Blood warm reperfusion: a necessary adjunct to heart-valve surgery in low-risk patients?

AIM: The aim of this prospective, randomized study was to determine whether blood warm reperfusion improves myocardial protection provided by cold crystalloid cardioplegia in patients undergoing first-time elective heart-valve surgery, using cardiac troponin I release as the criterion for evaluating the adequacy of myocardial protection. METHODS: Seventy patients with a left ventricular ejection fraction greater than 40% were randomly assigned to 1 of 2 myocardial protection strategies: 1) cold crystalloid cardioplegia with no reperfusion or 2) cold crystalloid cardioplegia followed by 2-minute blood warm reperfusion before aortic unclamping. Cardiac troponin I concentrations were measured in serial venous blood samples drawn immediately prior to cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 h. RESULTS: Randomization produced 2 equivalent groups. The total amount of cardiac troponin I released (7.17+/- 14.8 mg in the crystalloid cardioplegia with no reperfusion group and 5.82+/-4.66 mg in the crystalloid cardioplegia followed by blood warm reperfusion group) was not different (P > 0.2). Cardiac troponin I concentration did not differ for any sample in either of the 2 groups. The total amount of cardiac troponin I released was higher in patients who required inotropic support (9.14 +/-16.2 mg) than those who did not (4.73+/-4.52 mg; P = 0.009). CONCLUSIONS: Our study shows that adding blood warm reperfusion to cold crystalloid cardioplegia provides no additional myocardial protection in low-risk patients undergoing heart-valve surgery.

The effect of ginkgo biloba extract on free radical production in hypoxic rats.

In the present study, we assayed the antioxidant properties of Ginkgo biloba (Gb) extract on rats submitted to 21 d of chronic hypoxia. Doses of 25 and 50 mg/kg were examined. Oxygenated free radical production measured by the chemiluminescence technique was significantly decreased in treated rats compared to control rats placed in similar experimental conditions, and this effect was more significant at the 50 mg/kg dose. On the other hand, no antioxidant enzyme activities of the drug were observed towards red blood cells. These results suggest that ginkgo biloba extract has a free radical scavenging action. These antioxidant properties could explain the beneficial hematological properties of Gb extract.

Myocardial fixation of anticardiac troponin I antibody and cardiac troponin I release.

BACKGROUND: The threefold aim of this experimental study was to test the correlation of cardiac troponin I released to myocardial infarction size and myocardial fixation of anticardiac troponin I antibody and to determine how long after myocardial infarction the measure of cardiac troponin I concentration can evaluate myocardial infarction size. METHODS: Forty rabbits were assigned either to a control group or to an experimental preconditioned group. Infarction was obtained by tightening a snare around the left anterior descending artery. Serial venous blood samples were drawn for measurement of cardiac troponin I. The rabbits were sacrificed at 72 hours and a histological study was performed to determine the infarct size and the size of the area void of fixation of anticardiac troponin I antibody. RESULTS: There was a linear correlation between the total amount of CTn I released and both infarct size (r=0.45, p<0.02) and the size of the area void of anti-cardiac troponin I antibody (r=0.47, p<0.02). These two sizes were strongly correlated (r=0.95, p<0.02). The hour 9 CTn I sample was the best correlated with both the infarct size (r=0.47, p<0.02) and the size of area void of anticardiac troponin I antibody (r=0.45, p<0.02). CONCLUSIONS: Our study shows that: 1) cardiac troponin I release is correlated to both myocardial infarction size and the size of area void of fixation of anticardiac troponin I antibody, 2) the area void of anticardiac troponin I antibody fixation includes the whole ischemic area, and 3) evaluation of myocardial infarction size can be obtained by CTn I concentration as early as the ninth hour.

Intermediate lukewarm (20 degrees c) antegrade intermittent blood cardioplegia compared with cold and warm blood cardioplegia.

