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Creatine changes in heart muscle under various clinical conditions
CREATINE
CHAiSGES
IN HEART
CLlNT(‘Al,
MUSCLE
UNDER
VARIOUS
~‘ONDITIONS”t
T
HE establishment of a satisfactory explanation of the physiology of skeletal muscle conttaction on a chelnical basis involving phosphocreatine has revived int.erest iu the chemistry of heart muscle under various clinical and cxpcrimcntal conditions. The new approach seems to offer some promise of clucidatiou of such intricate problems as the finite basis of myocardial weakness, of carcliac hypertrophy, and A luore fundamental experhaps eren of phan~~acodynanlic action planation of heart. failure has long btvu dcn~andcd by clinicians, impressed by the frequent absence of adequate gross and microscopic findings to explain the clinically obscrvcd complete functiona. insufficiency of the cardiac n~usculature.‘L That somet,hing more than marphological changes must be sought out has been frequently indicated, and that biochemical changes may play an importnut r81e has been suggested. BIOCHEMIC.\I,
BXCKGROVSD
Constabel? in 1921, following the earlier suggestion of Pekelherin@ that increased muscle tonus \vas associated with higher creatine content, found that the creatine c,outeut of atomic, dilated or damaged human hearts was usually ion-. These observations were apparently lost for thirteen years. l3uring these intervening years, however, the great mass of experimental work on the physiological chemistry of skeletal muscle contraction has been carried out in Germany, in England, and in the United States. Since 1922 significant contributions t,o our knowledge of this subject of muscle physiology have been published from Embden’s laboratory. In out cJf the early papers Emhdeu and Lawaczech4 presented obserrations of reactions which demonst,rated the importance of organic phosphatrs in muscle physiology. The interpretation. that the observed increase in inorganic phosphates a.s well as the formation of lactic acid during II~LISC~~;~I’ contraction came from a hexosephosphate. luctacidogen, was apparently in error. Lohman11J later (192X) show4 that, by the method used by Embden, the orthophosphate yield came mostly from the splittiug of pyrophosphate and ouly in small part, from the lactacidogen. and “Ftnm the Depai‘tment of Medicine :m(l Pathology of the T:niversity of Texas. ;Read at the meeting of the American Heart Association held at Kansas City, Mo.. By an cnfottunnte VPOI the ~liscussion of this paper at that 12, 1936. tinrc was omitted from the Transxtions of that meeting ynhlisherl in the Octohcr issue of this Journal. on May
HERRMANN ET AL. :
CREATINE C’HASGES
691
contraction. Pollack, Flack, Essex and Bollnlan13 have made similar, but technically much more difficult, studies of phosphocreatine in The failure dogs’ hearts from the Starling heart-lung preparations. of these investigators to confirm Vollmer’s findings may be due in large measure to the difficulties inherent in mammalian heart studies, namely, the inability to freeze the muscle in the desired phase of contraction.
