Right Ventricular Dysfunction and Dilatation, Similar to Left Ventricular Changes, Characterize the Cardiac Depression of Septic Shock in Humans

Parker, Margaret M.; McCarthy, Karen; Ognibene, Frederick P.; Parrillo, Joseph E.

doi:10.1378/chest.97.1.126

Cited by 334 publications

(175 citation statements)

References 20 publications

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“…Although cardiac output is usually maintained in volume-resuscitated septic patients, a number of investigators (Parrillo et al, 1990;Holcroft et al, 2001;Parker et al, 1984Parker et al, , 1990) have demonstrated impairment of cardiac function. This myocardial dysfunction is characterized by decreased ejection fraction, ventricular dilation, impaired contractile response to volume loading, and a low peak systolic pressure to end-systolic volume ratio, a load-independent measure of ventricular function (Holcroft et al, 2001;Schaer et al, 1985;Reinelt et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Parker et al, (1984Parker et al, ( , 1990 described the phenomenon of sepsis-induced myocardial dysfunction (SIMD) in septic ICU patients, which is characterized by biventricular impairment of intrinsic myocardial contractility left and right ventricular contractile dysfunction. The clinically relevant polymicrobial septic rat model that has been characterized and standardized in our laboratory produces a prolonged hyperdynamic state of sepsis (Sam II et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction

Chopra

Sharma

2007

Life Sciences

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We hypothesized that progressive decline in myocardial performance would correlate with upregulation of markers for apoptotic mechanisms following increased duration of polymicrobial sepsis in the rat. Male Sprague-Dawley rats (350-400 g) were randomized into sham, 1-, 3-and 7-day sepsis groups. Each septic rat received 200 mg/kg cecal inoculum intraperitoneally (i.p). The post-mortem analysis showed a severely inflamed peritoneum with the presence of pus in all septic animals that was directly proportional to the duration of sepsis. We observed 10, 33 and 42% mortality in the 1-, 3-and 7-day sepsis groups, respectively. Septic animals at 3 and 7 days exhibited an increased wet lung/total body weight and heart weight/total body weight. A significant increase in total cardiac troponin I (cTnI) and C Reactive Protein (CRP) and endothelin-1 (ET-1) was also observed with an increased duration of sepsis. Myocardial ET-1 concentration in the 7-day postsepsis group was significantly elevated compared to the sham and 1-day post-sepsis groups. Sepsis also produced a significant decrease in the mean arterial pressure in the 7-day post-sepsis group and tachycardia in the 1-, 3-, and 7-day post-sepsis groups compared to the sham group. A significant prolongation of the left ventricular isovolumic relaxation rate constant, tau, and left ventricular enddiastolic pressure in the 1-, 3-and 7-day post-sepsis groups compared to the sham group was observed. In addition, a significant decrease in the rates of left ventricular relaxation (−dP/dt) and contraction (+dP/dt) in the 3-and 7-day post-sepsis groups compared to the sham and 1-day postsepsis group was observed. Sepsis produced a significant upregulation in the expression of myocardial TRADD, cytosolic active caspase-3, the Bax/Bcl 2 ratio, and the mitochondrial release of cytochrome C in the 3-and 7-day post-sepsis groups. We observed a progressive increase in the number of TUNEL positive nuclei, cytosolic caspase-3 activation and co-localization of PARP in the nuclei at 1, 3 and 7 days post-sepsis. These data suggest that the progression of sepsis from 1 day to 3-7 days produce distinct cardiodynamic characteristics with a more profound effect during later stages. The sepsis-induced decline in myocardial performance correlates with the induction of myocardial apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction

Chopra

Sharma

2007

Life Sciences

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“…Two additional studies have confirmed the correlation of NT pro-BNP with age, but not with sex (17,18). In contrast, obesity is associated with decreased levels of BNP, probably as a result of increased clearance through a receptor contained in adipose tissue (19).Parker et al (20) demonstrated that myocardial depression is also present in human septic shock and is associated with ventricular dilation and decreased LVEF (20). We present two cases of septic shock with markedly increased levels of NT pro-BNP with no evidence of myocardial dysfunction based on evaluation using echocardiography and catheterization.…”

mentioning

confidence: 99%

“…Parker et al (20) demonstrated that myocardial depression is also present in human septic shock and is associated with ventricular dilation and decreased LVEF (20). We present two cases of septic shock with markedly increased levels of NT pro-BNP with no evidence of myocardial dysfunction based on evaluation using echocardiography and catheterization.…”

mentioning

confidence: 99%

Nonheart failure-associated elevation of amino terminal pro-brain natriuretic peptide in the setting of sepsis

