The intrinsic limitations of coronary arteriography to predict the physiological effects of coronary obstructions are well known. Therefore, more direct assessments of the functional significance of coronary stenoses are becoming increasingly important. Study of contrast passage by electrocardiogram-triggered digital radiography has been proposed as a way of assessing changes in myocardial perfusion. The main problems in this approach are the limited time for motionless image acquisition, the potential alteration of vascular volume between different states, and the changing flow pattern induced by contrast agents. This has led to empiric substitution of mean transit time (Tmn) by other time parameters and to representation of vascular volume by maximal contrast intensity (D..). To avoid these problems, intact dogs were studied during almost motionless image acquisition of 20-25 consecutive paced heart beats obtained with synchronous radiographic pulses. In (weight, 26-36 kg) were anesthetized with sodium pentobarbital 25 mg/kg i.v., a left thoracotomy was performed, and epicardial pacing electrodes were sutured on the left atrium. The proximal part of the left circumflex artery (LCx) was gently dissected free, over a distance of 1.0-1.5 cm proximal of the origin of the first large obtuse marginal branch. A ring-mounted 20-MHz pulsed Doppler probe (Crystal Biotech Inc., Holliston, Massachusetts) was placed around the artery and a circular balloon occluder (R.E. Jones, Silver Springs, Maryland) was placed just distal to the Doppler probe. The pericardium and chest were closed, and the instrumentation leads were placed in a subcutaneous pocket until the time of study.At day 11 after instrumentation, each dog was anesthetized by nicomorphine 10 mg/hr i.v. and ethrane. The subcutaneous pocket was opened, and the wires of the Doppler probe were connected to the appropriate recording equipment (545C-4 Directional Pulsed Doppler Flowmeter, Department of Bioengineering, University of Iowa, Iowa City, Iowa). The pacing electrodes were attached to a trigger unit (Department of Bioengineering, University of Nijmegen, The Netherlands) and the occluder tube was connected to a 5-ml syringe. Both femoral arteries were dissected free. An 8F pigtail manometer catheter (Millar microtipped-catheter transducer SPC-780C) was introduced into the left femoral artery and positioned for simultaneous pressure recording in the left ventricle and the ascending aorta. A 5F left Judkins catheter was introduced into the right femoral artery and advanced into the ostium of the left main coronary artery. Electrocardiogram, left ventricular pressure and its first derivative, aortic pressure, and phasic and mean coronary blood flow velocity in the LCx were recorded on an eightchannel recorder (Hewlett-Packard).After intravenous infusion of 5 mg propranolol during 20 minutes to prevent disproportionate increase in heart rate, an initial dose of dipyridamole (0.75 mg/kg) was administered intravenously during 4 minutes to create maximal dilation ...

Over the last decade it has become more and more obvious that besides anatomical information about the severity of coronary artery stenoses, information about coronary and myocardial blood flow is necessary to understand the functional significance of these obstructions and to evaluate the result of an intervention. Several methods have been proposed for this purpose, each of these having their particular limitations. In this study a new method is shortly described which allows the accurate calculation of relative maximal myocardial perfusion by ECG-triggered digital radiography (videodensitometry), using mean transit time (Tmn) as time parameter; this technique is based on the original physiologic principles of indicator dilution theory. This method was validated in 8 instrumented dogs in which an excellent linear relation was present between 1/Tmn and flow (r = 0.96 +/- 0.03). Although this method does not allow assessment of resting flow and therefore coronary flow reserve (CFR), it provides a means for the reliable comparison of maximal myocardial flow in different situations and it is independent of most factors affecting coronary flow reserve. The ratio between maximal flow after and before an intervention is called maximal flow ratio (MFR) and this concept was applied in a pilot study in man to evaluate PTCA results in 10 patients undergoing elective angioplasty. MFR was compared with the result of exercise testing 24 hours before and 10 days after the angioplasty. MFR greater than or equal to 1.5 was always accompanied by reversal of exercise test result from positive to negative. We conclude that the accurate calculation of relative maximal perfusion of the myocardium is possible by videodensitometry and suggest that comparison of maximal flow after and before an intervention can be valuable in man for functional evaluation of the result of the intervention.

BACKGROUND In the setting of percutaneous transluminal coronary angioplasty (PTCA), immediate information about the result of the intervention is important, whereas morphological parameters are often less reliable than in diagnostic coronary arteriography. Recently, a new videodensitometric method was introduced and validated in animal experiments, which allows accurate comparison of maximal myocardial perfusion between situations with different degrees of stenosis. This method uses mean transit time (Tmn) of the contrast agent at maximal hyperemia as a parameter for maximal flow and is strictly in accordance with indicated dilation theory. METHODS AND RESULTS In 40 patients with angina pectoris, single-vessel disease, and a positive exercise test at the time of acceptance for PTCA, this approach was applied for evaluation of the improvement of maximal flow achieved by the PTCA. Maximal vasodilation was induced immediately before and 15 minutes after PTCA by intracoronary administration of papaverine, and digital angiographic studies were performed. By special breath-holding instruction, almost motionless, triggered image acquisition was possible during 15-20 heartbeats. Excellent subtraction images could be obtained, and reliable determination of Tmn at maximal hyperemia was possible in 33 patients both before and after PTCA. The ratio between maximal flow after and before PTCA, called maximal flow ratio (MFR), was represented by the ratio between Tmn before and after the intervention and compared with the results of exercise testing 24-48 hours before and 7-10 days after the procedure. After correction for pressure changes, MFR was 2.2 +/- 1.5 for the 33 dilated vessels and 1.0 +/- 0.2 for 25 normal vessels serving as a control. In 94% of all patients, an MFR value of more than 1.6 or less than 1.6 discriminated between presence or absence of reversal of exercise test result from positive to negative. If on-line judgment of success was based upon angiographic parameters or measurement of trans-stenotic pressure gradient, the relation with noninvasive functional improvement was present only in 66% and 74% of all patients, respectively. A definite range of what can be called normal Tmn at maximal hyperemia could be distinguished, and post-PTCA values for successfully dilated arteries returned completely to this normal range. CONCLUSIONS Accurate comparison of maximal myocardial perfusion before and after PTCA is possible in man, improvement of maximal flow is highly related to functional improvement as indicated by exercise test results, and, therefore, this method provides a straightforward way for on-line evaluation of the result of the intervention.

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In the assessment of myocardial perfusion by ECG-triggered digital radiography, time parameters are calculated from the time density curve (TDC) and related to blood flow. Recently we developed a method which uses mean transit time (Tmn) as time parameter, and which is in accordance with the original principles of indicator dilution theory. In this approach, variability in vascular volume is excluded and Tmn-1, determined at maximal hyperemia, showed an excellent correlation with maximal flow in animal validation studies. For calculation of Tmn, however, a large part of the descending limb of the TDC has to be known for reliable extrapolation, and especially this part of the curve is subject to variability in image quality in man. Therefore we tested reproducibility of Tmn in 30 arteries in 20 patients. Tmn was derived from the TDCs, obtained from paired studies under identical circumstances with an interval of 10 minutes. Satisfactory images could be obtained in all but one patient. Image processing was performed in an identical way in the paired studies. Reproducibility proved to be excellent for all three coronary arteries. The absolute value of the relative differences between the first and second determination was 7 +/- 7% for the LAD, 6 +/- 3% for LCx and 4 +/- 2% for the RCA (mean +/- SD). Correlation coefficients between both measurements were 0.97, 0.95 and 0.95 for the respective arteries. Therefore, it is concluded that, using this approach, Tmn at maximal hyperemia can be determined reproducibly in man and used for maximal myocardial flow assessment.