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PRESERVATION OF MECHANICAL AND ENERGETIC FUNCTION AFTER ADENOVIRAL GENE TRANSFER IN NORMAL RAT HEARTS
Author(s) -
Sakata Susumu,
Liang Lifan,
Sakata Naoya,
Sakata Yuri,
Chemaly Elie R,
Lebeche Djamel,
Takewa Yoshiaki,
Chen Jiqiu,
Park Woo Jin,
Kawase Yoshiaki,
Hajjar Roger J
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04742.x
Subject(s) - ex vivo , in vivo , contractility , medicine , green fluorescent protein , cardiac function curve , cardiology , chemistry , endocrinology , heart failure , biology , gene , biochemistry , microbiology and biotechnology
SUMMARY1 The aim of the present study was to examine the acute and chronic effects of adenoviral gene transfer on cardiac function in terms of left ventricular (LV) mechanoenergetic function. Recombinant adenoviral vector carrying β‐galactosidase and green fluorescent protein genes (Ad.βgal‐GFP) was used. Cardiac function was examined in cross‐circulated rat heart preparations, where end‐systolic/diastolic pressure–volume relationships (ESPVR/EDPVR), systolic pressure–volume area (PVA), LV relaxation rate, equivalent maximal elastance at mid‐range LV volume (eE max at mLVV), coronary blood flow, coronary vascular resistance and myocardial oxygen consumption (VO 2 ) were also measured. 2 To examine the ex vivo acute effects of the adenoviral vector, data were obtained before and 30–90 min after intracoronary infusion of Ad.βgal‐GFP in the excised, cross‐circulated hearts that underwent serotonin pretreatment. To examine the in vivo chronic effects of adenoviral gene transfer, normal rat hearts received Ad.βgal‐GFP or saline by a catheter‐based technique and data were obtained 3 days after the injection of Ad.βgal‐GFP or saline. 3 The ESPVR, EDPVR, LV relaxation rate, eE max at mLVV, coronary blood flow and coronary vascular resistance remained unchanged in Ad.βgal‐GFP‐transfected hearts in both ex vivo acute and in vivo chronic experiments. Moreover, the ex vivo and in vivo transfection caused no change in the slope and VO 2 intercept of the VO 2 –PVA relationship, VO 2 for basal metabolism and for Ca 2+ handling in excitation–contraction coupling and O 2 costs of LV contractility. 4 These results indicate that adenoviral gene transfer has neither acute nor chronic toxic effects on LV mechanical and energetic function. A special combination of in vivo adenoviral gene transfer and a cross‐circulation experimental system may provide a useful novel strategy to explore the functional and mechanoenergetic role of specifically targeted genes in the diseased heart.