Acta Med Scand 206: 299-302, 1979
Dobutamine in Left Heart Failure after Acute Myocardial Infarction N. Rehnqvist and T. Lundman From the Department of Medicine, Serafimerlasarettet , Stockholm, Sweden
ABSTRACT. Dobutamine, a new positive inotropic drug, was given as i.v. infusion at a rate of 2.5-7.5 pg/kg/min to nine male patients with a moderately severe left heart failure. The patients were treated in our CCU for acute myocardial infarction (AMI) and had PEP/LVET above 0.40 on routine registrations of systolic time intervals, PEP (preejection phase), PEPI (PEP corrected for heart rate), LVET (left ventricular ejection time) and LVETI (LVET corrected for heart rate). Dobutamine increased contractility, measured as shortening of PEP and PEPI, and also increased ejection fraction, measured as PEP/LVET. Concomitantly, heart rate increased significantly but no changes were noted in systolic or diastolic BPs. The positive inotropic effect of dobutamine was thus accompanied by a positive chronotropic effect, which limits the usefulness of the drug in patients with recent AMI. K e y words: dobutamine, acute myocardial infarction, left
heart failure, non-invasive parameters. Acta Med Scand 206: 299, 1979.
There is a lack of clinically useful positive inotropic drugs. Digitalis glucosides have their given place in therapy but there is a need for more potent agents. The drugs in general use include isoprenaline, noradrenaline and dopamine. Their use is associated with well recognized disadvantages, as these drugs are chronotropic, arrhythmogenic and change the peripheral resistance. To overcome these disadvantages, dobutamine was synthesized and was shown in animal experiments to selectively increase myocardial contractility without inducing arrhythmia, tachycardia or significant changes in preload or mean aortic perfusion pressures (8). This study was performed to assess the effects of dobutamine on myocardial performance, as measured by systolic time intervals, in patients with slightly impaired cardiac function after recent acute myocardial infarction (AMI).
PATIENTS AND METHODS Nine men, mean age 58 years, treated in our CCU for AM1 were investigated 5-17 (median 7) days after hospitalization for AMI. Patients who on routine recordings of systolic time intervals showed impaired cardiac function, who were not on digitalis or P-receptor blocking drugs and who received maximally 40 mg of furosemide (or a comparable diuretic) were included in the study. After 30 rnin rest, an i.v. infusion of dobutamine was given, using a constant-rate infusion pump. The drug was diluted in 5 % dextrose and given at a rate of 2.5, 5.0 and 7.5 pg/kg/min during 30 min at each concentration. The systolic time intervals, heart rate and BP-measured by brachial artery catheterization-were registered twice during the pretreatment period, after 15 and 30 min on each dose and 15 and 30 rnin after the infusion. The systolic time intervals were registered according to Weissler and Garrard (10) simultaneously with recordings of ECG, phonocardiogram and carotid pulse. The values registered were preejection phase (PEP), corrected for heart rate (PEPI), left ventricular ejection time (LVET), corrected for heart rate (LVETI), and PEP/LVET. Patients with PEP/LVET above 0.40 were included in the study. Infusion was discontinued when no further improvement in cardiac performance could be registered or if side-effects like severe palpitations, registered tachycardia or other severe arrhythmias supervened. The paired t-test was used to evaluate intraindividual changes in the registered parameters.
RESULTS One patient was investigated for only 15 rnin at 2.0 pglkglmin. The concentration and duration of infusion for the other patients were 5 pglkglmin for 30 rnin in three, 6 pg/kg/min for 30 rnin in one, 7.5 pg/kg/min for 15 rnin in two and 7.5 pglkglmin for 30 rnin in two patients. The concentrations of 2.0 and 6.0 pg/kg/min were due to a methodological Abbreviations: AM1 = acute myocardial infarction, CCU = coronary care unit, BP = blood pressure, PEP = preejection phase, PEPI = PEP corrected for heart rate, LVET = left ventricular ejection time, LVETI = LVET corrected for heart rate, VEB = vetnricular ectopic beat. Acta Mrd Scand 206
300
N . Kditiyvist irnd T . Liiridriiiiri
Table I . Piitirnt Pat. no.
Age (y.)
I 2 3 4 5 h 7 8 9 Mean
51 51 72 54 61 49 59 63 62 58
ilritir c i r d
Days after AM1
i : f f ' i ~ofdjfjcri~iit t do.w.\ of'tlohiittrniine o r 1 PEPILVET
Pretherapy
8
0.44 0.42 0.47 0.46 0.45 0.40 0.50 0.37 0.50 0.45
II
7 17 9 11 8 8 5 9
2.5 pg/kg/min
5 pg/kg/min
7.5 pg/kg/min
Posttherapy
Decrease
15 min
30min
15 min 30min
15 min 30min
15 min 30min
(%,)
0.53 0.46 0.40(2) 0.36 0.42 (2) 0.30 0.41 0.37 0.41 0.41
0.50 0.39 0.40(2) 0.38 0.29 0.35 0.33 0.44 0.39
0.47 0.37 0.40 0.33 0.31 0.41 0.30 0.38 0.37
0.38 0.38 0.34 0.40 0.28 (0.25) 0.34
0.41 0.38 0.46 0.34 0.41 0.47 0.32 0.45
0.49 0.30 0.48 0.39 0.43 0.46 0.43 0.45
14 12 28 28 24 22 30 24 24(50)
0.41*
0.43
23%***
0.45 0.46 0.36(4) 0.34 0.32 0.35 0.32 0.41 0.38
0.41 0.41 0.38(6) -
-
*p
Dobutamine in Left Heart Failure after Acute Myocardial Infarction N. Rehnqvist and T. Lundman From the Department of Medicine, Serafimerlasarettet , Stockholm, Sweden
ABSTRACT. Dobutamine, a new positive inotropic drug, was given as i.v. infusion at a rate of 2.5-7.5 pg/kg/min to nine male patients with a moderately severe left heart failure. The patients were treated in our CCU for acute myocardial infarction (AMI) and had PEP/LVET above 0.40 on routine registrations of systolic time intervals, PEP (preejection phase), PEPI (PEP corrected for heart rate), LVET (left ventricular ejection time) and LVETI (LVET corrected for heart rate). Dobutamine increased contractility, measured as shortening of PEP and PEPI, and also increased ejection fraction, measured as PEP/LVET. Concomitantly, heart rate increased significantly but no changes were noted in systolic or diastolic BPs. The positive inotropic effect of dobutamine was thus accompanied by a positive chronotropic effect, which limits the usefulness of the drug in patients with recent AMI. K e y words: dobutamine, acute myocardial infarction, left
heart failure, non-invasive parameters. Acta Med Scand 206: 299, 1979.