The experimental studies as to the creatinc and phosphocreatine changes in cardiac muscular contraction seemed to Indicate that processes similar to those of skeletal masclc physiology were at work. Renewed interest was aroused by these reports in the problems of human heart function. Constabel’s findings were recalled and extended by Vollmer and others and rarious other chemical studies were undertaken. Wilkens and Cullen14 noted a decrcasc in total phosphorus and potassium in the heart muscle from patient,s who had died in congestive failure. Scott,lj with material supplied him by one of us, confirmed the potassium loss. Seecof, Linegar and &lyers’G followed up Constabel’s and VollnIer’s studies of the creatine content and reported the creatine values for the various parts of 102 human hearts. They found the left ventricular muscle to contain uniformly more ereatine than the right, with a mean of 243 mg. per cent for the left and 188 mg. per cent for the right,, averages of 211 and 148 mg. per cent, respectively, and ranges of from 116 to 369 as against 93 to 283 mg. per cent. Vollmer had reported the left ventricle to contain 221 mg. per cent and tbc right 173 mg. per cent-a 20 per cent difference-whereas Constabel hiid clicit,ed only a 10 per cent difference. c,owan17 has supplied corroborative cvidcnce of Constabel’s early contention that lowered total myocardial creatine values were found in hearts that had been seriously damaged. In 11 of 17 hearts from patients who had died in congestive failure, he recorded total creatine values of from 92 to 152 mg. per cent. These figures are low as compared with those found in “normal” hearts (from pat,ients who had died of other causes) which sho\vcd mean values of 202 mg. per cent * 37. Under our direction in this laboratory W. 0. Bro\q Jr., analyzed, as our first series,ls the left ventricular muscle from 50 adults, kindly supplied US from autopsies by Dr. Tom Oliver, Dr. Jarrett Williams and Dr. Sion Halley, of the staff of the Department of Pathology. Thirteen of the 50 hearts were from patients with congestive failure and in these the creatine values ra.nged from 85 to 132 and averaged 111 ing. per cent, whereas in 10 hearts from patients with syphilitic aortic disease, the values ranged from 110 to 137, and averaged 123
mg. per cent. In a miscellaneous group without, prow heart. disease 123 to 205, with a11 average 0C 150 the creatine Aues ranged from mg. per cent.. L’RFSFv’I’ >A LV~r’nIES A second scrics of 105 human hearts, in which the left ventricular muscle has been analyzed in our lahorato~y.’ furnishes the basis fol this paper. The crcatine values in this stcond alltl large group of hearts correspond quite closely to the previously reported findings. bat t.hry will he set down in dfltail as a matter of wcord. ‘I’aHl.1: I
L’Il.7 +Il.ri:! 20.; 18.f: t’O.0 1x.1; 20.1 “l.!l .,a, --. (j 19.:: 19.S t’1l.L’ %.(I 20. I 20 ! ! ?I:1 20.6 “O.li 19.:: 2O.G “3.4 ‘0.1 18.1 13.7
+1.5.4
FT;i ‘20.7
-.--______ --__
+0.96 20.3 +0.x7
868 +76
HERR%XANN
ET
AL.:
CBEATINE
693
C’HASGES
The results were tabulated according to the-clinical and post-mortem data under the headings: 1, apparently normal hearts; 2, grossly abnormal hearts that had not shown failure; 3, hearts from patients hearts frnm dying of congestive cardiac failure ; and -I. infsrctcd patients with coronary thrombosis. Group analyses
l.-There were 34 hearts which were apparently of the left vcnt~ricular muscle of which showed T.\ur,v: HEART
DISEASE
normal, the an ayerage
II
TVITIIOKT
PAIIJJKE
AGF,
SES
RACE
CR. (AIG. %)
HT . WC\ .
A.
Fith
72
M
B
Hypertrnsiota 400
68 38 iis 48 45
M M M M M
B B IV B B
,511) 510 540 643 410
SOLIDS %
6.
89 60 45 72 43 70 64
M M M M M M M M M M IIt
M
Coromwy
Rheumntic
.-Lortic
B
450
SEVERE ‘42 55 6'7 29 72
M if M F
B TV w w W
221
21.6
"0.8 19.4 90.1 21.1 19.5
1022 989 814 992 937 1063 --
198
20.4
970
144 148 176 119 137 14:: 187 .I73 139 173 162
19.7 21.4 19.4 19.2 19.7 18.8 20.8 20.5 19.2 21.5 20.2
731 690 907 (j”” I& 7ti4 900 85:: 831 815 800
I57
20.0
7x::
19.9 20.1
105X X60 -____
144 t::7 119 310 17.7
17.2 19.7 19.2 20.0 20.5
837 735 622 1050 853
137
19.:
819
F 2 F M F
w B
150 169 14ti 165 159 168
19.6 20.0 20.7 21.8 19.2 22.0
785 845 706 756 831 763
: B B
159
20.3
791
Mitral
wad
“10 1;:: -__
WITH 435 400 400 280 260 420
Disraar -__.
Amhm,s
290 425 250 290 320
~LOMERULOSEPHRITIS 43 49 48 40 45 '9 r>
%)
,ScZrrosis
335 3% 295 230 325 475 350 ::20 260 “40 '85
s TV W TV H w w
(‘. Pith. 41
With
W w W
CR.
