Amrinone and dobutamine as primary treatment of low cardiac output syndrome following coronary artery surgery: a comparison of their effects on hemodynamics and outcome.

This study was undertaken in order to compare the effectiveness of amrinone and dobutamine as primary treatment of a low cardiac output (CO) after coronary artery bypass graft (CABG) surgery. Thirty patients with preoperative left ventricular dysfunction participated in this open-label randomized study. Patients were included if they failed to separate from cardiopulmonary bypass (CPB) without inotropic support or if they had a cardiac index (CI) less than 2.4 L/min/m2 after CPB regardless of the blood pressure, in the presence of adequate filling pressures. The treatment objectives were to separate from CPB and achieve a CI > or = 2.4 L/min/m2 and a mean arterial pressure > or = 70 mmHg. Patients treated with amrinone received 0.75 mg/kg followed by 10 micrograms/kg/min; when the objectives were not achieved within five minutes, another 0.75 mg/kg was given. Patients treated with dobutamine received an initial infusion of 5 micrograms/kg/min increased stepwise to 15 micrograms/kg/min if necessary. Eleven of 15 amrinone versus 6 of 15 dobutamine patients achieved the predefined treatment objectives with the test drug alone (P = NS). Comparisons of hemodynamics in patients treated solely with amrinone (n = 7) or dobutamine (n = 6) after CPB showed no significant differences between the treatment groups. The incidence of myocardial ischemia as detected by Holter monitor was 36% with amrinone and 33% with dobutamine. Two patients suffered ventricular fibrillation and two had significant supraventricular tachyarrhythmias (heart rate > 130/min) during treatment with dobutamine alone, whereas no significant arrhythmias occurred in the amrinone group (P = NS). Six dobutamine patients (40%) had postoperative myocardial infarction (MI) as opposed to none among the amrinone patients (P = 0.017). These results indicate that amrinone compares favorably with dobutamine as a primary treatment of low CO after CABG. Further study in a larger number of patients will be required in order to determine if the lower incidence of MI in the amrinone group was due to the treatment drug.     

A bolus dose of 1.5 mg/kg amrinone effectively improves low cardiac output state following separation from cardiopulmonary bypass in cardiac surgical patients

Background : The aim of this study was to evaluate the efficacy of 1.5 mg/kg bolus of amrinone on low cardiac output (CO) state following emergence from cardiopulmonary bypass (CPB) in cardiac surgical patients.
Methods : Immediately after emergence from CPB, 14 patients with a cardiac index (CI) less than 2.2 l min^-1 m^-2 despite administration of inotropes and nitroglycerin, received 1.5 mg/ kg amrinone over 3 min without changing catecholamine infusion rates (amrinone group). Hemodynamics and left ventricular short axis views with transesophageal echocardiography were recorded at baseline, 3, 5, and 10 min following amrinone administration. Left ventricular filling volumes were maintained constant by volume reinfusion from the CPB reservoir. We matched the data of the amrinone group with the other 14 patients who did not receive amrinone (non-amrinone group) to evaluate the efficacy of amrinone in low CO state.
Results : At baseline, CI (1.8±0.1 1 min^-1 m^-2) in the amrinone group was significantly lower than CI (3.0±0.2) in the non-amrinone group. Following amrinone administration, CI and velocity of circumferential fibershortening corrected for heart rate (Vcfc) significantly increased, and systemic vascular resistance index and pulmonary vascular resistance index significantly decreased from the baseline within 10 min without changes in heart rate, mean arterial blood pressure, or pulmonary artery occlusion pressure, and became equivalent with those of the non-amrinone group.
Conclusions : A 1.5 mg/kg amrinone loading dose to patients in a low CO state, despite catecholamine therapy immediately after emergence from CPB, effectively improves ventricular function when loading conditions are maintained constant.     

