Journal of molecular and cellular cardiology
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J. Mol. Cell. Cardiol. · Jan 1995
ReviewMyocardial contractile dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes.
A major determinant of survival in patients with advanced viral or bacterial infection, or following severe trauma or burns complicated by multiple organ failure, is the combination of clinical signs termed the systemic inflammatory response syndrome (SIRS). SIRS is characterized by hypotension, tachypnea, hypo- or hyperthermia and leukocytosis as well as other clinical signs and symptoms, including a depression in myocardial contractile function. Heart failure complicating systemic sepsis or other causes of SIRS is usually not accompanied by coronary artery ischemia due to hypotension, myocardial necrosis, or marked cardiac interstitial inflammatory infiltrates, and thus the cause of cardiac contractile dysfunction in this syndrome has remained unclear. ⋯ Activation of cNOS appears to modulate cardiac myocyte responsiveness to muscarinic cholinergic and beta-adrenergic receptor stimulation. Induction of iNOS by soluble inflammatory mediators, including cytokines, causes a marked depression in myocyte contractile responsiveness to beta-adrenergic agonists. Thus, inappropriate activation of cNOS or excessive or prolonged induction of iNOS in the myocardium may contribute to cardiac dysfunction complicating SIRS.
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J. Mol. Cell. Cardiol. · Jan 1995
Cesium effects on dual pacemaker mechanisms in guinea pig sinoatrial node.
The aim of the present experiments was to study the effects of cesium (Cs) on dual pacemaker potentials and the underlying mechanisms in isolated sinoatrial (SA) node of the guinea pig superfused in vitro. Cs (1-20 mM) initially hyperpolarized the maximum diastolic potential (MDP) and then depolarized it in a concentration-dependent manner. In subsidiary pacemaker cells of the SA node, increasing [Cs]o abolished diastolic depolarization (DD), but then (by depolarizing the cells to less negative potentials) Cs allowed the appearance of a shallow DD that maintained spontaneous discharge even in 20 mM Cs. ⋯ The pacemaker potential at more negative voltages is blocked by Cs, but the dominant type pacemaker potential is not blocked even by 20 mM Cs (which is known to completely block I(f). Cs initially hyperpolarizes apparently by stimulating the Na/K pump (not by blocking I(f)) and subsequently depolarizes the subsidiary pacemaker cells by blocking an outward current but not IK1 (absent in the SA node). Thus, in the SA node I(f) may play little role in pacemaker activity.