In vivo murine left ventricular pressure-volume  relations by miniaturized conductance micromanometry

The mouse is the species of choice for creating genetically engineered models of human disease. To study detailed systolic and diastolic left ventricular (LV) chamber mechanics in mice in vivo, we developed a miniaturized conductance-manometer system. α-Chloralose-urethan-anesthetized animals were instrumented with a two-electrode pressure-volume catheter advanced via the LV apex to the aortic root. Custom electronics provided time-varying conductances related to cavity volume. Baseline hemodynamics were similar to values in conscious animals: 634 ± 14 beats/min, 112 ± 4 mmHg, 5.3 ± 0.8 mmHg, and 11,777 ± 732 mmHg/s for heart rate, end-systolic and end-diastolic pressures, and maximum first derivative of ventricular pressure with respect to time (dP/d t max), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe ( r 2 = 0.98). This maneuver yielded end-systolic elastances of 79 ± 21 mmHg/μl, preload-recruitable stroke work of 82 ± 5.6 mmHg, and slope of dP/d t max-end-diastolic volume relation of 699 ± 100 mmHg ⋅ s−1 ⋅ μl−1, and these relations varied predictably with acute inotropic interventions. The control normalized time-varying elastance curve was similar to human data, further supporting comparable chamber mechanics between species. This novel approach should greatly help assess cardiovascular function in the blood-perfused murine heart.

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Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00405.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. H2132-H2137 ◽

Cited By ~ 86

Author(s):

Pál Pacher ◽

Jon G. Mabley ◽

Lucas Liaudet ◽

Oleg V. Evgenov ◽

Anita Marton ◽

...

Keyword(s):

Diastolic Pressure ◽

Systolic Pressure ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Male Rats ◽

Ventricular Pressure ◽

Stroke Work ◽

Effective Prevention ◽

Fischer 344 ◽

End Diastolic Volume

Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old (young) and 24- to 26-mo-old (old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/d t), and its relation to end-diastolic volume (+dP/d t-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/d t, maximal slope of the diastolic pressure decrement, +dP/d t-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats.

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Impact of ejection on magnitude and time course of ventricular pressure-generating capacity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.3.h899 ◽

1993 ◽

Vol 265 (3) ◽

pp. H899-H909 ◽

Cited By ~ 24

Author(s):

D. Burkhoff ◽

P. P. De Tombe ◽

W. C. Hunter

Keyword(s):

Time Course ◽

Cardiac Cycle ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

Time Varying ◽

Generating Capacity ◽

Ejection Phase ◽

Time Point ◽

Ventricular Dynamics

This study focuses on elucidating how ventricular afterloading conditions affect the time course of change of left ventricular pressure (LVP) throughout the cardiac cycle, with particular emphasis on revealing specific limitations in the time-varying elastance model of ventricular dynamics. Studies were performed in eight isolated canine hearts ejecting into a simulated windkessel afterload. LVP waves measured (LVPm) during ejection were compared with those predicted (LVPpred) according to the elastance theory. LVPm exceeded LVPpred from a time point shortly after the onset of ejection to the end of the beat. The instantaneous difference between LVPm and LVPpred increased steadily as ejection proceeded and reached between 45 and 65 mmHg near end ejection. This was in large part due to an average 35-ms prolongation of the time to end systole (tes) in ejecting compared with isovolumic beats. The time constant of relaxation was decreased on ejecting beats so that, despite the marked prolongation of tes, the overall duration of ejecting contractions was not greater than that of isovolumic beats. The results demonstrate a marked ejection-mediated enhancement and prolongation of ventricular pressure-generating capacity during the ejection phase of the cardiac cycle with concomitant acceleration of relaxation. None of these factors are accounted for by the time-varying elastance theory.

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In vivo safety and accuracy of a clinically applicable telemetered left ventricular pressure module: intermediate-term results

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2004.06.179 ◽

2004 ◽

Vol 10 (4) ◽

pp. S67 ◽

Cited By ~ 2

Author(s):

Patrick I. McConnell ◽

Daise de Cunha ◽

Tanya Shipkowitz ◽

Justin Van Hee ◽

Phillip H. Long ◽

...