Bar

Swiggum

Straatman

et al. 2006

Canadian Journal of Cardiology

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O ne-half of a century has been spent debating the etiology of depressed myocardial function in septic shock (1). Brain natriuretic peptide (BNP) is a new biomarker for cardiac dysfunction, and most data in the literature associate its increased levels with depressed myocardial function (2-5). However, increased levels of BNP have also been found in critical illnesses associated with shock (eg, sepsis), apparently not related to myocardial dysfunction. In human myocardium, BNP is secreted in response to myocardial stretch. Its release promotes natriuresis and diuresis, and it has a vasodilatory effect on systemic circulation (6). As such, it reduces preload, venous return and filling pressures with a subsequent reduction in cardiac output (7). The measured BNP increases in response to increases in left ventricular (LV) end-diastolic pressure, pulmonary artery wedge pressure, atrial pressure and LV hypertrophy (8). BNP level is also associated with echocardiographic dysfunction and clinical outcomes (9). The degree of cardiac dysfunction determines the magnitude of increase in BNP level (10).The BNP gene contains an encoded protein consisting of 108 peptides, called pro-BNP (11). The cleavage of pro-BNP within the heart results in two components produced in equal amounts: BNP 32 (the active hormone) and N-terminal (NT) pro-BNP (the inactive fragment) (12). The plasma half-life of NT pro-BNP is approximately 2 h in comparison with that of BNP 32 (20 min) (13), which explains the higher level of NT pro-BNP in myocardial dysfunction (14).In addition to the documented relationship between BNP and myocardial dysfunction mentioned above, there are other conditions associated with increased BNP level that include primary pulmonary hypertension, myocarditis, cardiac allograft rejection, arrhythmogenic right ventricle with decreased LV ejection fraction (EF), renal failure, Kawasaki disease, ascitic cirrhosis and endocrine diseases (Cushing's syndrome, primary hyperaldosteronism) (8). Other patient characteristics that may influence the BNP level, independent of disease, are advancing age, probably reflecting LV subclinical abnormalities (15) and female sex, both of which result in increased BNP level (15,16). Two additional studies have confirmed the correlation of NT pro-BNP with age, but not with sex (17,18). In contrast, obesity is associated with decreased levels of BNP, probably as a result of increased clearance through a receptor contained in adipose tissue (19).Parker et al (20) demonstrated that myocardial depression is also present in human septic shock and is associated with ventricular dilation and decreased LVEF (20). We present two cases of septic shock with markedly increased levels of NT pro-BNP with no evidence of myocardial dysfunction based on evaluation using echocardiography and catheterization. Also described are possible explanations of elevated NT pro-BNP in a setting not related to myocardial dysfunction. Thus, there are situations where the predictive value of BNP is not correlated with the magn...

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“…Cardiac dysfunction generally starts during the first 24 h of the development of septic shock and it is reversible in survivors within 7-10 days (7,8). In those individuals, there appear to be simultaneous right (RV) and left (LV) ventricle systolic and diastolic dysfunctions (9,10). These changes reflect both intrinsic cardiac dysfunction and hemodynamic alterations that are characteristic of septic shock.…”

mentioning

confidence: 99%

Identification, characterization, and gene expression profiling of endotoxin-induced myocarditis

Wong

O'Kirwan

Khan³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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T he pathophysiology of the systemic inflammatory response syndrome (SIRS) and sepsis involves the CNS (1-3) and several peripheral systems that affect gastrointestinal, renal, and cardiovascular functions (4-6). In previous work we described temporal and spatial patterns of expression for genes encoding nitric oxide synthase type 2 (NOS2 or iNOS) and elements of the interleukin-1 system in the CNS (1, 2) during the course of lipopolysaccharide (LPS)-induced SIRS. Those data supported our hypothesis that a mechanism for immune system-brain communication could occur in brain vasculature through interleukin-1␤-NOS2 interactions. To learn more about bidirectional brain-periphery immune system communications, we have studied the effects of systemic inflammation on peripheral tissues; here we focus on the heart. Cardiac dysfunction generally starts during the first 24 h of the development of septic shock and it is reversible in survivors within 7-10 days (7,8). In those individuals, there appear to be simultaneous right (RV) and left (LV) ventricle systolic and diastolic dysfunctions (9, 10). These changes reflect both intrinsic cardiac dysfunction and hemodynamic alterations that are characteristic of septic shock. Global myocardial ischemia has been refuted as an etiological hypotheses to explain intrinsic cardiac dysfunction during SIRS because myocardial lactate production is not increased (11), coronary blood flow is not decreased (12), and diminished oxygen extraction is more consistent with the notion of abnormal myocyte metabolism than with inadequate oxygen delivery. Currently, there is a consensus that myocardial dysfunction seems to result from myocardial depressant factors. Candidate mediators for myocardial depressant factor include NO as well as a series of other factors (such as endotoxin, cytokines, platelet-activating factor, arachidonic acid derivatives, kinins, complement components, endothelial factors, and reactive oxygen molecules) (10,13,14).NO modulates both contraction and diastolic cardiac function in physiological states and in sepsis, and it may also limit the oxidative damage to cells by scavenging reactive molecules (15). Activation of constitutive NOS or NOS2 in the myocardium may play a role in the cardiac dysfunction complicating SIRS (16). We conducted studies to examine the effects of systemic inflammation in the heart, specifically to test the following three hypotheses: (i) NOS2 gene expression might be an element of the heart's response to systemic inflammation; (ii) myocardium tissue injury could be an element of the pathophysiology of SIRS; (iii) the extent of myocardium involvement could be assessed by characterization of differential patterns of gene expression. Materials and MethodsAnimals. Studies were carried out in accordance with protocols approved by the National Institutes of Health. Animals were treated as described before (1). Virus-and pathogen-free male Sprague-Dawley (200-250 g, Harlan, Indianapolis) rats were housed in a light-and temperature-controlled environme...

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Right Ventricular Dysfunction and Dilatation, Similar to Left Ventricular Changes, Characterize the Cardiac Depression of Septic Shock in Humans

Cited by 334 publications

References 20 publications

Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction

Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction

Nonheart failure-associated elevation of amino terminal pro-brain natriuretic peptide in the setting of sepsis

Identification, characterization, and gene expression profiling of endotoxin-induced myocarditis

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