- Email: [email protected]
Hemodynamic response to acute mitral regurgitation in dogs with acute and chronic coronary artery disease
Hemodynamic response to acute mitral regurgitation in dogs with acute and chronic coronary artery disease Ryozo Omoto, M.D.,* Mortimer J. Buckley, M.D.,** and W. Gerald Austen, M.D.,*** Boston, Mass.
W i t h the availability of corrective openheart procedures, the evaluation of acute severe mitral regurgitation has become a common problem. Acute mitral regurgitation may occur secondary to dysfunction or rupture of a papillary muscle in association with a myocardial infarction or with ruptured chordae tendineae. Furthermore, severe regurgitation may be secondary either to trauma to the mitral valve or to leaflet destruction by bacterial endocarditis. Papillary muscle dysfunction or rupture is usually associated with coronary artery disease, whereas the other causes of acute mitral regurgitation generally are unrelated to this disease. Although many papers have been published on the hemodynamic effects of experimental acute mitral regurgitation in dogs From the Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass. 02114. Supported in part by U.S. Public Health Service Grant No. HE-06664 (HEPP) and PH43-67-1443. Received for publication March 30, 1972. ♦Clinical Fellow in Surgery, Massachusetts General Hospital. *'Assistant Professor of Surgery, Harvard Medical School; Assistant Surgeon, Massachusetts General Hospital. ***Professor of Surgery, Harvard Medical School; Chief, General Surgical Services, Massachusetts General Hospital.
254
with normal hearts, 13 no evaluation of this lesion has been carried out in animals with coronary insufficiency, either acute or chronic. The present experiments were conceived for two reasons: (1) to study the hemodynamic responses of experimentally induced, severe acute mitral regurgitation in dogs with either acute or chronic coronary insufficiency and (2) to determine if the changes were related to the extent of myocardial injury. Materials and methods Forty-one adult mongrel dogs weighing 16 to 24 kilograms were anesthetized with sodium pentobarbital (20 mg. per kilogram). A cuffed endotracheal tube was inserted, and ventilation was maintained by a positivepressure respirator with 100 per cent oxygen. A median sternotomy incision was made, and heparin (3 mg. per kilogram) was administered intravenously. Fig. 1 shows a schematic diagram of the preparation. A cuffed, silicone-coated Bardic Foley catheter (size 18 Fr.) was employed to cannulate the coronary sinus. This was inserted via the azygos vein and right atrium. The cuff was placed between the middle cardiac vein and the inferior cardiac vein and was expanded with an adequate amount of air for occlu-
Volume 64 Number 2 August, 1972
Mitral regurgitation in coronary artery disease
Subclovian V Sample Line
\
W
Electromagnetic Flow Meter
—
255
Lvp
Aortic P Azygos V
Pacemaker
Extra Corporeal Flow Meter
Metal Tip
Fig. 1. Artist"s depiction of the preparation described in the text. Special note is made of the coronary sinus catheter and the left ventricular-left atrial shunt. LVP, Left ventricular pressure. LAP, Left atrial pressure. PAP, Pulmonary arterial pressure.
sion of the coronary sinus. This technique of inserting the cannula into the coronary sinus results in a linear correlation between coronary sinus blood flow and the left coronary arterial blood flow. A second catheter was inserted into the right atrium via the subclavian vein and was connected to the coronary sinus cannula through an extracorporeal type 4 mm. electromagnetic flowmeter, making a closed circuit of the coronary line. This unit continuously monitored the flow rate of coronary sinus drainage. Mitral regurgitation was simulated by a left ventricular-left atrial shunt. This shunt usually was accomplished from the apex of the left ventricle to the appendage of the left atrium. Rarely, when the insertion of the cannula into the left atrium was found difficult because of adhesions in animals with chronic disease, cannulation of the left lower pulmonary vein was performed. The internal diameter of the shunt cannulas was 8 mm., thereby permitting maximum flow with minimal surgical damage to the myocardium. An extracorporeal electromagnetic flowmeter was inserted between the ventricular and atrial cannulas to measure the rate of shunt flow. The shunt was closed during control measurements and was
opened to produce acute mitral regurgitation. The rate of regurgitant flow was controlled by variable occlusion of the shunt. Aortic flow was measured by an electromagnetic flowmeter placed around the proximal ascending aorta. Pulsatile and electrically integrated mean flow (time constant 4 sec.) as well as the acceleration of aortic flow (dF/dt) was recorded simultaneously. The pulmonary artery was catheterized through the right ventricular outflow tract. Another catheter was inserted retrograde into the left ventricle via the right carotid artery, through which the left ventricular pressure and its first derivative (dp/dt) were recorded. Aortic pressure and the left atrial pressure were monitored via the right femoral artery and a peripheral branch of the right pulmonary vein, respectively. Pressures were recorded by means of Statham transducers and a direct-writing oscillograph. The right femoral vein and the left femoral artery were cannulated for intravenous infusion and for arterial blood sampling for gas analysis, dp/dt and dF/dt were determined with a resistance-capacitance (R-C) differentiating circuit (DL410, Biotronex Laboratory, Inc., Silver Spring, Md.). pH, Pco 2 , and oxygen satura-
256
The Journal of
Omoto, Buckley,
Austen
Thoracic and Cardiovascular Surgery
tion were determined in the blood samples from the arterial and coronary sinus catheters, before and after the production of acute mitral regurgitation. Multiple samples were taken in each stage. A stable hematocrit and blood volume were maintained with transfusion. Acidosis, which occurred occasionally in some experiments, was neutralized by the addition of sodium bicarbonate. Systolic ejection period and enddiastolic pressures of the left ventricle were measured from tracings at a paper speed of 100 mm. per second for an average of five cardiac cycles. After completion of the preparation, a period of time was allowed for stabilization. Control measurements of mean and pulsatile aortic flow, maximum dF/dt, aortic, left atrial, left ventricular, left ventricular enddiastolic (LVEDP), and main pulmonary arterial pressures were made. Maximum rate of change of (dp/dt) was determined, and coronary sinus flow was measured. Three pairs of blood samples were taken for blood gas measurement and determination of myocardial oxygen consumption. Mitral regurgitation was then produced by opening the ventricular-atrial shunt. The shunt flow was regulated to approximately the same volume as the previously recorded mean aortic flow (control cardiac output). All measurements were repeated after stabilization had occurred (2 to 8 minutes). All experiments in which a stable condition was not achieved were excluded from study. Arrhythmias frequently occurred but usually cleared. In a small number of experiments, ventricular irritability led to ventricular fibrillation; these preparations also were excluded. Heart rate was controlled in all animals by means of right atrial pacing. Grouping Thre groups of animals with acute disease and two groups with chronic disease were studied. Group I. Ten dogs with normal myocardium except for the surgical preparation were used as the control group for the acute studies. Acute mitral regurgitation
