New fluid therapy protocol in acute burn from a tertiary burn care centre.

BACKGROUND: Ringer lactate is the main fluid for resuscitation of acute burns. However it is not a complete fluid alone, as it does not take care of sugar and electrolyte balance adequately. This study has been carried out to compare the use of Ringer lactate (RL) alone and combination of RL with Dextrose Normal Saline (DNS) as fluid replacement therapy in acute burn. OBJECTIVE: To assess the biochemical parameters with the use of DNS as maintenance fluid in combination with Ringer lactate as resuscitation fluid in acute burns resuscitation. METHOD: A prospective randomized control study has been carried out by enrolling 200 patients into 2 groups, treated in ICU and resuscitated by using Modification of Brooke's formula (2mL/kg/% TBSA for resuscitation plus 2500mL maintenance). Group A received RL for resuscitation and DNS as maintenance in 1st 72h of burns. Group B received RL only for 1st 72h. The effects of this on various blood parameters were studied. RESULTS: Mean value of sodium at 24h was 137.79±3.89 in group A and was 133.2±4.57 (p<.0001) in group B. The sodium levels remained in range of 137-138 (p<.0001) in group A with only 22% patients showing lower range of sodium levels, whereas, there was a falling trend (p<.0001) of sodium levels in group B on subsequent days with 54.00% (p<.0001) showing hyponatremia on 1st day which increased to 76% on 3rd day. Mean values of early morning random blood sugar (RBS) levels in group A remained between 165.5±65.51mg/dL-115.82±32.52mg/dL on all 3days but in group B there was a falling trend from 127.49±46.11mg/dL to 102.84±22.92mg/dL by 3rd day. Thus, there was significant difference in levels of sodium and RBS in patients receiving DNS as maintenance fluid in addition to RL in acute phase. CONCLUSION: RL is not an ideal fluid for maintenance as it is low in sodium (130mEq/L) as well as potassium (4mEq/L) in view of daily electrolyte requirement. There is no glucose content in it to provide calories. Therefore, DNS should be added as daily maintenance fluid with RL as replacement for evaporative losses following burns.

Primary results from the SmartDelay determined AV optimization: a comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial: a randomized trial comparing empirical, echocardiography-guided, and algorithmic atrioventricular delay programming in cardiac resynchronization therapy.

BACKGROUND: one variable that may influence cardiac resynchronization therapy response is the programmed atrioventricular (AV) delay. The SmartDelay determined av optimization: a comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial prospectively randomized patients to a fixed empirical AV delay (120 milliseconds), echocardiographically optimized AV delay, or AV delay optimized with SmartDelay, an electrogram-based algorithm. METHODS AND RESULTS: a total of 1014 patients (68% men; mean age, 66 ± 11 years; mean left ventricular ejection fraction, 25 ± 7%) who met enrollment criteria received a cardiac resynchronization therapy defibrillator, and 980 patients were randomized in a 1:1:1 ratio. All patients were programmed (DDD-60 or DDDR-60) and evaluated after implantation and 3 and 6 months later. The primary end point was left ventricular end-systolic volume. Secondary end points included New York Heart Association class, quality-of-life score, 6-minute walk distance, left ventricular end-diastolic volume, and left ventricular ejection fraction. The medians (quartiles 1 and 3) for change in left ventricular end-systolic volume at 6 months for the SmartDelay, echocardiography, and fixed arms were -21 mL (-45 and 6 mL), -19 mL (-45 and 6 mL), and -15 mL (-41 and 6 mL), respectively. No difference in improvement in left ventricular end-systolic volume at 6 months was observed between the SmartDelay and echocardiography arms (P=0.52) or the SmartDelay and fixed arms (P=0.66). Secondary end points, including structural (left ventricular end-diastolic volume and left ventricular ejection fraction) and functional (6-minute walk, quality of life, and New York Heart Association classification) measures, were not significantly different between arms. CONCLUSIONS: neither SmartDelay nor echocardiography was superior to a fixed AV delay of 120 milliseconds. The routine use of AV optimization techniques assessed in this trial is not warranted. However, these data do not exclude possible utility in selected patients who do not respond to cardiac resynchronization therapy.

