Pharmacokinetics of ampicillin-sulbactam and the renal function-based optimization of dosing regimens for prophylaxis in patients undergoing cardiovascular surgery.

UNLABELLED: Surgical site infections are a major cause of postoperative morbidity and mortality in cardiovascular surgery. Proper antibiotic prophylaxis can reduce the rate of such infections, but the concentration of antibiotic must be maintained at an adequate level throughout the operation. This study aimed to use renal function to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used prophylactic antibiotic, to maintain adequate concentrations throughout the course of surgery. The mean volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 13.2 l, 0.652 h⁻¹, 1.32 h, and 8.45 l/h, respectively. A statistically significant (P < 0.0001) correlation (r = 0.771) was observed between the total clearance of ampicillin and creatinine clearance of the patients. Plasma concentrations of ampicillin were simulated with the pharmacokinetic parameters obtained. We developed a nomogram for adjusting the dosing interval according to renal function and predicted ampicillin trough concentrations. We revealed the best dosage and dosing interval for cardiovascular surgery by analyzing the perioperative pharmacokinetics of ampicillin-sulbactam administered prophylactically. We suggest that the dosage and dosing interval for ampicillin-sulbactam should be adjusted to optimize treatment efficacy and safety, on the basis of the MIC90 of methicillin-sensitive Staphylococcus aureus (MSSA) in each institution. TRIAL REGISTRATION: UMIN000007356.

Use of continuous retrograde gaseous oxygen persufflation for myocardial protection during open heart surgery.

PURPOSE: The infusion of a cardioplegic solution is the standard method of myocardial protection during open heart surgery. However, this method interrupts the surgical procedure and it is difficult to ensure a bloodless surgical field. To address these problems, the effect of continuous retrograde gaseous oxygen persufflation (ROP) on myocardial protection was assessed in comparison to St. Thomas' solution (STS). METHODS: Eighteen adult mongrel dogs were divided into three groups of six. Group G received continuous ROP, Group C received STS every 30 min, and Group N received hypothermia alone during the 120 min hypothermic ischemia. The myocardial metabolism was assessed by measuring the coronary sinus lactate concentration, lactate extraction ratio (LER), coronary sinus lipid peroxidation (LPO) concentration, left ventricular myocardial adenosine triphosphate (ATP) concentration, and water content. Cardiac function was assessed by the percent recovery relative to the baseline. RESULTS: In Group G, the lactate, LPO, and water content were significantly lower (P = 0.0062, P = 0.03, and P = 0.0065, respectively), and ATP was significantly higher (P = 0.028) than in Group C. The LER was only positive in Group G. In addition, the cardiac functions in Groups G and C were not significantly different. CONCLUSIONS: Retrograde gaseous oxygen persufflation was not inferior to STS in regard to myocardial protection. This technique could therefore represent a potentially promising cardioplegic method.

Right hemi-reconstruction of the left atrium using two equine pericardial patches for recurrent malignant fibrous histiocytoma: report of a case.

We report a case of recurrent malignant fibrous histiocytoma (MFH) in the left atrium, treated by removal of the tumor and the right half of the left atrium, which was reconstructed with two equine pericardial patches. Postoperative echocardiography showed patent right pulmonary veins and a properly shaped left atrium. The patient survived for 3 years after the operation with no cardiac symptoms.

Preoperative advanced left ventricular remodeling predisposes to recurrence of ischemic mitral regurgitation with less reverse remodeling.

