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Norepinephrine infusion following coronary occlusion: Ischemic injury limited by enhanced collateral flow
ABSTRACTS
THEANATOMICBASEOFLEFl'BUNDLEBFWiCHBLCCK MauriceLev, MD, FACC; Paul N. Unger, MD, FACC; KennethM. Rosen,MD, FACC; SarojaHharati,MD, Hektoen Institutefor MedicalResearch,Chicago,Ill.
DIFFERING
EFFECTS OF PROPRANOLOL,
BINED
THERAPY
IN PATIENTS
Martin
LeWinter,MD;
FACC;
John Ross,Jr.,MD,FACC;
Michael
AND
Crawford,MD;
Joel Karliner,MD,
Robert O’Rourke,MD,FACC
University
In all cases total or subtotaldestructionof the connectionbetweenthe left main bundle and the bundle of His was found. Pathologicchange in the left bundle branch (LBB)more distallywas also present. There was no differencein histologicfindingsbetweencases with and without left axis deviation. Pathologicchange in other parts of the conductionsystemwas not constant.
graphic left heart dimension (LHD), treadmill exercise and mean AP attack rate/week (AP/wk) were followed
Five cases had severeatherosclerotic narrowingof 3 main coronaryarteries,1of 2, and 1 of 1 coronary artery. All 7 of these cases had old and 5 had recent infarction, both anteroseptaland posteroseptal.Two were associatedwith hypertensionin addition. The eighthcase had rheumaticheart disease.
(p<.Ol).
Thirteen
tricular
(LV) function)
NOREPI NEPHRI NE OCCLUSION:
INFUSION FOLLOWI
ISCHEMIC
INJURY
COLLATERAL FLOW Jay A. Levine, MD; Michael
V. Cohen,
PhD, Peter Bent Brigham Hospital,
NG CORONARY
LIMITED
BY ENHANCED
MD; Edward S. Kirk,
Boston, Mass.
Norepinephrine (NE) has been used widely for the treatment of cardiogenic shock. However, NE, by raising blood pressure and myocardial
contractility,
increases myocardial
Unless oxygen supply increased
oxygen demand.
correspondingly,
ischemic
injury
following coronary artery occlusion would be augmented. To evaluate the effect of NE on the balance of supply and demand in ischemic
myocardium,
measurements were made shortly after
coronary artery occlusions in anesthetized, open-chest dogs. Collateral blood flow was measured in 10 dogs by the clearance of 133Xe from 0.01 ml depots of saline injected into the ischemic area; and myocardial injury was indicated by the sum of the S-T segment elevations in epicardial electragrams recorded from multiple sites in 6 dogs. which
increased
Intravenous
contractile
doses of NE (20-50
force and left ventricular
appeared to be maintained NE significantly enhanced ‘33Xe
clearance
decreased
in the ischemic area. Accordingly, collateral flow: the half-time for from a control
of 2.7
min to 1.6 min
(PcO.05). In contrast, doses of isoproterenol having similar inotropic effects greatly increased ischemia and decreased clearance. We conclude that the ability of NE to enhance collateral flow counters its effect on myocardial metabolism. The clinical usefulness of NE may depend on the balance of these opposing effects.
January
15 stable angina
(pts) for 2 weeks with propranolol
pectoris
(P, 160 mg/day),
response, serially.
Serum D levels were consistently in therapeutic range (0.5 to 2.0 mg/ml). During P alone, average resting heart rate (HR) decreased from 64 to 54 beats/min
(p<.OOl),
product at the end of treadmill 14.7x
103(p<.001),
HR-systolic
exercise
and LHD increased
blood pressure(BP)
decreased
from 21 .O to
from 46.7
to 47.9mm/M2
of the 15 pts(5 of whom had impaired improved on P, AP/wk
decreasing
left venfrom 17
to 6 (p<.O3); 3 pts no longer had chest pain with treadmill exercise and no pts developed X-ray evidence of pulmonary venous congestion.
With P plus D, resting HR, HR-BP product,
wk were the same as with P alone, pts, despite the persistence
but LHD decreased
of resting bradycardia.
and AP/ in 9 of 15
D alone de-
creased LHD and HR-BP product from control values(p<.05) but AP/wk increased in 7 of 15 pts(47%) from 5 to 15. In 3 pts with impaired pts AP/wk
LV function,
D decreased
was unchanged.
tive and subjective ducing cardiac
improvement
failure,
AP/wk
We conclude
and in the 5 remaining that P produces objec-
in unselected
despite an increase
of D often reduces the LHD without
AP pts without
in LHD.
diminishing
of P in these pts, but when used alone,
in-
The addition
the effectiveness
D can aggravate
AP.
