Severe heart failure is associated with a reduction in myocardial P3-adrenergic receptor density and an impaired contractile response to catecholamine stimulation. Metoprolol was administered during a 6-month period to 14 patients with dilated cardiomyopathy to examine its efrects on these abnormalities. The mean daily dose of metoprolol for the group was 105 mg (range, 75-150 mg). Myocardial ,B-receptor density, resting hemodynamic output, and peak left ventricular dP/dt response to dobutamine infusions were compared in 9, 14, and 7 patients, respectively, before and after 6 months of metoprolol therapy while the patients were on therapy. The second hemodynamic study was performed 1-2 hours after the morning dose of metoprolol had been given. Myocardial f-receptor density increased from 39±7 to 80±12 fmol/mg (p<0.05).Resting hemodynamic output showed a rise in stroke work index from 27±4 to 43±3 g/m/m2, p <0.05, and ejection fraction rose from 0.26± 0.03 to 0.39 ± 0.03 after 6 months of metoprolol therapy, p <0.05. Before metoprolol therapy, dobutamine caused a 21 ± 4% increase in peak positive left ventricular dP/dt; during metoprolol therapy, the same dobutamine infusion rate increased peak positive dP/dt by 74±18% (p<0.05). Thus, long-term metoprolol therapy is associated with an increase in myocardial X-receptor density, significant improvement in resting hemodynamic output, and improved contractile response to catecholamine stimulation. These changes indicate a restoration of f3-adrenergic sensitivity associated with metoprolol therapy, possibly related to the observed up-regulation of j3-adrenergic receptors. (Circulation 1989;79: 483-490) C ongestive heart failure is associated with activation of the sympathetic nervous system. Circulating levels and urinary excretion of norepinephrine are increased, whereas myocardial stores of norepinephrine are depleted.1-5 In patients with heart failure, net release of norepinephrine into the coronary sinus6 is partly due to reduced norepinephrine reuptake.7 Evidence exists

Regeneration of the damaged myocardium is one of the most challenging fronts in the field of tissue engineering due to the limited capacity of adult heart tissue to heal and to the mechanical and structural constraints of the cardiac tissue. In this study we demonstrate that an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties, improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted onto the infarcted myocardium in adult murine hearts immediately after ligation of left anterior descending artery and the physiological outcomes were monitored by echocardiography, and by hemodynamic and histological analyses four weeks post infarction. In comparison to infarcted hearts with no treatment, hearts bearing patches preserved contractility and significantly protected the cardiac tissue from injury at the anatomical and functional levels. This improvement was accompanied by attenuated left ventricular remodeling, diminished fibrosis, and formation of a network of interconnected blood vessels within the infarct. Histological and immunostaining confirmed integration of the patch with native cardiac cells including fibroblasts, smooth muscle cells, epicardial cells, and immature cardiomyocytes. In summary, an acellular biomaterial with specific biomechanical properties promotes the endogenous capacity of the infarcted myocardium to attenuate remodeling and improve heart function following myocardial infarction.

(2014) Use of bio-mimetic three-dimensional technology in therapeutics for heart disease, Bioengineered, 5:3,[193][194][195][196][197]