- Email: [email protected]
FALL OF ENDOCARDIAL POTENTIALS AFTER ACUTE MYOCARDIAL INFARCTION
1308
Chertsey, Surrey) with sodium-citrate buffers and the column temperature programmed for 300C and 60°C. Norleucine was used as an internal standard in each analysis. Recovery-rates
were determined separately for each The mean recovery-rate was 98-3% (range, 92-3-105-5%). The coefficient of variation for ten replicate determinations on the same sample of amniotic fluid ranged from 2-4 to 10-1% for different aminoacids with a mean of 6-7%. These results are comparable to those reported by other investigators with ion-exchange
aminoacid.
chromatography.10-12 Results for glutamine
and glutamic acid are reported with reservation since some samples of fluid had been stored before analysis, and the concentrations of these aminoacids may be affected even when samples are deproteinised and then stored at —68°C.10 Values for &bgr;-aminoisobutyric acid are not reported because this was present in only trace amounts ( < 0-04 mg. per 100 ml.). Values for ex-amino nitrogen were determined by a colorimetric ninhydrin method.13 Results
So far we have been able to identify 27 aminoacids and related compounds in human amniotic fluid. Results for all except &bgr;-amino-isobutyric acid are shown in the accompanying table. There is very close agreement between the values for the period 37-40 weeks and those obtained by more recent investigators who have studied amniotic fluid at term. 6,7a
Great Britain.
Requests
for
reprints should
be addressed to A. E. H. E.
REFERENCES
4. 5. 6.
Nelson, M. M., Emery, A. E. H. Br. med. J. 1970, i, 523. Emery, A. E. H. in Modern Trends in Human Genetics (edited by A. E. H. Emery); p. 267. London, 1970. Orlandi, C., Torsello, R. V., Bottiglioni, F. Attual. Ostet. Ginec. 1958, 4, 871. Wirtschafter, Z. T. Am. J. Obstet. Gynec. 1958, 76, 1219. Sassi, D. Monitore Ostet-Ginec. Endocr. Metab. 1962, 33, 683. Spackman, D. H. Technicon Monograph no. 3; p. 40. Geneva,
7. 8. 9.
Levy, H. L., Montag, P. P. Pediat. Res. 1969, 3, 113. Perry, T. L., Hansen, S. Clin. chim. Acta, 1969, 25, 53. Hamilton, P. B. in Technicon Monograph no. 3; p. 52. Geneva,
1. 2. 3.
1968.
1968.
There seem to be three patterns of change in the aminoacid composition of amniotic fluid at various stages of pregnancy. Firstly, the concentrations of some aminoacids remain more or less the same throughout pregnancy--e.g., cysteic acid phosphoethanolamine, ethanolamine, and proline. Secondly, the concentrations of other aminoacids decrease progressively from the first trimester and throughout the remainder of pregnancy-e.g., serine, glycine, phenylalanine, lysine, and arginine. Thirdly, the remaining aminoacids appear to have a lower concentration in the first trimester than in the period 13-16 weeks, but thereafter their concentrations decrease as pregnancy progresses. In most cases concentration rises in the last month of pregnancy. In early pregnancy (13-16 weeks) the concentrations of most aminoacids are greater in amniotic fluid than in neonatal or adult plasma (see table). However, at term, except for taurine and ethanolamine, the concentrations of all aminoacids in amniotic fluid are less than in neonatal or adult plasma. Some small, as yet unidentified, peaks have occasionally been observed in some samples of amniotic fluid. Three unidentified peaks have occurred fairly consistently, their positions on chromatograms being just after alanine, just before valine, and between ammonia and ornithine. Should any of these peaks be found in apparently increased amounts in a fetus at risk from a genetic disorder, then their identification would be important. This aspect of the problem is being further
investigated. Discussion
study 27 aminoacids and related been identified in amniotic fluid. have compounds The concentrations of these substances at various stages of pregnancy are presented in the hope that the In the present
information may be useful in antenatal diagnosis. It seems likely that changes in the aminoacid composition of amniotic fluid may prove diagnostic in such conditions as cystinuria, glycinuria, and Hartnup’s disease. Matalon et al.14 have reported that they have successfully diagnosed Hurler’s syndrome in utero by demonstrating a significantly raised level of acid mucopolysaccharides in amniotic fluid as early as the 14th week of gestation. The antenatal diagnosis of at least some genetic disorders associated with changes in urinary composition, by the biochemical analysis of amniotic fluid, therefore seems a distinct possibility. We acknowledge the technical assistance of Miss Helen Stein and Mr. A. Anderson. We also thank Dr. J. G. Robertson for his help in obtaining specimens of amniotic fluid in mid-pregnancy. This work was supported by research grants from the Secretary of State for Scotland and the Muscular Dystrophy Group of
Dickinson, J. C., Rosenblum, H., Hamilton, P. B. Pediatrics, Springfield, 1965, 36, 2. 11. Kerr, G. R., Kenna, A. L. Am. J. Obstet. Gynec. 1969, 105, 363. 12. Maskaleris, M. L., Gross, S., Milhorat, A. T. Clin. Chem. 1969, 15, 545. 13. Matthews, D. M., Muir, G. G., Baron, D. N. J. clin. Path. 1964, 17, 150. 14. Matalon, R., Dorfman, A., Nadler, H. L., Jacobson, C. B. Lancet, 1970, i, 83. 10.