Differences in hemodynamic effects of amrinone, milrinone and olprinon after cardiopulmonary bypass in valvular cardiac surgery

The differences in hemodynamic effects of amrinone, milrinone and olprinone were evaluated in 46 patients for valvular cardiac surgery after cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups; group A with amrinone infusion (17 patients); group M with milrinone infusion (15 patients); and group O with olprinone infusion (14 patients). Each drug was administrated as a single dose into the venous reservoir of the CPB circuit 15 min prior to the end of emergence from CPB, followed by continuous infusion. Hemodynamic parameters were measured at the time of preCPB (C0), just after the end of CPB (C1), one hour after the termination of CPB (C2) and after the chest closure (C3). Catecholamines were used in order of dopamine, norepinephrine and dobutamine. These doses were modulated to maintain the cardiac index > 3.0 l.min-1.m-2 by each anesthesiologist. Hemodynamic parameters (at C0, C1, C2 and C3) and the doses of cathecholamine (at C1, C2 and C3) were compared among the 3 drugs. The systolic blood pressure in group M was significantly higher than that of group A and group O after chest closure. In group M and A, the systolic blood pressure showed a significant increase after CPB. On the other hand, the systolic blood pressure showed no significant change in group O after CPB. Three drugs showed no significant difference in the dosages of catecholamines used.     

Amrinone reverses cardiac depression by enflurane in the dog]

To evaluate the interaction of amrinone with inhalational anesthetics, cardiovascular effects of amrinone were investigated in nine mongrel dogs anesthetized with enflurane. Each dog received enflurane and amrinone in the following sequence: 1) 2% enflurane alone, 2) continuous infusion of 20 micrograms.kg-1.min-1 during enflurane, 3) 40 micrograms.kg-1.min-1 infusion during enflurane. Amrinone 40 micrograms.kg-1.min-1 during enflurane anesthesia improved the maximum left ventricular dP/dt, stroke volume and decreased effective arterial elastance (Ea) without changes in left ventricular end-diastolic pressure and heart rate. Left ventricular pressure (LVP) and systolic femoral arterial pressure were stable, but diastolic femoral arterial pressure decreased significantly from enflurane anesthesia alone. These parameters at 20 micrograms.kg-1.min-1 of amrinone infusion during enflurane showed the same tendency with 40 micrograms.kg-1.min-1 infusion but not significantly different from enflurane alone. This result suggests that amrinone may be beneficial in the patients with depression of cardiac performance during anesthesia.     

Dose-related cardiovascular effects of amrinone during enflurane anesthesia in the dog

The dose-related cardiovascular effects of amrinone, a synthetic cardiotonic and vasodilating drug, were investigated in dogs anesthetized with enflurane (2.2-2.4% end-tidal concentration). Twelve mongrel dogs were divided into two groups of six animals: an enflurane group (E) that received only enflurane, and an amrinone group (A). In the latter group each dog received the following sequential boluses and 30-min infusions: 1) the amrinone solvent alone; 2) amrinone, 1 mg/kg + 5 micrograms X kg-1 X min-1; 3) amrinone, 2 mg/kg + 10 micrograms X kg-1 X min-1; 4) amrinone, 4 mg/kg + 20 micrograms X kg-1 X min-1. Over the course of the experiment, 2.2-2.4% end-tidal enflurane alone resulted in a gradual decrease in cardiac index (CI), stroke volume index (SVI), and the maximum left ventricular dP/dt (LV dP/dtmax), without changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), or pulmonary capillary wedge pressure (PCWP) in group E. Significant differences from group E after 30 min of the lowest dose of amrinone included higher CI and SVI with lower systemic vascular resistance (SVR). The medium dose of amrinone, in addition to the effects already observed with the lowest dose of amrinone, decreased MAP and pulmonary vascular resistance (PVR), and increased LV dP/dtmax, when compared to group E only. Furthermore, the highest dose of amrinone caused lower pulmonary artery mean pressure (PAM), PCWP, and higher HR with shortened PR interval. The differences in MAP, CI, LV dP/dtmax, PCWP, PAM, PR interval, SVR, and PVR compared to E were still significant 30 min after the cessation of the highest dose. This study shows that the myocardial depressant effects of enflurane in an unstimulated canine model with a previously healthy heart can be overcome in a dose-related manner by amrinone. In contrast to other vasodilators, no reflex increase in plasma catecholamines was seen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-related cardiovascular effects of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression

