Comparative force-frequency relationships in human and other mammalian ventricular myocardium

Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium.

“…This is in agreement with other reports (4,5,7,30). At the highest extracellular [Ca2+] (16 mM), there was no significant difference between myopathic and control muscles with respect to peak tension generated or peak intracellular calcium levels.…”

“…In addition, hemodynamic studies in patients with heart failure have shown little or no increase in contractility with increasing frequency of stimulation (6). Although it has been proposed that the negative force-frequency relationship in diseased human myocardium does not occur as a result of diminished sarcoplasmic reticulum calcium release (4,5), force-frequency relationships and postextrasystolic potentiation in human myocardium have not previously been studied in relation to calcium handling events. It was therefore of interest to us to investigate the force-frequency relationship and postextrasystolic potentiation in normal and diseased human myocardium in which sarcoplasmic reticulum calcium handling is impaired (7,8).…”

Altered myocardial force-frequency relation in human heart failure.

“…5 The present observation of a diminished or negative frequency treppe in BDM-pretreated failing myocardium has also been observed previously in studies that covered the lower frequency portion of the tensionfrequency curve in untreated myocardium. 4,5,1314 The slope of the present curve for BDM-treated failing myocardium (10%) in the 10-to 60-min-1 range of stimulation frequencies agrees well with the previously observed slope (3% to 4%) in this frequency range using untreated failing myocardium. 5 The correction is made for the 33% decrease expected6 in going from 30°C to 37°C.…”

“…12 In addition, peak rates of left ventricular pressure rise and fall are depressed and the heart rate-dependent potentiation of these parameters is greatly reduced or absent.3 Evidence suggesting that these deficiencies in cardiac performance in heart failure result from depressed contractility of the myocardium arises from observations of reduction or reversal of the normal positive inotropic response of isolated myocardium to increased stimulation frequency (frequency treppe). 4,5 cardiomyopathy (DCM). Excised hearts were cooled and washed of blood with chilled saline solution.…”

Pathophysiology of heart failure

“…However, it has been shown, using isolated left ventricular muscle preparations from patients with dilated cardiomyopathy, that the force of contraction does not increase significantly at higher rates of stimulation. [11][12][13][14] The Bowditch effect does not, therefore, apply to patients with severe heart failure. The reason for this is not fully understood.…”