204 1.38 199 19x 207 --
73 60 53 67
DR. (MG.
URENIh
--
reduced to about the same concentrations found in the hearts of patients with congestive failure (Table III, A). Ten hearts from patients with prolonged and complicated infectious diseases, with microscopic evidence only of myocardial damage, presented similarly low crcatine figures, arcraging 119 mg. per cent, with 20.8 per cent solids and 671 mg. per cent in terms of dried weight (Table III, IS). Groz~p &.-Thirty-two hearts from patients who had died in congestive failure were found upon analysis to contain about 30 per cent less crcatine than normal with the following values for the left ventricular myoeardium : creatine, 122 mg. per cent I 20.8; solids, 20.3 t 1.2 per cent,; and dried weight, 605 mg. per cent + 100 (Table IV). These values corroborate OLW previous reports and those of others except for the ten low values found in infectious diseases of a chronic complicated type. as shown in Table 111. K. iUlc1
B TV B B B w B B TV w IV R TV B TV iv TV B B B TV TV B B B B B ii B B
-
f3ciGrosix Hypertension Coronary sclerosis Hypertension Rgphilis Sclerosis Syphilis Hypertension Syphilis Hyperknsion Sclerosis Sclerosis Hypertension + C.O. Hypertension Syphilis + hnernis Hypertension + C.0. Hypertension
Hrlerosis
Averages
-
*C.O., coronary
+ C.O.
Hypertension Hypertension Hypertension Sclerosis + C.O. Hypertension + C.O. Syphilis + CO. Hypertension Hypertension Syphilis Hypertension Hypertension Syphilis Hypertension
occlusion.
2n.70 21.1
18.7 19.1 20.4 19.3 20.0 lS.c, "O.Ki 19.I) 21.0 30.0 18.3 20.1 19.7 33.4 20.5 20.5 21.0 19.1
i10 Ii10 425 700
380 275 540 ti50 460 ml 800 AOII 500 49.5 Gin 600 430 400 R-/l1
20.5 21.9 19.7 19.1 20.8 20.7 23.4 21.7 21.7 17.8 139
19.6
1""Y1
20.3
?20.8
rt1.22
512 738 455 497 577 72:t cillll 537 .F‘, 64.) 5ti3 (i18 625 56" 057 ti9ti
520 532 705 785 572 649 497 555 78Y 690 667 478 457 598 511 710 605 +100
________
-.- -__
NO.
11 23 34
CAUSE
Traumatic
Infections Controls Heart
6 11 IS ti
FRESII (m.
OF DEATH
tliwtsc~
without
q&b)
solIII~s (@/o)
DRIED (WC. %)
183 + 17.0 l’i’? _f 15 4 17; t 20:7
20.7 t O.fi2 20.1 -c 0.98 30.:: t 0.87
887 2 79 558 t 70 St% 5 70
21 0
19.9
1033
20.4 20.0 50.1 Xl.::
970 Lt 79 783 860 751
19.3 20.2 i 1.2 3.3
819
I’:tilurt~
Rheumatic, aortic, and mitxal Hvoertension Coronary sclerosis Total without failure Glomerulonephritis wit11 IA
19s i 137 1 i:: 1 .X
16.6
uremia 5 32 10
anemia Congestive heart failure Jnfedions with microsctJyi(* nlvoc~:lrtli:ll ~~ll:IngV severe
1.3;
1””.J..- + 20 . 8 1 “I
605 + 300 596
COWCI,lkxON8
The results of OUP studies,
and those of otheq c*onvince US that lo\\ human myocadial creatine values n10e more or less constant accom.paninients of congestirc failure and must be among the significant chemical changes that, aYe associated with myocardial damage and I’art~iculal~ly signific*ant k\rC the CXtlX'lllely IOIV tOtill insufficiency. creatine contents of the myocatdiuun fl*otn the infal~c,terl areas in CMPS of coronary Mroml~osis.
9. I’iske.
lvh.
C. H..
10. Eggleton, Some
’
and
Sul)barom,
I’., and Eggleton, Other Pl~osphorous
Y.:
Phoxphocreatine,
J.
