Shigeaki Ohtake

Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation

BACKGROUND In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma. METHODS Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups. RESULTS Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis. CONCLUSIONS Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.

Peroxynitrite formation from human myocardium after ischemia-reperfusion during open heart operation

BACKGROUND Current experimental studies have demonstrated that peroxynitrite (ONOO-) has both cytotoxic and cytoprotective effects on myocardial ischemia-reperfusion injury. However, even myocardial ONOO- formation has not yet been investigated in humans undergoing open heart operation. We measured plasma nitrotyrosine as an indicator of ONOO- formation during open heart operation and examined its association with myocardial ischemia-reperfusion injury. METHODS Twenty adult patients undergoing mitral valve replacement under cardiopulmonary bypass between 1997 and 1998 were enrolled in this study (6 men and 14 women). Arterial blood (Ao) and coronary sinus effluent (CS) were obtained: (1) before the initiation of cardiopulmonary bypass, (2) just after aortic unclamping, (3) at 5 minutes, (4) at 10 minutes, (5) at 15 minutes, and (6) at 20 minutes after aortic unclamping. RESULTS At every sampling point after reperfusion, plasma nitrate and nitrite was significantly lower in CS than in Ao, and the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr; an index of ONOO- formation) was significantly higher in CS than in Ao. The CS-Ao difference in %NO2-Tyr, myocardium-derived ONOO-, reached its peak at 5 minutes after reperfusion (2.17+/-0.74%), which was significantly correlated with the peak CS-Ao difference in plasma malondialdehyde, and with postoperative maximum creatine kinase-MB. CONCLUSIONS These results first demonstrate that ONOO- is produced from human myocardium after ischemia-reperfusion during open heart operation, and myocardium-derived ONOO- can be determined by the CS-Ao difference in %NO2-Tyr.

The long-term outcome of a surgical repair of sinus of valsalva aneurysm.

BACKGROUND In order to clarify the long-term outcome after surgical repair of a sinus of Valsalva aneurysm, we retrospectively assessed the operative results for patients treated in our institute. METHODS The subjects were 27 patients who had undergone an operation between 1958 and 1996. For associated aortic regurgitation (AR) aortic valve repair was performed in 13 patients, 12 of whom had a ventricular septal defect (VSD); and an aortic valve replacement was performed in 3 patients, 1 of whom had a VSD. RESULTS Five of the 13 patients who had aortic valve repair needed aortic valve replacement because AR developed after a period of between 7 and 13 years; those cases were complicated by VSD. Another 2 patients with mild AR also complicated by VSD are currently under observation. CONCLUSIONS Although the postoperative outcome of the aortic valve repairs was good, cases that were complicated by VSD plus associated AR tended to develop AR later after surgery. Therefore, careful observation of the postoperative course is necessary.

Controlled nicorandil administration for myocardial protection during coronary artery bypass grafting under cardiopulmonary bypass.

&NA; Nicorandil is a hybrid potassium channel opener, and recent experimental studies have demonstrated its efficacy in myocardial protection against ischemia‐reperfusion. This clinical study was designed to examine the myocardial protective effect of nicorandil administered during cardiopulmonary bypass. Seventy adult patients, 53 men and 17 women, undergoing elective coronary artery bypass grafting were randomly assigned to two groups, one receiving nicorandil during cardiopulmonary bypass (group N, n = 35) and the other receiving no nicorandil for control (group C, n = 35). Nicorandil was administered at each dose of 0.1 mg/kg into the cardiopulmonary bypass circuit according to the following schedule: (1) bolus injection at the initiation of cardiopulmonary bypass, (2) continuous infusion for 5 min before aortic cross‐clamping, (3) bolus administration at 5 min before reperfusion, and (4) continuous infusion for 5 min before reperfusion. The time required for achieving cardiac arrest after the initial cardioplegia was significantly reduced in group N in comparison with that in group C. After aortic unclamping, the number of patients showing a significant ST segment change on the electrocardiogram was significantly fewer in group N, whereas the number of patients showing spontaneous recovery of heart beat was significantly greater. As for the myocardial protective effect, group N showed lower plasma levels of malondialdehyde, human‐heart fatty acid‐binding protein, and peak creatine kinase‐MB, and required lower doses of catecholamine. Our results suggest that nicorandil administration during cardiopulmonary bypass provides enhanced myocardial protective effects against ischemia‐reperfusion in patients undergoing coronary artery bypass grafting.

Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation

BACKGROUND Blood cardioplegia (BCP) is widely used for myocardial protection during open heart operation. However, BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping. We clinically evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP) for initial and intermittent BCP administration in pediatric patients. METHODS Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were reviewed. Twenty-five were administered LDBCP for myocardial protection during ischemic periods (LDBCP group), and the remaining 25 were given BCP without leukocyte depletion (BCP group). RESULTS The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68 +/- 0.56 micromol/L) was significantly lower than that in the BCP group (2.35 +/- 0.62 micromol/L; p < 0.01). The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion (LDBCP group, 103.5 +/- 38.7 IU/L; BCP group, 144.8 +/- 48.8 IU/L; p < 0.01) and the peak value of creatine kinase-MB during the first 24 postoperative hours (LDBCP group, 17.0 +/- 8.5 IU/L; BCP group, 26.0 +/- 11.6 IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was significantly smaller in the LDBCP group (LDBCP group, 3.20 +/- 2.18 microg x kg(-1) x min(-1); BCP group, 5.60 +/- 2.83 microg x kg(-1) x min(-1); p < 0.01). CONCLUSIONS These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping.

