Leukocyte CD18 receptors may be a better target than ICAM-1 ligands for reducing histologic evidence of cellular and vascular rejection in the rabbit

Building evidence suggests that blocking the ICAM-1/CD18 interaction may affect the course of graft rejection. Treatment with monoclonal antibody (mAb) to CD18 was compared to antibody to ICAM-1 in a rabbit heterotopic heart transplant model to determine whether blocking the leukocyte receptor for ICAM-1, CD18, was more effective than antibody targeting of the ligand for ICAM-1. Following transplantation, 28 recipient rabbits were randomized to receive either placebo, mAb to CD18, or mAb to ICAM-1 for 7 days until sacrifice. The cellular rejection grade and percentage of arteries with vascular rejection were significantly lower in animals treated with anti-CD18 than with anti-ICAM-1. As assessed by histology, antibody treatment was more effective in reducing both cellular and vascular rejection when directed at the leukocyte receptor CD18 than the ICAM-1 ligand. These findings suggest that other ICAM ligands may play an active role in the immune response and that CD18 may be important for migration of lymphocytes through myocardium.This work was presented at the 29th Annual Meeting of The International Society for Heart and Lung Transplantation, Boca Raton, Aril 1993.     

Cardioventilatory coupling in heart rate variability: methods for qualitative and quantitative determination

In this study we sought to develop quantitative methods fordetermining the presence of cardioventilatory coupling in rawheart rate time series. The beat-to-beat RR interval time seriesof 98 anaesthetized, spontaneously breathing subjects were representedgraphically as (1) raw RR interval time series, (2) RR consecutivedifference time series and (3) a phase portrait of the RR consecutivedifference time series. We then examined the relationships betweenthe presence of cardioventilatory coupling in these epochs andthe plot appearance and entropy measures derived from theseplots. We observed that coupling was significantly associatedwith the presence of banding in the raw heart rate and RR consecutivedifference time series, and with discrete clustering withinthe RR consecutive difference phase portrait. A significantcorrelation was found between coupling and the entropy of theRR consecutive difference time series and its phase portrait.We conclude that, with some provisos, these simple graphicaland derived quantitative measures provide a basis for the determinationof cardioventilatory coupling from heart rate time series. Br J Anaesth 2001; 87: 827–33     

Cardioventilatory coupling in heart rate variability: the value of standard analytical techniques

In a group of spontaneously breathing anaesthetized subjects,we examined the ability of simple spectral and non-linear methodsto detect the presence of cardioventilatory coupling in heartrate time series. Using the proportional Shannon entropy (H_RI–1)of the RI_–1 interval (interval between inspiration andthe preceding ECG R wave) as a measure of coupling, we foundno correlation between H_RI–1 and either the fractal dimensionor approximate entropy of the heart rate time series. We alsoobserved no difference in the distribution of heart rate variability(HRV) spectral power in three frequency ranges (high, 0.15–0.45 Hz;low, 0.08–0.15 Hz; very low, 0.02–0.08 Hz)between uncoupled epochs and coupling patterns I, III and IV.Because of its association with low breathing frequencies, patternII coupling epochs showed exaggerated low-frequency power asthe high-frequency ‘respiratory’ peak fell intothe low-frequency range. We conclude that coupling pattern islargely independent of autonomic tone and that these standardmethods of HRV analysis are limited in their ability to detectthe presence of cardioventilatory coupling in heart rate timeseries. Br J Anaesth 2001; 87: 819–26     