FALL OF ENDOCARDIAL POTENTIALS
AFTER ACUTE MYOCARDIAL INFARCTION KANU
CHATTERJEE *
ALAN HARRIS St.
GEOFFREY DAVIES AUBREY LEATHAM
George’s Hospital, London S.W.1
Right ventricular endocardial potentials (E.C.P.) have been measured in twelve patients after acute myocardial infarction; endocardial electrodes had been inserted in the right Summary
ventricle for the treatment of transient atrioventricular block. The measurements have been compared with those in twenty patients with normal hæmodynamics, twenty with ventricular hypertrophy, and seven with chronic heart-block. E.C.P.S were also measured in five patients who had had open heart surgery. In all patients with infarction, irrespective of site, rhythm, or clinical state, the potential in the acute phase was significantly lower than at the time of recovery, and in some with severe hæmodynamic disturbances the potential was very much lower than normal. In the survivors, the potential increased gradually, sometimes long after clinical improvement. Conventional external electrocardiograms did not usually show the *
Present address: Cardiac Department, Brompton S.W.3.
Hospital, London
1309
variations observed in the E.C.P. Similar transient changes occurred in patients having open heart surgery
under
deep
hypothermia.
The
precise
TABLE I-E.C.P. (RECORDED FROM R.V. APEX) IN PATIENTS WITH NORMAL HNMODYNAAUCS AND WITH NO CLINICAL OR E.C.G. EVIDENCE OF VENTRICULAR HYPERTROPHY
mechanism remains obscure, but the fall of potential after infarction is of great practical importance when a demand pacing system has been installed and may
inappropriate
cause
ventricular
stimulation
with
increased risk of ventricular fibrillation. Introduction TRANSIENT falls in the amplitude of right ventricular
endocardial
potential (R.v. E.C.P.) were reported in patients with acute myocardial infarction complicated by heart-block.1,2 Since this fall in amplitude sometimes resulted in inappropriate stimulation by a demand pacemaker, thereby increasing the risk of ventricular fibrillation, and since the fall in E.C.P. was unexplained and not necessarily accompanied by similar changes in conventional external electrocardiograms (E.c.G.), we decided to monitor these potentials in patients with acute myocardial infarction and compared them with the findings in patients with normal hxmodynamics and in patients with ventricular hypertrophy, chronic heart-block, or after cardiac some
surgery. Of
fifty-nine
Patients and Methods patients investigated twelve had transient
block complicating acute myocardial infarction, diagnosed by characteristic E.c.G. changes and elevated serum-enzyme levels, and referred for temporary transvenous endocardial pacings. Forty patients with valve disease, suspected pulmonary embolism, or atypical chest pain, were investigated during routine cardiac catheterisation (twenty with normal hasmodynamics and no clinical or E.c.G. evidence of ventricular hypertrophy and twenty with both clinical and E.C.G. evidence of ventricular hypertrophy). Seven patients had chronic atrioventricular block and were investigated during the installation of permanent endocardial pacing systems. Five of these fifty-nine patients were investigated before and immediately after open heart surgery. The endocardial E.c.G.s were recorded by connecting the V chest lead of a standard electrocardiograph with the free end of an endocardial electrode passed transvenously into the right ventricle (R.v.) for pacing for atrioventricular block or during right heart catheterisation. In five patients, records were also obtained from the left ventricle (L.v.) during routine cardiac catheterisation, the electrode having been introduced by the retrograde aortic route in four and across an atrial septal defect in one. All E.c.G.s were recorded at 25 mm. per second paper speed with the The standardisation varied from 0-25 Cll1.=lmV to 1 cm=lmV. The E.C.P. was defined as the total deflection of QRS (without s-T) in mV, and the measurement taken was the average of ten complexes showing an S-T elevation contact pattern.3 To study variations in amplitudes of the E.C.P. in different sites, the electrode was positioned in the outflow, inflow, and apical regions of the R.v. in twenty-one patients during routine cardiac catheterisation, and the amplitudes were compared. Variations in the voltages of the consecutive QRS complexes when recorded from the same site without changing the electrode position were measured from 63 endocardial E.C.G.s (at least 20 consecutive complexes) from twenty-one patients. Daily variations of E.C.P. in patients with normal hæmodynamics could not be measured because the electrode was not kept in situ for more than a few minutes, but in eleven patients requiring temporary electrode insertion for treatment of transient heart-block (nine after heartblock and two following surgery) E.C.P.S were recorded for
I.H.D.=Ischæmic heartS.P.E. =Suspected pulmonary embolism. disease. M.S. =Mitral stenosis. p.s.=Pu!monary stenosis. v.S.D.= Ventricular-septal defect. A.S.D.=Atrial septal defect. M.H.= Mitral homograft (postoperative results). *= Children.
5-10 days when the patients hsemodynamic state. R.v.
and
endocardial
L.v.
were
clinically in
E.C.G.S were
a constant
recorded from
comparable sites in five patients by positioning the electrode in the outflow and apical regions of both right and left ventricles of the same patients, and the amplitudes were compared. For comparative studies the potentials from the apical region have been used since these are normally the greatest and this is the site used for endocardial pacing. Results " Control Series
"
The results for patients with normal or constant illustrate the range and variation of R.v. endocardial potentials. E.c.p.s recorded from the apex of the right ventricle in eighteen adults and two children with normal haemodynamics averaged 9-5 mV (S.D.±2.8) and, in all but one, lay between 6 and 13 mV (table i). In twenty patients with both clinical and E.C.G. evidence of ventricular hypertrophy (table II) R.v. endocardial potentials recorded from the apical region ranged between 13 and 24 mV (mean of 16633 mV) which is significantly higher than normal (P< 0-0001). Of seven patients with chronic heart-block without recent
hæmodynamics
TABLE II-E.C.P.