BACKGROUND: In the field of intermittent antegrade blood cardioplegia, 3 levels of temperature are commonly used: (1) cold (8 degrees C); (2) tepid (29 degrees C); and (3) warm (37 degrees C). Given the 21 degrees C spread and the metabolic changes that can occur between cold (8 degrees C) and tepid (29 degrees C) cardioplegia, we thought it worthwhile to test a temperature halfway between the cold and tepid levels. The aim of this study was to test the quality of myocardial protection provided by intermediate lukewarm (20 degrees C) cardioplegia by comparing it with cold and warm cardioplegia. Protection was assessed by measuring cardiac troponin I release. METHODS: One hundred thirty-five patients undergoing coronary artery bypass grafting were enrolled in a prospective randomized trial comparing cold (8 degrees C), intermediate lukewarm (20 degrees C), and warm (37 degrees C) antegrade intermittent blood cardioplegia. Cardiac troponin I concentrations were measured in serial venous blood samples. RESULTS: The total amount of cardiac troponin I released was significantly higher in the cold group (4.7 +/- 2.3 microg) than in the intermediate lukewarm (3.4 +/- 2.0 microg) or the warm (3.1 +/- 2.7 microg) groups. The cardiac troponin I concentration was significantly higher at hour 6 in the intermediate lukewarm group (1. 23 +/- 0.55 microg/L) than in the warm group (0.89 +/- 0.50 microg/L). CONCLUSIONS: Intermittent antegrade intermediate lukewarm blood cardioplegia is appropriate and clinically safe. Cardiac troponin I release suggests that intermediate lukewarm cardioplegia is better than cold cardioplegia but less effective than warm cardioplegia in low-risk patients. We therefore recommend the use of warm cardioplegia in low-risk patients.

Red blood cell metabolism and hemoglobin oxygen affinity. Effect of vinburnine on normobaric hypoxic rats.

The influence of Vinburnine on red blood cell metabolism and hemoglobin oxygen affinity was investigated in normobaric rats (FiO2: 10%). Two periods of hypoxic exposure were performed (10-21 d). In each experimental series, rats were divided into two groups: Treated rats received a daily intraperitoneal injection of drug (4 mg/kg). Control rats in the same conditions of hypoxia received an isotonic saline solution. For a 10 d exposure period, Vinburnine does not affect red blood cell metabolism nor hemoglobin oxygen affinity. At 21 d period exposure, 2, 3 diphosphoglycerate (2, 3 DPG) and ATP amounts increase in treated rats. The rate of increase was 10% (p<0.05) and 28% (p<0.01), respectively. Red blood cell metabolism effect of Vinburnine was not accompanied by a modification in affinity hemoglobin oxygen (Hb-O2); no statistically significant difference was observed between treated rats and control rats concerning p50 (partial pressure oxygen at half hemoglobin saturation). Results suggest that Vinburnine has a metabolic effect corresponding to a glycolysis anaerobic stimulation, which can improve oxygen delivery to tissues and could explain the favorable hemoreological action of Vinburnine observed in a previous investigation.

Determination of cardiac troponin I forms in the blood of patients with acute myocardial infarction and patients receiving crystalloid or cold blood cardioplegia.

To determine the forms of cardiac troponin I (cTnI) circulating in the bloodstream of patients with acute myocardial infarction (AMI) and patients receiving a cardioplegia during heart surgery, we developed three immunoenzymatic sandwich assays. The first assay involves the combination of two monoclonal antibodies (mAbs) specific for human cTnI. The second assay involves the combination of a mAb specific for troponin C (TnC) and an anti-cTnI mAb. The third assay was a combination of a mAb specific for human cardiac troponin T (cTnT) and an anti-cTnI mAb. Fifteen serum samples from patients with AMI, 10 serum samples from patients receiving crystalloid cardioplegia during heart surgery, and 10 serum samples from patients receiving cold blood cardioplegia during heart surgery were assayed by the three two-site immunoassays. We confirmed that cTnI circulates not only in free form but also complexed with the other troponin components (TnC and cTnT). We showed that the predominant form in blood is the cTnI-TnC binary complex (IC). Free cTnI, the cTnI-cTnT binary complex, and the cTnT-cTnI-TnC ternary complex were seldom present, and when present, were in small quantities compared with the binary complex IC. Similar results were obtained in both patient populations studied. These observations are essential for the development of new immunoassays with improved clinical sensitivity and for the selection of an appropriate cTnI primary calibrator.

