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Myocardial Blood Flow in Coronary Artery Disease Effect of Right Atrial Pacing and Nitroglycerin SUZANNE B. KNOEBEL, M.D., PAUL L. MCHENRY, M.D., ANTHONY J. BONNER, M.D., AND JOHN F. PHILLIPS, M.D. Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 SUMMARY Sixteen patients, 10 with significant three-vessel coronary artery disease (>50% occlusion of each vessel) and six without coronary disease, had nutrient myocardial blood flow, cardiac output, pressure time/ min and arterial pressure determinations at rest, with atrial pacing and with right atrial pacing plus nitroglycerin. In the patients with coronary disease, nutrient myocardial blood decreased an average of 16% (P < 0.001) with pacing alone but increased by 22% (P < 0.001) from the pacing flows with the addition of 0.4 mg sublingual nitroglycerin at the same pacing rate. The directional changes in myocardial blood flow were unrelated to perfusion pressure or pressure work. In the patients without coronary disease, opposite effects were observed. With right atrial pacing, nutrient myocardial blood flow increased by 23% (P < 0.02). With the addition of nitroglycerin, myocardial blood flow decreased by 15% (P < 0.02). These changes were directionally related to changes in pressure-work of the heart It is suggested that the findings in this study are consistent with observations made in the experimental animal which indicate that the effect of nitroglycerin may be partly due to a redistribution of myocardial blood flow. Additional Indexing Words: Autoregulation Coincidence technic S4Rubidium Nutrient blood flow IN THE PAST few years a number of studies have been reported utilizing acceleration of the heart rate by right atrial pacing as a stress intervention to study the hemodynamic, metabolic, and coronary flow characteristics in patients with coronary artery disease.' 14 The intervention has been of considerable interest because it is relatively safe, repeatable, and defines a threshold in terms of the tension-time index, pressure time/min, or triple product,6 having fewer independent variables than exercise or other forms of stress testing.4 5 9 13 The studies have demonstrated manifestations of ischemia such as impaired left ventricular function, electrocardiographic alterations, and lactate pro- Perfusion pressure duction. More recently, demonstrations of coronary flow inadequacy with atrial pacing in coronary artery disease have also been reported.15' 16 In addition, nitroglycerin has been shown to increase the threshold to right atrial pacing in that indirect reflections of myocardial blood flow deficiency have been reversed at identical pacing rates through the concomitant use of nitroglycerin.4' 17, 18 Whether the effect of nitroglycerin in this situation is manifested by reducing myocardial oxygen requirement or by altering the distribution of myocardial blood flow is unresolved.'9 Many of the problems concerning the effect of nitroglycerin are compounded by the varying methods used to determine myocardial blood flow. Some methods measure total coronary flow, not necessarily nutrient flow, some methods may be relatively insensitive to poorly perfused areas, some technics measure regional perfusion, and so forth.20-23 This study was designed to evaluate alteration in nutrient myocardial blood flow produced by sublingual nitroglycerin administered during right atrial pacing in patients with three-vessel coronary artery disease, as compared with patients without coronary artery disease. Nutrient myocardial blood From the Department of Medicine, Indiana University School of Medicine, the Krannert Institute of Cardiology, and Marion County General Hospital, Indianapolis, Indiana. Supported in part by the Herman C. Krannert Fund, U. S. Public Health Service Grants HL-06308, HL-05363, and HL-05749, the Indiana Heart Association, and the Northwest Indiana Heart Association. Address for reprints: Suzanne B. Knoebel, M.D., 1100 West Michigan Street, Indianapolis, Indiana 46202. Received August 28, 1972; revision accepted for publication November 30, 1972. 