[Emergencies in cardiac surgery: prophylaxis or correction?]. / Emergenze in cariochirurgia: profilassi o correzione?

Management of coagulation during cardiac surgery is always challenging for the anesthesiologist, even in elective operations. The strict linkage between coagulation and inflammation is amplified during cardiopulmonary bypass due to the contact of the blood with the foreign surfaces. In emergencies, coagulative derangement could be worse but the cardiocirculatory instability and parenchimal failure often overcome the attention to this problem.

Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

[Control of postoperative pain in heart surgery. Comparison of analgesics]. / Il controllo del dolore postoperatorio in cardiochirurgia. Analgesici a confronto.

BACKGROUND: Evaluation of the efficacy of three analgesic drugs (tramadol, ketorolac, and morphine) for the control of postoperative pain in cardiac surgery. DESIGN: prospective randomized study. SETTING: University Hospital, Postoperative intensive care unit. PARTICIPANTS AND INTERVENTION: sixty patients, who underwent cardiac surgery, were studied. They were randomly allocated in four groups, treated with a different postoperative analgesic therapy: A) tramadol in continuous infusion; B) ketorolac in continuous infusion; C) tramadol, in repeated boluses; D) morphine, in repeated boluses. MEASUREMENTS: the analgesic efficacy of each drug and administration protocol was evaluated by hemodynamic stability, arterial blood gases analysis, Visual Analogue Scale (VAS), resting and after cough, the VAS derivatives PID and SPID, the concentration of plasma epinephrine and norepinephrine, at eight postoperative times. Adverse effects were also registered. RESULTS: Only tramadol, in continuous i.v. infusion, achieves the required analgesic effect, significantly decreasing both VAS scores, at the end of the administration of the drug. This treatment reduced epinephrine plasma levels in the first postoperative day, when the residual analgesic effect of surgical anesthesia can be considered disappeared. CONCLUSIONS: Tramadol in continuous infusion (dose 12 mg/h) proved to be effective for the control of postoperative pain after cardiac surgery. The proposed dose represents a good compromise between analgesic efficacy and interference with the vital functions of operated patients.

Pulsatile normothermic cardiopulmonary bypass and plasma catecholamine levels.

The aim of the study was to assess plasma catecholamine levels in patients undergoing myocardial revascularization and relate them to pulsatile (P) and nonpulsatile (NP) normothermic cardiopulmonary bypass (CPB). Twenty-eight patients were randomly assigned to different CPB management: 15 patients were assigned to group 'P', 13 patients to group 'NP'. During normothermic extracorporeal circulation, group 'P' received pulsatile perfusion, while group 'NP' received nonpulsatile perfusion. Levels of epinephrine and norepinephrine were evaluated during the operation and in the intensive care unit (ICU), at seven time points. Haemodynamic assessment was performed at four time points in the same period. Demographic and surgical data were collected, and the postoperative course was analysed. Epinephrine levels were markedly increased during CPB in both groups, while norepinephrine increased more in group NP in comparison with group P. No significant difference was found in fluid administration, transfusion, drugs usage, or postoperative complications. Normothermic pulsatile CPB seems to achieve reduced levels of norepinephrine. A clinical beneficial effect of this finding was not demonstrated during the study.

Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study.

OBJECTIVES: We sought to investigate the effect of topical application of tranexamic acid into the pericardial cavity in reducing postoperative blood loss in coronary artery surgery. METHODS: A prospective, randomized, double-blind investigation with parallel groups was performed. Forty consecutive patients undergoing primary coronary surgery were randomly assigned to group 1 (tranexamic acid group) or group 2 (placebo group). Tranexamic acid (1 g in 100 mL of saline solution) or placebo was poured into the pericardial cavity and over the mediastinal tissues before sternal closure. The drainage of mediastinal blood was measured hourly. RESULTS: Chest tube drainage in the first 24 hours was 485 +/- 166 mL in the tranexamic acid group and 641 +/- 184 mL in the placebo group (P =.01). Total postoperative blood loss was 573 +/- 164 mL and 739 +/- 228 mL, respectively (P =.01). The use of banked donor blood products was not significantly different between the two groups. Tranexamic acid could not be detected in any of the blood samples blindly collected from 24 patients to verify whether any systemic absorption of the drug occurred. There were no deaths in either group. None of the patients required reoperation for bleeding. CONCLUSIONS: Topical application of tranexamic acid into the pericardial cavity after cardiopulmonary bypass in patients undergoing primary coronary bypass operations significantly reduces postoperative bleeding. Further studies must be carried out to clarify whether a more pronounced effect on both bleeding and blood products requirement might be seen in procedures with a higher risk of bleeding.

