Left Ventricular Function Studies in Constrictive Pericarditis Eiji SEKINO, Sohei SUZUKI,Takeshi MOMOKAWA,Takafumi KUDO, Akio IHAX'A and Norio ISHIZUKA A B S T R A C T : Left ventricular function studies were performed on five patients with constrictive pericarditis. Functional data were obtained from intracardiac pressure measurements and cineangiocardiographic films. Left ventricular end-diastolic volume(LVEDV), left ventricular endsystolic volume (LVESV), ejection fraction (EF), stroke work index (SWI), circumferential fiber shortening, and percent circumferencial shortening were significantly below normal values in the five cases. These changes are reflected mainly in the degree of pericardial restriction. Reduction in mean Vcf was also observed. Theoretically, the velocity of ventricular internal circumferential shortening is also affected by changes in ventricular volume or resting myocardial fiber length, however, in patients with constrictive pericarditis, reduction in mean Vcf suggests left ventricular dysfunction. Our clinical studies indicate that evaluation of mean Vcf is valuable in the assessment of postoperative prognoses. KEY W O R D S :
constrictive pericarditis, left ventricular function.
INTRODUCTION I n most constrictive pericarditis cases, pericardiectomy effects prompt clinical improvement although there are some cases with delayed recovery. In these cases, after eliminating inadequate decortication, ventricular dysfunction must be considered. While several hemodynamic studies have been reported, I-8 little has been published concerning preoperative left ventricular function in constrictive pericarditis.l, 9-11 The present report discusses left ventricular function in patients with constrictive pericarditis with or without protein-losing gastroenteropathy.
PATIENTS Between 1969 and 1976, 10 patients underwent pericardiectomy for constrictive pericarditis at our clinic. Important preoperative clinical data are summarized in Table 1. All patients showed the typical "dip and plateau" right ventricular pressure configuration. Six patients had hypoproteinemia, and in five, protein-losing gastroenteropathy was confirmed by radio-isotope methods. These five cases were used for the present left ventricular function studies.
First Department of Surgery, Hirosaki University Medical School, Hirosaki City, Aomori Pref., Japan. JAPANESEJOURNAL OF SURGERY, VOL. 8, No. 3, pp. 186-191, 1978
Volume 8 Number 3
Left Ventricular Function
187
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METHODS
Cineangiocardiography For all patients, premedication consisted of atropine sulfate (0.01 mg/kg) and pentazocine or meperidine (0.2 to 0.5 mg/kg). Left heart catheterization was performed using the retrograde arterial technique following standard right heart catheterization. Aortic and left ventricular pressures were recorded immediately prior to angiocardiography using the Toshiba polygraph (Type ST 2076A) and the fluid filled catheter method. One plain cineangiocardiography at 30 ~ of right anterior oblique projection was done (100 frames/see) using Iothalamate (Angioconray) 1 mg/kg injected at 8 to 10 kg/cm 2 of injection pressure. Angiographic films were analyzed with a Nac-image film motion analyzer. Parameters of left ventricular function: 1) Left ventricular volume Left ventricular volume was measured from the cineangiograms according to the method of Green.lZ End-diastolic volume (LVEDV) and end-systolic volume (LVESV) were measured and calculated from the films, which were corrected for magnification and normalized for body surface area with the equation, V = ~ - L M 29
(ml/m e)
Correction for position distortion was not made. 12 2) Stroke volume index (SVI) LVEDV-LVESV (ml/m z) SVI = Body surf. area 3) Stroke work index (SWI) SWI = SVI. (mean Ao-press.-LVEDP) • 1.36 100 (g. m/beat/m 2) 4) Left ventricular systolic ejection fraction (EF) LVEDV-LVESV EF~ LVEDV 5) Shortening of left ventricular internal circumference (Shortening of LV circ.) LVED circ.-LVES circ. Shortening of LV circ. = LVED circ. • 100 -
-
(% ED) 6) Velocity of left ventricular internal circumferencial shortening (mean Vcf and max Vcf) ALV circ. Vcf = t
(circ.]see.) ALV circ. means the difference between left ventricular internal circumferences of two adjoining cineangiographic frames. RESULTS
Left ventricular function data of the five constrictive pericarditis cases were compared
Volume 8 Number 3
Table 2. Case No. 6 7 8 9 10
Control n=5
189
Left Ventricular Function
LVEDV LVESV (ml/m~) (ml/m~) 100.23 71.20 89.76 66.24 40.75
12.75 33.04 33.66 23.55 16.74
Left ventricular function parameters constrictive pericarditis
EF 0.872 0.536 0.625 0.644 0.589
73.64 23.95 0.653 :k20.53 -4- 8.42 :k:0.115 98.81 26.24 0.729 :k18.16 :t: 8.63 :k0.031
SWI Shortening of circ. (g.m./beat/m 2) (era) (%ED) 64.27 23.87 54.93 37.16 26.95 41.44 =t=15.75 57.36 :J:ll.80
7.40 5.23 5.72 3.52 3.39
mean Vcf. max Vcf. (circ./see.) (circ./see.)