BACKGROUND AND AIM OF THE STUDY: The recurrence of ischemic mitral regurgitation (IMR) after mitral annuloplasty is a major determinant of patient survival. The study aim was to investigate, retrospectively, the characteristics of patients with postoperative recurrence of IMR. METHODS: Twenty patients who had no regurgitation immediately after mitral annuloplasty, were allocated to either recurrence (n = 8) or non-recurrence (n = 12) groups. Recurrence was defined as any interval upgrade of regurgitation. The patients' preoperative profiles and parameters of preoperative, immediate postoperative and intermediate postoperative echocardiography were compared. RESULTS: Patients with recurrence were more frequently dyspneic and had a significantly higher cardiothoracic ratio (p = 0.041) on radiologic examination. The preoperative left ventricular end-diastolic and end-systolic dimensions (p = 0.018 and 0.021), and left ventricular end-diastolic and end-systolic volumes (p = 0.038 and 0.041), and left ventricular wall motion score (p = 0.0002) were significantly greater in the recurrence group. These differences in left ventricular volume persisted at the immediate and intermediate postoperative stages. Reverse remodeling occurred at a ca. 50% lower rate in the recurrence group, and was associated with significantly smaller preoperative left ventricular dimension and volume. At intermediate follow up, the left ventricular ejection fraction was improved and significantly greater in the non-recurrence group (p = 0.024), but remained unchanged in the recurrence group. CONCLUSION: Advanced left ventricular remodeling and dilatation before surgery predispose to a recurrence of mitral regurgitation and a lesser incidence of reverse remodeling. Mitral annuloplasty alone may have a limited role in preventing the recurrence of regurgitation in the case of advanced IMR, without functional recovery.

Radical repair of cor triatriatum with partially unroofed coronary sinus and persistent left superior vena cava 35 years after operation for tetralogy of Fallot.

We report a rare case of simultaneous repair for Cor triatriatum (CT), partially unroofed coronary sinus (CS) with persistent left superior vena cava (PLSVC), moderately severe tricuspid regurgitation, and atrial flutter 35 years after radical operation for tetralogy of Fallot (TOF). A 40-year-old woman underwent patch closure of atrial septal defect as to drain blood from left SVC to right atrium (RA), excision of diaphragm in left atrium (LA), tricuspid annuloplasty, and cryoablation. Postoperative course was uneventful with successful anatomical correction.

Mechanism of recurrent/persistent ischemic/functional mitral regurgitation in the chronic phase after surgical annuloplasty: importance of augmented posterior leaflet tethering.

BACKGROUND: Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated. METHODS AND RESULTS: In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased (P<0.01), whereas PML tethering significantly worsened (P<0.01). Nine of the 30 patients showed recurrent/persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re-increase in posterior displacement of the coaptation, and progressive worsening in PML tethering (P<0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR (r2=0.60, P<0.0001), increased PML tethering was the primary determinant of late MR (r2=0.75, P<0.0001). CONCLUSIONS: Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.

Mid-term changes of left ventricular geometry and function after Dor, SAVE, and Overlapping procedures.

BACKGROUND: The aim of this study was to investigate the mid-term changes of left ventricular (LV) geometry and function after Dor, septal anterior ventricular exclusion (SAVE), and Overlapping ventricular remodeling procedures. METHODS: Forty-three patients who underwent LV reconstruction for end-stage ischemic heart disease, were divided into three groups, undergoing Dor (n=15), SAVE (n=12), and Overlapping procedures (n=16). Coronary artery bypass grafting and mitral annuloplasty were performed concomitantly when indicated. Left ventricular diastolic and systolic dimensions (LVDd and LVDs), LV end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI), LV ejection fraction (LVEF), deceleration time (DcT), sphericity index (SI), and grade of mitral regurgitation were measured on preoperative and postoperative (immediately and at intermediate-term) echocardiography. RESULTS: In the Dor group, the LVEDVI and LVESVI were significantly reduced immediately after the operation, and increased again at intermediate follow-up. The SI was significantly increased immediately after the operation and increased thereafter in a linear fashion. In the SAVE group, the DcT was significantly reduced immediately after the operation and was not improved in the later stage. In the Overlapping group, the LVEDVI and LVESVI were significantly reduced, and remained as such at intermediate follow-up. The SI was not increased and remained almost unchanged after the operation. CONCLUSION: Progression in LV sphericity after the Dor procedure and persistent reduction of the DcT after the SAVE procedure seem to be procedure-related problems. The Overlapping procedure provided significant LV volume reduction, maintaining the most elliptical LV shape with acceptable early and late mortality.

