JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2004
J. H. Alexander
Summary.,Background:,Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). Objectives:,To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. Patients and methods:,Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I,III were designed to achieve concentrations of >,100 ng mL,1, >,75 ng mL,1, and >,150 ng mL,1. Stage IV used the stage III regimen but included patients recently given heparin. Results:,At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL,1 in stages I,IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL,1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. Conclusions:,Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study. [source]

Psychological Characteristics and Social Integration of Patients with Ischemic and Non-Ischemic Heart Failure Newly Listed for Heart Transplantation: The Waiting for a New Heart Study

APPLIED PSYCHOLOGY: HEALTH AND WELL-BEING, Issue 2 2009
Heike Spaderna
It is not known whether psychosocial risk factors for coronary artery disease (CAD) are present in patients listed for heart transplantation (HTx). The aim of this study was to examine whether HTx candidates with ischemic heart failure (due to CAD) have an adverse psychological risk profile and reduced social integration compared to patients with non-ischemic etiology. In the multi-site study "Waiting for a New Heart", waiting-list-related stressors, depression, anxiety, trait-anger, anger-expression, dispositional coping, social integration, and social support were assessed in 318 newly registered HTx candidates (53.5 ± 11.4 years, 18% female, left ventricular ejection fraction <25%). Medical parameters at time of listing were provided by Eurotransplant. Analyses revealed a high level of stress (on average 70% of 50 HTx-related stressors), and signs of clinical depression in 39 per cent of the sample. Social integration was correlated with reduced depression (p < .05). While ischemic and non-ischemic groups were comparable in terms of disease severity, men with CAD reported significantly more anxiety, anger, anger-in, and less social integration than non-ischemic men after adjusting for age and marital status (ps < .05). To conclude, psychosocial stress is common in HTx candidates, particularly in men with underlying CAD. Thus, targeting psychosocial stress and increasing social integration may enhance well-being in patients waiting for a new heart. [source]

Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003
Anna Maria Pugliese
Ischemic preconditioning in the brain consists of reducing the sensitivity of neuronal tissue to further, more severe, ischemic insults. We recorded field epsps (fepsps) extracellularly from hippocampal slices to develop a model of in vitro ischemic preconditioning and to evaluate the role of A1, A2A and A3 adenosine receptors in this phenomenon. The application of an ischemic insult, obtained by glucose and oxygen deprivation for 7 min, produced an irreversible depression of synaptic transmission. Ischemic preconditioning was induced by four ischemic insults (2 min each) separated by 13 min of normoxic conditions. After 30 min, an ischemic insult of 7 min was applied. This protocol substantially protected the tissue from the irreversible depression of synaptic activity. The selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), completely prevented the protective effect of preconditioning. The selective adenosine A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3- a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 100 nM) did not modify the magnitude of fepsp recovery compared to control slices. The selective A3 adenosine receptor antagonists, 3-propyl-6-ethyl-5[ethyl(thio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523, 100 nM) significantly improved the recovery of fepsps after 7 min of ischemia. Our results show that in vitro ischemic preconditioning allows CA1 hippocampal neurons to become resistant to prolonged exposure to ischemia. Adenosine, by stimulating A1 receptors, plays a crucial role in eliciting the cell mechanisms underlying preconditioning; A2A receptors are not involved in this phenomenon, whereas A3 receptor activation is harmful to ischemic preconditioning. British Journal of Pharmacology (2003) 140, 305,314. doi:10.1038/sj.bjp.0705442 [source]

Carvedilol Produces Sustained Long-Term Benefits: Follow-Up at 12 Years

CONGESTIVE HEART FAILURE, Issue 1 2009
John F. MacGregor MD
The authors measured long-term outcomes of patients who initiated carvedilol between 1990 and 1992 to test the hypothesis that carvedilol produces sustained benefits in heart failure patients. The study population consisted of 57 patients who completed a carvedilol placebo-controlled phase II trial. Patients were given open-label carvedilol and were titrated to the maximum dose. Patients were assessed by serial multigated acquisition, echocardiography, and symptom scores. Survival was assessed for all patients and censored as of January 1, 2004. Survival for ischemic vs nonischemic patients was compared using the log-rank test and further compared using Cox regression, controlling for covariates. Etiology of heart failure was ischemic in 15 patients and nonischemic in 42 patients. Median follow-up was 12.9 years. Resting left ventricular ejection fraction (LVEF) and heart failure symptom scores improved at 4 months of treatment and were sustained at 24 months. Left ventricular internal diameter in systole (LVIDS) and left ventricular internal diameter in diastole decreased significantly at 4 and 8 months, respectively, and LVIDS continued to improve at 24 months. Overall mortality was 43% in nonischemic patients and 73% in ischemic patients. In a multivariate analysis, ischemic etiology and baseline LVEF were significant predictors of mortality. Carvedilol produces sustained improvements in left ventricular remodeling and symptoms. Long-term survival is good, particularly in nonischemic patients. [source]

Up-and-Coming Markers: Myeloperoxidase, a Novel Biomarker Test for Heart Failure and Acute Coronary Syndrome Application?