Background: To ascertain the efficacy of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression, we investigated the time course of recovery of cardiac function with 3 doses of both agents after bupivacaine administration. Methods: In sevoflurane-anaesthetized dogs, bupivacaine was infused intravenously at 1 mg . kg^?1 . min^?1 until mean arterial pressure fell to 60 mmHg or less. The 3 doses of amrinone (1, 2, and 4 mg . kg^?1) or the 3 doses of epinephrine (2, 5, and 10 μg . kg^?1) were administered as a bolus in randomized order in each dog. Results: Amrinone improved maximum left ventricular dP/dt, a time constant of left ventricular isovolemic relaxation and cardiac index persistently and dose-relatedly. Amrinone increased heart rate and decreased left ventricular end-diastolic pressure and systemic vascular resistance index. Amrinone at 1 and 2 mg . kg^?1 significantly increased mean arterial pressure, but amrinone at 4 mg . kg^?1 did not. Epinephrine increased mean arterial pressure, maximum left ventricular dP/dt, and systemic vascular resistance dose-relatedly. The duration of action of epinephrine, peaking at 1 min and subsequently decreasing by 10 min after administration, did not differ among the groups. Epinephrine at all doses failed to improve a time constant of left ventricular isovolemic relaxation and cardiac index. ECG evidence of serious ventricular dysrhythmias was seen in 1 out of 6 dogs after administrating each dose of amrinone and in 3, 3 and 5 out of 6 dogs after administrating 2, 5 and 10 μg . kg^?1 of epinephrine, respectively. Conclusion: Bolus amrinone may have a certain efficacy in reversing bupivacaine-induced cardiovascular depression, and improving cardiac contractility and relaxation dose-relatedly. In contrast to amrinone, bolus epinephrine remains indispensable for resuscitation, causing a rapid, massive, transient and doserelated rise in blood pressure. However, the use of amrinone may be limited predominantly by a decrease in systemic vascular resistance, while the use of epinephrine may be limited predominantly by the generation of serious ventricular dysrhythmias and lack of effectiveness on cardiac index and on cardiac relaxation.     

Hemodynamic effects of amrinone in low cardiac output after mitral valve replacement

The efficacy of amrinone was assessed in the treatment of low cardiac output states occurring within 24 h after mitral valve replacement in an open prospective trial. It included 7 women and 5 men, aged 58 +/- 10 years. Four patients had also had simultaneous aortic valve replacement. Patients entered in the study if their cardiac index (CI) remained less than 2.2 l.min-1.m-2 after pulmonary wedged pressure (Ppw) had been increased to at least 15 mmHg, the patient having a temperature greater than 36 degrees C. Amrinone was given so as to increase Cl by at least 30% and to decrease Ppw by at least 30%. Patients were given a mean of 1.5 mg.kg-1 amrinone during the first hour, followed by a constant rate infusion of 9 +/- 3 micrograms.kg-1.min-1 over at least 24 h. The usual haemodynamic parameters were measured and calculated before giving amrinone, and after 1, 3, 6, 24, and 48 h. After 1 h of treatment, systolic arterial pressure, cardiac index, systolic index and left ventricular stroke work increased by 22, 42, 23, and 47% respectively, whilst Ppw decreased by 27% (p less than 0.01). Heart rate rose and systemic vascular resistance decreased but not significantly. Right atrial pressure, right ventricular stroke work, pulmonary artery pressure and pulmonary vascular resistance did not change. These effects were all maintained throughout the 48 h infusion. Amrinone had to be replaced by another agent (a beta-agonist) in 3 cases because of arrhythmia, lack of efficacy or thrombocytopaenia. In this setting, amrinone increased left ventricular performance with little effect on the right ventricle.     

Amrinone before termination of cardiopulmonary bypass: haemodynamic variables and oxygen utilization in the postbypass period

One hundred patients were randomly allocated to receive saline or amrinone, 0.75 mg.kg-1, ten minutes before separation from cardiopulmonary bypass (CPB) after elective coronary artery bypass grafting, in order to determine the effects of this agent on haemodynamic variables and O2 utilization. Anaesthesia and CPB were managed in a standard fashion. Before induction of anaesthesia, at pericardiotomy, then at 1, 10, 20 and 30 min after CPB, haemodynamic profiles, haematocrit, and O2 saturation of arterial and mixed venous blood were measured. Incremental doses of ephedrine or phenylephrine, or an infusion of norepinephrine with phentolamine were administered when required. The groups were demographically similar and surgical variables were also similar. Haemodynamic measurements were similar between groups at all times; however, a higher dose of phenylephrine was given immediately before weaning from CPB in the amrinone group, and more patients in this group received phenylephrine in the first 30 min after CPB. Mixed venous saturation (SvO2) was higher in the amrinone patients at all times after CPB, leading to lower calculated oxygen consumption (VO2) (P less than 0.05). Insufficient dosage may explain the lack of haemodynamic effect, while possible reasons for the higher SvO2 and lower VO2 are either reduced whole body VO2 or peripheral shunting.     