690 Circulation, Volume XLVII, April 1973 691 MYOCARDIAL BLOOD FLOW IN CAD flow measured utilizing a coincidence counting and single bolus of 84Rb.24 25 was system Material and Methods Sixteen patients undergoing selective coronary cinearteriographic studies for diagnosis or evaluation of the severity of coronary arteriosclerotic occlusive disease had myocardial blood flow determinations at rest, with right atrial pacing, and with right atrial pacing concomitant with the administration of sublingual nitroglycerin. The studies were performed just prior to the arteriographic evaluation. All studies were performed in the morning with the patients in a fasting state and without sedation. Measurements were made with patients in the supine Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 position. A bipolar pacing catheter was passed through the basilic vein, positioned in the right atrium so that its tip was in contact with the high lateral wall, and connected to a battery-powered pacemaker (Medtronic). A short polyethylene catheter (approximately 18 gauge) was introduced percutaneously into the right femoral artery. Blood pressure was measured via the indwelling catheter in the femoral artery, connected to a Statham P23D strain-gauge transducer and recorded on a Sanborn recorder (model 150). The mean arterial pressure was obtained by electric integration and the mean systolic arterial pressure by planimetric integration. Pressure time/min, expressed in mm Hg-secs/min, was obtained as the product of systolic mean arterial pressure, heart rate, and systolic ejection period. Systolic ejection period, in seconds, was measured from the pressure records as the time interval between the onset of the femoral artery pulse and the dicrotic notch, and was expressed as the average figure of at least six beats taken at the extremes of respiratory fluctuation. Heart rate was measured from a simultaneously recorded electrocardiogram. The cardiac output was determined using 84RbCl as the indicator.26 Myocardial blood flow, in ml/min per total heart, was calculated using the formula: MBF= q(t)/ f-0AO (t)dt where q(t) is the myocardial uptake of 84RbC] as measured by the coincidence counting system and f ,A,, (t) dt represents the concentration of the isotope in arterial blood during the first circulation, determined by extrapolation after recirculation begins. The theoretic basis of this formulation, experimental verification, and critique have been reported in - detail.25' 27 Control measurements were made during sinus rhythm, after which pacing was begun. The heart rate was gradually elevated to the point where 1: 1 A-V conduction could just be maintained or angina intervened. The maximal heart rate achieved was maintained for 3 min before and during the taking of repeat measurements unless angina intervened. If angina intervened, the pacing was continued for the time period necessary to make the myocardial blood flow measurement (45 sec). Following a recovery period of 10 min, pacing was instituted at the same rate as on the previous determination and concomitantly 0.4 mg nitroglycerin was given sublingually. Repeat Circulation, Volume XLVII, April 1973 measurements were made at the precise time as the first stress measurement. After completion of the myocardial blo)d flow and hemodynamic determinations coronary cineangiography was performed. Multiple oblique views were obtained using renographic contrast media. Injections were made before and after administration of sublingual nitrates. Recording was performed with 35-mm Double-X film developed in Ethol-90. A Phillips 6-in image intensifier was utilized with a 100-mm lens at 64 frames/sec. Only patients whose cineangiograms were of good quality in multiple projections of all three major coronary vessels were included in this study. Coronary arterial lesions were classified as follows: Each of the three major coronary vessels (right, left anterior descending, and circumflex) was assigned a value of 100. A value of 200 was assigned to the left mainstem coronary artery. The number of vessels involved was then determined and the percentage of each vessel which remained open was estimated in increments of 25%. In the case of branch stenosis, the degree of occlusion was estimated according to the technic of Rowe et al.20 For example, if the anterior descending artery bifurcated, giving off a branch about 50% of the size of the parent vessel and if this vessel were 50% occluded, the estimated occlusion of the anterior descending vessel would be equivalent to 25% occlusion of the anterior descending coronary