was produced, and the response was recorded. Group II. In 9 dogs, acute myocardial ischemia of moderate degree was produced by ligation of small branches of the anterior descending and circumflex branches of the left coronary artery on the anterolateral surface of the left ventricle. The ischemic area was 15 to 20 sq. cm. Acute myocardial infarction or ischemia was confirmed by means of electrocardiographic, microscopic, and angiographic findings. Acute mitral regurgitation was produced, and the response was recorded. Group III. Seven dogs were subjected to severe acute myocardial damage. Severe myocardial damage to the lateral and posterior portions of the left ventricle was produced by ligation of small branches of the anterior descending and circumflex arteries first and then of the distal posterior descending coronary artery branches, producing an area of injury of 25 sq. cm. or more. Once a stable preparation was obtained, acute mitral regurgitation was produced, and the response was recorded. Group IV. Two dogs underwent the preliminary operations that will be described in Group V, but no Ameroid contrictors were placed on the coronary arteries. These animals were studied 6 weeks after the sham operations and served as controls for the animals with chronic ischemia. The effects of acute mitral regurgitation were evaluated in these dogs by the techniques described above. Group V. Thirteen dogs underwent operations under sterile conditions to produce chronic coronary insufficiency. The animals were anesthetized with intravenous sodium pentobarbital, and respirations were controlled with a Harvard-type respirator through a cuffed endotracheal tube. The dogs were ventilated with 100 per cent oxygen. A left thoracotomy was performed. An Ameroid constrictor, 2.77 mm. in internal diameter, was placed at the origin of the anterior descending coronary artery, and small branches of the circumflex artery were ligated for possible anastomosis. Ap-
Volume 64 Number 2 August, 1972
Mitral regurgitation in coronary artery disease
257
Table I. Average results of hemodynamic responses in Groups I to V (expressed in per cent change during acute mitral regurgitation as compared to the base-line, nonregurgitant period) Hemodynamics
Group I
Aortic systolic pressure dp/dt Peak aortic flow dF/dt Coronary sinus flow Coronary vascular resistance Myocardial oxygen consumption Systolic ejection period Forward mean systolic ejection rate Forward LV stroke work Aortic flow Mean aortic pressure* (mm. Hg) LVEDP* Heart rate Forward stroke volume Regurgitant backward stroke volumet Total stroke volume
14.1 26.7 21.1 24.8 14.9 - 14.6 + 18.4 - 10.9 + 4.0 - 11.3 - 7.7 - 2.0 + 0.95 0 - 7.7 + 109.8 + 102.1 + + + + +
Group + 8.7 + 22.7 + 18.3 + 9.3 + 9.2 - 15.2 + 6.1 - 5.5 - 9.5 - 21.7 - 13.4 - 3.4 + 1.9 0 - 13.6 + 23.6 + 110
II
Group - 9.4 -12.3 - 7.4 - 3.0 + 3.6 -14.6 - 8.3 - 3.4 -10.2 -25.8 -13.0 - 8.6 + 1.2 0 -13.0 +95.8 +82.8
III
Group + + + +
IV
12.1 21.4 15.5 30.0 0 0 3.1 - 14.0 + 20.1 + 2.9 + 3.7 0 + 0.5 0 + 3.7 +118.8 +1 22.5
Group V - 9.2 + 1.0 + 3.3 + 6.6 + 1.7 - 9.9 + 2.7 - 8.5 - 4.5 - 21.0 - 11.9 - 6.3 + 1.0 0 - 11.9 +111.3 + 99.4
Legend: dp/dt, First derivative of left ventricular pressure. dF/dt, Acceleration of aortic flow. LVEDP, left ventricular end-diastolic pressure. ♦Actual change in mm. Hg. fPer cent of forward stroke volume in base-line period.
proximately 6V2 weeks after the initial operations, the surviving dogs were subjected to the same hemodynamic study of acute mitral regurgitation which was described previously. Autopsies were performed on all animals after the study, and coronary insufficiency in this group was estimated by macroscopic, microscopic, and angiographic findings. Results Average results of all groups expressed in percentage change from control levels are summarized in Table I. Group I (10 animals). During the production of acute mitral regurgitation, regurgitant flow averaged 111.4 per cent of the aortic flow in the base-line period (Table I), dp/dt increased from 2,195 to 2,753 mm. Hg per second, and dF/dt increased 25 per cent. Aortic systolic pressure and peak aortic flow increased from 100.9 to 114.8 mm. Hg and from 4,812 to 5,693 ml. per minute, respectively. Coronary sinus flow increased from 52.6 to 60.4 ml. per minute, and myocardial oxygen
consumption rose from 5.54 to 6.43 ml. per minute. Coronary vascular resistance was reduced by 14.4 per cent. A slight reduction in mean forward aortic flow and mean aortic pressure were observed (1,130 to 1,050 ml. per minute and 78.5 to 76.5 mm. Hg, respectively). The elevation of LVEDP was also slight (4.35 to 5.3 mm. Hg). Systolic ejection period decreased from 0.1525 to 0.1353 second, whereas forward mean ejection rate increased from 48.36 to 50.93 ml. per systolic second. Forward left ventricular stroke work was reduced from 7.61 to 6.78 Gm. M., a result which came from the reduction of forward mean aortic flow and a smaller pressure gradient between mean aortic pressure and LVEDP. Group II (9 animals). A mildly depressed cardiac state was caused by the production of acute myocardial ischemia. The following comparisons were made between the postligation state and the state which followed production of acute mitral regurgitation. Shunt regurgitant flow was 123 per cent of the postligation base-line aortic flow, dp/dt and dF/dt increased from 1,850 to 2,050
The Journal of
258
Omoto, Buckley,
Austen
Fig. 2. X-ray film of a postmortem injection of contrast material into the main left coronary artery of a dog from Group III. There is a sharp cut-off in the distal left anterior descending artery and its distal diagonal branches. Absence of perfusion of the apex of the left ventricle should be noted. (Injection pressure 120 mm. Hg.)