Warm reperfusion and myocardial protection.

BACKGROUND: The aim of this study was to determine whether warm reperfusion improves myocardial protection with cardiac troponin I as the criteria for evaluating the adequacy of myocardial protection. METHODS: One hundred five patients undergoing first-time elective coronary bypass surgery were randomized to one of three cardioplegic strategies of either (1) cold crystalloid cardioplegia followed by warm reperfusion, (2) cold blood cardioplegia followed by warm reperfusion, or (3) cold blood cardioplegia with no reperfusion. RESULTS: The total amount of cardiac troponin I released tended to be higher in the cold blood cardioplegia with no reperfusion group (3.9+/-5.7 microg) than in the cold blood cardioplegia followed by warm reperfusion group (2.8+/-2.7 microg) or the cold crystalloid cardioplegia followed by warm reperfusion group (2.8+/-2.2 microg), but not significantly so. Cardiac troponin I concentration did not differ for any sample in any of the three groups. CONCLUSIONS: Our study showed that the addition of warm reperfusion to cold blood cardioplegia offers no advantage in a low-risk patient group.

Crystalloid versus cold blood cardioplegia and cardiac troponin I release.

BACKGROUND: Cardiac troponin I (CTnI) has been shown to be a marker of myocardial injury. The aim of this study was to compare antegrade crystalloid cardioplegia with antegrade cold blood cardioplegia with warm reperfusion using CTnI release as the criteria for evaluating the adequacy of myocardial protection. METHODS AND RESULTS: Seventy patients were randomly assigned to receive crystalloid or blood cardioplegia. CTnI concentrations were measured in serial venous blood samples drawn just before cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 hours and daily thereafter for 5 days. ANOVA with repeated measures was performed to test the effect of the type of cardioplegia on CTnI release. The total amount of CTnI released was higher in the crystalloid cardioplegia group than in the blood cardioplegia group (11.2 +/- 8.9 versus 7.8 +/- 8.6 micrograms, P < .02). CTnI concentration was significantly higher in the crystalloid group than in the blood group in the samples drawn at hours 9 and 12. Three patients in each group had ECG evidence of perioperative myocardial infarction. Eight patients in the crystalloid group and five patients in the blood group had CTnI evidence of perioperative myocardial infarction. CTnI release was significantly lower in patients requiring no electrical defibrillation after aortic unclamping. CONCLUSIONS: Cold blood cardioplegia followed by warm reperfusion is beneficial in an unselected group of patients with a preserved left ventricular function undergoing an elective first coronary artery bypass grafting. CTnI allowed the diagnosis of small perioperative necrotic myocardial areas. The need for electrical defibrillation after aortic unclamping was related to a higher release of CTnI. A further study is necessary to determine whether this technique was beneficial because of cold blood cardioplegia, warm reperfusion, or both.

Spectrofluorimetric determination of 5-methoxypsoralen pharmacokinetic in patients' serum.

