Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability.

Plaque destabilization leading to myocardial infarction is observed after surgery even if the intervention is of noncardiovascular nature. Mediators of peri- or postoperative stress responsible for such events could include catecholamines and lipopolysaccharide (LPS). Monocytes may be involved in destabilization of atherosclerotic plaques by production of matrix metalloproteinases (MMP). We examined whether catecholamines could affect the expression of MMPs in human monocytes/macrophages and whether catecholamines could modulate LPS-stimulated expression of particular MMPs in these cells. Epinephrine and norepinephrine up-regulated MMP-1 and potentiated LPS-induced expression of MMP-1 in peripheral blood monocytes and monocyte-derived macrophages. We further characterized this effect employing the monocytic cell line U937 and showed that catecholamines potentiate LPS-induced effects on MMP-1 and MMP-9 antigen and activity. mRNA levels of the respective MMPs also increased. These effects did not result from higher mRNA stability but rather from increased transcription possibly induced by enhanced DNA binding of AP-1 and were mediated by either beta1- or beta 2-receptors. If this mechanism is also effective in vivo, our findings might, at least in part, help to explain the observation that cardiac events are important causes of morbidity and mortality after noncardiac surgery and support the findings that peri-operative beta-blockade has been shown to reduce postoperative mortality from cardiac events.

Levosimendan, a new inotropic and vasodilator agent.

Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent increases in myocardial oxygen demand and arrhythmogenesis. Levosimendan, a myofilament Ca2+ sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This action may be of specific interest in the setting of myocardial ischemia. To date, levosimendan is approved in 31 countries worldwide, and more patients with heart failure have participated in randomized controlled trials with levosimendan than with any other intravenous inotropic agent.

Acute perioperative heart failure.

PURPOSE OF REVIEW: Changes in epidemiology and advances in the treatment of coronary artery disease, hypertension and diabetes mellitus have increased the prevalence of heart failure in the general population, and also the number of patients with heart failure presenting for surgery. Particularly in the perioperative period, patients with chronic heart failure are faced with numerous triggers of acute decompensation that can partly be avoided or treated. Patients without preexisting myocardial contractile dysfunction may sustain severe perioperative complications, e.g. myocardial infarction, with subsequent acute heart failure as a consequence. Approaches for diagnosis and treatment in these situations may vary considerably. RECENT FINDINGS: Patients with preexisting heart failure undergoing non-cardiac surgery suffer substantial morbidity and mortality despite advances in perioperative care. The importance of heart failure as an independent risk factor is underlined by the fact that patients with coronary artery disease but without heart failure have a similar 30-day mortality rate to the general population. B-type natriuretic peptide testing is an attractive and non-invasive tool in non-surgical patients for the diagnosis of heart failure, but its role in the perioperative period for the diagnosis of myocardial contractile dysfunction is less clear. For inotropic support, levosimendan, a myofilament calcium sensitizer, has become available in several European countries, and encouraging positive reports have recently been published in this area. SUMMARY: The role of B-type natriuretic peptide testing in the perioperative period is confounded by several variables that limit its use in that setting. New developments in positive inotropic therapy are challenging older and potentially harmful treatment strategies.