(RECORDED
FROM R.V.
APEX)
IN PATIENTS WITH
VENTRICULAR HYPERTROPHY
patient supine.
L.V.H. = Left ventricular hypertrophy. R.V.H. =Right ventricular hypertrophy. A.S. -Aortic stenosis. A.R. =Aortic regurgitation. M.R. _ Mitral regurgitation. B.A.s.D. =Eisenmenger atrial septal defect. Hyp. =Hypertension. Pulm. hyp. =Pulmonary hypertension.
1310 TABLE III-ENDOCARDIAL POTENTIAL RECORDED FROM R.V. APEX IN PATIENTS WITH CHRONIC HEART-BLOCK
TABLE V-VARIATIONS IN E.C.P. ACCORDING TO SITES OF RECORDING IN 20 PATIENTS
TABLE IV-VARIATIONS IN E.C.P. AT THE SAME TIME
(FROM
63
RECORDS)
Stokes-Adams attacks, potentials were within the normal range in six and high (20 mV) in one with clinical left ventricular hypertrophy (table III). Daily variations of the endocardial potentials recorded from the same site in eleven patients with apparently constant hxmodynamics were less than 1-5 mV (range 0.4-1.4 mV) except in one with left ventricular hypertrophy and very high potential (variation 2-4 mV). Variations in the amplitude of consecutive QRS complexes recorded from the same endocardial site averaged 4-9% (range 1-1-16%), and in 56 of 63 records analysed the maximum variation was less than 1-5 mV (table IV). These slight variations were mainly
related to deep breathing. Variations in the voltages of endocardial potentials when recorded from different sites of R.v. in twenty patients are shown in table v. There were considerable differences in the amplitude in some patients and in most (75%) the maximum amplitude was recorded from the apical region. E.C.P. amplitudes recorded from comparable sites in the right and left ventricles of the same patient are similar (table vi) even with hypertrophy of one or both ventricles. Acute
Myocardial Infarction
- The R.v. E.C.P.S were investigated in twelve patients after acute myocardial infarction complicated by transient heart-block and requiring temporary trans-
E.C.P. recorded at R.v. apex in fifteen patients (75%), outflow in four (20%), and inflow tract in one.
Highest tract
TABLE VI-COMPARISON OF THE E.C.P.’S FROM THE RIGHT AND LEFT VENTRICULES IN THE SAME PATIENT
endocardial pacing, thus giving the opportunity for measurement of E.C.P. through the course of their treatment (table vn, fig. 1). In four of these patients R.v. E.c.p.s were remeasured 2-18 months after recovery. In all patients, the E.C.P. at the time of admission (i.e., at the acute stage of infarction) was significantly lower (n<0.005) than at the time of discharge or follow-up after recovery. Of twelve patients, venous
TABLE VII-R.V. E.C.P.S IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION COMPLICATED BY A-V BLOCK
In survivors the E.C.P. on admission was mean 5233 mV and at discharge or follow-up, mean 115 ±4.8 mV-significantly higher as compared with the potential on admission (p<0.005). Inf.=Inferior infarct. Ant. =Anterior infarct. H.F.+=Mild heart-failure. H.F. + +=Severe heart-failure. Shock 0 =No shock Shock+= Mild shock. Shock +-)--= Severe shock. * Explained in the text. Figures in italics indicate approximately how many days or months after the onset of infarct the E.C.P.S were recorded.
1311
complicated by heart-block, had an E.C.P. of 4-8 mV at the time of admission when he was not in shock or heart-failure. In the next 24 hours severe heart-failure developed, and the E.c.p. dropped to 09 mV, which was less than the sensitivity of the " demand " pacemaker and permitted inappropriate stimulation (fig. 2). Electrode displacement had to be excluded by repositioning and E.C.P. was found to be low throughout the right ventricle (fig. 2). In three patients with shock and heart-failure E.c.p. dropped about a tenth of normal, and became less than the potential recorded in external E.C.G.S (figs. 2 and 3). In two patients with low E.C.P., administration of intravenous calcium, glucose, potassium, and insulin and small doses of isoprenaline did not produce any significant change. In one patient, correction of hypoxia did not influence the amplitude of the E.c.p. The effect of intravenous digitalis has not been tried although several patients received oral digitalis which did not produce any immediate significant change. In survivors, the amplitude of the E.c.p. slowly increased, reaching the normal range within 1-2 weeks, sometimes long after apparent clinical improvement. In two with acute 1—Potentials and clinical features of twelve patients Fig. myocardial infarcts. patients, the E.C.P. was low even at the time of discharge from hospital, but had returned had anterior seven inferior six to normal a few months later (fig. 1). five and infarction, had mild heart-failure, and six had both shock and Open Heart Surgery Nine patients who survived severe heart-failure. In four patients who had aortic-valve replacement returned to a sinus rhythm in 2-5 days. No correlaunder deep hypothermia, the R.v. E.C.P.S were recorded tion was found between the amplitude of the R.v. E.C.P. before, during, and after the operation. In all patients, and site of infarction or the rhythm. However, the the E.c.p. in the immediate postoperative period patients with shock and heart-failure had much lower potentials than those with slight hsemodynamic disturbances, and three patients who died in severe shock and heart-failure had extremely low potentials. One patient (no. 54, table vu) with inferior infarction to
Fig. 3-Serial
Fig. 2-Serial an
external E.C.G. and R.V. E.C.P. of inferior infarct.
a
patient with
On April 12, 1968, the records showed inappropriate pacing (P) to failure to inhibit the pacemaker because of low endocardial potential. By Sept. 15, 1969, the E.C.P. had returned to
due
normal.
