Kazuhiro Hashimoto

Heparin and antithrombin III levels during cardiopulmonary bypass: Correlation with subclinical plasma coagulation

The anticoagulant effect of heparin in the milieu of altered antithrombin III levels was investigated in adult (n = 7) and pediatric (n = 14) patients undergoing open heart operations. The pediatric patients were subdivided into a control group (n = 8) and an antithrombin III group (n = 6), which received 1,000 units of antithrombin III. The reduction in antithrombin III levels during cardiopulmonary bypass was obvious in patients of all ages, showing a greater reduction (although not statistically significant) in the pediatric patients. However, the antithrombin III group patients maintained their preoperative levels of antithrombin III. The elevated fibrinopeptide A levels in pediatric and adult control group patients suggested that considerable subclinical plasma coagulation occurred during open heart operations, especially during the normothermic period of cardiopulmonary bypass and after the administration of protamine. Antithrombin III levels in the children were the most predictive (r = -0.58; p < 0.001) for production of fibrinopeptide A during moderate hypothermic cardiopulmonary bypass, but the heparin levels were most predictive (r = -0.57, p < 0.03) in the adults. This result may be related to the different actions of heparin when antithrombin III levels are reduced. Supplementation with antithrombin III succeeded in suppressing the activation of the coagulation cascade and resulted in no statistical change in fibrinopeptide A levels at any time. We conclude that heparin and (in some patients) antithrombin III levels are important variables for the inhibition of fibrin formation and the possible preservation of coagulation proteins.

Prevalence of pannus formation after aortic valve replacement: clinical aspects and surgical management

Pannus formation after aortic valve replacement is not common, but obstruction due to chronic pannus is one of the most serious complications of valve replacement. The causes of pannus formation are still unknown and effective preventive methods have not been fully elucidated. We reviewed our clinical experience of all patients who underwent reoperation for prosthetic aortic valve obstruction due to pannus formation between 1973 and 2004. We compared the initial 18-year period of surgery, when the Björk–Shiley tilting-disk valve was used, and the subsequent 13-year period of surgery, when the St. Jude Medical valve was used. Seven of a total of 390 patients (1.8%) required reoperation for prosthetic aortic valve obstruction due to pannus formation. All seven patients were women; four patients underwent resection of the pannus and three patients needed replacement of the valve. The frequency of pannus formation in the early group was 2.4% (6/253), whereas it was 0.73% (1/137) in the late group (P < 0.05). Pannus was localized at the minor orifice of the Björk–Shiley valve in the early group and turbulent transvalvular blood flow was considered to be one of the important factors triggering its growth. We also consider that small bileaflet valves have the possibility of promoting pannus formation and that the implantation of a larger prosthesis can contribute to reducing the occurrence of pannus.

Total cavopulmonary connection without the use of prosthetic material: Technical considerations and hemodynamic consequences

Total cavopulmonary connection with use of an autogenous intraatrial tunnel to create a straight tube between the inferior vena cava and the pulmonary artery was attempted in several types of cardiac anomaly in eight consecutive candidates for the Fontan operation. A small right atrium with an extraordinary location of the inferior vena cava and a short superior vena cava prevented the use of this procedure in two cases. By preserving the crista terminalis and the sinus node and its arteries we prevented the development of postoperative atrial arrhythmias in the short follow-up period, and the P trigger-signal averaged P waves were not different from those of other cardiac anomalies. The proximal stump of the superior vena cava was not incised in any case to enlarge the anastomosis, even when size mismatch between the superior and inferior venae cavae existed, as in a case of bilateral superior venae cavae. Stretching the vessels by approximately 150% was possible and permitted an adequate anastomosis. Cavopulmonary connections via the intraatrial tunnel ensured smooth, nonturbulent, somewhat pulsatile flow without a pressure gradient. We concluded that the creation of an autogenous intraatrial tunnel was possible in many cases without serious complications and that this procedure has potential benefit for the pulmonary circulation in the aspect of pulsatility.

Pharmacological intervention for renal protection during cardiopulmonary bypass

SummaryThe possibility of minimizing organ damage following cardiopulmonary bypass (CPB) was examined. In the control group,n = 21, upon completion of CPB, elevation of the lysosomal enzyme β-glucuronidase, which is a sensitive indicator of cellular damage, was affected by the concentration of granulocyte elastase (r = 0.59) or the endothelial-derived constricting factor, endothelin, (r = 0.8). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-β-D-glucosaminidase and γ-glutamyltranspeptidase) in urine, was also affected by endothelin (r = 0.79, r = 0.56), elastase (r = 0.6, r = 0.71), and by free hemoglobin levels (r = 0.76, r = 0.82). Next, the efficacy of pharmacological intervention for the prevention of renal damage was evaluated. During CPB, the administration of an elastase inhibitor (ulinastatin, 3 × 105IU),n = 8, or a calcium antagonist (nicaldipine HCl, elastase release inhibitor; 5 γ/kg per min),n = 8, significantly reduced the elevation of β-glucuronidase and renal tubular enzymes (p < 0.05). Although the ulinastatin and nicardipine groups demonstrated low values of elastase in the Intensive Care Unit (ICU), only the values of the nicardipine group reached statistical significance (p < 0.05). A reduction in endothelin levels compared to the control group was observed in the nicardipine group. However, preventive and counteractive effects of nicardipine against vasoconstriction caused by endothelin were also considered to play an important role in the prevention of renal damage. The addition of haptoglobin (4,000 IU) to the priming solution of the CPB also reduced levels of renal tubular enzymes (p < 0.05). We concluded that elastase, endothelin, and free hemoglobin were causes of renal damage during CPB. The administration of ulinastatin, nicardipine, or haptoglobin possibly prevent apparent renal dysfunction after CPB.