CONGESTIVE HEART FAILURE, Issue 2008
Christoph Sinning MD
Myeloperoxidase (MPO) is a mammalian enzyme responsible for generation of hypochlorite. The advantage of myeloperoxidase for use as a biomarker in the setting of heart failure and acute coronary syndrome is the early increase of MPO concentration in response to the acute event. In the setting of heart failure the reported independency of coronary artery disease and general inflammation, as indicated by MPO concentration in comparison to other inflammatory markers or in subgroups of patients with ischemic and non-ischemic cardiomyopathy, has to be highlighted. In terms of ACS, inclusion of MPO into a multiple marker strategy might add to enhance diagnosis and therapy decision making. Therefore, MPO is a biomarker worthwhile of further evaluation in the setting of cardiovascular disease. Congest Heart Fail. 2008;14(4 suppl 1):46,48. ©2008 Le Jacq [source]

Myocardial Perfusion As Assessed by Positron Emission Tomography During Long-Term Mechanical Circulatory Support

CONGESTIVE HEART FAILURE, Issue 2 2006
George V. Letsou MD
Although mechanical circulatory support (MCS) can improve myocardial function in patients with advanced heart failure, its effects on relative myocardial perfusion are unclear. Using positron emission tomographic imaging techniques, the authors assessed relative myocardial perfusion in patients with ischemic or idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular assist device (pulsatile HeartMate [n=2] [Thoratec Corporation, Pleasanton, CA] or nonpulsatile Jarvik 2000 [n=4] [Jarvik Heart, Inc., New York, NY]). Relative myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100,110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000). The size and severity of perfusion defects at rest and after dipyridamole stress were measured objectively and subjectively by computer algorithms and visual inspection, respectively. Relative myocardial perfusion increased >5% from baseline in only one of six patients when MCS was increased. No change in relative myocardial perfusion of >5% was seen in any of the other five patients, even after subsequent dipyridamole stress positron emission tomographic imaging. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium. [source]

Thaliporphine protects ischemic and ischemic-reperfused rat hearts via an NO-dependent mechanism

DRUG DEVELOPMENT RESEARCH, Issue 3 2001
Li-Man Hung
Abstract In ischemia or ischemia-reperfusion (I/R), nitric oxide (NO) can potentially exert several beneficial effects. Thaliporphine, a natural alkaloid with Ca2+ channel-activating and Na+/K+ channel-blocking activities, increased NO levels and exerted cardioprotective action in ischemic or I/R rats. The role of NO in the cardioprotective actions of thaliporphine was assessed. The severity of rhythm disturbances and mortality in anesthetized rats with either coronary artery occlusion for 30 min, or 5 min followed by 30-min reperfusion, were monitored and compared in thaliporphine- vs. placebo-treated groups. Thaliporphine treatment significantly increased NO and decreased lactate dehydrogenase (LDH) levels in the blood during the end period of ischemia or I/R. These changes in NO and LDH levels by thaliporphine were associated with a reduction in the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during ischemic or I/R period. The mortality of animals was also completely prevented by 1 × 10,8 moles/kg of thaliporphine. In animals subjected to 4 h of left coronary artery occlusion, 1 × 10,7 moles/kg of thaliporphine dramatic reduced cardiac infarct zone from 46 ± 6% to 7.1 ± 1.9%. Inhibition of NO synthesis with 3.7 × 10,6 moles/kg of N, -nitro-L-arginine methyl ester (L-NAME) abolished the beneficial effects of thaliporphine during 30 min or 4 h myocardial ischemia. However, the antiarrhythmic activity and mortality reduction efficacy of thaliporphine during reperfusion after 5 min of ischemia was only partially antagonized by L-NAME. These results showed that thaliporphine efficiently exerted the cardioprotections either in acute or prolonged coronary artery occlusion or occlusion-reperfusion situations. The fact that thaliporphine induced cardioprotective effects were abrogated by L-NAME indicates that NO is an important mediator for the cardioprotective effects of thaliporphine in acute or prolonged ischemia, whereas antioxidant activities may contribute to the protection of I/R injury. Drug Dev. Res. 52:446,453, 2001. © 2001 Wiley-Liss, Inc. [source]

Differences in Echocardiographic Assessment with Standard Doppler and Tissue Doppler Imaging of Left Ventricular Filling Pressure in Idiopathic and Ischemic Dilated Cardiomyopathy

ECHOCARDIOGRAPHY, Issue 7 2008
Pierluigi Costanzo M.D.
Background: In idiopathic and ischemic dilated cardiomyopathy (DCM) there are differences in left atrial and ventricular relaxation. We assessed the hypothesis of an influence of these dissimilarities in assessing left ventricular filling pressure (LVFP) in these two DCMs by standard Doppler and tissue Doppler imaging. In particular, we focused on early transmitral flow to early diastolic motion velocity of mitral annulus ratio (E/Ea), useful to estimate normal or elevated LVFP. However, when found in intermediate range (8,15), its role is unclear. Methods and Results: We evaluated 26 patients with ischemic and 21 patients with idiopathic DCM. To validate the echocardiographic estimation of LVFP, a sample (12 patients) underwent LVFP assessment by catheterization. In idiopathic DCM, E/Ea directly related to duration of retrograde pulmonary venous flow (ARd) (r = 0.66 P = 0001). In ischemic DCM E/Ea inversely related only to systolic to diastolic velocity ratio of pulmonary venous flow (S/D) (r =,0.56 P = 0002). After a mean follow up of 6 months, by a second echocardiogram we observed a direct relation between E/Ea and ARd percentage variation (r = 0.52 P = 0.02) in idiopathic DCM group, whereas in the ischemic DCM group there was an inverse relation between E/Ea and S/D percentage variation (r =,0.59 P = 0.02).Conclusions: In conclusion, ARd in idiopathic and S/D in ischemic DCM might be used as specific additional information to estimate LVFP when E/Ea falls within intermediate range. [source]

Local Dysfunction and Asymmetrical Deformation of Mitral Annular Geometry in Ischemic Mitral Regurgitation: A Novel Computerized 3D Echocardiographic Analysis

