Preserved Frank–Starling mechanism in human end stage heart failure

Abstract

Objective: The goal of the present study was to examine the ability of failing myocardium to respond to enhanced preload with an Ž . increase in force development. Methods: The effect of various preload conditions 2.5-15 mN on force development was studied in Ž . right ventricular trabeculae carneae from explanted human failing hearts with ischemic cardiomyopathy ICM, n s 5, 42 preparations or Ž . idiopathic dilated cardiomyopathy DCM, n s 9, 77 preparations . To determine the severity of cardiac impairment we measured the Ž to length of maximal force development from 3.7 " 0.5 ICM and 2.7 " 0.4 DCM to 8.3 " 0.9 and 6.5 " 0.8 mNrmm , respectively Ž . Ž. The Frank-Starling mechanism is preserved in terminally failing human hearts irrespective of the underlying etiology. We found no relation between the severity of cardiac impairment as assessed by either ANP expression or the ISOrCa 2q ratio and the ability of failing human myocardium to respond to enhanced preload with an increase in force development. q 1998 Elsevier Science B.V.

Tissue Engineering of a Differentiated Cardiac Muscle Construct

“…3-5 (3) In accordance with the organized tissue-like morphology, circular EHTs exhibited a tissue-like ratio of TT to RT of 1.33, 3.29, and 14.02 under basal, maximal calcium, and maximal isoprenaline concentrations, respectively. The basal values are in line with similar ratios in intact trabeculae or papillary muscles from humans and rats, 19,20 indicating that in circular EHTs, the matrix contributes significantly less to mechanic properties than in the planar lattices, for which we have described a ratio of TT to RT of 0.2 to 0.3. 1,2,15 (4) The positive inotropic response to isoprenaline amounted to Ͼ100% of basal TT in circular EHTs compared with only Ϸ15% to 30% in the planar lattices.…”

A Proteolytic NH2-terminal Truncation of Cardiac Troponin I That Is Up-regulated in Simulated Microgravity

“…This decrease began at 2 weeks of tail suspension (data not shown) and became significant at 4 weeks of tail suspension. However, the lengthtension relationship was preserved in the cardiac muscle of tail suspension rats, similar to that seen in the failing cardiac muscle (42,43). The calculated V max of the papillary muscle was also decreased after 4 weeks of tail suspension (p Ͻ 0.05) (Fig.…”

Depressed inotropic response to increased preload in rabbit hearts with left-ventricular dysfunction induced by chronic myocardial infarction

“…As discussed, immediate contractile consequences of segment length changes are attributed to altered myofilament Ca 2+ sensitivity and actomyosin overlap [1,27] and is considered to be the cellular basis of the Frank-Starling mechanism. The reduced immediate response in the LVD group suggests an impaired Frank-Starling response in agreement with previous studies on a dog model [15] and one human study [14], but two other studies on human tissue failed to find any depression of the Frank-Starling mechanism in heart failure [12,13]. The reason for this disparity is unknown; extent and duration of the ventricular dysfunction may be important determinants.…”

“…Work on animal models and humans has characterised many aspects of the contractile dysfunction, including the reduced ability of the failing myocardium to respond to acute positive inotropic stimuli such as increased heart rate [10] and β-adrenergic stimulation [11]. However, the extent to which the acute positive inotropic response to an increased preload (the Frank-Starling relationship) is depressed in heart failure remains controversial [12,13,14,15]. Furthermore, the degree to which the secondary, slow inotropic response is maintained in hypertrophic myocardium has not been studied.…”