Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery

BACKGROUND: Milrinone is a phosphodiesterase inhibitor with positive inotropic and vasodilator effects that are useful in the treatment of ventricular dysfunction after cardiac surgery. However, the pharmacokinetics of the drug have been investigated only in healthy volunteers and in patients with chronic congestive heart failure. This study investigates the pharmacokinetics of milrinone in adult cardiac surgical patients after cardiopulmonary bypass. METHODS: Milrinone was administered to 25 patients just before or immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16 h and milrinone plasma concentrations were determined by high-performance liquid chromatography. Data were analyzed by extended nonlinear least-squares regression. The relation between milrinone plasma concentration and hemodynamic effect was examined in an additional 11 patients who had cardiac indices less than 2.5 l.min-1.m-2 immediately after separation from cardiopulmonary bypass. Milrinone was administered and plasma concentrations were related to changes in cardiac index during the next 10 min. RESULTS: A milrinone dose of 50 micrograms/kg in conjunction with an infusion of 0.5 micrograms.kg-1.min-1 consistently maintained plasma concentrations in excess of 100 ng/ml. A triexponential equation describing the plasma concentration as a function of time was used to describe the data. Central-compartment volume was 102 ml/kg, volume of distribution was 1,698 ml/kg, and elimination clearance was 1.88 ml.kg-1.min-1. Pharmacokinetic parameters were independent of dose. The relation between plasma concentration and percentage increase in cardiac index could be described by a sigmoidal curve with the plasma concentration associated with a 50% increase in cardiac index equal to 167 ng/ml. CONCLUSIONS: A milrinone dose of 50 micrograms/kg with an infusion at 0.5 micrograms.kg-1.min-1 maintains plasma concentrations at or above the threshold of therapeutic effects.     

Postoperative junctional ectopic tachycardia

PURPOSE: To report the management of junctional ectopic tachycardia after cardiac surgery in an infant. Postoperatively, the patient suffered profound cardiac decompensation secondary to the accelerated rhythm and required extracorporeal membrane oxygenation (ECMO) for haemodynamic support. CLINICAL FEATURES: A 14-day-old, 3.5 kg boy exhibited junctional ectopic tachycardia after cardiopulmonary bypass. Left atrial pressure was 25-28 mmHg. No impact on the tachycardia was seen after rapid overdrive atrial pacing or after 20 micrograms fentanyl i.v., 45 micrograms digitalis, 100 mg magnesium or procainamide (loading dose 15 mg, then 30 mg.kg-1.min-1). Active cooling decreased the nasopharyngeal temperature to 35.2 degrees C, when the heart rate decreased below 180 bpm with a left atrial pressure of 8-10 mmHg. Dopamine (2 micrograms.kg-1.min-1) and dobutamine (5 micrograms.kg-1.min-1) were added to improve the cardiac output. Sodium nitroprusside (0.25 to 1 microgram.kg-1.min) maintained the systolic pressure < 100 mmHg. On arrival in ICU, heart rate increased to 200 bpm. The patient received cardiac massage for severe hypotension 75 min after surgery. Emergency ECMO was instituted for circulatory support. Procainamide, digoxin, dopamine, dobutamine, sodium nitroprusside and hypothermia were continued. Sinus rhythm resumed on the first postoperative day, but procainamide and induced hypothermia at 34 degrees C were maintained for 36 hr after normalization of the rhythm to prevent recurrence of the tachycardia. Total duration of ECMO was three and a half days. Recovery was uneventful. CONCLUSION: The use of ECMO, as a first line of defence, is suitable for the emergency support of patients with JET because of the ease of support of circulation and precise control of hypothermia.     

Consequences of electroencephalographic-suppressive doses of propofol in conjunction with deep hypothermic circulatory arrest

BACKGROUND: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol. METHODS: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined. RESULTS: Prebypass propofol at 243 +/- 57 micrograms.kg-1.min-1 decreased vascular resistance from 34 +/- 8 to 27 +/- 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 +/- 2 micrograms/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 +/- 1.4 h. Three others had strokes and a fourth had cerebral swelling. CONCLUSIONS: Propofol infused at a rate sufficient to suppress the electroencephalogram does not depress the heart or excessively prolong emergence from anesthesia after cardiopulmonary bypass and deep hypothermic circulatory arrest.     

Effects of carperitide (alpha-human atrial natriuretic peptide) on acute congestive heart failure in dogs

Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF.     

