Abstract
IntroductionChronic left ventricular (LV) pressure overload causes relative ischemia with resultant LV dysfunction. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we thus examined whether LIPUS also ameliorates contractile dysfunction in LV pressure-overloaded hearts.Methods and resultsChronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. LIPUS was applied to the whole heart three times in the first week after TAC and was repeated once a week for 7 weeks thereafter (n = 22). Animals in the control groups received the sham treatment without LIPUS (n = 23). At 8 weeks after TAC, LV fractional shortening was depressed in the TAC-Control group, which was significantly ameliorated in the TAC-LIPUS group (30.4±0.5 vs. 36.2±3.8%, P<0.05). Capillary density was higher and perivascular fibrosis was less in the LV in the TAC-LIPUS group than in the TAC-Control group. Myocardial relative ischemia evaluated with hypoxyprobe was noted in the TAC-Control group, which was significantly attenuated in the TAC-LIPUS group. In the TAC-LIPUS group, as compared with the control group, mRNA expressions of BNP and collagen III were significantly lower (both P<0.05) and protein expressions of VEGF and eNOS were significantly up-regulated associated with Akt activation (all P<0.05). No adverse effect related to the LIPUS therapy was noted.ConclusionsThese results indicate that the LIPUS therapy ameliorates contractile dysfunction in chronically pressure-overloaded hearts through enhanced myocardial angiogenesis and attenuated perivascular fibrosis. Thus, the LIPUS therapy may be a promising, non-invasive treatment for cardiac dysfunction due to chronic pressure overload.
Highlights
Chronic left ventricular (LV) pressure overload causes relative ischemia with resultant LV dysfunction
These results indicate that the low-intensity pulsed ultrasound (LIPUS) therapy ameliorates contractile dysfunction in chronically pressure-overloaded hearts through enhanced myocardial angiogenesis and attenuated perivascular fibrosis
In patients with hypertension or aortic stenosis, the left ventricle (LV) is subjected to chronic pressure overload and the heart develops LV hypertrophy (LVH) as an adaptive response to increased workload, whereas sustained pressure overload causes maladaptive hypertrophy and decompensated Heart failure (HF) [8]. It is not fully elucidated how pressure-overloaded hearts transit from compensated LVH to decompensated HF, a mismatch between the number of capillaries and the size of cardiomyocytes due to insufficient myocardial angiogenesis has been reported to be involved in the development of HF [9,10,11,12]
Summary
Chronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. Male C57BL/6 mice (9-week-old, 23–28 g in body weight) underwent transverse aortic constriction (TAC) to induce chronic LV pressure overload. They were separated every three or six individuals in the cages where was kept the temperature (22 ̊C) and humidity (60%), and were given the food and water in the cages, and could access ad libitum. If the respiratory status was unstable and the movement was poor after the surgery, the animal was euthanized at the end of the experiments by cervical dislocation after anesthetic inhalation of overdose with isoflurane. Animals were euthanized at the end of the experiments by cervical dislocation under anesthetic inhalation overdose with isoflurane
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