mm. Hg per second and from 100 to 108.8 per cent, respectively. Aortic systolic pressure increased from 76.2 to 82.9 mm. Hg, while peak aortic flow increased from 3,780 to 4,470 ml. per minute. Coronary sinus flow and myocardial oxygen consumption also increased, from 55.3 to 60.4 ml. per minute and from 5.00 to 5.31 ml. per minute, respectively. Coronary vascular resistance was reduced by 15.4 per cent. Forward mean aortic flow decreased from 813 to 705 ml. per minute, while mean aortic pressure fell from 63.6 to 60.2 mm. Hg. The elevation of LVEDP was from 4.91 to 6.77 mm. Hg; this was the largest change in all groups. Both systolic ejection period and forward mean ejection rate decreased (0.163 to 0.154 second and 37.3 to 33.8 ml. per minute, respectively). Forward left ventricular stroke work reduced from 4.82 to 3.80 Gm.-M. Fig. 2 illustrates the postmortem angiogram of the left coronary artery in one typical example from this group and demon-
Thoracic and Cardiovascular Surgery
strates experimentally produced acute myocardial ischemia in the anterolateral portion of the left ventricle. Contrast material was injected at a pressure of 120 mm. Hg. Group III (7 animals). A moderately depressed cardiac state was produced by serial ligation. The following comparisons were made between the postligation state and the state which followed production of acute mitral regurgitation. Shunt regurgitant flow was 95.8 per cent of the postligation baseline aortic flow, dp/dt and dF/dt decreased from 2,335 to 2,050 mm. Hg per second and from 100 to 94.3 per cent, respectively. Aortic systolic pressure decreased from 96.4 to 87.8 mm. Hg, whereas peak aortic flow fell from 5,300 to 4,900 ml. per minute. The changes in coronary sinus flow and myocardial oxygen consumption were minimal (60.2 to 62.7 ml. per minute and 7.64 to 7.29 ml. per minute, respectively). Coronary vascular resistance decreased by 14.3 per cent. Forward mean aortic flow and mean aortic pressure both decreased, from 1,032 to 885 ml. per minute and from 74.5 to 65.4 mm. Hg, respectively. LVEDP was observed to increase from 6.02 to 7.14 mm. Hg. The decrease in systolic ejection period was very slight (from 0.1650 to 0.1640 second), whereas the decrease in forward mean ejection rate was pronounced (47.0 to 41.8 ml. per systolic second). A reduction in the forward left ventricular stroke work was observed (7.470 to 5.451 Gm.M.). Group IV (2 animals). Regurgitant flow averaged 118.8 per cent of base-line aortic flow, dp/dt and dF/dt increased remarkably (18.62 to 22.61 mm. Hg per second and 100 to 130 per cent, respectively). Aortic systolic pressure increased from 102.5 to 115 mm. Hg, and peak aortic flow rose from 2,812 to 3,250 ml. per minute. Coronary sinus flow remained unchanged, (42.5 ml. per minute). A slight increase in myocardial oxygen consumption was observed (3.75 to 3.91 ml. per minute). Coronary vascular resistance remained unchanged. Forward mean aortic flow increased from 675 to 700 ml. per minute. Mean aortic pressure
Volume 64
Number 2
Mitral regurgitation in coronary artery disease
August, 1972
remained unchanged (79 mm. Hg). LVEDP increased from 7.5 to 8.0 mm. Hg. Systolic ejection period decreased from 0.150 to 0.129 second, while forward mean ejection rate increased from 27.3 to 32.8 ml. per systolic second. Forward left ventricular stroke work increased slightly (4.207 to 4.333 Gm. M.). Group V (13 animals). Regurgitant flow averaged 111.3 per cent of base-line aortic flow. The changes in dp/dt and dF/dt were slight (1,802 to 1,820 mm. Hg per second and 100 to 106.6 per cent, respectively). Aortic systolic pressure and peak aortic flow decreased from 92.1 to 80.5 mm. Hg and from 4,998 to 4,806 ml. per minute, respectively. The changes in coronary sinus flow and myocardial oxygen consumption were very small (54.19 to 55.06 ml. per minute and 5.33 to 5.46 ml. per minute). Coronary vascular resistance was reduced by 9.9 per cent, whereas the decreases in forward mean aortic flow and mean aortic pressure were marked (732.2 to 645.9 ml. per minute and 79.5 to 61.0 mm. Hg). LVEDP increased from 4.58 to 5.38 mm. Hg. Systolic ejection period decreased from 0.165 to 0.142 second, while forward mean ejection rate fell from 32.4 to 30.9 ml. per minute. Forward left ventricular stroke work decreased from 4.60 to 3.64 ml. per minute. Fig. 3 illustrates the postmortem angiogram of the left coronary artery in a typical example from this group. There is complete occlusion of the anterior descending artery with myocardial infarction in the anterior and lateral portion of the left ventricle. Contrast material was injected at a pressure of 120 mm. Hg. All animals included in this group were positively proved to have coronary insufficiency with myocardial infarction by the criteria described in the section on materials. Discussion There have been numerous hemodynamic studies of experimentally induced mitral regurgitation. MacCallum and McClure 1 produced acute mitral incompetence in dogs by means of rather qualitative approaches.
259
Fig. 3. X-ray film of a postmortem injection of contrast material into the main left coronary artery of a dog from Group V. No filling of the left anterior descending is noted beyond the Ameroid constrictor. The apex and septum of the left ventricle has no perfusion. This area was fibrotic on microscopic evaluation.
Braunwald and associates2 studied the hemodynamic effects of mitral regurgitation in anesthetized open-chest dogs. They found that mitral regurgitant flows from zero to three times the resting cardiac output were tolerated with only slight alterations of cardiac performance. It was observed also that the effect of any given regurgitant volume on left atrial pressure was a function of the filling pressure prior to the induction of regurgitation, suggesting an important relationship between myocardial contractility and the hemodynamic response. Ross and colleagues,3 using similar techniques, described quantitatively the phasic pressureflow relationship between the left ventricle and the left atrium. Wegria's group" demonstrated that acutely induced mitral regurgitation increased coronary flow and oxygen consumption of the myocardium. Others have studied the effect of acute mitral regurgitation upon aortic flow and cardiac
260
Omoto, Buckley,
The Journal of Thoracic and Cardiovascular Surgery
Austen
Table II. Hemodynamic responses following acute mitral regurgitation Hemodynamics
Pattern I
Pattern 11
dp/dt
Elevation
Depression
Aortic systolic pressure
Elevation
Depression
Peak aortic flow
Elevation
Depression
Coronary flow
Elevation
No change
Myocardial oxygen consumption
Elevation
No change
Coronary vascular resistance
Depression
Depression
Systolic ejection period
Depression
Depression
Forward mean ejection rate
Elevation
Depression
Legend: dp/dt, First derivative of left ventricular pressure.