Bcl-2转录抑制因子1在肝癌组织中的表达及意义

背景与目的:已有研究显示,Bcl-2转录抑制因子1(Bit1)在多种肿瘤中异常表达并在肿瘤进展中发挥重要作用,Bit1在肝细胞癌(HCC)中的表达水平及临床意义值得探讨。本研究通过检测Bit1在HCC组织中的表达,分析其与HCC患者临床病理特征及预后的关系,从而探讨Bit1在HCC中的临床意义。方法:采用q RT-PCR、Westernblot检测34例HCC患者手术切除癌组织及对应癌旁组织Bit1m RNA及蛋白表达情况,用免疫组化法检测组织芯片中90例HCC患者癌组织与对应癌旁组织Bit1蛋白表达情况并分析其表达与HCC患者临床病理参数及预后的关系。结果:q RT-PCR与Westernblot检测结果显示,与癌旁组织比较,Bit1在HCC组织中的m RNA及蛋白表达水平均明显上调(P0.05)。免疫组化结果显示,Bit1蛋白定位于细胞质,其在癌组织中的高表达率明显高于癌旁组织(P0.05),且Bit1在HCC组织中的表达与HCC患者肿瘤的复发及病理分级明显有关(均P0.05),Kaplan-Meier分析显示,Bit1蛋白高表达患者总生存率和无病生存率低于Bit1蛋白低表达患者,但差异均未达统计学意义(P=0.547、0.414)。结论:Bit1在HCC组织中高表达,且Bit1表达与肿瘤的复发及病理分级密切相关,提示Bit1可能是影响肿瘤进展的重要分子,其有望成为HCC患者个体化治疗靶点。     

Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine administered during coronary artery stenosis in the presence of beta blockade in pigs

Background. This study examines the effects of phosphodiesterasetype III (PDEIII) inhibition vs beta stimulation on global functionof the left ventricle (LV) and systemic haemodynamics in a porcinemodel of acute coronary stenosis with beta blockade. Methods. A total of 18 adult swine were anaesthetized. Micromanometer-tippedcatheters were placed in the ascending aorta and LV. Two pairsof ultrasonic dimension transducers were placed in the subendocardiumon the short axis proximal to a left anterior descending (LAD)artery occluder and the long axis of the LV. Before ischaemia,i.v. esmolol was infused to decrease baseline heart rate (HR)by approximately 25%, and all animals received an esmolol infusion(150 µg kg^–1 min^–1). Ischaemia was producedby reducing the flow in the LAD artery by approximately 80%,from 17(4) to 3(2) ml min^–1. Animals were randomized toreceive (after esmolol) one of the following: no drug, shamonly (Group 1, n=6), control (C); 50 µg kg^–1 i.v.milrinone (Group 2, n=6) followed by 0.375 µg kg^–1min^–1 (M); or incremental doses of dobutamine (Group 3,n=6) every 10 min (5, 10 and 20 µg kg^–1 min^–1)(D). Left ventricular function data obtained included HR, arterialand LV pressures, cardiac output (CO), Emax and dP/dT. Measurementswere taken during five time periods: before ischaemia (at baseline,after esmolol) and every 10 min during ischaemia (at 10, 20and 30 min). Results. The effects of beta blockade and ischaemia had a significantimpact on contractility (Emax) in Group M and myocardial performance(left ventricular end-diastolic pressure, LVEDP) in all groups.Left ventricular function (Emax, CO, LVEDP and SVR) was betterpreserved when milrinone was added in Group M. A moderate doseof dobutamine (10 µg kg^–1 min^–1) increasedCO. Only the high dose (20 µg kg^–1 min^–1)improved contractility (Emax), but at the expense of increasedSVR. Also, LVEDP with either dose of dobutamine remained highand unchanged. Conclusions. From our limited findings, it would appear thatthere may, theoretically, be some benefit for using milrinonein preference to other inotropic drugs in the presence of betablockade. Milrinone administration should be considered in patientswith acute ischaemic LV dysfunction and preexisting beta blockadebefore using other inotropic drugs such as beta stimulants. Presented in part at: the 27th Annual Meeting of the Societyof Cardiovascular Anesthesiologists, May 14–18, 2005,Baltimore, MD, USA (Anesth Analg 2005; 100: 5CA60).     

