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Intraventricular pressure and electrocardiographic recordings of the dying rabbit heart
INTRAVENTRICULAR RECORDINGS
PRESSURE AND ELECTROCARDIOGRAPHIC OF THE DYING RABBIT HEART
FREDERICK R. FRANKE, M.D., D.Sc. (MED.), ROBERT GEORGE, M.D., AND SHELDON COHEN, M.D. PITTSBURGH,
S.
PA.
Rhomer’s’ original work, frequent reports have been made on electroSINCE cardiographic observations during death. Turner2 presented a review of the electrocardiographic changes during death in seventy cases in which the most frequent findings were slowing of the rate and the appearance of an atrioventricular. nodal, or idioventricular rhythm. Hanson, Purks, and Anderson? reported similar changes during and after death in twenty-five cases and stated that a slow nodal rhythm occasionally occurred after the patient was clinically dead. Grieco and Schwartz4 reported a case of a patient with acute coronary thrombosis in whom electrocardiographic activity continued for twenty-eight minutes after the patient appeared to be dead. Goodrich and Needle9 and Krel16 have reported similar cases in which no evidence of life existed except that in the electrocardiogram. This study was designed to record the intracardiac pressure and the electrocardiogram in order to observe simultaneously electrical and muscular activity in the dying animal. METHODS
Intracardiac pressures and standard Lead I I electrocardiograms were simultaneously recorded on a constant speed kymograph on ten rabbits (Group I) lightly anesthetized by intravenous pentobarbital sodium. Blood pressures within the right ventricle were obtained with a No. 6 ureteral catheter introduced through the exposed right jugular vein and attached to a Statham P23A pressure transducer coupled to a 60 cycle carrier system and a high-gain stabilized amplifier which drove an Esterline-Angus 1 Ma. recorder. The transducer system was calibrated against a mercury manometer. Heparinized saline solution was used to fill the transducer and catheter system. Fatal anaphylaxis was produced by the sudden intravenous administration of 500 mg. of bovine gamma globulin (fraction II, Armour) in 10 ml. of physiological saline in five sensitized animals Similarly five anim,als after the technique of Bukantz, Johnson, and Alexander.’ were given 1.5 mg. per kilogram of body weight of histamine base as a rapid lethal dose. In each experiment the catheter position was checked at autopsy and carefully examined for patency. From the Addison H. Gibson Laboratory of the School of Medicine of the University of Pittsburgh. This project was wpported in part by a grant from the Sweh Mellon Scaife Foundation. Received for publication Au& 31. 1951. 246
FRANKE
ET
AL.:
ECG
RECORDINGS
OF
DYING
RABBIT
HEART
247
In a second group of eight rabbits weighing 4.0 to 5.0 kg. right intraventricular pressures and Lead II electrocardiograms were recorded while the heart In two animals was directly observed through a right anterior thoracotomy. ventricular contractions were recorded on a revolving smoked drum via a lever system from a small tissue hook attached to the epicardium. Catheter position was determined by palpation through the chest opening, and contractions could be observed in both auricles and the right and portions of the left ventricle. Death was produced either by exsanguination or the administration of lethal intravenous doses of pentobarbital sodium. RESULTS
In the first group of animals death came rapidly after the injection of the globulin or histamine and was marked by cessation of respiration and a transitory rise in right ventricular pressure which gradually decreased in amplitude until no ventricular pulsatile changes could be demonstrated. Prior to the disappearance of pulsatile changes the animals appeared to be clinically dead, i.e., respiration and heart beat were absent and no eye reflex could be elicited. Table I summarizes the results obtained in this group of animals. In each animal electrocardiographic activity was present after clinical death and after pulsatile recordings from the ventricle had ceased. Persistence of electrocardiographic activity after cessation of intracardiac pressure changes varied from one to twelve minutes. The electrocardiographic changes after clinical death were not constant: tachycardia or bradycardia often appeared early with ventricular irregularity, idioventricular rhythm, ventricular fibrillation, and block occurring later. Table II presents the results obtained in the second group of animals. Electrocardiographic activity was present as long as twenty-three minutes after cessation of pressure changes and for as long as eighteen minutes after myocardial contractions could no longer be observed. For varying periods of time after cessation of pulsatile changes minute superficial muscular undulations which finally stopped could be correlated with the electrocardiographic record. In animal E, after the electrocardiogram lost its ventricular complex, persistent P waves were associated with a small focal movement in the right auricle. In this series, as in Group I, each animal appeared clinica!ly dead before pressure recordings ceased. The progressive development of various arrhythmias in the absence of pulsatile activity is demonstrated in Figs. 1 and 2. The final recording (Fig. 1) appears as definite ventricular fibrillation. DISCUSSION
Origin conduction that injured tion of the
of electrical changes during death could be from either the myoneural system or from the heart muscle itself. It has been demonstrated6 nerve tissue produces an altered electrical state and partial depolarizacell membranes with a resultant hyperexcitability. Ischemic heart
i 10
-
240 180 240 210 240
6
180
6 7
3.3
11
210
I
2.2
8
240
1.3 0.5 0.7 0.9 0.7
AMPL ITI JDE OF , / PULSATION (CM.)
