differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation

Nemoto, Shintaro; Hamawaki, Masayoshi; Freitas, Gilberto De; Carabello, Blasé A.

doi:10.1016/s0735-1097(02)01926-5

Cited by 81 publications

(64 citation statements)

References 25 publications

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“…However, in this model, there is no progressive change in the severity of the MR. These differences may relate to the severity of the initial insult: in previous studies initial induction of RF was ϳ60 -70% (25,26), whereas in our model initial RF was 50%.…”

Section: Discussioncontrasting

confidence: 52%

Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes

Neilan¹,

Ton-Nu²,

Kawase³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussioncontrasting

confidence: 52%

Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes

Neilan¹,

Ton-Nu²,

Kawase³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…In 1 study, 3-month treatment with atenolol reduced mitral regurgitant volume, improved LV end-systolic stiffness, and decreased left atrial and pulmonary artery pressures, but an angiotensin-converting enzyme inhibitor did not have these favorable effects. 19 ␤-Blockers improve the contractile function of cardiomyocytes isolated from dogs with severe mitral regurgitation by restoring contractile elements. 20 However, ␤-blockers had no favorable effect when pacing is added to increase heart rate, suggesting that slowing of heart rate is an important mechanism of benefit.…”

Section: Discussionmentioning

confidence: 99%

Pilot Study to Assess the Influence of β-Blockade on Mitral Regurgitant Volume and Left Ventricular Work in Degenerative Mitral Valve Disease

et al. 2008

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Background-A medical treatment that decreases the likelihood of left ventricular (LV) dysfunction or symptoms would benefit patients with moderate to severe degenerative mitral regurgitation. The aim of this pilot study was to determine the short-term effects of a ␤-blocker on mitral regurgitant volume and LV work in these patients. Methods and Results-Twenty-five patients with moderate or severe degenerative mitral regurgitation were randomized in a double-blind crossover study to the ␤ 1 -selective adrenergic blocker metoprolol (mean daily dose, 119 mg; range 23.75 to 190 mg) and placebo for 14Ϯ3 days. At the end of each treatment period, ascending aortic flow and LV stroke volume were measured by cardiac magnetic resonance imaging, and mitral regurgitant volume was calculated. On ␤-blocker, heart rate decreased from 65Ϯ10 by 10Ϯ7 bpm (meanϮSD) and systolic blood pressure decreased from 138Ϯ18 by 16Ϯ12 mm Hg (PϽ0.0001 for both). No significant change occurred in LV ejection fraction (from 65Ϯ5%; change, Ϫ0.6Ϯ2.7%; Pϭ0.3) or mitral regurgitant volume (from 59Ϯ36 mL; change, 3Ϯ13 mL; Pϭ0.3), but forward stroke volume increased from 89Ϯ21 by 5Ϯ11 mL (Pϭ0.03). Because heart rate was lower on metoprolol, cardiac output decreased from 5.68Ϯ1.04 by 0.56Ϯ0.78 L/min (Pϭ0.001), but a greater decrease occurred in LV output, from 9.51Ϯ2.22 by 1.30Ϯ1.08 L/min (PϽ0.0001). Mitral regurgitant volume per minute decreased from 3.83Ϯ2.41 by 0.74Ϯ1.00 L/min (Pϭ0.001). The decrease in LV work on ␤-blocker (mean, 21%; 95% confidence interval, 15 to 27) was greater (Pϭ0.001) than the decrease in cardiac output (mean, 9%; 95% confidence interval, 3 to 15). Conclusions-In this pilot study, short-term treatment with a ␤-blocker did not change mitral regurgitant volume per beat but decreased LV work in patients with moderate to severe degenerative mitral regurgitation. Further research is needed to determine whether longer-term treatment with ␤-blockers will decrease progressive LV dysfunction and symptomatic deterioration.

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“…In particular, the benefits might be more pronounced if β-blockade was started early, before the development of irreversible LV dysfunction. Animal studies have shown that β-blockade could improve LV systolic function in chronic MR. [9][10][11] Recent clinical studies have also shown that β1-blockade may improve LV systolic function in chronic organic MR, but a beneficial effect on LV remodeling is uncertain. 12,13 There have been no studies yet demonstrating that β-blockade improves LV remodeling in chronic organic MR.…”

Section: Editorial See P 624 Clinical Perspective On P 762mentioning

confidence: 99%

“…23 Carabello et al 10 reported that β1-blockade restored impaired LV systolic function in a canine model of chronic organic MR with congestive heart failure. This beneficial There are no differences in LVEDV, LVESV, LV mass index, LVFS, and LVEF between the control and β-blockade groups at baseline and week 2 (all P values >0.05).…”

Section: β-Blockade In Chronic Organic Mrmentioning

confidence: 99%

“…40 In addition, MR is acutely and mechanically induced in all animal models of organic MR. [9][10][11]14,16,40 Progression of LV remodeling, therefore, may be different from patients with degenerative mitral valve disease in which the severity of MR often increases gradually unless rupture of the chordae tendineae of the mitral valve occurs. Although this study evaluated the effect of β-blockade in acute and chronic stages of organic MR by designating the early and late β-blockade groups, one should not overextrapolate experimental results to clinical patients.…”

Section: Limitationsmentioning

confidence: 99%

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Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Gao

et al. 2013

Circ: Heart Failure

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Background-Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined. Methods and Results-Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308±25 versus 351±31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2±0.7 versus 1.59±0.6 mL; P<0.001), end-systolic volumes (0.72±0.42 versus 0.40±0.19 mL; P<0.001), and mass index (2.40±0.55 versus 2.06±0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33±7% versus 38±7%; P<0.001) and ejection fraction (69±11% versus 75±7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114±10 versus 93±12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03). 14 This dissociation creates a possible pathophysiological contradiction because adverse LV remolding is often associated with LV dysfunction and poor long-term outcome in all forms of congestive heart failure. Therefore, it is important to determine whether beneficial effects of β-blockade could be demonstrated if chronic organic MR was treated in the early stages before the development of LV dysfunction and if treatment is long-term. It is also imperative to determine whether LV remodeling associated with β-blocker therapy could ultimately have a negative impact on LV function in chronic organic MR or if the early improvement in LV function and myocardial contractility observed in prior studies could lead to improvement in LV remodeling if treatment was initiated early and long-term. To clarify this important issue, we performed a prospective study to determine the effects of early, late, and long-term β-blockade on LV remodeling, systolic function, and survival in experimental chronic MR. The study design had the following unique characteristics: (1) the study used a unique rat model of chronic MR developed in our laboratory, 15 allowing us to use a large numbers of animals to test the hypothesis; (2) carvedilol (a nonselective β-adrenergic blocking agent with α 1 -blocking activity) was administered early before the development of LV systolic dysfunction; and (3) a long-term treatment strategy was applied. Conclusions-Early Methods Rat Model of MRThe study protocol was approved by the Institution's Animal Care and Use Committee of the Pennsylvania State University College of Medicine (assurance number A3045-01). The study was performed according to the guidelines of the Amer...

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differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation

Abstract: Although lisinopril significantly reduced preload, its effect on LV contractility was insignificant in experimental MR. Conversely, atenolol, when added to lisinopril, achieved maximum hemodynamic benefit and also restored LV contractility.

Cited by 81 publications

References 25 publications

Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes

Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes

Pilot Study to Assess the Influence of β-Blockade on Mitral Regurgitant Volume and Left Ventricular Work in Degenerative Mitral Valve Disease

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

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