Prevention of reperfusion injury in ischemic-reperfused hearts by oxypurinol and allopurinol

We investigated the effects of the xanthine oxidase inhibitor allopurinol and its metabolite oxypurinol on isolated rabbit hearts. To assess the potential role of these drugs in preventing reperfusion injury, hearts were perfused using Langendorff techniques, held globally ischemic for 3 h at 15°C, and then reperfused. During perfusion, hearts received Krebs-Henseleit solution maintained at 37°C. Aortic perfusion pressure was held constant at 80 cm H₂O. Prior to ischemia, hearts were arrested with a constant volume of KCl cardioplegia. Using a left ventricular (LV) balloon, developed pressures were measured prior to and following global ischemia. In addition, coronary circulation (CC) was measured before and after ischemia. All hearts were paced at 260 beats/min. We studied four groups: group 1 received 1 mM allopurinol, group 2 received 1 mM oxypurinol, group 3 received 90 IU/ml superoxide dismutase (SOD) plus 8085 IU/ml catalase (CAT), and group 4 received no treatment and served as a control. Each group consisted of 8 animals. Hearts receiving drug treatment did so during the first 5 min of reperfusion. Displaying all data as a function of LV volume, postischemic values were compared to preischemic values. Multivariate analysis and Tukey tests were used to detect significant differences between groups. When compared to the control group, all drug-treated groups significantly recovered end-diastolic function. Peak systolic pressure decreased significantly in the SOD/CAT group as compared to all other groups. LV isovolumetric work decreased significantly more in the SOD/CAT and control groups than in the oxypurinol group. Coronary circulation decreased significantly in the SOD/CAT and control groups as compared to the allopurinol and oxypurinol groups. Our results demonstrate an enhanced recovery of function when oxypurinol and allopurinol are given at the time of reperfusion. Recent evidence has supported the view that rabbit myocardium, as well as human myocardium, lacks xanthine oxidase. The beneficial effects seen with these drugs may therefore be unrelated to the presence of xanthine oxidase.     

Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS)

Background and objectives. Diffuse mesangial sclerosis (DMS)is a histologically distinct variant of nephrotic syndrome (NS)that is characterized by early onset and by progression to end-stagekidney disease (ESKD). Besides syndromic DMS, isolated (non-syndromic)DMS (IDMS) has been described. The etiology and pathogenesisof DMS is not understood. We recently identified by positionalcloning recessive mutations in the gene PLCE1/NPHS3 as a novelcause of IDMS. We demonstrated a role of PLCE1 in glomerulogenesis.Mutations in two other genes WT1 and LAMB2 may also cause IDMS.We therefore determine in this study the relative frequencyof mutations in PLCE1, WT1 or LAMB2 as the cause of IDMS ina worldwide cohort. Methods. We identified 40 children from 35 families with IDMSfrom a worldwide cohort of 1368 children with NS. All the subjectswere analyzed for mutations in all exons of PLCE1 by multiplexcapillary heteroduplex analysis and direct sequencing, by directsequencing of exons 8 and 9 of WT1, and all the exons of LAMB2. Results. The median (range) age at onset of NS was 11 (1–72)months. We detected truncating mutations in PLCE1 in 10/35 (28.6%)families and WT1 mutations in 3/35 (8.5%) families. We foundno mutations in LAMB2. Conclusions. PLCE1 mutation is the most common cause of IDMSin this cohort. We previously reported that one child with truncatingmutation in PLCE1 responded to cyclosporine therapy. If thisobservation is confirmed in a larger study, mutations in PLCE1may serve as a biomarker for selecting patients with IDMS whomay benefit from treatment.     

