K. M. Vermeyen

Influence of thiopental, etomidate, and propofol on regional myocardial function in the normal and acute ischemic heart segment in dogs

The effects of 30-min infusions of thiopental (20, 30, 40, 50, 60 and 70 mg·kg−1·h−1), etomidute (2.4, 3.6, 7.2, 9.6, 12, and 14.4 mg·kg−1·h−1), and propofol (6, 9, 12, 15, 18, and 21 mg·kg−1·h−1) On regional hemodynamic variables In the normal and acute ischemic heart segment were studied in dogs using ultrasonic segment length gauges. The three agents were associated with a dose-dependent decrease in end-diastolic length, indicating u decrease in left ventricular filling. This effect was most pronounced for propofol. At the doses tested, etomidate did not significantly alter regional myocardial function. Thiopental, however, was associated with a dose-dependent decrease in systolic shortening, which was significantly greater in the ischemic segment. These findings confirm the hemodynamic stability seen with etomidate and show that thiopental depresses myocardial function more in the acute ischemic heart than in the normal heart. The decrease in systolic shortening associated with propofol was similar in the normal and in the acute ischemic heart segment.

Comparison of two different loading doses of milrinone for weaning from cardiopulmonary bypass.

OBJECTIVE To compare the hemodynamic effects, pharmacokinetic profiles, and the need for vasoactive agents between a low (20 micrograms/kg during 15 minutes [group 1; n = 10]) and a high (40 micrograms/kg during 15 minutes [group 2; n = 10]) loading dose of milrinone. DESIGN Prospective, randomized, double-blind. SETTING University hospital. PARTICIPANTS Twenty patients scheduled for elective coronary artery surgery. INTERVENTIONS Weaning from CPB was achieved using a strict protocol. After atrioventricular pacing at 90 beats per minute and preload optimalization, a first weaning attempt was started with only calcium and nitroglycerin as support. If this attempt was unsuccessful (cardiac index < 2L/min/m2), CPB was reinitiated and weaning level 2 was prepared, consisting of inotropic support with milrinone. Patients received either the low (group 1) or the high (group 2) loading dose of milrinone. After the end of the loading dose, a continuous infusion of milrinone of 0.5 micrograms/kg/min was started in both groups. MEASUREMENTS AND MAIN RESULTS Both groups were comparable regarding preoperative and intraoperative data. Hemodynamic data were comparable in both groups at each time of measurement (p = 0.941). The need for vasoactive medication (norepinephrine [NE]) in order to keep mean arterial pressure > or = 50 mm Hg was significantly higher in group 2 (p = 0.004). Need for NE during the loading infusion was 9.6 +/- 4.9 micrograms (mean +/- SEM) in group 1 and 41.6 +/- 7.6 micrograms in group 2 (p = 0.004). Need for NE during the immediate post-CPB period was also higher in group 2 (16.0 +/- 10.4 micrograms in group 1 and 232.5 +/- 82.8 micrograms in group 2 (p = 0.002)). Plasma clearance of milrinone after CPB was less in both groups than in healthy volunteers. However, clearance of milrinone was significantly higher in group 2 (p = 0.006), and consequently, half-life of milrinone was significantly less in group 2 (p = 0.007). CONCLUSIONS The present results demonstrate that when milrinone is used during weaning from CPB, a loading dose of 20 micrograms/kg provided to similar hemodynamic support a loading dose of 40 micrograms/kg. The need for vasoconstrictive medication was significantly less in the group with the low loading dose.

Central-to-peripheral arterial pressure gradient during cardiopulmonary bypass: relation to pre- and intra-operative data and effects of vasoactive agents.

