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Research was conducted to examine the involvement of microtubules in early hypertrophic responses of myocardium during pressure overload. The objective is to determine whether the inhibition of microtubule function led to a decreased expression of the immediate early gene c-fos and fetal contractile protein genes. Results revealed another possible physiological function of microtubule cytoskeleton which is the induction of the hypertrophic gene program in reaction to the mechanical load.

The effects of heart failure on the expression of the sarcoplasmic reticulum (SR) calcium-adenosine triphosphatase (Ca2+-ATPase) and the subsequent effect on contractility was investigated in isolated myocyte from dogs with pacing-induced heart failure and normal controls. Results reveal that heart failure depresses the expression of Ca2+-ATPase resulting in a reduction in SR calcium uptake. This leads to a depression in myocardial contractility.

Objective: Contractile function is depressed at the isolated myocyte level in heart failure (HF), which could result from the decreased availability of intracellular calcium ([Ca2+]i) to the myofibrils and/or the depressed sensitivity of myofilaments to [Ca2+]i. However, the cellular basis of contractile dysfunction remains unestablished. Methods: We isolated left ventricular myocytes from dogs with rapid pacing-induced HF. Cell shortening and [Ca2+]i transients were measured by indo-1 fluorescence and the myofilament Ca2+ sensitivity was analyzed by the shortening–[Ca2+]i relation in intact myocytes as well as by the pCa–tension relation in skinned cells. Results: Peak cell shortening magnitude was depressed in HF, associated with a parallel decrease of [Ca2+]i transient amplitude. There was a significant positive correlation between these two variables (r=0.71, P<0.01). In contrast, myofibrillar sensitivity to Ca2+, determined by both intact and skinned myocytes, was comparable between control and HF. Further, there was no significant difference in Ca2+ sensitivity between control and HF even at shorter (1.8 μm) or longer (2.2 μm) sarcomere length. Conclusions: Using both intact and skinned cellular preparations, a potential defect in myocyte contractile function in HF was a reduction in Ca2+ availability to the myofilaments, rather than the inherent defects in myofilament sensitivity to Ca2+. [ABSTRACT FROM PUBLISHER]

Sarcoplasmic reticulum (SR) Ca2+-adenosine triphosphatase (ATPase) mRNA expression is reduced in the failing human myocardium. However, it is not known whether SR Ca2+-regulatory protein gene expression is altered in human myocardial tissue subjected to pressure overload or volume overload. We sought to determine whether SR Ca2+-regulatory protein gene expression is altered in human atrial tissue subjected to mechanical overload. We obtained right atrial myocardial tissue (about 250mg) at open-heart surgery from three groups of patients: no hemodynamic overload to the right atrium (control group; 12 patients), atrial septal defect (ASD group; 8 patients), and tricuspid regurgitation (TR group; 7 patients). We measured the myocyte size, the area of interstitial fibrosis, SR Ca2+-ATPase, and ryanodine receptor mRNA abundance. The isolated cardiocyte area and the percent area of interstitial fibrosis were in the order TR > ASD > control ( P < 0.05). The SR Ca2+-ATPase mRNA level in TR was significantly decreased ( P = 0.004) compared with the control, whereas in the ASD group it did not differ significantly from control. There were no significant differences in ryanodine receptor mRNA levels among the three groups. SR Ca2+-ATPase gene expression was downregulated in human atrial tissue with TR but not in ASD, which might have resulted from the differences in the degree and/or the type of hemodynamic overload to the myocardium. [ABSTRACT FROM AUTHOR]

Determines the functional consequence of a decreased expression of sarcoplasmic reticulum (SR) Ca[sup 2+]-ATPase in tachycardia-induced heart failure. Myocyte contractile function and gene expression of SR Ca[sup 2+]-ATPase; Effects of thapsigargin and cyclopiazonic acid on contractile function and intracellular free Ca[sup 2+] concentration transient in normal myocytes.