Biol.
G;. P.: A Jlethod of Estimating J. ~‘on~1~oon~ln in .\lusclr Tissue,
Chem.
81:
6?!),
Phosphagen 1’11ysi01. 68:
and 19::.
1 ‘)‘“I . -. .
11. 12.
13. 14. 15. 16. 17. IS.
or van Tonen fiir die MusEml~den, Cr.? and Lehnnrtz, I.:.: 1.elrer dir liedeutun, kelfunktlon, Ztschr. f. physiol, chrm. 134: 243, 1924. Vollmer, iK. Z. : Untersuchungen nebcr llcn Iirratin un(l I’l~ospllo~s~ur~ellalt versshiedener Herzteile, Bcr. d. ges:. I’hys. II. t~spcr. PhnrmakoI. 51: 503. I!)‘“). Pollack, H., Flack, E., Essex, H. I:., rind H~llm:t~~, ;r. I,.: Phosphorus Cornpounds in the Perfused Heart of the Dog. Am. *T. Phvsiol. 110: 97, 1934. Wiikens, ?V. E., and C’ulleu, I:. K.: I?lect’rol,vtes in H;ln~an Tissue,’ J. c’lizt. Investigation 12: 1063, 1%X<. Scott, I,. C~‘.: The Determination uf Plotassium in C’ardiae Muscle, J. Clin. Investigation 10: 74.5, 1931. Seecof, D: P., Linegar, il. R., and ;\I\-ers, V. C.: The Difference in Creatine Concentration of the Left and Right Ventricular C’artliac Muscles. Arch. ._ ht. Med. 53: 674, 1934. Cowan, D. W.: The Creatine Content of the 1Iyocardium of Eormal and Al>normal Human Hearts, AX. HEART J. 9: 375, 1934. Herrmann, (:eorge: Some l~iochemical Factors in Heart Failure, Medical Papws dedicated to Henry Asbury C’hristinn, wnvrrl~ Prrss (lLM>) . 17.33, 2nd South. M. J. 29: %G, 193G.
CHAiSGES
IN HEART
CLlNT(‘Al,
MUSCLE
UNDER
VARIOUS
~‘ONDITIONS”t
T
HE establishment of a satisfactory explanation of the physiology of skeletal muscle conttaction on a chelnical basis involving phosphocreatine has revived int.erest iu the chemistry of heart muscle under various clinical and cxpcrimcntal conditions. The new approach seems to offer some promise of clucidatiou of such intricate problems as the finite basis of myocardial weakness, of carcliac hypertrophy, and A luore fundamental experhaps eren of phan~~acodynanlic action planation of heart. failure has long btvu dcn~andcd by clinicians, impressed by the frequent absence of adequate gross and microscopic findings to explain the clinically obscrvcd complete functiona. insufficiency of the cardiac n~usculature.‘L That somet,hing more than marphological changes must be sought out has been frequently indicated, and that biochemical changes may play an importnut r81e has been suggested. BIOCHEMIC.\I,
BXCKGROVSD
Constabel? in 1921, following the earlier suggestion of Pekelherin@ that increased muscle tonus \vas associated with higher creatine content, found that the creatine c,outeut of atomic, dilated or damaged human hearts was usually ion-. These observations were apparently lost for thirteen years. l3uring these intervening years, however, the great mass of experimental work on the physiological chemistry of skeletal muscle contraction has been carried out in Germany, in England, and in the United States. Since 1922 significant contributions t,o our knowledge of this subject of muscle physiology have been published from Embden’s laboratory. In out cJf the early papers Emhdeu and Lawaczech4 presented obserrations of reactions which demonst,rated the importance of organic phosphatrs in muscle physiology. The interpretation. that the observed increase in inorganic phosphates a.s well as the formation of lactic acid during II~LISC~~;~I’ contraction came from a hexosephosphate. luctacidogen, was apparently in error. Lohman11J later (192X) show4 that, by the method used by Embden, the orthophosphate yield came mostly from the splittiug of pyrophosphate and ouly in small part, from the lactacidogen. and “Ftnm the Depai‘tment of Medicine :m(l Pathology of the T:niversity of Texas. ;Read at the meeting of the American Heart Association held at Kansas City, Mo.. By an cnfottunnte VPOI the ~liscussion of this paper at that 12, 1936. tinrc was omitted from the Transxtions of that meeting ynhlisherl in the Octohcr issue of this Journal. on May
HERRMANN ET AL. :
CREATINE C’HASGES
691
contraction. Pollack, Flack, Essex and Bollnlan13 have made similar, but technically much more difficult, studies of phosphocreatine in The failure dogs’ hearts from the Starling heart-lung preparations. of these investigators to confirm Vollmer’s findings may be due in large measure to the difficulties inherent in mammalian heart studies, namely, the inability to freeze the muscle in the desired phase of contraction.