A significant central–to–peripheral arterial pressure gradient may exist during and after cardiopulmonary bypass (CPB). The etiology and mechanisms of this phenomenon remain controversial. We studied the pressure gradient between aorta, brachial artery and radial artery in 68 patients, scheduled for elective coronary artery bypass surgery. We evaluated whether choice of cardioprotection during CPB (use of cold cardioplegic solution or use of intermittent crossclamping under protection with lidoflazine), and choice of pulsatile or nonpulsatile flow during the course of CPB, affected the magnitude and duration of the systolic pressure gradient. We also studied whether central–to–peripheral pressure gradient was influenced by administration on CPB of different vasoactive drugs with different mode of action: sodium nitroprusside (direct action on the vessels), droperidol (alpha–adrenergic blocking action), ketanserin (5–hydroxytryptamine antagonist) and phenylephrine (selective alpha,–agonist).

Efficacy and safety of aprotinin in aortocoronary bypass and valve replacement operations: a placebo-controlled randomized double-blind study

To assess the efficacy and safety of the use of a high-dose regimen of aprotinin in routine cardiac operations, a placebo-controlled randomized double- blind study was conducted in 93 adult patients undergoing cardiopulmonary bypass. Aprotinin-treated patients (group A, n = 46) received 2 × 106 Kallikrein Inactivating Units (KIU) of aprotinin before incision, 2 × 106 KIU in the priming solution and 5 x 105 KIU/h during CPB. Control patients (group B, n = 47) received the same volume of normal saline. Mean postoperative blood loss in ml after six hours and in total until removal of thoracic drains decreased significantly from 752 and 1933 in controls, to 358 and 1051 in treated patients (p < 0.001). Mean total transfusion needs were 2.6 (A) and 4.8 (B) units per patient. Adverse events were evenly distributed between both groups and could not be attributed to aprotinin use. We, therefore, recommend the use of a high-dose regimen of aprotinin for routine cardiac operations despite its cost.

Use of the right-sided precordial lead V4R in the detection of intraoperative myocardial ischemia.

This study evaluated the benefit of additional electrocardiographic monitoring of the right precordial lead V4R for detection of ST segment changes during elective coronary artery bypass surgery in 210 patients. ST segment analysis was performed for leads I, II, CB5, and V4R. ST segment changes were noted in 60 patients. Of these, 32 had combined left-sided and right-sided coronary artery disease (group A), and 28 had only left-sided coronary artery disease on coronary angiography (group B). Lead sensitivity was estimated assuming that all ST segment changes were true positive responses. Sensitivity using a single lead was greatest for lead CB5 in the two groups (76% in group A and 78% in group B). Sensitivity for lead I was low in both groups (34% in group A and 26% in group B). Sensitivity for lead II was 63% in group A and 52% in group B, and sensitivity for lead V4R was 71% in group A but only 37% in group B. Combination of leads V4R and CB5 increased sensitivity to 98% in group A. In group B, this lead combination had a sensitivity of 93%, but lead combinations I-CB5-V4R and II-CB5-V4R were more sensitive (97% and 100%, respectively). The monitoring of lead V4R allowed detection of 20% of ST segment changes in group A that would have passed undetected if only leads I, II, and CB5 were monitored. These results demonstrate the value of additional electrocardiographic monitoring of the right precordial lead V4R during coronary artery bypass grafting in patients with right-sided coronary artery disease.

Effects of Calcium on Left Ventricular Function Early After Cardiopulmonary Bypass

OBJECTIVES Evaluation of the effects of intravenous CaCl2 on systolic and diastolic function early after separation from cardiopulmonary bypass (CPB) DESIGN: Prospective study SETTING University hospital PARTICIPANTS Twenty patients scheduled for elective coronary artery surgery INTERVENTIONS Left ventricular (LV) pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the LV were simultaneously recorded on videotape. Measurements were obtained before the start of CPB, 10 minutes after termination of CPB, after intravenous administration of CaCl2, 5 mg/kg, and 10 minutes later. MEASUREMENTS AND MAIN RESULTS Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relation. CaCl2 increased Ees from 2.62 +/- 0.46 to 5.58 +/- 0.61 (mean +/- SD), but induced diastolic dysfunction with an increase in Kc from 0.011 +/- 0.006 to 0.019 +/- 0.007. These changes were transient and had disappeared within 10 minutes after administration of CaCl2. CONCLUSIONS CaCl2 early after CPB transiently improved systolic function at the expense of an increase in ventricular stiffness, suggesting temporary diastolic dysfunction.