Effects of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass

To estimate the effectiveness of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass (CPB), a clinical study was made, in elective coronary artery bypass grafting (CABG) cases. 24 consecutive patients underwent elective CABG in our institute. In all cases, moderate hypothermia and cardioplegic(St. Thomas solution) cardiac arrest were performed. In 12 cases, continuous intravenous 0.25 microgram/kg/min of milrinone, 3 micrograms/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly as inotropic agents (Group-I). The same initial doses of catecholamine (DOB and DOA) as the Group-I were administered in another 12 patients (Group-II). When the pump flow of CPB decreased to a half, these drugs were administered in both groups. Hemodynamic data were measured before CPB, just after operation, 3, 6, 12, 24, 48, and 72 hours after operation. There were no significant differences in aortic and pulmonary artery pressure between both groups. However, cardiac index (CI) of the Group-I demonstrated significantly (p < 0.01) higher values than that of Group-II until 24 hours after surgery. Systemic vascular resistance index (SVRI) of the Group-I demonstrated significantly (p < 0.01) lower value than that of Group-II from 3 to 12 hours after operation. There were no significant differences in oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. These results suggested that concomitant usage of milrinone and low dose catecholamine increased CI and decreased SVRI, and made weaning from CPB very easy, demonstrating excellent hemodynamics. This high potential phosphodiesterase inhibitor may be suitable for not only weaning from CPB but also post-cardiotomy cardiogenic shock.     

Anesthesia for heart transplantation in newborn and suckling infants. Special aspects of the hypoplastic left heart syndrome

Paediatric cardiac transplantation (pHTX) has gained widespread acceptance as a therapy in end-stage myocardial failure and some forms of congenital heart disease, particularly hypoplastic left heart syndrome (HLHS). The major problems to the anaesthesiologist in these patients are induction of anaesthesia in infants with HLHS and treatment of pulmonary hypertension in the early post-bypass period. PATIENTS AND METHODS. Anaesthesia for pHTX was performed in 15 children < 1 year of age (4-237 days); 12 suffered from HLHS, 2 from endocardial fibroelastosis, and 1 from dilatative cardiomyopathy. Induction of anaesthesia in patients with HLHS IS a challenge to the anaesthesiologist, as he has to maintain the delicate balance between pulmonary and systemic blood flow. Anaesthesia was induced with fentanyl (10-15 micrograms/kg) and pancuronium (0.2-0.4 mg/kg) and maintained with fentanyl (total dosage 70-100 micrograms/kg). Modification of ventilatory parameters such as FiO2, PaCO2, and airway pressure (PEEP, I:E ratio) was used to influence systemic and pulmonary blood distribution in the pre-bypass period according to changes in haemodynamics (target: O2 saturation approximately 75%-80%, PaCO2 45-50 mmHg). Treatment of pulmonary hypertension in the weaning and early post-bypass period consisted of respiratory (PaCO2 < 30 mmHg) and metabolic alkalinisation (pH 7.45-7.55, BE > +3 mmol/l), the use of prostaglandin E1 (3-6-12 micrograms/kg.h), and the phosphodiesterase inhibitor enoximone (10-15 micrograms/kg.min). Additional positive inotropic support was achieved with dobutamine (5-10 micrograms/kg.min), adrenaline (0.1-0.5 micrograms/kg.min), and/or orciprenaline (0.1-0.2 micrograms/kg.min) and calcium chloride (25-100 mg/kg). RESULTS. Two children died intraoperatively and 1 on the 1st postoperative day from overwhelming pulmonary vascular resistance and right ventricular failure. Three children died between 3 and 4 weeks postoperatively, 1 from cytomegalovirus infection, 1 from sepsis, and 1 from acute rejection. Nine patients survived and are well up to 5.5 years after transplantation. CONCLUSION. Pulmonary hypertension in the weaning and early post-bypass period is the main anaesthesiological problem of pHTX, particularly in children with HLHS. A polypragmatic approach to this problem consisting of alkalinisation, pulmonary vasodilatation, and inotropic support is presented and seems to be effective. Further improvements in concepts of pHTX are limited by the lack of donor organs. Though the experience with pHTX in neonates and infants is growing slowly, it might be a routine procedure from the anaesthesiological point of view within a few years in some selected centres.     

