Out-of-hospital cardiac arrest survivors sent for emergency angiography: a clinical score for predicting acute myocardial infarction.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Emergency coronary angiography and percutaneous coronary intervention might improve survival, especially when cardiac arrest is caused by acute myocardial infarction (AMI). However, identifying patients with AMI after OHCA remains challenging. The aim of this study was to determine the clinical and ECG criteria in OHCA that may help to identify better the patients with AMI. METHODS: Consecutive OHCA patients who underwent emergency coronary angiography in our centre between 2009 and 2013 were included in this retrospective single-centre observational study. RESULTS: A total of 177 patients with complete datasets were included. Significant coronary artery disease was found in 71% of the patients, and 43% presented with AMI. The independent predictors of AMI were ST elevation in any lead including aVR (odds ratio (OR) 18.06; 95% confidence interval (CI) 6.6-49.38), chest pain before cardiac arrest (OR 4.05; 95% CI 1.55-10.54) and an initial shockable rhythm (OR 2.99; 95% CI 1.34-6.45). An additive score that included these three predictors yielded a sensitivity and a specificity for detecting AMI of 93% and 63%, respectively. CONCLUSIONS: These data suggest that fewer than half of patients with OHCA undergoing emergency coronary angiography present with AMI. The identification of OHCA patients with AMI might be improved by a simple score using post-resuscitation ECG and simple clinical criteria.

Impact of Prosthesis-Patient Mismatch on Long-term Functional Capacity After Mechanical Aortic Valve Replacement.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) for aortic stenosis on exercise capacity remains controversial. The aim of this study was to analyze the long-term impact of PPM after mechanical AVR on maximal oxygen uptake (VO2max). METHODS: The study included 75 patients who had undergone isolated mechanical AVR for aortic stenosis with normal left ventricular (LV) function between 1994 and 2012. Their functional capacity was evaluated on average 4.6 years after AVR by exercise testing, including measurement of their VO2max, and by determining their New York Heart Association functional class and Short Form-36 score. Two groups were defined by measuring the patients' indexed effective orifice area (iEOA) by transthoracic echocardiography: a PPM group (iEOA < 0.85 cm2/m2) and a no-PPM group (iEOA ≥ 0.85 cm2/m2). RESULTS: PPM was present in 37.0% of the patients. The percentage of the predicted VO2max achieved was significantly lower in the PPM group (86.7 ± 19.5% vs 97.5 ± 23.0% in the no-PPM group; P = 0.04). Compared with the no-PPM group, the PPM group contained fewer patients in New York Heart Association functional class I and their mean Short Form-36 physical component summary score was significantly lower. The mean transvalvular gradient was significantly higher in the PPM group than in the no-PPM group (P < 0.001). Systolic and diastolic function and LV mass had normalized in both groups. CONCLUSIONS: PPM is associated in the long term with moderate but significant impairment of functional capacity, despite optimal LV reverse remodelling and normalization of LV systolic and diastolic function.

Exclusive low-molecular-weight heparin as bridging anticoagulant after mechanical valve replacement.

BACKGROUND: Unfractionated heparin has been the standard anticoagulant used immediately after mechanical heart valve replacement (MHVR). The purpose of this study was to assess a postoperative anticoagulation protocol with low-molecular-weight heparin (LMWH) immediately after MHVR without the use of unfractionated heparin or anti-factor Xa monitoring. METHODS: We performed a prospective, single-center, observational study of 1,063 consecutive patients undergoing elective MHVR with postoperative LMWH anticoagulation treatment. The exclusion criteria were as follows: renal failure, intraaortic balloon counterpulsation, critical perioperative state, or a recent neurologic event. The postoperative anticoagulation protocol used subcutaneous enoxaparin as a bridging anticoagulant treatment beginning on the first postoperative day and continuing until vitamin K antagonist treatment was fully effective. Patients were followed for 6 weeks. The primary endpoints were the incidence of thromboembolic or major bleeding events. RESULTS: Eleven (1%) thromboembolic events occurred. Ten of these events were transient or permanent strokes. Major bleeding events occurred in 44 patients (4.1%), 7 of which were observed before the enoxaparin treatment period. At the time of discharge, 570 patients (53.6%) were no longer receiving LMWH treatment due to achieving the target international normalized ratio. The mean length of hospital stay was 8.5 ± 2.9 days. There were no deaths during the 6-week follow-up period. CONCLUSIONS: In our highly selected population, after MHVR, postoperative anticoagulation using LMWH is associated with a low rate of thromboembolic and major bleeding events. This large observational study demonstrates that the use of LMWH as an anticoagulant is effective and safe after MHVR.