There is a lack of clinically useful positive inotropic drugs. Digitalis glucosides have their given place in therapy but there is a need for more potent agents. The drugs in general use include isoprenaline, noradrenaline and dopamine. Their use is associated with well recognized disadvantages, as these drugs are chronotropic, arrhythmogenic and change the peripheral resistance. To overcome these disadvantages, dobutamine was synthesized and was shown in animal experiments to selectively increase myocardial contractility without inducing arrhythmia, tachycardia or significant changes in preload or mean aortic perfusion pressures (8). This study was performed to assess the effects of dobutamine on myocardial performance, as measured by systolic time intervals, in patients with slightly impaired cardiac function after recent acute myocardial infarction (AMI).
PATIENTS AND METHODS Nine men, mean age 58 years, treated in our CCU for AM1 were investigated 5-17 (median 7) days after hospitalization for AMI. Patients who on routine recordings of systolic time intervals showed impaired cardiac function, who were not on digitalis or P-receptor blocking drugs and who received maximally 40 mg of furosemide (or a comparable diuretic) were included in the study. After 30 rnin rest, an i.v. infusion of dobutamine was given, using a constant-rate infusion pump. The drug was diluted in 5 % dextrose and given at a rate of 2.5, 5.0 and 7.5 pg/kg/min during 30 min at each concentration. The systolic time intervals, heart rate and BP-measured by brachial artery catheterization-were registered twice during the pretreatment period, after 15 and 30 min on each dose and 15 and 30 rnin after the infusion. The systolic time intervals were registered according to Weissler and Garrard (10) simultaneously with recordings of ECG, phonocardiogram and carotid pulse. The values registered were preejection phase (PEP), corrected for heart rate (PEPI), left ventricular ejection time (LVET), corrected for heart rate (LVETI), and PEP/LVET. Patients with PEP/LVET above 0.40 were included in the study. Infusion was discontinued when no further improvement in cardiac performance could be registered or if side-effects like severe palpitations, registered tachycardia or other severe arrhythmias supervened. The paired t-test was used to evaluate intraindividual changes in the registered parameters.
RESULTS One patient was investigated for only 15 rnin at 2.0 pglkglmin. The concentration and duration of infusion for the other patients were 5 pglkglmin for 30 rnin in three, 6 pg/kg/min for 30 rnin in one, 7.5 pg/kg/min for 15 rnin in two and 7.5 pglkglmin for 30 rnin in two patients. The concentrations of 2.0 and 6.0 pg/kg/min were due to a methodological Abbreviations: AM1 = acute myocardial infarction, CCU = coronary care unit, BP = blood pressure, PEP = preejection phase, PEPI = PEP corrected for heart rate, LVET = left ventricular ejection time, LVETI = LVET corrected for heart rate, VEB = vetnricular ectopic beat. Acta Mrd Scand 206
300
N . Kditiyvist irnd T . Liiridriiiiri
Table I . Piitirnt Pat. no.
Age (y.)
I 2 3 4 5 h 7 8 9 Mean
51 51 72 54 61 49 59 63 62 58
ilritir c i r d
Days after AM1
i : f f ' i ~ofdjfjcri~iit t do.w.\ of'tlohiittrniine o r 1 PEPILVET
Pretherapy
8
0.44 0.42 0.47 0.46 0.45 0.40 0.50 0.37 0.50 0.45
II
7 17 9 11 8 8 5 9
2.5 pg/kg/min
5 pg/kg/min
7.5 pg/kg/min
Posttherapy
Decrease
15 min
30min
15 min 30min
15 min 30min
15 min 30min
(%,)
0.53 0.46 0.40(2) 0.36 0.42 (2) 0.30 0.41 0.37 0.41 0.41
0.50 0.39 0.40(2) 0.38 0.29 0.35 0.33 0.44 0.39
0.47 0.37 0.40 0.33 0.31 0.41 0.30 0.38 0.37
0.38 0.38 0.34 0.40 0.28 (0.25) 0.34
0.41 0.38 0.46 0.34 0.41 0.47 0.32 0.45
0.49 0.30 0.48 0.39 0.43 0.46 0.43 0.45
14 12 28 28 24 22 30 24 24(50)
0.41*
0.43
23%***
0.45 0.46 0.36(4) 0.34 0.32 0.35 0.32 0.41 0.38
0.41 0.41 0.38(6) -
-
*p