impedance.5 All of these studies have been carried out in normal hearts. Since Davidson6 described a case report of spontaneous rupture of a papillary muscle with associated mitral regurgitation and Sanders7 further evaluated the acute hemodynamic responses seen in 61 cases of ruptured papillary muscle, the clinical distinction between acute severe mitral regurgitation associated with ruptured papillary muscle or papillary muscle dysfunction from that seen with chronic mitral regurgitation associated with rheumtic heart disease8-10 has been stressed. Furthermore, the responses to acute severe mitral regurgitation, seen secondary to idiopathic ruptured chordae tendineae or acute bacterial endocarditis, are often different from those seen with papillary muscle disease secondary to coronary artery occlusion. An increasing number of cases of severe acute mitral regurgitation secondary to ruptured papillary muscle, as well as other types of acute mitral regurgitation, have occurred with or without coronary disease. This experience has directed our interest toward seeking further delineation of the hemodynamic response to acute mitral regurgitation in the ischemic
Table III. Response to acute regurgitation Group Group Group Group Group
I II III IV V
mitral Pattern Pattern Pattern Pattern Pattern
I I II I II
heart as opposed to the hemodynamic response previously described in the normal heart. From the present study, it is evident that acute mitral regurgitation may produce two different hemodynamic responses in normal and ischemic hearts (Table II). The first response, Pattern I, usually found in the normal heart, was characterized by an elevation of the dp/dt, dF/dt, aortic systolic pressure, and peak aortic flow. The second response, Pattern II, was found predominantly in cases of severe myocardial damage and was characterized by an unchanged or depressed dp/dt, dF/dt, aortic systolic pressure, and peak aortic flow. Changes in coronary sinus flow and myocardial oxygen consumption seemed to follow these hemodynamic response patterns in most cases. It should be stressed that Pattern I and Pattern II are only convenient classifications for recognizing the responses to acute mitral regurgitation in varied conditions of the hearts. The responses usually seen in the groups studied are shown in Table III. In the preparation described, the ability of the heart to compensate for the increased work required by mitral regurgitation is dependent upon the residual normal myocardium. When the myocardial injury exceeded an estimated 20 per cent of the left ventricle, a very depressed response to acute mitral regurgitation was evident. This degree of injury is less than that seen in patients dying from cardiogenic shock secondary to acute myocardial infarction without mitral regurgitation,11 but it is similar to that injury seen with acute ventricular septal defect subsequent to myocardial infarction.12
Volume 64
Number 2
Mitral regurgitation in coronary artery disease
261
August, 1972
These findings would suggest that, in cases of acute mitral regurgitation associated with coronary artery disease and severe depression of ventricular function, an evaluation of myocardial performance should be carried out prior to surgery. The latter should include left ventricular angiography and coronary angiography to determine if other surgical procedures such as coronary revascularization or myocardial resection should be carried out at the time of mitral valve replacement. At the present time, the left ventriculogram seems to be most relevant in determining the extent of myocardial injury. Summary Acute mitral regurgitation was simulated in dogs by creating a controlled shunt between the left ventricle and left atrium. The hemodynamic response to acute regurgitation was studied in dogs with normal hearts and in dogs with hearts having acute and chronic ischemia. The usual hyperdynamic response to acute mitral regurgitation seen in normal hearts was depressed by myocardial ischemia, especially when the latter was extensive. REFERENCES 1 MacCallum, W. G., and McClure, R. D.: On the Mechanical Effects of Experimental Mitral Stenosis and Insufficiency, Johns Hopkins Med. J. 17: 260, 1906. 2 Braunwald, E., Welch, G. H., Jr., and Sarnoff, S. J.: Hemodynamic Effects of Quantitatively Varied Experimental Mitral Regurgitation, Circ. Res. 5: 539, 1957. 3 Ross, J., Jr., Cooper, T., and Lombardo, C. R.: Hemodynamic Observations in Experimental Mitral Regurgitation, Surgery, 47: 795, 1960. 4 Wegria, R., Muelheims, G., Jreissaty, R., and Nakano, J.: Effect of Acute Mitral Insufficiency of Various Degrees on Mean Arterial Blood Pressure, Coronary Blood Flow, Cardiac Output and Oxygen Consumption, Circ. Res. 6: 301, 1958. 5 Elkins, R. C , Morrow, A. G., Vasko, J. S., and Braunwald, E.: The Effects of Mitral Regurgitation on the Pattern of Instantaneous Aortic Blood Flow, Circulation 36: 45, 1967.
6 Davidson, S.: Spontaneous Rupture of a Papillary Muscle of the Heart; A Report of Three Cases and a Review of the Literature, Mt. Sinai J. Med. N. Y. 14: 94, 1948. 7 Sanders, R. J., Neubuerger, K. T., and Ravin, A.: Rupture of Papillary Muscles: Occurrence of Rupture of the Posterior Muscle in Posterior Myocardial Infarction, Dis. Chest 31: 316, 1957. 8 Sanders, C. A., Scannell, J. G., Hawthorne, J. W., and Austen, W. G.: Severe Mitral Regurgitation Secondary to Ruptured Chordae Tendineae, Circulation 31: 506, 1965. 9 Austen, W. G., Sanders, C. A., Averill, J. H., and Friedlich, A. L.: Ruptured Papillary Muscle: Report of Case With Successful Mitral Valve Replacement, Circulation 32: 597, 1965. 10 Austen, W. G., Sokol, D., DeSanctis, R. W., and Sanders, C. A.: The Surgical Treatment of Papillary Muscle Rupture Complicating Myocardial Infarction, N. Engl. J. Med. 278: 1137, 1968. 11 Page, D. L., Caulfield, J. B., Kastor, J. A., DeSanctis, R. W., and Sanders, C. A.: Myocardial Changes in Cardiogenic Shock, N. Engl. J. Med. 285: 133, 1971. 12 Buckley, M. J., Mundth, E. D., Daggett, W. M., DeSanctis, R. W., Sanders, C. A., and Austen, W. G.: Surgical Therapy for Early Complications of Myocardial Infarction, Surgery 70: 814, 1971. 13 Daggett, W. M., Burwell, L. R., Lawson, D. W., and Austen, W. G.: Resection of Acute Ventricular Aneurysm and Ruptured Interventricular Septum After Myocardial Infarction, N. Engl. J. Med. 283: 1507, 1970. 14 Mundth, E. D., Buckley, M. J., Leinbach, R. C , DeSanctis, R. W., Sanders, C. A., Kantrowitz, A. R., and Austen, W. G.: Myocardial Revascularization for the Treatment of Cardiogenic Shock Complicating Acute Myocardial Infarction, Surgery 70: 78, 1971. Appendix The oxygen consumption of the myocardium (MOC) drained by the coronary sinus was calculated according to the following formula: MOC (c.c./min.) = Wet CP 19.8 x j i - j x ■— x (difference of O2 saturation)
where 19.8 is the oxygen capacity of 100 per cent saturated normal blood per 100 c.c; 45.5 is the normal hematocrit index (Hct) (per cent); and CF is the flow rate of blood drained by the coronary sinus (ml./min.). j T irc„, (mAP - LVEDP) x SV x 13.6 x 1.055 Forward LVSW = ~r^r
where LVSW is the left ventricular stroke work
The Journal of
2 6 2 Omoto, Buckley, Austen
( G m . - M . ) ; m A P is the mean aortic pressure (mm. H g ) ; L V E D P is the left ventricular end-diastolic pressure (mm. H g ) ; SV is the forward stroke volume of the left ventricle (ml.) and equals mean aortic flow (ml./min.) . heart rate (beats/min.) ' 13.6 is the specific gravity of mercury; and 1.055 is the specific gravity of normal blood. C V R L V K
=
mAP CF
Thoracic and Cardiovascular Surgery
where CVR is the coronary vascular resistance (expressed in per cent of control). mean aortic flow (ml./min.) systolic seconds per min. where SER is the forward mean ejection rate (ml./systolic second) and systolic seconds per minute means the systolic ejection period (sec.) (the time from the onset of forward flow to that of zero flow). SER
_
W i t h the availability of corrective openheart procedures, the evaluation of acute severe mitral regurgitation has become a common problem. Acute mitral regurgitation may occur secondary to dysfunction or rupture of a papillary muscle in association with a myocardial infarction or with ruptured chordae tendineae. Furthermore, severe regurgitation may be secondary either to trauma to the mitral valve or to leaflet destruction by bacterial endocarditis. Papillary muscle dysfunction or rupture is usually associated with coronary artery disease, whereas the other causes of acute mitral regurgitation generally are unrelated to this disease. Although many papers have been published on the hemodynamic effects of experimental acute mitral regurgitation in dogs From the Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass. 02114. Supported in part by U.S. Public Health Service Grant No. HE-06664 (HEPP) and PH43-67-1443. Received for publication March 30, 1972. ♦Clinical Fellow in Surgery, Massachusetts General Hospital. *'Assistant Professor of Surgery, Harvard Medical School; Assistant Surgeon, Massachusetts General Hospital. ***Professor of Surgery, Harvard Medical School; Chief, General Surgical Services, Massachusetts General Hospital.