E.C.P. and external E.C.G. measurements after
myocardial infarction. During the acute phase after a myocardial infarct the E.C.P. fell and was still low on day 14. A normal potential was recorded 18 months later. The external E.C.G. potential was higher than the E.C.P. between the 2nd and 6th days. I=Lead 1. R.v.=Endocardial potential. V2=Lead V2.
1312 the haemodynamic disturbance and the degree of fall of the E.C.P., but return of the potential to the normal range did not coincide with improvement in the haemodynamic state, the potential remaining low in some patients as long as 3 weeks after clinical
improvement.
Fig. 4-Preoperative
and
postoperative
R.V. E.C.P.s in five
patients undergoing cardiac surgery. The patient represented by open circles had a Vineberg procedure and there was no change in the R.V. E.C.P.; all the others had open heart surgery under profound hypothermia and showed striking change in R.v. E.c.p. The patient presented by solid triangle showed a low R.v. E.c.p. when he developed heartfailure 20 days after surgery.
significantly low, and gradually increased to the preoperative value in 24-48 hours (fig. 4). In one patient, who developed severe heartfailure a few days postoperatively, the amplitude of the E.C.P. became low again, but it increased in the next few days as the heart-failure diminished (fig. 4). In one patient having a revascularisation operation for coronary-artery disease, not requiring hypothermia and cardiac arrest, the E.C.P. amplitude did not fluctuate significantly (fig. 4). became almost
Discussion without ventricular
hypertrophy and relatively normal hæmodynamics, R.v. E.C.P.s were usually within the range of 6-13 mV, and maximal at the apex, as reported in normal subjects by Bertrand et awl.4 In patients with ventricular hypertrophy, much higher potentials were recorded. The amplitude of R.v. endocardial potential remained relatively constant when recorded from the same site in patients with constant haemodynamics. There was In
patients
with normal,
some
or
variation with different sites in the R.v.,
as
reported previously.4,5 In twelve patients with acute myocardial infarction, the R.v. was invariably lower at the acute stage than at the time of recovery, and in six it was reduced to 2 mV or less-much lower than in patients with normal haemodynamics. The low potentials were not related to heart-block since they remained low after return to sinus rhythm, nor to the site of infarction. There seemed to be a relation between the severity of
A low R.v. E.C.P. was not specific to infarction since it was noted in the immediate postoperative period after open heart surgery under deep hypothermia; however, in these patients the potential returned much more rapidly to the preoperative range (24-48 hours). In one patient the E.C.P. fell when severe heartfailure developed a few days postoperatively. Thus the mechanism of the fall in R.v. E.C.P. remains obscure and is not solely related to myocardial infarction. It is possible that a fall in endocardial perfusion preferentially reduced the potential since external potentials recorded by a conventional E.c.G. may remain unchanged. The practical importance of the fall of E.c.p. after infarction, lies in the use of demand pacing if atrioventricular block ensues. Failure of inhibition of the pacemaker may lead to inappropriate stimulation and ventricular fibrillation. In such patients, especially those with shock and heart-failure, E.C.P.S should be checked daily. If the potential is reduced to a level near the minimum required for inhibition, it is probably safer to use fixed-rate pacing at a fast rate to reduce the chance of competition, and at the same time it is essential to check that adequate suppressant drugs are
being given.s
We thank Mr. Charles Drew and Mr. Harold Siddons for
permitting us to investigate patients under their care. Requests for reprints should be addressed to A. L. REFERENCES 1. 2. 3.
4. 5. 6.
Chatterjee, K., Sutton, R., Davies, J. G. Lancet, 1968, i, 511. Parker, B., Furman, S., Escher, D. W. J. Ann. N.Y. Acad. Sci. 1968, 167, 823. Levine, D. H., Hellems, H. K., Dexter, L., Tucker, S. A. Am. Heart J. 1949, 37, 64. Bertrand, C. A., Zohman, L. R., Williams, M. H. Am. J. Med. 1959, 25, 534. Kossman, C. E., Bergen, A. R., Rader, B., Brumick, J., Briller, S. A., Donelly, J. H. Circulation, 1950, 2, 10. Chatterjee, K., Harris, A., Leatham, A. Lancet, 1969, ii, 1061.