ECHOCARDIOGRAPHY, Issue 4 2008
Masao Daimon M.D.
Objective: Most studies of the pathogenesis of functional mitral regurgitation (MR) have focused on alterations in ventricular function and geometry. We used a novel 3D echocardiographic method to assess abnormalities in mitral annular (MA) geometry and motion in patients with ischemic MR (IMR) and compared these data to those obtained from normal subjects and from patients with MR caused by dilated cardiomyopathy (DMR). Methods: Real time 3D echo was performed in 12 normal subjects, 25 with IMR, and 14 with DMR. Eight points along the saddle-shaped MA were identified using our software at systole and diastole. From these eight points, four annular diameters at each cardiac phase were determined. Annular motion was assessed by measuring local displacement (LD) of a given point between systole and diastole. Results: Annular motion was different between groups: IMR had smaller LD in posterior MA segments than did normals (2.6 ± 1.1 vs 4.8 ± 1.9 mm, P < 0.01), while DMR had globally reduced LD. In IMR systolic MA dilatation was striking in the anterior,posterior (diameter; IMR vs controls, 28.3 ± 3.5 vs 22.5 ± 2.2 mm, P< 0.05) and anterolateral,posteromedial (31.7 ± 3.5 vs 25.1 ± 2.2 mm, P < 0.05) directions; in IMR, systolic MA diameters in these two directions correlated with MR severity(P = 0.02). MA dilatation occurred globally in DMR. Conclusion: This novel 3D echo method demonstrated that MA motion and dilatation were asymmetric in IMR and symmetric in DMR. These differences in MA geometry and motion may aid in the development of distinct new therapies for IMR and DMR. [source]

Proximal Coronary Hemodynamic Changes Evaluated by Intracardiac Echocardiography during Myocardial Ischemia and Reperfusion in a Canine Model

ECHOCARDIOGRAPHY, Issue 3 2008
Beibei Han M.D.
Background: The purpose of this study was to assess whether the dynamic changes in coronary flow velocity and coronary flow velocity reserve (CFVR) by intracardiac echocardiography (ICE) within proximal coronary arteries are related to myocardial perfusion status and infarct size in a myocardial ischemia-reperfusion injury model. Methods: In 14 dogs, left anterior descending coronary artery (LAD) was ligated for 2 hours followed by 2 hours reperfusion. Coronary flow velocity was obtained by ICE within coronary arteries at baseline, and at the end of both occlusion and reperfusion period. The CFVR was calculated as the ratio of hyperemic to resting peak diastolic velocity (PDV). Myocardial perfusion was evaluated by real time myocardial contrast echocardiography (MCE). The infarct area was detected by triphenyltetrazolium chloride (TTC) staining and expressed as the percentage of the whole left ventricular (LV) area. Results: CFVR significantly decreased both in proximal LAD and left circumflex (LCx) artery at the end of occlusion, and did not recover at the end of reperfusion. However, no significant difference in flow parameters was observed between dogs with myocardial perfusion defect and those without. CFVR in LAD at the end of reperfusion did not correlate with the infarct size (r =,0.182, P = NS) either. Conclusions: Decreased CFVR detected by ICE occurs both in ischemic and in nonischemic proximal arteries during myocardial ischemia and early stage of reperfusion. This change in CFVR has poor correlation with the extent of microvascular impairment and cannot be used to predict infarct size. [source]

Role of Echocardiography in Assessing the Mechanism and Effect of Ramipril on Functional Mitral Regurgitation in Dilated Cardiomyopathy

ECHOCARDIOGRAPHY, Issue 4 2005
D.M. (Card), F.I.A.E., F.I.A.M.S., F.I.C.C., F.I.C.P., I.B. Vijayalakshmi M.D.
The objectives of this article are to determine the possible mechanism of functional mitral regurgitation in patients with dilated cardiomyopathy (DCM) and to know the effect of ramipril on left ventricle (LV) and mitral regurgitation by ECHO. Several postulates are put forth for functional mitral regurgitation in DCM, and mitral annular dilatation is said to be the primary mechanism in the past, but the exact mechanism is not clear. Though angiotensin converting enzyme (ACE) inhibitors are known to remodel the LV, their beneficial effect in patients with DCM with functional mitral regurgitation is not known. Various cardiac dimensions and degree of mitral regurgitation were measured by echocardiography in 30 normal control group and in 30 patients with DCM of various etiologies except ischemic, before and after ramipril therapy. There was a significant difference in all parameters especially sphericity of left ventricle and position of papillary muscles (P < 0.0003) in DCM patients, but mitral valve annulus did not show significant change (P < 0.3) compared to control group. In 50% of the patients, the functional mitral regurgitation totally disappeared. In 30% of patients, it came down from grade II to I or became trivial. In 20% of patients, it remained unchanged. There was remarkable improvement in sphericity, LV dimension, volumes, and EF%, which increased from 31 ± 9.81 to 39.3 ± 8.3% (P < 0.0003). It is concluded that echocardiography clearly demonstrates the increased sphericity of LV in DCM. The lateral migration of papillary muscles possibly plays a major role in functional mitral regurgitation. Ramipril significantly reduces not only sphericity but also functional mitral regurgitation. [source]