Proteomic analysis of IgE-mediated secretion by LAD2 mast cells.

The LAD2 cell line is a relatively recent addition to the range of mast cell analogues and is of particular importance as it is the only human analogue which can be stimulated to degranulate in an IgE-dependent manner. Mast cells are tissue-based effector cells which have historically been shown to play an important role in the adaptive immune response, though there is now gathering evidence of their significance as a component of the innate immune system. These functions can be attributed to the ability of mast cells to regulate secretion of a wide variety of potent biologically active mediators through immediate and delayed responses. This well-orchestrated secretory mechanism of the mast cell makes it an ideal model in which to study this event. In this investigation, two-dimensional electrophoresis was employed as part of the proteomic characterization of the LAD2 human mast cell line, focusing in particular on a global analysis of membrane protein relocation after an IgE-mediated stimulatory event. This investigation has identified six membrane-associated protein spots which became phosphorylated upon IgE-mediated activation, 31 protein spots which displayed consistent recruitment to the membrane fraction, and three which were consistently lost from the soluble fraction. The scenario which emerges reveals a series of substantial changes which affect every compartment of the cell, providing evidence for a coordinated response to a secretory stimulus.

Myocardial Fas and cytokine expression in end-stage heart failure: impact of LVAD support.

Left ventricular assist device (LVAD) support may facilitate myocardial recovery. We evaluated the impact of LVAD support on Fas expression in a cohort with end-stage heart failure. Myocardial gene expression was assessed pre- and post-LVAD by RNase protection assay and compared to control donor hearts. The expression of Fas is markedly elevated at the time of LVAD support and is tightly correlated with TNF expression. While interleukin (IL)-6 was significantly reduced by LVAD support, the impact of support on Fas was highly variable and tightly linked to tumor necrosis factor (TNF). The role of Fas in predicting recovery after LVAD support requires further investigation.

Ventricular arrhythmias during left ventricular assist device support.

Left ventricular assist devices (LVADs) have been used effectively as a "bridge" to cardiac transplantation and as destination therapy in patients with advanced heart failure. Ventricular arrhythmias (VAs) have been reported to occur in LVAD-supported patients, although their incidence, risk factors, and clinical significance have not been characterized. In this study, 111 patients who received LVAD support as a bridge to cardiac transplantation at the University of Pittsburgh Medical Center from January 1987 to June 2001 were evaluated. Clinically significant VA was defined as ventricular fibrillation, sustained ventricular tachycardia, or nonsustained ventricular tachycardia with symptoms requiring antiarrhythmic therapy. Patients were grouped on the basis of the presence or absence of VAs. VAs occurred in 24 patients (22%) during device support. Ischemic heart disease was the cause of heart failure in 71% of patients (17 of 24) in the VA group and 45% of patients (39 of 87) in the group without VAs (p <0.05). The mortality rate was significantly higher (p <0.001) during LVAD support in the group with VAs (33%) compared with the group without VAs (18%). In the group with VAs, the early (1 week) occurrence (9%). In conclusion, although clinically significant VAs occur in patients with heart failure receiving LVAD support, the overall incidence is low. VAs are more frequent in patients with ischemic heart failure, and their occurrence is associated with greater mortality. The occurrence of VAs early after LVAD implantation, in particular, predicts a higher mortality rate.

Effect of concordance between sites of left ventricular pacing and dyssynchrony on acute electrocardiographic and echocardiographic parameters in patients with heart failure undergoing cardiac resynchronization therapy.

