Ryuzo Sakata

Mechanism of ischemic mitral regurgitation

The basic mechanism of ischemic mitral regurgitation (MR) is believed augmented leaflet tethering due to the outward displacement of the papillary muscles by left ventricular (LV) remodeling or dilatation. Annular dilatation and LV dysfunction may not be the central mechanism, but contribute to the development of MR in the presence of augmented tethering. Papillary muscle dysfunction was initially expected to cause leaflet prolapse and MR. However, multiple studies have confirmed that papillary muscle dysfunction per se does not usually cause ischemic MR and recent studies further suggest that papillary muscle dysfunction may occasionally attenuate tethering and MR. Although surgical annuloplasty is usually effective to treat ischemic MR, occasional patients with persistent or recurrent ischemic MR after surgical ring annuloplasty even with advanced downsizing suggest the need for approaches to address tethering. Finally, leaflet tethering in patients with ischemic MR can be heterogeneous, indicating the need for individualized approaches to correct ischemic MR in affected patients.

Functional mitral stenosis after surgical annuloplasty for ischemic mitral regurgitation: Importance of subvalvular tethering in the mechanism and dynamic deterioration during exertion

OBJECTIVE Diastolic subvalvular mitral leaflet tethering by left ventricular remodeling that restricts leaflet opening in the presence of annular size reduction by surgery for ischemic mitral regurgitation potentially causes functional mitral stenosis in the absence of organic leaflet lesions. Exercise, known to worsen systolic tethering and ischemic mitral regurgitation, might also dynamically exacerbate such mitral stenosis by increasing tethering. This study evaluates the mechanism and response of such mitral stenosis to exercise. METHODS We measured the diastolic mitral valve area, annular area, and peak and mean transmitral pressure gradient by echocardiography in 20 healthy individuals and 31 patients who underwent surgical annuloplasty for ischemic mitral regurgitation. RESULTS Although the mitral valve area and annular area did not significantly differ in healthy individuals (4.7 +/- 0.6 cm(2) vs 5.2 +/- 0.6 cm(2), not significant), mitral valve area was significantly smaller than the annular area in patients after annuloplasty (1.6 +/- 0.2 cm(2) vs 3.3 +/- 0.5 cm(2), P < .01). The mitral valve area was less than 1.5 cm(2) only after the surgery (P < .01) and was significantly correlated with restricted leaflet opening (r(2) = 0.74, P < .001), left ventricular dilatation (r(2) = 0.17, P < .05), and New York Heart Association functional class (P < .05). Exercise stress echocardiography of 12 patients demonstrated dynamic worsening in functional mitral stenosis (mitral valve area: 2.0 +/- 0.5 cm(2) to 1.4 +/- 0.2 cm(2), P < .01; mean pressure gradient: 1.5 +/- 0.9 mm Hg to 6.0 +/- 2.2 mm Hg, P < .01). CONCLUSIONS Persistent subvalvular leaflet tethering in the presence of annular size reduction by surgery in ischemic mitral regurgitation frequently causes functional mitral stenosis at the leaflet tip level, which is related to heart failure symptoms and can be dynamic with significant exercise-induced worsening.

Cerebral ischemic disorders and cerebral oxygen balance during cardiopulmonary bypass surgery : Preoperative evaluation using magnetic resonance imaging and angiography

We compared the preoperative prevalence of small cerebral infarctions and carotid stenosis to jugular venous oxygen saturation (SjVO2) during coronary artery bypass grafting (CABG).SjVO2 served as an indicator of whether cerebral oxygen supply meets demand in patients on cardiopulmonary bypass (CPB). The study population consisted of 121 patients who were either older than 65 yr or had a history of cerebrovascular disease. The patients underwent preoperative cerebral magnetic resonance imaging (MRI) and cervical magnetic resonance angiography (MRA) to detect small cerebral infarctions and carotid artery stenosis. Patients with atherosclerosis of the ascending aorta were identified by intraoperative epiaortic ultrasonography. Liberation of emboli from the aorta in these patients was prevented by modification of the standard operation. From preoperative MRI and MRA, 65 patients (54%) had small cerebral infarctions in the white matter or basal ganglia and nine patients (7%) demonstrated moderate or severe stenosis in the carotid arteries. Thirteen patients (11%) had moderate or severe atheromatous disease of the ascending aorta. The severity of aortic atherosclerosis was significantly correlated with the grade of carotid stenosis (P < 0.05). In patients with small infarctions, SjVO2 was significantly lower than in patients without infarctions (controls) at initiation of CPB, 30 min after aortic cross-clamping, and during the rewarming period of CPB (P < 0.05). Thus, small cerebral infarctions were not uncommon in elderly patients undergoing CABG. Patients with small cerebral infarctions may be at risk for an imbalance in cerebral oxygen supply and demand during the rewarming period because they are unable to deliver the necessary compensatory blood flow. (Anesth Analg 1997;84:5-11)