41.5 26.7 27.2 25.8 28.1
1.09 1.29 0.93 0.77 0.71
3.92 1.68 1.76 1.64 1.81
29.9 :t:7.5 39.2 :k6.6
0.96 :j:_ 0 . 2 1 I. 11 :k0.12
2.16 i0.88 2.33 :k0.39
with similar data from a group cinsisting of five cases with either innocent murmurs or atrial septal defects with minimal shunts (Table 2). The left ventricular end-diastolic pressure in constrictive pericarditis ranged from 16 to 36 rnmHg, which is distinctly higher than L V E D P in the comparative group. In the five constrictive pericarditis cases, the mean end-diastolic volume was 73.64~:20.53 ml/m 2, the mean end-systolic volume 23.95 ::k 8.42 ml/m 2, the mean ejection fraction 0.653• and the mean stroke work index 41.44:J: 15.75 g. m/beat/m s. There was a correlation between left ventricular end-diastolic volume and the grade ofpericardial constriction. Since there was no significant difference in the end-systolic volumes between the two groups, the ejection fractions and stroke work indices were significantly reduced below the comparative group values. The average observed mean Vcf in constrictive pericarditis was 0.96:J:0.21 circ./see, with a mean max Vcf of 2.16:J:0.88 circ./see, and an average percent circumferential shortening of 2 9 . 9 • 0 . 2 1 % E D . T h e average comparative group values were mean Vcf 1.11-50.12 circ./see., m a x Vcf 2.33:t:0.39 circ./see, and percent circumferential shortening 39.2• %ED. DmCuss~oN In our clinical experience, persistent elevation of ventricular diastolic pressure and delayed clinical recovery sometimes occur despite surgically adequate decortication for constrictive pericarditis, and good hemodynamic improvement and clinical recovery usually take place within several months following surgery. This suggests that myocardial functional capacity must be evaluated to assess accurately the postoperative prognosis in coustrictive pericarditis. Schepers 13 attributed myocardial degeneration in constrictive pericarditis to myocardial fibrous invasion and/or restriction of coronary flow. Dines, Edwards and Burchelp4 found myocardial fiber atrophy in 11 autopsies of constrictive pericarditis and proposed that diminished ventricular size, low systolic wall stress, decreased output and stroke work possibly result in myocardial fiber atrophy which could explain a prolonged return to hemodynamic normal. It is also well known that constrictive pericarditis is often accompanied by hypoproteinemia secondary to protein losing gastroenteropathy. I f there is poor hemodynamic improvement after adequate pericardiectomy, the recovery from hypoproteinemia m a y also be delayed. In our case No. 4, hypoproteinemia did not improve during the first several weeks after surgery. However, after a few months, the patient gradually regained full health with normal serum
Jpn. J. Surg. Sept. 1978
Sekino et al.
190
(g/d/) ..... ca.z:diaefailure 8 ~N O ~8 CNo~ ~
..... prompt improvement T ..... prompt improvement
No.6 ~
/
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~:~_-:~.
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z
~:~a~p~ improvementrecovery
. . . . inadequate decortication little evidence of improvement . . . . cardiac failure
... ....