OVARIAN SUPPRESSANTS IN DOGS PILOT STUDY OF AN APPROACH TO RABIES CONTROL
CHAMROON YASMUTH
TIMOTHY O. ROWE
THEODORE C. DOEGE
HATCHA NA BANGXANG Department of Preventive Medicine and Illinois Project, Chiang Mai University, Chiang Mai, Thailand
controlled trial among 60 bitches villages in northern Thailand, 100 mg. (2 ml.) subcutaneous doses of medroxyprogesterone acetate significantly reduced the number of litters born over a 14-month period. The efficacy of this ovarian suppressant in preventing dog reproduction was 81%. The agent appears to offer promise in limiting the canine reservoir and vector populations, especially in countries such as Thailand where rabies is endemic. Summary
In of
a
two
Chertsey, Surrey) with sodium-citrate buffers and the column temperature programmed for 300C and 60°C. Norleucine was used as an internal standard in each analysis. Recovery-rates
were determined separately for each The mean recovery-rate was 98-3% (range, 92-3-105-5%). The coefficient of variation for ten replicate determinations on the same sample of amniotic fluid ranged from 2-4 to 10-1% for different aminoacids with a mean of 6-7%. These results are comparable to those reported by other investigators with ion-exchange
aminoacid.
chromatography.10-12 Results for glutamine
and glutamic acid are reported with reservation since some samples of fluid had been stored before analysis, and the concentrations of these aminoacids may be affected even when samples are deproteinised and then stored at —68°C.10 Values for &bgr;-aminoisobutyric acid are not reported because this was present in only trace amounts ( < 0-04 mg. per 100 ml.). Values for ex-amino nitrogen were determined by a colorimetric ninhydrin method.13 Results
So far we have been able to identify 27 aminoacids and related compounds in human amniotic fluid. Results for all except &bgr;-amino-isobutyric acid are shown in the accompanying table. There is very close agreement between the values for the period 37-40 weeks and those obtained by more recent investigators who have studied amniotic fluid at term. 6,7a
Great Britain.
Requests
for
reprints should
be addressed to A. E. H. E.
REFERENCES
4. 5. 6.
Nelson, M. M., Emery, A. E. H. Br. med. J. 1970, i, 523. Emery, A. E. H. in Modern Trends in Human Genetics (edited by A. E. H. Emery); p. 267. London, 1970. Orlandi, C., Torsello, R. V., Bottiglioni, F. Attual. Ostet. Ginec. 1958, 4, 871. Wirtschafter, Z. T. Am. J. Obstet. Gynec. 1958, 76, 1219. Sassi, D. Monitore Ostet-Ginec. Endocr. Metab. 1962, 33, 683. Spackman, D. H. Technicon Monograph no. 3; p. 40. Geneva,
7. 8. 9.
Levy, H. L., Montag, P. P. Pediat. Res. 1969, 3, 113. Perry, T. L., Hansen, S. Clin. chim. Acta, 1969, 25, 53. Hamilton, P. B. in Technicon Monograph no. 3; p. 52. Geneva,
1. 2. 3.
1968.
1968.
There seem to be three patterns of change in the aminoacid composition of amniotic fluid at various stages of pregnancy. Firstly, the concentrations of some aminoacids remain more or less the same throughout pregnancy--e.g., cysteic acid phosphoethanolamine, ethanolamine, and proline. Secondly, the concentrations of other aminoacids decrease progressively from the first trimester and throughout the remainder of pregnancy-e.g., serine, glycine, phenylalanine, lysine, and arginine. Thirdly, the remaining aminoacids appear to have a lower concentration in the first trimester than in the period 13-16 weeks, but thereafter their concentrations decrease as pregnancy progresses. In most cases concentration rises in the last month of pregnancy. In early pregnancy (13-16 weeks) the concentrations of most aminoacids are greater in amniotic fluid than in neonatal or adult plasma (see table). However, at term, except for taurine and ethanolamine, the concentrations of all aminoacids in amniotic fluid are less than in neonatal or adult plasma. Some small, as yet unidentified, peaks have occasionally been observed in some samples of amniotic fluid. Three unidentified peaks have occurred fairly consistently, their positions on chromatograms being just after alanine, just before valine, and between ammonia and ornithine. Should any of these peaks be found in apparently increased amounts in a fetus at risk from a genetic disorder, then their identification would be important. This aspect of the problem is being further
investigated. Discussion
study 27 aminoacids and related been identified in amniotic fluid. have compounds The concentrations of these substances at various stages of pregnancy are presented in the hope that the In the present
information may be useful in antenatal diagnosis. It seems likely that changes in the aminoacid composition of amniotic fluid may prove diagnostic in such conditions as cystinuria, glycinuria, and Hartnup’s disease. Matalon et al.14 have reported that they have successfully diagnosed Hurler’s syndrome in utero by demonstrating a significantly raised level of acid mucopolysaccharides in amniotic fluid as early as the 14th week of gestation. The antenatal diagnosis of at least some genetic disorders associated with changes in urinary composition, by the biochemical analysis of amniotic fluid, therefore seems a distinct possibility. We acknowledge the technical assistance of Miss Helen Stein and Mr. A. Anderson. We also thank Dr. J. G. Robertson for his help in obtaining specimens of amniotic fluid in mid-pregnancy. This work was supported by research grants from the Secretary of State for Scotland and the Muscular Dystrophy Group of
Dickinson, J. C., Rosenblum, H., Hamilton, P. B. Pediatrics, Springfield, 1965, 36, 2. 11. Kerr, G. R., Kenna, A. L. Am. J. Obstet. Gynec. 1969, 105, 363. 12. Maskaleris, M. L., Gross, S., Milhorat, A. T. Clin. Chem. 1969, 15, 545. 13. Matthews, D. M., Muir, G. G., Baron, D. N. J. clin. Path. 1964, 17, 150. 14. Matalon, R., Dorfman, A., Nadler, H. L., Jacobson, C. B. Lancet, 1970, i, 83. 10.
FALL OF ENDOCARDIAL POTENTIALS
AFTER ACUTE MYOCARDIAL INFARCTION KANU
CHATTERJEE *
ALAN HARRIS St.