artery. A final coronary artery index was then based on the estimated percentage of lumen of all three vessels remaining open (300 equaling no occlusive disease). The cinearteriograms were interpreted independently by three investigators without availability of the physiologic data. Ten consecutive patients with coronary artery indices of 50 or less and six patients without coronary artery disease were included in this study. All data analyzed as the significances of the difference between the means of paired data. Results Coronary Artery Disease Patients None of the 10 patients with coronary artery disease and coronary artery indices of 50 or less was able to increase myocardial blood flow significantly with pacing to an average rate of 131 beats/min (range 120-158) (table 1). Seven of the 10 experienced angina with pacing. All of these patients experienced pain after at least 2 min of pacing so that the disparity between pacing times for patients with and without angina was minimal. The average myocardial blood flow for the group changed from 207 ± 53 ml/min, representing 4% of the cardiac output at rest, to 178 ± 50 ml/min, 3.4% of the cardiac output, with atrial pacing (P < 0.001). Pressure time/min rose 34% with pacing (P <0.001). Mean arterial blood pressure increased from an average of 98± 14 to 107±22 mm Hg (P < 0.05), and the diastolic pressure from 75 ± 10 to 90 ± 17 mm Hg (P < 0.01). There was a 692 KNOEBEL ET AL. z 0 00 ) c ) C W 0 O 0)00)000~ zz ¢ P. 0 9 0) z X °O O t- CS0 C0 X 1 X000 - C V P. E m0 1- C; t01O - C0. OC - V 9 10^ _ 1 r X C0 n N e b = N X 0 0 1` X C b ;c 0 0 0) - 0) 0) 40)s X 0, ~z S 0 X Xb 1A 0 --- V 0 N 01 0X1 00 N 0 ov 0 n t P.0 P -_ 1 0 1 10 0 0 V -il Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 kQ 4. 0 '4- SZ X0 - CO 00O C01 5 0 Xo m Lt X XOC -4 r ) C0 Nc 0) S 5 0) :tP. 0t 0C c . c0 O C cO s X 000 '-i 01 0O 01 N CO CO 10 CO 0101 CO ,- -- --- --4-~ -- --- -- 0) Cl U ccO Cc CD cc X 1 CO 0 0nCm 10 Cn --- 000 O 01 COCO N ---- - -i --- V 4-. 0).- X 0 CO O00 X 0, 0 CO 0 0 t- Co cc 1- X X Cb t- t --- 0) $_E F, ,P-4z. 0) S 00 010 CO LO ~c 0 CO - 1X °O C -O to X 10C 101 tn t- c C.0 LC t- sc C: 0 mCD CA N ". ^.' C, cq nM C, 0 0 ,-.0 6 0 0 10 Cm L- d 0 Co r- N m 0 m X c,1 00 CO m T4 'd4 C1 0) E..I c, - 01 N ± 1- 01 0 0 m nt4 1m CO m X X CO '- CO m Cl CO 01 CO CM CO , L. 0. V 4- 0 C. t- X 30 t0101 0X 9 O 0 C1 4 cc 0 t-. Cm 0 CM 0 -f 0 X 0 m 10 CO -01 10X X t N- c4 LO CO c0 10 C,01 01 C- 0 I 0. 0) z N- 01 l CO 0) tIl U Tt C-: ' X In. O4 LO 0zc C O N "R Ct 'It 1-. liD R CO CO rN : LnO t CO 10, 10) t1 't z -4 C '- 0C cc) z 0)0. Q4-. .0'-. ` i 0: .S i A 1 CO X '`t o m zC 'd ml 04cl] r 11 COl U 0 `C -0 4- z -'9 ,1 C91 0 C ce:L le C Cc -c) so tn t_ c3 X Co o --- -+" --- X c -4-- V 0 C0 m --4 " 4-.0) 0) 0I SQ 0 z V '=4 i 0) U ---4 --1 - C,1010101C -- 0 1C C pp:+ 0) U4) 00 Ot. 4-4 b 11 O0 O O O O b b 0)0) CO bi) 4'~ Cd U cc ce" m m -. 0) negative correlation between the change in myocardial blood flow and diastolic blood pressure (r=0.6783; P <0.05). With pacing to the same rate but with 0.4 mg sublingual nitroglycerin administered at the onset of pacing, myocardial blood flow increased significantly (P < 0.001), as compared with pacing alone, from an average of 178 ± 50 to 217 + 48 ml/min. The change was not significantly different from that of the resting state. The pacing plus nitroglycerin flows represented 3.4 and 4.2% of the cardiac output, respectively. Pressure time/min decreased 13% (P < 0.001), mean blood pressure and diastolic blood pressure decreased 12% and 9%, respectively (P < 0.02), with pacing and nitroglycerin. Five patients with three-vessel coronary artery disease had previously been studied with two pacing myocardial blood flow determinations separated by a 3-5-min time interval. This was done to determine if a first pacing had, in some manner, influenced a second pacing result, and, thus, nullified the nitroglycerin results. There was no significant change in myocardial blood flow, in this group, between the two pacing flow determinations. There were no significant changes in cardiac output with pacing or with pacing and nitroglycerin. Patients without Coronary Disease In the six patients without coronary occlusive disease, myocardial blood flow increased 23% (P < 0.02) from a control average of 235 ml/min to 288 ml/min, representing 5% and 6% of the cardiac