The experimental studies as to the creatinc and phosphocreatine changes in cardiac muscular contraction seemed to Indicate that processes similar to those of skeletal masclc physiology were at work. Renewed interest was aroused by these reports in the problems of human heart function. Constabel’s findings were recalled and extended by Vollmer and others and rarious other chemical studies were undertaken. Wilkens and Cullen14 noted a decrcasc in total phosphorus and potassium in the heart muscle from patient,s who had died in congestive failure. Scott,lj with material supplied him by one of us, confirmed the potassium loss. Seecof, Linegar and &lyers’G followed up Constabel’s and VollnIer’s studies of the creatine content and reported the creatine values for the various parts of 102 human hearts. They found the left ventricular muscle to contain uniformly more ereatine than the right, with a mean of 243 mg. per cent for the left and 188 mg. per cent for the right,, averages of 211 and 148 mg. per cent, respectively, and ranges of from 116 to 369 as against 93 to 283 mg. per cent. Vollmer had reported the left ventricle to contain 221 mg. per cent and tbc right 173 mg. per cent-a 20 per cent difference-whereas Constabel hiid clicit,ed only a 10 per cent difference. c,owan17 has supplied corroborative cvidcnce of Constabel’s early contention that lowered total myocardial creatine values were found in hearts that had been seriously damaged. In 11 of 17 hearts from patients who had died in congestive failure, he recorded total creatine values of from 92 to 152 mg. per cent. These figures are low as compared with those found in “normal” hearts (from pat,ients who had died of other causes) which sho\vcd mean values of 202 mg. per cent * 37. Under our direction in this laboratory W. 0. Bro\q Jr., analyzed, as our first series,ls the left ventricular muscle from 50 adults, kindly supplied US from autopsies by Dr. Tom Oliver, Dr. Jarrett Williams and Dr. Sion Halley, of the staff of the Department of Pathology. Thirteen of the 50 hearts were from patients with congestive failure and in these the creatine values ra.nged from 85 to 132 and averaged 111 ing. per cent, whereas in 10 hearts from patients with syphilitic aortic disease, the values ranged from 110 to 137, and averaged 123
mg. per cent. In a miscellaneous group without, prow heart. disease 123 to 205, with a11 average 0C 150 the creatine Aues ranged from mg. per cent.. L’RFSFv’I’ >A LV~r’nIES A second scrics of 105 human hearts, in which the left ventricular muscle has been analyzed in our lahorato~y.’ furnishes the basis fol this paper. The crcatine values in this stcond alltl large group of hearts correspond quite closely to the previously reported findings. bat t.hry will he set down in dfltail as a matter of wcord. ‘I’aHl.1: I
L’Il.7 +Il.ri:! 20.; 18.f: t’O.0 1x.1; 20.1 “l.!l .,a, --. (j 19.:: 19.S t’1l.L’ %.(I 20. I 20 ! ! ?I:1 20.6 “O.li 19.:: 2O.G “3.4 ‘0.1 18.1 13.7
+1.5.4
FT;i ‘20.7
-.--______ --__
+0.96 20.3 +0.x7
868 +76
HERR%XANN
ET
AL.:
CBEATINE
693
C’HASGES
The results were tabulated according to the-clinical and post-mortem data under the headings: 1, apparently normal hearts; 2, grossly abnormal hearts that had not shown failure; 3, hearts from patients hearts frnm dying of congestive cardiac failure ; and -I. infsrctcd patients with coronary thrombosis. Group analyses
l.-There were 34 hearts which were apparently of the left vcnt~ricular muscle of which showed T.\ur,v: HEART
DISEASE
normal, the an ayerage
II
TVITIIOKT
PAIIJJKE
AGF,
SES
RACE
CR. (AIG. %)
HT . WC\ .