Effects of toborinone on systemic circulation in patients under general anesthesia

Patients with suppressed systemic circulation under general anesthesia received a 20-minute continuous infusion of toborinone at a rate of 5, 10, or 15 micrograms.kg-1.min-1, and the efficacy and safety of the drug were evaluated. Toborinone increased cardiac index (CI) and stroke volume index (SVI) dose-dependently, with significant increases at 10 and 15 micrograms.kg-1.min-1. An increase in CI was observed from 10 minutes after the start of infusion, with a return to the baseline value at 20-30 minutes after the completion of infusion. Toborinone did not affect heart rate at any dose tested, but the drug tended to decrease mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial blood pressure tended to decrease after the start of infusion at all doses tested, and was significantly decreased at 20 minutes after the start of infusion at 10 and 15 micrograms.kg-1.min-1. Systemic vascular resistance and pulmonary vascular resistance decreased at all doses tested. T-wave amplitude on electrocardiaogram (ECG) and oxygen partial pressure in arterial blood decreased at 10 and 15 micrograms.kg-1.min-1. Toborinone increases cardiac output and decreases pre-load and after-load with no effects on heart rate, and, therefore, is thought to be a positive inotropic agent useful in the treatment of circulatory insufficiency. Due care should be exercised to monitor blood pressure, ECG, and arterial blood gas parameters of the patients. The effects of toborinone need to be further investigated in patients with complicated cardiac diseases under general anesthesia and in patients with circulatory insufficiency after surgery, including patients following extracorporeal circulation.     

Amrinone versus dopamine-nitroglycerin after reconstructive surgery for complete atrioventricular septal defect

OBJECTIVES: To compare the effectiveness and safety of amrinone and a combination of dopamine and nitroglycerin in infants after reconstructive surgery for congenital heart disease. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Thirty-two infants with complete atrioventricular septal defect. INTERVENTIONS: Amrinone loading dose, 2 mg/kg, followed by a maintenance infusion, 7.5 micrograms/kg/min, was given to 17 infants before separation from cardiopulmonary bypass. The remaining 15 patients received a combination of dopamine, 5 micrograms/kg/min, and nitroglycerin, 1 microgram/kg/min. MEASUREMENTS AND MAIN RESULTS: The circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (2.5 +/- 0.7 L/min/m2) compared with the dopamine-nitroglycerin group (2.0 +/- 0.6 L/min/m2, mean +/- SD). The pulmonary blood flow index in the amrinone group was higher (2.9 +/- 0.6 L/min/m2) than in the dopamine-nitroglycerin group (2.2 +/- 0.6 L/min/m2); no significant difference was noted in the mean pulmonary artery pressure. The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.41 +/- 0.07) compared with the amrinone group (0.34 +/- 0.08). Despite lower platelet counts in the amrinone group, no hemorrhagic complications were seen in any patient. CONCLUSIONS: With this dosage regimen, amrinone provides a higher cardiac output, more favorable oxygen dynamics, and lower pulmonary vascular resistance than dopamine and nitroglycerin.     

Ischemic heart disease and postoperative mortality in major vascular surgery. An up-to-date diagnostic approach

BACKGROUND: The aim of this study is to evaluate the efficacy the dobutamine stress echocardiography in predicting the perioperative cardiac risk of patients undergoing major vascular surgery. METHODS: Seventy-seven consecutive and not selected patients, undergoing a surgical treatment requiring aortic cross clamping, were assessed also with a transthoracic dobutamine stress echocardiography. With electrocardiographic and echocardiographic monitoring ventricular ischemia or wall motion abnormalities, 5 micrograms/kg per min of chlorhydrate dobutamine for 5 minutes were infused, followed by other 10 micrograms/kg per min increased up to 40 micrograms/kg per min. During the last 4 minutes 0.25 mg of atropin were infused increasingly up to 1 mg. RESULTS: Of all these patients, 26 had a stress ischemia but only 4 cases underwent a coronary angiography and only 2 of these underwent a preventive myocardial revascularization. Due to poor cardiac conditions pointed out with the dobutamine stress, 3 patients were not treated surgically. With an aggressive intra- and perioperative monitoring 73 patients underwent a surgical treatment: they were 28 aorto-bifemoral, 3 aorto-aortic grafts, 1 aorto-bisiliac thoraco-abdominal interposition graft, and 20 aorto-bifemoral, 4 aorto-femoral, 1 aorto-aortic thoraco-abdominal, 1 aorto-renal by-pass and 7 aorto-iliac-femoral thromboendoarterectomies. In the postoperative period 4 cardiac ischemic complications and 2 deaths (2.5%) were observed. CONCLUSIONS: According to our personal opinion, stress echocardiography can be considered a test with a excellent feasibility and safety rate, not expensive and with a good reproducibility and reliability. It allowed to predict the cardiac risk in our patients suggesting not only the surgical but also the anesthesiologic and the perioperative therapeutic management.     

Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study

OBJECTIVE: To assess the effects of dobutamine at a rate of 5 micrograms/kg/min on hemodynamics and gastric intramucosal acidosis in patients with hyperdynamic septic shock treated with epinephrine. DESIGN: A prospective, interventional, clinical trial. SETTING: An adult, 16-bed medical/surgical intensive care unit of a university hospital. PATIENTS: Twenty septic shock patients with a mean arterial pressure of > 75 mm Hg and a cardiac index of > 3.5 L/min/m2. INTERVENTIONS: After baseline measurements (H0), each patient received dobutamine at a rate of 5 micrograms/kg/min. Baseline measurements included: hemodynamic parameters, tonometric parameters, arterial and mixed venous gases, and arterial lactate concentrations. These measurements were repeated after 1 (H1), 2 (H2), and 3 (H3) hrs. After H2 measurements, dobutamine was stopped. The patients were separated into two groups according to their PCO2 gap (tonometer PCO2-PaCO2). The increased PCO2 gap group was defined by a PCO2 gap > 8 torr (> 1.1 kPa) (n = 13), and the normal PCO2 gap group by a PCO2 gap < or = 8 torr (< or = 1.1 kPa)(n = 7). MEASUREMENTS AND MAIN RESULTS: Dobutamine at 5 micrograms/kg/min had no significant effects on mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, oxygen delivery, and oxygen consumption in epinephrine-treated septic shock. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. During dobutamine infusion, arterial lactate concentration decreased from 5.1 +/- 0.4 in the increased PCO2 gap group and 4.2 +/- 0.4 in the normal PCO2 gap group to 3.9 +/- 0.3 and 3.5 +/- 0.3 mmol/L, respectively (p < .01). The PCO2 gap decreased and gastric intramucosal pH increased in the increased PCO2 gap group from 12 +/- 0.8 (1.6 +/- 0.1 kPa) to 3.5 +/- 0.8 torr (0.5 +/- 0.1 kPa) (p < .01) and from 7.11 +/- 0.03 to 7.18 +/- 0.02 (p < .01), respectively, and did not change in the normal PCO2 gap group. After stopping dobutamine infusion, the PCO2 gap and intramucosal pH returned to baseline values in the increased PCO2 gap group. CONCLUSION: The addition of 5 micrograms/kg/min of dobutamine added to epinephrine in hyperdynamic septic shock selectively improved the adequacy of gastric mucosal perfusion without modification in systemic hemodynamics.     

The haemodynamic effects of milrinone HCl in halothane anaesthetised horses

The haemodynamic effects of milrinone hydrochloride were determined in halothane-anaesthetised horses. Six healthy adult horses were anaesthetised with guaifenesin and thiamylal and maintained with halothane in oxygen (end-tidal halothane concentration of 1.15%). Baseline haemodynamic data were recorded after a 45 min stabilisation period. All 6 horses received a single loading dose of milrinone HCl, 0.2 microgram/kg i.v., followed by progressively increasing infusions of 2.5, 5, 10 and 20 micrograms/kg bwt/min. Each infusion lasted for 15 min and produced dose related increases in heart rate, mean arterial blood pressure, cardiac output, maximum rate of increase and decrease of left ventricular pressure (+/- dP/dtmax) and ejection fraction in halothane anesthetised horses. Median artery blood flow increased following milrinone administration. Right atrial and pulmonary artery pressures, systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes decreased. Most haemodynamic changes were sustained throughout the infusion period and for 30 min following the termination of milrinone infusion. Systemic vascular resistance was increased above baseline values at 30 min following the termination of milrinone infusion. No adverse side effects were observed during this study although a milrinone infusion rate of 20 micrograms/kg bwt/min increased heart rate to values greater than 50 beats/min. The results of this study suggest that milrinone produces beneficial haemodynamic effects in halothane anaesthetised horses and is potentially useful in the treatment of patients with a reduced cardiac output.     

