CORONARY BLOOD FLOW Transluminal , subselective

Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was varied from 0.1 to 5.7 times control CBFV. Changes in mean CBFV measured intraluminally by catheter in the left anterior descending and left circumflex arteries were similar to those measured simultaneously with an epicardial Doppler probe on the surface of the same vessel (n = 85, r = .95, slope = 1.04) and to changes in coronary sinus flow (n = 69, r .97, slope 1.06) measured with timed venous collections. Identical maximal coronary reactive hyperemic responses with the catheter present and absent in the artery being studied demonstrated that coronary obstruction by the catheter was minimal. Safety studies in six additional calves demonstrated that the catheter caused small changes in coronary endothelial permeability. Histologic studies revealed no endothelial denudation or thrombus formation. Stable phasic recordings of coronary blood flow velocity have been obtained in 58 of 70 patients studied. One of the 70 patients studied had abrupt coronary occlusion probably related to catheter-induced vasospasm. In 10 normal patients, intracoronary meglumine diatrizoate increased CBFV to 3.5 times that at rest (range 2.8 to 5.0). CBFV rose 5.0-fold after an intravenous infusion of dipyridamole (range 3.8 to 7.0). In each patient, dipyridamole produced greater vasodilation than meglumine diatrizoate. The timeand dose-response characteristics to dipyridamole infusion were heterogeneous, underscoring the advantage of continuous on-line measurement of CBFV in the measurement of vasodilator reserve. This method of measuring CBFV and assessing vasodilator reserve in the catheterization laboratory should facilitate studies of the coronary circulation in man. Circulation 72, No. 1, 82-92, 1985. MEASUREMENT OF phasic coronary blood flow velocity (CBFV) and the flow reserve capacity of individual coronary vessels has been hampered by methodologic limitations. Such data, if obtainable, could provide a means of assessing the physiologic significance of obstructive coronary artery disease at the time of cardiac catheterization. Current methods of measuring coronary blood flow in conscious man have many limitations. Inert gas clearance techniques measure global myocardial blood From the Department of Internal Medicine and the Cardiovascular Center, University of Iowa Hospitals and Clinics, the Veterans Administration Hospital, Iowa City, and the University of Texas Health Science Center at Houston. Supported by grants from the National Heart, Lung, and Blood Institute (HL 27633, 14388, and 29976), the Ischemic SCOR (HL 3229501), and the Veterans Administration (MRIS 1100.2). Address for correspondence: Robert F. Wilson, M.D., Department of Internal Medicine, University of Iowa Hospitals, Iowa City, IA 52240. Received June 13, 1984; revision accepted March 28, 1985. 82 flow but cannot detect rapid changes in flow. 'Radionuclide techniques (e.g., 133Xe clearance) measure regional blood flow, but do not permit on-line continuous assessment of coronary blood flow and are not accurate if blood flow is greater than 200 ml/min/100 g tissue.4 5 The coronary sinus thermodilution technique measures coronary venous effluent, but, except for that in the left anterior descending artery, cannot relate flow to an individual coronary artery. The technique is hampered further by catheter movement within the coronary sinus and inconsistencies in venous drainage patterns.3'6 These methodologic problems have prevented accurate measurements of coronary blood flow and the flow reserve capacity of individual vessels in conscious humans. Furthermore, the inability to obtain on-line flow measurements has prevented characterization of the timeand dose-response characteristics of coronary vasodilators. CIRCULATION by gest on O cber 9, 2017 http://ciajournals.org/ D ow nladed from DIAGNOSTIC METHODS-CORONARY BLOOD FLOW Previous techniques of measuring instantaneous phasic changes in coronary blood flow in conscious humans have used pulsed Doppler technology to measure CBFV. CBFV has been shown to correlate highly with volumetric measurements of coronary blood flow.' The Doppler technique of measuring flow velocity is advantageous because rapid changes in flow can be detected, on-line recordings can be obtained, and the method lends itself to miniaturization. In 1974, Hartley and Cole8 developed a No. 5F (tip) Doppler catheter capable of measuring CBFV at the coronary ostium by placing a piezoelectric crystal at the tip of a Sones catheter. A major limitation of this and other coronary Doppler catheters available was that they were too large to place subselectively into coronary arteries. Furthermore, because the Doppler crystal is mounted on the catheter tip and the tip position is unstable, signal instability over time was a significant problem. Additionally, validation studies over a wide range of coronary flows have not been presented. The purpose of our study was twofold: to develop and validate a coronary Doppler catheter that could be subselectively placed into individual coronary vessels to measure instantaneous changes in CBFV and to develop a method for determining subselective coronary vasodilator reserve at the time of cardiac catheterization. t;000:} 000.000*evo* 0. Rentrop catheter (woven dacron. resin coated) t; ~~~~~~. .., ,.,,, ... .... copper --4wire (to doppler unit). 7 degassed epoxy Methods The subselective coronary Doppler catheter was constructed by placing a 20 MHz piezoelectric crystal into the wall of a Rentrop reperfusion catheter (United States Catheter and Instrument, Co.) and used a 20 MHz pulsed Doppler imneter (Bioengineering Department, University of Iowa) to measure blood flow velocity. The woven Dacron catheter is 120 cm in length and has a 1.6 mm outer diameter at the proximal end; the distal 20 cm tapers to 1 .0 mm outer diameter (figure 1). This catheter has been approved for investigational use in humans by the U.S. Food and Drug Administration. Details of the catheter construetion and specifications of the pulsed Doppler meter are con tained in the Appendix. To determine the relationship between mean flow velocity and Doppler frequency shift measured with the coronary Doppler catheter, the catheter was placed into the lumen of a 1.8 mm internal diameter polyethylene tube system filled with a mixture of water and laundry starch and connected to a roller pump (Sarns Co.). A windkessel chamber was used to minimize pulsatile flow. The starch has ultrasonic reflective characteristics similar to blood.7 Mean flow velocity was calculated with the use of timed volume collections of tube flow. Paired measurements of flow velocity and Doppler frequency shift, obtained over a broad range of flows, were closely correlated (r = .99; figure 2). Animal validation studies. Seven calves were anesthetized with ketamine (20 mg/kg im and iv) and pentobarbital sodium (10 mg/kg iv) and mechanically ventilated. A left thoractomy was performed and a 6.5 mm internal diameter catheter passed through the right atrial appendage into the proximal coronary sinus and secured with a ligature. Blood from the coronary sinus catheter could be returned to the jugular vein or diverted to a graduated cylinder for timed volume collections. Catheters were placed in the left femoral artery and both femoral veins for measurement of arterial pressure, withdrawal of blood samples, and drug infusions. A metal introducer was placed into the right 20 mHz piezoelectric crystal / (compressional gold plated. / 1mm diameter)