254
with normal hearts, 13 no evaluation of this lesion has been carried out in animals with coronary insufficiency, either acute or chronic. The present experiments were conceived for two reasons: (1) to study the hemodynamic responses of experimentally induced, severe acute mitral regurgitation in dogs with either acute or chronic coronary insufficiency and (2) to determine if the changes were related to the extent of myocardial injury. Materials and methods Forty-one adult mongrel dogs weighing 16 to 24 kilograms were anesthetized with sodium pentobarbital (20 mg. per kilogram). A cuffed endotracheal tube was inserted, and ventilation was maintained by a positivepressure respirator with 100 per cent oxygen. A median sternotomy incision was made, and heparin (3 mg. per kilogram) was administered intravenously. Fig. 1 shows a schematic diagram of the preparation. A cuffed, silicone-coated Bardic Foley catheter (size 18 Fr.) was employed to cannulate the coronary sinus. This was inserted via the azygos vein and right atrium. The cuff was placed between the middle cardiac vein and the inferior cardiac vein and was expanded with an adequate amount of air for occlu-
Volume 64 Number 2 August, 1972
Mitral regurgitation in coronary artery disease
Subclovian V Sample Line
\
W
Electromagnetic Flow Meter
—
255
Lvp
Aortic P Azygos V
Pacemaker
Extra Corporeal Flow Meter
Metal Tip
Fig. 1. Artist"s depiction of the preparation described in the text. Special note is made of the coronary sinus catheter and the left ventricular-left atrial shunt. LVP, Left ventricular pressure. LAP, Left atrial pressure. PAP, Pulmonary arterial pressure.
sion of the coronary sinus. This technique of inserting the cannula into the coronary sinus results in a linear correlation between coronary sinus blood flow and the left coronary arterial blood flow. A second catheter was inserted into the right atrium via the subclavian vein and was connected to the coronary sinus cannula through an extracorporeal type 4 mm. electromagnetic flowmeter, making a closed circuit of the coronary line. This unit continuously monitored the flow rate of coronary sinus drainage. Mitral regurgitation was simulated by a left ventricular-left atrial shunt. This shunt usually was accomplished from the apex of the left ventricle to the appendage of the left atrium. Rarely, when the insertion of the cannula into the left atrium was found difficult because of adhesions in animals with chronic disease, cannulation of the left lower pulmonary vein was performed. The internal diameter of the shunt cannulas was 8 mm., thereby permitting maximum flow with minimal surgical damage to the myocardium. An extracorporeal electromagnetic flowmeter was inserted between the ventricular and atrial cannulas to measure the rate of shunt flow. The shunt was closed during control measurements and was
opened to produce acute mitral regurgitation. The rate of regurgitant flow was controlled by variable occlusion of the shunt. Aortic flow was measured by an electromagnetic flowmeter placed around the proximal ascending aorta. Pulsatile and electrically integrated mean flow (time constant 4 sec.) as well as the acceleration of aortic flow (dF/dt) was recorded simultaneously. The pulmonary artery was catheterized through the right ventricular outflow tract. Another catheter was inserted retrograde into the left ventricle via the right carotid artery, through which the left ventricular pressure and its first derivative (dp/dt) were recorded. Aortic pressure and the left atrial pressure were monitored via the right femoral artery and a peripheral branch of the right pulmonary vein, respectively. Pressures were recorded by means of Statham transducers and a direct-writing oscillograph. The right femoral vein and the left femoral artery were cannulated for intravenous infusion and for arterial blood sampling for gas analysis, dp/dt and dF/dt were determined with a resistance-capacitance (R-C) differentiating circuit (DL410, Biotronex Laboratory, Inc., Silver Spring, Md.). pH, Pco 2 , and oxygen satura-
256
The Journal of
Omoto, Buckley,
Austen
Thoracic and Cardiovascular Surgery
tion were determined in the blood samples from the arterial and coronary sinus catheters, before and after the production of acute mitral regurgitation. Multiple samples were taken in each stage. A stable hematocrit and blood volume were maintained with transfusion. Acidosis, which occurred occasionally in some experiments, was neutralized by the addition of sodium bicarbonate. Systolic ejection period and enddiastolic pressures of the left ventricle were measured from tracings at a paper speed of 100 mm. per second for an average of five cardiac cycles. After completion of the preparation, a period of time was allowed for stabilization. Control measurements of mean and pulsatile aortic flow, maximum dF/dt, aortic, left atrial, left ventricular, left ventricular enddiastolic (LVEDP), and main pulmonary arterial pressures were made. Maximum rate of change of (dp/dt) was determined, and coronary sinus flow was measured. Three pairs of blood samples were taken for blood gas measurement and determination of myocardial oxygen consumption. Mitral regurgitation was then produced by opening the ventricular-atrial shunt. The shunt flow was regulated to approximately the same volume as the previously recorded mean aortic flow (control cardiac output). All measurements were repeated after stabilization had occurred (2 to 8 minutes). All experiments in which a stable condition was not achieved were excluded from study. Arrhythmias frequently occurred but usually cleared. In a small number of experiments, ventricular irritability led to ventricular fibrillation; these preparations also were excluded. Heart rate was controlled in all animals by means of right atrial pacing. Grouping Thre groups of animals with acute disease and two groups with chronic disease were studied. Group I. Ten dogs with normal myocardium except for the surgical preparation were used as the control group for the acute studies. Acute mitral regurgitation