Combined Surgery for cardiac and carotid disease: management and results of a rational approach.

OBJECTIVES: The aim of the present study was to apply a rational plan for simultaneous cardiac and carotid surgery in high-risk patients. MATERIALS AND METHODS: A consecutive series of 89 patients with coexisting severe cardiac and carotid disease were operated on during a 5-year period with routinary carotid shunting, moderate hypothermia and balanced anaesthesia. The combined surgical procedures were coronary artery by-pass grafts (CABG) + carotid endarterectomy (CEA) in 81 patients, CABG + CEA + aortic valve replacement (AVR) in four patients, and four cases of CEA + AVR. RESSULTS: Two deaths (2%), three acute myocardial infarctions (3%) and one (1%) major stroke occurred in five patients during the perioperative (30 days) period for a combined rate of death and/or disabling stroke of 3%. There were five reversible neurological deficits. Carotid and aortic mean clamping times were 9 and 60 min respectively. Patients were discharged after a mean length of stay in Intensive Care Unit (ICU) of 131 h and 7 days of hospitalisation post-ICU. CONCLUSIONS: Based on our results, combined interventions of CEA and CABG can be performed with an acceptable morbidity and mortality when severe carotid stenosis is associated with advanced, symptomatic cardiac disease. The management of these patients needs careful and appropriate pre-intra and post-operative assessment and timing aimed to reduce the ischaemic injuries, both cardiac and cerebral, especially during CBP time.

Red blood cell energy metabolism during cardiopulmonary bypass.

BACKGROUND: During cardiopulmonary bypass (CPB) an intracellular ATP deficit could theoretically play a role in changes of erythrocyte shape and deformability caused by mechanical trauma. We therefore studied erythrocyte energy metabolism in 12 patients undergoing normothermic CPB for myocardial revascularization. METHODS: Blood samples were collected prior to and 45 minutes after CPB beginning and analyzed for erythrocyte ATP, ADP, and AMP and their metabolites, erythrocyte NAD and NADP, plasma and whole blood lactate (Lact(p) and Lact(b) respectively), and whole blood pyruvate (Pyr(b)). RESULTS: Values were expressed as mean +/- standard deviation or median (lower and higher quartiles) on the ground of a test for normality. During CPB erythrocyte nucleotides and their metabolites did not change significantly (ATP: 60.2+/-12.1 vs. 68.3+/-13.0; ADP: 12.2+/-3.6 vs. 12.0+/-3.1; AMP: 0.43+/-24 vs. 0.44+/-0.26; adenosine: 0.063 (0.034-0.203) vs. 0.77 (0.032-0.221); inosine: 0.064 (0.023-0.072) vs. 0.075 (0.025-0.111); hypoxanthine: 0.330+/-0.272 vs. 0.367+/-0.223; xanthine: 0.193+/-0.090 vs. 0.220+/-0.095; NAD: 3.149+/-0.743 vs. 3.358+/-0.851; values in microM/mM packed red blood cell hemoglobin) while NADP increased (2.110+/-0.390 vs. 2.433+/-0.288 microM/mM packed red blood cell hemoglobin; p<0.05). Ringer lactate, with which the extracorporeal circuit was primed, caused Lact(p) to increase (1.87+/-0.81 vs. 3.27+/-1.15 mM/l; p<0.01). Some lactate entered erythrocytes since Lact(p)/Lact(b) ratio did not change (1.09+/-0.25 vs. 1.07+/-0.23) and some was transformed into pyruvate since Pyr(b) increased [62.9 (30.3-73.3) vs. 100.5 (61.0-146.9) microM/l; p<0.01]. Lact(b)/Pyr(b) ratio did not change significantly [22.6 (16.1-40.5) vs. 27.9 (17.5-35.2)] so that NAD/NADH ratio and, consequently, the rate of glycolysis were unlikely to change too. CONCLUSIONS: Erythrocyte energy metabolism is not affected by CPB, at least during the period of time taken into account in this study.