output, respectively, with right atrial pacing to an average rate of 133 beats/min (table 2). Cardiac output increased insignificantly with pacing from 4.7 liters/min to 4.8 liters/min average for the group. Pressure time/min increased significantly by 21% (P < 0.01) from 2598 to 3168 mm Hg-sec/min. The mean arterial and diastolic blood pressures increased insignificantly with pacing. With atrial pacing and nitroglycerin, myocardial blood flow decreased by 15% (P<0.01) from 288 ml/min to 245 ml/min. This was a change from 6% of the cardiac output to 5.7% of the cardiac output. The cardiac output decreased from 4.8 liters/min to 4.3 liters/min, a significant change (P <0.02). There were no significant changes in blood pressure. A graphic presentation of the changes in myocardial blood flow with pacing plus nitroglycerin for both groups is shown in figure 1. Circulation, Volume XLVII, April 1973 MYC)CARDIAL BLOOD FLOW IN CAD Z =Z = Z= = )r' Discussion ~1 z z 5L, z be Pq oc o~oi Ic: X He CC CC M 'D C - Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 2 CD M~ p, L Ge- VC M CS CC X GC CO C: I' Co 4 v 4.. % \ z D ~~~~~~~~~~~Tt l1 C 4 C NNCl) CID N '1 C\X"O.1mC4 C 0I Nl DC CO: Cl Cl t t - C. lCC f'I L : t:~~~~~~~~~~~~~c X N cD Co t9 v ^ cs e GeGer > e: Ice: O v : CX S Vl w c C.) v CC; 'c CC ot CCH t CC CI*^), .-X Circlatin, Vlum C) L ce GeII APriC 1973 C) C) E = C.' C4-'-0 Ct o Z= C) _c3 .. W- C) C),°, 693 The hemodynamic data from this study are similar to those reported in a number of other studies. Right atrial pacing has been demonstrated to increase pressure time/min and not to affect cardiac output significantly.2 4 7 Nitroglycerin decreases pressure time/min with pacing, reduces systemic blood pressure, and probably results in decreased ventricular dimensions.17' 18, 28 In addition, nitroglycerin seems to decrease myocardial blood flow in normal subjects if the pressure timework of the heart also decreases.29 30 This has been taken to suggest that nitroglycerin does not affect autoregulatory mechanisms in the normal heart.29 31 Further comparison with previous studies is probably not warranted as there is great variation in experimental design, amount, and route of nitroglycerin administration, times at which measurements were made, sedation used and, in particular, methods of determination of coronary and myocardial blood flow. The validity of the myocardial blood flow changes demonstrated in this study needs to be assessed. The possible problems inherent in the coincidence technic itself have been previously discussed at length.'5 25-27 Basically, the ability to quantitate flows has been questioned, changing extraction ratios have been an issue, and clearance dependency on flow rate is a consideration. For these reasons we have not attempted to place significance on absolute flows in ml/min, but have relied on directional changes; and directional changes in coronary patients have been interpreted only as compared to patients without large-vessel coronary artery disease. While the exact mechanisms for the reduction in nutrient myocardial blood flow with right atrial pacing and the increase with sublingual nitroglycerin are not resolved by the study, the following considerations may be applicable. The same considerations also may be a partial explanation for the discrepancy between these data and data from previous studies measuring coronary blood flow with other technics. Further resolution of the mechanisms operative in patients with coronary artery disease, in particular, will come through the use of technics measuring regional flow more directly than does the coincidence system. A characteristic of the coincidence system for measuring myocardial blood flow is that detection of a decrease in regional perfusion, if of sufficient size, is possible as total myocardial uptake of isotope KNOEBEL ET AL. 694 +35- z -9. +30- o- +25 +20- E+15 -40 Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 PACING PACING NITROGLYCERIN PACING PACING NITROGLYCERIN Figure 1 (Left) The percent change in myocardial blood flow with right atrial pacing, and pacing and nBitroglycerin, in patients with three-v;essel coronary art;ery disease. (Right) The changes induced by the same interventions in patients without coronary artery disease. decreases.15, 32 Thus, the coincidence system may reflect alterations in regional