趋化因子CXCL1通过整合素β1调控胃癌转移的机制研究

目的探讨过表达趋化因子CXCL1促进胃癌细胞迁移及相关分子机制。 方法应用胃癌细胞株（SGC-7901、BGC-823）,重组慢病毒方法构建过表达CXCL1细胞株,siRNA敲低胃癌细胞表达整合素β1（integrin β1）。Western blotting法检测CXCL1、integrin β1、基质金属蛋白酶（MMP）-2、MMP-9、FAK、SRC和ERK的表达,Transwell实验评估胃癌细胞的迁移能力。 结果过表达CXCL1的SGC-7901和BGC-823细胞中integrin β1表达水平高于对照细胞,siRNA干扰CXCL1表达后,胃癌细胞integrin β1表达水平下降。外源性CXCL1分别增强SGC-7901和BGC-823细胞迁移能力（2.40±0.44）倍（P=0.002）和（2.08±0.30）倍（P=0.001）。此外,CXCL1还增强FAK、SRC和ERK的磷酸化水平。integrin β1-siRNA可以阻断CXCL1所引起的SGC-7901和BGC-823细胞迁移能力增强（P<0.05）及FAK、SRC和ERK的磷酸化水平。CXCL1调控SGC-7901和BGC-823细胞的MMP-2、MMP-9表达,而敲低integrin β1后MMP-2、MMP-9表达随之下调。MMP抑制剂GM6001抑制7901-CXCL1和823-CXCL1细胞的迁移能力（P<0.05）。 结论CXCL1通过integrin β1激活FAK-SRC-ERK通路和调控MMP-2、MMP-9的表达,最终调控胃癌细胞迁移。     

Electrophysiological effects of morphine in an in vitro model of the 'border zone' between normal and ischaemic-reperfused guinea-pig myocardium

Background. Morphine is commonly used in clinical practice inpain management. Although morphine has been shown to preconditionthe myocardium, its effects on action potential parameters andischaemia–reperfusion-induced arrhythmias and conductionblocks remain unknown. Methods. In a double-chamber bath, guinea-pig right ventricularmuscle strips were subjected partly to normal conditions andpartly to 30 min of simulated ischaemia (hypoxia, hyperkalaemia,acidosis, and lack of nutritional substrate) followed by 30 minof reperfusion. Action potential parameters were recorded continuouslyin the normal zone and in the ischaemic– reperfused zone.Spontaneous arrhythmias and conduction blocks were noted. Theelectro physiological effects of morphine were studied at 0.01and 0.1 µM. Results. In control conditions, morphine did not modify actionpotential parameters of resting membrane potential, maximalupstroke velocity (V_max), action potential amplitude (APA) andaction potential duration at 50 and 90% of repolarization. Morphinereduced ischaemia-induced depolarization and lessened the ischaemia-induceddecrease in APA and V_max. Morphine significantly decreased theoccurrence of conduction block during simulated ischaemia (20%at 0.01 and 0.1 µM vs 67% in the control group, P<0.05)and reperfusion-induced arrhythmias (40% at 0.01 µMand 30% at 0.1 µM vs 92% in the control group, P<0.05). Conclusions. In ischaemic–reperfused guinea-pig myocardium,morphine at clinically relevant concentrations decreased ischaemia-inducedconduction blocks and reperfusion-induced ventricular arrhythmias. Br J Anaesth 2002; 89: 888–95     

Implantation of the Total Artificial Heart by Lateral Thoracotomy

Progress in the techniques for surgical implantation of the artificial heart has progressed in parallel with the technology and design of the prosthesis. In the author's first experience with total artificial heart (TAH) implantation (1968) a trans-sternal split was used opening the sixth intercostal space on the right side across the sternum to the left space. This obviously was not the optimum approach but the complexity, design and size of the prosthesis required maximum exposure of the atria and great vessels. Subsequently the mid-sternal split incision was used. The Dacron fibril coated silicone rubber 8 cm Kwan-Gett ventricles implanted by the mid-sternal split sustained a calf for 14 days in 1972. A calf with the improved Jarvik 3 ventricles fabricated with the same material and implanted via mid-sternal split survived 19 days in early 1973. The surgical techniques for lateral (right) thoracotomy were adopted in this laboratory in 1973. These techniques were applicable only when the prosthesis fit better in the chest. This procedure has been adopted by other laboratories replacing the natural heart of the calf with a TAH. This report describes in detail the stepwise procedure for implantation of the total artificial heart by a lateral thoracotomy in the calf.     