Effects of ultrasonic skeletonization on internal thoracic and gastroepiploic arteries for coronary artery bypass grafting.

OBJECTIVE: There are few data available on the effect of ultrasonic skeletonization with the harmonic scalpel on internal thoracic artery (ITA) and gastroepiploic artery (GEA) vessel function. METHODS: Rings of segments of the skeletonized ITA, pedicled ITA, skeletonized GEA, and pedicled GEA were studied. Arterial segments were treated with high KCl and norepinephrine (NE) to obtain smooth muscle contractions. Endothelium-dependent and independent vasorelaxant potencies in 10(-6)mol/l NE-pre-constricted arteries were assessed by acetylcholine (ACh), and isosorbide dinitrate (ISDN) and diltiazem, respectively. RESULTS: There were no differences in contractile potencies induced by high KCl and NE between the rings cut from skeletonized and pedicled grafts. The rings from skeletonized and pedicled vessels also showed equal sensitivity to ISDN and diltiazem. However, the rings from pedicled grafts showed greater relaxation responses to ACh than rings from skeletonized grafts. CONCLUSION: Ultrasonic complete skeletonization with the harmonic scalpel may retain smooth muscle function of skeletonized grafts, whereas endothelial function of ultrasonic skeletonized grafts may be significantly compromised.

Intraoperative infusion of epoprostenol sodium for patients with heparin-induced thrombocytopenia undergoing cardiac surgery.

Prevention of catastrophic thromboembolic complications during surgery in patients with heparin-induced thrombocytopenia (HIT) remains a challenging problem during cardiac surgery. We infused an increasing dose of epoprostenol sodium, which is one of three anti-HIT regimens available in Japan, ahead of administration of heparin and performed a mitral valve operation for a patient with type II HIT. The absence of thromboembolic events and platelet consumption during cardiopulmonary bypass, together with considerable reduction of platelet adhesion to the fibers of the membrane oxygenator, support the efficacy and safety of our strategy.

Posterior mitral annuloplasty through the aortic root.

A case of mitral regurgitation associated with aortic root aneurysm treated with posterior mitral annuloplasty is presented. The annuloplasty was performed through the aortic annulus using valve-preserving aortic root reconstruction. Postoperatively, mitral regurgitation resolved, and the degree of aortic regurgitation decreased from severe to mild. Thus, we conclude that the transaortic approach is useful for simple mitral valve repair with concomitant aortic root surgery.

Late development of mitral regurgitation after left ventricular reconstruction surgery.

PURPOSE: Late presence of mitral regurgitation (MR) after the Dor procedure (left ventricular (LV) reconstruction associated with coronary artery bypass grafting) for postinfarction patients carries a poor prognosis. The aim of this study was to review our experience with the Dor procedure and to analyze the correlation of surgical results with late MR. METHODS: The study group comprised 19 patients with previous anterior transmural myocardial infarction (MI). Ten patients were classified as New York Heart Association (NYHA) functional class III or IV at surgery. MR was moderate in 2 patients and mild in 15 patients. RESULTS: Myocardial revascularization was performed in all patients, with a mean of 3.7+/-1.2 grafts. Mitral valve was repaired in 6 patients. Four patients with mild MR underwent posterior annuloplasty, and 2 with moderate MR underwent rigid annular remodeling. Early postoperative NYHA functional class improved from 2.7+/-0.9 to 1.3+/-0.5; however, MR deteriorated to moderate in 5 patients with worsening NYHA functional class 3 months after surgery. Although the valve was not repaired during surgery in 4 patients with preoperative mild MR, 1 patient with moderate MR underwent annuloplasty with a rigid ring. All patients with late MR underwent more than 30-mL/m2 reduction of end-diastolic volume index at surgery. Cumulative 4-year survival including hospital deaths was 89.5%. CONCLUSION: To prevent the risk of late MR, a more than 30-mL/m2 reduction of end-diastolic volume index should be avoided and mitral valve repair should be performed even if preoperative functional MR is only mild.

Extra-Anatomic Bypass Operation for an Infected Aortic Arch Aneurysm with Broad Mediastinal Abscess: A Case Report.