Superior extension of intraoperative brain damage in case of normothermic systemic perfusion during coronary artery bypass operations.

OBJECTIVE: Despite the controversies on the potential detrimental effects of normothermic cardiopulmonary bypass on neurologic outcome, to date no correlation between the severity of intraoperative brain lesions and the cardiopulmonary bypass temperature used at operation has been reported. This study compares the prevalence and the severity of brain lesions in patients who underwent operation in condition of normothermic versus hypothermic systemic perfusion. METHODS: Data are derived from the analysis of 2987 consecutive primary isolated myocardial revascularizations performed at our institution between April 1990 and January 1997. Of these cases, 1385 procedures were hypothermic and 1602 procedures were normothermic systemic perfusion. In all cases the neurologic outcome and extent of ischemic areas were prospectively recorded. RESULTS: Overall, 31 patients had a perioperative stroke (1.0%). The prevalence of neurologic events was similar in the 2 groups (15 cases in the hypothermic group and 16 cases in the normothermic perfusion group; P, not significant). However, the mean Glasgow Outcome Scale score and computed tomography-demonstrated extent of brain lesions were significantly worse in the normothermic group. CONCLUSIONS: Although the prevalence of intraoperative stroke was similar with hypothermic or normothermic cardiopulmonary bypass, the use of normothermic systemic perfusion was associated with more extended brain damage at computed tomographic scan and with a worse neurologic outcome. These results demand caution in the use of normothermic cardiopulmonary bypass and claim further investigation on the neurologic safety of normothermia.

Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events.

C-reactive protein was measured in 86 patients undergoing coronary artery bypass graft surgery. Patients were followed up for 3.2 years (range 1 to 6). Patients with C-reactive protein > or = 3 mg/L had significantly increased risk of recurrent ischemia at 1 to 6 years after intervention.

Individualized surgical strategy for the reduction of stroke risk in patients undergoing coronary artery bypass grafting.

BACKGROUND: This study was designed to evaluate the efficacy of a protocol of systematic screening of the ascending aorta and internal carotid arteries and individualization of the surgical strategy to the ascending aorta and internal carotid arteries status in reducing the stroke incidence among patients undergoing coronary artery bypass grafting. METHODS: On the basis of a pre- and intraoperative screening of the ascending aorta and internal carotid arteries, 2,326 consecutive patients undergoing coronary artery bypass grafting were divided in low, moderate, and high neurologic risk groups. In the high-risk group dedicated surgical techniques were always adopted and the reduction of the neurologic risk was considered more important than the achievement of total revascularization. RESULTS: The incidence of perioperative stroke in the high-risk group was similar to those of the other two groups (1.1 versus 1.3 and 1.1%, respectively; p = not significant); however, angina recurrence was significantly more frequent in the high-risk group. CONCLUSIONS: The described strategy allows a low rate of perioperative stroke in high-risk patients undergoing coronary artery bypass grafting. Whether the reduction of the neurologic risk outweighs the benefits of complete revascularization remains to be determined.

Perioperative management of a patient with Werlhof disease undergoing myocardial revascularization.

We herein report the case of a patient with idiopathic thrombocytopenic purpura (Werlhof disease) and coronary artery disease undergoing myocardial revascularization. The use of monomeric immunoglobulins, corticosteroids, platelets transfusion, use of a cell saver, normothermic cardiopulmonary bypass, aprotinine and homologous blood transfusion were combined in order to minimize the risk of bleeding complications in the postoperative period.

Comparison of response to serotonin of radial artery grafts and internal mammary grafts to native coronary arteries and the effect of diltiazem.

We studied the response of radial artery (RA) or left internal mammary artery grafts to the intraluminal infusion of serotonin in 22 consecutive patients 1 year after the operation, subsequently evaluating the effect of diltiazem in 9 patients. Serotonin causes a significant vasoconstriction of the RA grafts, but not of the left internal mammary artery grafts, whereas oral diltiazem treatment does not prevent the effect of the higher dose of serotonin on RA grafts.