was produced, and the response was recorded. Group II. In 9 dogs, acute myocardial ischemia of moderate degree was produced by ligation of small branches of the anterior descending and circumflex branches of the left coronary artery on the anterolateral surface of the left ventricle. The ischemic area was 15 to 20 sq. cm. Acute myocardial infarction or ischemia was confirmed by means of electrocardiographic, microscopic, and angiographic findings. Acute mitral regurgitation was produced, and the response was recorded. Group III. Seven dogs were subjected to severe acute myocardial damage. Severe myocardial damage to the lateral and posterior portions of the left ventricle was produced by ligation of small branches of the anterior descending and circumflex arteries first and then of the distal posterior descending coronary artery branches, producing an area of injury of 25 sq. cm. or more. Once a stable preparation was obtained, acute mitral regurgitation was produced, and the response was recorded. Group IV. Two dogs underwent the preliminary operations that will be described in Group V, but no Ameroid contrictors were placed on the coronary arteries. These animals were studied 6 weeks after the sham operations and served as controls for the animals with chronic ischemia. The effects of acute mitral regurgitation were evaluated in these dogs by the techniques described above. Group V. Thirteen dogs underwent operations under sterile conditions to produce chronic coronary insufficiency. The animals were anesthetized with intravenous sodium pentobarbital, and respirations were controlled with a Harvard-type respirator through a cuffed endotracheal tube. The dogs were ventilated with 100 per cent oxygen. A left thoracotomy was performed. An Ameroid constrictor, 2.77 mm. in internal diameter, was placed at the origin of the anterior descending coronary artery, and small branches of the circumflex artery were ligated for possible anastomosis. Ap-
Volume 64 Number 2 August, 1972
Mitral regurgitation in coronary artery disease
257
Table I. Average results of hemodynamic responses in Groups I to V (expressed in per cent change during acute mitral regurgitation as compared to the base-line, nonregurgitant period) Hemodynamics
Group I
Aortic systolic pressure dp/dt Peak aortic flow dF/dt Coronary sinus flow Coronary vascular resistance Myocardial oxygen consumption Systolic ejection period Forward mean systolic ejection rate Forward LV stroke work Aortic flow Mean aortic pressure* (mm. Hg) LVEDP* Heart rate Forward stroke volume Regurgitant backward stroke volumet Total stroke volume
14.1 26.7 21.1 24.8 14.9 - 14.6 + 18.4 - 10.9 + 4.0 - 11.3 - 7.7 - 2.0 + 0.95 0 - 7.7 + 109.8 + 102.1 + + + + +
Group + 8.7 + 22.7 + 18.3 + 9.3 + 9.2 - 15.2 + 6.1 - 5.5 - 9.5 - 21.7 - 13.4 - 3.4 + 1.9 0 - 13.6 + 23.6 + 110
II
Group - 9.4 -12.3 - 7.4 - 3.0 + 3.6 -14.6 - 8.3 - 3.4 -10.2 -25.8 -13.0 - 8.6 + 1.2 0 -13.0 +95.8 +82.8
III
Group + + + +
IV
12.1 21.4 15.5 30.0 0 0 3.1 - 14.0 + 20.1 + 2.9 + 3.7 0 + 0.5 0 + 3.7 +118.8 +1 22.5
Group V - 9.2 + 1.0 + 3.3 + 6.6 + 1.7 - 9.9 + 2.7 - 8.5 - 4.5 - 21.0 - 11.9 - 6.3 + 1.0 0 - 11.9 +111.3 + 99.4
Legend: dp/dt, First derivative of left ventricular pressure. dF/dt, Acceleration of aortic flow. LVEDP, left ventricular end-diastolic pressure. ♦Actual change in mm. Hg. fPer cent of forward stroke volume in base-line period.
proximately 6V2 weeks after the initial operations, the surviving dogs were subjected to the same hemodynamic study of acute mitral regurgitation which was described previously. Autopsies were performed on all animals after the study, and coronary insufficiency in this group was estimated by macroscopic, microscopic, and angiographic findings. Results Average results of all groups expressed in percentage change from control levels are summarized in Table I. Group I (10 animals). During the production of acute mitral regurgitation, regurgitant flow averaged 111.4 per cent of the aortic flow in the base-line period (Table I), dp/dt increased from 2,195 to 2,753 mm. Hg per second, and dF/dt increased 25 per cent. Aortic systolic pressure and peak aortic flow increased from 100.9 to 114.8 mm. Hg and from 4,812 to 5,693 ml. per minute, respectively. Coronary sinus flow increased from 52.6 to 60.4 ml. per minute, and myocardial oxygen
consumption rose from 5.54 to 6.43 ml. per minute. Coronary vascular resistance was reduced by 14.4 per cent. A slight reduction in mean forward aortic flow and mean aortic pressure were observed (1,130 to 1,050 ml. per minute and 78.5 to 76.5 mm. Hg, respectively). The elevation of LVEDP was also slight (4.35 to 5.3 mm. Hg). Systolic ejection period decreased from 0.1525 to 0.1353 second, whereas forward mean ejection rate increased from 48.36 to 50.93 ml. per systolic second. Forward left ventricular stroke work was reduced from 7.61 to 6.78 Gm. M., a result which came from the reduction of forward mean aortic flow and a smaller pressure gradient between mean aortic pressure and LVEDP. Group II (9 animals). A mildly depressed cardiac state was caused by the production of acute myocardial ischemia. The following comparisons were made between the postligation state and the state which followed production of acute mitral regurgitation. Shunt regurgitant flow was 123 per cent of the postligation base-line aortic flow, dp/dt and dF/dt increased from 1,850 to 2,050
The Journal of
258
Omoto, Buckley,
Austen
Fig. 2. X-ray film of a postmortem injection of contrast material into the main left coronary artery of a dog from Group III. There is a sharp cut-off in the distal left anterior descending artery and its distal diagonal branches. Absence of perfusion of the apex of the left ventricle should be noted. (Injection pressure 120 mm. Hg.)
