Eisaku Nakamura

BOTH 5-HYDROXYTRYPTAMINE 5-HT2A AND 5-HT1B RECEPTORS ARE INVOLVED IN THE VASOCONSTRICTOR RESPONSE TO 5-HT IN THE HUMAN ISOLATED INTERNAL THORACIC ARTERY

1 The 5‐hydroxytryptamine (5‐HT, serotonin) receptor subtypes that mediate vasoconstriction in the human internal thoracic artery (ITA), which is frequently used as an arterial graft, remain unclear. The aim of the present study was to elucidate the 5‐HT receptor subtypes responsible for 5‐HT‐induced contraction of the human ITA. 2 The contractile responses to 5‐HT of endothelium‐denuded human ITA obtained from patients undergoing coronary bypass surgery were examined. In addition, we investigated the effects of sarpogrelate and SB224289, antagonists of 5‐HT2A and 5‐HT1B receptors, respectively, on the 5‐HT‐induced vasoconstriction. Finally, 5‐HT2A and 5‐HT1B receptors in the human ITA were immunolabelled. 3 5‐Hydroxytryptamine (1 nmol/L–10 mmol/L) caused vasoconstriction in a concentration‐dependent manner. Both sarpogrelate (1 mmol/L) and SB224289 (1 mmol/L) significantly, but not completely, inhibited 5‐HT‐induced vasoconstriction. 4 Conversely, simultaneous pretreatment with supramaximum concentrations (1 mmol/L for both) of sarpogrelate and SB224289 almost completely inhibited the 5‐HT‐induced vasoconstriction. 5 Immunopositive staining for 5‐HT2A and 5‐HT1B receptors was detected in smooth muscle cells of the human ITA. 6 These results demonstrate that, in human ITA, 5‐HT‐induced vasoconstriction is mediated by activation of both 5‐HT2A and 5‐HT1B receptors. Thus, when the human ITA is used as an arterial graft, a combination of 5‐HT2A and 5‐HT1B receptor antagonists would appear to be most useful to prevent 5‐HT‐induced vasospasm.

Clinical Implications of Additional Pedal Artery Angioplasty in Critical Limb Ischemia Patients With Infrapopliteal and Pedal Artery Disease.

Purpose: To evaluate the clinical implications of additional pedal artery angioplasty (PAA) for patients with critical limb ischemia (CLI). Methods: Twenty-nine patients (mean age 77.8±8.6 years; 21 men) with CLI (32 limbs) presenting with de novo infrapopliteal and pedal artery (Kawarada type 2/3) disease were reviewed. The need for PAA was based on the existence of sufficient wound blush (WB) around the target wounds after conventional above-the-ankle revascularization. Fourteen patients with insufficient WB in 14 limbs received additional PAA, while 15 patients with sufficient WB in 18 limbs did not. The groups were compared for overall survival, limb salvage, and amputation-free survival within 1 year after the procedure. The wound healing rate, time to wound healing, and freedom from reintervention rate were also evaluated. Result: The success rate of additional PAA was 93% (13/14). All limbs with successful PAA achieved sufficient WB (13/13). Despite insufficient WB before the additional PAA, overall survival (86% vs 73%, p=0.350), limb salvage (93% vs 83%, p=0.400), amputation-free survival (79% vs 53%, p=0.102), and freedom from reintervention (64% vs 73%, p=0.668) rates were similar in both groups. Furthermore, the wound healing rate (93% vs 60%, p=0.05) was higher and time to wound healing (86.0±18.7 vs 152.0±60.2 days, p=0.05) was shorter in the patients who received PAA. Conclusion: Additional PAA might improve the WB and clinical outcomes (especially speed and extent of wound healing) in patients with CLI attributed to infrapopliteal and pedal artery disease.

The defective protein level of myosin light chain phosphatase (MLCP) in the isolated saphenous vein, as a vascular conduit in coronary artery bypass grafting (CABG), harvested from patients with diabetes mellitus (DM)

We examined the contractile reactivity to 5-hydroxytryptamine (5-HT) in isolated human saphenous vein (SV), as a vascular conduit in coronary artery bypass grafting (CABG), harvested from patients with diabetes mellitus (DM) and non-DM (NDM). Vascular rings of endothelium-denuded SV were used for functional and biochemical experiments. The vasoconstrictions caused by 5-HT were significantly greater (hyperreactivity) in the DM group than in the NDM group. RhoA/ROCK pathway is activated by various G-protein-coupled receptor agonists and consequently induces phosphorylation of myosin phosphatase target subunit 1 (MYPT1), a subunit of myosin light chain phosphatase (MLCP), which inhibits MLCP activity. In the resting state of the vessels, total tissue protein levels of 5-HT(2A) receptor, 5-HT(1B) receptor, RhoA, ROCK1, and ROCK2 did not differ between NDM and DM groups. However, the total protein level of MYPT1 was significantly lower in the DM group than in the NDM group. Furthermore, the ratio of P(Thr(696))-MYPT1 to total MYPT1 was significantly higher in the DM group than in the NDM group. These results suggest that the hyperreactivity to 5-HT in the SV smooth muscle of patients with DM is due to not only enhanced phosphorylation of MLCP but also defective protein level of MLCP. Thus, we reveal for the first time that the defective protein level of MLCP in the DM group can partially explain the poor patency of SV graft harvested from patients with DM.

