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(Circulation. 1999;100:2303.)
© 1999 American Heart Association, Inc.

Editorials

Molecular Inotropy

A Future Approach to the Treatment of Heart Failure?

William H. Barry, MD

From the University of Utah Health Sciences Center, Salt Lake City.

Correspondence to William H. Barry, MD, University of Utah Health Sciences Center, 50 North Medical Dr, Salt Lake City, UT 84132.

Key Words: Editorials • inotropic agents • heart failure • transfection • sarcoplasmic reticulum

Maurice et al¹ recently reported that a global ventricular 10-fold overexpression of the ß-2 adrenergic receptor, mediated by the intracoronary injection of an adenoviral vector, can be produced in the rabbit. This overexpression resulted in an increased maximum rate of change in left ventricular pressure, dp/dt_max, both at baseline and in response to isoproterenol infusion at 6 days after transgene delivery, with the enhanced isoproterenol response persisting for up to 21 days. They concluded that genetic modulation to improve the function of the intact heart is feasible. In this issue of Circulation, del Monte et al² describe experiments that indicate that gene therapy can improve failing human cardiac myocyte function. These investigators demonstrated that the abnormal contraction, relaxation, and contraction amplitude-frequency relationship of isolated myocytes obtained from patients with dilated cardiomyopathy could be normalized by transfection of the myocytes in vitro with an adenovirus expressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase, SERCA2a; transfection increased Ca²⁺ ATPase activity by 80%. The enhanced function of the myocytes was associated with corresponding improvements in the kinetics of the Ca²⁺ transient. The isolated myocyte results confirm previous in vitro findings by Meyer et al³ in normal rabbit myocytes that indicated that adenoviral transfection of SERCA2a can improve contraction and relaxation.

Early studies by Lindenmayer et al⁴ suggested that the Ca²⁺ uptake of isolated SR vesicles was impaired in failing human myocardium, and Grossman et al⁵ found that the peak dp/dt of left ventricular pressure decline and the velocity of circumferential fiber lengthening . . . [Full Text of this Article]

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