mm. Hg per second and from 100 to 108.8 per cent, respectively. Aortic systolic pressure increased from 76.2 to 82.9 mm. Hg, while peak aortic flow increased from 3,780 to 4,470 ml. per minute. Coronary sinus flow and myocardial oxygen consumption also increased, from 55.3 to 60.4 ml. per minute and from 5.00 to 5.31 ml. per minute, respectively. Coronary vascular resistance was reduced by 15.4 per cent. Forward mean aortic flow decreased from 813 to 705 ml. per minute, while mean aortic pressure fell from 63.6 to 60.2 mm. Hg. The elevation of LVEDP was from 4.91 to 6.77 mm. Hg; this was the largest change in all groups. Both systolic ejection period and forward mean ejection rate decreased (0.163 to 0.154 second and 37.3 to 33.8 ml. per minute, respectively). Forward left ventricular stroke work reduced from 4.82 to 3.80 Gm.-M. Fig. 2 illustrates the postmortem angiogram of the left coronary artery in one typical example from this group and demon-
Thoracic and Cardiovascular Surgery
strates experimentally produced acute myocardial ischemia in the anterolateral portion of the left ventricle. Contrast material was injected at a pressure of 120 mm. Hg. Group III (7 animals). A moderately depressed cardiac state was produced by serial ligation. The following comparisons were made between the postligation state and the state which followed production of acute mitral regurgitation. Shunt regurgitant flow was 95.8 per cent of the postligation baseline aortic flow, dp/dt and dF/dt decreased from 2,335 to 2,050 mm. Hg per second and from 100 to 94.3 per cent, respectively. Aortic systolic pressure decreased from 96.4 to 87.8 mm. Hg, whereas peak aortic flow fell from 5,300 to 4,900 ml. per minute. The changes in coronary sinus flow and myocardial oxygen consumption were minimal (60.2 to 62.7 ml. per minute and 7.64 to 7.29 ml. per minute, respectively). Coronary vascular resistance decreased by 14.3 per cent. Forward mean aortic flow and mean aortic pressure both decreased, from 1,032 to 885 ml. per minute and from 74.5 to 65.4 mm. Hg, respectively. LVEDP was observed to increase from 6.02 to 7.14 mm. Hg. The decrease in systolic ejection period was very slight (from 0.1650 to 0.1640 second), whereas the decrease in forward mean ejection rate was pronounced (47.0 to 41.8 ml. per systolic second). A reduction in the forward left ventricular stroke work was observed (7.470 to 5.451 Gm.M.). Group IV (2 animals). Regurgitant flow averaged 118.8 per cent of base-line aortic flow, dp/dt and dF/dt increased remarkably (18.62 to 22.61 mm. Hg per second and 100 to 130 per cent, respectively). Aortic systolic pressure increased from 102.5 to 115 mm. Hg, and peak aortic flow rose from 2,812 to 3,250 ml. per minute. Coronary sinus flow remained unchanged, (42.5 ml. per minute). A slight increase in myocardial oxygen consumption was observed (3.75 to 3.91 ml. per minute). Coronary vascular resistance remained unchanged. Forward mean aortic flow increased from 675 to 700 ml. per minute. Mean aortic pressure
Volume 64
Number 2
Mitral regurgitation in coronary artery disease
August, 1972
remained unchanged (79 mm. Hg). LVEDP increased from 7.5 to 8.0 mm. Hg. Systolic ejection period decreased from 0.150 to 0.129 second, while forward mean ejection rate increased from 27.3 to 32.8 ml. per systolic second. Forward left ventricular stroke work increased slightly (4.207 to 4.333 Gm. M.). Group V (13 animals). Regurgitant flow averaged 111.3 per cent of base-line aortic flow. The changes in dp/dt and dF/dt were slight (1,802 to 1,820 mm. Hg per second and 100 to 106.6 per cent, respectively). Aortic systolic pressure and peak aortic flow decreased from 92.1 to 80.5 mm. Hg and from 4,998 to 4,806 ml. per minute, respectively. The changes in coronary sinus flow and myocardial oxygen consumption were very small (54.19 to 55.06 ml. per minute and 5.33 to 5.46 ml. per minute). Coronary vascular resistance was reduced by 9.9 per cent, whereas the decreases in forward mean aortic flow and mean aortic pressure were marked (732.2 to 645.9 ml. per minute and 79.5 to 61.0 mm. Hg). LVEDP increased from 4.58 to 5.38 mm. Hg. Systolic ejection period decreased from 0.165 to 0.142 second, while forward mean ejection rate fell from 32.4 to 30.9 ml. per minute. Forward left ventricular stroke work decreased from 4.60 to 3.64 ml. per minute. Fig. 3 illustrates the postmortem angiogram of the left coronary artery in a typical example from this group. There is complete occlusion of the anterior descending artery with myocardial infarction in the anterior and lateral portion of the left ventricle. Contrast material was injected at a pressure of 120 mm. Hg. All animals included in this group were positively proved to have coronary insufficiency with myocardial infarction by the criteria described in the section on materials. Discussion There have been numerous hemodynamic studies of experimentally induced mitral regurgitation. MacCallum and McClure 1 produced acute mitral incompetence in dogs by means of rather qualitative approaches.
259
Fig. 3. X-ray film of a postmortem injection of contrast material into the main left coronary artery of a dog from Group V. No filling of the left anterior descending is noted beyond the Ameroid constrictor. The apex and septum of the left ventricle has no perfusion. This area was fibrotic on microscopic evaluation.
Braunwald and associates2 studied the hemodynamic effects of mitral regurgitation in anesthetized open-chest dogs. They found that mitral regurgitant flows from zero to three times the resting cardiac output were tolerated with only slight alterations of cardiac performance. It was observed also that the effect of any given regurgitant volume on left atrial pressure was a function of the filling pressure prior to the induction of regurgitation, suggesting an important relationship between myocardial contractility and the hemodynamic response. Ross and colleagues,3 using similar techniques, described quantitatively the phasic pressureflow relationship between the left ventricle and the left atrium. Wegria's group" demonstrated that acutely induced mitral regurgitation increased coronary flow and oxygen consumption of the myocardium. Others have studied the effect of acute mitral regurgitation upon aortic flow and cardiac
260
Omoto, Buckley,
The Journal of Thoracic and Cardiovascular Surgery
Austen
Table II. Hemodynamic responses following acute mitral regurgitation Hemodynamics
Pattern I
Pattern 11
dp/dt
Elevation
Depression
Aortic systolic pressure
Elevation
Depression
Peak aortic flow
Elevation
Depression
Coronary flow
Elevation
No change
Myocardial oxygen consumption
Elevation
No change
Coronary vascular resistance
Depression
Depression
Systolic ejection period
Depression
Depression
Forward mean ejection rate
Elevation
Depression
Legend: dp/dt, First derivative of left ventricular pressure.