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I
Fig. 1
protein. In case No. 9, the patient required continuous post-operative administration of digitalis and diuretics because of progressive cardiac enlargement, oliguria, ascites and bilateral pleural effusion secondary to cardiac failure and serum protein levels remained low. These cases point out the importance of preoperative evaluation of ventricular myocardial function in constrictive pericarditis patients. Ordinary parameters used to evaluate left ventricular function do not represent reliable indicators in constrictive pericarditis. Left ventricular end-diastolic pressure, for example, does not reflect the transmural myocardial distending force alone but are contributed to pericardial restriction. Sonnenblick 15 noted that if maximal contractile element velocity and isometric force can be determined, the effect of changes in resting fiber length could be distinguished from the effects related to changes in the muscle's functional competence. Theoretically, left ventricular internal circumferential shortening and the measurement of its velocity by our technique is affected by changes in ventricular volume or resting myocardial fiber length. However, a reduction in the mean velocity of left ventricular internal circumferencial shortening indicates a relative reduction in ventricular myocardial competence, assuming similar degrees of pericardial restriction. In cases No. 8, 10 and 9, the mean Vcf's were 0.77, 0.71 and 0.93 respectively, which is significantly less than the other cases as well as the comparative group cases. Cases No. 8 and 10 showed poor postoperative clinical recovery requiring digitalis and diuretic therapy, although serum protein levels promptly returned to normal. Case No. 9 had progressive cardiomegaly and bradycardia postoperatively. A cardiac pacemaker was implanted on the 1 lth postoperative day and the response was excellent with an increase
Volume 8 Number 3
Left Ventricular Function
191
in c a r d i a c o u t p u t a n d d i s a p p e a r a n c e o f a n a s a r c a . In constrictive pericarditis, myocardial d y s f u n c t i o n m a y be a r e f l e c t i o n o f disuse r a t h e r t h a n m y o c a r d i a l a t r o p h y o r disease. As H a r r i s o n 9 p o i n t e d out, t h e o n l y c e r t a i n m e a n s o f d i f f e r e n t i a t i o n w o u l d be a biopsy o f the m y o c a r d i u m . However, preoperative evaluation of cardiac function by means of the m e a n v e l o c i t y o f left v e n t r i c u l a r f i b e r s h o r t e n i n g c a l c u l a t e d f r o m c i n e a n g i o c a r d i o g r a m s is o f d i a g n o s t i c v a l u e . (Received for publication on J a n u a r y 14, 1978) References 1. Kudo, T. : Experimental and clinical studies of left ventricular function using left ventricular cineangiography, Hirosaki Igaku (Hirosaki Med. J.) 29:93-115, 1977 (in Japanese with English summary). 2. Kloster, F.E., Crislip, R.L., Bristow, J.D. et al. : Hemodynamic studies following pericardiectomy for constrictive pericarditis, Circulation 32: 415-424, 1965. 3. Lazarides, D.P., Avgoustakis, D.G. and Lekos, D.: Evaluation of radical pericardiectomy for constrictive pericarditis (a clinical, hemodynamic and electrocardiographic study of twenty cases), J. Thorac. Cardiovasc. Surg. 51 : 821-833, 1966. 4. Mohiuddin, A.B. : Constrictive pericarditis, an analysis of seventeen cases, Dis Chest 51: 298-303, 1967. 5. Cordell, A.R. and Beason, E.A.: Pericardiectomy for constrictive pericarditis, jr, Cardiovasc. Surg. 9: 44-48, 1968. 6. Kesteloot, H. and Denef, B. : Value of reference tracings in diagnosis and assessment of constrictive epi- and pericarditis, Br. Heart J. 32: 675-682, 1970. 7. Shabetai, R., Fowler, N.O. and Guntheroth, W.G. : The hemodynamics of cardiac tamponade and constrictive periearditis, Am. J. Cardiol. 26: 480-489, 1970.
8. Hancock, E.W.: Subacute effusive- constrictive pericarditis, Circulation 43: 183-192, 1971. 9. Harrison, E.G., Crawford, D.W. and Lau, F.Y.K.: Squential left ventricular function studies before and after pericardiectomy for constrictive pericarditis, Am. aT. Cardiol. 26: 319-323, 1970. 10. Vogel, J.H.K., Horgan, J.A. and Strahl, C.L. : Left ventricular dysfunction in chronic constrictive pericarditis, Chest 59 : 484~1~92, 1971. 11. Lewis, B.S. and Gotsman, M.S.: Left ventricular function in systole and diastole in constrictive pericarditis, Am. Heart J. 86: 23-41, 1973. 12. Green, D.G., Carlisle, R. and Bunnell, I.L.: Estimation of left ventricular volume by oneplanecineangiography, Circulation 35: 61-69, 1967. 13. Schepers, G.W.H.: Tuberculous pericarditis, Am. J. Cardiol. 9: 248-276, 1962. 14. Dines, D.E., Edwards, J.E. and Burchell, H.B. : Myocardial atrophy in constrictive pericarditis, Mqyo Clinic Proc. 33 : 93-99, 1958. 15. Sonnenblick, E.H.: Force-velocity relations in mammalian heart muscle, Am. J. Physiol. 202: 931-939, 1962.
constrictive pericarditis, left ventricular function.
