Dynamic correction for parallel conductance, G<sub>P</sub>, and gain factor, α, in invasive murine left ventricular volume measurements

Porterfield, John E.; Kottam, Anil; Raghavan, Karthik; Escobedo, Daniel; Jenkins, James T.; Larson, Erik R.; Trevino, Rodolfo J.; Valvano, Jonathan W.; Pearce, John A.; Feldman, Marc D.

doi:10.1152/japplphysiol.91322.2008

Cited by 71 publications

(72 citation statements)

References 30 publications

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“…In the CTL mice assessed here at baseline, the ventricle operated at a maximum efficiency and submaximal stroke work such that E es /E a was greater than 0.5 on average. This value is remarkably lower than values reported in other species (7,60) but similar to normal E es /E a values reported for left ventricular-aortic coupling in mice (13,44).…”

Section: Discussionsupporting

confidence: 68%

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Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Tabima¹,

Hacker

Chesler

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Tabima DM, Hacker TA, Chesler NC. Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops. Am J Physiol Heart Circ Physiol 299: H2069 -H2075, 2010. First published October 8, 2010 doi:10.1152/ajpheart.00805.2010.-Mice are a widely used animal model for investigating cardiovascular disease. Novel technologies have been used to quantify left ventricular function in this species, but techniques appropriate for determining right ventricular (RV) function are less well demonstrated. Detecting RV dysfunction is critical to assessing the progression of pulmonary vascular diseases such as pulmonary hypertension. We used an admittance catheter to measure pressure-volume loops in anesthetized, open-chested mice before and during vena cava occlusion. Mice exposed to chronic hypoxia for 10 days, which causes hypoxia-induced pulmonary hypertension (HPH), were compared with control (CTL) mice. HPH resulted in a 27.9% increase in RV mass (P Ͻ 0.005), a 67.5% increase in RV systolic pressure (P Ͻ 0.005), and a 61.2% decrease in cardiac output (P Ͻ 0.05). Preload recruitable stroke work (PRSW) and slope of the maximum derivative of pressure (dP/dtmax)-end-diastolic volume (EDV) relationship increased with HPH (P Ͻ 0.05). Although HPH increased effective arterial elastance (Ea) over fivefold (from 2.7 Ϯ 1.2 to 16.4 Ϯ 2.5 mmHg/l), only a mild increase in the ventricular end-systolic elastance (Ees) was observed. As a result, a dramatic decrease in the efficiency of ventricular-vascular coupling occurred (Ees/Ea decreased from 0.71 Ϯ 0.27 to 0.35 Ϯ 0.17; P Ͻ 0.005). Changes in cardiac reserve were evaluated by dobutamine infusion. In CTL mice, dobutamine significantly enhanced Ees and dP/dtmax-EDV but also increased Ea, causing a decrease in Ees/Ea. In HPH mice, slight but nonsignificant decreases in Ees, PRSW, dP/dtmax-EDV, and Ea were observed. Thus 10 days of HPH resulted in RV hypertrophy, ventricular-vascular decoupling, and a mild decrease in RV contractile reserve. This study demonstrates the feasibility of obtaining RV pressure-volume measurements in mice. These measurements provide insight into ventricular-vascular interactions healthy and diseased states. cardiopulmonary hemodynamics; catheterization; chronic hypoxia; inotropic agents MOUSE IS A WIDELY USED SPECIES for investigating a growing number of disease states. In particular, the availability of knockout and transgenic mice allows the molecular mechanisms of disease to be understood with ever more clarity. Cardiopulmonary status, including right ventricular function, pulmonary vascular function, and right ventricular-pulmonary vascular interactions, is an important facet of health and disease. Recently, different methods for assessing left ventricular function, systemic vascular function, and the efficiency of left ventricular-systemic vascular hemodynamic interactions in mice in situ have been described (13,16,17,39,41,47,53,54,64). However, the feasibility and utility of these techniques in ...

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Section: Discussionsupporting

confidence: 68%

“…The chest wall and lungs were carefully retracted to expose the right ventricle. Hydroxyethylstarch (6%; 2 mg/g body weight) was injected intravenously to restore vascular volumes as previously reported (41,44).…”

Section: Methodsmentioning

confidence: 99%

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Tabima¹,

Hacker

Chesler

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…The upper abdomen and diaphragm were opened, and a 1.2 French mouse P-V catheter (Scisense) was inserted into the LV apex through an apical stab performed with a 25-gauge needle. To determine the absolute ventricular volumes via admittance technology, myocardial and blood conductances were obtained prior to placement in the LV (53). Hemodynamic recordings were performed after 5 minutes of a stable heart rate.…”

Section: Methodsmentioning

confidence: 99%

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

Cook¹,

Carta²,

Bénard³

et al. 2014

J. Clin. Invest.

121

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Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.