Endothelial dysfunction in sepsis.

The endothelium takes part in the regulation of numerous physiological functions and lies at the interface of circulating blood and the vessel wall. Under physiological conditions, it is responsible for anticoagulant and anti-adhesive properties, and it regulates vasomotor tone and vascular homeostasis. Endothelial dysfunction has been associated with many pathophysiological processes, such as inflammation and oxidative and nitrosative stresses. Endothelial cells are precociously exposed to circulating signaling molecules and physical stresses, like in sepsis and septic shock. Septic shock is associated with hypotension and frequently with disseminated intravascular coagulation contributing to multiple organ failure and a high mortality rate. Impairment of endothelial function leads to phenotypic and physical changes of the endothelium, with deregulated release of potent vasodilators nitric oxide and prostacyclin, reduction of vascular reactivity to vasoconstrictors, associated with leukocytes' and platelets' aggregation, and increase in inducible nitric oxide synthase expression that can exert a negative feedback on endothelial nitric oxide synthase expression, with subsequent deregulation of nitric oxide signaling. Endothelial dysfunction therefore plays a major role in the pathophysiology of septic shock and organ dysfunction, and has been suggested to be a predictor of mortality in sepsis. Thus, early detection of endothelial dysfunction could be of great interest to adapt treatment in initial stage of sepsis. Current therapeutics used in sepsis mostly aim at controlling inflammation, vascular function and coagulation. Fluid administration, vasopressors, vasodilators and recombinant human activated protein C are also part of the treatments with the ultimate goal to exert beneficial effects on organ function and survival.

Human serum albumin improves endothelial dysfunction and survival during experimental endotoxemia: concentration-dependent properties.

OBJECTIVES: The mechanisms by which human serum albumin might protect against sepsis-induced organ dysfunction and improve survival are not elucidated. The present study was designed to assess the effects of two concentrations of human serum albumin on endotoxin-induced mortality as well as on endothelial and organ dysfunctions in both mouse and cell models. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratories. SUBJECTS: Swiss mice (n = 10-15/group) were injected with either lipopolysaccharide or vehicle. Four and 12 hrs later, mice were infused or not with human serum albumin HSA (4% or 20%, 10 mL/kg) or normal saline (0.9% NaCl, 30 mL/kg). Human uterine vein endothelial cells were exposed to both lipopolysaccharide and tumor necrosis factor-α during 8 hrs in the presence or absence of human serum albumin (4% or 20%). MEASUREMENTS AND MAIN RESULTS: Mice survival, reactivity of mesenteric arteries, and Western blot protein analysis were assessed. Circulating endothelin-1, gluthatione, gluthatione disulfide, and creatinine plasma levels were measured. Nitric oxide production, oxidative, and nitrosative stresses were also measured in situ in endothelial cells. Human serum albumin 4%, but not human serum albumin 20% or normal saline solution, improved survival time of endotoxemic mice. Furthermore, human serum albumin 4% activated endothelial nitric oxide synthase and restored lipopolysaccharide-impaired flow-dependent endothelial dilation in mesenteric arteries. This was associated with a downregulation of nuclear factor κB and an upregulation of nuclear respiratory factor-2 and heme oxygenase-1. Human serum albumin 4% reduced lipopolysaccharide-induced renal dysfunction, enhanced endothelin-1 production and glutathione plasmatic levels, whereas human serum albumin 20% increased gluthatione disulfide. Furthermore, human serum albumin 4% but not 20% blunted lipopolysaccharide-tumor necrosis factor-α-induced oxidative and nitrosative stresses in endothelial cells and increased their gluthatione levels. CONCLUSIONS: The present data confirm a protective effect of 4% human serum albumin treatment both on mice survival and endothelial dysfunction by inhibiting inflammatory and oxidative stress pathways induced by endotoxins. Conversely, higher concentrations of human serum albumin were detrimental suggesting a dose-dependent effect.

Expression and biological activity of parathyroid hormone-related peptide in pregnant rat uterine artery: any role for 8-iso-prostaglandin F2alpha?