INTRODUCTION I n most constrictive pericarditis cases, pericardiectomy effects prompt clinical improvement although there are some cases with delayed recovery. In these cases, after eliminating inadequate decortication, ventricular dysfunction must be considered. While several hemodynamic studies have been reported, I-8 little has been published concerning preoperative left ventricular function in constrictive pericarditis.l, 9-11 The present report discusses left ventricular function in patients with constrictive pericarditis with or without protein-losing gastroenteropathy.
PATIENTS Between 1969 and 1976, 10 patients underwent pericardiectomy for constrictive pericarditis at our clinic. Important preoperative clinical data are summarized in Table 1. All patients showed the typical "dip and plateau" right ventricular pressure configuration. Six patients had hypoproteinemia, and in five, protein-losing gastroenteropathy was confirmed by radio-isotope methods. These five cases were used for the present left ventricular function studies.
First Department of Surgery, Hirosaki University Medical School, Hirosaki City, Aomori Pref., Japan. JAPANESEJOURNAL OF SURGERY, VOL. 8, No. 3, pp. 186-191, 1978
Volume 8 Number 3
Left Ventricular Function
187
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Jpn. J. Surg. Sept. 1978
METHODS
Cineangiocardiography For all patients, premedication consisted of atropine sulfate (0.01 mg/kg) and pentazocine or meperidine (0.2 to 0.5 mg/kg). Left heart catheterization was performed using the retrograde arterial technique following standard right heart catheterization. Aortic and left ventricular pressures were recorded immediately prior to angiocardiography using the Toshiba polygraph (Type ST 2076A) and the fluid filled catheter method. One plain cineangiocardiography at 30 ~ of right anterior oblique projection was done (100 frames/see) using Iothalamate (Angioconray) 1 mg/kg injected at 8 to 10 kg/cm 2 of injection pressure. Angiographic films were analyzed with a Nac-image film motion analyzer. Parameters of left ventricular function: 1) Left ventricular volume Left ventricular volume was measured from the cineangiograms according to the method of Green.lZ End-diastolic volume (LVEDV) and end-systolic volume (LVESV) were measured and calculated from the films, which were corrected for magnification and normalized for body surface area with the equation, V = ~ - L M 29
(ml/m e)
Correction for position distortion was not made. 12 2) Stroke volume index (SVI) LVEDV-LVESV (ml/m z) SVI = Body surf. area 3) Stroke work index (SWI) SWI = SVI. (mean Ao-press.-LVEDP) • 1.36 100 (g. m/beat/m 2) 4) Left ventricular systolic ejection fraction (EF) LVEDV-LVESV EF~ LVEDV 5) Shortening of left ventricular internal circumference (Shortening of LV circ.) LVED circ.-LVES circ. Shortening of LV circ. = LVED circ. • 100 -
-
(% ED) 6) Velocity of left ventricular internal circumferencial shortening (mean Vcf and max Vcf) ALV circ. Vcf = t
(circ.]see.) ALV circ. means the difference between left ventricular internal circumferences of two adjoining cineangiographic frames. RESULTS
Left ventricular function data of the five constrictive pericarditis cases were compared
Volume 8 Number 3
Table 2. Case No. 6 7 8 9 10
Control n=5
189
Left Ventricular Function
LVEDV LVESV (ml/m~) (ml/m~) 100.23 71.20 89.76 66.24 40.75
12.75 33.04 33.66 23.55 16.74
Left ventricular function parameters constrictive pericarditis
EF 0.872 0.536 0.625 0.644 0.589
73.64 23.95 0.653 :k20.53 -4- 8.42 :k:0.115 98.81 26.24 0.729 :k18.16 :t: 8.63 :k0.031
SWI Shortening of circ. (g.m./beat/m 2) (era) (%ED) 64.27 23.87 54.93 37.16 26.95 41.44 =t=15.75 57.36 :J:ll.80
7.40 5.23 5.72 3.52 3.39
mean Vcf. max Vcf. (circ./see.) (circ./see.)
