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.
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J. Mol. Cell. Cardiol. · Apr 1994
Brain-death-induced cardiac contractile dysfunction: studies of possible neurohormonal and blood-borne mediators.
The aim of these studies was to investigate the mechanism underlying the haemodynamic changes associated with brain death. The initial series of studies were to assess whether these changes involved some blood-borne factor. When control rats (n = 6) were exsanguinated whilst being simultaneously transfused with blood from rats that had been brain-dead for 60 min, their haemodynamic function did not deteriorate. ⋯ Finally, we used L-NAME and naloxone in an attempt to identify roles for nitric oxide and endogenous opioid peptides but were again unable to influence the cardiac events. In conclusion, the initial transient hyperdynamic response induced by brain death appears to be mediated through cardiac innervation and can be inhibited by beta-adrenoreceptor blockade. However, the autonomic nervous system, nitric oxide, endogenous opioid peptides and blood-borne factors do not appear to be involved in the subsequent deterioration of cardiac function.
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J. Mol. Cell. Cardiol. · Mar 1994
Titin, myosin light chains and C-protein in the developing and failing human heart.
We investigated relative amounts of titin, myosin light chains (MLC), C-protein, and myosin heavy chains (MHC) in the functionally intact contractile apparatus of embryonic, adult normal, and adult failing human left ventricle by SDS polyacrylamide gel electrophoresis and Western blot analysis. The amount of titin and the titin-MHC ratio was significantly (P < 0.05) lower in the embryonic and adult failing human compared to the adult normal fibres. Additionally, we found a protein band having a lower molecular weight but the same immunoreactivity as native titin (fast-migrating titin; FM-titin) in the failing heart only. ⋯ Relative amount of C-protein was the same in normal and failing fibres but lower in the embryonic ventricles. Length-tension ratio of chemically skinned fibres prepared from terminally failing hearts was impaired compared to normal heart fibres. We conclude that both the reduced titin/MHC ratio and the expression of a structurally different titin form may be involved in the impaired contractile function of the terminally failing human heart.
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J. Mol. Cell. Cardiol. · Aug 1990
Are reperfusion-induced arrhythmias caused by disinhibition of an arrhythmogenic component of ischemia?
Isolated rat hearts were used to examine whether reperfusion-induced arrhythmias may be caused by washout of substances accumulating during ischemia. This was achieved by subjecting hearts to 10 min of regional ischemia and rendering them transiently inexcitable during the first 1.5 min of reperfusion. Transient inexcitability was induced by switching to cold solution (4 degrees C) shortly before reperfusion (-1.5 min). ⋯ The results indicated that transient hypothermia was antiarrhythmic as a result of a reduction of excitability, not because of bradycardia or impairment of recovery of flow. The data support the hypothesis that reperfusion unmasks (disinhibits) latent arrhythmogenic components of ischemia (particularly during the first 1.5 min of reperfusion) and that, by inducing inexcitability, transient hypothermia allows these substances to be washed out without their arrhythmogenic effects being manifested. The identities of the arrhythmogenic and antiarrhythmic substances remain to be determined; we suggest that cyclic AMP and potassium, respectively, are likely candidates.