Acute effects of beta-blocker with intrinsic sympathomimetic activity on stress-induced cardiac dysfunction in rats

AbstractBackgroundWe have reported that α and β adrenergic blockers could protect against emotional stress-induced cardiac dysfunction but those protective effects of β adrenergic blockers with intrinsic sympathomimetic activity (ISA), such as celiprolol, are unknown. The purpose of this study is to evaluate whether ISA could relate with this protective effect.Methods and resultsRats medicated with celiprolol (8mg/kg), metoprolol (4mg/kg), or vehicle, were restrained for 30min (immobilization stress: IMO) to reproduce emotional stress, and anesthetized to release stress. We measured the fractional area change (FAC) using an echocardiography (SONOS5500) with s12 probe (frequency: 5–12MHz, frame rate: 120Hz) at the end of IMO and every 10min for 1h. During IMO, FAC in rats with a premedication of metoprolol was lower than in those with a premedication of vehicle or celiprolol. At 20min after IMO, FAC in rats with a premedication of celiprolol was significantly higher than that with a premedication of metoprolol or vehicle (84±9% vs. 65±3% or 60±7%, p<0.05). At 60min after IMO, FAC in rats with a premedication of vehicle or celiprolol recovered, but FAC in rats with a premedication of metoprolol did not.ConclusionAcute premedication with celiprolol could prevent a sudden drop of cardiac function after acute stress such as IMO. ISA might have an important role in preventing stress-induced cardiac dysfunction

Noninvasive quantification of regional ventricular function in rats: Assessment of serial change and spatial distribution using ultrasound strain analysis

Background: The optimal method for quantitative assessment of regional ventricular function in rats remains unclear. The goal of this study was to investigate the use of ultrasonic strain rate (SR) and strain analysis in evaluating the serial change and spatial distribution of regional contractile function in rats. Methods: In all, 22 anesthetized rats underwent incremental dobutamine infusion (protocol 1) for assessment of serial change or underwent coronary ligation (protocol 2) for assessment of spatial distribution. For protocol 1, the serial change of systolic SR and strain during dobutamine was measured in the posterior myocardium on the short-axis view, and the systolic strain was compared with the percent change in wall thickening. For protocol 2, the spatial distribution of strain profile was analyzed in normal, peripheral ischemic, and central ischemic regions that were identified by myocardial contrast echocardiography. Results: In protocol 1, the incremental dobutamine infusion resulted in a gradual increase in peak systolic SR. In contrast, peak systolic strain increased with low-dose dobutamine but tended to decrease for higher doses of dobutamine. Further, the serial change of peak systolic strain corresponded to changes in percent change in wall thickening, but the strain values were always lower than percent change in wall thickening. In protocol 2, the strain profile indicated postsystolic thickening in the peripheral ischemic region and indicated systolic wall thinning in the central ischemic region. Conclusions: Ultrasonic determination of SR and strain is an accurate and noninvasive method of quantitation of the serial change and spatial distribution of regional contractile function in rats. Copyright 2005 by the American Society of Echocardiography.Hirano T, Asanuma T, Azakami R, Okuda K, Ishikura F, Beppu S. Noninvasive quantification of regional ventricular function in rats: assessment of serial change and spatial distribution using ultrasound strain analysis. J Am Soc Echocardiogr. 2005 Sep;18(9):907-12. doi: 10.1016/j.echo.2005.01.009

Noninvasive vessel-selective perfusion imaging with intravenous myocardial contrast echocardiography

Background Intravenous myocardial contrast echocardiography (MCE) cannot identify each perfusion area of coronary vessels separately. However, by destroying microbubbles passing through a specific vessel using high-power ultrasound during intravenous MCE, vessel-selective perfusion imaging (VSPI) may be feasible. Methods In 10 open-chest dogs, intermittent short-axis images were obtained during contrast agent infusion using an ultrasound system. For VSPI, a probe coupled to another ultrasound machine was placed on the proximal left circumflex coronary artery (LCx). High-power ultrasound pulses were transmitted to destroy bubbles passing through the LCx. A negative contrast area on VSPI was considered to represent the perfusion area of the LCx (LCx-VSPI). A negative contrast area on conventional MCE during LCx occlusion and a region without staining by Evans blue dye were used as gold standards for defining the LCx perfusion area. LCx-VSPI was compared with a negative contrast area on conventional MCE during LCx occlusion and a region without staining by Evans blue dye. Results Despite lack of LCx occlusion, high-power destructive pulses produced a definite area of negative contrast on the LCx region. Decreased power of ultrasound pulses resulted in disappearance of the negative contrast area. An excellent relationship was demonstrated between both LCx-VSPI and a negative contrast area on conventional MCE during LCx occlusion (r = 0.93, P < .0001), and LCx-VSPI and a region without staining by Evans blue dye (r = 0.92, P = .0002). Conclusion: VSPI during intravenous MCE may be feasible for noninvasive assessment of perfusion areas associated with specific vessels.Asanuma T, Fujihara T, Otani K, Miki A, Ishikura F, Beppu S. Noninvasive vessel-selective perfusion imaging with intravenous myocardial contrast echocardiography. J Am Soc Echocardiogr. 2004 Jun;17(6):654-8. doi: 10.1016/j.echo.2004.03.011

Impact of the Coronary Flow Reduction at Rest on Myocardial Perfusion and Functional Indices Derived from Myocardial Contrast and Strain Echocardiography

Background: The severity of the coronary flow reduction that corresponds to myocardial perfusion and functional abnormalities remains unclear. We estimated the impact of various severities of flow-limiting coronary stenosis at rest on myocardial perfusion and functional indices from myocardial contrast echocardiography and tissue strain imaging and characterized the relationship between both the indices. Methods: Four levels of flow-limiting stenoses (slight, mild, moderate, severe) of the left circumflex coronary artery were examined in 10 open-chest dogs. In the left circumflex coronary artery area, plateau videointensity and time to plateau (TP) of the replenishment curve from myocardial contrast echocardiography were calculated for perfusion analysis, and peak systolic strain and postsystolic strain index (PSI) from tissue strain imaging were measured for functional analysis. Results: Plateau videointensity and peak systolic strain tended to decrease with increased severity of stenosis, although these differences did not reach the level of statistical significance. TP and PSI were significantly increased in the context of moderate (≥30-<50%) and severe (≥50%) flow reduction when compared to baseline values (TP, moderate 1.69 ± 0.20 and severe 1.77 ± 0.25 vs baseline 0.93 ± 0.17, P < .01, respectively; PSI, moderate 0.96 ± 0.15 and severe 1.28 ± 0.32 vs baseline 0.59 ± 0.18, P < .05 and P < .01, respectively). Further, TP and PSI were positively correlated with flow reduction (r = 0.81 and r = 0.84, P < .0001, respectively), and PSI was positively correlated with TP (r = 0.72, P < .0001). Conclusions: In contrast to conventional indices, such as plateau videointensity and peak systolic strain, novel indices, such as TP and PSI, were both able to detect 30% or greater coronary flow reduction at rest. © 2006 American Society of Echocardiography.Okuda K, Asanuma T, Hirano T, Masuda K, Otani K, Ishikura F, Beppu S. Impact of the coronary flow reduction at rest on myocardial perfusion and functional indices derived from myocardial contrast and strain echocardiography. J Am Soc Echocardiogr. 2006 Jun;19(6):781-7. doi: 10.1016/j.echo.2005.10.016