2.8
3.3
8
240
4.5
2
10
DIASTOLIC --
200
SYSTOLIC
___-
CONTROLRIGHTINTRAJENTRICLJLARPRESSURE (MM. Hp.)
1
CONTROL RABBI T HEaRT NO. RATE (PER MINUTE) --
zz
1.5 1.5 2.0 3.0 4.0
12.0
6.0
2.0
3.0
1.0
(MINUTES),
;
ZZ
120 270
180 60
60
60
90
100
(PER MINUTE)
FINAL HEART RATE
=
OBSERVATIONSONTHE
'URATIONOFEC( AFTER ABSENCE OF PULSATILE CHANGE
TABLE].
tachycardia
Gnus bradycardia Sinus bradycardia Pachycardia Jentricular tachycardia iuricular tachycardia (small complex)
Sinus tachycardia, then ventricular tachycardia
Sinus bradycardia
%nus mechanism; ventricular premature beats Sinus bradycardia
$entricular
IMMEDIATE ECG CHANGE
DYINGRABBITHEART
-
rhythm
A-V block; idioventricular rhythm
1Jentricufar tachycardia ‘ Sinus bradycardia 7~lntr$ar fibrillation : <: 1dentricular tachycardia (large complexes)
!:l
1[dioventricular rhythm; rare P wave 1ventricular fibrillation
1frregular ventricular complexes
1[dioventricular
LATE ECG CHANGE
persistence
persistence ! &estionable persistence ! &estionable persistence ! &testionable 1Bizarre complexes
1fntermediate period of minute complexes 2 minutes of apparent electrical inactivity
!Ijuestionable
persistence of electrical activity 3 second periods of arrest
!2uestionabIe
REMARKS
FRANKE
ET
AL.:
ECG
RECORDINGS
OF DYING
RABBIT
HEART
249
250
AMERICAN
HEART
JOURNAL
muscle has been observed” to be negative with respect to normal muscle, and a sharp electrical boundary persists at the injured area of the zone of diastolic negativity.‘O Strong catelectrotonic effects of injury potential exist in this boundary zone which have been related to ectopic ventricular excitation.” The records of electrical activity observed during death in this study may be related to similar electrical and chemical changes associated with rapid muscle and conduction system degeneration. 'GABLE
II.
=
RABBIT
DURATION OFECG AFTER ABSENCE OF PULSATILE CHANGE (MINUTES)
8.5
18.0 0.75 14.5 23.0 1.0 2.0 1.5
DURATION OFECG AFTERABSENCEOF CONTRACTIONS (MINUTES) ---__ ---~
I JISIBLE
4.0 7.5 0.75 10.0 18.0 1.0 1.5 1.5
FINAL
MECHANISM
Ventricular tachycardia Ventricular fibrillation Sinus bradycardia 4:l heart block Only P waves 3:l heart block Bradycardia A-V block; ventricular
and
fibrillation
fibrillation
Persistence of electrical complexes during the period of absent pulsatile change again demonstrates the lack of correlation between the electrocardiogram and the functional ability of heart muscle. Ventricular fibrillation as recorded may be a result rather than the cause of clinical death. SUMMARY
Eighteen experiments on the dying rabbit heart have been studied by simultaneously recorded right ventricular pressures and Lead II electrocardiograms. The persistence of electrical activity beyond apparent clinical death of the animals, demonstrable right intraventricular pulsatile changes, and visible muscular contractions has been presented. Injury potentials associated with the degenerating heart may be a factor in the production of the electrocardiographic changes. REFERENCES
1. 2. 3.