GEOFFREY DAVIES AUBREY LEATHAM
George’s Hospital, London S.W.1
Right ventricular endocardial potentials (E.C.P.) have been measured in twelve patients after acute myocardial infarction; endocardial electrodes had been inserted in the right Summary
ventricle for the treatment of transient atrioventricular block. The measurements have been compared with those in twenty patients with normal hæmodynamics, twenty with ventricular hypertrophy, and seven with chronic heart-block. E.C.P.S were also measured in five patients who had had open heart surgery. In all patients with infarction, irrespective of site, rhythm, or clinical state, the potential in the acute phase was significantly lower than at the time of recovery, and in some with severe hæmodynamic disturbances the potential was very much lower than normal. In the survivors, the potential increased gradually, sometimes long after clinical improvement. Conventional external electrocardiograms did not usually show the *
Present address: Cardiac Department, Brompton S.W.3.
Hospital, London
1309
variations observed in the E.C.P. Similar transient changes occurred in patients having open heart surgery
under
deep
hypothermia.
The
precise
TABLE I-E.C.P. (RECORDED FROM R.V. APEX) IN PATIENTS WITH NORMAL HNMODYNAAUCS AND WITH NO CLINICAL OR E.C.G. EVIDENCE OF VENTRICULAR HYPERTROPHY
mechanism remains obscure, but the fall of potential after infarction is of great practical importance when a demand pacing system has been installed and may
inappropriate
cause
ventricular
stimulation
with
increased risk of ventricular fibrillation. Introduction TRANSIENT falls in the amplitude of right ventricular
endocardial
potential (R.v. E.C.P.) were reported in patients with acute myocardial infarction complicated by heart-block.1,2 Since this fall in amplitude sometimes resulted in inappropriate stimulation by a demand pacemaker, thereby increasing the risk of ventricular fibrillation, and since the fall in E.C.P. was unexplained and not necessarily accompanied by similar changes in conventional external electrocardiograms (E.c.G.), we decided to monitor these potentials in patients with acute myocardial infarction and compared them with the findings in patients with normal hxmodynamics and in patients with ventricular hypertrophy, chronic heart-block, or after cardiac some
surgery. Of
fifty-nine
Patients and Methods patients investigated twelve had transient
block complicating acute myocardial infarction, diagnosed by characteristic E.c.G. changes and elevated serum-enzyme levels, and referred for temporary transvenous endocardial pacings. Forty patients with valve disease, suspected pulmonary embolism, or atypical chest pain, were investigated during routine cardiac catheterisation (twenty with normal hasmodynamics and no clinical or E.c.G. evidence of ventricular hypertrophy and twenty with both clinical and E.C.G. evidence of ventricular hypertrophy). Seven patients had chronic atrioventricular block and were investigated during the installation of permanent endocardial pacing systems. Five of these fifty-nine patients were investigated before and immediately after open heart surgery. The endocardial E.c.G.s were recorded by connecting the V chest lead of a standard electrocardiograph with the free end of an endocardial electrode passed transvenously into the right ventricle (R.v.) for pacing for atrioventricular block or during right heart catheterisation. In five patients, records were also obtained from the left ventricle (L.v.) during routine cardiac catheterisation, the electrode having been introduced by the retrograde aortic route in four and across an atrial septal defect in one. All E.c.G.s were recorded at 25 mm. per second paper speed with the The standardisation varied from 0-25 Cll1.=lmV to 1 cm=lmV. The E.C.P. was defined as the total deflection of QRS (without s-T) in mV, and the measurement taken was the average of ten complexes showing an S-T elevation contact pattern.3 To study variations in amplitudes of the E.C.P. in different sites, the electrode was positioned in the outflow, inflow, and apical regions of the R.v. in twenty-one patients during routine cardiac catheterisation, and the amplitudes were compared. Variations in the voltages of the consecutive QRS complexes when recorded from the same site without changing the electrode position were measured from 63 endocardial E.C.G.s (at least 20 consecutive complexes) from twenty-one patients. Daily variations of E.C.P. in patients with normal hæmodynamics could not be measured because the electrode was not kept in situ for more than a few minutes, but in eleven patients requiring temporary electrode insertion for treatment of transient heart-block (nine after heartblock and two following surgery) E.C.P.S were recorded for
I.H.D.=Ischæmic heartS.P.E. =Suspected pulmonary embolism. disease. M.S. =Mitral stenosis. p.s.=Pu!monary stenosis. v.S.D.= Ventricular-septal defect. A.S.D.=Atrial septal defect. M.H.= Mitral homograft (postoperative results). *= Children.
5-10 days when the patients hsemodynamic state. R.v.
and
endocardial
L.v.
were
clinically in
E.C.G.S were
a constant
recorded from
comparable sites in five patients by positioning the electrode in the outflow and apical regions of both right and left ventricles of the same patients, and the amplitudes were compared. For comparative studies the potentials from the apical region have been used since these are normally the greatest and this is the site used for endocardial pacing. Results " Control Series
"
The results for patients with normal or constant illustrate the range and variation of R.v. endocardial potentials. E.c.p.s recorded from the apex of the right ventricle in eighteen adults and two children with normal haemodynamics averaged 9-5 mV (S.D.±2.8) and, in all but one, lay between 6 and 13 mV (table i). In twenty patients with both clinical and E.C.G. evidence of ventricular hypertrophy (table II) R.v. endocardial potentials recorded from the apical region ranged between 13 and 24 mV (mean of 16633 mV) which is significantly higher than normal (P< 0-0001). Of seven patients with chronic heart-block without recent
hæmodynamics
TABLE II-E.C.P.
