Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.

Schwinger, Robert H. G.; Böhm, Michael; Müller‐Ehmsen, Jochen; Uhlmann, Rainer; Schmidt, Ulrich; Stäblein, Alexander; Überführ, P.; Kreuzer, E; Reichart, Bruno; Eissner, Hans-Joachim

doi:10.1161/01.cir.88.5.2267

Cited by 113 publications

(49 citation statements)

References 28 publications

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“…Schwinger et al 35 demonstrated partial reversal of the negative forcefrequency relationship in failing human myocardium with low-dose isoprenaline, and similar in vitro effects have been observed with gene transfer of sarcoplasmic reticulum calcium ATPase. 36 Myocyte "recovery" after mechanical circulatory support is also associated with improved forcefrequency.…”

Section: Force-frequency and Relaxation-frequency Relationshipsmentioning

confidence: 61%

Direct Myocardial Effects of Levosimendan in Humans With Left Ventricular Dysfunction

et al. 2007

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Background-Enthusiasm for the development of Ca 2ϩ sensitizers as inotropic agents for heart failure has been tempered by reports of impaired relaxation. Levosimendan, which increases myofilament Ca 2ϩ sensitivity via Ca 2ϩ -dependent binding to troponin C, exerts positive inotropic and lusitropic effects in failing human myocardium in vitro. We sought to determine the direct effects of levosimendan on failing human myocardium in vivo, and in particular whether levosimendan exerts heart rate-dependent effects on systolic or diastolic function. Methods and Results-Ten patients with left ventricular dysfunction caused by nonischemic dilated cardiomyopathy (mean left ventricular ejection fraction, 27Ϯ2%) were instrumented with an infusion catheter in the left main coronary artery, a high-fidelity micromanometer-tipped catheter in the left ventricle, and a bipolar pacing wire in the right atrium. Inotropic (peak ϩdP/dt) and lusitropic (Tau) responses were assessed during continuous intracoronary drug infusion in sinus rhythm followed by atrial pacing at 20, 40, and 60 beats per minute above the sinus rate. Under control conditions (intracoronary 5% dextrose in water), atrial-pacing tachycardia decreased Tau by 13% (PϽ0.05), but did not increase ϩdP/dt. Intracoronary levosimendan (3.75 and 12.5 g/min for 15 minutes each) increased ϩdP/dt dose-dependently and decreased Tau over a range of heart rates, but did not alter the slope of the force-frequency or relaxation-frequency relationship. Conclusions-Myocardial

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Section: Force-frequency and Relaxation-frequency Relationshipsmentioning

confidence: 61%

Direct Myocardial Effects of Levosimendan in Humans With Left Ventricular Dysfunction

et al. 2007

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“…Measurements of active tension in these preparations consistently showed that the HCM muscle displays a positive force-frequency relationship (Figure 5A and 5B), in contrast to failing human myocardium 21 or end-stage human HCM. 22 In addition, muscle contractile reserve was preserved, as indicated by the positive inotropic response to isoproterenol.…”

Section: Contractile Function Of Hcm Trabeculae: I Nal Inhibition Impmentioning

confidence: 71%

Late Sodium Current Inhibition Reverses Electromechanical Dysfunction in Human Hypertrophic Cardiomyopathy

et al. 2013

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“…Experiments were performed as described in detail previously (30). Immediately after excision, the atrial muscle strips and ventricular papillary muscle strips were placed in ice-cold, preaerated Tyrode's solution and delivered to the laboratory within 10 min.…”

Section: Methodsmentioning

confidence: 99%

Regional expression of sodium pump subunits isoforms and Na+-Ca++ exchanger in the human heart.

Wang

Schwinger²,

Frank³

et al. 1996

J. Clin. Invest.

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Cardiac glycosides exert a positive inotropic effect by inhibiting sodium pump (Na,K-ATPase) activity, decreasing the driving force for Na ϩ -Ca ϩϩ exchange, and increasing cellular content and release of Ca ϩϩ during depolarization. Since the inotropic response will be a function of the level of expression of sodium pumps, which are ␣␤ heterodimers, and of Na ϩ -Ca ϩϩ exchangers, this study aimed to determine the regional pattern of expression of these transporters in the heart. Immunoblot assays of homogenate from atria, ventricles, and septa of 14 nonfailing human hearts established expression of Na,K-ATPase ␣ 1, ␣ 2, ␣ 3, ␤ 1, and Na ϩ -Ca ϩϩ exchangers in all regions. Na,K-ATPase ␤ 2 expression is negligible, indicating that the human cardiac glycoside receptors are ␣ 1 ␤ 1,, ␣ 2 ␤ 1, and ␣ 3 ␤ 1. ␣ 3, ␤ 1, sodium pump activity, and Na ϩ -Ca ϩϩ exchanger levels were 30-50% lower in atria compared to ventricles and/or septum; differences between ventricles and septum were insignificant. Functionally, the EC 50 of the sodium channel activator BDF 9148 to increase force of contraction was lower in atria than ventricle muscle strips (0.36 vs. 1.54 M). These results define the distribution of the cardiac glycoside receptor isoforms in the human heart and they demonstrate that atria have fewer sodium pumps, fewer Na ϩ -Ca ϩϩ exchangers, and enhanced sensitivity to inotropic stimulation compared to ventricles. ( J. Clin. Invest. 1996. 98:1650-1658.)

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Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.

Cited by 113 publications

References 28 publications

Direct Myocardial Effects of Levosimendan in Humans With Left Ventricular Dysfunction

Direct Myocardial Effects of Levosimendan in Humans With Left Ventricular Dysfunction

Late Sodium Current Inhibition Reverses Electromechanical Dysfunction in Human Hypertrophic Cardiomyopathy

Regional expression of sodium pump subunits isoforms and Na+-Ca++ exchanger in the human heart.

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