perfusion. Other technics measuring single-vessel flow or dominated by single-vessel flow might register no increase (fixed flow) with an intervention which acts primarily by redistribution of flow or an actual increase in flow through nonoccluded vessels.15'23 With these considerations in mind, we propose that our data support the concept that, in the patient with coronary artery disease, when ischemia is caused by an increase in myocardial oxygen requirement with atrial pacing, a redistribution of blood flow occurs, the nutritional flow to the endocardium being limited by flow in the large conducting vessels.33 The decreased nutritional flow to the endocardium, by adding a zero count to the myocardial uptake of rubidium, results in the coincidence system measuring a decreased flow. Nitroglycerin, in addition to reducing cardiac work so that a better ratio exists between nutritional circulation toi the endocardium and requirement, also results in a redistribution of nutritional blood supply,33 reflected by an increased flow measured by the coincidence system. Data from experimental animal studies utilizing microsphere injection technics and intramyocardial oxygen tension measurements34-37 are in accord with the concepts outlined above. It has been demonstrated that, in addition to a reduction in total blood flow following acute experimental coronary artery occlusion, there is also a disproportionate reduction in subendocardial flow within the ischemic area.34 The possible mechanisms for this altered flow pattern have been discussed by Becker and Pitt,35 including a change in resistance gradient between endo- and epicardium, a possible perfusion pressure drop in perforating vessels, and an increase in extravascular compressive forces, all essentially mechanical effects following ischemia. Another model proposed by McGregor and Fam3' also warrants consideration and is, perhaps, more appropriate for the chronic state. In their model, a decrease in resistance at the arteriolar level of nonoccluded vessels when oxygen requirement is increased, might result in a decrease in blood flow to a portion of the myocardium previously supplied by that artery through collaterals, a "coronary steal" syndrome. Whichever mechanism, i.e., mechanical Circulation, Volume XLVII, April 1973 MYOCARDIAL BLOOD FLOW IN CAD Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 effects as proposed by Becker and Pitt or "coronary steal" as proposed by McGregor and Fam, is operative in patients with coronary disease, nitroglycerin could result in a redistribution of flow into an ischemic area as has been shown in the experimental animal.4-3 By decreasing myocardial oxygen demands through reduction in arterial pressulres, wall tension, and ventricular volume, the increased extravascular compressive forces caused by ischemia could be reversed and flow reestablished. Or, by allowing vasoconstriction to again maintain in nonoccluded vessels, the "steal" might be eliminated by reestablishing resting pressure relationships. Another possibility is that nitroglycerin may dilate collateral vessels in coronary patients and, thus, partially decrease the resistance quantum of the proximal occlusive lesions, effectively allowing a greater coronary reserve.'9 38 Nitroglycerin has been shown to dilate collateral vessels and increase flow to areas supplied by such vessels.38 However, it would seem that if the arteriolar bed were fully dilated because of increased oxygen demand by right atrial pacing, or if extravascular resistance were increased in an ischemic area, an increased volume of flow through collaterals would simply continue to traverse the path of least resistance and would not necessarily become nutrient flow. It is possible, however, that nitroglycerin by decreasing wall tension could permit collateral flow, which had been prevented by the ischemic changes, to resume33 and, perhaps, be augmented.39 The questions raised may prove to have some clinical relevance. Regardless of the mechanisms involved, the diseased coronary circulation does not appear to be entirely a passive one. It is not a perfusion pressure-dependent system, in the sense of epicardial vessel perfusion pressure, within normal ranges of blood pressure. The nutrient myocardial blood flow can be manipulated through the use of drugs which either decrease the pressure