Volumetric preload measurement by thermodilution: a comparison with transoesophageal echocardiography

Background. End-diastolic volume indices determined by transpulmonarythermodilution and pulmonary artery thermodilution may givea better estimate of left ventricular preload than pulmonarycapillary wedge pressure monitoring. The aim of this study wasto compare volume preload monitoring using the two differentthermodilution techniques with left ventricular preload assessmentby transoesophageal echocardiography (TOE). Methods. Twenty patients undergoing elective cardiac surgerywith preserved left–right ventricular function were studiedafter induction of anaesthesia. Conventional haemodynamic variables,global end-diastolic volume index using the pulse contour cardiacoutput (PiCCO) system (GEDVI_PiCCO), continuous end-diastolicvolume index (CEDVI_PAC) measured by a modified pulmonary arterycatheter (PAC), left ventricular end-diastolic area index (LVEDAI)using TOE and stroke volume indices (SVI) were recorded beforeand 20 and 40 min after fluid replacement therapy. Analysisof variance (Bonferroni–Dunn), Bland–Altman analysisand linear regression were performed. Results. GEDVI_PiCCO, CEDVI_PAC, LVEDAI and SVI_PiCCO/PAC increasedsignificantly after fluid load (P<0.05). An increase >10%for GEDVI_PiCCO and LVEDAI was observed in 85% and 90% of thepatients compared with 45% for CEDVI_PAC. Mean bias (2 SD) betweenpercentage changes (     

Comparison of University of Wisconsin and University of Pittsburgh solutions for heart transplantation

The effectiveness of University of Wisconsin (UW) and University of Pittsburgh (UP) solutions for the preservation of rat hearts was compared. Lewis rat hearts were preserved with UW (group A, n=45) or UP (group B, n=45) solution for 0 or 24 h and then transplanted heterotopically into the recipients' abdomen. Ten recipients in each group were observed to obtain 1-week graft survival rates. Tissue water content and tissue content of adenine nucleotides were measured 2 h after transplantation in six grafts from each group. Six hearts preserved for 0 h and seven hearts preserved for 24 h were taken from each group 24 h after grafting for histopathology. The 1-week graft survival rates of groups A24 and B24 were 60% and 10%, respectively. In the 24-h preserved grafts, adenosine triphosphate (ATP) and energy charge [(ATP+adenosine diphosphate/2)/(ATP+adenosine diphosphate+adenosine monophosphate)] of groups A and B were 0.972±0.165 and 0.200±0.123 mg/g wet tissue (P<0.05) and 74.4% and 61.1% (P<0.05), respectively. The tissue water content of group A24 was 71.7%, whereas that of group B24 was 74.1% (P<0.05). Histopathology revealed more severe muscle edema and necrosis and infiltration of polymorphonuclear cells in group B24 than in group A24. We conclude that UW solution is more appropriate for rat heart preservation than UP solution.     

Validation of pulse contour derived stroke volume variation during modifications of cardiac afterload

Background: Left ventricular stroke volume variation (SVV) or its surrogatesare useful tools to assess fluid responsiveness in mechanicallyventilated patients. So far it is unknown, how changes in cardiacafterload affect SVV. Therefore, this study compared left ventricularSVV derived by pulse contour analysis with SVV measured usingan ultrasonic flow probe and investigated the influence of cardiacafterload on left ventricular SVV. Methods: In 13 anaesthetized, mechanically ventilated pigs [31(SD 6)kg], we compared cardiac output (CO), stroke volume (SV), andSVV determined by pulse contour analysis and by an ultrasonicaortic flow signal (Bland–Altman analysis). After obtainingbaseline measurements, cardiac afterload was increased usingphenylephrine and decreased using adenosine (both continuouslyadministered). Measurements were performed with a constant tidalvolume (12 ml kg^–1) without PEEP. Results: Neither increasing mean arterial pressure (MAP) [from 59 (7)to 116 (19)] nor decreasing MAP [from 63 (7) to 39 (4)] affectedCO, SV, and SVV (both methods). Method comparison revealed abias for SVV of 0.1% [standard error of the mean (SE) 0.8] atbaseline, –1.2% (SE 0.8) during decreased and 4.0% (SE0.7) during increased afterload, the latter being significantlydifferent from the others (P < 0.05). Thereby, pulse contouranalysis tended to underestimate SVV during decreased afterloadand to overestimate SVV during increased afterload. Limits ofagreement were approximately 6% for all points of measurement. Conclusions: Left ventricular SVV is not affected by changes in cardiac afterload.There is a good agreement of pulse contour with flow derivedSVV. The agreement decreases, if afterload is extensively augmented.     

