Force-frequency effect is a powerful determinant of myocardial contractility in the mouse

Palakodeti, Vachaspathi; Oh, Sam S.; Oh, BH; Mao, Lan; Hongo, Minoru; Peterson, Kirk L.; Ross, John

doi:10.1152/ajpheart.1997.273.3.h1283

Cited by 44 publications

(45 citation statements)

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“…4, UcnII amplified peak (ϩ) dP͞dt well above that associated with a pacinginduced increase in heart rate alone. This observed amplification of the force-frequency relation is similar to the inf luence exerted by dobutamine (33).…”

Section: Discussionsupporting

confidence: 67%

“…In a subset of wild-type mice (n ϭ 5), the direct effect on myocardial contractility of UcnII, as opposed to a secondary effect through heart rate augmentation (forcefrequency relation), was evaluated. In these experiments, the heart rate was first slowed by using zatebradine and thereafter controlled and augmented by using a pacing wire placed in the right atrium (33). Administration of UcnII.…”

Section: Methodsmentioning

confidence: 99%

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The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

Bale

Hoshijima

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

120

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Corticotropin-releasing factor (CRF) and its paralogues urocortin (Ucn)I, -II, and -III signal by activating their receptors, CRF receptors (CRFR)1 and -2, to maintain homeostasis through endocrine, autonomic, and behavioral responses. CRFR2 is found in cardiomyocytes and in endothelial and smooth muscle cells of the systemic vasculature. Echocardiography and cardiac catheterization were used in mice to assess the physiologic effects of i.v. UcnII and CRFR2 deficiency on left ventricular function and the systemic vasculature. UcnII treatment augmented heart rate, exhibited potent inotropic and lusitropic actions on the left ventricle, and induced a downward shift of the diastolic pressure-volume relation. UcnII also reduced systemic arterial pressure, associated with a lowering of systemic arterial elastance (end-systolic pressure͞stroke volume) and systemic vascular resistance. CRFR2-deficient mice showed no alteration in cardiac contractility or blood pressure in response to UcnII administration, suggesting that the effects of UcnII are specific to CRFR2 function. Pretreatment with a ␤-adrenergic receptor antagonist, esmalol, had no effect on the inotropic or lusitropic effects of UcnII in vivo, indicating that its actions are independent of ␤-adrenergic receptors. Single i.v. bolus administration of UcnII to a heart failure model (muscle-specific LIM protein-deficient mice) produced significant enhancement of inotropic and lusitropic effects on left ventricular function and improved cardiac output. These results demonstrate the potent cardiovascular physiologic actions of UcnII in both wild-type and cardiomyopathic mice and support a potential beneficial use of this peptide in therapy of congestive heart failure.corticotropin-releasing factor receptor 2 ͉ hemodynamics ͉ inotropic agents ͉ lusitropic agents ͉ afterload reduction C orticotropin-releasing factor (CRF), a coordinator of the hypothalamic-pituitary-adrenal axis (1), is one of a family of peptides that includes urocortin (Ucn)I (2), UcnII (also known as stresscopin-related peptide) (3, 4), and UcnIII (also known as stresscopin) (4, 5). These peptides signal through two G proteincoupled receptors, CRF receptors (CRFR)1 and -2, to modulate endocrine, autonomic, and behavioral responses to stress. Although both receptors are found in the central nervous system, CRFR2 is particularly abundant in the periphery, including the heart and systemic vasculature (6-10). UcnII and -III bind selectively to CRFR2, with no appreciable activity at CRFR1 (3, 5).CRF and UcnI both demonstrate vasodilatory, inotropic, and chronotropic effects on the cardiovascular system via activation of CRFR2 on cardiac myocytes and in the systemic vasculature (2,(11)(12)(13)(14). These actions are absent in CRFR2-deficient mice (15, 16). However, both CRF and UcnI also activate CRFR1 in the pituitary and thus stimulate the hypothalamic-pituitaryadrenal axis, complicating the potential use of these peptides for treatment of cardiovascular disorders (14). Therefore, to characterize the...