time/min, redistribute myocardial blood flow, or, perhaps, increase collateral flow. If, for example, it were necessary to artificially increase heart rate in patients with coronary artery disease for the control of ventricular tachycardia or other tachyarrhythmia, it might be possible to "protect" the blood supply to the myocardium through the concomitant use of an agent such as nitroglycerin. Other combinations of interventions could be similarly considered. Elevation of arterial blood pressure designed to increase coronary perfusion pressure might rather Circulation, Volume XLVII, April 1973 695 increase pressure work and myocardial consumption to the point where coronary reserve would be exceeded. These considerations are of particular importance in dealing with patients with myocardial infarction or impending infarction where a prime concern is in preserving as much myocardial blood flow as possible in order to reduce to a minimum the area of myocardial ischemia. Each patient, however, should be assessed individually. Not all of our patients had angina induced by pacing nor did nitroglycerin consistently relieve induced angina. Other investigators have observed similar variability.'2 The relationship between myocardial oxygen demand induced by any particular stress, the mechanisms by which various agents exert influence on collateral vessels, and work of the heart may vary considerably from patient to patient. It is the algebraic sum of all effects that is probably important and may account for differing clinical responses. References 1. NEILL WA: Myocardial hypoxia and anaerobic metabolism in coronary heart disease. Amer J Cardiol 22: 507, 1968 2. LINHART JW: Pacing-induced changes in stroke volume in the evaluation of myocardial function. Circulation 43: 253, 1971 3. PARKER JO, KHAJA F, CASE R: Analysis of left ventricular function by atrial pacing. Circulation 43: 241, 1971 4. PARKER JO, LEDWICH JR, WEST RO, CASE RB: Reversible cardiac failure during angina pectoris: Hemodynamic effects of atrial pacing in coronary artery disease. Circulation 39: 745, 1969 5. BALCON R, HOy J, MALLOY W, SOWTON E: Haemodynamic comparisons of atrial pacing and exercise in patients with angina pectoris. Brit Heart J 31: 168, 1969 6. O'BRIEN KP, HIGGs LM, CLANCY DL, EPSTEIN SE: Hemodynamic accompaniments of angina: A comparison during angina induced by exercise and by atrial pacing. Circulation 39: 735, 1969 7. LINHART JW: Myocardial function in coronary artery disease determined by atrial pacing. Circulation 44: 203, 1971 8. LEIGHTON RF, ZARON SJ, ROBINSON JL, WEISSLER AM: Effects of atrial pacing on left ventricular performance in patients with heart disease. Circulation 40: 615, 1969 9. PARKER JO, CHIONG MA, WEST RO, CASE RB: Sequential alterations in myocardial lactate metabolism, S-T segments, and left ventricular function during angina induced by atrial pacing. Circulation 40: 113, 1969 10. COLLINS M, OBEID A, RYAN GF, SMULYAN H, EICH RH: Hemodynamic effects of increasing the heart rate in patients with arteriosclerotic heart disease. Amer Heart J 77: 466, 1969 696 1 1. LAU SH, COHEN SI, STEIN E, HAFT JI, KINNEY MJ, YOUNTG MW, HELFANT RH, DAMATO AN: Controlled heart rate by atrial pacing in angina pectoris: A determinant of electrocardiographic S-T depression. Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 Circulation 38: 711, 1968 12. SOWTON GE, BALCON R, CRoss D, FRicK MH: Measurement of the angina threshold using atrial pacing: A new technique for the study of angina pectoris. Cardiovasc Res 1: 301, 1967 13. FORRESTER JS, HELFANT RH, PASTERNAC A, AMSTERDAm EA, MOST AS, KEMP HG, GORLIN R: Atrial pacing in coronary heart disease: Effect on hemodynamics, metabolism, and coronary circulation. Amer J Cardiol 27: 237, 1971 14. HORVAT M, YOSHIDA S, PRAKASH R, MARCUS HS, SWAN HJC, GANZ W: Effect of oxygen breathing on pacing-induced angina pectoris and other manifestations of coronary insufficiency. Circulation 45: 837, 1972 15. KNOEBEL SB, ELLIOTT WC, McHENRY PL, Ross E: Myocardial blood flow in coronary artery disease. Amer J Cardiol 27: 51, 1971 16. YOSHIDA S, GANZ W, DoNoso R, MARCUS HS, SWAN HJC: Coronary hemodynamics during successive elevation of heart rate by pacing in subjects with angina pectoris. Circulation 44: 1062, 1971 17. FRICK MH, BALCON R, CROSs D, SOWTON E: Hemodynamic effects of nitroglycerin