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Cardiac and Vascular Mechanics

We have made a mathematical model of mechanical properties of the circulatory system to deal with a variety of the hemodynamic conditions seen in the clinical settings. Using this model, we are developing an automated therapeutic system that can evaluate and predict hemodynamics during acute heart failure and provide optimal drug administrations. We also developed a conductance catheter system useful for evaluating the cardiac function and a novel method to estimate the ventricular elastance, an essential index of the cardiac function, in clinical settings. Echocardiography is particularly useful in evaluating cardiac function non-invasively in clinical settings. Evaluation of ventricular mechanics by tissue Doppler echocardiography is also one of our research interests.

(1) Comprehensive Physiological Model of Circulatory System Using Cardiac Output Curve and Venous Return Surface

We have developed a novel framework of circulatory equilibrium by extending Guyton's original concept to deal with complicated hemodynamic conditions such as unilateral ventricular failure. In this model, the circulatory system is decomposed into a cardiac compartment comprised of the right and the left ventricles and a vascular compartment comprised of the systemic and the pulmonary vasculatures. In a 3-D diagram of cardiac output, right and left atrial pressures, pumping ability of the cardiac compartment is characterized by the integrated cardiac output curve, where cardiac output increases as the atrial pressures increase (Frank-Starling mechanisms). Venous return property of the vascular compartment is characterized by the venous return surface, where venous return decreases as the atrial pressure increase. Cardiac output and the right and left atrial pressures are predicted from the intersection point between the curve and the surface. Combining the cardiac output curve with the venous return surface enabled us to evaluate the progression of circulatory diseases and the effects of drug in terms of each element of the circulatory system. As a result, it became evident that dobutamine increased cardiac output by a blood transfusion effect via blood redistribution on top of an inotropic effect, and it decreased vasular resistance. Although both nitroprusside and nitroglycerin showed a blood withdrawal effect via vascular dilation, nitroprusside showed a stronger effect of decreasing vascular resistance. The novel circulatory model may enable us to select therapeutic drugs according to hemodynamics, providing more effective treatment (see the next section).

References:

  1. Uemura K, Sugimachi M, Kawada T, Kamiya A, Jin Y, Kashihara K, Sunagawa K. A novel framework of circulatory equilibrium. Am J Physiol Heart Circ Physiol 286: H2376-H2385, 2004.
  2. Uemura K, Kawada T, Kamiya A, Aiba T, Hidaka I, Sunagawa K, Sugimachi M. Prediction of circulatory equilibrium in response to changes in stressed blood volume. Am J Physiol Heart Circ Physiol 289: H301-H307, 2005.

(2) Autopilot System for Hemodynamic Management of Acute Heart Failure After Acute Myocardial Infarction

To rescue patients developing heart failure after acute myocardial infarction (AMI), emergency treatment by doctors who specialized in cardiovascular care is highly effective. However, such specialists account for only 4% of the whole medical doctors in Japan. To improve survival of AMI throughout the entire society, it is mandatory to boost the level of the AMI treatment capability of the general doctors to that of the specialists. On these backgrounds, we have been developing an automated hemodynamic management system (Autopilot System). To rescue from acute heart failure after AMI, Autopilot System needs to increase cardiac output and arterial pressure while lowering left atrial pressure. However, the fact that various mechanisms could alter those variables made their simultaneous control difficult. To avoid this problem, we modeled the total cardiovascular system by extending the Guyton’s equilibrium model (see the previous section). Based on the integrated model, Autopilot System feedback controls cardiac output curve with dobutamine, venous return surface with dextran/furosemide, and arterial resistance with nitroprusside, thereby controlling cardiac output, arterial pressure and left atrial pressure. In dogs with acutely created heart failure, Autopilot System rapidly restored and precisely maintained normal hemodynamic variables. It is expected that with the use of Autopilot System, the general doctors will be able to manage patients with AMI as properly as the specialists, thereby improving the survival of AMI throughout the entire society.