Hemodynamic evaluation of 19-mm Carpentier-Edwards pericardial bioprosthesis in aortic position

BACKGROUND The aortic Carpentier-Edwards pericardial bioprosthesis offers good long-term clinical outcomes with a low rate of structural deterioration. However, little in vivo hemodynamic data is available for this bioprosthesis. METHODS To determine the hemodynamic performance of the 19-mm Carpentier-Edwards pericardial valve, both cardiac catheterization and dobutamine stress echocardiography were electively performed in 10 patients. The mean age at the study was 71.6 +/- 4.4 years and the mean body surface area was 1.39 +/- 0.11 m2. The peak-to-peak gradient, instantaneous peak gradient, mean gradient, and valve orifice area were measured by standard cardiac catheterization. The Doppler-derived gradients and valve orifice area were also measured both at rest and during dobutamine infusion. RESULTS The average peak-to-peak gradient, instantaneous peak gradient, mean gradient, and valve orifice area measured by catheterization were 13.0 +/- 5.4 mmHg, 28.5 +/- 7.7 mmHg, 12.0 +/- 4.9 mmHg, and 1.55 +/- 0.45 cm2, respectively. The peak and mean Doppler gradients, and valve orifice area by resting echocardiography were 27.7 +/- 9.5 mmHg, 12.3 +/- 4.8 mmHg, and 1.39 +/- 0.26 cm2, respectively. At a dosage of 10 microg/kg/min of dobutamine, the mean Doppler gradient rose mildly to 22.2 +/- 4.8 mmHg, while the cardiac output increased from 4.49 +/- 0.44 to 6.64 +/- 0.87 L/min. The valve orifice area during the 10 microg/kg/min dobutamine infusion (1.55 +/- 0.25 cm2) was significantly larger than its value at rest (p < 0.05). CONCLUSIONS With acceptable hemodynamic performance, use of the aortic 19-mm Carpentier-Edwards pericardial valve is a reliable option for elderly patients with a small annulus.

Optimal timing of surgery for active infective endocarditis with cerebral complications: a Japanese multicentre study

OBJECTIVES The aim of this study was to investigate the effect of the timing of valve surgery on the clinical outcomes of patients with active infective endocarditis (IE) accompanied by cerebral complications. METHODS We retrospectively analysed a cohort of 568 patients, comprising 118 with non-haemorrhagic cerebral infarction (CI), 54 with intracranial haemorrhage (ICH) and 396 without cerebral events (C; control), who underwent surgery for left-sided active IE in 15 Japanese institutes from 2000 to 2011. The mean age was 58.4 ± 16.9 years in the CI group; 54.5 ± 17.4 years in the ICH group and 56.9 ± 16.0 years in the C group. Clinical outcomes were analysed according to the timing of surgery after the diagnosis of CI or ICH was made. RESULTS In the CI group, there were 9 (7.6%) hospital deaths, 13 (11%) new cerebral events and 1 (0.8%) redo valve surgery. In the ICH group, there were 3 (5.6%) hospital deaths, 8 (14.8%) new cerebral events and 2 (3.7%) redo valve surgeries. In the C group, there were 36 (9.1%) hospital deaths, 23 (5.8%) new cerebral events and 9 (2.3%) redo valve surgeries. Risk factors for hospital death were prosthetic valve endocarditis (P = 0.045), high C-reactive protein (CRP; P < 0.001) and the elderly (P < 0.001) in the CI group. Delayed surgery (2 weeks after CI) seemed result in a higher incidence of hospital death in the CI group. Patients who had surgery between 15 and 28 days or after 29 days from the onset of CI had higher incidences of hospital death [odds ratio 5.90 (P = 0.107) and 4.92 (P = 0.137), respectively] compared with those who had surgery within 7 days. In the ICH group, risk factors for hospital death were high CRP (P = 0.002) and elderly (P < 0.001). Contrary to CI patients, patients who had surgery between 8 and 21 days or after 22 days after the onset of ICH had lower incidences of hospital death [odds ratio 0.79 (P = 0.843) and 0.12 (P = 0.200), respectively] compared with those who had surgery within 7 days. CONCLUSIONS Although statistically insignificant, early surgery in active IE patients with CI is safe, but very early surgery (within 7 days) should be avoided in patients with ICH.