Inhibition of Platelet Aggregation and the Release of P-Selectin from Platelets by Cilostazol

To evaluate the in vitro effects of cilostazol, a phosphodiesterase III inhibitor, on platelet responses, we measured platelet aggregation and the levels of soluble P-selectin, a glycoprotein present on the alpha-granule membrane in resting platelets, and cAMP. Platelet-rich plasma and washed platelets from healthy human volunteers were treated with cilostazol (5, 25 and 50 microM). Platelet-rich plasma was stimulated by ADP (1 and 5 microM) or collagen (5 microg/ml). Washed platelets were stimulated by thrombin (4 U/ml) in the presence or absence of 1 microM forskolin. In vehicle-treated samples, soluble P-selectin levels in response to 1 microM ADP-induced primary aggregation were similar to those of circulating levels of healthy volunteers but the levels in response to 5 microM ADP-induced secondary aggregation and collagen-induced aggregation increased markedly compared to those in response to primary aggregation. This result suggests that P-selectin is released from platelets according to the extent of platelet aggregation. Cilostazol inhibited platelet aggregation as well as P-selectin release in a concentration-dependent manner. Cilostazol inhibited completely thrombin-induced aggregation in the presence of 1 microM forskolin, when cAMP levels were two-fold higher than those in the absence of forskolin. Cilostazol, which increases intracellular cAMP in platelets, may be useful in the treatment of arterial occlusive diseases.

Intracardiac thrombus, superior vena cava syndrome, and pulmonary embolism in a patient with Behçet's disease: a case report and literature review

A 26-year-old woman with intermittent fever was admitted to our hospital, and gradually developed facial edema. Examinations including computed tomography, transesophageal echocardiography, digital subtraction angiography, and pulmonary perfusion scintigraphy revealed intracardiac thrombus, superior vena cava syndrome, and pulmonary embolism. Clinical findings and laboratory data led us to make a diagnosis of Behçets disease. Combination of intracardiac thrombus, superior vena cava syndrome, and pulmonary embolism are rare complications in Behçets disease. Behçets disease should be considered in the differential diagnosis of intracardiac mass of the right heart, and early diagnosis and treatment are essential for the management of Behçets disease especially with large-vessel manifestations. In addition to a case report, we review the literature and report the characteristics of intracardiac thrombus in Behçets disease.

Serial measurement of serum S-100B protein as a marker of cerebral damage after cardiac surgery

BACKGROUND We used serial measurements of serum S-100B protein to evaluate the time course of serum S-100B protein concentration after cardiovascular surgery and to determine the clinical relevance of its concentration and cerebral damage. METHODS We assessed neurologic function in 149 patients undergoing cardiovascular surgery with cardiopulmonary bypass. The patients were classified into three groups according to their early postoperative outcome: those without complications (group A), those having unconsciousness or convulsion or both but no hemiplegia (group B), and those having unconsciousness and hemiplegia either with or without convulsion (group C). Serum S-100B protein concentrations were measured with a commercially available immunoluminometric assay, Sangtec 100 LIA, at seven time-points: before cardiopulmonary bypass, at the end of cardiopulmonary bypass, and at 5, 12, 24, 48, and 72 hours after cardiopulmonary bypass. RESULTS At 5 hours after cardiopulmonary bypass, the S-100B values in groups B and C were significantly higher than the value in group A. Although the S-100B level decreased in group C during the first 5 hours after cardiopulmonary bypass, it increased thereafter (12 through 24 hours) and continued at a high level until the final measurement at 72 hours. At 12 hours after cardiopulmonary bypass, S-100B was significantly higher in group C than in group B. This late increase in S-100B was associated with radiologically detected abnormalities and cerebral damage. CONCLUSIONS Serial measurement of serum S-100B protein in the initial 12 hours after cardiopulmonary bypass can be used to predict early postoperative brain injury.

