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Experimental studies on heart tonics. IV. The main factors of digitalis standardization with a new assay method
ABSTRACTS *
Bock, A. V., Dill, D. B., and Edwards, H. T.: Cn the Relation of Changes in Blood Velocity and Volume Flow of Blood to Change of Posture. J. Clh Investigation
8:
533,
1930.
Estimations of the circulation time as measured by reaction to histamine indicate a retardation of the velocity of blood flow in the standing position in man. The authors believe this fact supports previous experimental evidence showing a reduction of the total output of the heart when the subject stands still.
Pardee, Harold E. B.: Q-wave in Lead III.
The Significance arch. Int. Med.
of an Electrocardiogram 46: 476, 1930.
with
a Large
Attention is directed to the occurrence of records showing left axis deviation of QRS or a normal electrical nsis, combined with a large Q-nxre in Lead III, one that is 05 per cent or more of the lnrgest detlcction of QRR in whichever lead this may occur. The majority of such records are obtained from patients with the angina1 syndrome, but certain patients with myocardial fibrosis and congestive failure, crrtain patients with rheumatic heart disease, especially with pericarditis, and a few with hypertension will give such records. Certain patients who have cardiac symptoms but no definite evidence of cardiac disease have been found to show this large Q-III, and rarely (twice in 277 cases) such records are obtained from apparently normal hearts. These records show a clockwise rotation of the vectors of the QRS group, and frequently there is an inversion of T-III or of T-II and T-III. Both of these features depend on right ventricular activity, and it is suggested that the finding of a large Q-III indicates disease of the left ventricle, so that the right ventricle predominates during the spreading of the contraction in spite of the left axis deviation or normal axis direction of QRS. The effect of diaphragmatic movements on the large Q-III is noted and it is suggested that the occasional finding of a large Q-III in normal hearts may be due to an unusual distribution of the branches of the A-V bundle and that a high position of the diaphragm may be a contributory factor.
Nyiri, William, and DuBois, Louis: Experimental The Main Factors of Digitalis Standardization J. Pharmacol.
& Erpcr.
Thcrap.
40:
3i3,
Studies on Heart Tonics. IV. with a New Assay Method.
1930.
The authors believe that warm-blooded animals are to be preferred as test material to animals lower in the animal scale and to plants. They a o believe that the best way of administering heart tonics in the assag is the in+i xavenous injection. Intravenous ancsthcsia is also to be preferred to the former methods of narcosis in animal experimentation in general and for the standardization of heart tonics in particular. The fall of blood pressure to zero, approaches closest the theoretically espccted cm1 point of the experiment and thus is to bc preferred to the observation of the stoppage of the heart and the general death of the animal. Based on the study of thcsc principal factors a practical method of digitalis standardization is described using the rabbit as trst animal. This method has the following advantages: the animal is always easily available. The end point of tho assay obtained by means of tho drop of the blood prcssurc, supplementing the test of the use of ouabain, is definite and as close to the theoretical end point as may he expected. Because of tho higher resistance to digitalis the methotl allows the testing of drugs of high concentration as well as drugs of great dilution without preliminary injurious manipulations of the heart tonics.
438
THE
AME,I:J(‘AiY
IJEART
JOURNAL
All methorls of standardization of heart tonics: inchilling t,hc one herein dtxscribe~l, arc toxicity tests ant1 us,’ the tlcnth of the heart or of the entire organism as final criterion. Tn \-iclc of the therapeutic pur1~1sc of the heart tonic3 any method tlcaling Trith the tlctcrlrrination of the therapeutic ethciency in&all of the fatal dose obviously 1, ~111 be l)ref~~r:rl~le. TVnfortnn:rtely, such a mot.hotl is not a\-ailable at present.
Dawson, M. H., and Boots, R. H.: Subcutaneous Nodules in Rheumatoid Infectious) Arthritis. J. A. M. A. 95: 1891, 1930.