We encountered an informative case of infected aortic arch aneurysm. The proximal descending aorta, left common carotid artery, and left subclavian artery were severely involved in an abscess; thus, typical in situ reconstruction of the arch was considered impossible. Therefore, to secure more distal branches appropriate for anastomosis, a modified extra-anatomic arch repair was performed through additional incisions. The patient developed renal and respiratory failure and died of septicemia five and a half months after the operation. However, postoperative computed tomograms demonstrated that the abscess had disappeared.

Aortic valve replacement in a patient with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a disorder of heme synthesis that causes excessive accumulation of protoporphyrin. The predominant clinical feature is photosensitivity triggered by light at wavelengths near 400 nm. We describe a 52-year-old man with EPP who underwent aortic valve replacement due to severe regurgitation. To prevent burn injuries, astral lamps in the operating room were covered with yellow film filters. Preoperative autologous blood donation was not undertaken. Blood priming of the extracorporeal circuit was performed to maintain adequate hemoglobin concentrations, which resulted in reduction of heme synthesis. The patient was discharged in good health without any signs or symptoms of EPP.

Evaluation of anti-platelet aggregatory effects of aspirin, cilostazol and ramatroban on platelet-rich plasma and whole blood.

To compare property in anti-platelet effects of aspirin (a cyclooxygenase inhibitor), cilostazol (a phosphodiesterase III inhibitor) and ramatroban (a specific thromboxane A2 receptor antagonist), we measured human platelet-rich plasma (PRP) aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid, and whole blood (WB) aggregation induced by ADP. The release of P-selectin, transforming growth factor-beta 1, and the formation of thromboxane A2 in response to agonists were also investigated. Inhibitory effects of 100 micromol/l aspirin, 10 micromol/l cilostazol and 1 micromol/l ramatroban on 5 micromol/l ADP-induced PRP aggregation were similar. However, aspirin strongly inhibited thromboxane A2 formation in response to 5 micromol/l ADP compared with other drugs. Inhibitory effects of 10 micromol/l cilostazol on PRP aggregation and the release of molecules were quite similar in responsiveness induced by the three agonists. Aspirin and cilostazol inhibited platelet aggregation in a concentration-dependent, non-linear fashion, while ramatroban inhibited linearly with increasing concentration. Anti-platelet effects of drugs having different pharmacological mechanisms were demonstrated clearly by measuring PRP aggregation induced by the three agonists, and by measuring WB aggregation that most probably reflects not only platelet-platelet interactions, but also platelet-leukocyte interactions, as well as the release of intraplatelet molecules.

Long-term follow up in patients receiving a small aortic valve prosthesis.

BACKGROUND AND AIMS OF THE STUDY: Concern persists regarding the long-term effects of aortic valve replacement (AVR) in the small aortic root. METHODS: Twenty-eight patients (21 females, seven males; mean age 54.1+/-11.7 years; mean body surface area (BSA) 1.39+/-0.07 m2) who underwent AVR with a 19 mm mechanical valve more than 10 years previously at the authors' institute, were followed up. Long-term echocardiographic evaluations were performed in 18 of 21 survivors. RESULTS: Follow up in the 28 patients was complete for up to 19.2 years (mean 11.4 years); cumulative follow up was 318.1 patient-years. Actuarial survival rates at 5, 10 and 15 years were 88.5+/-6.3%, 72.0+/-9.0% and 72.0+/-9.0%, respectively. In general, NYHA class showed satisfactory improvement. Long-term echocardiography showed significant reductions in left ventricular (LV) wall thickness and mass index compared with preoperative values, despite the existence of pressure gradients. A negative correlation was found between the rate of reduction of LV wall thickness and BSA. CONCLUSION: Implantation of the 19 mm aortic mechanical prosthesis was viable in patients with a small aortic annulus, especially if their BSA was <1.45 m2.

Congenital quadricuspid aortic valve: report of nine surgical cases.

