Preserved ventricular contractility in infarcted mouse heart overexpressing beta(2)-adrenergic receptors.
Effects of cardiac specific overexpression of beta(2)-adrenergic receptors (beta(2)-AR) on the development of heart failure (HF) were studied in wild-type (WT) and transgenic (TG) mice following myocardial infarction (MI) by coronary artery occlusion. Animals were studied by echocardiography at weeks 7 to 8 and by catheterization at week 9 after surgery. Post-infarct mortality, due to HF or cardiac rupture, was not different among WT mice, and there was no difference in infarct size (IS). Compared with the sham-operated group (all P < 0.01), WT mice with moderate (<36%) and large (>36%) IS developed lung congestion, cardiac hypertrophy, left ventricular (LV) dilatation, elevated LV end-diastolic pressure (LVEDP), and suppressed maximal rate of increase of LV pressure (LV dP/dt(max)) and fractional shortening (FS). Whereas changes in organ weights and echo parameters were similar to those in infarcted WT groups, TG mice had significantly higher levels of LV contractility in both moderate (dP/dt(max) 4,862 +/- 133 vs. 3,694 +/- 191 mmHg/s) and large IS groups (dP/dt(max) 4,556 +/- 252 vs. 3,145 +/- 312 mmHg/s, both P < 0.01). Incidence of pleural effusion (36% vs. 85%, P < 0.05) and LVEDP levels (6 +/- 0.3 vs. 9 +/- 0.8 mmHg, P < 0.05) were also lower in TG than in WT mice with large IS. Thus beta(2)-AR overexpression preserved LV contractility following MI without adverse consequence.
Du
X J
XJ
Baker Medical Research Institute and Alfred Heart Centre, Alfred Hospital, Melbourne 8008, Victoria, Australia. xiaojun.du@baker.edu.au
Gao
X M
XM
Jennings
G L
GL
Dart
A M
AM
Woodcock
E A
EA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002304:Cardiac Pacing, Artificial; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D004452:Echocardiography; D015870:Gene Expression; D006339:Heart Rate; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015996:Survival Rate; D016276:Ventricular Function / Q000187:drug effects / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D004280:Dobutamine