(RECORDED
FROM R.V.
APEX)
IN PATIENTS WITH
VENTRICULAR HYPERTROPHY
patient supine.
L.V.H. = Left ventricular hypertrophy. R.V.H. =Right ventricular hypertrophy. A.S. -Aortic stenosis. A.R. =Aortic regurgitation. M.R. _ Mitral regurgitation. B.A.s.D. =Eisenmenger atrial septal defect. Hyp. =Hypertension. Pulm. hyp. =Pulmonary hypertension.
1310 TABLE III-ENDOCARDIAL POTENTIAL RECORDED FROM R.V. APEX IN PATIENTS WITH CHRONIC HEART-BLOCK
TABLE V-VARIATIONS IN E.C.P. ACCORDING TO SITES OF RECORDING IN 20 PATIENTS
TABLE IV-VARIATIONS IN E.C.P. AT THE SAME TIME
(FROM
63
RECORDS)
Stokes-Adams attacks, potentials were within the normal range in six and high (20 mV) in one with clinical left ventricular hypertrophy (table III). Daily variations of the endocardial potentials recorded from the same site in eleven patients with apparently constant hxmodynamics were less than 1-5 mV (range 0.4-1.4 mV) except in one with left ventricular hypertrophy and very high potential (variation 2-4 mV). Variations in the amplitude of consecutive QRS complexes recorded from the same endocardial site averaged 4-9% (range 1-1-16%), and in 56 of 63 records analysed the maximum variation was less than 1-5 mV (table IV). These slight variations were mainly
related to deep breathing. Variations in the voltages of endocardial potentials when recorded from different sites of R.v. in twenty patients are shown in table v. There were considerable differences in the amplitude in some patients and in most (75%) the maximum amplitude was recorded from the apical region. E.C.P. amplitudes recorded from comparable sites in the right and left ventricles of the same patient are similar (table vi) even with hypertrophy of one or both ventricles. Acute
Myocardial Infarction
- The R.v. E.C.P.S were investigated in twelve patients after acute myocardial infarction complicated by transient heart-block and requiring temporary trans-
E.C.P. recorded at R.v. apex in fifteen patients (75%), outflow in four (20%), and inflow tract in one.
Highest tract
TABLE VI-COMPARISON OF THE E.C.P.’S FROM THE RIGHT AND LEFT VENTRICULES IN THE SAME PATIENT
endocardial pacing, thus giving the opportunity for measurement of E.C.P. through the course of their treatment (table vn, fig. 1). In four of these patients R.v. E.c.p.s were remeasured 2-18 months after recovery. In all patients, the E.C.P. at the time of admission (i.e., at the acute stage of infarction) was significantly lower (n<0.005) than at the time of discharge or follow-up after recovery. Of twelve patients, venous
TABLE VII-R.V. E.C.P.S IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION COMPLICATED BY A-V BLOCK
In survivors the E.C.P. on admission was mean 5233 mV and at discharge or follow-up, mean 115 ±4.8 mV-significantly higher as compared with the potential on admission (p<0.005). Inf.=Inferior infarct. Ant. =Anterior infarct. H.F.+=Mild heart-failure. H.F. + +=Severe heart-failure. Shock 0 =No shock Shock+= Mild shock. Shock +-)--= Severe shock. * Explained in the text. Figures in italics indicate approximately how many days or months after the onset of infarct the E.C.P.S were recorded.
1311
complicated by heart-block, had an E.C.P. of 4-8 mV at the time of admission when he was not in shock or heart-failure. In the next 24 hours severe heart-failure developed, and the E.c.p. dropped to 09 mV, which was less than the sensitivity of the " demand " pacemaker and permitted inappropriate stimulation (fig. 2). Electrode displacement had to be excluded by repositioning and E.C.P. was found to be low throughout the right ventricle (fig. 2). In three patients with shock and heart-failure E.c.p. dropped about a tenth of normal, and became less than the potential recorded in external E.C.G.S (figs. 2 and 3). In two patients with low E.C.P., administration of intravenous calcium, glucose, potassium, and insulin and small doses of isoprenaline did not produce any significant change. In one patient, correction of hypoxia did not influence the amplitude of the E.c.p. The effect of intravenous digitalis has not been tried although several patients received oral digitalis which did not produce any immediate significant change. In survivors, the amplitude of the E.c.p. slowly increased, reaching the normal range within 1-2 weeks, sometimes long after apparent clinical improvement. In two with acute 1—Potentials and clinical features of twelve patients Fig. myocardial infarcts. patients, the E.C.P. was low even at the time of discharge from hospital, but had returned had anterior seven inferior six to normal a few months later (fig. 1). five and infarction, had mild heart-failure, and six had both shock and Open Heart Surgery Nine patients who survived severe heart-failure. In four patients who had aortic-valve replacement returned to a sinus rhythm in 2-5 days. No correlaunder deep hypothermia, the R.v. E.C.P.S were recorded tion was found between the amplitude of the R.v. E.C.P. before, during, and after the operation. In all patients, and site of infarction or the rhythm. However, the the E.c.p. in the immediate postoperative period patients with shock and heart-failure had much lower potentials than those with slight hsemodynamic disturbances, and three patients who died in severe shock and heart-failure had extremely low potentials. One patient (no. 54, table vu) with inferior infarction to
Fig. 3-Serial
Fig. 2-Serial an
external E.C.G. and R.V. E.C.P. of inferior infarct.
a
patient with
On April 12, 1968, the records showed inappropriate pacing (P) to failure to inhibit the pacemaker because of low endocardial potential. By Sept. 15, 1969, the E.C.P. had returned to
due
normal.
