Biomedical subjects

Alexandre Mebazaa

Publications and source records attributed to Alexandre Mebazaa.

28 records · Page 2Linked to original sources

PubMed2004

High incidence of myocardial ischemia during postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia. METHODS: On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia. RESULTS: A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty-eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively) and increased heart rate (> 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels. CONCLUSIONS: These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients.

Adult↗

PubMed2004

Human septic myopathy: induction of cyclooxygenase, heme oxygenase and activation of the ubiquitin proteolytic pathway.

BACKGROUND: Skeletal muscle failure and wasting are manifestations of sepsis in humans that leads to serious and prolonged complications. The authors investigated the role of the major proinflammatory and antiinflammatory pathways, namely the inducible isoforms cyclooxygenase (COX-2) and heme oxygenase (HO-1), and the ubiquitin proteolytic pathway in skeletal muscle of septic patients. METHODS: Protein expression was detected by Western blot techniques. Muscle biopsies were taken from two muscle groups, rectus abdominis and vastus lateralis, of septic and control patients. RESULTS: The study showed an increase in COX-2 and HO-1 proteins expression and an activation of the proteolytic ubiquitin pathway with a parallel increase in free ubiquitin and ubiquitinated proteins in skeletal muscle of septic but not of control patients. In addition, those patients who would die from septic shock expressed more COX-2 and HO-1 proteins in muscle biopsies than did those patients who would survive. CONCLUSIONS: This study showed a marked involvement of local proinflammatory and antiinflammatory pathways and, more importantly, demonstrated the existence of an active ubiquitin proteolytic pathway in skeletal muscle of septic patients. Activation of ubiquitin pathway could be involved in sepsis-related muscle catabolism and wasting.

Adult↗

PubMed2004

ATP-dependent potassium channels as a key target for the treatment of myocardial and vascular dysfunction.

PURPOSE OF REVIEW: The aim of this review is to highlight the most recent and interesting articles on the physiologic properties and functions of ATP-dependent potassium channels in the cardiovascular system and on the role of the potassium channel openers for the treatment of cardiovascular dysfunction. RECENT FINDINGS: The initial efforts in the development of potassium channel openers focused on the management of systemic hypertension. Lately, the range of possible indications for potassium channel openers has increased to include pulmonary hypertension and stable angina pectoris. The discovery of a connection between the mitochondrial ATP-dependent potassium channels and the phenomenon of cardiac preconditioning created potential new uses for potassium channel openers in myocardial ischemia, inn unstable angina, in preoperative and perioperative settings, and for the preservation of organs for transplant. SUMMARY: The most recent data on the physiologic roles of sarcolemmal and mitochondrial ATP-dependent potassium channels and the pharmacology of potassium channel openers in the cardiovascular system are summarized and discussed. Finally, the effects of potassium channel opener drugs including minoxidil, nicorandil, pinacidil, bimakalin, and levosimendan, a dual-action potassium channel opener and calcium sensitizer with inodilator and cardioprotective activity, are discussed.

Adenosine Triphosphate↗

PubMed2004

Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock.

Although the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR has been shown to be decreased during human sepsis, its level of expression in other nonseptic critical conditions is unclear. The aim of this study was to compare the level of HLA-DR expression on circulating monocytes among patients with septic, hemorrhagic, and cardiogenic shocks and severe sepsis without shock. At admission, HLA-DR expression was exclusively decreased in patients with septic shock (n = 30; P < 0.001), whereas the expression was similar between the other studied groups: cardiogenic shock (n = 16), hemorrhagic shock (n = 11), severe sepsis without shock (n = 18), and healthy volunteers (n = 8). HLA-DR expression was not predictive for overall mortality, but at day 1, an HLA-DR expression of less than 14 of mean fluorescence intensity (that corresponds to 40% labeled monocytes) was predictive of mortality exclusively in patients with septic shock (odds ratio, 11.4 and 95% confidence interval, 1.7; 78.4; P < 0.008). Catecholamine infusion, mechanical ventilation, positive blood culture, and number of units of blood or plasma transfused did not correlate with decreased HLA-DR expression. Thus, the decrease in HLA-DR expression is specific to septic shock and is associated, in septic shock patients, with increased mortality risk.