The role of antithrombin III in the perioperative management of the patient with unstable angina.

BACKGROUND: To evaluate the effectiveness of intraoperative administration of antithrombin III (AT III) to improve anticoagulation and preserve the hemostatic mechanisms during cardiopulmonary bypass (CPB) in patients with unstable angina under heparin treatment. METHODS: We divided 22 patients, scheduled for coronary artery bypass grafting, into two groups. Group A (11 patients) received 3000 International Units (IU) of AT III concentrates plus heparin before aortic cannulation. Group B (11 patients) received only heparin. Blood drainage, allogeneic blood transfusions, and intraoperative activated coagulation time were recorded. Also, AT III, thrombin-antithrombin complex (TAT), fragment 1.2 (F 1.2), and D-dimers were measured during the operation and the first postoperative day. RESULTS: Group A patients had fewer transfusions and had less chest-tube drainage. In group A, AT III levels increased after AT III concentrates administration and were always higher than in group B. In group B, F 1.2 and TAT increased significantly more after CPB and at the end of operation. Differences in D-dimers between the groups were not significant. CONCLUSIONS: Intraoperative administration of AT III concentrates allowed adequate anticoagulation during CPB and attenuated the coagulative cascade activation and the consequent consumptive coagulopathy.

A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.

OBJECTIVES: To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS: Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS: Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION: Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.

Use of the radial artery for myocardial revascularization.

BACKGROUND: The radial artery was first used as a coronary graft by Carpentier and associates in 1973 but, due to the disappointing results, it was abandoned. In 1992 its revival coincided with the widespread use of calcium-channel blockers in cardiovascular surgery, in the belief they could prevent spasm. METHODS: From January 1993 to October 1995 we operated on 109 patients for myocardial revascularization employing the radial artery with two different surgical techniques: in 95 patients (group 1) it was "pretreated" by opening its fascia after a gentle hydrostatic dilation and then anastomosed to the aorta; in 14 patients (group 2) it was branched to another conduit. We had two operative deaths (1.82%). RESULTS: At a mean interval of 532.42 days 105 patients are still alive, 2 (1.86%) having died of abdominal tumors. Fifty-six patients (52.33%) underwent angiography at a mean interval of 334.42 days: the patency of the radial artery was 88.88% in group 1 and 62.50% in group 2. Indications and contraindications are discussed. CONCLUSIONS: The radial artery is an easily manageable conduit whose early patency is very promising, although a longer follow-up is mandatory.

Arterial-venous PCO2 gradient in early postoperative hours following myocardial revascularization.

OBJECTIVE: To investigate the utility of the arterial-venous PCO2 gradient (P(a-v)CO2) as a marker of the increased risk of postoperative complications in the early postoperative hours following myocardial revascularization. EXPERIMENTAL DESIGN: Prospective study. SETTING: The Postoperative Intensive Care Unit (ICU) of a University Hospital. PATIENTS: Thirty patients (28 males and 2 females; aged 39-70) that consecutively underwent myocardial revascularization. INTERVENTIONS: None. MEASURES: Thirty minutes following arrival at the ICU the hemodynamic parameters were recorder; the arterial and mixed venous hemogasanalyses were obtained; the mixed venous blood hemoglobin saturation (SvO2) and the O2 consumption (VO2) were calculated; and plasma lactate was determined. The arterial and mixed venous hemogasanalyses were determined again 90 minutes after the admission to the ICU. RESULTS: P(a-v)CO2 at 30 minutes was 8.1+/-2.3 mmHg and was only slightly lower at 90 minutes (7.5+/-2.3 mmHg) so that any significant influence of patient transport to the ICU could be ruled out. P(a-v)CO2 did not significantly relate with cardiac index, mixed venous blood O2 saturation, and blood lactate. Twenty-one patients (70%) showed P(a-v)CO2 values higher than 7 mmHg at 30 minutes: in comparison with the others they were characterized by higher arterial blood PCO2 (PACO2) (37+/-5 vs 32+/-3 mmHg; p<0.05) in spite of similar ventilatory variables, by higher mixed venous blood PCO2 (PVCO2) (47+/-6 vs 37+/-3 mmHg; p<0.01), and by lower cardiac index values (2.0+/-0.3 vs 2.3+/-0.6 1/min/m2; p<0.05). The patients that presented abnormally high P(a-v)CO2 values showed a higher rate of postoperative complications, including inadequate cardiac performance, cardiac arrhythmias, prolonged mechanical ventilation, increased plasma creatinine, and jaundice (11 patients out of 21 vs 1 patient out of 9; p<0.05). Finally P(a-v)CO2 was related with arterial-mixed venous O2 content difference (regarded as an index of O2 consumption), hematocrit, blood temperature and PACO2 by multiple linear regression (R=0.74; p<0.01). The coefficients of all factors but hematocrit were significant; hence, apart from the cardiac index, P(a-v)CO2 was influenced by the metabolic rate, the body temperature (possibly because of CO2 release during rewarming), and the impaired CO2 elimination through the lungs. CONCLUSIONS: P(a-v)CO2 represents a useful even if aspecific parameter to monitor patients during the early postoperative period after myocardial revascularization.

