for analysis of pancreas islet cells and edema. Groups B and CB were histologically similar (P = .001) and different from groups SF and C. CONCLUSION: Sequential perfusion using Euro-Collins and Belzer solutions was effective for pancreas preservation in rats up to 24 hours.     

Surgical management of patent ductus arteriosus in low body weight infants

Between January 1980 and December 1994, seventeen premature infants weighing less than 2500 g underwent surgical management for the isolated patent ductus arteriosus (PDA). Indometacine therapy for closure of PDA was not effective for all these patients. In terms of the body weight at birth, they were divided into two groups; Group I (G-I) consisted of ten patients with birth weight less than 1000 g and Group II (G-II) of seven patients weighing more than 1000 g. The age at operation was 22.1 ± 15.4 days in the G-I and 14.3 ± 11.4 days in the G-II. The ductus was ligated in all patients but one of the G-II, in whom it was divided. There were five (50%) hospital deaths in the G-I and none in the G-II. The causes of death in the G-I were related to necrotizing enterocolitis (NEC) in two and infant respiratory distress syndrome (IRDS), acute renal failure, and broncho-esophagial fistula in each. The age at operation tended to be older in nonsurvivors rather than in survivors in the G-I (28.0 ± 16.8 days vs. 16.2 ± 14.0 days, respectively, but the difference did not reach significance). Before surgery, all patients in the G-I required mechanical ventilator support and nine of them were associated with IRDS. In contrast, only two patients in the G-II needed mechanical ventilation preoperatively. The postoperative period of intubation was also significantly longer in the G-I than in the G-II (51.6 ± 35.2 days vs. 2.2 ± 1.5 days, respectively, p<0.05). In conclusions, the surgery for PDA can be safely performed even in small premature babies weighing less than 1000 g. When the medical therapy for PDA is not effective in the premature patients, the surgical management should be considered as early as possible before their conditions become worse due to such critical complications as NEC, IRDS, and renal failure.     

Emergency coronary artery bypass grafting in patients with severe pump failure complicating acute myocardial infarction]

Thirty patients with severe pump failure (Killip's degree III or more) complicating acute myocardial infarction (MI) underwent emergency coronary bypass grafting (CABG). Average age was 66 years old and CABG was performed 2.6 days after the onset of MI. The patients were divided into two groups according to the mechanisms that can bring about severe pump failure: 19 patients had large MI alone (G-I). The other 11 patients had severe ischemia occurring either at areas distant from the site of coronary occlusion or in the previous area at risk (G-II). To estimate the ventricular wall motion quantitatively, the left ventricular wall was divided into 17 segments. Each segment was graded on a four-point scale: akinesis, 3; severe hypokinesis, 2; hypokinesis, 1; normal 0. Wall motion score was estimated by summing the number of asynergic segments score. In G-I, Cardiac index (CI (l/min/m2)) increased from 2.03 +/- 0.91 to 2.68 +/- 0.73 and pulmonary wedge pressure (PCWP (mmHg)) decreased from 28 +/- 5 to 15 +/- 5, 72 hours after the surgery (p < 0.01). In G-II, CI increased from 2.17 +/- 0.78 to 3.17 +/- 1.01 and PCWP decreased from 29 +/- 6 to 13 +/- 5 after the surgery (p < 0.01). There was no difference in preoperative and postoperative hemodynamics between two groups. The wall motion score at the risk area did not change postoperatively (from 16 +/- 7 to 17 +/- 9 in G-I, from 15 +/- 8 to 11 +/- 5 in G-II).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rewarming, ultraprofound hypothermia and cardiopulmonary bypass

Rewarming, a key event in resuscitation from accidental, experimental and clinical hypothermia, is sometimes followed by neurologic, cardiac, and respiratory sequelae and may lead to death. The rate of rewarming has been implicated but not quantified as etiologic in these sequelae. Under anesthesia fifteen dogs were cannulated and connected to an extracorporeal circuit for oxygenation, core cooling and rewarming. They were subjected to ultra-profound hypothermia with a core (esophageal) temperature as low as 1.3 degrees C, cardiac arrest, blood substitution, and continuous low flow perfusion. After 2-3 hours of cardiac arrest, rewarming began. Mechanical activity of the heart was seen between 10 degrees and 28 degrees C and respiration resumed at 29 degrees C. The rewarming rates of the 15 dogs were retrospectively studied. They were placed into three categories (G) based on the outcome. G-I (N=2):no neurological complications, G-II (N=8):transient neurological problems, and G-III (N=5):death, mainly from cardiovascular and respiratory complications confirmed at death by autopsy. Heat gain by each animal was recorded as a function of time for all experiments. The time it took each dog to reach 35 degrees C was determined and a mean was calculated (rewarming rate). Normal body temperature for a dog is 37.8 degrees C. Statistical analysis (ANOVA) was performed ex post facto to determine the relationship between rewarming rate and outcome. Our data contradicts the notion that slow core rewarming from nadir to normal temperature offers better outcome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid peroxidation after cold storage and normothermic reperfusion: the effect of trimetazidine

Abstract Ischemia reperfusion injury is still a leading cause of early graft dysfunction after transplantation. Trimetazidine (TMZ) has been postulated to be protective against renal damage from oxygen free radicals. The aim of this study was to assess the effect TMZ during cold storage (CS) and normothermic reperfusion in an isolated perfused pig kidney model. Three groups were studied: control group, immediately perfused (GO), 48 h CS in Euro-Collins solution (G1), and 48 h CS in Euro-Collins solution plus TMZ (G2). Glomerular filtration rate (GFR) and fractional sodium reabsorption (FRNa⁺) were calculated during reperfusion from urine and perfusate samples. Lipid peroxidation was determined by the renal tissue level of Schiff bases (SB) and malondialdehyde (MDA) after reperfusion. A histological evaluation was performed after reperfusion. Renal function was significantly improved and lipid peroxidation reduced after preservation in Euro-Collins solution plus TMZ. Functional data were closely related to histological damage. In conclusion, TMZ is a useful protective agent against renal damage induced by CS.     