3 ISCHEMIC MITRAL VALVE REPAIR: THE IMPACT OF THE MECHANISM OF MITRAL REGURGITATION ON LATE POSTOPERATIVE RESULTS

ECHOCARDIOGRAPHY, Issue 1 2004
E. Ereminien
Aim: The aim of our study was to establish the anatomical-functional mechanisms of ischemic mitral regurgitation (MR) and to analyse its impact on late results after mitral valve (MV) reconstructive surgery. Methods: The study included 53 patients with ischemic MR, who underwent CABG and MV repair. MV surgery consisted of subvalvular apparatus repair and/or annuloplasty. 2D Doppler investigations performed pre-, 10,14 days, and 12 months after surgery included evaluation of MV and left ventricular (LV) geometry and function. Results: Analysis of the mechanisms of ischemic MR permitted dividing patients into two groups: group 1,29 patients with inferobasal scar and posterior papillary muscle (PM) displacement, including 22 patients with PM infarction and 7 patients without it, and group 2,24 patients with isolated mitral annulus (MA) dilation. In the case of PM infarction two different mechanisms of MR were stated: (a) P3 restriction and A3 prolapse due to chordal tethering, (b) A3 P3 (commissural) prolapse due to chordal papillary elongation. Preoperatively LV geometry and function were better preserved in group 1 and late MV repair results were better versus (vs.) group 2: LV end-systolic diameter index decreased from 22.9 ± 3.1 mm/m2 to 20.9 ± 3.6 mm/m2 at 1 year, p < 0.05, LV ejection fraction increased from 34.9 ± 8.4 to 41.8 ± 8.1%, respectively, p < 0.05. No significant changes in LV geometry and function were noted in group 2. Conclusions: The underlying mechanism of ischemic MR has an impact on MV repair results. In patients with MR due to posterobasal infarction MV repair resulted in more favorable postoperative effect-marked improvement in LV geometry and function late after surgery versus MR due to isolated MA dilation. [source]

Time-sensitive enhancement of motor learning with the less-affected forelimb after unilateral sensorimotor cortex lesions in rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2005
J. Edward Hsu
Abstract Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) results in time-dependent changes in neuronal activity, structure and connectivity in the contralateral motor cortex of adult rats. These changes have been linked to facilitation of motor skill learning in the less-affected/ipsilesional forelimb, which is likely to promote its use in the development of behavioral compensation. The goal of this study was to determine whether an early post-lesion-sensitive time period exists for this enhanced learning and whether it is linked to synaptogenesis in the contralesional motor cortex. Rats were trained for 21 days on a skilled reaching task with the ipsilesional forelimb beginning 4 or 25 days after unilateral ischemic (endothelin-1-induced) FLsmc lesions or sham operations. As found previously, reaching performance was significantly enhanced in rats trained early post-lesion compared with sham-operates. In rats trained later post-lesion, performance was neither significantly different from time-matched sham-operates nor strikingly different from animals trained earlier post-lesion. In layer V of the contralesional motor cortex, stereological methods for light and electron microscopy revealed significantly more total, multisynaptic bouton and perforated synapses per neuron compared with sham-operates, but there were no significant differences between early- and late-trained lesion groups. Thus, there appears to be a sensitive time window for the maximal expression of the enhanced learning capacity of the less-affected forelimb but this window is broadly, rather than sharply, defined. These results indicate that relatively long-lasting lesion-induced neuronal changes are likely to underlie the facilitation of learning with the less-affected forelimb. [source]

Does rat global transient cerebral ischemia serve as an appropriate model to study emotional disturbances?

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004
Guy Bernard Bantsiele
Abstract We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (imipramine) and anti-anxiety drugs (diazepam). Twelve days after surgery to provoke transient global ischemia, spontaneous motor activity was 40% higher in ischemic rats than in sham-operated controls. Duration of immobility during the FST 20 min and 5 min was 28 and 30% shorter, respectively, than in controls. Treatment with imipramine (3 × 30 mg/kg i.p.) induced a significantly shorter duration of immobility during the FST 5 min, but with no difference between ischemia and control rats. The EPM demonstrated that ischemia did not induce any change in the six behavior parameters measured. Diazepam (1.5 mg/kg i.p.) induced significant anxiolytic effects which were similar in ischemic and sham-operated animals. Both tests failed to demonstrate perturbed performance but conversely, these findings did disclose the sensitivity of ischemia-exposed rats to the action of imipramine and diazepam, demonstrating the usefulness of these tests as psychopharmocological tools for evaluating the effect of psychotropics in the ischemic rat. [source]

Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusion

HEPATOLOGY, Issue 3 2004
Anna Serafín
The present study evaluates the effect of ischemic preconditioning on interleukin-1 (IL-1) and interleukin-10 (IL-10) generation following hepatic ischemia/reperfusion (I/R) in normal and steatotic livers as well as the role of nitric oxide (NO) in this process. Increased IL-1, and IL-10 levels were observed in normal livers after I/R. Steatotic livers showed higher IL-1, levels than normal livers, and IL-10 at control levels. The injurious role of IL-1, and the benefits of IL-10 on hepatic I/R injury was shown with the use of IL-1 receptor antagonist (IL-1ra), anti-IL-10 polyclonal antibody against IL-10 (anti-IL-10) and exogenous IL-10. The effective dose of these treatments was different in both types of livers. Preconditioning prevented IL-1, release and increased IL-10 generation after I/R in normal and steatotic livers. IL-1, or anti-IL-10 pretreatments reversed the benefits of preconditioning. IL-1, action inhibition in a preconditioned group that was pretreated with anti-IL-10 did not modify the benefits of preconditioning. In addition, anti-IL-10 pretreatment in the preconditioned group resulted in IL-1, levels comparable to those observed after I/R. NO inhibition eliminated the benefits of preconditioning on IL-10 release, IL-1, levels, and hepatic injury. In conclusion, preconditioning, through IL-10 overproduction, inhibits IL-1, release and the ensuing hepatic I/R injury in normal and steatotic livers. IL-10 generation induced by preconditioning could be mediated by NO. (HEPATOLOGY 2004;39:688,698.) [source]

Low-dose TNF-, protects against hepatic ischemia-reperfusion injury in mice: Implications for preconditioning