A.
Fith
72
M
B
Hypertrnsiota 400
68 38 iis 48 45
M M M M M
B B IV B B
,511) 510 540 643 410
SOLIDS %
6.
89 60 45 72 43 70 64
M M M M M M M M M M IIt
M
Coromwy
Rheumntic
.-Lortic
B
450
SEVERE ‘42 55 6'7 29 72
M if M F
B TV w w W
221
21.6
"0.8 19.4 90.1 21.1 19.5
1022 989 814 992 937 1063 --
198
20.4
970
144 148 176 119 137 14:: 187 .I73 139 173 162
19.7 21.4 19.4 19.2 19.7 18.8 20.8 20.5 19.2 21.5 20.2
731 690 907 (j”” I& 7ti4 900 85:: 831 815 800
I57
20.0
7x::
19.9 20.1
105X X60 -____
144 t::7 119 310 17.7
17.2 19.7 19.2 20.0 20.5
837 735 622 1050 853
137
19.:
819
F 2 F M F
w B
150 169 14ti 165 159 168
19.6 20.0 20.7 21.8 19.2 22.0
785 845 706 756 831 763
: B B
159
20.3
791
Mitral
wad
“10 1;:: -__
WITH 435 400 400 280 260 420
Disraar -__.
Amhm,s
290 425 250 290 320
~LOMERULOSEPHRITIS 43 49 48 40 45 '9 r>
%)
,ScZrrosis
335 3% 295 230 325 475 350 ::20 260 “40 '85
s TV W TV H w w
(‘. Pith. 41
With
W w W
CR.
204 1.38 199 19x 207 --
73 60 53 67
DR. (MG.
URENIh
--
reduced to about the same concentrations found in the hearts of patients with congestive failure (Table III, A). Ten hearts from patients with prolonged and complicated infectious diseases, with microscopic evidence only of myocardial damage, presented similarly low crcatine figures, arcraging 119 mg. per cent, with 20.8 per cent solids and 671 mg. per cent in terms of dried weight (Table III, IS). Groz~p &.-Thirty-two hearts from patients who had died in congestive failure were found upon analysis to contain about 30 per cent less crcatine than normal with the following values for the left ventricular myoeardium : creatine, 122 mg. per cent I 20.8; solids, 20.3 t 1.2 per cent,; and dried weight, 605 mg. per cent + 100 (Table IV). These values corroborate OLW previous reports and those of others except for the ten low values found in infectious diseases of a chronic complicated type. as shown in Table 111. K. iUlc1
B TV B B B w B B TV w IV R TV B TV iv TV B B B TV TV B B B B B ii B B
-
f3ciGrosix Hypertension Coronary sclerosis Hypertension Rgphilis Sclerosis Syphilis Hypertension Syphilis Hyperknsion Sclerosis Sclerosis Hypertension + C.O. Hypertension Syphilis + hnernis Hypertension + C.0. Hypertension
Hrlerosis
Averages
-
*C.O., coronary
+ C.O.
Hypertension Hypertension Hypertension Sclerosis + C.O. Hypertension + C.O. Syphilis + CO. Hypertension Hypertension Syphilis Hypertension Hypertension Syphilis Hypertension
occlusion.
2n.70 21.1
18.7 19.1 20.4 19.3 20.0 lS.c, "O.Ki 19.I) 21.0 30.0 18.3 20.1 19.7 33.4 20.5 20.5 21.0 19.1
i10 Ii10 425 700
380 275 540 ti50 460 ml 800 AOII 500 49.5 Gin 600 430 400 R-/l1
20.5 21.9 19.7 19.1 20.8 20.7 23.4 21.7 21.7 17.8 139
19.6
1""Y1
20.3
?20.8
rt1.22
512 738 455 497 577 72:t cillll 537 .F‘, 64.) 5ti3 (i18 625 56" 057 ti9ti
520 532 705 785 572 649 497 555 78Y 690 667 478 457 598 511 710 605 +100
________
-.- -__
NO.