References:

  1. Kashihara K, Kawada T, Uemura K, Sugimachi M, Sunagawa K. Adaptive predictive control of arterial blood pressure based on a neural network during acute hypotension. Ann Biomed Eng 32: 1365-1383, 2004.
  2. Uemura K, Kamiya A, Hidaka I, Kawada T, Shimizu S, Shishido T, Yoshizawa M, Sugimachi M, Sunagawa K. Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure. J Appl Physiol 100: 1278-1286, 2006.
  3. Uemura K, Sunagawa K, Sugimachi M. Computationally managed bradycardia improved cardiac energetics while restoring normal hemodynamics in heart failure. Ann Biomed Eng. 37: 82-93, 2009.

(3) Development of Telemetry System for Ventricular Volumetry

To measure ventricular volume and function in conscious, small animals, we miniaturized the ventricular conductance catheter system and developed the telemetry system. The telemetry system can measure blood resistivity and parallel conductance that are necessary for calculating ventricular volume from the conductance signal using on-catherter extra-microelectrodes. We also developed a digital signal processing circuit that generates alternative current for conductance catheter and calculates the ventiricular volume from a conductance signal. The system enabled us to trace the progression of the circulatory diseases in small animal models, which contributes to studies on the circulatory diseases.

References:

  1. Uemura K, Sugimachi M, Shishido T, Kawada T, Inagaki M, Zheng C, Sato T, Sunagawa K: Convenient automated conductance volumetric system. Jpn J Physiol 52:497-503, 2002.
  2. Uemura K, Kawada T, Sugimachi M, Zheng C, Kashihara K, Sato T, Sunagawa K. A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats. Am J Physiol Heart Circ Physiol 287: H2906-2913, 2004.

(4) Single-Beat Estimation of End-Systolic Elastance

Although left ventricular end-systolic elastance (Ees) has often been used as an index of contractility, technical difficulties in measuring volume and in changing loading conditions have limited its clinical application. By approximating the time-varying elastance curve by two linear functions (isovolumic contraction phase and ejection phase) and estimating the slope ratio of these, we developed a method to estimate Ees on a single-beat basis from pressure values, systolic time intervals, and stroke volume. Ees estimated by the novel method matched with that estimated by conventional caval occlusion method reasonably well. The novel method allows us to estimate Ees in clinical settings.

References:

  1. Shishido T, Hayashi K, Shigemi K, Sato T, Sugimachi M, Sunagawa K: Single-beat estimation of end-systolic elastance using bilinearly approximated time-varying elastance curve. Circulation 102: 1983-1989, 2000.

(5) Tissue Doppler Echocardiography

We have been evaluating the assessment of cardiac function by tissue Doppler echocardiography recently introduced into routine clinical practice. Assessment of transmural strain profile using tissue strain imaging by tissue Doppler echocardiography was useful to quantify transmural distribution of the viable myocardium in sub-endocardial and transmural myocardial infarction. Assessment of peak systolic mitral annulus velocity by tissue Doppler echocardiography is useful to detect cardiac dysfunction sensitively and predict prognosis of cardiac patients. Theoretical analysis and animal experiments disclosed that peak systolic mitral annulus velocity strongly reflects the status of ventricular–arterial coupling.

References:

  1. Maruo T, Nakatani S, Jin Y, Uemura K, Sugimachi M, Ueda-Ishibashi H, Kitakaze M, Ohe T, Sunagawa K, Miyatake K. Evaluation of transmural distribution of viable muscle by myocardial strain profile and dobutamine stress echocardiography. Am J Physiol Heart Circ Physiol. 292: H921-7, 2007.
  2. Uemura K, Kawada T, Sunagawa K, Sugimachi M. Peak systolic mitral annulus velocity reflects the status of ventricular-arterial coupling -Theoretical and experimental analyses -. J Am Soc Echocardiogr. (2011 In press)
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