Exhibit no. ID ^
`
`of the letter / report / expert
`opinion/ plaint/defense
`
`Intraoperative Coronary Angiography
`Using Fluorescein
`T. Takayama, MD, Y. Wanibuchi, MD, H. Suma, MD, Y. Terada, MD, T. Saito, MD,
`S. Fukuda, MD, S. Furuta, MD, and T. Minemura, MD
`Department of Cardiovascular Surgery and Division of Medical Photo Service, Mitsui Memorial Hospital, Tokyo, Japan
`
`dated
`HOFFMANN • EITLE
`Patent- und Rechtsanwalte
`81925 Munchen, Arabellastr. 4
`
`Intraoperative coronary angiography using fluorescein
`was applied to evaluate the patency of saphenous vein
`grafts just after completion of the distal anastomosis. By
`this technique, the area of the revascularized myocar­
`dium was well estimated in real time. This intraoperative
`direct-vision examination gives us more timely and pre­
`cise information during coronary artery bypass grafting.
`(Ann Thorac Surg 1991^1:140-5)
`
`Intraoperative measurement of the amount of graft flow
`
`by magnetic flow meter is the only way to determine
`the area of revascularized myocardium and graft patency.
`To obtain more precise and direct information during
`coronary revascularization, a reliable intraoperative visual
`examination method is desirable. Intraoperative coronary
`angiography using fluorescein was applied for this pur­
`pose in 29 consecutive cases of coronary artery bypass
`grafting.
`
`anastomosis, coronary artery, its branch, myocardial wall,
`and coronary vein. The revascularized area through the
`graft showed bright fluorescence in clear contrast with the
`nonperfused adjacent area. The distribution of the graft
`flow and the anastomotic state could be easily recognized
`by the naked eye. Prolongation of the aortic cross-clamp
`time by this examination was only 1 to 2 minutes.
`In Figure 2, a saphenous vein graft was anastomosed to
`the left anterior descending artery (LAD). A large per­
`fused area including the first and the second diagonal 1
`branches of the LAD was clearly observed.
`Figure 3 shows the seqential bypass graft to the poste­
`rior descending branch of the right coronary artery and
`the posterolateral branch of the circumflex artery. The
`fluorescein perfused the inferior and lateral cardiac walls
`through two anastomoses, and it showed bright fluores­
`cence with a clear border. The first diagonal branch of the
`LAD was also detected by collateral flow from the poste-
`
`Methods
`As a contrast medium, 3 mL of 10% fluorescein sodium
`was diluted with 500 mL of normal saline solution (0.06%
`fluorescein solution) and 5 mL of 0.7% sodium bicarbon­
`ate; 3 mL of heparin was added to adjust the pH and to
`keep the anticoagulability. A 6-W black fluorescent light
`bulb was used as the fluorescence-evoking source.
`After the distal anastomoses using saphenous vein graft
`were performed, all lights in the operating room were
`turned off, and the fluorescent black light bulb was hung
`10 cm over the heart to illuminate the cardiac wall. Then
`20 to 40 mL of fluorescent contrast media was injected
`from the proximal end of the saphenous vein graft using
`a pressure of 150 mm Hg (Fig 1).
`
`Results
`In all cases, bright green-yellow fluorescence was clearly
`observed in real time in the following order: bypass graft,
`
`Accepted for publication Aug 23, 1990.
`Address reprint requests to Dr Takayama, Department of Cardiovascular
`Surgery, Mitsui Memorial Hospital, Kanda-Izumicho 1, Chiyoda-ku, To­
`kyo 101, Japan.
`
`Fig 1. Schema of the examination method. The contrast medium was
`injected from the proximal end of the bypass graft.