impedance.5 All of these studies have been carried out in normal hearts. Since Davidson6 described a case report of spontaneous rupture of a papillary muscle with associated mitral regurgitation and Sanders7 further evaluated the acute hemodynamic responses seen in 61 cases of ruptured papillary muscle, the clinical distinction between acute severe mitral regurgitation associated with ruptured papillary muscle or papillary muscle dysfunction from that seen with chronic mitral regurgitation associated with rheumtic heart disease8-10 has been stressed. Furthermore, the responses to acute severe mitral regurgitation, seen secondary to idiopathic ruptured chordae tendineae or acute bacterial endocarditis, are often different from those seen with papillary muscle disease secondary to coronary artery occlusion. An increasing number of cases of severe acute mitral regurgitation secondary to ruptured papillary muscle, as well as other types of acute mitral regurgitation, have occurred with or without coronary disease. This experience has directed our interest toward seeking further delineation of the hemodynamic response to acute mitral regurgitation in the ischemic
Table III. Response to acute regurgitation Group Group Group Group Group
I II III IV V
mitral Pattern Pattern Pattern Pattern Pattern
I I II I II
heart as opposed to the hemodynamic response previously described in the normal heart. From the present study, it is evident that acute mitral regurgitation may produce two different hemodynamic responses in normal and ischemic hearts (Table II). The first response, Pattern I, usually found in the normal heart, was characterized by an elevation of the dp/dt, dF/dt, aortic systolic pressure, and peak aortic flow. The second response, Pattern II, was found predominantly in cases of severe myocardial damage and was characterized by an unchanged or depressed dp/dt, dF/dt, aortic systolic pressure, and peak aortic flow. Changes in coronary sinus flow and myocardial oxygen consumption seemed to follow these hemodynamic response patterns in most cases. It should be stressed that Pattern I and Pattern II are only convenient classifications for recognizing the responses to acute mitral regurgitation in varied conditions of the hearts. The responses usually seen in the groups studied are shown in Table III. In the preparation described, the ability of the heart to compensate for the increased work required by mitral regurgitation is dependent upon the residual normal myocardium. When the myocardial injury exceeded an estimated 20 per cent of the left ventricle, a very depressed response to acute mitral regurgitation was evident. This degree of injury is less than that seen in patients dying from cardiogenic shock secondary to acute myocardial infarction without mitral regurgitation,11 but it is similar to that injury seen with acute ventricular septal defect subsequent to myocardial infarction.12
Volume 64
Number 2
Mitral regurgitation in coronary artery disease
261
August, 1972
These findings would suggest that, in cases of acute mitral regurgitation associated with coronary artery disease and severe depression of ventricular function, an evaluation of myocardial performance should be carried out prior to surgery. The latter should include left ventricular angiography and coronary angiography to determine if other surgical procedures such as coronary revascularization or myocardial resection should be carried out at the time of mitral valve replacement. At the present time, the left ventriculogram seems to be most relevant in determining the extent of myocardial injury. Summary Acute mitral regurgitation was simulated in dogs by creating a controlled shunt between the left ventricle and left atrium. The hemodynamic response to acute regurgitation was studied in dogs with normal hearts and in dogs with hearts having acute and chronic ischemia. The usual hyperdynamic response to acute mitral regurgitation seen in normal hearts was depressed by myocardial ischemia, especially when the latter was extensive. REFERENCES 1 MacCallum, W. G., and McClure, R. D.: On the Mechanical Effects of Experimental Mitral Stenosis and Insufficiency, Johns Hopkins Med. J. 17: 260, 1906. 2 Braunwald, E., Welch, G. H., Jr., and Sarnoff, S. J.: Hemodynamic Effects of Quantitatively Varied Experimental Mitral Regurgitation, Circ. Res. 5: 539, 1957. 3 Ross, J., Jr., Cooper, T., and Lombardo, C. R.: Hemodynamic Observations in Experimental Mitral Regurgitation, Surgery, 47: 795, 1960. 4 Wegria, R., Muelheims, G., Jreissaty, R., and Nakano, J.: Effect of Acute Mitral Insufficiency of Various Degrees on Mean Arterial Blood Pressure, Coronary Blood Flow, Cardiac Output and Oxygen Consumption, Circ. Res. 6: 301, 1958. 5 Elkins, R. C , Morrow, A. G., Vasko, J. S., and Braunwald, E.: The Effects of Mitral Regurgitation on the Pattern of Instantaneous Aortic Blood Flow, Circulation 36: 45, 1967.
6 Davidson, S.: Spontaneous Rupture of a Papillary Muscle of the Heart; A Report of Three Cases and a Review of the Literature, Mt. Sinai J. Med. N. Y. 14: 94, 1948. 7 Sanders, R. J., Neubuerger, K. T., and Ravin, A.: Rupture of Papillary Muscles: Occurrence of Rupture of the Posterior Muscle in Posterior Myocardial Infarction, Dis. Chest 31: 316, 1957. 8 Sanders, C. A., Scannell, J. G., Hawthorne, J. W., and Austen, W. G.: Severe Mitral Regurgitation Secondary to Ruptured Chordae Tendineae, Circulation 31: 506, 1965. 9 Austen, W. G., Sanders, C. A., Averill, J. H., and Friedlich, A. L.: Ruptured Papillary Muscle: Report of Case With Successful Mitral Valve Replacement, Circulation 32: 597, 1965. 10 Austen, W. G., Sokol, D., DeSanctis, R. W., and Sanders, C. A.: The Surgical Treatment of Papillary Muscle Rupture Complicating Myocardial Infarction, N. Engl. J. Med. 278: 1137, 1968. 11 Page, D. L., Caulfield, J. B., Kastor, J. A., DeSanctis, R. W., and Sanders, C. A.: Myocardial Changes in Cardiogenic Shock, N. Engl. J. Med. 285: 133, 1971. 12 Buckley, M. J., Mundth, E. D., Daggett, W. M., DeSanctis, R. W., Sanders, C. A., and Austen, W. G.: Surgical Therapy for Early Complications of Myocardial Infarction, Surgery 70: 814, 1971. 13 Daggett, W. M., Burwell, L. R., Lawson, D. W., and Austen, W. G.: Resection of Acute Ventricular Aneurysm and Ruptured Interventricular Septum After Myocardial Infarction, N. Engl. J. Med. 283: 1507, 1970. 14 Mundth, E. D., Buckley, M. J., Leinbach, R. C , DeSanctis, R. W., Sanders, C. A., Kantrowitz, A. R., and Austen, W. G.: Myocardial Revascularization for the Treatment of Cardiogenic Shock Complicating Acute Myocardial Infarction, Surgery 70: 78, 1971. Appendix The oxygen consumption of the myocardium (MOC) drained by the coronary sinus was calculated according to the following formula: MOC (c.c./min.) = Wet CP 19.8 x j i - j x ■— x (difference of O2 saturation)
where 19.8 is the oxygen capacity of 100 per cent saturated normal blood per 100 c.c; 45.5 is the normal hematocrit index (Hct) (per cent); and CF is the flow rate of blood drained by the coronary sinus (ml./min.). j T irc„, (mAP - LVEDP) x SV x 13.6 x 1.055 Forward LVSW = ~r^r
where LVSW is the left ventricular stroke work
The Journal of
2 6 2 Omoto, Buckley, Austen
( G m . - M . ) ; m A P is the mean aortic pressure (mm. H g ) ; L V E D P is the left ventricular end-diastolic pressure (mm. H g ) ; SV is the forward stroke volume of the left ventricle (ml.) and equals mean aortic flow (ml./min.) . heart rate (beats/min.) ' 13.6 is the specific gravity of mercury; and 1.055 is the specific gravity of normal blood. C V R L V K
=
mAP CF
Thoracic and Cardiovascular Surgery
where CVR is the coronary vascular resistance (expressed in per cent of control). mean aortic flow (ml./min.) systolic seconds per min. where SER is the forward mean ejection rate (ml./systolic second) and systolic seconds per minute means the systolic ejection period (sec.) (the time from the onset of forward flow to that of zero flow). SER
_