Amrinone and verapamil-propranolol induced cardiac depression during isoflurane anesthesia in dogs

This study was designed to investigate the possibility of whether verapamil diminishes the effects of amrinone, whether amrinone can reverse verapamil-propranolol depression, and also to evaluate whether the order of administering the drugs would have any effect during 1.7-1.8% end-tidal isoflurane anesthesia in dogs. At 3-4-week intervals, each of six conditioned mongrel dogs (23 +/- 1 kg) received amrinone (A) (4 mg/kg plus 100 micrograms X kg-1 X min-1), verapamil (V) (200 micrograms/kg plus 7.5 micrograms X kg-1 X min-1) and propranolol (P) (150 micrograms/kg plus 0.8 microgram X kg-1 X min-1) in four different orders of administration: VAP, AVP, VPA, and PVA. Plasma levels achieved were 15 +/- 1 to 24 +/- 2 micrograms/ml for amrinone, 24 +/- 2 to 59 +/- 10 ng/ml for propranolol, and 81 +/- 10 to 163 +/- 17 ng/ml for verapamil, equivalent to high therapeutic (amrinone) and therapeutic (propranolol, verapamil) levels in humans. The results of this study show that amrinone is able to reverse many of the effects of verapamil (group VAP) and also many of the effects of verapamil-propranolol or propranolol-verapamil (groups VPA, PVA) combinations. Amrinone improved cardiac index, left ventricular dP/dtmax, pulmonary capillary wedge pressure, and central venous pressure without increasing catecholamines. However, mean arterial pressure remained decreased with decreased systemic vascular resistance, which necessitates careful consideration depending upon patient circumstances. The results also show that verapamil-propranolol can reverse the positive inotropic effects of amrinone (group AVP).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of fentanyl and sufentanil combined with flunitrazepam in coronary artery surgery

Because sufentanil has been reported as being able to prevent or treat peroperative hypertensive crises during aorto-coronary artery graft surgery, a study was carried out to compare the haemodynamic effects of sufentanil with those of fentanyl. 20 patients who were to undergo aortocoronary bypass grafting (CABG) were randomly allocated to two equal groups, sufentanil (Sf) and fentanyl (F) groups. A 1 to 5 dose ratio was used so as to have equipotent doses of sufentanil and fentanyl. Induction doses were 10 micrograms.kg-1 sufentanil and 50 micrograms.kg-1 fentanyl. Up to 20 micrograms.kg-1 sufentanil and 100 micrograms.kg-1 fentanyl were then used between intubation and the setting-up of cardiopulmonary bypass (CPB). A bolus of 10 micrograms.kg-1 flunitrazepam was given if necessary, so as to lower the mean arterial pressure (Pa) to below 100 mmHg after intubation, and under 80 mmHg during CPB. Heart rate, Pa, mean pulmonary arterial pressure, pulmonary wedge pressure (Ppw), central venous pressure and cardiac output were measured before anaesthesia, 2 min after intubation, before incision, 2 min after sternotomy, 10 min after the end of CPB, after chest closure, 30 min and 2h after arrival of the patient in the intensive care unit. The only difference found between the two groups was a more rapid drop in left ventricular preload after induction with sufentanil; 2 min after intubation, there was a 26% fall in Ppw with sufentanil (p less than 0.01) and 8% with fentanyl. Before skin incision, this drop was of 32% (p less than 0.01) and 24% (p less than 0.01) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin E1 infusion fails to inhibit the increase of serum granulocyte elastase and myeloperoxidase and the decrease of plasma angiotensin converting enzyme in patients undergoing open-heart surgery]