`
`© 1991 by The Society of Thoracic Surgeons
`
`0003-4975/91/S3.50
`
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`Ann Thorac Sure
`1991;51:140-3
`
`TAKAYAMA ET AL
`HOW TO DO IT
`CORONARY ANGIOGRAPHY USING FLUORESCEIN
`
`141
`
`rolateral branch. In Figure 4, the saphenous vein was
`anastomosed to the LAD just distal to the second diagonal
`branch. At fluorescein angiography, the diagonal
`branches were well visualized first by the retrograde flow
`from the anastomosis (Fig 4A), and the antegrade stream
`to the LAD was observed with delay (Fig 4B). Through
`these findings, the pronounced stenosis at the anastomo­
`sis was strongly suspected. Because the extent of the
`fluorescence at the LAD area finally seemed to be enough
`
`(Fig 4B), no additional procedure was performed. The
`flow volume of this bypass graft measured by the mag­
`netic flow meter was 65 mL/min, and the postoperative
`course was quite uneventful without showing any ST
`change on the electrocardiogram. Through findings in
`postoperative coronary angiography as well as in intraop­
`erative examination, the preferential flow to the diagonal
`branches and the more than 50% stenosis of the anasto­
`mosis were confirmed (Fig 5A, B),
`
`1
`Fig 3. (A) Sequential bypass grafting to the posterior descending artery from right coronary artery f4-PDj and the posterolateral branch of the
`circumflex artery (PL). Fluorescein perfused through both anastomoses and also through the area of the first diagonal branch CDjJ of the left ante­
`rior descending artery. (B) The schema. CSV = saphenous vein graft.)
`
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`142 HOW TO DO IT TAKAYAMA ET AL
`CORONARY ANGIOGRAPHY USING FLUORESCEIN
`
`Ann Thorac Surg
`1991^51:140—3
`
`Fig 4. Saphenous vein graft (SV) was anastomosed to
`the left anterior descending artery CLAD). (A) Initial
`phase: only the area of the diagonal branches showed
`the fluorescence. (B) Late phase: the area of LAD also
`showed enough fluorescence. (C) Schema of (A). ID-,
`= second diagonal branch.)
`
`Comment
`
`There is no other conventional method except magnetic
`flow meter to evaluate the surgical results intraoperatively
`in coronary artery bypass grafting. If the graft flow
`volume measured by magnetic flow meter is unexpectedly
`low, the question arises whether it is due to anastomotic
`stenosis or to poor peripheral run-off. Surgeons cannot
`get any information until postoperative coronary angiog­
`raphy is performed.
`The results of intraoperative thermography [1] for this
`purpose are sometimes misunderstood owing to many
`kinds of artifacts such as cold saline solution used for
`topical cooling, cardioplegic solution, and the surgeon's
`finger. Furthermore, the necessity of special equipment
`makes this method unpopular.
`Intraoperative coronary angiography using fluorescein
`was performed for indirect myocardial revascularization
`by Armellini and colleagues [2], but it was not applied to
`visualize directly the coronary arteries. Through our
`method, exact quantitative evaluation of the stenosis
`
`such as given by coronary angiography was difficult but
`enough clinical information as to whether the stenosis of
`the anastomosis is critical or whether the distribution of
`the graft flow is normal could be obtained by observing
`the passage and smoothness of the fluorescent stream
`through the anastomosis.
`The safety of the fluorescein has been fully studied in
`the field of the ophthalmography [3], Sodium bicarbonate
`was added to the contrast media to adjust the pH between
`7.0 and 9.0, at which fluorescein showed best contrast.
`The 6-W fluorescent black light evoked enough fluores­
`cence from the contrast medium. Application of this
`method is now limited to the vein graft because of the
`difficulty of finding feasible access for the fluorescein
`injection into arterial grafts.
`In conclusion, this technique was quite easy and repro­
`ducible within a minimum time without any special
`equipment. We believe intraoperative coronary angiogra­
`phy using fluorescein is a useful and practical examina­
`tion for performing more precise coronary artery bypass
`grafting.
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`Ann Thorac Surg
`1991;51:140-3
`
`HOW TO DO rr TAKAYAMAETAl 143
`CORONARY ANGIOGRAPHY USING RUORE5CEIN
`
`C
`
`Fig 5. Postoperative coronary angiography of the pa­
`tient shown in Figure 4. (A) Initial phase: the diago­
`nal branches were visualized before the left anterior
`descending artery CLAD) distal to the anastomosis.
`(B) Late phase: LAD now well seen. (C) Schema of
`(A). CD2 = second diagonal; SV = saphenous vein
`graft.)
`
`References
`1. Pantaieo D, Rocco P, Marchese AR, Iorio D, Lino D, Spamp-
`inato N. Thermographic evaluation of myocardial cooling and
`intraoperative control of graft patency in patients with coro­
`nary artery disease. ] Cardiovasc Surg 1984;25:554-9.
`
`2. Armellini C, Merscheimer WL, Burman SO. The use of
`fluorescein for determining the site for internal mammary
`artery implantation. ] Thorac Cardiovasc Surg 1968;56:643-6.
`3. Maurice DM. The use of fluorescein in opthalmological re­
`search. Invest Ophthalmol 1967;6:464-77.
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