In medicine, psoriasis and vitiligo are most often treated with PUVA therapy (psoralen plus ultraviolet A). The determination of psoralen in patients' blood is necessary, as it is admitted that the therapeutic efficiency depends on drug concentration in patients' serum. The amount of UVA to administer is inversely proportional to serum peak concentration. High-performance liquid chromatography (HPLC) and gas chromatography are the most employed methods for determining psoralens in patients' serum. The 2 techniques are precise and very sensitive, but time consuming. The aim of this paper is to propose a suitable method which is rapid and simple. It is a spectrofluorimetric technique for 5-methoxypsoralen (5-MOP) determination in the serum of patients treated with PUVA therapy. 5-MOP extraction was carried out with an heptane/dichloromethane mixture (4/1; v/v), according to the Stolk method (1980). A calibration curve (CC) was plotted from 5-MOP concentrations (range 50, 100, 200, 300, 400, 500 ng/ml). The CC was linear with a good coefficient of correlation: r = 0.9971, and a suitable coefficient of variation (CV) of 7.0%. The recovery of the method ranged from 85.3 +/- 4.2 to 108 +/- 4.1%. The assay precision gave a CV ranging from 0.10 to 6.90%, with an error inferior to +/-10%. The method did not reveal any interference from serum components on the 5-MOP emission wavelength. The limit of detection of 5-MOP was 15 ng/ml. The proposed procedure was proved to be appropriate for a rapid determination of 5-MOP in patients' serum. This technique could also be employed for other psoralens used in PUVA therapy (e.g., 8-methoxypsoralen).

Crystalloid cardioplegia route of delivery and cardiac troponin I release.

BACKGROUND: Cardiac troponin I (CTn I) has been shown to be a marker of myocardial injury. Incomplete distribution of cardioplegic solution may be responsible for injury in jeopardized myocardial areas. The aim of this study was to compare CTn I release with respect to the route of delivery of crystalloid cardioplegia, either antegrade only or initially antegrade followed by retrograde cardioplegia for the remainder of the operation, in patients undergoing elective coronary artery bypass grafting. METHODS: Sixty patients were randomly assigned to one of two cardioplegia groups. Cardiac troponin I concentrations were measured in serial venous blood samples drawn just before cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 hours and daily thereafter for 5 days. Analysis of variance with repeated measures was performed to test the effect of route of delivery, coronary disease, collateral circulation, risk of cardioplegia maldistribution, and number of grafts on release of CTn I. RESULTS: Compared with the antegrade route, the combined route offered no advantage in an unselected group of patients undergoing an elective first cardiac operation and having preserved left ventricular function. The CTn I concentration did not differ between groups for any of the samples considered. In patients with major left main coronary artery stenosis, CTn I release was significantly higher at hour 9 in the antegrade group than in the group with combined delivery. CONCLUSIONS: A combined route of delivery of crystalloid cardioplegia is beneficial in patients with major stenosis of the left main coronary artery. Cardiac troponin I sensitivity is relevant in this study. Release of CTn I should be useful in determining the best form of myocardial protection for each patient.

Effects of myocardial ischemia on the release of cardiac troponin I in isolated rat hearts.

BACKGROUND: The twofold aim of this experimental study was (1) to verify the correlation between the duration of ischemia and concentration of cardiac troponin I and (2) to compare the release of cardiac troponin I with histologic findings. METHODS: Experiments were done on 18 rat hearts, which were perfused according to the Langendorff method, immediately after excision in group I (control group) and after immersion for 3 hours (group II) and 6 hours (group III) in St. Thomas' Hospital solution at 4 degrees C. During reperfusion, the release of cardiac troponin I, creatine kinase isoenzyme MB, and lactate dehydrogenase, the recovery of left ventricular pressure, and heart rates were compared among the three groups. After the experiment, three samples of myocardium (left ventricle, right ventricle, and septum) were taken for histologic examination. RESULTS: Cardiac troponin I concentration was significantly higher in group III than in groups I and II and in group II compared with group I. Cardiac troponin I concentration increased as the ischemic period increased. The relation between cardiac troponin I release and ischemic duration tended to be linear. Creatine kinase MB and lactate dehydrogenase concentrations did not differ from one group to the other. Left ventricular pressure was not significantly different among the groups. In the control group, no heart had more than 10% of the myocytes affected. One of six hearts in group II and three of six in group III had more than 10% of myocytes affected. CONCLUSION: This experimental study showed (1) that cardiac troponin I is an early marker of ischemic injury and (2) that cardiac troponin I concentration increases as the ischemic period increases. Early cardiac troponin I release appears to correlate with the extent of ischemic injury in rats undergoing buffer perfusion.