Effects of sarpogrelate hydrochloride on adenosine diphosphate- or collagen-induced platelet responses in arteriosclerosis obliterans.

To evaluate the effects of the 5-HT2 receptor antagonist sarpogrelate hydrochloride (sarpogrelate) on platelet responses in arteriosclerosis obliterans (ASO), we examined platelet aggregation and its relationships to platelet-derived growth factor (PDGF), soluble P-selectin (sP-selectin), and transforming growth factor-beta 1 (TGF-β1). Circulating plasma levels of PDGF and sP-selectin in 13 patients with ASO after 1 week of medication with sarpogrelate were significantly lower than those before medication. In contrast, circulating plasma levels of TGF-β1 after medication were significantly higher than those before medication. When platelet-rich plasma obtained from ASO patients after medication was stimulated with adenosine diphosphate (ADP) or collagen, platelet aggregation was suppressed compared with rates before medication. Significant decreases in levels of PDGF, sP-selectin and TGF-β1 released from platelets in response to 5 μmol/l ADP and 1 μg/ml collagen after taking of sarpogrelate were found. There were close correlations between platelet aggregation and respective molecules released from platelets. In conclusion, since platelet activation is involved in pathogenesis of thrombotic disease, sarpogrelate may suppress the development of obstructive arteriosclerosis. PDGF and TGF-β1, as well as sP-selectin, appear to be useful markers for clinical evaluation of anti-platelet drugs.

Effect of a neutrophil elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using the left-sided heterotopic canine heart transplantation model

BACKGROUND Ischemia/reperfusion injury is a major cause of transplanted heart dysfunction. Several reports have demonstrated that polymorphonuclear neutrophil (PMN) elastase derived from the activated neutrophils might play an important role in this injury. Herein, we investigated the protective effects of PMN elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using a left-sided canine heterotopic heart transplantation model. METHODS We used 10 pairs of adult beagle dogs. The donor heart was transplanted heterotopically into the left thoracic cavity of the recipient without cardiopulmonary bypass. A bolus of ONO-5046 Na (10 mg/kg) was introduced intravenously to 5 recipients (group II) at 15 minutes before reperfusion and was followed by continuous infusion (10 mg/kg per hour) for 180 minutes. Five dogs (group I) did not receive ONO-5046 Na and thus served as a control. After reperfusion, we evaluated transplanted heart function and obtained blood samples from the coronary sinus over a 360-minute period. RESULTS E(max) and pre-load recruitable stroke work in group II showed significantly better recovery than group I. Blood levels of PMN elastase, creatine kinase MB, lactate and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-8) were significantly lower in group II. Depletion of myocardial concentration of adenosine triphosphate at 120 minutes after reperfusion and myocardial water content was significantly lower in group II. CONCLUSIONS ONO-5046 Na, which inhibits PMN elastase, could reduce ischemia/reperfusion injury in heart transplantation. These results indicate that clinical application of ONO-5046 Na should be considered.

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 μmol/l aspirin, 10 μmol/l cilostazol and 1 μmol/l ramatroban on 5 μmol/l ADP-induced PRP aggregation were similar. However, aspirin strongly inhibited thromboxane A2 formation in response to 5 μmol/l ADP compared with other drugs. Inhibitory effects of 10 μmol/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.

Aortoenteric fistula after endovascular stent grafting for an abdominal aortic aneurysm: report of a case.

We report a case of an aortoenteric fistula (AEF) developing after endovascular stent grafting (EVSG) for an abdominal aortic aneurysm (AAA). A 69-year-old male patient with a history of panperitonitis caused by rectal perforation underwent EVSG for an AAA. A follow-up contrast-enhanced computed tomography (CT) scan, done 12 months after the EVSG, confirmed shrinkage of the AAA with no endoleak. However, 19 months postoperatively, an AEF developed between the AAA and the jejunum. Although there was no endoleak on a subsequent CT scan, we noted enlargement of the AAA and inflammatory changes in the surrounding tissue. The patient was treated surgically and discharged in good health 74 days postoperatively. Thus, one should consider the possibility of this devastating complication, even in patients without an endoleak, after EVSG for AAA.