Peptide containing the BCR oligomerization domain (AA 1-160) reverses the transformed phenotype of p210bcr-abl positive 32D myeloid leukemia cells

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 emergency 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, 4, 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 l.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.     

Comparison of haemodynamic responses to cilnidipine and nicardipine in an experimental model of acute congestive heart failure

1. The haemodynamic effects of cilnidipine, a new calcium channel blocker, were examined in a canine model of acute congestive heart failure and were compared with those of nicardipine at equihypotensive doses. 2. The model was prepared by injections of saponin into coronary arteries of anaesthetized open-chest dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF) and left ventricular dP/dt markedly decreased, while left ventricular end-diastolic pressure (LVEDP), right atrial pressure and systemic vascular resistance (SVR) increased. Cilnidipine (0.3, 1.0 and 3.0 micrograms/kg per min), nicardipine (0.3, 1.0 and 3.0 micrograms/kg per min) or the respective vehicle was given i.v. after accomplishment of heart failure. 3. These drugs both produced a comparable reduction in aortic pressure and an increase in AoF associated with profound decreases in LVEDP, SVR and coronary vascular resistance. In contrast, administration of nicardipine was associated with significant increases in heart rate and cardiac contractility but that of cilnidipine was not. 4. These results indicate that cilnidipine as well as nicardipine can exert beneficial haemodynamic effects in a model of acute heart failure probably through lessening afterload and cilnidipine may moderate reflex-induced sympathetic stimulation.     

Cerebral oxygenation during cardiopulmonary bypass in children

OBJECTIVE: Previous work has found cerebral oxygen extraction to decrease during hypothermic cardiopulmonary bypass in children. To elucidate cardiopulmonary bypass factors controlling cerebral oxygen extraction, we examined the effect of perfusate temperature, pump flow rate, and hematocrit value on cerebral hemoglobin-oxygen saturation as measured by near infrared spectroscopy. METHODS: Forty children less than 7 years of age scheduled for cardiac operations with continuous cardiopulmonary bypass were randomly assigned to warm bypass, hypothermic bypass, hypothermic low-flow bypass, or hypothermic low-hematocrit bypass. For warm bypass, arterial perfusate was 37 degrees C, hematocrit value 23%, and pump flow 150 ml/kg per minute. Hypothermic bypass differed from warm bypass only in initial perfusate temperature (22 degrees C); hypothermic low-flow bypass and low-hematocrit bypass differed from hypothermic bypass only in pump flow (75 ml/kg per minute) and hematocrit value (16%), respectively. Cerebral oxygen saturation was recorded before bypass (baseline), during bypass, and for 15 minutes after bypass had been discontinued. RESULTS: In the warm bypass group, cerebral oxygen saturation remained at baseline levels during and after bypass. In the hypothermic bypass group, cerebral oxygen saturation increased 20% +/- 2% during bypass cooling (p < 0.001), returned to baseline during bypass rewarming, and remained at baseline after bypass. In the hypothermic low-flow and hypothermic low-hematocrit bypass groups, cerebral oxygen saturation remained at baseline levels during bypass but increased 6% +/- 2% (p = 0.05) and 10% +/- 2% (p < 0.03), respectively, after bypass was discontinued. CONCLUSIONS: In children, cortical oxygen extraction is maintained during warm cardiopulmonary bypass at full flow and moderate hemodilution. Bypass cooling can decrease cortical oxygen extraction but requires a certain pump flow and hematocrit value to do so. Low-hematocrit hypothermic bypass and low-flow hypothermic bypass can also alter cortical oxygen extraction after discontinuation of cardiopulmonary bypass.     

Cardiorespiratory effects of induction and maintenance of anesthesia with ketamine-midazolam combination, with and without prior administration of butorphanol or oxymorphone

