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Effect of restoration of normal levels of membrane potential on ouabain toxicity in cardiac Purkinje fibers
ABSTRACTS
ANGIOGRAPHIC PATTERNS EARLY IN THE ONSET OF THE CORONARY SYNDROMES Valentin Fuster, MD; Daniel C. Connolly, MD,FACC; Robert L. Frye, MD,FACC; Margaret A. Danielson; Lila R. Elveback, PhD; Leonard T. Kurland, MD. Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Little information is available regarding angiographic patterns soon after the onset of different coronary syndromes. Coronary angiography was performed in 300 patients (pts) within one year of onset of symptoms of coronaryartery disease. 164 pts had angina pectoris alone (AP), 63 subendocardial myocardial infarction (SMI), and 73 transmural myocardial infarction (TMI). In the three groups there was an equal distribution of one, two, or three vessel disease (50% or more obstruction). The distribution of obstruction was also similar in the three groups--left anterior descending 81%, right coronary 60%, circumflex 49%, left main coronary 7%. Of the vessels not totally occluded, the degree of stenosis was also similar in the three groups. However, the percentage of vessels with total occlusion was much higher in TM1 (53%) than in the SMI (30%) or AP (24%) groups. Of the total number of diseased vessels with associated collaterals (30%), 84% were completely occluded and only 16% were not. The association of collaterals with occlusion was greater in AP (85%) and SMI (85%) than in TM1 (61%) pts. The presence of collaterals was not apparently related to duration of symptoms. Ventriculography was performed in 297 pts. Localized or diffuse reduction of contractility was present in 75% of TM1 and only in 29% of SMI and 26% of AP pts. The degree and distribution of coronary lesions could not be correlated with hypertension, cigarette smoking or elevated serum lipids in any of the three groups. In conclusion, within one year of onset of AP, SMI or TMI, angiography showed strikingly similar patterns in apart from the high incidence of vessel all three groups, occlusion and abnormal ventriculography in TMI. Coronary angiographic patterns were unrelated to risk factors in this selective group of patients.
CLINICAL
USE
MAKER.
OF AN ISOTOPIC
Andrew
Chardack,
M.D.
Veterans
capsule
contains
is converted thermocouple. mrem/hr
J.
Federico,
about
demand
150 mg
electricity Radiation
is
and found
credible
New
York
safe
The
at the
Heat
telluride
surface
is
5 mrem/hour The design
It has under
been
by
fuel
of Plutonium-238.
level
10 years. to be
type.
by a bismuth
and is expected to reach well within safety limits.
5 years, the pacemaker
M.D.
Buffalo,
3 after life of
extensively
all conditions
of
accident.
first
clinical
us in July
of
patients.
Primary
myocardial
use
1972
in the
and since
United then
installations
electrodes
to avoid
we
States have
(5) were potential
was
made
treated made
by
18 with
dislodgement,
occasionally seen with endocardiac electrodes. Replacements (13)were made with myocardial or endocardiac electrodes which had been shown to be stable. All patients have made an uneventful recovery and all pacemakers have functioned satisfactorily. At the present time, about 400 such units have been used,
mostly in Europe, pacemaker
139
and at the time of this writing,
malfunction
January 1974
has
not been
Detailed clinical and laboratory observations have shown that a great disparity may exist between the severity of coronary lesions and heart muscle damage in patients with coronary heart disease (CHD), a disparity which depends on the heart’s ability to protect jeopardized muscle through collateral circu lation. In 300 CHO patients undergoing coronary arteriography, coronary morphology was correlated with ventriculographically-observed left ventricular contractions and left ventricular dynamics measured by post-contrast injection enddiastolic pressure (EDP) and ejection fraction (EF). Single-vessel involvement did not significantly alter ventricular dynamics, except in lesions proximal to the origin of the first sepeal artery (SA); here the EDP was increased to 21+ 7 mm Hg. The incidence of left ventricular asynergy and proximal lesion aneurysm was markedly higher (43y,) than in lesions involving other vessels. Patients with triple-vessel disease showed decreased left ventricular function: lesions proximal to the first SA - EF 44+ 13.2%, EDP 28+ 8.2 mm Hg and lesions distal to the first SAY EF 48+14.3Y,,EDP 22+ 7.3 mm Hg. In this patient group, the occurrence of left vencicular aneurysms was identical to that in lesions proximal and distal to the first SA (39%). These findings clearly confirm the very important role that collateral blood flow through the septum, via either the first SA or the posterior descending system, plays in preserving myo cardium.
