Ernest M. Stokely

Analog Computer Model for the ACTH-Glucocorticoid System

A closed-loop analog computer model for corticosterone dynamics in the male rat is presented in an attempt to examine some existing experimental evidence which suggests contradictory characteristics of the ACTH-glucocorticoid system. First-order compartmental kinetics model the removal of ACTH and corticosterone from the blood. Nonlinear models are used to describe the release of corticosterone by the rat adrenal cortex in response to ACTH in blood, and for the release of ACTH by the anterior pituitary in response to corticotrophin-releasing factor (CRF) in the hypophyseal portal system. Curve-fitting techniques are used for each system function to adjust the analog to obtain good agreement with laboratory data. The gross characteristics of the neurosecretion of CRF and the resulting ACTH secretion are identified by using portions of the model to simulate various physical experiments.

A heterogeneous tissue model for measurement of regional blood perfusion in the myocardium using inert gas isotopes

Abstract Inert gas isotopes are finding increasing application in the measurement of blood perfusion in the capillary beds of muscle, especially the myocardium. When measuring blood perfusion of the myocardium, washout curves are first produced by precordial monitoring of isotope activity following intracoronary artery injection of an inert gas isotope dissolved in saline. The washout curve data are then applied to a mathematical model to yield blood perfusion rate. Present models for this purpose either ignore any diffusive effects of gas movement (Kety-Schmidt model), or diffusive effects are accounted for by weighting the calculated perfusion value (Zierlers height-over-area technique). A new model is described here for convective and diffusive movement of an inert, nonpolar gas in myocardial tissue. A digital computer simulation of the model equations is used both to simply the model and to show agreement between the model response and experimental 133 Xe washout curves from normal and infracted canine hearts. The model assumes that the tail of the washout curves (portion after roughly 1.5 minutes) is caused by a heterogeneous, diffusion-limited tissue structure. The model provides two parameters which can be adjusted to washout curve data using model-matching techniques. These are perfusion rate, and a parameter which is an index of the diffusive nature of the particular myocardial area under study.

Technetium-99m-Pyrophosphate Myocardial Imaging in Acute Myocardial Infarction

The recognition of acute myocardial infarcts is not always easily accomplished. Infarct recognition is especially difficult using electrocardiography in individuals who had previous myocardial infarcts, those with left bundle branch block, those who have been cardioverted, and those with acute non-transmural (subendocardial) myocardial infarcts. Even the most sophisticated enzymatic techniques presently available have certain limitations in identifying the presence of absence of acute myocardial infarcts in patients including: (1) there is a temporal dependency in the ability of various enzyme markers to detect acute myocardial infarcts, and (2) certain clinical settings preclude using traditional enzyme techniques (including creatine kinase — MB isoenzyme) for infarct recognition and to be emphasized in this regard is the perioperative and postoperative setting after coronary artery revascularization. Therefore, it is important to have additional relatively noninvasive means that allow infarct detection, localization and provide some estimate of the size of the lesion.

Mechanisms of Technetium-99m-Pyrophosphate Accumulation in Damaged Myocardium

The purpose of this chapter is to summarize the available information concerning the pathophysiological basis for the use of the “hot spot” myocardial imaging technique, 99mTc stannous pyrophosphate in the detection of irreversibly damaged myocardial tissue, including acute myocardial infarcts. 99mTc-pyrophosphate is classified as a “hot spot” imaging technique since it concentrates in acutely infarcted myocardium. Table 3-1 identifies other “hot spot” imaging techniques that also allow the recognition of acute myocardial necrosis. This chapter will concentrate on the use of 99mTc-pyrophosphate as an “infarct avid” or “hot spot” agent to detect acute myocardial infarcts.

Technetium-99m-Pyrophosphate Myocardial Imaging in Patients with Atypical Chest Pain

Technetium-99m-pyrophosphate myocardial scintigrams may be utilized to help exclude the presence of acute myocardial infarcts in patients with atypical chest pain that are admitted to the coronary care unit. Our previous clinicopathologic correlates have suggested that 99mTc-pyrophosphate myocardial scintigrams are capable of identifying acute myocardial necrosis with 89% sensitivity and high specificity; this scintigraphic approach has an even higher sensitivity (one approaching 100%) in the identification of acute myocardial necrosis amounting to 3 g or more in weight when serial myocardial imaging is utilized and imaging is performed within the proper time frame (Table 13-1) [1–3]. When two 99mTc-pyrophosphate myocardial scintigrams are obtained in the first 24 hr to 5 days after acute myocardial infarction, one may be confident that serial negative 99mTc-pyrophosphate myocardial scintigrams exclude acute myocardial necrosis amounting to 3 g or more tissue with better than 95% sensitivity (Table 13-1)[1,2]. This, of course, requires optimal imaging technique and imaging within the appropriate time periods after the onset of symptoms (chapters 3 and 7) and some experience so that one may properly interpret the 99mTc-pyrophosphate myocardial scintigrams.

Instrumentation for Radionuclide Cardiology

Radioactive tracers have been employed for the evaluation of cardiac structure and function for over 50 years. The discipline had its genesis in 1927 with the innovative experiments of Blumgart and Weiss [1]. These investigators, utilizing the principles of the radioactive tracer method devised by Hevesy [2], measured circulation in man by injecting a dose of radium C-salt (radon) into an antecubital vein detecting its arrival in the contralateral brachial artery with a Wilson cloud chamber. This technique was revived by Prinzmetal and associates [3] in 1948 with the advent of atomic age technology. Using a Geiger-Muller counter and the artifical radionuclide 24Na, these investigators repeated the Blumgart and Weiss determination of circulation time also recording temporal changes in the radioactivity over the heart and lungs. The radionuclide angiocardiogram was thus discovered. Many improvements in instrumentation and radiopharmaceuticals have since been introduced to facilitate evaluation of the central circulation. Cardiovascular nuclear medicine procedures today encompass a myriad of qualitative and quantitative techniques including: (1) detection and quantitation of intracardiac shunts, (2) measurements of regional myocardial blood flow, (3) visualization of anatomic relationships of major cardiovascular structures — such as chamber dilatation, ventricular or septal hypertrophy, pericardial effusion, or ventricular aneu-rysm, (4) identification of intracardiac clot or mass, (5) evaluation of heart mechanical function, (6) identification, anatomic localization, and sizing of acute myocardial infarcts, (7) noninvasive assessment of myocardial perfusion at rest and during exercise or pharmacologic stress, (8) assessment of severity of valvular regurgitation, and (9) evaluation of regional myocardial metabolism.