Cardiorespiratory effects of an IV administered bolus of ketamine (7.5 mg/kg of body weight) and midazolam (0.375 mg/kg) followed by IV infusion of ketamine (200 micrograms/kg/min) and midazolam (10 micrograms/kg/min) for 60 minutes was determined in 6 dogs. Ketamine-midazolam combination was administered to dogs on 3 occasions to determine effects of prior administration of IV administered saline solution (1 ml), butorphanol (0.2 mg/kg), or oxymorphone (0.1 mg/kg). The infusion rate of ketamine and midazolam was decreased by 25% for anesthetic maintenance after opioid administration. There were no significant differences in cardiorespiratory variables after saline solution or butorphanol administration; however, oxymorphone caused significant (P < 0.05) increases in mean arterial blood pressure, systemic vascular resistance, and breathing rate. Bolus administration of ketamine-midazolam combination after saline solution caused significant (P < 0.05) increases in heart rate, mean arterial blood pressure, cardiac index, mean pulmonary blood pressure, venous admixture, and significant decreases in stroke index, pulmonary capillary wedge pressure, arterial and mixed venous oxygen tension, arterial oxygen content, and alveolar-arterial oxygen gradient. Opioid administration was associated with significantly (P < 0.05) lower values than was saline administration for heart rate, mean arterial blood pressure, and arterial and mixed venous pH and with higher values for stroke index, pulmonary capillary wedge pressure, and arterial and mixed venous carbon dioxide tension. Prior oxymorphone administration resulted in the highest (P < 0.05) values for mean pulmonary blood pressure, venous admixture, and arterial and mixed venous carbon dioxide tension, and the lowest values for arterial oxygen tension, and arterial and mixed venous pH. Each treatment provided otherwise uncomplicated anesthetic induction, maintenance, and recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous MIDCAB and subtotal gastrectomy in an elderly patient with severe ischemic heart disease

An 81 year old man with severe ischemic heart disease and left ventricular dysfunction was scheduled for a subtotal gastrectomy for his advanced gastric cancer. His cardiac function was so poor that we performed minimally invasive coronary artery bypass grafting (MIDCAB; coronary artery bypass grafting without cardiopulmonary bypass for LAD through a small left thoracotomy), just before the abdominal operation. Anesthesia was induced and maintained with fentanyl, vecuronium and sevoflurane. To control heart rate below 60 bpm during local coronary occlusion for bypass grafting, edrophonium 5 mg was administered just before the occlusion. During the bypass grafting procedure, the patient's heart rate was maintained at 50-60 bpm and his hemodynamic profile slightly declined but was permissible. After bypass grafting, his cardiac performance was improved with low dose dobutamine. Subsequently subtotal gastrectomy was carried out. His postoperative course was uneventful. Combined MIDCAB and abdominal operation may be beneficial for selected patients with severe ischemic heart disease.     

Reflex cardiovascular changes with veratridine in the conscious dog

The present study was undertaken to examine the reflex responses of activation of cardiac sensory receptors in the conscious dog. Intracoronary (left circumflex coronary artery) injection of veratridine (0.10 micrograms/kg) reduced mean arterial pressure (-40 mmHg, P less than 0.05), heart rate (-34 beats/min, P less than 0.05), and maximum rate of rise of left ventricular pressure (LV dP/dtmax) (-419 mmHg/s, P less than 0.05). Bilateral cervical vagal cold block (BVB) eliminated the depressor and bradycardic responses of veratridine. BVB not only eliminated the negative inotropic response to veratridine but reversed it to a positive inotropic response (LV dP/dtmax increased 313 +/- 76 mmHg/s). Ganglionic blockade abolished all effects of veratridine. The bradycardia and negative inotropic effects caused by veratridine were attenuated by either atropine or metoprolol and completely eliminated by the combination of the two antagonists. Veratridine also produced a decrease in renal artery blood flow but had no effect on renal vascular resistance. In contrast, iliac blood flow was increased with veratridine, and this, combined with the depressor effect, resulted in a decrease in iliac vascular resistance (-37%), P less than 0.05). BVB abolished the changes in renal and iliac blood flow or resistance caused by veratridine. The results indicate that activation of cardiac receptors in the conscious dog elicits inhibitory reflexes to the heart and peripheral circulation that are mediated by vagal afferents. After vagotomy, veratridine elicited a reflex positive inotropic response, which may have resulted from activation of cardiac sympathetic afferent fibers.     