EFFECT OF RESTORATION OF NORMAL LEVELS OF MRMBRANE POTENTIAL ON OUABAIN TOXICITY IN CARDIAC PURKINJE FIBERS. Jeremiah M. Gelles, HD; Ronald S. Aronson, MD; Brian F. Hoffman, MD, Columbia University College of Physicians and Surgeons, New York, N.Y.
M.
pacemakers were first used in April of 1970. The Medtronic-
is of the
into
PACE-
William
Hospital,
radioisotope and Piwnica pacemaker
CARDIAC
M.D.,
and Anthony
Alcatel
The
Gage,
Administration
Long-lived Laurens
tested
A.
CORONARY PATHOLOGY AND LEFT VEmRICULAR FUNC TION IN PATIENTS WITH CORONARY HEART DISEASE Martin P. Gander, MD; Bruce Ham; Melvin P. Judkins, MD FACC Loma Linda University, Loma Linda, CA 92354
observed.
The American Journal of CARDIOLOGY
A principal manifestation of ouabaln (0) toxicity in Purkinje fibers (PP) is transmembrane depolarization presumably due to inhibition of the Na-K pump. To determine whether other manifestations of 0 toxicity derive from this principal effect, we restored the transmembrane potential (RIP) to control levels during 0 exposure and studied the effect of this maneuver on action potential (AP) parameters. A two-microelectrode technique was used. One electrode passed current while the other measured TMP. A third electrode was used for extracellular stimulation (cycle lengths 630-1300 msec). Shortened sheep cardiac PP (previously described) were superfused in vitro with Tyrode sol. (K=4.OmM; T,36oC). During 0 (2x10-TM) superfusion, polarizing current was passed intermittently to restore the TI4P to control levels. The rate of rise and overshoot of the AP returned towards control levels. Spontaneous activity that had developed during 0 toxicity was suppressed. O-induced enhanced phase 4 depolarization (P4D) was decreased. In PF that had become inexcitable, restoration of the 'IMP to control levels restored excitability. Repetitive stimulation at this time resulted in a gradual increase in P4D, escape from the stimulus, and depolarization of the fiber. These results indicate that restoring TMP to control levels can substantially ameliorate the toxic effects of 0 on the AP. In conjunction with voltage clamp experiments (previously described) these results further support the hypothesis that 0 exert8 its effects on PF by disrupting the integrity of the Aa-K PumP.
Volume 33
ANGIOGRAPHIC PATTERNS EARLY IN THE ONSET OF THE CORONARY SYNDROMES Valentin Fuster, MD; Daniel C. Connolly, MD,FACC; Robert L. Frye, MD,FACC; Margaret A. Danielson; Lila R. Elveback, PhD; Leonard T. Kurland, MD. Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Little information is available regarding angiographic patterns soon after the onset of different coronary syndromes. Coronary angiography was performed in 300 patients (pts) within one year of onset of symptoms of coronaryartery disease. 164 pts had angina pectoris alone (AP), 63 subendocardial myocardial infarction (SMI), and 73 transmural myocardial infarction (TMI). In the three groups there was an equal distribution of one, two, or three vessel disease (50% or more obstruction). The distribution of obstruction was also similar in the three groups--left anterior descending 81%, right coronary 60%, circumflex 49%, left main coronary 7%. Of the vessels not totally occluded, the degree of stenosis was also similar in the three groups. However, the percentage of vessels with total occlusion was much higher in TM1 (53%) than in the SMI (30%) or AP (24%) groups. Of the total number of diseased vessels with associated collaterals (30%), 84% were completely occluded and only 16% were not. The association of collaterals with occlusion was greater in AP (85%) and SMI (85%) than in TM1 (61%) pts. The presence of collaterals was not apparently related to duration of symptoms. Ventriculography was performed in 297 pts. Localized or diffuse reduction of contractility was present in 75% of TM1 and only in 29% of SMI and 26% of AP pts. The degree and distribution of coronary lesions could not be correlated with hypertension, cigarette smoking or elevated serum lipids in any of the three groups. In conclusion, within one year of onset of AP, SMI or TMI, angiography showed strikingly similar patterns in apart from the high incidence of vessel all three groups, occlusion and abnormal ventriculography in TMI. Coronary angiographic patterns were unrelated to risk factors in this selective group of patients.
CLINICAL
USE
MAKER.
OF AN ISOTOPIC
Andrew
Chardack,
M.D.
Veterans
capsule
contains
is converted thermocouple. mrem/hr
J.