We studied whether prostaglandin E1 (PGE1) could inhibit the increase of serum granulocyte elastase (GEL) and myeloperoxidase (MPO), and the decrease of plasma angiotensin converting enzyme (ACE) induced by oxygenator in 19 patients undergoing open-heart surgery. The patients were randomly allocated into 2 groups: one group (PGE1 group, n = 9) received a continuous infusion of PGE1 at a rate of 30 ng.kg-1.min-1 during cardiopulmonary bypass (CPB), and the other group (control group, n = 10) received saline infusion. GEL, MPO and ACE were measured serially at 8 points: before induction of anesthesia (as baseline), immediately before initiation of CPB, 10 min after initiation, 60 min after initiation, immediately after the end of CPB, 60 min after CPB, 120 min after CPB, and on the first postoperative day. Serum levels of GEL and MPO during 120 min after the end of CPB in both groups increased significantly compared with the baseline values. There was no significant difference between the two groups. Plasma levels of ACE in both groups decreased significantly immediately after the end of CPB compared with values taken 10 min after the initiation of CPB. There was no significant difference between the groups. We conclude that the infusion of PGE1 30 ng.kg-1.min-1 failed to inhibit the increase of GEL as well as MPO, and the decrease of ACE.     

Amrinone,in combination with norepinephrine,is an effective first-line drug for difficult separation from cardiopulmonary bypass

A crucial element for weaning patients from cardiopulmonary bypass (CPB) rests on the selection of an appropriate therapeutic regimen. Amrinone, a phosphodiesterase III inhibitor, combines inotropic support with pulmonary and systemic vasodilatation, without increasing heart rate (HR) or myocardial oxygen consumption. These characteristics should be useful in the failing heart during weaning from CPB. Nineteen patients were included in this prospective, open-labelled, phase IV study when systolic blood pressure (SBP) <80 mmHg, and diastolic pulmonary artery pressure (DPAP) > 15 mmHg or central venous pressure (CVP) > 75 mmHg, during progressive separation from CPB. At that moment, CPB flow was increased to alleviate heart failure and amrinone administered as a bolus (0.75 mg · kg^?1) followed by an infusion (10 μg · kg^?1 · min^?1). Weaning from CPB was then resumed and haemodynamic variables (SBP, DPAP, CVP and HR) were compared with those measured at CPB flow when failure had first occurred. Failure to wean from CPB occurred at 57 ± 25% of full pump flow. After the amrinone bolus, DPAP and CVP decreased by 20% and 21% respectively. Subsequently, 16 patients required the infusion of norepinephrine (4-8 fig-min^?1) to maintain a SBP > 80 mmHg. Heart rate remained unchanged after the bolus of amrinone, after separation from CPB, and no arrhythmias were noted. Successful weaning from CPB was possible 12 ± 8 min after the amrinone bolus. Weaning resulted in a cardiac index similar to that measured pre-bypass. Amrinone is rapidly effective during weaning from CPB and, in combination with norepinephrine, provides the necessary inotropic support during this unstable period.     

Cardiovascular effects of, and catecholamine response to, high dose fentanyl or NLA in patients for valve replacement]

We measured the cardiovascular effect of, and catecholamine and other hormonal responses to, anesthetic doses of fentanyl and original NLA in 25 patients for open heart surgery. The patients were randomly divided into three groups (group N, F30, F75). During induction, in group N; droperidol 0.25 mg.kg-1 and fentanyl 5 micrograms.kg-1, in group F30; fentanyl 30 micrograms.kg-1, and in group F75; fentanyl 75 micrograms.kg-1 were administered intravenously. Additional fentanyl was administered at a rate of 100 to 200 micrograms.h-1. Droperidol 0.25 mg.kg-1 was administered in group N when cardiopulmonary bypass (CPB) was disconnected. Plasma samples were assayed for norepinephrine, epinephrine, ACTH and cortisol before and after induction, during sternotomy, 60 minutes after institution of CPB, after weaning from CPB, and before as well as after extubation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and rate pressure product (RPP) were calculated simultaneously at the blood samplings. In all groups, no remarkable change in cardiovascular dynamics was observed. CPB was associated with marked increases in catecholamines, but high dose fentanyl in dose of 75 micrograms.kg-1 was able to suppress epinephrine level more than in group N. In high dose fentanyl group (F30, F75) ACTH was within normal ranges, even during CPB. The results suggest that high dose fentanyl is a complete anesthetic in patients for cardiac surgery. But a large dose of fentanyl causes small decreases in heart rate and arterial blood pressure. Our data indicate that group F30 is an attractive anesthetic technique for patients with valvular disease.     

