Regional Myocardial Tissue Blood Flow Research Articles

Contrast echocardiographic quantification of regional myocardial perfusion: Validation with an isolated rabbit heart model

Quantification of regional myocardial tissue blood flow (RMBF) based on contrast echocardiography has yet to be achieved. This study validated our recently proposed algorithm for quantification of RMBF with colored microspheres. Experiments were carried out in an isolated rabbit heart preparation ( n = 11). Aortic root injections of perfluoropropane-filled albumin microsphere solution (FS069) and colored microspheres were performed at five levels of coronary flow achieved by altering perfusion pressure. During each injection of contrast material, consecutive end-diastolic images of the heart and an extracardiac reference chamber were acquired with a 7.5 MHz transducer and digitized. Time-intensity curves from the reference chamber and myocardial regions of interest, corresponding to the anatomic segments used for colored microsphere analysis, were analyzed for RMBF. Blood flow was calculated as the intravascular volume fraction (ratio of areas under myocardial and reference curves) divided by mean transit time (deconvolution of impulse response) and compared with those obtained with colored microspheres. Injections of FS069 resulted in highly reproducible enhancement of myocardial contrast. Analysis of time-intensity curves provided consistent measurements of RMBF ( r = 0.91), which correlated highly with microsphere data ( r = 0.84). The use of this new algorithm allows accurate quantification of RMBF in the isolated heart model. Further validation of this approach in an animal model with peripheral intravenous injections of contrast material will allow noninvasive clinical measurements of RMBF.

971-55 Can Regional Myocardial Tissue Blood Flow be Measured in Terms of ml/min/g Using Contrast Echocardiography?

Absolute quantification of regional myocardial tissue blood flow (RMBF) based on contrast echocardiography has not yet been achieved. The aim of this study was to validate of our recently proposed algorithm for the quantification of RMBF and examine its reproducibility. This approach evaluates RMBF as the intravascular volume fraction (ratio of the areas under myocardial time intensity curve and a curve obtained from a reference region of interest) divided by mean transit time (obtained using deconvolution of impulse response). Experiments were carried out using an isolated rabbit heart model (N = 8), wherein coronary blood flow was controlled by varying perfusion pressure. Factors confounding in-vivo experimentation, such as cardiac translation and limited image quality, were eliminated in this setup. Aortic root injections of FS069, a new stable contrast solution (MBI, 1:200 in saline, filtered using a 8 /μ-pore filter) and colored microspheres, used as the “gold” standard for reference, were performed at different levels of coronary flow. During contrast injections, end-diastolic images of the heart and an extracardiac reference chamber were acquired using a 7.5 MHz transducer and digitized on-line and processed using the above algorithm. Contrast echocardiographic measurements of RMBF highly correlated with microsphere flow (figure). Bland-Altman analysis revealed an insignificant bias of 0.07 ml/min/gr, with 95% limits of agreement at 0.69 ml/min/g. Using this algorithm, repeated evaluations of RMBF were highly reproducible (r = 0.92). In summary, the use of this new algorithm in conjunction with stable contrast agents, such as FS069, allows accurate and reproducible quantification of RMBF.

Myocardial transit time of the echocardiographic contrast media

The mean transit time of a tracer through a sample of tissue is a quantitative marker most closely related to regional tissue blood flow. Therefore, an accurate estimation of the mean time of transit of an ultrasonic tracer through a sample of myocardial tissue, obtained by contrast echocardiography, may provide a quantitative noninvasive estimate of myocardial perfusion. We hereby present an algorithm for the determination of the mean transit time by computerized analysis of a series of contrast-enhanced echocardiographic images. The algorithm comprises the evaluation of the echocardiographic impulse response function of a selected region of interest, using a deconvolution technique based on a fast Fourier transform and a frequency domain division of the videointensities measured in the sample, by that measured in a predetermined reference region. An extensive computer simulation study was designed to facilitate the optimization of the steps of analysis. We present the results of the evaluation study performed in order to assess the accuracy of the procedure in computer-simulated echocardiographic images. Within a wide range of parameters chosen to define these functions, the analysis is shown to be essentially independent of the rise and decay times of the impulse response function of the tissue sample as well as of the simulated intensities. The effects of random noise introduced into the simulated intensity curves and of their variable width were investigated. The mean transit time was found to be accurately evaluated within about 10% of error for the variety of widths and noise levels permitted. The reconvolution error did not correlate with the accuracy of the evaluation of the mean transit time, indicating that the reconvolution error cannot be used as an estimate of the accuracy of the procedure. The numerical methods and the results of the computer study are discussed in detail. The approach is proposed to be used as part of a more general technique for the quantitative measurement of regional myocardial tissue blood flow.

Collateral Blood Flow Following Acute Coronary Artery Occlusion

The effects of a new intracellular calcium antagonist, KT-362 (150 and 300 micrograms/kg per min), on hemodynamics and collateral function (retrograde pressure and flow, radioactive microspheres) distal to an acute coronary artery occlusion were studied in anesthetized dogs and compared with the effects of the structurally related classical calcium channel blocker, diltiazem (15 and 30 micrograms/kg per min), and a saline-treated control group. In the saline series, there were no changes in systemic hemodynamics or coronary collateral blood flow over the 90-min ischemic period. KT-362 reduced mean aortic pressure, heart rate, and dP/dt whereas diltiazem only decreased aortic blood pressure. When blood pressure was controlled by a distal aortic cuff, heart rate was significantly reduced in both groups and dP/dt was reduced in the KT-362 series and increased in diltiazem-treated dogs. In both drug-treated groups, retrograde pressure and flow were significantly increased only when aortic pressure was controlled. Regional myocardial tissue blood flow in the nonischemic or ischemic region did not change significantly after KT-362 treatment despite its hypotensive actions, and in the presence of a constant aortic pressure, transmural collateral blood flow and the ischemic/nonischemic blood flow ratio tended to increase. In contrast, diltiazem treatment resulted in a significant decrease in the ischemic/nonischemic blood flow ratio in the absence of blood pressure control. In the presence of constant aortic pressure, blood flow to the nonischemic area was markedly increased by diltiazem whereas subendocardial blood flow was significantly increased in the ischemic area.(ABSTRACT TRUNCATED AT 250 WORDS)

Does α1‐adrenergic blockade influence regional blood flow regulation in hearts with coronary artery occlusion?