HEPATOLOGY, Issue 1 2003
Narci Teoh
Tumor necrosis factor , (TNF-,) is implicated in the pathogenesis of hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR) liver injury and is associated with activation of nuclear factor ,B (NF-,B) and cell cycle entry. We examined the pattern of TNF-, release during hepatic IR in the presence or absence of ischemic preconditioning, and we tested whether a single low-dose injection of TNF could mimic the biologic effects of ischemic preconditioning. In naïve mice, hepatic and plasma levels of TNF-, rose during hepatic ischemia, reaching high levels after 90 minutes; values remained elevated during reperfusion until 44 hours. Following the ischemic preconditioning stimulus, there was an early rise in hepatic and serum TNF-, levels, but, during a second prolonged ischemic interval peak, TNF-, values were lower than in naïve mice and declined to negligible levels by 2 hours reperfusion. An injection with 1 ,g or 5 ,g/kg body weight TNF-, 30 minutes prior to hepatic IR substantially reduced liver injury determined by liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic preconditioning, TNF-, pretreatment activated NF-,B DNA binding, STAT3, cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry, determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be simulated by TNF-, injection, which has identical downstream effects on cell cycle entry. We propose that transient increases in TNF-, levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury. [source]

Remifentanil post-conditioning attenuates cardiac ischemia,reperfusion injury via , or , opioid receptor activation

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010
G. T. C. WONG
Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective , opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia,reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 ,g/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific ,, , and , opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose,response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia,reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves , and , but not , opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. [source]

Searching for Neuroglobin's role in the brain

IUBMB LIFE, Issue 8-9 2007
Karin Nienhaus
Abstract Neuroglobin is a small globin that plays an important role in the protection of brain neurons from ischemic and hypoxic injuries. The molecular mechanisms by which Ngb performs its physiological function are still under debate. Suggestions include oxygen storage and delivery, scavenging of NO and/or reactive oxygen species, oxygen sensing and signal transduction. In recent years, the molecular structures of Ngb with carbon monoxide bound to the heme iron and without an exogenous ligand have been solved, and interesting structural changes have been noticed upon ligand binding. Moreover, equilibrium and kinetic properties of the reactions with ligands have been examined in great detail. Here we summarize the molecular properties of Ngb and discuss them in relation to the potential physiological functions. [source]

Vascular Dementia: Distinguishing Characteristics, Treatment, and Prevention

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5s2 2003
Gustavo C. Román MD
Vascular dementia (VaD) is the second-most-common cause of dementia in the elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the following criteria: cognitive loss, often predominantly subcortical; vascular brain lesions demonstrated by imaging; a temporal link between stroke and dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused by large-vessel disease with multiple strokes (multiinfarct dementia) or by a single stroke (strategic stroke VaD). A common form is subcortical ischemic VaD caused by small-vessel occlusions with multiple lacunas and by hypoperfusive lesions resulting from stenosis of medullary arterioles, as in Binswanger's disease. Unlike with AD, in VaD, executive dysfunction is commonly seen, but memory impairment is mild or may not even be present. The cholinesterase inhibitors used for AD are also useful in VaD. Prevention strategies should focus on reduction of stroke and cardiovascular disease, with attention to control of risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and hyperhomocysteinemia. [source]

Levosimendan cardioprotection in acutely ,-1 adrenergic receptor blocked open chest pigs

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2010
C. METZSCH
Background: Levosimendan and volatile anesthetics have myocardial pre-conditioning effects. ,-1 adrenergic receptor antagonists may inhibit the protective effect of volatile anesthetics. No information exists as to whether this also applies to the pre-conditioning effect of levosimendan. We therefore investigated whether levosimendan added to metoprolol would demonstrate a cardioprotective effect. Methods: Three groups of anesthetized open chest pigs underwent 30 min of myocardial ischemia and 90 min of reperfusion by temporary occlusion of the largest side branch from the circumflex artery or the left anterior descending artery. One group (CTRL) served as a control, in another group (BETA), a metoprolol-loading dose was intravenously injected 30 min before ischemia, and in a third group (BETA+L), a levosimendan infusion was added to metoprolol. Myocardial tissue concentrations of glucose, glycerol, and lactate/pyruvate ratio as the primary end-points were investigated with microdialysis in ischemic and non-ischemic tissues. Results: At the end of the ischemic period, statistically significant differences were only found between CTRL and BETA+L in the ischemic myocardium, with a lower lactate/pyruvate ratio, lower glycerol, and higher glucose concentrations in BETA+L as compared with CTRL. There were no differences in non-ischemic myocardium. From 10 to 90 min of reperfusion, no more differences were found between groups. Conclusion: The cardioprotective effect of levosimendan on ischemic metabolism with a reduction in the myocardial lactate/pyruvate ratio, less glycerol accumulation, and better preserved glucose concentration does not seem to be prevented by ,-1 adrenergic receptor antagonism with metoprolol. [source]

Chordal Cutting VIA Aortotomy in Ischemic Mitral Regurgitation: Surgical and Echocardiographic Study

JOURNAL OF CARDIAC SURGERY, Issue 1 2008
Georges Fayad M.D.
In addition, MR may exacerbate during exercise not only trough exercise-induced ischemia but also through an increase in tenting area. Accordingly, we aimed to perform chordal cutting through aortotomy in patients with exercise-induced ischemic worsening of MR. Methods: Five patients with ischemic MR, due to anterior leaflet tenting, whichworsened during exercise echocardiography were enrolled. All patients underwent cutting of the 2 basal chordae attached to the anterior mitral leaflet associated with myocardial revascularization. Three patients had additional mitral valve annuloplasty. Postoperative MR was evaluated using exercise echocardiography. Results: Age ranged from 63 to 78 years and 4 patients were male. Preoperative LV ejection fraction averaged 39 ± 3%. Chordal cutting was performed through aortotomy allowing comfortable access to the anterior mitral valve. Mitral effective regurgitant orifice at rest and at peak exercise was reduced by surgery (10 ± 3 to 0.6 ± 0.5 mm2 at rest and from 20 ± 3 to 6 ± 2 mm2 at peak exercise; p = 0.03). Mitral tenting area at rest and at peak exercise was concomitantly reduced by surgery (1.83 ± 0.21 cm2 to 0.50 ± 0.4 cm2 at rest and from 3.11 ± 0.58 to 1.7 ± 0.5 cm2 at peak exercise; p = 0.03). Left ventricular size and function remained unchanged after surgery. Conclusions: Chordal cutting through aortotomy may be an effective option to treat ischemic MR due to anterior leaflet tenting. Associated with myocardial revascularization, it resulted in a decrease of MR at rest and during exercise through a decrease in tenting area without impairment of LV function. [source]