(Chronic
The authors have found a relati\:cly high-a~ploxirl~atcly t1O per ccnt-inciIlcnee of patients with suhcntaneous nodules in a group of approximately 336 inllividuals suffering lvith true rhcumatoitl arthritis. The nodules have been observccl only in cases of typical rheumatoirl arthritis, and in one case of Still’s disease. Three of the patients in Tvhom the nodulrs occurrell presentotl a history of a previous attack of rheumatic fever; four patients sho~od definite evidence of rheumatic heart involvement; in one patient the tlevclopmcnt of arthritis and the appearance of nodules aplmarcd to bear a dellnit? relationship to a previous attack of scarlet fcvcr. Nodules have been cserciscd from 11 patients and subjected to careful histological and bacteriological examination. The material examined shoTvcd a striking uniform and characteristic picture. This study sustains the follo~ving conclusions: The subcutaneous notlulc occurring in rheumatoid arthritis is a classic lesion of this disease. The histologic appearance of these nodules is uniform and highly characteristic. There is a striking histologic rcscmbloncc bet\\-eon the subcutancons notlulcs occurring in rheumatic fever and those observed in rheumatoid arthritis.
Sprague, Howard Sixty Cases.
B., a.nd Gragbiel, Nen- England J.
Ashton: Med. 204:
Salyrgan
as
a Diuretic.
Report
of
1.51, 1931.
Sixty cases treated lvith salyrgan are reported. Forty-six patients had cardiac tiiscascs uith digestive failure ; eight ha11 cirrhosis of the li\cr; four had cancer; Diuresis was secured in 80 per cent and one each nephrosis and ovarian cyst. of the cases and in 65 per cent this diurcsis rxcec~letl twice t.ho fluid intake. The diuretic effect may often be increaacd by the USC of ammonium chloride or nitrate. The authors feel that the drug is an active and safe (liurctic of particular value in the treatment of congestive heart failure with edema of ascites from various causes, and of nephrosis. It should be usr~l early in the therapy of these conditions and not reserved as a drug of last resort. The toxic effects from Ralyrgan are very rare and consist of mild renal, gastrointestinal or skin irritation. This lvork supports the riem that the chief cffcct of mercurial diuretics is directly upon t,he kidney.
Wolferth, Charles C., and Margolies, Alexander: The Influence of Auricular traction on the First Heart Sound and the Radial Pulse. Arch. Int. 46:
1045,
ConMed.
1930.
A series of 7 cases with varying auriculoventricular relationships all showed inequalities of the first heart sound which could be related to the lengths of the intervals between aurieular and ventricular systoles. These time relations tended to be characteristic for each case, although the degree of inequality varied and exceptionally could not be recorded.
Bock, A. V., Dill, D. B., and Edwards, H. T.: Cn the Relation of Changes in Blood Velocity and Volume Flow of Blood to Change of Posture. J. Clh Investigation
8:
533,
1930.
Estimations of the circulation time as measured by reaction to histamine indicate a retardation of the velocity of blood flow in the standing position in man. The authors believe this fact supports previous experimental evidence showing a reduction of the total output of the heart when the subject stands still.
Pardee, Harold E. B.: Q-wave in Lead III.
The Significance arch. Int. Med.
of an Electrocardiogram 46: 476, 1930.
with
a Large
Attention is directed to the occurrence of records showing left axis deviation of QRS or a normal electrical nsis, combined with a large Q-nxre in Lead III, one that is 05 per cent or more of the lnrgest detlcction of QRR in whichever lead this may occur. The majority of such records are obtained from patients with the angina1 syndrome, but certain patients with myocardial fibrosis and congestive failure, crrtain patients with rheumatic heart disease, especially with pericarditis, and a few with hypertension will give such records. Certain patients who have cardiac symptoms but no definite evidence of cardiac disease have been found to show this large Q-III, and rarely (twice in 277 cases) such records are obtained from apparently normal hearts. These records show a clockwise rotation of the vectors of the QRS group, and frequently there is an inversion of T-III or of T-II and T-III. Both of these features depend on right ventricular activity, and it is suggested that the finding of a large Q-III indicates disease of the left ventricle, so that the right ventricle predominates during the spreading of the contraction in spite of the left axis deviation or normal axis direction of QRS. The effect of diaphragmatic movements on the large Q-III is noted and it is suggested that the occasional finding of a large Q-III in normal hearts may be due to an unusual distribution of the branches of the A-V bundle and that a high position of the diaphragm may be a contributory factor.
Nyiri, William, and DuBois, Louis: Experimental The Main Factors of Digitalis Standardization J. Pharmacol.
& Erpcr.
Thcrap.
40:
3i3,
Studies on Heart Tonics. IV. with a New Assay Method.
1930.