PTHrP is produced in vessels and acts as a local modulator of tone. We recently reported that PTHrP(1-34) is able to induce vasorelaxation in rat uterine arteries, but in pregnancy, this response is blunted and becomes strictly endothelium dependent. The present study aimed to get insights into the mechanisms involved in these changes because the adaptation of uterine blood flow is essential for fetal development. On d 20 of gestation, RT-PCR analysis of uterine arteries showed that PTH/PTHrP receptor (PTH1R) mRNA expression was decreased, whereas that of PTHrP mRNA was increased. This was associated with a redistribution of the PTHrP/PTH1R system, with both PTH1R protein and PTHrP peptide becoming concentrated in the intimal layer of arteries from pregnant rats. On the other hand, the blunted vasorelaxation induced by PTHrP(1-34) in uterine arteries from pregnant rats was specifically restored by indomethacin and a specific cyclooxygenase-2 inhibitor, NS 398. This was associated with an increase in cyclooxygenase-2 expression and in 8-iso-prostaglandin F(2alpha) release when uterine arteries from pregnant rats were exposed to high levels of PTHrP(1-34). Most interestingly, 8-iso-prostaglandin F(2alpha) itself was able to increase PTHrP expression and reduce PTH1R expression in cultured rat aortic smooth muscle cells. These results suggest a local regulation of uterine artery functions by PTHrP during pregnancy resulting from PTH1R redistribution. Moreover, they shed light on a potential role of 8-iso-prostaglandin F(2alpha).

Human serum albumin improves arterial dysfunction during early resuscitation in mouse endotoxic model via reduced oxidative and nitrosative stresses.

Human serum albumin (HSA) is used as a resuscitation fluid in sepsis. This study investigated the potential protective properties of HSA on vascular function in a mouse endotoxic model in terms of oxidative and nitrosative stresses. Swiss mice were treated with either lipopolysaccharide (LPS) (50 mg/kg i.p.) or vehicle. One and five hours later, mice were infused with HSA (4%, 10 ml/kg), normal saline (0.9% NaCl, 30 ml/kg), or no fluid. Six hours after treatment, vascular reactivity was assessed on aortae and small mesenteric arteries. Measurements of NO and superoxide anion (O2(-)) by spin trapping and nuclear factor (NF)-kappaB, inducible NO synthase (iNOS), and peroxynitrite by Western blotting and immunohistochemical studies were conducted. HSA partially prevented the reduction of blood pressure induced by LPS and completely prevented both vascular hyporeactivity to phenylephrine and myogenic tone as well as endothelial dysfunction induced by the endotoxin. This was associated with a decreased up-regulation of NF-kappa B, iNOS, and peroxynitrite in the vascular wall. LPS-induced tissue increases in both NO and O2(-) production was decreased by HSA. These data demonstrate the protective effect of HSA treatment in experimental endotoxic shock by reducing the inflammatory process leading to oxidative and nitrosative stresses and vascular hyporeactivity.

Microparticles from preeclamptic women induce vascular hyporeactivity in vessels from pregnant mice through an overproduction of NO.

Preeclampsia is associated with an increase of circulating levels of microparticles (MPs), but their role in vascular dysfunction during the course of preeclampsia is not understood. Inasmuch as preeclampsia is a gestational disease, we tested the effect of MPs from preeclamptic women (PrMPs) and MPs from normal pregnant women (CMPs) on vessels from pregnant mice. We exposed aortic rings from pregnant mice to circulating levels of PrMPs or CMPs for 24 h and evaluated their response to serotonin (5-HT). PrMPs, but not CMPs, were able to induce hyporeactivity in response to 5-HT in aortas from pregnant mice. The nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine strongly enhanced the response to 5-HT in PrMP-treated vessels but had no significant effect on CMP-treated vessels. The 5-HT-induced contraction in PrMP-treated vessels was completely abolished by the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 but was only reduced in CMP-treated vessels, suggesting an increased participation of COX-2 vasoconstrictor products in the effect of PrMPs. Consistent with this hypothesis, PrMPs enhanced levels of 8-isoprostane and PGE(2) in vessels, despite reduction of thromboxane B(2). These results strengthen the main concept that MPs in preeclampsia could act as vectors to stimulate intracellular cascades in vascular cells, leading to an enhanced NO production to counteract increased COX-2 vasoconstrictor metabolites by taking into account pregnancy.