The effects of selective alpha 1-adrenergic blockade with doxazosin on regional myocardial tissue blood flow was studied in anaesthetized cats with acute coronary artery occlusion. Reflex tachycardia was prevented by selective beta 1-adrenergic blockade with atenolol and coronary perfusion pressure was kept constant by partial stenosis of the descending aorta. Administration of atenolol reduced cardiac mechanical work-load by its negative inotropic and chronotropic effects, and reduced myocardial tissue blood flow in normally perfused myocardium. This reduction was most pronounced in the endocardial half-layer of the myocardium adjacent to the ischaemic region. Administration of doxazosin in this situation clearly reduced peak systolic and coronary perfusion pressure. But when coronary perfusion pressure was raised to pre-administration values, measurements of regional blood flow revealed no changes either in ischaemic or non-ischaemic myocardium. Also, there was no sign of redistribution of blood flow between endocardial and epicardial tissue in any area. This study, therefore, indicates that alpha 1-adrenoceptors play a minor role in the regulation of coronary blood flow in normal myocardium as well as ischaemic myocardium.

Regional myocardial tissue blood flow during beta-adrenergic blockade in cat hearts with acute ischaemia.

Selective beta 1- or beta 2-adrenergic blockade was achieved by practolol or IPS 339, respectively, in cats with acute ligation of a coronary artery. During blockade, heart rate was kept constant by atrial pacing and blood pressure reduction was prevented by aortic clamping. Regional myocardial blood flow was measured by the distribution of 15 micron labelled microspheres. Practolol slightly reduced epicardial blood flow in ischaemic myocardium, while blood flow in border and normally perfused myocardium remained unchanged. Following IPS 339, myocardial tissue flow increased in normally perfused myocardium, on average by 37% in the endocardium and 30% in the epicardium. No changes occurred in the other regions. The flow changes brought about by IPS 339 were unrelated to haemodynamic changes, and the coronary vascular resistance was reduced. These results are indicative of coronary vasodilation related to beta 2-adrenergic receptor blockade and was confined to well-oxygenated areas surrounding the acutely ischaemic zone.

Regional myocardial tissue blood flow during sequential β1 - and β2-adrenergic blockade in cat hearts with acute ischaemia

β-adrenergic blockade was imposed on cats with ischaemic regions of the left ventricle produced by coronary artery occlusion. Ten animals first received a β1-blocking agent (atenolol) followed by a β2-blocking agent (IPS 339). In ten more animals this sequence was reversed. Combined blockade, obtained after both agents were administered, showed clear reduction of tissue blood flow in all areas of the ventricle, except for the central ischaemic zone. The flow reduction could be ascribed to bradycardia and reduced coronary perfusion pressure. By analysing the sequential changes it was evident that blockade of β1-adrenergic receptors was responsible for the haemodynamic changes, and the coronary vascular resistance rose so as to match the quantity of blood flow to the functional state of the ventricle. Blockade of β2-receptors by IPS 339, however, showed no evidence of coronary vasoconstriction but rather maintained vascular resistance at an unchanged level despite a weak β1-adrenergic blocking effect.

Regional myocardial tissue blood flow during sequential beta 1- and beta 2-adrenergic blockade in cat hearts with acute ischaemia.

beta-Adrenergic blockade was imposed on cats with ischaemic regions of the left ventricle produced by coronary artery occlusion. Ten animals first received a beta 1-blocking agent (atenolol) followed by a beta 2-blocking agent (IPS 339). In ten more animals this sequence was reversed. Combined blockade, obtained after both agents were administered, showed clear reduction of tissue blood flow in all areas of the ventricle, except for the central ischaemic zone. The flow reduction could be ascribed to bradycardia and reduced coronary perfusion pressure. By analysing the sequential changes it was evident that blockade of beta 1-adrenergic receptors was responsible for the haemodynamic changes, and the coronary vascular resistance rose so as to match the quantity of blood flow to the functional state of the ventricle. Blockade of beta 2-receptors by IPS 339, however, showed no evidence of coronary vasoconstriction but rather maintained vascular resistance at an unchanged level despite a weak beta 1-adrenergic blocking effect.

Effect of practolol on blood flow distribution in the myocardium during acute regional ischaemia in cats

The β-adrenergic blocking agent practolol was given to 11 cats with acute coronary artery ligation, and regional myocardial tissue blood flow was measured by the distribution of 15 μm labelled microspheres. Practolol reduced heart rate and cardiac contractility, but left ventricular end-diastolic pressure rose in eight animals. In three animals, however, the haemodynamics were essentially unchanged and these are referred to as non-responders. No changes in regional myocardial blood flow were observed after practolol administration, either in ischaemic, border or normal areas of the left ventricle. This indicates less serious imbalance between oxygen demand and delivery in ischaemic tissue. There was no endocardial/epicardial redistribution of tissue flow. Practolol did not appear to improve coronary perfusion, and beneficial clinical effects of practolol are therefore probably related to reduction of myocardial oxygen demands.