Lipophilicity determination of psoralens used in therapy through solubility and partitioning: comparison of theoretical and experimental approaches.

The aim of this study was to determine and to compare experimental and theoretical solubilities (S) as well as partition coefficients (PC) in an octanol/water system of psoralen (P), 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP). For each psoralen, experimental results were performed in triplicate with a spectrofluorimetric technique. The measurements were achieved 10 times for each solution. The obtained order of the solubilities in pure octanol was 5-MOP approximately TMP > P > 8-MOP, while in water-saturated octanol it was expressed as follows: TMP approximately 5-MOP > P > 8-MOP. However, the following order was found for hydrophobicity: TMP > 5-MOP > 8-MOP > P. The solubility ratios (SR) in pure octanol and water were assessed (mean +/- SD): 3.13 +/- 0.01 (P), 2.60 +/- 0.01 (8-MOP), 3.75 +/- 0.01 (5-MOP), and 5.11 +/- 0.01 (TMP). In saturated phases, they were 3.27 +/- 0.01, 2.63 +/- 0.01, 3.85 +/- 0.01, and 5.32 +/- 0.01, respectively. The PCs were determined with low concentrations according to the Dearden and Bresnen32 method and they were 1.67 +/- 0.01, 1.93 +/- 0.01, 2.00 +/- 0.01, and 3.14 +/- 0.01, respectively. Solubility parameters (delta), in Hildebrand unit (H) or in (cal/cm3)1/2, were evaluated. They confirmed the polarity of psoralens, previously expressed through the PC, although the positional isomers (5-MOP and 8-MOP) revealed no difference. Hildebrand's approach to the solubility of regular solutions and Yalkowsky's concept of the solubility of nonelectrolytes and weak electrolytes in an octanol/water system permitted a comparison of the theoretical and experimental results. The perspective of this work is to use the physicochemical properties of the psoralens in practice for insuring convenient experimental assays and the prediction, in vitro, of the percutaneous absorption of these compounds.

Effects of a selective sleep deprivation on subsequent anaerobic performance.

The aim of the study was to investigate the effects of a partial sleep deprivation on a subsequent supramaximal exercise evaluated from the 30 second Wingate test, and on the following recovery. To take into account the active muscle mass, the Wingate test was performed against a constant braking force related to the data of a force-velocity test conducted on a Monark cycle ergometer (Model 814 E with weights) one week before the experimental test. Eight highly trained athletes were enrolled for this study. The changes in ventilatory and metabolic responses were analyzed during and upon completion of physical 30 second exercise, taking place after two nights, in other words, after a reference night and after a night with reduced sleep. Partial sleep deprivation was obtained by delaying bedtime until 3 a.m. The 30 second Wingate test was performed between 9 a.m. and noon the following days, using a Monark ergometer (Model 814 F). The analyses of change scores disclosed that there were no main significant effects for measures of ventilation, lactates and pH(v) levels under the two experimental conditions. The peak power, the mean power output and the peak velocity recorded after partial sleep deprivation were not modified in comparison with the values obtained after the reference night. These findings suggest that acute sleep loss did not contribute to alterations in supramaximal exercise.

Use of cardiac troponin I as a marker of perioperative myocardial ischemia.

