Fumihiko Kajiya

Optimal control of medical treatment: Adaptive control of blood glucose level in diabetic coma

Abstract The primary purpose of clinical decision-making is to determine the most adequate treatment for individual pathological conditions, and the process of diagnosis and treatment constitutes a feedback loop. The present study was undertaken to apply “optimal control theory” to this process of clinical decision-making. The basic requirements for the application of optimal control theory in the clinical setting is presented and a clinical application, “adaptive control program,” is proposed for the control of blood glucose level in diabetic coma using a simulation model of blood glucose kinetics.

A digital computer model of the renal medullary countercurrent system. I

Abstract A mathematical model of the renal medulla was made, integrating structural and functional concepts into a unified understanding of the mechanisms involved. The medulla was assumed to have vasa recta, the loops of Henle, collecting tubules and interstitium. Numerical studies were carried out to simulate the movement of water, sodium and urea in nonsteady states on an assumption that sodium pump exists along the loops of Henle and collecting tubules, and that no active transport of urea exists in the kidney. The model yielded piecewise continuous curves for volume flow rate, and sodium and urea concentration profiles which reasonably agree with available data along the consecutive segments. It was shown that the osmolality gradient could not be reproduced reasonably well without taking the presence of sodium pump along the thin loops of Henle. It was also shown that the concentration gradient for urea could become steeper than that of sodium without resulting in its active transport.

Evaluation of Coronary Blood Flow by Fiber-Optic Laser Doppler Velocimeter

Our laser Doppler velocimeter (LDV) with an optical fiber is a powerful tool for the measurement of both coronary artery and vein flow velocities because of its excellent accessibility to the coronary vessels of a moving heart. In this paper, we briefly describe the optical arrangement of the LDV and then introduce some results of measurements of the blood velocity patterns of epicardial large coronary vessels, and epicardial small arteries and veins obtained by two different routes of access of fiber probe. We also touch upon the dual-core-fiber system which is probably promising as a Doppler catheter for clinical use

Coronary Venous Flow

It is well known that coronary arterial flow is predominantly diastolic, whereas coronary venous flow is predominantly systolic. Since coronary venous flow is squeezed out from the myocardial vascular bed by direct and indirect extravascular compressive forces of the myocardium, the coronary venous system is therefore very unique and offers a suitable model to investigate the relationship between cardiac contraction and coronary blood flow. Moreover, the intramyocardial coronary venous system has a negative feedback control system against arterial inflow into the myocardium; that is the increase of intramyocardial venous blood volume decreases arterial inflow and this decrement enhances arterial inflow. Therefore, analysis of coronary venous outflow in relation to the mechanical control of coronary arterial inflow is also important. We overviewed the phasic blood flow patterns of proximal and distal coronary vessels of the left ventricle, right ventricle, and left atrium.

Blood Flow in Coronary Vessels

The anatomical characteristics of the coronary circulation are summarized (Gregg and Fisher 1963; Berne and Rubio 1979; Marcus 1983) as follows: Two major coronary arteries (Fig. 6.1), a right and left, arise respectively from the right anterior and left anterior aortic sinuses of Valsalva. The left main coronary artery in adult humans is about 4–5 mm in diameter, and the mean length of this artery is 1.3 cm. The right coronary artery as its origin is about 3–4 mm in diameter. The left anterior descending coronary artery and its diagonal branches in humans perfuse most of the left ventricular myocardium. The septal perforating branches from the left anterior descending artery supply the interventricular septum. The left circumflex coronary artery follows the respective auriculoventricular groove to the left and terminates at a variable distance from the posterior longitudinal sulcus. In contrast to humans, the circumflex coronary artery in the dog supplies the largest area of cardiac muscle. The right coronary artery follows the respective auriculoventricular groove to the right. In man it usually (in about 80%) reaches the posterior sulcus and becomes the posterior descending artery.

Blood Velocity Profiles Along Poststenotic Coronary Artery and Stenotic Intramyocardial Flow

To evaluate the effect of coronary stenosis on coronary flow, we evaluated: (1) the blood velocity profiles across the vessel at portions distal to stenosis, (2) the velocity waveform in the septal artery during left main coronary artery stenosis with or without vasodilators, and (3) transmural flow distribution with low perfusion pressure as in stenosis before and after intracoronary nitroglycerin. The experiments were performed in 29 dogs using our 80-channel 20 MHz ultrasound velocimeter. The poststenotic velocity configuration was characterized by a narrow region of high velocity with diastolic reverse flows near the wall which may dissipate energy. Septal artery blood flow velocity which reflected myocardial inflow showed a diastolic-predominant waveform always accompanied by a systolic retrograde blood velocity component. Coronary artery stenosis enhanced the systolic retrograde flow with a decrease in diastolic flow, reducing myocardial inflow. The systolic retrograde flow was augmented further by coronary vasodilation (intracoronary adenosine or nitroglycerin) and did not improve myocardial inflow (or decreased it). Intracoronary nitroglycerin increased epimyocardial flow, but did not increase endomyocardial flow. In conclusion, an augmented retrograde flow which is increased by vasodilators plays an important role in disturbing myocardial inflow during coronary artery stenosis. This could be called a “coronary slosh phenomenon”. Thus, increased systolic retrograde flow and the decreased diastolic flow are closely related in reducing myocardial flow, especially subendocardial flow.

A Study of Coronary Circulation by Laser Doppler Velocimetry

Our laser Doppler velocimeter (LDV) with an optical fiber is a powerful tool for the measurement of both coronary artery and vein flow velocities because of its excellent accessibility to coronary vessels of the beating heart. We designed four different accesses of a fiber probe to measure blood velocities, depending upon the objectives of the measurements, i. e., epicardial large coronary vessels, the epicardial small artery and vein, the intramyocardial artery and vein, and a laser catheter. The blood flow velocities showed a diastolic-predominant pattern in the coronary artery and a systolic-predominant pattern in the coronary vein. The phase opposition between arterial and venous flows was more remarkable in intramyocardial vessels, i. e., the systolic reverse flow in the artery showed a reciprocal relation to the systolic forward flow in the vein. In veins, suction of blood from superficial veins to a deeper portion may occur during diastole. The laser Doppler catheter was found to be useful for monitoring coronary vein flows in the coronary sinus and the great cardiac vein. We found that the four different routes of access of optical fiber probe are useful for the evaluation of coronary flows.

Simulation Study of Flow Distribution across Myocardium

The distribution of intramyocardial blood flow is influenced by several flow determinants such as perfusion pressure, vascular active tension, intramyocardial pressure and heart rate, Among these factors, the contribution of vascular active tension and intramyocardial pressure to flow distribution within myocardiurrris not clarified, explicitly due to a difficulty in measuring these factors directly.