The authors believe that warm-blooded animals are to be preferred as test material to animals lower in the animal scale and to plants. They a o believe that the best way of administering heart tonics in the assag is the in+i xavenous injection. Intravenous ancsthcsia is also to be preferred to the former methods of narcosis in animal experimentation in general and for the standardization of heart tonics in particular. The fall of blood pressure to zero, approaches closest the theoretically espccted cm1 point of the experiment and thus is to bc preferred to the observation of the stoppage of the heart and the general death of the animal. Based on the study of thcsc principal factors a practical method of digitalis standardization is described using the rabbit as trst animal. This method has the following advantages: the animal is always easily available. The end point of tho assay obtained by means of tho drop of the blood prcssurc, supplementing the test of the use of ouabain, is definite and as close to the theoretical end point as may he expected. Because of tho higher resistance to digitalis the methotl allows the testing of drugs of high concentration as well as drugs of great dilution without preliminary injurious manipulations of the heart tonics.
438
THE
AME,I:J(‘AiY
IJEART
JOURNAL
All methorls of standardization of heart tonics: inchilling t,hc one herein dtxscribe~l, arc toxicity tests ant1 us,’ the tlcnth of the heart or of the entire organism as final criterion. Tn \-iclc of the therapeutic pur1~1sc of the heart tonic3 any method tlcaling Trith the tlctcrlrrination of the therapeutic ethciency in&all of the fatal dose obviously 1, ~111 be l)ref~~r:rl~le. TVnfortnn:rtely, such a mot.hotl is not a\-ailable at present.
Dawson, M. H., and Boots, R. H.: Subcutaneous Nodules in Rheumatoid Infectious) Arthritis. J. A. M. A. 95: 1891, 1930.
(Chronic
The authors have found a relati\:cly high-a~ploxirl~atcly t1O per ccnt-inciIlcnee of patients with suhcntaneous nodules in a group of approximately 336 inllividuals suffering lvith true rhcumatoitl arthritis. The nodules have been observccl only in cases of typical rheumatoirl arthritis, and in one case of Still’s disease. Three of the patients in Tvhom the nodulrs occurrell presentotl a history of a previous attack of rheumatic fever; four patients sho~od definite evidence of rheumatic heart involvement; in one patient the tlevclopmcnt of arthritis and the appearance of nodules aplmarcd to bear a dellnit? relationship to a previous attack of scarlet fcvcr. Nodules have been cserciscd from 11 patients and subjected to careful histological and bacteriological examination. The material examined shoTvcd a striking uniform and characteristic picture. This study sustains the follo~ving conclusions: The subcutaneous notlulc occurring in rheumatoid arthritis is a classic lesion of this disease. The histologic appearance of these nodules is uniform and highly characteristic. There is a striking histologic rcscmbloncc bet\\-eon the subcutancons notlulcs occurring in rheumatic fever and those observed in rheumatoid arthritis.
Sprague, Howard Sixty Cases.
B., a.nd Gragbiel, Nen- England J.
Ashton: Med. 204:
Salyrgan
as
a Diuretic.
Report
of
1.51, 1931.
Sixty cases treated lvith salyrgan are reported. Forty-six patients had cardiac tiiscascs uith digestive failure ; eight ha11 cirrhosis of the li\cr; four had cancer; Diuresis was secured in 80 per cent and one each nephrosis and ovarian cyst. of the cases and in 65 per cent this diurcsis rxcec~letl twice t.ho fluid intake. The diuretic effect may often be increaacd by the USC of ammonium chloride or nitrate. The authors feel that the drug is an active and safe (liurctic of particular value in the treatment of congestive heart failure with edema of ascites from various causes, and of nephrosis. It should be usr~l early in the therapy of these conditions and not reserved as a drug of last resort. The toxic effects from Ralyrgan are very rare and consist of mild renal, gastrointestinal or skin irritation. This lvork supports the riem that the chief cffcct of mercurial diuretics is directly upon t,he kidney.
Wolferth, Charles C., and Margolies, Alexander: The Influence of Auricular traction on the First Heart Sound and the Radial Pulse. Arch. Int. 46:
1045,
ConMed.
1930.
A series of 7 cases with varying auriculoventricular relationships all showed inequalities of the first heart sound which could be related to the lengths of the intervals between aurieular and ventricular systoles. These time relations tended to be characteristic for each case, although the degree of inequality varied and exceptionally could not be recorded.