High-dose Amrinone Is Required to Accelerate Rewarming from Deliberate Mild Intraoperative Hypothermia for Neurosurgical Procedures

Background: Since the time available to provide the cooling and rewarming is limited during deliberate mild hypothermia, the technique to accelerate the cooling and rewarming rate of core temperature has been studied. Amrinone has been reported to accelerate the cooling rate but not the rewarming rate of core temperature during deliberate mild hypothermia. The failure of amrinone effect on the rewarming rate might be due to an insufficient dose of amrinone during hypothermic conditions. The authors therefore tested whether higher doses of amrinone can accelerate the rewarming rate of core temperature during deliberate mild hypothermia for neurosurgery.

Methods: After institutional approval and informed consent, 30 patients were randomly assigned to one of three groups. Patients in the control group (n = 10) did not receive amrinone; patients in the AMR 15 group (n = 10) received 15 [mu]g [middle dot] kg-1 [middle dot] min-1 amrinone with a 1.0-mg/kg loading dose of amrinone at the beginning of cooling; and patients in the ReAMR group (n = 10) received 5 [mu]g [middle dot] kg-1 [middle dot] min-1 amrinone with 1.0-mg/kg loading and reloading doses of amrinone at the beginning of cooling and rewarming, respectively. Administration of amrinone was started just after the induction of cooling and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, propofol, and fentanyl. After induction of anesthesia, patients were cooled, and tympanic membrane temperature was maintained at 34.5[degrees]C. After completion of the main surgical procedures, patients were actively rewarmed and extubated in the operating room.

Results: The cooling and rewarming rates of core temperature were both significantly faster in both amrinone groups than in the control group. During the cooling and rewarming periods, forearm minus fingertip temperature gradient was significantly smaller in both amrinone groups than in the control group. During the rewarming period, heart rate and mean arterial pressure in the AMR 15 group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group.     

Effects of olprinone hydrochloride on intraocular pressure and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass

BACKGROUND: We evaluated the effect of olprinone hydrochloride on intraocular pressure (IOP) and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass (CPB). METHODS: Nine patients after cardiac surgery under CPB were investigated. We measured IOP of the left eye using tonometer (Tonopen XL, BIO RAD, Osaka), and mean blood flow velocity in the left ophthalmic artery (Vm) and calculated the pulsatility index in the left ophthalmic artery (PI) using 2 MHz Doppler ultrasound system (Multidop P, DWL, Germany). After baseline measurement, the olprinone hydrochloride loading dosage was increased from 0.15 to 0.3 microgram.kg-1.min-1 every 60 minutes. The intraocular pressure and ocular blood flow were measured at each point. RESULTS: IOP and PI decreased significantly, and Vm increased significantly at the infusion rate of 0.3 microgram.kg-1.min-1 from baseline. There was a significant linear correlations between IOP and Vm. CONCLUSION: We demonstrated that olprinone hydrochloride led to a decrease in IOP and an increase in ocular blood flow in patients after cardiac surgery under CPB.     

The effect of amrinone on recovery from severe bupivacaine intoxication in pigs.

Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo-controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FIO2 0.21, 0.5% bupivacaine 2 mg.kg-1.min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg.kg-1 in the control and 19 +/- 5 mg.kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19 micrograms.ml-1, respectively. A bolus of amrinone 4 mg.kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg.kg-1.min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FIO2 1.0 without anaesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P less than 0.01). The animals receiving amrinone survived without cardiac compression (P less than 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of amrinone, milrinone and olprinone in reversing bupivacaine-induced cardiovascular depression

BACKGROUND: Increasing evidence indicates that amrinone, a phosphodiesterase fraction III (PDE-III) inhibitor, has relative efficacy as an initial treatment for cardiovascular depression after bupivacaine in an experimental setting. This study was performed to compare the cardiovascular effects of the other new PDE-III inhibitors, milrinone and olprinone, with those of amrinone in reversing bupivacaine-induced cardiovascular depression. METHODS: In sevoflurane-anaesthetized dogs, bupivacaine was infused intravenously at 1 mg x kg(-1) x min(-1) until mean arterial pressure fell to 60 mmHg or less. The dogs received either amrinone (2 mg x kg(-1)), milrinone (0.2 mg x kg(-1)), olprinone (0.12 mg x kg(-1)) or 0.9% saline (0.5 ml x kg(-1)). RESULTS: Amrinone, milrinone and olprinone improved left ventricular systolic and diastolic function, resulting in an increase in cardiac index. The most significant difference observed among the three drugs was the change in heart rate (HR) after treatment. Milrinone significantly increased HR, but olprinone did not. CONCLUSION: Milrinone and olprinone are as effective as amrinone in reversing bupivacaine-induced cardiovascular depression.     