Long-Term Results of Cardiac Transplantation

JOURNAL OF CARDIAC SURGERY, Issue 3 2003
Alberto Juffe M.D.
From April 1991 to December 2000, 345 patients underwent heart transplantation at the Juan Canalejo Hospital. The mean age of recipients was54.5 ± 11.4 years; 286 (83%) were male patients. Idiopathic (52.2%) and ischemic (34.9%) end-stage cardiomyopathy were the main causes leading to transplantation. Ninety-four patients had undergone a previous heart operation. The mean left ventricular ejection fraction was22.8 ± 11.4. Forty patients (11.5%) were transplanted in urgent (status I) condition. The mean time spent on the waiting list was 35.9 days. In-hospital mortality was 10.6% and 24% for transplantations performed on an elective and urgent basis, respectively. Operative (30-day), one-year and six-year survival was 87.2%, 81.3% and 64%, respectively. In terms of actuarial survival, there were no significant differences with regard to the recipient's age, sex, previous cardiac surgery, and the etiology of the end-stage cardiomyopathy. The six-year actuarial survival for recipients receiving hearts from female donors was 59% compared with 72% for male donors(p = 0.05). There has been a low incidence of rejection, as well as cardiac graft vasculopathy. Actuarial survival at six years was 66% for patients transplantated on an elective basis compared with 57% for patients transplanted on an urgent basis(p = 0.04). The aim of the study was to evaluate long-term results for patients who underwent orthotopic heart transplantation. In our experience, status I is associated with a higher mortality.(J Card Surg 2003;18:183-189) [source]

Early and Late Results of Partial Left Ventriculectomy: Single Center Experience and Review of the Literature

JOURNAL OF CARDIAC SURGERY, Issue 3 2003
Raimondo Ascione M.D.
Methods: From February 1996 to August 2001, 24 patients with dilated cardiomyopathy (DCM) (12 idiopathic, 12 ischemic) underwent PLV. Perioperative and follow-up data were prospectively entered into a database and analyzed. An observational analysis of the literature was carried out of all the published series of PLV reporting on ,15 patients. Results: In our series there were 22 males with amean age of 65 years (range 49 to73]). Of the 22, there were 3 (12.5%) in-hospital deaths. Mean duration of follow-up was 26 months (range 3 to 71) with 9 late deaths (38%), 6 in the idiopathic group. The five-year actuarial survival was 74% in the ischemic group and 33% in the idiopathic group. The observational analysis of literature included a total of 506 patients (425 males, age 50.2 ± 5.2 years)]. The etiology was idiopathic in 255 (50.4%), and ischemic in 89 (17.6%) patients. Baseline characteristics of the whole population include: ejection fraction 18.9 ± 3.9%, NYHA functional class 3.7 ± 0.2, and LVEDD of 7.7 ± 0.4 cm. Severe mitral regurgitation was present in 368 (72.7%) patients. There were 88 (17.4%) in-hospital deaths. Cause of death included 55 due to (62.5%) low cardiac output, 10 (11.3%) due to severe bleeding, 7 (7.95%) caused by malignant arrhythmias, 8 (9%) due to sepsis, and 5 (5.7%) as a result of stroke. Ten of the selected series (overall 386 patients) reported late outcome. There were 89 (22.9%) late deaths, 12 (13.5%) were not cardiac-related, 50 (56.2%) were due to recurrence of congestive heart failure (CHF), 20 (22.5%) caused by sudden arrhythmias, 5 (5.6%) due to infections, and 2 (2.2%) from strokes. Overall, there were 248 (64.2%) survivors, of whom 179 (72.17%) were reported to be in NYHA functional class I or II. All 10 papers reported one-year survival ranging from 50% to 85%. Seven reported a two-year survival of 45% to 72%, and 4 reported a three-year survival of 33% to 64%. Conclusions: Our results and the review of the literature seem to suggest a relatively high early mortality with satisfactory late results of PLV in patients with dilated cardiomyopathy.(J Card Surg 2003;18:190-196) [source]

Incidence and Predictors of Periprocedural Cerebrovascular Accident in Patients Undergoing Catheter Ablation of Atrial Fibrillation

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2009
DANIEL SCHERR M.D.
Background: Cerebrovascular accident (CVA) is a serious complication of catheter ablation of atrial fibrillation (AF). The incidence and clinical predictors of periprocedural CVA in patients undergoing AF ablation are not fully understood. Methods: This study included 721 cases (age 57 ± 11 years; 23% female; 345 persistent AF) in 579 consecutive patients referred for AF ablation. Periprocedural CVA was defined as onset of a new neurologic deficit that occurred anytime between the start of the procedure and 30 days after the AF ablation, and was confirmed by a neurologist. Cranial imaging with CT and/or MRI was performed in each case. Patients were anticoagulated with warfarin for at least 4 weeks pre- and immediately postprocedure and were bridged with enoxaparin. Transesophageal echocardiography was performed within 24 hours prior to ablation in all cases. Results: Periprocedural CVA occurred in 10 of 721 cases (1.4%). The risk of periprocedural CVA did not vary significantly during the course of the study. Among these 10 patients (age 62 ± 11 years; 1 female; 5 persistent AF), 6 manifested neurological deficits within 24 hours, 3 after 24,48 hours, and 1 patient had a CVA 6 days following AF ablation despite a therapeutic INR level. All CVAs were ischemic. Five patients had residual deficits after 30 days. Four of 43 patients (9.3%) with a prior history of CVA had periprocedural CVA. Periprocedural CVA occurred in 0.3%, 1.0%, and 4.7% of patients with CHADS2 scores of 0, 1, and , 2 (P < 0.001). In 2 separate multivariate analyses, a CHADS2 score , 2 (OR 7.1, P = 0.02) and history of CVA (OR 9.5, P < 0.01) remained independent predictors of periprocedural CVA. Conclusions: Despite periprocedural anticoagulation and transesophageal echocardiography, we found a 1.4% incidence of periprocedural CVA in AF ablation patients. A CHADS2 score , 2 and a history of CVA are independent predictors of CVA after AF ablation. The CVA risk is low in patients with CHADS2 score of 0. [source]