4. 5. 6.
Rhomer,
H.: Ueber das Elektrokardiogramm des Diphtherieherztodes, Mtinchen. med. Wchnschr. 58:2358, 1911. Turner, K. B.: Mechanism of Death of Human Heart as Ret&rded in Electrocardiogram, AM. HEART J. 6:743, 1931. Hanson, J. F., Purks, W. K., and Anderson, R. G.: Electrocardiographic Studies of Dying Human Heart, With Observations on Intracardiac Injection of Epinephrine, Arch. Int. Med. 51:965, 1933. Grieco, E. H., and Schwartz, S. P.: Observation on Mechanism of Dying Heart in Patient With Ventricular Tachycardia, ,4~. HEART J. 16:595, 1938. Goodrich, B. E., and Needles, R. J.: Terminal Cardiac Mechanism in Coronary Artery Disease; Report of Two Cases, AM. HEART J. 20:637, 1949. Krell, S.: Electrocardiographic Record of the Dying Heart, Ann. Int. Med. 21:903, 1944.
FRANKE
7. 8. 9.
10. 11.
Bukantz, Lorente,
ET
AL.
:
ECG
RECORDINGS
OF
DYING
RABBIT
HEART
251
S. C., Johnson, M. C., and Alexander, H. L.: Personal communication. D. R.: A Study of Nerve Physiology, Part I, New York, 1947, Rockefeller Institute for Medical Research. Bayley, R. H., La Due, J. S., and York, D. J.: Electrocardiographic Changes Produced in Dogs by Temporary Occlusion of the Coronary Artery, Showing a New Stage in Evolution of Myocardial Infarction, AM. HEART J. 27:164, 1944. Sugarman, H., Katz; L. N., Sanders, A., and Jochim, K.: Observations On the Genesis of Electrical Currents Established by Injury to the Heart, Am. J. Physiol. 130:130, 1940. Delayed Development of Ventricular Ectopic Rhythm Following ExperiHarris, A. S.: mental Coronary Occlusion, Circulation 1:1318, 1950.
PRESSURE AND ELECTROCARDIOGRAPHIC OF THE DYING RABBIT HEART
FREDERICK R. FRANKE, M.D., D.Sc. (MED.), ROBERT GEORGE, M.D., AND SHELDON COHEN, M.D. PITTSBURGH,
S.
PA.
Rhomer’s’ original work, frequent reports have been made on electroSINCE cardiographic observations during death. Turner2 presented a review of the electrocardiographic changes during death in seventy cases in which the most frequent findings were slowing of the rate and the appearance of an atrioventricular. nodal, or idioventricular rhythm. Hanson, Purks, and Anderson? reported similar changes during and after death in twenty-five cases and stated that a slow nodal rhythm occasionally occurred after the patient was clinically dead. Grieco and Schwartz4 reported a case of a patient with acute coronary thrombosis in whom electrocardiographic activity continued for twenty-eight minutes after the patient appeared to be dead. Goodrich and Needle9 and Krel16 have reported similar cases in which no evidence of life existed except that in the electrocardiogram. This study was designed to record the intracardiac pressure and the electrocardiogram in order to observe simultaneously electrical and muscular activity in the dying animal. METHODS
Intracardiac pressures and standard Lead I I electrocardiograms were simultaneously recorded on a constant speed kymograph on ten rabbits (Group I) lightly anesthetized by intravenous pentobarbital sodium. Blood pressures within the right ventricle were obtained with a No. 6 ureteral catheter introduced through the exposed right jugular vein and attached to a Statham P23A pressure transducer coupled to a 60 cycle carrier system and a high-gain stabilized amplifier which drove an Esterline-Angus 1 Ma. recorder. The transducer system was calibrated against a mercury manometer. Heparinized saline solution was used to fill the transducer and catheter system. Fatal anaphylaxis was produced by the sudden intravenous administration of 500 mg. of bovine gamma globulin (fraction II, Armour) in 10 ml. of physiological saline in five sensitized animals Similarly five anim,als after the technique of Bukantz, Johnson, and Alexander.’ were given 1.5 mg. per kilogram of body weight of histamine base as a rapid lethal dose. In each experiment the catheter position was checked at autopsy and carefully examined for patency. From the Addison H. Gibson Laboratory of the School of Medicine of the University of Pittsburgh. This project was wpported in part by a grant from the Sweh Mellon Scaife Foundation. Received for publication Au& 31. 1951. 246