E.C.P. and external E.C.G. measurements after
myocardial infarction. During the acute phase after a myocardial infarct the E.C.P. fell and was still low on day 14. A normal potential was recorded 18 months later. The external E.C.G. potential was higher than the E.C.P. between the 2nd and 6th days. I=Lead 1. R.v.=Endocardial potential. V2=Lead V2.
1312 the haemodynamic disturbance and the degree of fall of the E.C.P., but return of the potential to the normal range did not coincide with improvement in the haemodynamic state, the potential remaining low in some patients as long as 3 weeks after clinical
improvement.
Fig. 4-Preoperative
and
postoperative
R.V. E.C.P.s in five
patients undergoing cardiac surgery. The patient represented by open circles had a Vineberg procedure and there was no change in the R.V. E.C.P.; all the others had open heart surgery under profound hypothermia and showed striking change in R.v. E.c.p. The patient presented by solid triangle showed a low R.v. E.c.p. when he developed heartfailure 20 days after surgery.
significantly low, and gradually increased to the preoperative value in 24-48 hours (fig. 4). In one patient, who developed severe heartfailure a few days postoperatively, the amplitude of the E.C.P. became low again, but it increased in the next few days as the heart-failure diminished (fig. 4). In one patient having a revascularisation operation for coronary-artery disease, not requiring hypothermia and cardiac arrest, the E.C.P. amplitude did not fluctuate significantly (fig. 4). became almost
Discussion without ventricular
hypertrophy and relatively normal hæmodynamics, R.v. E.C.P.s were usually within the range of 6-13 mV, and maximal at the apex, as reported in normal subjects by Bertrand et awl.4 In patients with ventricular hypertrophy, much higher potentials were recorded. The amplitude of R.v. endocardial potential remained relatively constant when recorded from the same site in patients with constant haemodynamics. There was In
patients
with normal,
some
or
variation with different sites in the R.v.,
as
reported previously.4,5 In twelve patients with acute myocardial infarction, the R.v. was invariably lower at the acute stage than at the time of recovery, and in six it was reduced to 2 mV or less-much lower than in patients with normal haemodynamics. The low potentials were not related to heart-block since they remained low after return to sinus rhythm, nor to the site of infarction. There seemed to be a relation between the severity of
A low R.v. E.C.P. was not specific to infarction since it was noted in the immediate postoperative period after open heart surgery under deep hypothermia; however, in these patients the potential returned much more rapidly to the preoperative range (24-48 hours). In one patient the E.C.P. fell when severe heartfailure developed a few days postoperatively. Thus the mechanism of the fall in R.v. E.C.P. remains obscure and is not solely related to myocardial infarction. It is possible that a fall in endocardial perfusion preferentially reduced the potential since external potentials recorded by a conventional E.c.G. may remain unchanged. The practical importance of the fall of E.c.p. after infarction, lies in the use of demand pacing if atrioventricular block ensues. Failure of inhibition of the pacemaker may lead to inappropriate stimulation and ventricular fibrillation. In such patients, especially those with shock and heart-failure, E.C.P.S should be checked daily. If the potential is reduced to a level near the minimum required for inhibition, it is probably safer to use fixed-rate pacing at a fast rate to reduce the chance of competition, and at the same time it is essential to check that adequate suppressant drugs are
being given.s
We thank Mr. Charles Drew and Mr. Harold Siddons for
permitting us to investigate patients under their care. Requests for reprints should be addressed to A. L. REFERENCES 1. 2. 3.
4. 5. 6.
Chatterjee, K., Sutton, R., Davies, J. G. Lancet, 1968, i, 511. Parker, B., Furman, S., Escher, D. W. J. Ann. N.Y. Acad. Sci. 1968, 167, 823. Levine, D. H., Hellems, H. K., Dexter, L., Tucker, S. A. Am. Heart J. 1949, 37, 64. Bertrand, C. A., Zohman, L. R., Williams, M. H. Am. J. Med. 1959, 25, 534. Kossman, C. E., Bergen, A. R., Rader, B., Brumick, J., Briller, S. A., Donelly, J. H. Circulation, 1950, 2, 10. Chatterjee, K., Harris, A., Leatham, A. Lancet, 1969, ii, 1061.
OVARIAN SUPPRESSANTS IN DOGS PILOT STUDY OF AN APPROACH TO RABIES CONTROL
CHAMROON YASMUTH
TIMOTHY O. ROWE
THEODORE C. DOEGE
HATCHA NA BANGXANG Department of Preventive Medicine and Illinois Project, Chiang Mai University, Chiang Mai, Thailand
controlled trial among 60 bitches villages in northern Thailand, 100 mg. (2 ml.) subcutaneous doses of medroxyprogesterone acetate significantly reduced the number of litters born over a 14-month period. The efficacy of this ovarian suppressant in preventing dog reproduction was 81%. The agent appears to offer promise in limiting the canine reservoir and vector populations, especially in countries such as Thailand where rabies is endemic. Summary
In of
a
two