Dobutamine increases oxygen consumption during constant flow cardiopulmonary bypass

We have studied the effects of flow and dobutamine on systemic haemodynamic variables, oxygen delivery (DO2) and oxygen consumption (VO2) in 20 patients during cardiopulmonary bypass (CPB) with mild hypothermia (34 degrees C). In a subgroup of seven patients, we also studied the effects on gastric microcirculatory blood flow (MCF) using laser Doppler flowmetry. During CPB, measurements were made before and after two interventions: the first consisted of increasing flow from 2.4 to 3.0 litre min-1 m-2 for 10 min; the second consisted of an infusion of dobutamine at a rate of 6 micrograms kg-1 min-1 for 10 min during constant flow CPB. There were no significant differences in DO2, VO2 or haemodynamic variables between the two baseline measurements. The increase in flow raised DO2 (27%, P < 0.001), mean arterial pressure (P < 0.01) and MCF (P < 0.01), but failed to increase VO2. In contrast, dobutamine infusion increased VO2 (11%, P < 0.001) during constant flow CPB without significant changes in DO2, systemic haemodynamic variables or MCF. These results indicate that increases in VO2 during dobutamine may be flow-independent.      

Amrinone reverses bupivacaine-induced regional myocardial dysfunction

Amrinone has been shown to have therapeutic effects on bupivacaine-induced cardiovascular toxicity, but its exact effects on the heart are not well understood.
This study evaluated the regional myocardial effect of amrinone on bupivacaine-induced cardiovascular toxicity in in situ beating hearts in 10 dogs using a selective coronary perfusion and sono-micrometry. In the control group, bupivacaine was administered into the left anterior descending coronary artery (LAD) for 15 min at tour steps: baseline, step 1, step 2 and step 3, (calculated LAD plasma concentrations; 0, 5, 5 and 10 μg·ml^-1, respectively). In the amrinone group, amrinone (5 μg·ml^-1) was simultaneously infused at steps 2 and 3 in addition to bupivacaine infusions. Regional myocardial function of the LAD supplied area was evaluated by analysis of the left ventricular pressure-segment length loop.
In the control group, systolic shortening decreased from the baseline (10.5±1.3%, mean ± SEM) to step 3 (0.1±1.3%), and post-systolic shortening increased from the baseline (18.0±3.7%) to step 3 (52.3±5.5%) dose-dependently. In contrast, with amrinone infusion at steps 2 and 3, both variables returned to near baseline values.
These results indicate that amrinone reverses bupivacaine-induced regional myocardial dysfunction.     

Effect of intraoperative angiotensin-converting enzyme inhibition by quinaprilat on hypertension after coronary artery surgery

Activation of the renin-angiotensin system during cardiopulmonary bypass (CPB) may be involved in early postoperative hypertension after coronary artery bypass grafting (CABG). As hypertensive episodes may be deleterious in the immediate postoperative period, we have assessed the effects of prophylactic treatment with the angiotensin-converting enzyme inhibitor quinaprilat in an open study. During steady state CPB, patients received quinaprilat 0.02 mg kg-1 (group A, n = 10), quinaprilat 0.04 mg kg-1 (group B, n = 10) or saline solution (group C, n = 10) as an i.v. bolus dose. Sodium nitroprusside (SNP) was given after operation when systolic arterial pressure was > 150 mm Hg. Requirements for SNP 1 h after arrival in the ICU were significantly less in groups A (two of 10) and B (two of 10) than in group C (eight of 10). Also, patients in group C had a greater systolic arterial pressure compared with groups A and B. There were no significant differences between groups in diastolic arterial pressure, heart rate, cardiac index or cardiac filling pressures. We conclude that quinaprilat can be used during CABG to reduce the incidence of postoperative hypertension. Further studies of the efficacy and safety of this technique are necessary.