41.5 26.7 27.2 25.8 28.1
1.09 1.29 0.93 0.77 0.71
3.92 1.68 1.76 1.64 1.81
29.9 :t:7.5 39.2 :k6.6
0.96 :j:_ 0 . 2 1 I. 11 :k0.12
2.16 i0.88 2.33 :k0.39
with similar data from a group cinsisting of five cases with either innocent murmurs or atrial septal defects with minimal shunts (Table 2). The left ventricular end-diastolic pressure in constrictive pericarditis ranged from 16 to 36 rnmHg, which is distinctly higher than L V E D P in the comparative group. In the five constrictive pericarditis cases, the mean end-diastolic volume was 73.64~:20.53 ml/m 2, the mean end-systolic volume 23.95 ::k 8.42 ml/m 2, the mean ejection fraction 0.653• and the mean stroke work index 41.44:J: 15.75 g. m/beat/m s. There was a correlation between left ventricular end-diastolic volume and the grade ofpericardial constriction. Since there was no significant difference in the end-systolic volumes between the two groups, the ejection fractions and stroke work indices were significantly reduced below the comparative group values. The average observed mean Vcf in constrictive pericarditis was 0.96:J:0.21 circ./see, with a mean max Vcf of 2.16:J:0.88 circ./see, and an average percent circumferential shortening of 2 9 . 9 • 0 . 2 1 % E D . T h e average comparative group values were mean Vcf 1.11-50.12 circ./see., m a x Vcf 2.33:t:0.39 circ./see, and percent circumferential shortening 39.2• %ED. DmCuss~oN In our clinical experience, persistent elevation of ventricular diastolic pressure and delayed clinical recovery sometimes occur despite surgically adequate decortication for constrictive pericarditis, and good hemodynamic improvement and clinical recovery usually take place within several months following surgery. This suggests that myocardial functional capacity must be evaluated to assess accurately the postoperative prognosis in coustrictive pericarditis. Schepers 13 attributed myocardial degeneration in constrictive pericarditis to myocardial fibrous invasion and/or restriction of coronary flow. Dines, Edwards and Burchelp4 found myocardial fiber atrophy in 11 autopsies of constrictive pericarditis and proposed that diminished ventricular size, low systolic wall stress, decreased output and stroke work possibly result in myocardial fiber atrophy which could explain a prolonged return to hemodynamic normal. It is also well known that constrictive pericarditis is often accompanied by hypoproteinemia secondary to protein losing gastroenteropathy. I f there is poor hemodynamic improvement after adequate pericardiectomy, the recovery from hypoproteinemia m a y also be delayed. In our case No. 4, hypoproteinemia did not improve during the first several weeks after surgery. However, after a few months, the patient gradually regained full health with normal serum
Jpn. J. Surg. Sept. 1978
Sekino et al.
190
(g/d/) ..... ca.z:diaefailure 8 ~N O ~8 CNo~ ~
..... prompt improvement T ..... prompt improvement
No.6 ~
/
7
56
..... iprompt improvement
~:~_-:~.
,p No.~ ~ No.~ No.4 No.1 ~~
I
Pre-op.
z
~:~a~p~ improvementrecovery
. . . . inadequate decortication little evidence of improvement . . . . cardiac failure
... ....