Vascular and cardiac effects of amlodipine in acute heart failure in dogs

BACKGROUND: Amlodipine improves exercise capacity in patients with chronic congestive heart failure (HF), but the mechanisms of this effect are unknown. OBJECTIVE: To test the hypothesis, in a canine model of acute, ischemic HF, that amlodipine increases vascular capacitance and reduces cardiac filling pressures. METHODS: Amlodipine was given to 13 anesthetized, splenectomized dogs (six controls and seven with HF). Aortic, left ventricular end-diastolic (LVEDP) and portal venous (Pportal) pressures, cardiac output, portal flow (ultrasonic probe) and intestinal blood volume (IBV, 99mTc blood-pool scintigraphy) were measured. Intestinal vascular conductance (= 1/resistance) and vascular capacitance (CAP) were measured before and 15 mins after repetitive 150 micrograms/kg dosages of amlodipine (maximum cumulative dosage, 1000 micrograms/kg). Pportal-IBV curves were obtained by impeding portal flow (pneumatic cuff), and change in CAP was defined by the change in IBV at Pportal = 7.5 mmHg. HF was induced by microsphere embolization of the left coronary artery. RESULTS: CAP increased in the control group (+ 28%, P < 0.01) but decreased (-9%, P < 0.05) in the HF group. Left ventricular stroke work increased in the control group (P < 0.05), while it decreased (P < 0.05) in the HF group, suggesting a negative inotropic effect. In the control group, LVEDP increased after amlodipine was given (P < 0.05) but did not change significantly in the HF group. CONCLUSIONS: In the acute experimental HF model, amlodipine failed to increase intestinal vascular CAP or decrease filling pressures, and may have had a negative inotropic effect. The experiment failed to demonstrate a beneficial hemodynamic effect of amlodipine in acute HF, and the mechanism of benefit of this agent in chronic HF remains unclear.     

Peripheral vascular versus direct cardiac effects of calcium

Peripheral vascular and direct cardiac effects of calcium chloride were determined in a new animal model, the unanesthetized calf, before and after replacement of its natural heart (NH) with a pneumatically driven artificial heart (AH). Calcium (5 and 10 mg/kg) significantly increased cardiac output (Qt) and reduced systemic vascular resistance (SVR) before and after AH implantation. Increases in Qt in AH calves and reductions in SVR in both NH and AH calves were, however, transient, being present 5 minutes but not 15 minutes after both doses of calcium. Increases in Qt and reductions in SVR were significantly (P less than .05) greater after 10 mg/kg than after 5 mg/kg calcium in NH and AH calves. Both doses of calcium produced greater (P less than .05) increases of Qt in NH than in AH animals but similar reductions in SVR. Pulmonary vascular resitance, heart rate and pulmonary arterial and right atrial pressures were not significantly altered by either dose of calcium in NH or AH calves. Mean aortic pressure was influenced by 10 mg/kg calcium only, being transiently reduced in AH calves and increased in NH animals. Pulmonary shunt (QS/Qt) was increased by both doses of calcium in NH calves but only by 10 mg/kg in AH animals. Correlations of mean change in QS/Qt with mean change in Qt were high both before (r=.99) and after (r=.97) AH implantation. These data demonstrate that calcium significantly reduces SVR in a dose-related manner as well as exerting a positive inotropic effect on the myocardium.     

Breath-hold dobutamine magnetic resonance myocardial tagging: normal left ventricular response

Analysis of the changes in myocardial deformation produced by adrenergic stress has been limited by the imaging techniques used. We used rapid magnetic resonance imaging (MRI) myocardial tagging to map the dose-dependent response to incremental dobutamine in the normal human left ventricle. Thirteen volunteers underwent breath-hold tagged cine MRI during dobutamine infusion. Images were acquired throughout systole to a peak dose of 20 microg/kg/min. End-systolic percent circumferential shortening (%S) was measured at 3 transmural locations and 4 circumferential locations at 3 long-axis positions. Mean circumferential shortening velocity (CSV) was also calculated at each location and dose. Mean %S reached a maximum of 26 +/- 3% at 10 microg/kg/min compared with 21 +/- 4% at baseline (p <0.003). Peak %S was reached by 10 microg/kg/min before a significant increase in heart rate or blood pressure and was unchanged at higher doses. In contrast, CSV increased linearly with dobutamine dose from 4.4 +/- 0.9 mm/s at baseline to 9.8 +/- 1.4 mm/s at 20 microg/kg/min (p <0.0001). Breath-hold tagged dobutamine MRI is safe and effective in detecting regional and transmural changes in function during incremental dobutamine. CSV increased continuously across the dobutamine dose range. At low dose (< or =10 microg/kg/min) %S increased without any change in blood pressure or heart rate. Maintenance of peak %S beyond 10 microg/kg/min in the presence of decreasing systolic intervals resulted from a continued increase in CSV. Thus, CSV may be the preferred measure of contractile function during dobutamine stimulation in human myocardium.