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Section: Discussionsupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

Bale

Hoshijima

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

120

View full text Add to dashboard Cite

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“…Hemodynamic data revealed significant increases of RV contractility (assessed by RV dp/dt max ) and diastolic function (assessed by RV dp/dt min ) at baseline in cav-1 Ϫ/Ϫ mice compared with those in age-and gender-matched wild-type mice (Fig. 4 A and B) (43). The RV͞body weight ratio (1.61 Ϯ 0.36, n ϭ 8) was significantly increased compared with that of cav-1 ϩ/ϩ mice (0.92 Ϯ 0.15, n ϭ 8; P ϭ 0.001).…”

Section: Cav-1 Deficiency Causes Pulmonary Hypertension and Resultingmentioning

confidence: 94%

“…Transthoracic echocardiography (39), hemodynamic evaluation (43), and pulmonary artery pressure measurement (39) were performed as described.…”

Section: Methodsmentioning

confidence: 99%

Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice

Zhao

Liu

Stan

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

432

382

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Caveolins are important components of caveolae, which have been implicated in vesicular trafficking and signal transduction. To investigate the in vivo significance of Caveolins in mammals, we generated mice deficient in the caveolin-1 (cav-1) gene and have shown that, in the absence of Cav-1, no caveolae structures were observed in several nonmuscle cell types. Although cav-1 ؊/؊ mice are viable, histological examination and echocardiography identified a spectrum of characteristics of dilated cardiomyopathy in the left ventricular chamber of the cav-1-deficient hearts, including an enlarged ventricular chamber diameter, thin posterior wall, and decreased contractility. These animals also have marked right ventricular hypertrophy, suggesting a chronic increase in pulmonary artery pressure. Direct measurement of pulmonary artery pressure and histological analysis revealed that the cav-1 ؊/؊ mice exhibit pulmonary hypertension, which may contribute to the right ventricle hypertrophy. In addition, the loss of Cav-1 leads to a dramatic increase in systemic NO levels. Our studies provided in vivo evidence that cav-1 is essential for the control of systemic NO levels and normal cardiopulmonary function.

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“…10 Although there have been reports of AdV-mediated cardiac gene transfer via the aorta in rats 12 and with intracoronary AdV vector transfer in rabbits, 13 efficient cardiac gene transfer has largely failed in the mouse in vivo, because of technical limitations related to the animal size (the body weight: 20-40 g), the organ size (heart weight: 100-200 mg), a very narrow range between toxic and effective doses of vasoactive reagents, and high sensitivity to fluid overload. With our recent success in accomplishing highefficiency in vivo gene transfer in the cardiomyopathic hamster heart using AdV 18 and AAV vectors, 19 as well as our extensive use of microsurgical techniques and miniaturized methods for assessing cardiac function in the mouse, [20][21][22] we undertook to determine whether a modified approach would be feasible for application in the mouse.…”

Section: Discussionmentioning

confidence: 99%

In vivo high-efficiency transcoronary gene delivery and Cre–LoxP gene switching in the adult mouse heart

Iwatate

Dieterle

et al. 2003

Gene Ther

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High-efficiency somatic gene transfer in adult mouse heart has not yet been achieved in vivo. Here, we demonstrate high-efficiency in vivo transcoronary gene delivery to the adult murine myocardium using a catheter-based technique with recombinant adenovirus (AdV) and adeno-associated virus (AAV) vectors in normal and genetically engineered mice. The method involves immersion hypothermia followed by transient aortic and pulmonary artery occlusion with proximal intra-aortic segmental injection of cardioplegic solution containing substance P and viral vectors. Gene expression measured using a LacZ marker gene was observed throughout both ventricles. The expression efficiency of a cytoplasmic LacZ marker gene in the left ventricular myocardium was 56.4714.5% (mean7s.d.) at 4 days with an AdV vector, and with an AAV vector it was 81.075.9% at 4 weeks. Following AAV gene transfer, no gene expression was found in kidney, brain, lung, and spleen, but there was slight expression in liver. In addition, we demonstrate temporally controlled genetic manipulation in the heart with an efficiency of 54.675.2%, by transferring an AdV vector carrying Cre recombinase in ROSA26 floxLacZ reporter mice. Procedure-related mortality was 16% for AdV and zero for AAV transfer. Thus, this method provides efficient, relatively homogeneous gene expression in both ventricles of the adult mouse heart, and offers a novel approach for conditional gene rescue or ablation in genetically engineered mouse models.

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Force-frequency effect is a powerful determinant of myocardial contractility in the mouse

Cited by 44 publications

References 0 publications

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice

In vivo high-efficiency transcoronary gene delivery and Cre–LoxP gene switching in the adult mouse heart

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