Treatment of cardiogenic shock with levosimendan in combination with beta-adrenergic antagonists

Levosimendan, a calcium sensitizer, was used in combinationwith ß-adrenergic antagonists in a man aged 56 yrwith cardiogenic shock, complicating acute myocardial infarction,who developed severe tachycardia after dobutamine administration.The patient's trachea was intubated, his lungs were ventilated,and he was started on dopamine 5 µg kg^–1 min^–1and dobutamine 5 µg kg^–1 min^–1, titrated toa mean arterial pressure 65 mm Hg. He progressively became tachycardiac(>120 beats min^–1) with a cardiac index (CI) of 1.4litre min^–1 m^–2 despite adequate preload. Levosimendan6 µg kg^–1 was administered intravenously over 10min followed by a continuous infusion of 0.2 µg kg^–1min^–1 for 24 h. Within 30 min, the patient's CI increasedto 2.2 litre min^–1 m^–2, but the heart rate (HR)also increased from 142 to 155 beats min^–1. Esmolol 1mg kg^–1 i.v. was administered with a consequent transientdecrease in HR to 110 beats min^–1 without adverse haemodynamiceffects; however, HR increased again shortly afterwards. Carvedilol3.125 mg orally twice a day was then administered, and the dosewas increased to 6.25 mg orally twice daily on the followingday. Subsequently, HR decreased over time and both catecholamineswere discontinued 14 h after starting levosimendan infusion.The trachea was extubated within 20 h and the patient was dischargedto the ward on day 4 after admission. In conclusion, levosimendanin combination with a ß-adrenergic antagonist mayhave beneficial effects in patients with cardiogenic shock whoexhibit tachycardia in response to inotropic agents.     

Comparison of intermittent injection of nondepolarizing solution with a single flush of UW solution for donor heart preservation

Isolated canine hearts were preserved for 6 h at 5°C followed by normothermic reperfusion for 2 h. The dogs were divided into two groups of nine hearts each; group 1 received a nondepolarizing preservation solution in multidose, and group 2 received a single flush of University of Wisconsin (UW) solution. Serum MB-CK and mitochondrial aspartate aminotransferase (m-AAT) concentrations and calcium overload during reperfusion were lower in group 1 than in group 2. At the end of reperfusion, myocardial ATP and total adenine nucleotide concentrations were higher and mitochondrial morphology appeared more intact in group 1 than in group 2. Left ventricular diatolic function was preserved better in group 1 than in group 2. These results suggest that in 6-h heart preservation, a nondepolarizing solution applied in multidose fashion protects the myocardium from the deleterious effects of hypothermia and cardioplegia better than a single flush of UW solution.     

Plasmapheresis as a rescue therapy to resolve cardiac rejection with vasculitis and severe heart failure. A report of five cases

The predominant causes of late graft loss and death after cardiac transplantation are graft rejection and infection. The histopathological classification of acute rejection is based on cellular phenomena such as lymphocytic infiltration and myocyte damage. The adverse prognostic importance of vascular or humoral rejection has been reported, but there is no well-documented treatment available. In our experience, comprising 151 orthotopic transplants, five patients presented with graft rejection characterized by a lymphocytic vasculitis that did not respond to conventional therapy. Because of a deteriorating condition, in spite of vigorous antirejection treatment that included inotropic drugs and circulatory support, plasmapheresis was tried as a last, desperate means to stop the process from developing further. The clinical symptoms rapidly subsided in all five patients after the first couple of plasma exchanges. All of the patients are alive and well after 2–3.5 years of follow-up. Although the mechanism of action is unclear, plasmapheresis was beneficial in these critically ill patients.     