Obesity As a Risk Factor for Sustained Ventricular Tachyarrhythmias in MADIT II Patients

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2007
GRZEGORZ PIETRASIK M.D.
Background: Obesity, as defined by body mass index ,30 kg/m2, has been shown to be a risk factor for cardiovascular disease. However, data on the relationship between body mass index (BMI) and the risk of ventricular arrhythmias and sudden cardiac death are limited. The aim of this study was to evaluate the risk of ventricular tachyarrhythmias and sudden death by BMI in patients after myocardial infarction with severe left ventricular dysfunction. Methods: The risk of appropriate defibrillator therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) by BMI status was analyzed in 476 nondiabetic patients with left ventricular dysfunction who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT II). Results: Mean BMI was 27 ± 5 kg/m2. Obese patients comprised 25% of the study population. After 2 years of follow-up, the cumulative rates of appropriate ICD therapy for VT/VF were 39% in obese and 24% in nonobese patients, respectively (P = 0.014). In multivariate analysis, there was a significant 64% increase in the risk for appropriate ICD therapy among obese patients as compared with nonobese patients, which was attributed mainly to an 86% increase in the risk of appropriate ICD shocks (P = 0.006). Consistent with these results, the risk of the combined endpoint of appropriate VT/VF therapy or sudden cardiac death (SCD) was also significantly increased among obese patients (Hazard Ratio 1.59; P = 0.01). Conclusions: Our findings suggest that in nondiabetic patients with ischemic left ventricular dysfunction, a BMI ,30 kg/m2 is an independent risk factor for ventricular tachyarrhythmias. [source]

Clustering of Ventricular Tachyarrhythmias in Heart Failure Patients Implanted with a Biventricular Cardioverter Defibrillator

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2006
MAURIZIO LUNATI M.D.
Background: Temporal patterns of ventricular tachyarrhythmia (VT/VF) have been studied only in patients who have received implantable cardioverter defibrillators (ICD) for secondary prevention of sudden death, and mainly in ischemic patients. The aim of this study was to evaluate VT/VF recurrence patterns in heart failure (HF) patients with biventricular ICD and to stratify results according to HF etiology and ICD indication. Methods and Results: We studied 421 patients (91% male, 66 ± 9 years). HF etiology was ischemic in 292 patients and nonischemic in 129. ICD indication was for primary prevention in 227 patients and secondary prevention in 194. Baseline left ventricular ejection fraction (LVEF) was 26 ± 7%, QRS duration 168 ± 32 msec, and NYHA class 2.9 ± 0.6. In a follow-up of 19 ± 11 months, 1,838 VT/VF in 110 patients were appropriately detected. In 59 patients who had ,4 episodes, we tried to determine whether VT/VF occurred randomly or rather tended to cluster by fitting the frequency distribution of tachycardia interdetection intervals with exponential functions: VT/VF clusters were observed in 46 patients (78% of the subgroup of patients with ,4 episodes and 11% of the overall population). On multivariate logistic analysis, VT/VF clusters were significantly (P < 0.01) associated with ICD indication for secondary prevention (odds ratio [OR]= 3.12; confidence interval [CI]= 1.56,6.92), nonischemic HF etiology (OR = 4.34; CI = 2.02,9.32), monomorphic VT (OR = 4.96; CI = 2.28,10.8), and LVEF < 25% (OR = 3.34; CI = 1.54,7.23). Cardiovascular hospitalizations and deaths occurred more frequently in cluster (21/46 [46%]) than in noncluster patients (63/375 (17%), P < 0.0001). Conclusions: In HF patients with biventricular ICDs, VT/VF clusters may be regarded as the epiphenomenon of HF deterioration or as a marker of suboptimal response to cardiac resynchronization therapy. [source]

Cigarette Smoking and the Risk of Supraventricular and Ventricular Tachyarrhythmias in High-Risk Cardiac Patients with Implantable Cardioverter Defibrillators

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2006
ILAN GOLDENBERG M.D.
Introduction: Nicotine elevates serum catecholamine concentration and is therefore potentially arrhythmogenic. However, the effect of cigarette smoking on arrhythmic risk in coronary heart disease patients is not well established. Methods and Results: The risk of appropriate and inappropriate defibrillator therapy by smoking status was analyzed in 717 patients who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II. Compared with patients who had quit smoking before study entry (past smokers) and patients who had never smoked (never smokers), patients who continued smoking (current smokers) were significantly younger and generally had more favorable baseline clinical characteristics. Despite this, the adjusted hazard ratio (HR) for appropriate ICD therapy for fast ventricular tachycardia (at heart rates ,180 b.p.m) or ventricular fibrillation was highest among current smokers (HR = 2.11 [95% CI 1.11,3.99]) and intermediate among past smokers (HR = 1.57 [95% CI 0.95,2.58]), as compared with never smokers (P for trend = 0.02). Current smokers also exhibited a higher risk of inappropriate ICD shocks (HR = 2.93 [95% CI 1.30,6.63]) than past (HR = 1.91 [95% CI 0.97,3.77]) and never smokers (P for trend = 0.008). Conclusions: In patients with ischemic left ventricular dysfunction, continued cigarette smoking is associated with a significant increase in the risk of life-threatening ventricular tachyarrhythmias and inappropriate ICD shocks induced by rapid supraventricular arrhythmias. Our findings stress the importance of complete smoking cessation in this high-risk population. [source]