Oxygen transport and myocardial function after the administration of albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% to rabbits

Background and objective: The effects of administering albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% on oxygen transport and left ventricular function were prospectively investigated in different experimental conditions: baseline, fluid load, after 10 min of myocardial ischaemia and after reperfusion. Methods: Twenty-seven rabbits received at random one of three colloids in escalating boluses over 10-15 min to achieve left ventricular end-diastolic pressures (LVEDP) between 8 and 10 mmHg. A branch of the left anterior descending coronary artery was then temporarily occluded by a ligature and released after 10 min. Myocardial function was assessed using left ventricular pressure recordings and dimension data obtained from ultrasound crystals inserted onto the ventricular wall. Blood was sampled for the determination of oxygen delivery and consumption, the oxygen extraction ratio, acid-base status, and glucose and lactate concentrations. Results: Administration of the colloids similarly increased oxygen delivery and improved left ventricular function in all groups. Peak rate of pressure development (dP/dtmax) and oxygen delivery were reduced during ischaemia and reperfusion. The decrease in dP/dtmax was more pronounced in the hydroxyethylstarch group. Conclusions: Administration of albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% had similar effects on oxygen delivery and myocardial function. After ischaemia and during reperfusion, the decrease in myocardial function was most pronounced with hydroxyethylstarch 6%.

Onset of segmental relaxation dysfunction with decreased myocardial tissue perfusion: Modulation by propofol

OBJECTIVES To estimate myocardial oxygen needs by studying the effects of reduced coronary blood flow on segmental myocardial function. To study the tolerance of limited oxygen supply to a myocardial segment during propofol administration. DESIGN A prospective experimental study. SETTING An experimental animal laboratory in a university. PARTICIPANTS Eighteen adult dogs, weighing 20 to 35 kg. INTERVENTIONS Open thorax open pericardium experiments were performed under standard anesthetic conditions. Segment length gauges were placed subendocardially in an anteroapical and in a basal segment. Flow to the anteroapical segment was reduced by tightening a micrometer-controlled snare placed around the second diagonal coronary artery. Left ventricular pressure-length signals allowed for identification of onset of relaxation dysfunction. Myocardial tissue flow at onset of relaxation dysfunction was defined as critical flow. Tracer microspheres were used to measure subepicardial, midwall, and subendocardial flow at critical flow. MEASUREMENTS AND MAIN RESULTS Stability of the model and reproducibility of critical flow were studied in a first series of six dogs with the hearts paced at 110 beats/min. Hemodynamics, left ventricular, and segmental myocardial function during critical flow were stable. Subendocardial critical flow was identical with each flow reduction (45% +/- 5, 44% +/- 8, and 43% +/- 5 of baseline myocardial tissue flow). In a second series of six dogs, critical flow was measured at pacing rates 100 beats/min, 150 beats/min, and 100 beats/min with propranolol, 0.1 mg/kg, pretreatment. Critical flows were 38% +/- 5, 55% +/- 6, and 17% +/- 2 of baseline, respectively (p < 0.05). In a third series of six dogs, critical flow was measured during sufentanil, 0.6 microgram/kg/min, and increasing doses of propofol (P0: 0.0 mg/kg/h, P4: 4.0 mg/kg/h and P8: 8.0 mg/kg/h). Heart rate was kept constant at 110 beats/min. When compared with P0, hemodynamic and left ventricular contraction parameters were stable at P4 but were decreased at P8. At P0, critical flow was: 0.63 +/- 0.14, at P4: 0.34 +/- 0.09, and at P8: 0.25 +/- 0.07 mL/min/g (p < 0.05). CONCLUSION Critical myocardial tissue flow was reproducible and sensitive for altered myocardial oxygen needs. The negative inotropic properties of P decreased myocardial oxygen needs during unchanged hemodynamic and left ventricular contraction parameters. A higher P dose depressed left ventricular function.