Chronic peritoneal sepsis: myocardial dysfunction, endothelin and signaling mechanisms

Gupta, Akanksha; Brahmbhatt, Sachin; Kapoor, Ruchita; Loken, Lisa; Sharma, Avadhesh C.

doi:10.2741/1774

Cited by 10 publications

(9 citation statements)

References 214 publications

(185 reference statements)

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“…Therein lies possibly the explanation for the diverging reports. The manner by which endotoxin is infused is also important, where a continuous infusion of endotoxin is preferable to bolus infusions as a model of human sepsis because it generally produces a more persistent pathophysiological response (20). Our current results suggest that endotoxin did not cause detectable LV contractile impairment, but sympathetic activation in response to endotoxin may very well have compensated for a negative inotropic effect of endotoxin, as suggested by Smith et al (12,50).…”

Section: Discussionsupporting

confidence: 61%

Cardiac effects of endothelin receptor antagonism in endotoxemic pigs

Konrad¹,

Haney²,

Johansson³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Myocardial depression in sepsis is frequently encountered clinically and contributes to morbidity and mortality. Increased plasma levels of endothelin-1 (ET-1) have been described in septic shock, and previous reports have shown beneficial effects on cardiovascular performance and survival in septic models using ET receptor antagonists. The aim of the current study was to investigate specific cardiac effects of ET receptor antagonism in endotoxicosis. Sixteen domestic pigs were anesthetized and subjected to endotoxin for 5 h. Eight of these pigs were given tezosentan (dual ET receptor antagonist) after 3 h. Cardiac effects were evaluated using the left ventricular (LV) pressure-volume relationship. Endotoxin was not associated with any effects on parameters of LV contractile function [end-systolic elastance (Ees), preload recruitable stroke work (PRSW), power(max)/end-diastolic volume (PWR(max)/EDV) and dP/dt(max)/end-diastolic volume (dP/dt(max)/EDV)] but with impairments in isovolumic relaxation (time constant for pressure decay, tau) and mechanical efficiency. Tezosentan administration decreased Ees, PWR(max)/EDV, and dP/dt(max)/EDV, while improving tau and LV stiffness. Thus, dual ET receptor antagonism was associated with a decline in contractile function but, in contrast, improved diastolic function. Positive hemodynamic effects from ET receptor antagonism in acute endotoxemia may be due to changes in cardiac load and enhanced diastolic function rather than improved contractile function.

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Section: Discussionsupporting

confidence: 61%

Cardiac effects of endothelin receptor antagonism in endotoxemic pigs

Konrad¹,

Haney²,

Johansson³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Our data also demonstrated the role of mitochondrial-mediated intrinsic apoptosis cascade and stress-mediated mitogen-activated protein kinases in the regulation of sepsis-induced adult rat ventricular myocyte (ARVM) dysfunction [9], [10], [11], [12]. In experimental endotoxemia, mitochondrial dysfunction has been characterized by mitochondrial membrane potential collapse and transitional changes in mitochondrial membrane permeability, along with the release of cytochrome C [8], [13], [14], [15].…”

Section: Introductionsupporting

confidence: 53%

“…For the last several years, our laboratory demonstrated sepsis-induced myocardial contractile dysfunction in both in vivo and in vitro paradigms of polymicrobial sepsis [8], [11], [12], [22]–[27]. Sepsis-induced myocardial contractile dysfunction was found to be associated with the induction of intrinsic apoptosis cascade [8], [10], [11], [22], [23].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Myocardial Mitochondrial Mechanisms during Severe Polymicrobial Sepsis in the Rat

Chopra

Golden

Mullapudi³

et al. 2011

PLoS ONE

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BackgroundWe tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoKATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival.Methodology/Principal FindingsMale Sprague-Dawley rats (350–400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (−40%) and at 6 hr post-sepsis (−20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C.ConclusionThe data suggest that Bax activation is an upstream event that may precede the opening of the mitoKATP channels in sepsis. We concluded that mitoKATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.

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“…Although sepsis is known to cause increased coronary blood flow, it also has been linked to improper oxygen utilization . Other mechanisms such as upregulation of endothelin 1 have also been demonstrated to play a role in these patients and could be the trigger for endothelial dysfunction . Furthermore, an increase in cardiac myocyte permeability in septic patients may also play a role in troponin leakage .…”

Section: Discussionmentioning

confidence: 99%

Impact of Type 2 Myocardial Infarction (MI) on Hospital‐Level MI Outcomes: Implications for Quality and Public Reporting

Arora

Strassle

Qamar

et al. 2018

JAHA

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BackgroundThe International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction (MI) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non–ST‐segment–elevation myocardial infarction (NSTEMI). We aim to evaluate the impact of type 2 MI on hospital‐level NSTEMI metrics and discuss the implications for quality and public reporting.Methods and ResultsWe conducted a single‐center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI. Weighted Kaplan–Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI. Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P<0.0001) and were more likely to die from noncardiovascular causes (71.7% versus 25.0%, P<0.0001). Despite weighting for patient characteristics and discharge medications, patients with type 2 MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67–7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44–2.73) after discharge. Type 2 MI was also associated with a lower 30‐day cardiovascular‐related readmission (risk ratio: 0.49; 95% confidence interval, 0.12–2.06).Conclusions NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics.

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Chronic peritoneal sepsis: myocardial dysfunction, endothelin and signaling mechanisms

Cited by 10 publications

References 214 publications

Cardiac effects of endothelin receptor antagonism in endotoxemic pigs

Cardiac effects of endothelin receptor antagonism in endotoxemic pigs

Modulation of Myocardial Mitochondrial Mechanisms during Severe Polymicrobial Sepsis in the Rat

Impact of Type 2 Myocardial Infarction (MI) on Hospital‐Level MI Outcomes: Implications for Quality and Public Reporting

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