Interaction of Implantable Defibrillator Therapy with Angiotensin-Converting Enzyme Deletion/Insertion Polymorphism

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2004
MANINDER S. BEDI M.D.
Introduction: The angiotensin-converting enzyme deletion allele (ACE D) decreases survival in patients with advanced heart failure. Whether the adverse impact on survival reflects an increased risk of pump failure or arrhythmic sudden death remains uncertain. If the ACE D genotype increases the risk of sudden death, implantable cardioverter defibrillator (ICD) therapy should diminish its negative impact. We sought to evaluate the effect of ICD therapy on ACE D genetic risk. Methods and Results: The Genetic Risk Assessment of Cardiac Events (GRACE) study enrolled 479 patients at the University of Pittsburgh between 1996 and 2001. Blood was genotyped for the ACE D/I (deletion/insertion) polymorphism. Of the 479 patients, 82 (77% male, 84% Caucasian, age 56 ± 11 years, 60% ischemic, left ventricular ejection fraction 0.23 ± 0.08) received an ICD and were selected for outcomes analysis (mean follow-up 871 ± 538 days). Transplant-free survival and survival alone were compared in ACE DD patients (n = 24, 29%) versus ACE DI/II patients (n = 58, 71%). Survival was significantly improved in ACE DI/II patients compared to those without an ICD (1 year: 93% vs 87%; 2 year: 89% vs 77%; P = 0.02) but not in ACE DD patients. Transplant-free survival among patients with an ICD was significantly worse in ACE DD versus ACE DI/II (1 year: 67% vs 88%, 2 year: 55% vs 80%, P = 0.03). Analysis of survival as a single endpoint revealed a similar result (1 year = 78% vs 94%; 2 year: 72% vs 88%; P = 0.05). ICD telemetry data showed a nonsignificant trend toward fewer individuals with arrhythmias in the ACE-DD group (46% vs 65%, P = 0.22) Conclusion: ICDs do not diminish the adverse influence of the ACE DD genotype on survival. This finding suggests that mortality in this high-risk genetic subset of patients is due to progression of heart failure rather than arrhythmic sudden death. [source]

Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2002
Nilanjana Maulik
Abstract This review is intended to discuss the newly discovered role of preconditioning which should make it an attractive therapeutic stimulus for repairing the injured myocardium. We recently found that apart from rendering the myocardium tolerant to ischemic reperfusion injury, preconditioning also potentiates angiogenesis. Our study demonstrated for the first time that both ischemic and hypoxic preconditioning triggered myocardial angiogenesis at the capillary and arteriolar levels which nicely corroborated with the improved myocardial contractile function.Hypoxic preconditioning resulted in the stimulation of VEGF, the most potent angiogenic factor known to date. In concert, endothelial cell specific tyrosine kinase receptors, Tie 1, Tie 2 and Flt-1 and Flk-1 were also significantly enhanced in the preconditioned myocardium. The redox-regulated transcription factor NFkB was found to play an essential role in the preconditioning regulation of angiogenesis [source]

Advances in mechanisms of postsurgical gastroparesis syndrome and its diagnosis and treatment

JOURNAL OF DIGESTIVE DISEASES, Issue 2 2006
Ke DONG
Postsurgical gastroparesis syndrome (PGS) is a complex disorder characterized by post-prandial nausea and vomiting, and gastric atony in the absence of mechanical gastric outlet obstruction, and is often caused by operation at the upper abdomen, especially by gastric or pancreatic resection, and sometimes also by operation at the lower abdomen, such as gynecological or obstetrical procedures. PGS occurs easily with oral intake of food or change in the form of food after operation. These symptoms can be disabling and often fail to be alleviated by drug therapy, and gastric reoperations usually prove unsuccessful. The cause of PGS has not been identified, nor has its mechanism quite been clarified. PGS after gastrectomy has been reported in many previous studies, with an incidence of approximately 0.4,5.0%. PGS is also a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD), and the complication occurs in the early postoperative period in 20,50% of patients. PGS caused by pancreatic cancer cryoablation (PCC) has been reported about in 50,70% of patients. Therefore, PGS has a complex etiology and might be caused by multiple factors and mechanisms. The frequency of this complication varies directly with the type and number of gastric operations performed. The loss of gastric parasympathetic control resulting from vagotomy contributes to PGS via several mechanisms. It has been reported that the interstitial cells of Cajal (ICC) may play a role in the pathogenesis of PGS. Recent studies in animal models of diabetes suggest specific molecular changes in the enteric nervous system may result in delayed gastric emptying. The absence of the duodenum, and hence gastric phase III, may be a cause of gastric stasis. It was thought that PGS after PPPD might be attributable, at least in part, to delayed recovery of gastric phase III, due to lowered concentrations of plasma motilin after resection of the duodenum. The damage to ICC might play a role in the pathogenesis of PGS after PCC, for which multiple factors are possibly responsible, including ischemic and neural injury to the antropyloric muscle and the duodenum after freezing of the pancreatoduodenal regions or reduction of circulating levels of motilin. As the treatment of gastroparesis is far from ideal, non-conventional approaches and non-standard medications might be of use. Multiple treatments are better than single treatment. This article reviews almost all the papers related to PGS from various journals published in English and Chinese in recent years in order to facilitate a better understanding of PGS. [source]