FRANKE
ET
AL.:
ECG
RECORDINGS
OF
DYING
RABBIT
HEART
247
In a second group of eight rabbits weighing 4.0 to 5.0 kg. right intraventricular pressures and Lead II electrocardiograms were recorded while the heart In two animals was directly observed through a right anterior thoracotomy. ventricular contractions were recorded on a revolving smoked drum via a lever system from a small tissue hook attached to the epicardium. Catheter position was determined by palpation through the chest opening, and contractions could be observed in both auricles and the right and portions of the left ventricle. Death was produced either by exsanguination or the administration of lethal intravenous doses of pentobarbital sodium. RESULTS
In the first group of animals death came rapidly after the injection of the globulin or histamine and was marked by cessation of respiration and a transitory rise in right ventricular pressure which gradually decreased in amplitude until no ventricular pulsatile changes could be demonstrated. Prior to the disappearance of pulsatile changes the animals appeared to be clinically dead, i.e., respiration and heart beat were absent and no eye reflex could be elicited. Table I summarizes the results obtained in this group of animals. In each animal electrocardiographic activity was present after clinical death and after pulsatile recordings from the ventricle had ceased. Persistence of electrocardiographic activity after cessation of intracardiac pressure changes varied from one to twelve minutes. The electrocardiographic changes after clinical death were not constant: tachycardia or bradycardia often appeared early with ventricular irregularity, idioventricular rhythm, ventricular fibrillation, and block occurring later. Table II presents the results obtained in the second group of animals. Electrocardiographic activity was present as long as twenty-three minutes after cessation of pressure changes and for as long as eighteen minutes after myocardial contractions could no longer be observed. For varying periods of time after cessation of pulsatile changes minute superficial muscular undulations which finally stopped could be correlated with the electrocardiographic record. In animal E, after the electrocardiogram lost its ventricular complex, persistent P waves were associated with a small focal movement in the right auricle. In this series, as in Group I, each animal appeared clinica!ly dead before pressure recordings ceased. The progressive development of various arrhythmias in the absence of pulsatile activity is demonstrated in Figs. 1 and 2. The final recording (Fig. 1) appears as definite ventricular fibrillation. DISCUSSION
Origin conduction that injured tion of the
of electrical changes during death could be from either the myoneural system or from the heart muscle itself. It has been demonstrated6 nerve tissue produces an altered electrical state and partial depolarizacell membranes with a resultant hyperexcitability. Ischemic heart
i 10
-
240 180 240 210 240
6
180
6 7
3.3
11
210
I
2.2
8
240
1.3 0.5 0.7 0.9 0.7
AMPL ITI JDE OF , / PULSATION (CM.)
2.8
3.3
8
240
4.5
2
10
DIASTOLIC --
200
SYSTOLIC
___-
CONTROLRIGHTINTRAJENTRICLJLARPRESSURE (MM. Hp.)
1
CONTROL RABBI T HEaRT NO. RATE (PER MINUTE) --
zz
1.5 1.5 2.0 3.0 4.0
12.0
6.0
2.0
3.0
1.0
(MINUTES),
;
ZZ
120 270
180 60
60
60
90
100
(PER MINUTE)
FINAL HEART RATE
=
OBSERVATIONSONTHE
'URATIONOFEC( AFTER ABSENCE OF PULSATILE CHANGE
TABLE].
