Evaluation of a lumped parameter model for isolated working rat hearts

Wright, G.; Korchazhkina, Olga; Zhang, S.

doi:10.1007/bf02513286

Cited by 3 publications

(2 citation statements)

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“…We have used an isolated working heart model to characterize the vasodilation induced by intravascular ATP in the coronary circulation of the rat. The heart model we have used is a close approximation of a working heart in vivo and has been developed to take into account inotropic and chronotropic influences upon coronary vasodilation ( Wright et al ., 1999 ). We have defined the vasodilatory response to a continuous perfusion of ATP in the terms of its sensitivity to the apparent ATP concentration and, at the minimum apparent concentration of ATP required to produce a maximum coronary vasodilation, we have determined the relative contributions to this response of ligands for both P2Y and P1 receptors.…”

Section: Introductionmentioning

confidence: 99%

Intravascular ATP and coronary vasodilation in the isolated working rat heart

Korchazhkina

Wright

Exley

1999

British J Pharmacology

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1 Adenosine-5'-triphosphate (ATP) is a potent coronary vasodilator. Because of the e cient hydrolysis of ATP, adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) by ectonucleotidases located in the coronary endothelium ATP-induced vasodilation may be mediated via both P1 (AMP and adenosine) and P2Y (ATP and ADP) receptors. We have used the change in total coronary resistance (TCR) induced by intravascular ATP in the isolated working rat heart to determine both the component of the vasodilation mediated via P2Y receptors and the identity of the subclass of receptor involved. 2 The dose response for ATP revealed a half maximal e ect at an apparent ATP concentration of 0.08+0.009 mM. The response was saturated at apparent ATP concentrations greater than 0.23 mM. Contrary to much of the current literature, the perfusion of a 0.25 mM concentration of adenosine resulted in the identical response to an equimolar concentration of ATP suggesting a signi®cant role for adenosine in coronary vasodilation. 3 The non-selective P1 receptor antagonist 8-(p-Sulfophenyl)theophylline (8-SPT) was used to show that the response to ATP was mediated via both P1 and P2Y receptors. Whilst 8-SPT abolished the e ect of adenosine it reduced the e ect of ATP by only 50%. Thus, at a saturating concentration of ATP, P1 and P2Y receptors were shown to contribute equally to the observed vasodilation. 4 Uridine-5'-triphosphate (UTP), ADP and adenosine-5'-O-thiotriphosphate (ATPgS) were used to characterize the component of coronary vasodilation that was mediated via P2Y receptors. UTP at 0.25 mM was ine ective and did not induce vasodilation. Perfusion with 0.25 mM ADP resulted in a vasodilation that was identical to 0.25 mM ATP. In the absence of 8-SPT the perfusion of 0.25 mM ATPgS produced a vasodilation that was signi®cantly (P50.05) less than ATP. However, the vasodilation due to ATPgS, like that of adenosine, but unlike that of both ATP and ADP, was abolished in the presence of 8-SPT. The ability of ADP to induce vasodilation combined with both the lack of response to UTP and the ability of 8-SPT to abolish the vasodilation induced by ATPgS suggested very strongly that the component of ATP-induced coronary vasodilation in the isolated working rat heart that was mediated via P2Y receptors was achieved by the action of ADP (and not ATP) at P2Y 1 receptors. 5 These results suggest that the vasodilatory action of intravascular ATP in the coronary circulation should be attributed to the dual and equal activities of adenosine and ADP acting at P1 and P2Y 1 receptors respectively.

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Section: Introductionmentioning

confidence: 99%

Intravascular ATP and coronary vasodilation in the isolated working rat heart

Korchazhkina

Wright

Exley

1999

British J Pharmacology

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“…Originally, cardiovascular physiology was simulated by mathematical [1–4] or analog [5–8] approaches. Recently, computer simulations using lumped parameter models of the cardiovascular system (alone or in combination with numerical methods) have been introduced [9–15].…”

Section: Introductionmentioning

confidence: 99%

Simulation of the Frank-Starling Law of the Heart

Ribarič

Kordaš

2012

Computational and Mathematical Methods in Medicine

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We developed a lumped parameter, computer-based model of an equivalent electronic circuit for a one-atrium one-ventricle (frog) heart attached to a vascular circuit, to simulate a basic concept of cardiovascular physiology, the Frank-Starling Law of the Heart. A series of simulations was performed, to observe changes in cardiovascular variables (e.g., arterial pressure, ventricular volume, and valve flows) if either preload or afterload was increased. The simulated data agreed qualitatively, and quantitatively when experimental data are available, with data obtained on amphibian or on mammalian myocardium. In addition, the data obtained in these simulations improve our understanding of the mechanism(s) whereby the heart muscle adapts itself to increased distension (increased preload) or to impeded systolic contraction (increased afterload). The analysis of the measured valve flows suggests that the ventricle is a highly input sensitive pump because the input pressure determines the diastolic distension and, consequently, the force of ventricular systolic contraction. On the other hand, the ventricle is a relatively output insensitive pump. Therefore, not only atrium contraction, but also predominantly the preceding ventricular systolic contraction is the main mechanism of the subsequent diastolic ventricular filling. We conclude that the presented model enables the study of basic concepts of cardiovascular physiology.

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