Masaki Tsukashita

Spironolactone alleviates late cardiac remodeling after left ventricular restoration surgery

OBJECTIVE Although left ventricular restoration is effective for treating ischemic cardiomyopathy caused by left ventricular remodeling and redilation, the initial improvement in left ventricular function is not always sustained. We have reported that the inhibition of the renin-angiotensin-aldosterone system by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is effective in preventing late remodeling after left ventricular restoration. However, the effects of spironolactone--an aldosterone blocker--after left ventricular restoration have not been elucidated. METHODS Myocardial infarction was induced by ligating the left anterior descending artery. The rats developed left ventricular aneurysms and underwent left ventricular restoration by the plication of the left ventricular aneurysm 4 weeks after the ligation. Thereafter, the rats were randomized into a left ventricular restoration (vehicle) group and left ventricular restoration with spironolactone (100 mg/kg/d, by mouth) group. RESULTS Echocardiography revealed that in the left ventricular restoration with spironolactone group, late cardiac redilation was significantly attenuated (left ventricular end-diastolic area: 0.51 +/- 0.03 cm(2) vs 0.63 +/- 0.03 cm(2), P < .05) and late left ventricular function was preserved (fractional area change: 48.8% +/- 3.0% vs 35.8% +/- 2.4%, P < .01). Hemodynamically, rats in the left ventricular restoration with spironolactone group exhibited improved systolic function (maximal end-systolic pressure-volume relationship: 0.38 +/- 0.03 mm Hg/microL vs 0.11 +/- 0.04 mm Hg/microL, P < .01) and diastolic function (tau: 18.5 +/- 1.5 sec vs 23.1 +/- 1.4 sec, P < .05) than those in the LVR group. Histologically, interstitial fibrosis in the remote area was significantly reduced (5.6% +/- 1.3% vs 12% +/- 1.0%, P < .01), and fibrosis around the pledgets (near area) was also attenuated in the left ventricular restoration with spironolactone group. The myocardial messenger ribonucleic acid expressions of transforming growth factor-beta1 and brain natriuretic peptide measured using the real-time polymerase chain reaction were lower in the left ventricular restoration with spironolactone group (transforming growth factor-beta1: 0.13 +/- 0.02 vs 0.28 +/- 0.02, P < .01; brain natriuretic peptide: 0.99 +/- 0.14 vs 1.54 +/- 0.18, P < .05). The systemic blood pressure and heart rate did not differ between the 2 groups. CONCLUSION Spironolactone reduced the gene expression of transforming growth factor-beta1 and brain natriuretic peptide and alleviated not only cardiac redilation but also the deterioration of left ventricular function late after left ventricular restoration without inducing hypotension, a major side effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker. Spironolactone is a promising therapeutic option for alleviating remodeling after left ventricular restoration.

Carvedilol may alleviate late cardiac remodelling following surgical ventricular restoration

OBJECTIVE Surgical ventricular restoration (SVR) can be effective to treat ischaemic cardiomyopathy or left ventricular (LV) aneurysm. However, the initial improvement in LV function does not always last long because of LV remodelling. Beta-blockers prevent LV remodelling of failing hearts; however, their effects following SVR have not been elucidated. Thus, we sought to investigate the effects of a potent beta-blocker, carvedilol, on LV remodelling and function following SVR in rats with myocardial infarction. METHODS Rats, which developed LV aneurysm 4 weeks after coronary artery ligation, underwent SVR. They were orally administered a vehicle (vehicle group), and low or high dose of carvedilol (20 or 50 mg kg(-1)day(-1) for C20 or C50 group) for 4 weeks following SVR (n=7 in each group). RESULTS Four weeks following SVR, late cardiac remodelling was alleviated only in the C50 group (LV end-diastolic area: 65+/-4 mm(2) vs 74+/-11 mm(2) and 76+/-11 mm(2) for C50, C20 and vehicle groups; p=0.039 and p=0.013, respectively). There was no difference in LV systolic function (end-systolic elastance) among the three groups; however, LV diastolic functions (LV end-diastolic pressure and the time constant of isovolumic relaxation) were significantly better in the C20 and C50 groups. Histologically, the percentage of myocardial fibrosis in the C50 group (4.1+/-0.2%) was lower than those in the C20 (6.7+/-0.4%, p<0.0001) and vehicle (7.5+/-0.6%, p<0.0001) groups. The mRNA expression of transforming growth factor-beta1 and brain natriuretic peptide in the C50 group were lower than those in the C20 and the vehicle groups. CONCLUSIONS High-dose carvedilol alleviated LV remodelling and diastolic dysfunction following SVR accompanying with reduction in myocardial fibrosis. Blockade of beta-adrenergic receptor may be a promising adjuvant therapy in patients following SVR.

A potential of autologous pericardium for a sustained-release carrier of vancomycin: a pilot study in vitro.

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