in patients with angina pectoris studied by an atrial pacing method. Circu]ation 37: 160, 1968 18. CHIONG MA, WEST RO, PARKER JO: Influence of nitroglycerin on myocardial metabolism and hemodynamics during angina induced by atrial pacing. Circulation 45: 1044, 1972 19. GOLDSTEIN RE, EPSTEIN SE: Medical management of patients with angina pectoris. Progr Cardiovasc Dis 14: 360, 1972 20. ROWE GG, THOMSEN JH, STENLUND RR, MCKENNA DH, SIALER S, CORLISS RJ: A study of hemodynamics and coronary blood flow in man with coronary artery disease. Circulation 39: 139, 1969 21. COWAN C, DURAN PVM, CORSINI G, GOLDSCHLAGER N, BING RJ: The effects of nitroglycerin on myocardial blood flow in man: Measured by coincidence counting and bolus injection of 84rubidium. Amer J Cardiol 24: 154, 1969 22. BOETTCHER D, CORSINI G, DANIELS CG, COWAN D, BING RJ: The determination of myocardial blood flow in the anesthetized dog following a slug injection of 84rubidium. J Nucl Med 10: 83, 1969 23. KLOCKE FJ, ROSING DR, PITTMAN DE: Inert gas measurement of coronary blood flow. Amer J Cardiol 23: 548, 1969 24. BING RJ, BEMMISH A, BLUEMCHEN G, COHEN A, GALLAGHER JP, ZALESKI EJ: The determination of coronary flow equivalent with coincidence counting technic. Circulation 29: 833, 1964 25. MCHENRY PL, KNOEBEL SB: Measurement of coronary flow by coincidence counting and a bolus of 84RbCl, J Appl Physiol 22: 495, 1967 KNOEBEL ET AL. 26. KNOEBEL SB, MCHENRY PL, STEIN L, SONEL A: Myocardial blood flow in man as measured by a coincidence counting system and a single bolus of 84RbCl. Circulation 36: 187, 1967 27. KNOEBEL SB, MCHENRY PL: Myocardial blood flow: Measurement by a coincidence counting system and single bolus of 84Rb. Arch Intern Med (Chicago) 127: 768, 1971 28. ROBIN E, COWAN C, PURI P, GANGULY S, DEBOYRIE E, MARTINEZ M, STOCK T, BING RJ: A comparative study of nitroglycerin and propranolol. Circulation 36. 175, 1967 29. KNOEBEL SB, MCHENRY PL, ROBERTS D, STEIN I: Myocardial blood flow in man measured by a coincidence counting system and a single bolus of 84rubidium: Effect of nitroglycerin. Circulation 37: 932, 1968 30. BERNSTEIN L, FRIESINGER GC, LICHrLEN PR, ROSS RS: The effect of nitroglycerin on the systemic and coronary circulation in man and dogs: Myocardial blood flow measured with xenon133. Circulation 33: 107, 1966 31. MCGREGOR M, FAMI WM: Regulation of coronary blood flow. Bull NY Acad Med 42: 940, 1966 32. DAMATO L, BARTOLOMEI G, GIORDANI R: Evaluation of myocardial blood perfusion in man with radioactive potassium or rubidium and precordial counting. Circulation 29: 195, 1964 33. WINBURY MM, HowE BB, HEFNER MA: Effect of nitrates and other coronary dilators on large and small coronary vessels: An hypothesis for the mechanism of action of nitrates. J Pharmacol Exp Ther 168: 70, 1969 34. BECKER LC, FORTUIN NJ, PITT B: Effect of ischemia and antianginal drugs on the distribution of radioactive microspheres in the canine left ventricle. Circ Res 28: 263, 1971 35. BECKER LC, PirT B: Regional myocardial blood flow, ischemia, and antianginal drugs. Ann Clin Res 3: 353, 1971 36. WINBURY MM, WEISS HR, HOWE BB: Effects of Badrenoreceptor blockade and nitroglycerin on myocardial oxygenation. Europ J Pharmacol 16: 271, 1971 37. FAM WM, NAKJHAVAN FK, SEKELY P, MCGREGOR M: The effects of oxygen breathing, nitroglycerin, and dipyridamole on oxygen tension in healthy and ischemic areas of the myocardium. In Proceedings of the International Symposium on Cardiovascular Respiration Effects and Hypoxia (Kingston, Ontario). Basel/New York, S. Karger, 1966, p 375 38. SCHAPER W: The Collateral Circulation of the Heart. Amsterdam and London, North-Holland Publishing Co., 1971, p 175 39. WINBURY MM, HOWE BB, WEISS HR: Effect of nitroglycerin and dipyridamole on epicardial and endocardial oxygen tension: Further evidence for redistribution of myocardial blood flow. J Pharmacol Exp Ther 176: 184, 1971 Circulation, Volume XLVII, April 1973 Myocardial Blood Flow in Coronary Artery Disease: Effect of Right Atrial Pacing and Nitroglycerin SUZANNE B. KNOEBEL, PAUL L. MCHENRY, ANTHONY J. BONNER and JOHN F. PHILLIPS Circulation. 1973;47:690-696 doi: 10.1161/01.CIR.47.4.690 Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1973 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/47/4/690 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/