We report the clinicopathologic characteristics of the congenital quadricuspid aortic valve necessitating surgery. Among 616 patients for whom we performed an aortic valve operation over the past 20 years, nine patients (1.46%) (five men and four women, mean age 60 years) with quadricuspid aortic valve were encountered. All had aortic regurgitation (AR) except one with aortic stenosis and mild regurgitation (ASr). All were free of cardiac anomaly including that of the coronary arterial system. Macroscopically, severe calcification of the valve was seen in the one case of ASr. Fenestration of the cusp was seen in five cases of AR. Infective endocarditis was not seen. Histological study disclosed fibrous thickening and myxoid degeneration in the AR cases. In accordance with the Hurwitz and Roberts classification, four valves were type b (three equal-sized cusps and one smaller cusp), two valves were type a (four equal-sized cusps), two valves were type d (one large, two intermediate, and one small cusp), and one valve was type g (four unequal-sized cusps). Valve repair failed in one patient and was converted to valve replacement during the operation. All patients underwent successful aortic valve replacement (AVR).

Posterior mitral annuloplasty with a flexible linear reducer.

OBJECTIVES: We evaluated posterior annuloplasty results using a flexible linear reducer, especially as a cardiac surgical procedure. METHODS: Subjects were 24 patients consisting of 20 men and 4 women aged 7 to 79 years (mean; 61.3 years) with mitral regurgitation who underwent mitral valve reconstruction using a flexible linear reducer from May 1999 to April 2001. Mitral regurgitation was attributed to myocardial ischemia in 9 (37.5%). Isolated mitral valve repair was conducted only in 3 (12.5%) and concomitant procedures in 21 (87.5%). RESULTS: No operative deaths occurred. One hospital death (4.2%) occurred due to cardiac failure on postoperative day 58. Four late deaths (16.7%) occurred 8 to 15 months after surgery due to heart failure, stroke, and cancer. No patients required reoperation and no perioperative complications occurred. Doppler echocardiography conducted in all patients within a month postoperatively showed excellent valve function: 11 (45.8%) had no residual regurgitation, 5 (20.8%) had trivial insufficiency, 6 (25%) had mild insufficiency, 2 (8.3%) had moderate insufficiency, and none had severe insufficiency. We observed significantly reducted enddiastolic and systolic left ventricular diameter while ejection fraction remained unchanged. CONCLUSIONS: Posterior mitral annuloplasty using a flexible linear reducer is simple, saves time, and is useful for the small left atrium and as an additional procedure in other cardiac surgery.

Herpes simplex viral pneumonia after coronary artery bypass grafting.

We report a case of herpes simplex viral (HSV) pneumonia as a post-CABG pulmonary complication in a 70-year-old man. Chest radiography on postoperative day 9, showed a glass-like shadow and pleural effusion in the left lung field, and the man's condition began deteriorating rapidly. Bronchofiberscopy to detect the pathogen and a bronchoalveolar lavage with polymerase chain reaction (PCR) yielded a definitive diagnosis of HSV pneumonia. Once therapy with acyclovir was begun, his condition improved markedly. Our case suggests that 1 viral pulmonary infection should be considered as a possible cause in postoperative cardiac patients with unexplained progressive pulmonary infiltrates, and 2 DNA amplification using PCR is rapid--it can be completed within 1 day--and sensitive and specific in diagnosing such infections.

Off-pump coronary artery bypass grafting in a patient with Behçet's disease.

We report the case of a 58-year-old man with Behçet's disease who developed chest pain. Coronary angiography showed severe triple-vessel disease, and the patient was transferred to our department for urgent coronary artery bypass grafting. Because of the risk of anastomotic leakage or pseudoaneurysm formation, we performed off-pump coronary artery bypass grafting with the aortic no-touch technique. Postoperative coronary angiography showed that all the grafts were patent and no anastomotic pseudoaneurysms were observed. Pathological examination of the right internal thoracic artery specimen revealed mild intimal thickening and disruption of elastic fibers in the medial layer, both of which are characteristics of Behçet's disease. These findings indicated that the patient must be monitored carefully for postoperative pseudoaneurysm formation.