I
Post-op. (4 - 6'weeks)
I
Fig. 1
protein. In case No. 9, the patient required continuous post-operative administration of digitalis and diuretics because of progressive cardiac enlargement, oliguria, ascites and bilateral pleural effusion secondary to cardiac failure and serum protein levels remained low. These cases point out the importance of preoperative evaluation of ventricular myocardial function in constrictive pericarditis patients. Ordinary parameters used to evaluate left ventricular function do not represent reliable indicators in constrictive pericarditis. Left ventricular end-diastolic pressure, for example, does not reflect the transmural myocardial distending force alone but are contributed to pericardial restriction. Sonnenblick 15 noted that if maximal contractile element velocity and isometric force can be determined, the effect of changes in resting fiber length could be distinguished from the effects related to changes in the muscle's functional competence. Theoretically, left ventricular internal circumferential shortening and the measurement of its velocity by our technique is affected by changes in ventricular volume or resting myocardial fiber length. However, a reduction in the mean velocity of left ventricular internal circumferencial shortening indicates a relative reduction in ventricular myocardial competence, assuming similar degrees of pericardial restriction. In cases No. 8, 10 and 9, the mean Vcf's were 0.77, 0.71 and 0.93 respectively, which is significantly less than the other cases as well as the comparative group cases. Cases No. 8 and 10 showed poor postoperative clinical recovery requiring digitalis and diuretic therapy, although serum protein levels promptly returned to normal. Case No. 9 had progressive cardiomegaly and bradycardia postoperatively. A cardiac pacemaker was implanted on the 1 lth postoperative day and the response was excellent with an increase
Volume 8 Number 3
Left Ventricular Function
191
in c a r d i a c o u t p u t a n d d i s a p p e a r a n c e o f a n a s a r c a . In constrictive pericarditis, myocardial d y s f u n c t i o n m a y be a r e f l e c t i o n o f disuse r a t h e r t h a n m y o c a r d i a l a t r o p h y o r disease. As H a r r i s o n 9 p o i n t e d out, t h e o n l y c e r t a i n m e a n s o f d i f f e r e n t i a t i o n w o u l d be a biopsy o f the m y o c a r d i u m . However, preoperative evaluation of cardiac function by means of the m e a n v e l o c i t y o f left v e n t r i c u l a r f i b e r s h o r t e n i n g c a l c u l a t e d f r o m c i n e a n g i o c a r d i o g r a m s is o f d i a g n o s t i c v a l u e . (Received for publication on J a n u a r y 14, 1978) References 1. Kudo, T. : Experimental and clinical studies of left ventricular function using left ventricular cineangiography, Hirosaki Igaku (Hirosaki Med. J.) 29:93-115, 1977 (in Japanese with English summary). 2. Kloster, F.E., Crislip, R.L., Bristow, J.D. et al. : Hemodynamic studies following pericardiectomy for constrictive pericarditis, Circulation 32: 415-424, 1965. 3. Lazarides, D.P., Avgoustakis, D.G. and Lekos, D.: Evaluation of radical pericardiectomy for constrictive pericarditis (a clinical, hemodynamic and electrocardiographic study of twenty cases), J. Thorac. Cardiovasc. Surg. 51 : 821-833, 1966. 4. Mohiuddin, A.B. : Constrictive pericarditis, an analysis of seventeen cases, Dis Chest 51: 298-303, 1967. 5. Cordell, A.R. and Beason, E.A.: Pericardiectomy for constrictive pericarditis, jr, Cardiovasc. Surg. 9: 44-48, 1968. 6. Kesteloot, H. and Denef, B. : Value of reference tracings in diagnosis and assessment of constrictive epi- and pericarditis, Br. Heart J. 32: 675-682, 1970. 7. Shabetai, R., Fowler, N.O. and Guntheroth, W.G. : The hemodynamics of cardiac tamponade and constrictive periearditis, Am. J. Cardiol. 26: 480-489, 1970.
8. Hancock, E.W.: Subacute effusive- constrictive pericarditis, Circulation 43: 183-192, 1971. 9. Harrison, E.G., Crawford, D.W. and Lau, F.Y.K.: Squential left ventricular function studies before and after pericardiectomy for constrictive pericarditis, Am. aT. Cardiol. 26: 319-323, 1970. 10. Vogel, J.H.K., Horgan, J.A. and Strahl, C.L. : Left ventricular dysfunction in chronic constrictive pericarditis, Chest 59 : 484~1~92, 1971. 11. Lewis, B.S. and Gotsman, M.S.: Left ventricular function in systole and diastole in constrictive pericarditis, Am. Heart J. 86: 23-41, 1973. 12. Green, D.G., Carlisle, R. and Bunnell, I.L.: Estimation of left ventricular volume by oneplanecineangiography, Circulation 35: 61-69, 1967. 13. Schepers, G.W.H.: Tuberculous pericarditis, Am. J. Cardiol. 9: 248-276, 1962. 14. Dines, D.E., Edwards, J.E. and Burchell, H.B. : Myocardial atrophy in constrictive pericarditis, Mqyo Clinic Proc. 33 : 93-99, 1958. 15. Sonnenblick, E.H.: Force-velocity relations in mammalian heart muscle, Am. J. Physiol. 202: 931-939, 1962.