Troponin I is a contractile protein comprising three isoforms, two related to the skeletal muscle and one to the cardiac fibers. Cardiac troponin I (CTn I) is specific, without any cross-reactivity with the other two. Several studies have demonstrated its release after acute myocardial infarction. In contrast, CTn I never has been found in a healthy population, marathon runners, people with skeletal disease, or patients undergoing non-cardiac operations. Thus, CTn I is a more specific marker of cardiac damage than common serum enzymes. It is also more sensitive, allowing diagnosis of perioperative microinfarction and detection of acute myocardial infarction much earlier after the onset of ischemia (4 hours). Using a rapid one-step assay, we measured the release of CTn I in two groups of patients after operation: 20 with calcified aortic stenosis and normal coronary arteries (aortic valve replacement group and control group) and 20 undergoing coronary artery bypass grafting. In the overall population CTn I peaked at hour 6 and practically disappeared after day 5. Mean values were higher in the coronary artery bypass grafting group. In the aortic valve replacement group, a positive correlation was found between aortic cross-clamping time and CTn I, which is a reliable marker of cardiac ischemia during heart operations and can be used to evaluate cardioprotective procedures.

[In vitro study, in perfused rabbit heart, of interaction between two anti-arrhythmia agents: amiodarone and disopyramide]. / Etude in vitro, sur le coeur perfusé de lapin, de l'interaction entre deux antiarythmiques: l'amiodarone et le disopyramide.

The influence of 15 day's amiodarone administration (30 mg/kg/day) on myocardial uptake kinetics and electrocardiographic changes of disopyramide was examined on the isolated perfused rabbit heart (n = 24) under electrical stimulation. Amiodarone significantly reduced myocardial uptake and potentialized the effect of disopyramide on intraventricular conduction.

[Platelet antioxidant enzyme activities in arteriopathy]. / Activités des enzymes antioxydantes plaquettaires au cours de l'artériopathie.

Some publications have pointed out that oxygen free radicals can induce injury of vessel wall and increase platelet aggregation and clotting, which can suppose a dependent relationship with arteriosclerotic process. We therefore studied the hypothesis of a possible abnormal platelet antioxidant enzymatic equipment in arteriopathic patients. A control group of 20 healthy subjects and an other one of 40 non diabetic patients with peripheral arterial disease were investigated, and the following tests were performed: measure of transcutaneous oxygen tension (PTCO2), determination of activity of platelet superoxide dismutase (SOD), glutathione-peroxidase (G-Px) and catalase (CAT). A significant decrease of SOD and G-Px is observed in platelets of arteriopathic patients. This decrease seems to be correlated with the severity of ischemia. The pathological reduction of platelet antioxidant equipment can be one factor enhancing thrombotic complications in chronic arterial disease.

[Analytical interference of lipid parenteral feeding with the determination of methemoglobin levels by an autoanalyzer]. / Interférence analytique de l'alimentation parentérale lipidique avec la détermination du taux de méthémoglobine par autoanalyseur.

We report here an unusual cause of analytical interference observed in methemoglobin values of patients parenterally given nutritive lipid emulsions. In these patients, harboured in intensive care department, T Hb, % O2 Hb, % COHb, Met Hb values are systematically measured using IL 282 CO-Oximeter autoanalyser in addition to daily blood gas determination (pH, PaCO2, PaO2). An increase in % Met Hb rate up to 10-20% was observed in lipid emulsions receiving patients. We first verified that washing red blood cells with saline instantaneously lowers Met Hb values to less than 1%. The mechanism of this interference was addressed by performing three Met Hb determination methods in normal blood in vitro added with variable amounts of lipid emulsions: CO-Oximeter determination, classical Evelyn Malloy method, analysis of continuous absorption spectra between 480 and 640 nm. Results corroborate the spectral origin of the analytical interference observed with CO-Oximeter and leading to false positive values. Blood lipids increase unspecifically the wave length proportional absorption between 480 and 640 nm. Evelyn Malloy's technique suppresses this interference since it uses the ratio of differences in optical densities. Our results emphasize the necessity of knowing patients therapeutics when performing laboratory investigations.

[Proceedings: Erythrocyte 2,3-diphosphoglycerate during the development of myocardial infarct. Concerning 118 cases]. / Le 2,3-diphosphoglycérate érythrocytaire au cours de l'évolution de l'infarctus du myocarde

In four groups of patients with myocardial infarction the increase of 2.3-DPG concentration in erythrocyte was important when complications appeared during the evolution or when the patients died.