The relationship between systemic oxygen uptake and delivery during moderate hypothermic cardiopulmonary bypass: critical values and effects of vasodilation by hydralazine.

The relationship between oxygen delivery (DO2) and uptake (VO2) has been studied during moderately hypothermic cardiopulmonary bypass (CPB) in 15 patients undergoing myocardial revascularization. As soon as nasopharyngeal temperature was lowered to 32 degrees C, blood flow was decreased from 2.4 to 2.0 l/min/m2. Arterial and mixed venous blood gas analyses were performed five and eight minutes later and DO2 and VO2 were calculated; VO2 stabilized in five minutes after changing blood flow and neither DO2 nor VO2 values changed three minutes later (DO2: 217 +/- 19 versus 215 +/- 17 ml/min/m2; VO2: 63 +/- 12 versus 66 +/- 14 ml/min/m2). Blood flow then was increased to 2.3 l/min/m2 and DO2 and VO2 were determined again, five minutes later; they both increased significantly, to 243 +/- 20 and 74 +/- 13 ml/min/m2, respectively. However, a further blood flow increase to 2.6 l/min/m2 which caused DO2 to increase to 277 +/- 24 ml/min/m2, did not affect VO2 which was unchanged five minutes later (76 +/- 13 ml/min/m2); VO2 dependence on DO2 values higher than 243 +/- 20 ml/min/m2 was consequently ruled out. Ten patients, having a mean arterial pressure higher than 80 mmHg, were eventually vasodilated with hydralazine, 0.1 mg/kg intravenously, and DO2 and VO2 were determined after five and ten minutes. As blood flow did not change, DO2 was unaffected while a slight increase in VO2 mean values was observed which was not statistically significant (prior to hydralazine: 78 +/- 15 ml/min/m2; five minutes later: 82 +/- 17 ml/min/m2; 10 minutes later: 76 +/- 18 ml/min/m2). In conclusion, during hypothermic CPB at 32 degrees C, VO2 plateau ranges between 48 and 102 ml/min/m2 (mean +/- 2 SD) in 95% of patients, corresponding to 66 and 141 ml/min/m2 at 37 degrees C; this finding closely matches other literature reports. Consequently, lower VO2 values suggest inadequate oxygen supply to tissues. Critical DO2 at 32 degrees C is lower than 283 ml/min/m2 in 97.5% of patients. Finally, arterial vasoconstriction does not seem to play a significant role in tissue hypoperfusion.

Secondary alcohol metabolites mediate iron delocalization in cytosolic fractions of myocardial biopsies exposed to anticancer anthracyclines. Novel linkage between anthracycline metabolism and iron-induced cardiotoxicity.