Toll-like receptor expression and signaling in human diabetic wounds

AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic patients with informed consent. Total RNA and protein were isolated and subjected to real-time polymerase chain reaction and Western blot analyses. RESULTS: TLR1, 2, 4, and 6 mRNA expressions were increased significantly in wounds of diabetic patients compared with non-diabetic wounds(P 0.05). MyD88 protein expression was significantly increased in diabetic wounds compared to non-diabetic wounds. Interleukin-1beta, tumor necrosis factor-alpha concentration nuclear factor-kappa B activation, and thiobarbituric acid reactive substances were increased in diabetic wounds compared to non-diabetic wounds(P 0.01). CONCLUSION: Collectively, our novel findings show that increased TLR expression, signaling, and activation may contribute to the hyper inflammation in the human diabetic wounds.     

The effect of sodium concentration on myocardial viability in donor heart preservation using a nondepolarizing solution

This study examined the effect of different sodium concentrations in a nondepolarizing solution on myocardial viability and functional recovery of the canine donor heart. Isolated canine hearts were preserved for 6 h at 5°C, followed by normothermic reperfusion for 2 h. Dogs were divided into two groups of nine dogs each: group 1 received a nondepolarizing solution with 70mm Na⁺ and group 2 with 30mm Na⁺. The myocardial Ca²⁺ concentration at the end of preservation was significantly higher in group 1 than in group 2 and increased after reperfusion in both groups without any intergroup difference. Myocardial concentrations of ATP, ADP, and total adenine nucleotide at the end of reperfusion were significantly higher in group 1 than in group 2. Myocardial cyclic adenosine monophosphate concentration was significantly higher in group 1 than in group 2 at the end of both preservation and reperfusion. The myocardial cyclic guanosine monophosphate concentration in group 1 increased and was higher than in group 2 at the end of preservation, but had returned to normal levels by the end of reperfusion. However, it remained unchanged through preservation and reperfusion in group 2. The left ventricular systolic and diastolic function, assessed by pressurevolume relationship, was better in group 1 than in group 2. Mitochondrial ultrastructural changes were similar. These results suggest that a nondepolarizing solution containing 70mm Na⁺ provides better myocardial protection than a solution containing 30mm Na⁺.     

Lidocaine reduces ischaemic but not reperfusion injury in isolated rat heart

The local anaesthetic lidocaine protects the myocardium in ischaemia–reperfusionsituations. It is not known if this is the consequence of ananti-ischaemic effect or an effect on reperfusion injury. Therefore,we investigated the effect of two concentrations of lidocaineon myocardial ischaemia–reperfusion injury and on reperfusioninjury alone. We used an isolated rat heart model where heartrate, ventricular volume and coronary flow were kept constant.Hearts underwent 45 min of low-flow ischaemia followed by 90min reperfusion. Two groups received lidocaine 1.7 or 17 µgml^–1 starting 5 min before the onset of reperfusion. Intwo additional groups, lidocaine infusion started 5 min beforelow-flow ischaemia. In all groups, lidocaine administrationwas stopped after 15 min of reperfusion. One group served asan untreated control (n=11 in each group). Left ventriculardeveloped pressure (LVDP) and total creatine kinase release(CKR) were measured. Lidocaine administration during ischaemiaand reperfusion led to an improved recovery of LVDP during reperfusion(1.7 µg ml^–1, 54 (SEM 10) mm Hg; 17 µg ml^–1,71 (9) mm Hg at 30 min of reperfusion; both significantly differentfrom control (21 (4) mm Hg) (P<0.05)) and a reduced CKR (1.7µg ml^–1, 79 (13) IU; 17 µg ml^–1, 52(8) IU at 30 min of reperfusion; both significantly differentfrom control (130 (8) IU (P<0.05)). Lidocaine given duringearly reperfusion only, affected neither LVDP during reperfusion(1.7 µg ml^–1, 19 (6) mm Hg (P=1.0); 17 µgml^–1, 36 (8) mm Hg (P=0.46)) nor CKR (156 (21) IU (P=0.50)and 106 (14) IU (P=0.57)). We conclude that lidocaine protectsthe myocardium against ischaemic but not against reperfusioninjury in the isolated rat heart. Br J Anaesth 2001; 86: 846–52