Analysis of sympathetic nerve activity in end-stage cardiomyopathy patients receiving left ventricular support

BACKGROUND The left ventricular assist system (LVAS) has been used increasingly for patients with end-stage heart failure who are awaiting transplantation. Sympathetic nerve activity is known to correlate with cardiac function in chronic heart failure patients, but little is known about sympathetic nerve activity during LVAS support. In this study, we examined the status of sympathetic nerve activity in relation to mechanical support. METHODS In this study, we included 10 consecutive patients with end-stage cardiomyopathy who were on LVAS support for at least 2 months (duration, 222 +/- 59 days). None of these patients achieved enough functional recovery to be taken off LVAS. In these patients, we used iodine-125-metaiodobenzylguanidine (125I-MIBG) scintigraphy to examine the change of sympathetic nerve activity after LVAS implantation, and compared the results with the change of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels as well as with histologic optional findings. Samples for ANP and BNP measurement were obtained before and 30 days after LVAS implantation. Specimens for histologic analysis were obtained at the time of LVAS implantation and at the time of cardiac transplantation or autopsy. RESULTS We observed marked decrease in serum levels of ANP and BNP 1 month after LVAS implantation. But myocardial sympathetic nerve function, which was evaluated with 125I-MIBG scintigraphy and expressed as the heart-to-mediastinum activity ratio, remained below normal even 2 months after the LVAS implantation (1.57 +/- 0.19; normal, 2.34 +/- 0.36). Serial histologic analysis in these 10 patients showed continuous increase in percentage of fibrosis and cell diameter despite ventricular unloading by the LVAS. CONCLUSIONS Sympathetic nerve function, which was evaluated on 125I-MIBG scintigraphy, did not improve during left ventricular support. Because none of the patients included in our study showed improvement in cardiac function or histologic findings, the recovery of myocardial sympathetic nerve function may be an important factor in myocardial recovery for cardiomyopathy patients on LVAS support.

Hemodynamic effect of inhaled nitric oxide in dilated cardiomyopathy patients on LVAD support.

Recently it has been shown that inhaled nitric oxide (NO), which has been proven to contribute to improvement in critical pulmonary hypertension, may provide a favorable effect early after left ventricular assist device (LVAD) support. To improve right ventricular function, inhalation of NO was added to treatment with conventional catecholamines for four consecutive dilated cardiomyopathy (DCM) patients following institution of LVAD. In two patients 1 hr after inhalation of NO, central venous pressure (CVP), mean pulmonary arterial pressure (PAm), and pulmonary vascular resistance (PVR) were improved. These results led to better LVAD output and resulted in an adequate cardiac index. On the other hand, a right VAD (RVAD) was implemented in one patient whose high CVP, PAm, and PVR continued; he was weaned after 8 days of RVAD support. Another patient who had a high CVP but normal PAm and PVR before and after inhalation of NO had no improvement in his hemodynamic state. These data suggest that inhaled NO may improve systemic circulation by reducing right ventricular afterload and may become a promising and convenient therapy before placing RVAD in DCM patients under LVAD support. RVAD should be conducted in patients with right ventricular failure or when pulmonary hypertension is associated with impaired right ventricular reserve, even after inhalation of NO. ASAIO Journal 1997;43:M418-M421.

Thyroid carcinoma with extensive tumor thrombus in the atrium.

To our knowledge, only a few cases of thyroid carcinoma with an extensive tumor thrombus in the atrium have been reported in literature. We describe a unique case of papillary carcinoma of the thyroid with extensive tumor thrombus in the atrium. A 74-year-old man consulted our hospital because of thyroid carcinoma with an extensive tumor thrombus in the atrium. Computed tomography (CT) revealed a 2-cm tumor with extensive continuous tumor thrombus in the left jugular vein, innominate vein, superior vena cava, and atrium. The tumor was resected to reduce the risk of sudden death from tumor embolism into the pulmonary arteries. Histologically, the diagnosis was papillary carcinoma of the thyroid. Thyroid carcinoma, especially papillary carcinoma, rarely develops a macroscopic tumor thrombus. Patients with an extensive tumor thrombus generally have poor prognoses and high mortality. This patient has been followed for 7 months after successful operation without recurrence.

The freestyle stentless bioprosthesis for prosthetic valve endocarditis

We report a case of methicillin-resistant Staphylococcus aureus-induced prosthetic valve endocarditis, which was successfully treated with aortic valve replacement using the Freestyle stentless bioprosthesis. The total root and stentless design of this bioprosthesis allows for more radical removal of infected tissue and easier treatment for annular abscess, while requiring less prosthetic materials than a conventional prosthesis. This bioprosthesis thus seems to be a valuable option for active endocarditis.

Early result of heart transplantation in Japan: Osaka University experience.

Since the new organ transplantation law was established in 1997, 17 heart transplantations have been performed in Japan, 7 of which were carried out at Osaka University Hospital. Recipient diagnosis was dilated cardiomyopathy in 2, dilated phase of hypertrophic cardiomyopathy in 4, and post-myocarditis cardiomyopathy in 1. Ages ranged from 8 to 49 years with a mean of 35.3 years. Five patients were bridged with a left ventricular assist device. The waiting period was 182–977 days (mean, 643 days). There was no early or late death during follow-up of 1–4.8 years. Under a standard triple-drug regimen using mycophenolate, there were 3 rejection episodes greater than grade 3 in 2 patients, and humoral rejection requiring plasmapheresis in one. A young boy whose donor was a hemodynamically compromised adult developed neurological sequelae after resuscitation following ventricular tachycardia. All patients were discharged and went back to work or their regular daily life. Although the donor shortage is still severe in Japan, the resumption of heart transplantation has been satisfactory, and left ventricular assist devices have played a crucial role.