The cardiotoxicity of doxorubicin (DOX) and other quinone-containing antitumor anthracyclines has been tentatively attributed to the formation of drug semiquinones which generate superoxide anion and reduce ferritin-bound Fe(III), favoring the release of Fe(II) and its subsequent involvement in free radical reactions. In the present study NADPH- and DOX-supplemented cytosolic fractions from human myocardial biopsies are shown to support a two-step reaction favoring an alternative mechanism of Fe(II) mobilization. The first step is an enzymatic two-electron reduction of the C-13 carbonyl group in the side chain of DOX, yielding a secondary alcohol metabolite which is called doxorubicinol (3.9 +/- 0.4 nmoles/mg protein per 4 h, mean +/- SEM). The second step is a nonenzymatic and superoxide anion-independent redox coupling of a large fraction of doxorubicinol (3.2 +/- 0.4 nmol/mg protein per 4 h) with Fe(III)-binding proteins distinct from ferritin, regenerating stoichiometric amounts of DOX, and mobilizing a twofold excess of Fe(II) ions (6.1 +/- 0.7 nmol/mg protein per 4 h). The formation of secondary alcohol metabolites decreases significantly (Pi < 0.01) when DOX is replaced by less cardiotoxic anthracyclines such as daunorubicin, 4'-epi DOX, and 4-demethoxy daunorubicin (2.1 +/- 0.1, 1.2 +/- 0.2, and 0.6 +/- 0.2 nmol/mg protein per 4 h, respectively). Therefore, daunorubicin, 4'-epi DOX, and 4-demethoxy daunorubicin are significantly (P < 0.01) less effective than DOX in mobilizing Fe(II) (3.5 +/- 0.1, 1.8 +/- 0.2, and 0.9 +/- 0.3 nmol/mg protein per 4 h, respectively). These results highlight the formation of secondary alcohol metabolites and the availability of nonferritin sources of Fe(III) as novel and critical determinants of Fe(II) delocalization and cardiac damage by structurally distinct anthracyclines, thus providing alternative routes to the design of cardioprotectants for anthracycline-treated patients.

Haemodynamic and metabolic effects of surface rewarming after coronary revascularization.

Cardiac surgery is often associated with a postoperative increase in the patient's metabolic rate; surface rewarming has been suggested to decrease the energy expenditure by preventing hypothermia. Thirty patients, undergoing coronary revascularization, were randomly divided into two groups; after surgery group A was rewarmed by a new device that acts by both conduction and convection, while group B was just covered with cotton blankets. Blood, oesophagus and skin (thigh and foot) temperatures were recorded on admission to the intensive care unit (ICU) and 30, 60, 90, 180, 270, and 450 min later. Haemodynamic parameters, oxygen delivery, calculated oxygen consumption, and plasma lactate concentration were assessed as well. Group A warmed up quicker than group B as far as the skin was concerned while the core temperature was unaffected. Group A was also characterized by lower cardiac indices and oxygen consumption. As the occurrence of a dependence of oxygen consumption on delivery could be reasonably ruled out in warmed patients because blood lactate levels were lower than in the controls, we conclude that surface rewarming might have some positive effect in decreasing metabolic demand after cardiac surgery even if the patient's core temperature is little affected. The inhibition of skin temperature receptors could possibly explain this finding.

Rush desensitization in heparin hypersensitivity: a case report.

Among all the known drug intolerances, adverse reactions to heparin are not very common. No desensitization in patients with heparin hypersensitivity has ever been attempted. We report the case of a 55-year-old female patient with mitral stenosis and insufficiency, and tricuspid and aortic insufficiency. The patient underwent heparin treatment, and urticaria occurred with either s.c. calcium heparin or i.v. sodium heparin. Allergy testing (skin tests and patch tests) was negative. A pseudoallergic intolerance was diagnosed. Mitral valve replacement with the extracorporeal circulation method was necessary; therefore, heparin treatment was administered. A heparin rush desensitization together with antihistamine drugs (4 mg clorpheniramine maleate for 3 d) was started: 50 UI (0.5 mg) s.c. sodium heparin were first administered; within 4 d, 5000 UI (50 mg) sodium heparin was administered i.v. with no side-effects. A full-dosage heparin treatment was then administered and heart surgery was easily performed. During the postsurgical course, i.v. sodium heparin was smoothly replaced with s.c. calcium heparin (25,000 UI s.c. per day) and with oral anticoagulants (sodium warfarin).