BENEFICIAL EFFECT OF INTRAVENOUS ATROPINE IN THE PREHOSPITAL PHASE OF ACUTE MYOCARDIAL INFARCTION Richard P. Lewis, M.D., FACC and James V. Warren, M.D., FACC, The Ohio State University College of Medicine, Columbus, Ohio. Recent animal studies of experimental myocardial infarction (MI) have suggested that atropine (A) may be undesirable in the presence of acute ischemia. The development of a mobile coronary care system has allowed clinical evaluation of A in the earliest stage of acute MI. Seventy patients (pts) with bradyarrhythmia (BA) defined as any rhythm with HRC60 were studied. Fifty-six percent were seen within 1 hour of onset of symptoms. The pts were divided according to systolic blood pressure (SBP) and treatment (Rx). Six pts received isoproterenol (I) as well as A. The average dose of A was 0.86 mg (0.4-2.0 mg). Mean HR Mortality SBP Rx ;3 50 + 8 (SD) 13% A NL 21 53T7‘ 14% none NL
cl00 mmHg
2 to
3 fold, and increased mean aortic pressure by IO%, caused only minor increases in myocardial injury. The local energy balance
California
we treated
digoxin (D, 0.5 mg/doy) and P plus D. This sequence was preceded and followed by 2 weeks of placebo therapy. The radio-
pg/min) dP/dt
San Diego,
Using a single blind protocol, (AP) patients
COM-
PECTORIS
The anatomicbase of left bundle branch block (LBBB)is at presentdisputed. Accordinglythe entire conduction systemsof 8 heartsdiagnosedelectrocardiographically as having LBBB were studiedhistologically by serial section.
This study thereforeshows that (1) there is an anatomic base in the conductionsystem in most if not all cases of LBBB, (2) the lesionsfound are in the main left bundle or predi&ional and (3) the lesionsare pathogenetically both ischemicand mechanical. The mechanicalfactoris relatedto the vulnerabilityof the beginnina: of the LBB to mechanicalstressesat the summit0: the ientricular septum,exacerbatedby hypertension, sclerosisof the left side of the cardiacskeleton,and by infarction of the septum.
of California,
DIGOXIN
WITH ANGINA
A A&I none
16 6 4
47 T 10 33 r 9 51 T 5
25% 33% 75%
In the 16 hypotensive pts treated only with A, 9 were restored to nl BP and HR. The mortality for these pts was only 11%. A HR response b100 occurred in only one treated pt. There were two unexpected episodes of ventricular fibrillation (VF) in the untreated normotensive pts and only 1 in the treated normotensive group. Only 12% of untreated pts had a spontaneous remission of BA. After hospitalization BA recurred in 80% of pts who had initially been restored to normal by A. Thus the tendency for BA in the early phase of MI is persistent. In conclusion, atropine did not affect mortality when BP was normal but may have reduced the incidence of VF. Atropine clearly reduces mortality when hypotension is present.
1974
The American Journal of CARDIOLOGY
Volume 33
151
THEANATOMICBASEOFLEFl'BUNDLEBFWiCHBLCCK MauriceLev, MD, FACC; Paul N. Unger, MD, FACC; KennethM. Rosen,MD, FACC; SarojaHharati,MD, Hektoen Institutefor MedicalResearch,Chicago,Ill.
DIFFERING
EFFECTS OF PROPRANOLOL,
BINED
THERAPY
IN PATIENTS
Martin
LeWinter,MD;
FACC;
John Ross,Jr.,MD,FACC;
Michael
AND
Crawford,MD;
Joel Karliner,MD,
Robert O’Rourke,MD,FACC
University
In all cases total or subtotaldestructionof the connectionbetweenthe left main bundle and the bundle of His was found. Pathologicchange in the left bundle branch (LBB)more distallywas also present. There was no differencein histologicfindingsbetweencases with and without left axis deviation. Pathologicchange in other parts of the conductionsystemwas not constant.
graphic left heart dimension (LHD), treadmill exercise and mean AP attack rate/week (AP/wk) were followed
Five cases had severeatherosclerotic narrowingof 3 main coronaryarteries,1of 2, and 1 of 1 coronary artery. All 7 of these cases had old and 5 had recent infarction, both anteroseptaland posteroseptal.Two were associatedwith hypertensionin addition. The eighthcase had rheumaticheart disease.
(p<.Ol).
Thirteen
tricular
(LV) function)
NOREPI NEPHRI NE OCCLUSION:
INFUSION FOLLOWI
ISCHEMIC
INJURY
COLLATERAL FLOW Jay A. Levine, MD; Michael
V. Cohen,
PhD, Peter Bent Brigham Hospital,
NG CORONARY
LIMITED
BY ENHANCED
MD; Edward S. Kirk,
Boston, Mass.
Norepinephrine (NE) has been used widely for the treatment of cardiogenic shock. However, NE, by raising blood pressure and myocardial
contractility,
increases myocardial
Unless oxygen supply increased
oxygen demand.
correspondingly,
ischemic
injury
following coronary artery occlusion would be augmented. To evaluate the effect of NE on the balance of supply and demand in ischemic
myocardium,
measurements were made shortly after
coronary artery occlusions in anesthetized, open-chest dogs. Collateral blood flow was measured in 10 dogs by the clearance of 133Xe from 0.01 ml depots of saline injected into the ischemic area; and myocardial injury was indicated by the sum of the S-T segment elevations in epicardial electragrams recorded from multiple sites in 6 dogs. which
increased
Intravenous
contractile
doses of NE (20-50
force and left ventricular
appeared to be maintained NE significantly enhanced ‘33Xe
clearance
decreased
in the ischemic area. Accordingly, collateral flow: the half-time for from a control
of 2.7
min to 1.6 min
(PcO.05). In contrast, doses of isoproterenol having similar inotropic effects greatly increased ischemia and decreased clearance. We conclude that the ability of NE to enhance collateral flow counters its effect on myocardial metabolism. The clinical usefulness of NE may depend on the balance of these opposing effects.