Prevention of ischemia/reperfusion-induced pulmonary dysfunction after cardiopulmonary bypass with terminal leukocyte-depleted lung reperfusion

OBJECTIVE Pulmonary ischemia and reperfusion during routine open heart surgery with cardiopulmonary bypass can lead to pulmonary dysfunction and vasoconstriction, resulting in a high morbidity and mortality. We investigated whether ischemia/reperfusion-induced pulmonary dysfunction after full-flow cardiopulmonary bypass could be prevented by the infusion of leukocyte-depleted hypoxemic blood during the early phase of reperfusion (terminal leukocyte-depleted lung reperfusion) and whether the benefits of this method were nullified by using hyperoxemic blood for reperfusion. METHODS Twenty-one neonatal piglets underwent 180 minutes of full-flow cardiopulmonary bypass with pulmonary artery occlusion, followed by reperfusion. The piglets were divided into 3 groups of 7 animals. In group I, uncontrolled reperfusion was achieved by unclamping the pulmonary artery. In contrast, pulmonary reperfusion was done with leukocyte-depleted hyperoxemic blood in group II or with leukocyte-depleted hypoxemic blood in group III for 15 minutes at a flow rate of 10 mL/min/kg before pulmonary artery unclamping. Then the animals were monitored for 120 minutes to evaluate post-cardiopulmonary bypass pulmonary function. RESULTS Group I developed pulmonary dysfunction that was characterized by an increased alveolar-arterial oxygen difference (204 + or - 57.7 mm Hg), pulmonary vasoconstriction, and decreased static lung compliance. Terminal leukocyte-depleted lung reperfusion attenuated post-cardiopulmonary bypass pulmonary dysfunction and vasoconstriction when hypoxemic blood was used for reperfusion (alveolar-arterial oxygen difference, 162 + or - 61.0 mm Hg). In contrast, no benefit of terminal leukocyte-depleted lung reperfusion was detected after reperfusion with hyperoxemic blood (alveolar-arterial oxygen difference, 207 + or - 60.8 mm Hg). CONCLUSION Reperfusion with leukocyte-depleted hypoxemic blood has a protective effect against ischemia/reperfusion-induced pulmonary dysfunction by reducing endothelial damage, cytokine release, and leukocyte activation.

Right atrial myxoma complicated with pulmonary embolism

A 25-year-old woman was admitted to our hospital with chest pain and dyspnea, and was diagnosed as having a right atrial myxoma complicated with pulmonary embolism. An emergency operation was performed with cardiopulmonary bypass. A papillary pedunculated tumor was found having a narrow-based attachment to the free atrial wall. After the tumor was carefully removed together with the atrial wall around the attachment, pulmonary embolectomy was performed. Several fragments of the tumor were removed, and sufficient back-flow from the pulmonary artery was established. The postoperative course was uneventful. However, a non-perfused area was observed in the left lower lung on pulmonary hemodynamic scintigraphy at 3 months after the operation. Long-term observation is required due to the high risk for metastasis and recurrence, and further surgical treatment remains the most appropriate treatment option. A second operation may be needed to prevent progression in complications.

Congenital mitral regurgitation from absence of the anterolateral papillary muscle

A 21-year-old woman had congenital mitral regurgitation. Echocardiography showed absence of the anterolateral papillary muscle and corresponding marginal chordae. This rare abnormality was corrected by anterolateral commissural annuloplasty and insertion of artificial chordae to prevent prolapse of the anterior leaflet. Postoperatively, there was no regurgitation, and an appropriate mitral valve area was achieved.

Reconsideration of Patient-Prosthesis Mismatch Definition From the Valve Indexed Effective Orifice Area

BACKGROUND The objective of this study was to reassess the validity of defining patient-prosthesis mismatch (PPM) in the aortic position on the basis of an indexed effective orifice area (iEOA) less than 0.85 cm(2)/m(2). METHODS From June 1996 to March 2008, 342 patients underwent aortic valve replacement with a Carpentier-Edwards Perimount valve. From the data collected, the transvalvular pressure gradient was determined by the modified Bernoulli equation, and EOA was calculated from the standard continuity equation. RESULTS The actuarial survival rate at 10 years after surgery was 84.0% +/- 8.2%. The prevalence of PPM was 6.1% when a projected iEOA less than 0.85 cm(2)/m(2) was defined as indicating significant PPM. There was no difference between patients with moderate PPM (85.2% +/- 9.8%) and patients without PPM (81.0% +/- 8.7%; p = 0.44). The relation between mean transvalvular pressure gradient and iEOA demonstrated a gentler slope than that reported previously. Postoperative mean transvalvular pressure gradient was 17.4 +/- 5.6 mm Hg and 14.5 +/- 5.6 mm Hg in patients with an iEOA less than 0.85 and 0.85 or greater, respectively. Most patients had a postoperative mean transvalvular pressure gradient more than 10 mm Hg regardless of PPM. CONCLUSIONS Our analysis suggested that an iEOA less than 2.0 cm(2)/m(2) might be the threshold for PPM, which should not be passed to achieve a low mean transvalvular pressure gradient (less than 10 mm Hg) with the Carpentier-Edwards Perimount valve. The implications of these findings include the necessity for reassessing the hemodynamic performance of each type of prosthesis when attempting to define PPM, to avoid residual significant transvalvular pressure gradient.