Disruption of sarcolemmal dystrophin and β-dystroglycan may be a potential mechanism for myocardial dysfunction in severe sepsis

Abstract

Introduction In 2002, the Surviving Sepsis Campaign defi ned a strategy that aimed to reduce the high mortality due to sepsis. One point of this strategy was a recommendation to recognize that sepsis is a frequent cause of death and high economic costs in the pediatric intensive care unit. Knowledge of the disease is the fi rst step to impact it. There are few studies on pediatric sepsis epidemiology in the world and none in Colombia. Hypothesis The epidemiological features of Colombian children are diff erent from other countries. Methods We constructed a website where 14 intensive care units across the country reported in a prospective way the epidemiological features of children with sepsis using an electronic process [1]. We asked for sociodemographics, microbiological data, sepsis classifi cation, complications, and outcome. Results We collected 253 patients from March to May 2009. Fifty-fi ve percent of the cases were male and 45% were female; 53% were less than 1 year old. A total of 67.2% came from urban areas and 33% came from rural villages. Eighty-fi ve percent were very poor (score 1 and 2 over 6 used in Colombia as socioeconomic classifi cation). Forty-fi ve percent have governmentsupported insurance. In total, 23.72% of the population presented with sepsis; 30.04% with severe sepsis; and 46.5% with septic shock. The infection origin was respiratory in 54.55%, followed by abdominal in 17.39%. In 50.2% no cause was identifi ed. A total of 75.1% required mechanical ventilation. The mortality rate was 20.4%. Conclusions Sepsis, severe sepsis, or septic shock is a common diagnosis in Colombian intensive care units. The majority of pediatric patients are 2 years or younger and from the poorest communities. It aff ected males more. In the majority, the process starts in the respiratory system. We had diffi culty identifying the cause. The disease causes high mortality and cost for a developing society. We need a complete survey to fi nd a correct approach to the problem. Reference 1. Sepsis en Columbia [www.sepsisencolombia.com] P2 Randomized controlled trials are not designed to prove the safety of third-generation hydroxyethyl starch for resuscitation: results from a systematic review

Inhibition of Coxsackievirus-associated dystrophin cleavage prevents cardiomyopathy

“…This is consistent with our previous data demonstrating that the absence of dystrophin increased susceptibility to viral infection (5). Apart from the loss of dystrophin at the sarcolemma, which has been shown to increase susceptibility to viral infection, there are other genetic and secondary alterations in the dystrophin-glycoprotein complex (DGC) that affect sarcolemmal stability and could affect susceptibility to viral infection (12)(13)(14)(15)(16)(17). Therefore, it is possible that genetic variability in the core components of the DGC or alterations that affect the level of dystrophin expression (such as occurs in Becker muscular dystrophy or X-linked dilated cardiomyopathy) (18) could have a profound permissive or inhibitory effect on susceptibility to enteroviral infection.…”

Effect of Verapamil, an L‐Type Calcium Channel Inhibitor, on Caveolin‐3 Expression in Septic Mouse Hearts

“…The reduction of connexin-43 and N-cadherin resulted in the loss of structural integrity of intercalated discs, hindering communication between myocardial cells [11]. Subsequently, cardiomyocyte degeneration and lysis of actin and myosin filaments, all caused by sepsis, were associated with reduced expression of dystrophin [12].…”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…On the basis of these data Parker thought that LV dilatation were an adaptive mechanism apt to increase systolic stroke through a better utilization of Starling mechanism (early preload adaptation). Successive studies by echocardiography have not confirmed however a significant LV dilatation while observing an altered biventricular relaxation and a systolic dysfunction of the right ventricle in 41% of the p, isolated or in conjunction with a LV dysfunction [182][183][184][185].The apparently better cardiac function in non survivors is currently perceived as a consequence of the persistent septic hemodynamic pattern with decreased SVR causing higher CI and LVEF, both being heavily load-dependent indexes [186]. A LV depressed contractile performance is constant in human and experimental sepsis [187] if related to pre and after-load, it is explained by the global ventricular hypokinesia observed in 60% of the p. in septic shock [188]: the impairment of LV contractility may be unravelled also by the reduction of CI in response to norepinephrine infusion [181].…”