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“…The chest wall and lungs were carefully retracted to expose the right ventricle. Hydroxyethyl starch (24 lg) (6%; 2 mg/g body weight) was injected intravenously to restore vascular volumes as previously reported [3,4].…”

Section: Methodsmentioning

confidence: 99%

“…A common model of PAH is hypoxic pulmonary hypertension, which acutely causes vasoconstriction of distal arterioles in the lungs and chronically causes proximal and distal pulmonary artery remodeling as well as right ventricular hypertrophy, analogous to PAH. While distal arterial narrowing largely determines the increase in pulmonary vascular resistance, by which pulmonary hypertension severity is typically gauged, proximal pulmonary artery stiffening is a better predictor of mortality [3], which is most often caused by RV failure [4].…”

Section: Introductionmentioning

confidence: 99%

The Role of Collagen Synthesis in Ventricular and Vascular Adaptation to Hypoxic Pulmonary Hypertension

Schreier

Hacker

Song

et al. 2012

ASME 2012 Summer Bioengineering Conference, Parts a and B

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Pulmonary arterial hypertension (PAH) is a rapidly fatal disease in which mortality is typically due to right ventricular (RV) failure. An excellent predictor of mortality in PAH is proximal pulmonary artery stiffening, which is mediated by collagen accumulation in hypoxia-induced pulmonary hypertension (HPH) in mice. We sought to investigate the impact of limiting vascular and ventricular collagen accumulation on RV function and the hemodynamic coupling efficiency between the RV and pulmonary vasculature. Inbred mice were exposed to chronic hypoxia for 10 days with either no treatment (HPH) or with treatment with a proline analog that impairs collagen synthesis (CHOP-PEG; HPH þ CP). Both groups were compared to control mice (CTL) exposed only to normoxia (no treatment). An admittance catheter was used to measure pressure-volume loops at baseline and during vena cava occlusion, with mice ventilated with either room air or 8% oxygen, from which pulmonary hemodynamics, RV function, and ventricularvascular coupling efficiency (g vvc ) were calculated. Proline analog treatment limited increases in RV afterload (neither effective arterial elastance E a nor total pulmonary vascular resistance significantly increased compared to CTL with CHOP-PEG), limited the development of pulmonary hypertension (CHOP-PEG reduced right ventricular systolic pressure by 10% compared to HPH, p < 0.05), and limited RV hypertrophy (CHOP-PEG reduced RV mass by 18% compared to HPH, p < 0.005). In an acutely hypoxic state, treatment improved RV function (CHOP-PEG increased end-systolic elastance E es by 43%, p < 0.05) and maintained g vvc at control, room air levels. CHOP-PEG also decreased lung collagen content by 12% measured biochemically compared to HPH (p < 0.01), with differences evident in large and small pulmonary arteries by histology. Our results demonstrate that preventing new collagen synthesis limits pulmonary hypertension development by reducing collagen accumulation in the pulmonary arteries that affect RV afterload. In particular, the proline analog limited structural and functional changes in distal pulmonary arteries in this model of early and somewhat mild pulmonary hypertension. We conclude that collagen plays an important role in small pulmonary artery remodeling and, thereby, affects RV structure and function changes induced by chronic hypoxia.

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Dynamic correction for parallel conductance, G_P, and gain factor, α, in invasive murine left ventricular volume measurements

Cited by 71 publications

References 30 publications

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

The Role of Collagen Synthesis in Ventricular and Vascular Adaptation to Hypoxic Pulmonary Hypertension

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Dynamic correction for parallel conductance, GP, and gain factor, α, in invasive murine left ventricular volume measurements

Cited by 71 publications

References 30 publications

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

The Role of Collagen Synthesis in Ventricular and Vascular Adaptation to Hypoxic Pulmonary Hypertension

Contact Info

Product

Resources

About

Dynamic correction for parallel conductance, G_P, and gain factor, α, in invasive murine left ventricular volume measurements