Keyword(s):

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure

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Effects of arterial input impedance on mean ventricular pressure-flow relation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1984.247.6.h978 ◽

1984 ◽

Vol 247 (6) ◽

pp. H978-H983 ◽

Cited By ~ 1

Author(s):

W. L. Maughan ◽

K. Sunagawa ◽

K. Sagawa

Keyword(s):

Characteristic Impedance ◽

Peripheral Resistance ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

Pressure Flow ◽

Inotropic State ◽

End Diastolic Volume ◽

State Compliance ◽

Slope Change

The mean left ventricular pressure-flow relationship (Pv-Fv), determined under a constant preload and variable peripheral resistance, has been proposed as a quantitative representation of ventricular pump function (9). We determined the Pv-Fv relation in seven isolated cross-perfused canine hearts by varying resistance of a simulated arterial load in five steps from 6.0 to 0.375 mmHg X s X ml-1 while keeping end-diastolic volume, inotropic state, compliance, and characteristic impedance at various constant values. All of the 27 Pv-Fv relations thus determined were moderately nonlinear. Varying end-diastolic volume at three levels shifted the relation curve in an approximately parallel fashion (P less than 0.0001). At three levels of inotropic state (mean LVP of isovolumic contractions 34.3 +/- 8.2, 48.0 +/- 6.3, and 59.2 +/- 9.6 mmHg), the Pv-Fv relation shifted with predominantly a slope change (P less than 0.0001). Changing compliance at three levels (0.2, 0.4, and 0.8 ml/mmHg) caused a statistically significant but quantitatively small crossover of the Pv-Fv curves (P less than 0.0001). Changing characteristic impedance to 0.1, 0.2, and 0.4 mmHg X s X ml-1 caused a highly significant (P less than 0.0001) divergence of Pv-Fv relation over the high Fv range. We conclude that this sensitivity of the Pv-Fv relation to characteristic impedance limits its use as a contractility index.

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Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.258.6.h1889 ◽

1990 ◽

Vol 258 (6) ◽

pp. H1889-H1898 ◽

Cited By ~ 5

Author(s):

R. Krams ◽

P. Sipkema ◽

N. Westerhof

Keyword(s):

Oscillatory Flow ◽

Perfusion Pressure ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Cardiac Contraction ◽

Ventricular Pressure ◽

Time Varying ◽

Waterfall Model ◽

Developed Pressure ◽

Phasic Flow

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

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Synergistic Model of Cardiac Function with a Heart Assist Device

Bioengineering ◽

10.3390/bioengineering7010001 ◽

2019 ◽

Vol 7 (1) ◽

pp. 1

Author(s):

Eun-jin Kim ◽

Massimo Capoccia

Keyword(s):

Cardiac Function ◽

Heart Diseases ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Self Organization ◽

Ventricular Pressure ◽

Time Varying ◽

Assist Device ◽

Clinical Scenarios ◽

Volume Relation

The breakdown of cardiac self-organization leads to heart diseases and failure, the number one cause of death worldwide. The left ventricular pressure–volume relation plays a key role in the diagnosis and treatment of heart diseases. Lumped-parameter models combined with pressure–volume loop analysis are very effective in simulating clinical scenarios with a view to treatment optimization and outcome prediction. Unfortunately, often invoked in this analysis is the traditional, time-varying elastance concept, in which the ratio of the ventricular pressure to its volume is prescribed by a periodic function of time, instead of being calculated consistently according to the change in feedback mechanisms (e.g., the lack or breakdown of self-organization) in heart diseases. Therefore, the application of the time-varying elastance for the analysis of left ventricular assist device (LVAD)–heart interactions has been questioned. We propose a paradigm shift from the time-varying elastance concept to a synergistic model of cardiac function by integrating the mechanical, electric, and chemical activity on microscale sarcomere and macroscale heart levels and investigating the effect of an axial rotary pump on a failing heart. We show that our synergistic model works better than the time-varying elastance model in reproducing LVAD–heart interactions with sufficient accuracy to describe the left ventricular pressure–volume relation.

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Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y98-138 ◽

1998 ◽

Vol 76 (12) ◽

pp. 1103-1109 ◽

Cited By ~ 6

Author(s):

Takeshi Iwai ◽

Hiroyuki Nakamura ◽

Hisanori Takanashi ◽

Kenji Yogo ◽

Ken-Ichi Ozaki ◽

...

Keyword(s):

Mesenteric Artery ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Gastric Antrum ◽

Ventricular Pressure ◽

High Dose ◽

Aortic Blood Flow ◽

Arterial Blood

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol·kg-1, i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol·kg-1, [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla]betatrifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol·kg-1) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10-7 M), [Leu13]motilin (10-8-10-5 M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with Nomega-nitro-L-arginine, a competitive inhibitor of NO synthase (10-4 M). A high dose (10-4 M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.Key words: motilin, gastrointestinal motility, hypotension, hemodynamics, anesthetized dog, mesenteric artery, endothelium, nitric oxide.

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