BACKGROUND: Wide QRS complexes are associated with left ventricular (LV) dyssynchrony, but an optimal site of LV pacing has not been established. HYPOTHESIS: We hypothesized that concordance between the sites of LV pacing and of latest LV mechanical activation during cardiac resynchronization therapy (CRT) is associated with more favorable acute echocardiographic changes. METHODS: An analysis of 28 consecutive patients (64+/-15 years, 46% male, 52% ischemic heart disease, LV ejection fraction 0.24+/-0.07, QRS 163+/-22 ms, New York Heart Association > or = 3 93%) implanted with biventricular (BIV) defibrillators was performed. Sites of latest LV activation were determined by tissue Doppler imaging (TDI) and speckle tracking (ST). The site of LV pacing was determined by fluoroscopy in two views. A concordance score (0-5) was created to describe the proximity of the pacing site to the site of the latest mechanical activation. RESULTS: Compared with the worst concordance score, a perfect score was associated with shorter QRS width with LV (187+/-40 vs. 246+/-8 ms, p= 0.048) and BIV (134+/-19 ms vs. 179+/-39 ms, p = 0.05) but not with right ventricular pacing. A perfect concordance score was also associated with a greater acute reduction in LV volumes in systole (42+/-36 ms 16+/-22 ms, p = 0.068) and diastole (47+/-37 vs. 8+/-31 ml, p = 0.043) 24 h after CRT device implantation. CONCLUSIONS: A high concordance is associated with shorter QRS width with LV and BIV pacing and greater acute reduction in LV volumes. The effect of concordance on the intermediate and long-term response to BIV pacing deserves further evaluation.

Genetic susceptibility to atrial fibrillation in patients with congestive heart failure.

BACKGROUND: Previous reports demonstrate an association between atrial fibrillation (AF) and certain polymorphisms in genes controlling the production of angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS). OBJECTIVES: The purpose of this study was to examine the association between polymorphisms of ACE and eNOS gene complexes and AF in an unselected series of patients with congestive heart failure (CHF). METHODS: In each of the 340 unselected, unrelated patients with CHF, common polymorphisms in ACE (I/D) and eNOS (T786C, G894T, and intron 4b/a) gene complexes were evaluated. Associations between individual genotypes and the presence of AF were assayed. RESULTS: AF was present in 51 patients (15%) and was significantly associated with the ACE D/D (odds ratio 1.5) and eNOS 894 T/T genotypes (odds ratio 3.2). There were no significant associations between AF and eNOS 786 or eNOS intron 4 genotypes. CONCLUSION: In patients with CHF, the presence of AF was significantly associated with certain ACE and eNOS genotypes.

Renal insufficiency predicts the time to first appropriate defibrillator shock.

BACKGROUND: Indications for implantable cardioverter defibrillator (ICD) implantation are expanding, but many primary and secondary ICD trials have excluded patients with advanced renal insufficiency. We investigated the effect of renal function on the incidence and time to first appropriate ICD shock. METHOD: We analyzed data from all new ICD implantations at a tertiary care center from July 2001 to December 2002. RESULTS: During a mean follow-up time of 445 +/- 285 days, 29 (13%) of 230 patients (age 63 +/- 14 years, 79% men, 77% white, 75% coronary artery disease, left ventricular ejection fraction 0.28 +/- 0.14) received 41 appropriate shocks. Patients were divided into tertiles according to their serum creatinine level. The 1-year incidence of appropriate ICD shock was 3.8%, 10.8%, and 22.7% in the first, second, and third tertiles, respectively (P = .003). Using the same cut off values of serum creatinine, the 1-year incidence of appropriate ICD therapy (shock and antitachycardia pacing) was 8.8%, 20.8%, and 26.3% (P = .02). After correcting for age, sex, race, left ventricular ejection fraction, indication for ICD implantation, and use of beta-blockers in a Cox regression model, serum creatinine was still an independent predictor of the time to first appropriate ICD shock (hazard ratio 6.0 for the third compared with the first tertile, P = .001). CONCLUSION: Renal insufficiency is a strong predictor of appropriate ICD shocks. Defibrillator therapy should therefore not be withheld based on the presence of this comorbidity. The mechanisms underlying the relationship between renal function and ventricular arrhythmias deserve further investigation.