Adult↗

PubMed2004

Successful use of levosimendan in a patient with peripartum cardiomyopathy.

UNLABELLED: This case represents the first reported use of levosimendan, a calcium-sensitizing drug with additional vasodilation properties, for treatment of a woman with peripartum cardiomyopathy. Levosimendan induced a steady decline of increased pulmonary capillary wedge pressure, followed by a definitive increase in cardiac stroke volume. The patient recovered from this serious episode of heart failure, and she ultimately regained left ventricular function. IMPLICATIONS: Acute heart failure is a life-threatening event that only rarely occurs during childbirth. We report a case of a woman who experienced cardiovascular collapse during vaginal delivery. We determined that she met current diagnostic criteria for peripartum cardiomyopathy, and we successfully treated her with levosimendan, a calcium-sensitizing drug with additional vasodilation properties.

Adult↗

PubMed2003

Acute right ventricular failure--from pathophysiology to new treatments.

The right ventricle (RV) provides sustained low-pressure perfusion of the pulmonary vasculature, but is sensitive to changes in loading conditions and intrinsic contractility. Factors that affect right ventricular preload, afterload or left ventricular function can adversely influence the functioning of the RV, causing ischaemia and right ventricular failure (RVF). As RVF progresses, a pronounced tricuspid regurgitation further decreases cardiac output and worsens organ congestion. This can degenerate into an irreversible vicious cycle. The effective diagnosis of RVF is optimally performed by a combination of techniques including echocardiography and catheterisation, which can also be used to monitor treatment efficacy. Treatment of RVF focuses on alleviating congestion, improving right ventricular contractility and right coronary artery perfusion and reducing right ventricular afterload. As part of the treatment, inhaled nitric oxide or prostacyclin effectively reduces afterload by vasodilating the pulmonary vasculature. Traditional positive inotropic drugs enhance contractility by increasing the intracellular calcium concentration and oxygen consumption of cardiac myocytes, while vasopressors such as norepinephrine increase arterial blood pressure, which improves cardiac perfusion but increases afterload. A new treatment, the calcium sensitiser, levosimendan, increases cardiac contractility without increasing myocardial oxygen demand, while preserving myocardial relaxation. Furthermore, it increases coronary perfusion and decreases afterload. Conversely, traditional treatments of circulatory failure, such as mechanical ventilation and volume loading, could be harmful in the case of RVF. This review outlines the pathophysiology, diagnosis and treatment of RVF, illustrated with clinical case studies.

Acute Disease↗

PubMed2003

Sternal puncture allows an early diagnosis of poststernotomy mediastinitis.

OBJECTIVES: Poststernotomy mediastinitis after cardiac operations is a nosocomial infection involving the mediastinal space and the sternum, with a high mortality rate mostly related to a late diagnosis. We investigated whether sternal puncture might facilitate and shorten the delay in the diagnosis of mediastinitis. METHODS: Of 1024 patients undergoing sternotomy for cardiac surgery, sternal puncture was performed in a subgroup of 49 patients in whom mediastinitis was suspected. RESULTS: Sternal puncture culture results were positive for all patients with true mediastinitis (n = 23) and negative in 24 of 26 patients without mediastinitis. In addition, sternal puncture allowed diagnosis of mediastinitis with a shorter delay (9 +/- 5 days vs 13 +/- 8 days, P =.04) and caused a reduction in the length of mechanical ventilation (3 +/- 4 days vs 10 +/- 13 days, P =.02) and stay in the intensive care unit (9 +/- 7 days vs 18 +/- 15 days, P =.02) compared with that found in another group of patients (n = 20) operated on for true mediastinitis on the basis of the presence of classic, delayed, clinical signs. CONCLUSIONS: Our study shows that sternal puncture is a rapid and safe method to ensure the diagnosis of poststernotomy mediastinitis.

Aged↗

PubMed2003

Efficacy of esmolol as a myocardial protective agent during continuous retrograde blood cardioplegia.