山莨菪碱对肝脏缺血再灌注损伤的保护作用

目的 探讨山莨菪碱对肝脏缺血再灌注损伤的保护作用。方法 将雄性Wistar大鼠制成肝脏缺血再灌注模型,随机分为正常对照组、缺血再灌注组、生理盐水组和山莨菪碱组,观察肝脏缺血60min再灌注1、3、6、12及24h后血浆和／或肝组织中内皮素－1（ET－1）、透明质酸（HA）、丙氨酸转氨酶（ALT）、丙二醛（MDA）和再灌注1h后肝细胞内游离Ca^2 ([Ca^2 ]i)、ATP含量变化以及肝组织病理学改变。结果 肝脏缺血再灌注后血浆和／或肝细胞中ET－1、HA、ALT、MDA和肝细胞内[Ca^2 ]u含量均显著升高,而肝组织中ATP含量明显降低;肝脏缺血再灌注前应用山莨菪碱2.0mg/kg者,血浆HA和肝细胞内[Ca^2 ]i含量明显降低,肝组织中MDA也有不同程度的降低,而肝组织中ATP含量明显升高,同时肝酶的漏出减少,肝组织病理学损害明显减轻。结论 山莨菪碱对肝脏缺血再灌注损伤具有保护作用。     

线粒体ATP敏感性钾通道在利多卡因预先给药减轻大鼠离体心脏缺血再灌注损伤中的作用

目的 评价线粒体ATP敏感性钾通道在利多卡因预先给药减轻大鼠离体心脏缺血再灌注损伤中的作用.方法 雌性成年Wistar大鼠,体重220～250 g,采用Langendorff装置建立大鼠离体心脏缺血再灌注模型.取模型制备成功的大鼠心脏24个,随机分为3组(n=8):缺血再灌注组(IR组)、利多卡因组(L组)和利多卡因+格列苯脲组(LG组).K-H液平衡灌注10 min后,C组、L组和LG组分别灌注K-H液、含2.5 mg/L利多卡因的K-H液、含2.5 mg/L利多卡因+10μmol/L格列苯脲(线粒体ATP敏感性钾通道阻断剂)的K-H液20 min,然后缺血30 min,再灌注60 min.分别于平衡灌注末(T0)、再灌注15 min(T1)、30 min(T2)、45 min(T3)和60 min(T4)时,记录HR、左心室发展压(LVDP)、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dtmax).于T0和T4时,收集冠状动脉流出液,测定乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性.于T4时取心尖周围心肌组织,测定Na+-K+-ATP酶和SOD的活性、MDA和Ca2+的含量.结果 与IR组比较,L组HR、LVDP、+dp/dtmax和-dp/dtmax升高,CK和LDH的活性降低,心肌Na+-K+-ATP酶和SOD的活性升高,Ca2+和MDA的含量降低(P＜0.05),LG组上述各指标差异无统计学意义(P＞0.05).与L组比较,LG组HR、LVDP、+dp/dtmax和-dp/dmax.降低,CK和LDH的活性升高,心肌Na+-K+-ATP酶和SOD的活性降低,Ca2+和MDA的含量升高(P＜0.05).结论 利多卡因预先给药减轻大鼠离体心脏缺血再灌注损伤与促进线粒体ATP敏感性钾通道的开放有关.     

The role of theophylline in contrast-induced nephropathy: a case-control study.

BACKGROUND: Various strategies for the prevention of contrast-induced nephropathy (CN) have been studied, with conflicting results. Adenosine may play an important role in the pathogenesis of CN. This study prospectively assessed the role of oral theophylline in the prevention of CN. METHODS: We randomized into two groups 70 patients with diabetes mellitus who were undergoing coronary angiography (CAG) with high-osmolar contrast media. Group I (n=35) underwent routine CAG, and group II (n=35) received oral theophylline 200 mg b.d. 24 h before and for 48 h after CAG. Serum Na(+), K(+), blood urea nitrogen (BUN), creatinine, osmolality, glomerular filtration rate (GFR) and urinalysis were performed before and after CAG. The (99m)Tc-DTPA-clearance method was used to assess GFR. RESULTS: Following angiography, patients in the control group showed a significant rise in serum creatinine (1.19+/-0.23 vs 1.44+/-0.32 mg/dl, P=0.003) and BUN (13.95+/-2.61 vs 17.55+/-3.9 mg/dl, P=0.01) along with a fall in GFR (85.4+/-14.7 vs 66.85+/-14.8 ml/min, P=0.008). The mean percentage fall in GFR was 35.8%. There was no significant change in serum creatinine (1.16+/-0.18 vs 1.24+/-0.21 mg/dl), BUN (12.8+/-3.36 vs 14.8+/-2.5 mg/dl) and GFR (86.8+/-15.8 vs 80.3+/-16.0 ml/min) in those receiving theophylline. No patient in the theophylline group had a >25% rise in serum creatinine, compared with 7/35 in the control group (P=0.017). In the control group, 11/35 (31%) developed CN, as demonstrated by a >/=25% fall in GFR, while only one patient in the theophylline group had a fall in GFR (P=0.004). None of the pre-angiographic variables could predict the development of CN. CONCLUSIONS: Following the use of high-osmolar contrast media for routine CAG, CN may develop in 31% of diabetic patients. Patients who received prophylactic oral theophylline had a significantly lower risk of CN than those who did not.