January
15 stable angina
(pts) for 2 weeks with propranolol
pectoris
(P, 160 mg/day),
response, serially.
Serum D levels were consistently in therapeutic range (0.5 to 2.0 mg/ml). During P alone, average resting heart rate (HR) decreased from 64 to 54 beats/min
(p<.OOl),
product at the end of treadmill 14.7x
103(p<.001),
HR-systolic
exercise
and LHD increased
blood pressure(BP)
decreased
from 21 .O to
from 46.7
to 47.9mm/M2
of the 15 pts(5 of whom had impaired improved on P, AP/wk
decreasing
left venfrom 17
to 6 (p<.O3); 3 pts no longer had chest pain with treadmill exercise and no pts developed X-ray evidence of pulmonary venous congestion.
With P plus D, resting HR, HR-BP product,
wk were the same as with P alone, pts, despite the persistence
but LHD decreased
of resting bradycardia.
and AP/ in 9 of 15
D alone de-
creased LHD and HR-BP product from control values(p<.05) but AP/wk increased in 7 of 15 pts(47%) from 5 to 15. In 3 pts with impaired pts AP/wk
LV function,
D decreased
was unchanged.
tive and subjective ducing cardiac
improvement
failure,
AP/wk
We conclude
and in the 5 remaining that P produces objec-
in unselected
despite an increase
of D often reduces the LHD without
AP pts without
in LHD.
diminishing
of P in these pts, but when used alone,
in-
The addition
the effectiveness
D can aggravate
AP.
BENEFICIAL EFFECT OF INTRAVENOUS ATROPINE IN THE PREHOSPITAL PHASE OF ACUTE MYOCARDIAL INFARCTION Richard P. Lewis, M.D., FACC and James V. Warren, M.D., FACC, The Ohio State University College of Medicine, Columbus, Ohio. Recent animal studies of experimental myocardial infarction (MI) have suggested that atropine (A) may be undesirable in the presence of acute ischemia. The development of a mobile coronary care system has allowed clinical evaluation of A in the earliest stage of acute MI. Seventy patients (pts) with bradyarrhythmia (BA) defined as any rhythm with HRC60 were studied. Fifty-six percent were seen within 1 hour of onset of symptoms. The pts were divided according to systolic blood pressure (SBP) and treatment (Rx). Six pts received isoproterenol (I) as well as A. The average dose of A was 0.86 mg (0.4-2.0 mg). Mean HR Mortality SBP Rx ;3 50 + 8 (SD) 13% A NL 21 53T7‘ 14% none NL
cl00 mmHg
2 to
3 fold, and increased mean aortic pressure by IO%, caused only minor increases in myocardial injury. The local energy balance
California
we treated
digoxin (D, 0.5 mg/doy) and P plus D. This sequence was preceded and followed by 2 weeks of placebo therapy. The radio-
pg/min) dP/dt
San Diego,
Using a single blind protocol, (AP) patients
COM-
PECTORIS
The anatomicbase of left bundle branch block (LBBB)is at presentdisputed. Accordinglythe entire conduction systemsof 8 heartsdiagnosedelectrocardiographically as having LBBB were studiedhistologically by serial section.
This study thereforeshows that (1) there is an anatomic base in the conductionsystem in most if not all cases of LBBB, (2) the lesionsfound are in the main left bundle or predi&ional and (3) the lesionsare pathogenetically both ischemicand mechanical. The mechanicalfactoris relatedto the vulnerabilityof the beginnina: of the LBB to mechanicalstressesat the summit0: the ientricular septum,exacerbatedby hypertension, sclerosisof the left side of the cardiacskeleton,and by infarction of the septum.
of California,
DIGOXIN
WITH ANGINA
A A&I none
16 6 4
47 T 10 33 r 9 51 T 5
25% 33% 75%
In the 16 hypotensive pts treated only with A, 9 were restored to nl BP and HR. The mortality for these pts was only 11%. A HR response b100 occurred in only one treated pt. There were two unexpected episodes of ventricular fibrillation (VF) in the untreated normotensive pts and only 1 in the treated normotensive group. Only 12% of untreated pts had a spontaneous remission of BA. After hospitalization BA recurred in 80% of pts who had initially been restored to normal by A. Thus the tendency for BA in the early phase of MI is persistent. In conclusion, atropine did not affect mortality when BP was normal but may have reduced the incidence of VF. Atropine clearly reduces mortality when hypotension is present.
1974
The American Journal of CARDIOLOGY
Volume 33
151