11 23 34
CAUSE
Traumatic
Infections Controls Heart
6 11 IS ti
FRESII (m.
OF DEATH
tliwtsc~
without
q&b)
solIII~s (@/o)
DRIED (WC. %)
183 + 17.0 l’i’? _f 15 4 17; t 20:7
20.7 t O.fi2 20.1 -c 0.98 30.:: t 0.87
887 2 79 558 t 70 St% 5 70
21 0
19.9
1033
20.4 20.0 50.1 Xl.::
970 Lt 79 783 860 751
19.3 20.2 i 1.2 3.3
819
I’:tilurt~
Rheumatic, aortic, and mitxal Hvoertension Coronary sclerosis Total without failure Glomerulonephritis wit11 IA
19s i 137 1 i:: 1 .X
16.6
uremia 5 32 10
anemia Congestive heart failure Jnfedions with microsctJyi(* nlvoc~:lrtli:ll ~~ll:IngV severe
1.3;
1””.J..- + 20 . 8 1 “I
605 + 300 596
COWCI,lkxON8
The results of OUP studies,
and those of otheq c*onvince US that lo\\ human myocadial creatine values n10e more or less constant accom.paninients of congestirc failure and must be among the significant chemical changes that, aYe associated with myocardial damage and I’art~iculal~ly signific*ant k\rC the CXtlX'lllely IOIV tOtill insufficiency. creatine contents of the myocatdiuun fl*otn the infal~c,terl areas in CMPS of coronary Mroml~osis.
9. I’iske.
lvh.
C. H..
10. Eggleton, Some
’
and
Sul)barom,
I’., and Eggleton, Other Pl~osphorous
Y.:
Phoxphocreatine,
J.
Biol.
G;. P.: A Jlethod of Estimating J. ~‘on~1~oon~ln in .\lusclr Tissue,
Chem.
81:
6?!),
Phosphagen 1’11ysi01. 68:
and 19::.
1 ‘)‘“I . -. .
11. 12.
13. 14. 15. 16. 17. IS.
or van Tonen fiir die MusEml~den, Cr.? and Lehnnrtz, I.:.: 1.elrer dir liedeutun, kelfunktlon, Ztschr. f. physiol, chrm. 134: 243, 1924. Vollmer, iK. Z. : Untersuchungen nebcr llcn Iirratin un(l I’l~ospllo~s~ur~ellalt versshiedener Herzteile, Bcr. d. ges:. I’hys. II. t~spcr. PhnrmakoI. 51: 503. I!)‘“). Pollack, H., Flack, E., Essex, H. I:., rind H~llm:t~~, ;r. I,.: Phosphorus Cornpounds in the Perfused Heart of the Dog. Am. *T. Phvsiol. 110: 97, 1934. Wiikens, ?V. E., and C’ulleu, I:. K.: I?lect’rol,vtes in H;ln~an Tissue,’ J. c’lizt. Investigation 12: 1063, 1%X<. Scott, I,. C~‘.: The Determination uf Plotassium in C’ardiae Muscle, J. Clin. Investigation 10: 74.5, 1931. Seecof, D: P., Linegar, il. R., and ;\I\-ers, V. C.: The Difference in Creatine Concentration of the Left and Right Ventricular C’artliac Muscles. Arch. ._ ht. Med. 53: 674, 1934. Cowan, D. W.: The Creatine Content of the 1Iyocardium of Eormal and Al>normal Human Hearts, AX. HEART J. 9: 375, 1934. Herrmann, (:eorge: Some l~iochemical Factors in Heart Failure, Medical Papws dedicated to Henry Asbury C’hristinn, wnvrrl~ Prrss (lLM>) . 17.33, 2nd South. M. J. 29: %G, 193G.