Federico,
about
demand
150 mg
electricity Radiation
is
and found
credible
New
York
safe
The
at the
Heat
telluride
surface
is
5 mrem/hour The design
It has under
been
by
fuel
of Plutonium-238.
level
10 years. to be
type.
by a bismuth
and is expected to reach well within safety limits.
5 years, the pacemaker
M.D.
Buffalo,
3 after life of
extensively
all conditions
of
accident.
first
clinical
us in July
of
patients.
Primary
myocardial
use
1972
in the
and since
United then
installations
electrodes
to avoid
we
States have
(5) were potential
was
made
treated made
by
18 with
dislodgement,
occasionally seen with endocardiac electrodes. Replacements (13)were made with myocardial or endocardiac electrodes which had been shown to be stable. All patients have made an uneventful recovery and all pacemakers have functioned satisfactorily. At the present time, about 400 such units have been used,
mostly in Europe, pacemaker
139
and at the time of this writing,
malfunction
January 1974
has
not been
Detailed clinical and laboratory observations have shown that a great disparity may exist between the severity of coronary lesions and heart muscle damage in patients with coronary heart disease (CHD), a disparity which depends on the heart’s ability to protect jeopardized muscle through collateral circu lation. In 300 CHO patients undergoing coronary arteriography, coronary morphology was correlated with ventriculographically-observed left ventricular contractions and left ventricular dynamics measured by post-contrast injection enddiastolic pressure (EDP) and ejection fraction (EF). Single-vessel involvement did not significantly alter ventricular dynamics, except in lesions proximal to the origin of the first sepeal artery (SA); here the EDP was increased to 21+ 7 mm Hg. The incidence of left ventricular asynergy and proximal lesion aneurysm was markedly higher (43y,) than in lesions involving other vessels. Patients with triple-vessel disease showed decreased left ventricular function: lesions proximal to the first SA - EF 44+ 13.2%, EDP 28+ 8.2 mm Hg and lesions distal to the first SAY EF 48+14.3Y,,EDP 22+ 7.3 mm Hg. In this patient group, the occurrence of left vencicular aneurysms was identical to that in lesions proximal and distal to the first SA (39%). These findings clearly confirm the very important role that collateral blood flow through the septum, via either the first SA or the posterior descending system, plays in preserving myo cardium.
EFFECT OF RESTORATION OF NORMAL LEVELS OF MRMBRANE POTENTIAL ON OUABAIN TOXICITY IN CARDIAC PURKINJE FIBERS. Jeremiah M. Gelles, HD; Ronald S. Aronson, MD; Brian F. Hoffman, MD, Columbia University College of Physicians and Surgeons, New York, N.Y.
M.
pacemakers were first used in April of 1970. The Medtronic-
is of the
into
PACE-
William
Hospital,
radioisotope and Piwnica pacemaker
CARDIAC
M.D.,
and Anthony
Alcatel
The
Gage,
Administration
Long-lived Laurens
tested
A.
CORONARY PATHOLOGY AND LEFT VEmRICULAR FUNC TION IN PATIENTS WITH CORONARY HEART DISEASE Martin P. Gander, MD; Bruce Ham; Melvin P. Judkins, MD FACC Loma Linda University, Loma Linda, CA 92354
observed.
The American Journal of CARDIOLOGY
A principal manifestation of ouabaln (0) toxicity in Purkinje fibers (PP) is transmembrane depolarization presumably due to inhibition of the Na-K pump. To determine whether other manifestations of 0 toxicity derive from this principal effect, we restored the transmembrane potential (RIP) to control levels during 0 exposure and studied the effect of this maneuver on action potential (AP) parameters. A two-microelectrode technique was used. One electrode passed current while the other measured TMP. A third electrode was used for extracellular stimulation (cycle lengths 630-1300 msec). Shortened sheep cardiac PP (previously described) were superfused in vitro with Tyrode sol. (K=4.OmM; T,36oC). During 0 (2x10-TM) superfusion, polarizing current was passed intermittently to restore the TI4P to control levels. The rate of rise and overshoot of the AP returned towards control levels. Spontaneous activity that had developed during 0 toxicity was suppressed. O-induced enhanced phase 4 depolarization (P4D) was decreased. In PF that had become inexcitable, restoration of the 'IMP to control levels restored excitability. Repetitive stimulation at this time resulted in a gradual increase in P4D, escape from the stimulus, and depolarization of the fiber. These results indicate that restoring TMP to control levels can substantially ameliorate the toxic effects of 0 on the AP. In conjunction with voltage clamp experiments (previously described) these results further support the hypothesis that 0 exert8 its effects on PF by disrupting the integrity of the Aa-K PumP.
Volume 33