Blood from the right atrium may provide closer estimates of mixed venous saturation than blood from the superior vena cava. A pilot study.

BACKGROUND: As a rule, central venous catheters (CVC) should not be positioned in the right atrium (RA) to avoid the risk of perforation and cardiac tamponade. However, in ICUs where ECG monitoring can detect any initial damage of the atrial wall, CVCs may probably be safely positioned in the RA. We investigated whether mixed venous saturation (SvO2) was better estimated by measuring central venous saturation (ScvO2) in the RA or in the superior vena cava (SVC) in patients undergoing cardiac surgery. METHODS: A CVC and a pulmonary artery catheter (PAC) were positioned before surgical coronary revascularization in sixty patients. Under transesophageal echocardiographic guidance, CVC tips were randomly positioned inside the RA (group A) or the SVC (group C). In each patient, eight pairs of blood samples were collected from CVC and PAC distal ports and saturation measured. Cardiac arrhythmias that occurred in the first 48 postoperative hours and CVC tip position on chest X-rays were also registered. RESULTS: ScvO2 and SvO2 correlated better in group A (r=0.95) than in group C (r=0.84). The 95% interval of confidence of the gap between ScvO2 and SvO2 was narrower in group A (-6.9/+ 3.2 vs. -11.6/+5.5; p<.01). The incidence of arrhythmias was equal in the two groups (16.7%). On chest X-rays, CVC tips were 5.4 (SD=3.6) cm below the tracheal carina in group A and 5.3 (SD=3.9) cm in group C. CONCLUSION: In monitored patients, positioning CVC tips in the RA rather than in the SVC may allow closer estimates of SvO2 and may be safe. Yet, safety should be confirmed by further studies with larger samples of patients.

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.

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.

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.

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.

[Effectiveness of low-dose neostigmine in the treatment of sinus tachycardia during aortocoronary bypass]. / Efficacia della neostigmina a basse dosi nel trattamento della tachicardia sinusale negli interventi di bypass aortocoronarico.

Thirteen patients, who underwent surgery for myocardial revascularization, were given neostigmine, 0.25-1 mg i.v., in order to control intraoperative sinus tachycardia. Three minutes after the administration, the drug was effective in all patients, by decreasing the heart rate and improving the indices of the risk of myocardial ischemia. Seven minutes later the heart rate decreased further. In 5 patients out of 13, short periods of bradycardia were observed during surgical compression or dislocation of the heart. As cardiac rate decreased, P and T waves and ST, QT, and QTc intervals lengthened without reaching pathological levels. Three minutes after neostigmine, the stroke volume was unchanged in spite of the decrease of the heart rate; consequently cardiac index decreased. Seven minutes later a slight increase of the stroke volume balanced the further decrease of the heart rate; so cardiac index did not change any more. Arterial pressure decreased slightly after neostigmine whereas systemic vascular resistance was unaffected. Also central venous pressure did not change while pulmonary capillary wedge pressure showed a small increase 10 minutes after neostigmine. Finally airway resistance did not change significantly.

[Results of surgical treatment in supraventricular tachycardias]. / Risultati del trattamento chirurgico delle tachicardie sopraventricolari.

From May 1989 to May 1992, 44 patients (mean age 41 years, range 15-66) underwent surgery for supraventricular tachycardias: in 35 patients with atrioventricular reentrant tachycardia or atrial fibrillation associated with accessory pathway and refractory to medical treatment, the epicardial approach was used; in 8 with atrioventricular nodal reentrant tachycardia, a perinodal cryosurgery of the atrioventricular node was used, and in 1 patient with atrial flutter a cryosurgical ablation around the orifice of the coronary sinus and surrounding tissues was performed. All 38 accessory pathways were successfully ablated in 35 patients and no recurrences of delta wave or tachycardia were observed during a mean follow-up of 17 +/- 10 months. Atrial perforation during surgery and pericarditis were the only complications observed. All 8 patients with atrioventricular nodal reentrant tachycardia were successfully treated: in 2 patients dual pathways persisted after surgery but tachycardia was no longer inducible. No recurrences were observed during a mean follow-up of 15 +/- 4 months. Since surgery (15 months), the patient with atrial flutter has been free of recurrent episodes of atrial flutter. In conclusion, surgical treatment of supraventricular tachycardias is highly successful, with no mortality and very low morbidity. Should transcatheter ablation fail, surgery should be the treatment of choice in patients with frequent and symptomatic supraventricular tachycardias.

Surgical treatment of cardiac arrhythmias.

This report describes 20 consecutive patients who underwent surgical procedures for treatment of cardiac arrhythmias. 16 patients have been operated for WPW syndrome, always using the epicardial approach, without extracorporeal circulation. Three patients underwent surgery for atrio-ventricular nodal reentrant tachycardia, using a discrete perinodal cryotreatment, during normothermic extracorporeal circulation. In one case we used cryoablation of the atrial myocardium below the coronary sinus to treat atrial flutter. This operation was performed under normothermic extracorporeal circulation. In our observations, there was no early or late death; postoperative complications developed in 1 patient (5%) due to pericarditis. Ablation of the AP was completely successful in all the cases (100%) operated for WPW as well as for AVNRT syndromes and atrial flutter.

[Changes in intraerythrocyte electrolytes in open-heart cardiosurgical interventions]. / Variazioni degli elettroliti intraeritrocitari negli interventi cardiochirgici a cuore aperto.

The changes of erythrocyte Na, K, C1, and Mg during open-heart surgery were studied in 10 patients undergoing aorto-coronary bypass and in 10 patients undergoing valvular replacement and chronically treated with digitalis and diuretics. The results showed: initial Mg levels lower in both groups of patients than in 10 healthy subjects utilized as controls (p less than .01); higher initial Na levels in patients treated with digitalis and diuretics than in controls (p less than .001); no electrolyte change during extracorporeal circulation; significantly increased Na values at the end of surgery and in the 1st postoperative day, that were probably caused by erythrocyte damage during CPB. The increase was observed following the CPB because of the slow rate of erythrocyte Na changes.

Magnesium metabolism in open-heart surgery.

The levels of magnesium in serum, urine and erythrocytes were studied in 22 patients undergoing cardiac surgery for valvular prosthesis. Magnesium values were correlated with serum albumin and non-esterified fatty acids (NEFA). Data were collected before anesthesia, 10 min after sternotomy, heparinization and declamping of the aorta and in the 1st postoperative day. A slight decrease in magnesemia was observed before extracorporeal circulation (ECC) and was mainly due to haemodilution. The correlation of magnesium with NEFA was significant only after heparinization. The use of the St Thomas solution as cardioplegia fully corrected the hypomagnesemia previously reported during ECC as well as in the 1st postoperative day. A moderate hypermagnesemia was observed at the end of ECC, but no patient reached dangerous levels of serum magnesium. Urinary losses increased during and after ECC. Red blood cell magnesium showed a slight increase before ECC, followed by a significant reduction at the end of ECC.

Zinc and copper metabolism during open-heart surgery.

Zinc and copper changes were studied in plasma, whole blood, urine and myocardium in 15 patients undergoing valve replacement in hypothermic cardiopulmonary bypass with hemodilution. During the cardiopulmonary bypass, a fall in plasma copper and zinc concentration was related to hemodilution. The zinc concentration also decreased in whole blood, but remained unchanged intracellularly. The urinary concentration of both cations, but not the output, decreased at the end of the operation in relation to the baseline values. The myocardial copper and zinc concentrations increased during the aortic cross-clamping period. The possible causes and significance of these changes are considered.