Indications for internal cardioverter defibrillator implantation predict time to first shock and the modulating effect of beta-blockers.

BACKGROUND: Patients receive implantable cardioverter defibrillator (ICD) for varying indications. Whether these indications influence the time to first ICD shock is suspected but not confirmed. The modulating effect of beta-blockers on shock-free survival is not fully elucidated. METHOD: A retrospective analysis of 230 consecutive patients (age 63 +/- 14 years, 79% men, 75% ischemic, 70% beta-blockers) implanted with an ICD was performed. Patients were divided into 4 groups depending on the ICD indication: groups A (secondary prevention of sudden death), B (left ventricular ejection fraction < or = 35% and positive electrophysiology study [EPS]), C (left ventricular ejection fraction < or = 35% and negative EPS or no EPS performed), and D (patients who did not meet inclusion criteria for groups A, B, or C). Time to shock was analyzed by the Kaplan-Meier method. RESULTS: During a mean follow-up of 489 +/- 280 days, 57 (24.7%) patients received 82 shocks (49% appropriate). The 1-year shock-free survival for patients in groups A, B, C, and D were 57%, 77%, 79%, and 91%, respectively (P = .03), for total shocks and 75%, 92%, 92%, and 100%, respectively (P = .007), for appropriate shocks. For patients in group A, the use of beta-blockers increased the 1-year shock-free survival from 48% to 61% for total shocks and from 65% to 79% for appropriate shocks. CONCLUSION: Time to first shock is determined by the indication for ICD implantation and is not predicted by the results of EPS. Patients with secondary indications for ICD implantation are at highest risk of shocks and may deserve consideration for prophylactic antiarrhythmic drugs. beta-Blockers increase the time to first ICD shock in patients implanted for secondary prevention of sudden death.

Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy.

OBJECTIVES: This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy. BACKGROUND: Apoptosis may limit ventricular recovery. We examined the myocardial expression of Fas, Fas ligand (FasL), tumor necrosis factor (TNF)-alpha, and TNF receptor 1 (TNFR1), and myocardial recovery in patients from the multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC) study. METHODS: Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (<6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] < or =0.40). The LVEF was assessed at baseline and at 6 and 12 months by nuclear scans. Myocardial expression was assessed by ribonuclease (RNase) protection, normalized to a constitutively active gene (glyceraldehydes 3-phosphate dehydrogenase [GAPDH]) and reported as percent GAPDH expression. The change in LVEF at 6 and 12 months was compared by tertiles of expression. RESULTS: For all patients (14 men, 6 women; age 46.5 +/- 10.7 years), the mean LVEF was 0.28 +/- 0.05 at baseline and 0.40 +/- 0.14 at six months. Patients in the highest tertile of Fas expression had minimal improvement at six months (DeltaEF = 0.03 +/- 0.05) when compared with the intermediate (DeltaEF = 0.10 +/- 0.13) and lowest tertiles (DeltaEF = 0.21 +/- 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, DeltaEF = 0.06 +/- 0.07; lowest tertile, DeltaEF = 0.21 +/- 0.11, p = 0.02). In contrast with Fas and TNFR1, expression of TNF-alpha and FasL did not predict recovery of LV function. CONCLUSIONS: In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention.

Interaction of implantable defibrillator therapy with angiotensin-converting enzyme deletion/insertion polymorphism.

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.

Effect of the TNF-alpha-promoter polymorphism on cardiac allograft rejection.

BACKGROUND: A polymorphism exists in the tumor necrosis factor alpha (TNF-alpha) promoter (position -308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-alpha production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients. METHODS: We prospectively analyzed 57 subjects (aged 54 +/- 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 +/- 605 days) and the frequency of allograft rejection (biopsy Grade > or =2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups. RESULTS: The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 +/- 11 days; Group B, 20 +/- 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35). CONCLUSION: The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.