OBJECTIVE: Esmolol, an ultra-short-acting beta-blocker, is known to attenuate myocardial ischemia-reperfusion injury. The aim of this study was to compare the effects of esmolol and potassium on myocardial metabolism during continuous normothermic retrograde blood cardioplegia. METHODS: Forty-one patients operated on for isolated aortic valve stenosis were randomly assigned to continuous coronary infusion with either potassium or esmolol during cardiopulmonary bypass. Myocardial metabolism was assessed by measuring the transmyocardial gradient of oxygen content indexed to left ventricular mass of glucose, lactate, and nitric oxide. To do so, blood samples were simultaneously withdrawn upstream (in the cardioplegia line) and downstream of the myocardium (in the left coronary ostium) 10 and 30 minutes after aortic crossclamping. RESULTS: Although the cardioplegia flow rate and pressure were similar, esmolol markedly reduced the transmyocardial gradient of oxygen content indexed to left ventricular mass compared with potassium: 13 +/- 6 vs 20 +/- 6 mL of oxygen per liter of blood per 100 g of myocardium, respectively, at 10 minutes and 16 +/- 8 vs 24 +/- 8 mL of oxygen per liter of blood per 100 g of myocardium, respectively, at 30 minutes (P =.009). Coronary glucose and lactate transmyocardial gradients were similar in both groups, indicating adequate myocardial perfusion in all patients at all times. In addition, during retrograde cardioplegia, esmolol showed a lower nitric oxide release compared with that caused by potassium (39 +/- 49 micro mol x L(-1) for potassium vs 14 +/- 8 micro mol x L(-1) for esmolol at 10 minutes and 39 +/- 47 micro mol x L(-1) for potassium vs 6 +/- 8 micro mol x L(-1) for esmolol at 30 minutes, P =.05). However, hemodynamic parameters and plasma troponin I levels remained unchanged postoperatively between the 2 types of cardioplegia. CONCLUSION: Esmolol provides potent myocardial protection in hypertrophied hearts, at least in part, by reducing myocardial oxygen metabolism.

Adrenergic beta-Antagonists↗

PubMed2003

The clinical experience with levosimendan in anesthesiology and in the intensive care unit.

In the present review striking data showing that intensive care unit patients with acute heart failure and high-risk surgical patients may markedly benefit from the use of levosimendan are presented. Indeed, levosimendan is an effective new agent that acts via two complementary mechanisms. It enhances cardiac contractility by improving the response of the myofilaments to intracellular calcium, and it reduces the cardiac workload by opening the adenosine triphosphate-dependent potassium channels for the dilation of blood vessels. Because the therapeutic levels of levosimendan do not increase the intracellular calcium concentrations, levosimendan is less likely than traditional inotropes (beta-agonist inotropes or phosphodiesterase inhibitors) to elicit arrhythmias or impair diastolic relaxation. In fact, the results of recent clinical studies indicate that levosimendan offers significant hemodynamic and survival benefits when given to patients who are hospitalized for acute heart failure. Indeed, in the near future, it is likely that levosimendan may also prove effective for the treatment of patients with diastolic heart failure or for those with a low cardiac output following coronary artery bypass grafting. In addition, levosimendan has the potential of supporting the cardiac function during the initiation of beta-blocker therapy, for weaning patients from cardiopulmonary bypass, for individuals with valvular abnormalities and for those with myocarditis. Preliminary results also suggest that levosimendan may be beneficial for the treatment of patients with right ventricular heart failure. Although the use of levosimendan has been fully validated for the most common causes of acute heart failure, additional clinical trials are needed to safety broaden its therapeutic indications.

Adrenergic beta-Antagonists↗

PubMed2002

Inducible nitric oxide synthase (NOS2) expressed in septic patients is nitrated on selected tyrosine residues: implications for enzymic activity.

Tyrosine nitration is a post-translational protein modification with potentially significant biological implications. In the present study we demonstrate, for the first time, that tyrosine residues of human inducible nitric oxide synthase (NOS2) can be nitrated by peroxynitrite in vitro, leading to a decreased activity. Moreover, we show that NOS2 expressed in a skeletal muscle from septic patients is nitrated on selective tyrosine residues belonging to a canonic sequence. This phenomenon could be an endogenous mechanism of in vivo modulation of NOS2 enzymic activity.

Amino Acid Sequence↗