tachycardia
Gnus bradycardia Sinus bradycardia Pachycardia Jentricular tachycardia iuricular tachycardia (small complex)
Sinus tachycardia, then ventricular tachycardia
Sinus bradycardia
%nus mechanism; ventricular premature beats Sinus bradycardia
$entricular
IMMEDIATE ECG CHANGE
DYINGRABBITHEART
-
rhythm
A-V block; idioventricular rhythm
1Jentricufar tachycardia ‘ Sinus bradycardia 7~lntr$ar fibrillation : <: 1dentricular tachycardia (large complexes)
!:l
1[dioventricular rhythm; rare P wave 1ventricular fibrillation
1frregular ventricular complexes
1[dioventricular
LATE ECG CHANGE
persistence
persistence ! &estionable persistence ! &estionable persistence ! &testionable 1Bizarre complexes
1fntermediate period of minute complexes 2 minutes of apparent electrical inactivity
!Ijuestionable
persistence of electrical activity 3 second periods of arrest
!2uestionabIe
REMARKS
FRANKE
ET
AL.:
ECG
RECORDINGS
OF DYING
RABBIT
HEART
249
250
AMERICAN
HEART
JOURNAL
muscle has been observed” to be negative with respect to normal muscle, and a sharp electrical boundary persists at the injured area of the zone of diastolic negativity.‘O Strong catelectrotonic effects of injury potential exist in this boundary zone which have been related to ectopic ventricular excitation.” The records of electrical activity observed during death in this study may be related to similar electrical and chemical changes associated with rapid muscle and conduction system degeneration. 'GABLE
II.
=
RABBIT
DURATION OFECG AFTER ABSENCE OF PULSATILE CHANGE (MINUTES)
8.5
18.0 0.75 14.5 23.0 1.0 2.0 1.5
DURATION OFECG AFTERABSENCEOF CONTRACTIONS (MINUTES) ---__ ---~
I JISIBLE
4.0 7.5 0.75 10.0 18.0 1.0 1.5 1.5
FINAL
MECHANISM
Ventricular tachycardia Ventricular fibrillation Sinus bradycardia 4:l heart block Only P waves 3:l heart block Bradycardia A-V block; ventricular
and
fibrillation
fibrillation
Persistence of electrical complexes during the period of absent pulsatile change again demonstrates the lack of correlation between the electrocardiogram and the functional ability of heart muscle. Ventricular fibrillation as recorded may be a result rather than the cause of clinical death. SUMMARY
Eighteen experiments on the dying rabbit heart have been studied by simultaneously recorded right ventricular pressures and Lead II electrocardiograms. The persistence of electrical activity beyond apparent clinical death of the animals, demonstrable right intraventricular pulsatile changes, and visible muscular contractions has been presented. Injury potentials associated with the degenerating heart may be a factor in the production of the electrocardiographic changes. REFERENCES
1. 2. 3.
4. 5. 6.
Rhomer,
H.: Ueber das Elektrokardiogramm des Diphtherieherztodes, Mtinchen. med. Wchnschr. 58:2358, 1911. Turner, K. B.: Mechanism of Death of Human Heart as Ret&rded in Electrocardiogram, AM. HEART J. 6:743, 1931. Hanson, J. F., Purks, W. K., and Anderson, R. G.: Electrocardiographic Studies of Dying Human Heart, With Observations on Intracardiac Injection of Epinephrine, Arch. Int. Med. 51:965, 1933. Grieco, E. H., and Schwartz, S. P.: Observation on Mechanism of Dying Heart in Patient With Ventricular Tachycardia, ,4~. HEART J. 16:595, 1938. Goodrich, B. E., and Needles, R. J.: Terminal Cardiac Mechanism in Coronary Artery Disease; Report of Two Cases, AM. HEART J. 20:637, 1949. Krell, S.: Electrocardiographic Record of the Dying Heart, Ann. Int. Med. 21:903, 1944.
FRANKE
7. 8. 9.
10. 11.
Bukantz, Lorente,
ET
AL.
:
ECG
RECORDINGS
OF
DYING
RABBIT
HEART
251
S. C., Johnson, M. C., and Alexander, H. L.: Personal communication. D. R.: A Study of Nerve Physiology, Part I, New York, 1947, Rockefeller Institute for Medical Research. Bayley, R. H., La Due, J. S., and York, D. J.: Electrocardiographic Changes Produced in Dogs by Temporary Occlusion of the Coronary Artery, Showing a New Stage in Evolution of Myocardial Infarction, AM. HEART J. 27:164, 1944. Sugarman, H., Katz; L. N., Sanders, A., and Jochim, K.: Observations On the Genesis of Electrical Currents Established by Injury to the Heart, Am. J. Physiol. 130:130, 1940. Delayed Development of Ventricular Ectopic Rhythm Following ExperiHarris, A. S.: mental Coronary Occlusion, Circulation 1:1318, 1950.