Outcome after valve surgery in octogenarians and efficacy of early mobilization with early cardiac rehabilitation

PurposeThis study aimed to compare postoperative complications and the surgical outcome in patients aged <80 years versus octogenarian patients. Another aim was to evaluate the safety and efficacy of early mobilization with early cardiac rehabilitation in octogenarians.MethodsA retrospective analysis was performed in 138 consecutive patients (group Y comprised 118 patients <80 years, and group O comprised 20 octogenarians) who had undergone valve surgery at the authors’ institution between July 2007 and December 2009. Furthermore, the efficacy of early mobilization with early cardiac rehabilitation and long-term results were analyzed in 40 consecutive octogenarian patients undergoing valve surgery from 2000. The late survival follow-up was 100% complete.ResultsRedo cardiac operations were more frequent (O group 15.0% vs. Y group 3.4%, P = 0.011), and the preoperative EuroSCORE was significantly higher in group O than in group Y (group O 16.4 ± 18.3 vs. group Y 7.5 ± 9.1, P = 0.001). The incidence of delirium/confusion and worsening of renal function after surgery was higher in group O. The hospital mortality was 1.7% in group Y and no hospital death in group O (P > 0.99). Early mobilization with early cardiac rehabilitation significantly reduced the incidence of postoperative delirium/confusion and increased the number of patients who could return directly home. The actuarial 5-year survival rate was 77.7% for octogenarians.ConclusionAlthough there were more high-risk patients among the octogenarians, valve surgery was a safe, lowrisk procedure with excellent long-term results. Early mobilization with early cardiac rehabilitation was significantly effective and safe for postoperative recovery in octogenarians after cardiac valve surgery.

Nafamostat mesilate treatment during open heart operation in immune thrombocytopenic purpura

A 58-year old woman with idiopathic thrombocytopenic purpura underwent mitral and aortic valve replacements and tricuspid annuloplasty. Preoperative therapeutic interventions including prednisone and immunoglobulin were successful in elevating the platelet count to 93,000/ mm2. Furthermore, we used nafamostat mesilate for coagulopathy prophylaxis during cardiopulmonary bypass. Postoperative bleeding was average and clinical course was uneventful. The perioperative management for patients with idiopathic thrombocytopenic purpura requiring cardiac operation is reviewed.

Spontaneous left subclavian artery dissection with concurrent thrombosis and embolic occlusion of the lower limbs: report of a case.

A subclavian artery dissection (SAD) is usually associated with coexisting aortic disease, and spontaneous SAD is extremely rare. This report presents the case of a spontaneous SAD patient who developed atypical clinical symptoms. A 41-year-old woman presented with bilateral ischemia of her lower limbs. An urgent bilateral femoral thrombo-embolectomy was performed using a balloon catheter. Postoperative enhanced computed tomography (CT) demonstrated a localized thrombus in the left subclavian artery extending toward the descending thoracic aorta, and a follow-up CT angiogram obtained 3 months later revealed left SAD and complete resolution of the thrombus. The patient was anticoagulated with warfarin in addition to antiplatelet drugs after the balloon catheter thromboembolectomy. This is the first report of lower limb ischemia caused by an embolism from a mural thrombus of the descending thoracic aorta extending from spontaneous SAD.

Open surgery or stent repair for descending aortic diseases: Results and risk factor analysis

Objectives. Less invasive stent graft (SG) repair was compared with open surgery for patients with descending thoracic aortic diseases. Design. Thirty six patients undergoing SG repair (SG group) were matched for age, sex, location and pathology of aortic disease with a 36-patient surgical cohort (OS group), and retrospective matched case-control study was performed with respect to outcomes and risk factors for adverse outcomes. Results. Mortality rate was 5.6% in OS group and none in SG group (p=0.4930), and there was no significant difference in stroke and paraplegia rates between two groups. A higher prevalence of secondary procedures due to endoleak was seen in the patients of SG group (p=0.0113). Perioperative hypotension was an independent risk factor for in-hospital mortality (p=0.0071, odds ratio=34) and preoperative renal dysfunction was independent risk factor for paraplegia (p=0.0076, odds ratio=17.6). Conclusions. Although the importance of patient selection is emphasized to prevent endoleak, mortality rate was low in patients who underwent SG repair. SG repair is a promising alternative technique to open surgery for thoracic aortic diseases.

Protruding Thrombus in the Left Atrium Found 7 Years After Percutaneous Transvenous Mitral Commissurotomy: Report of a Case

Abstract.A 50-year-old man was transferred to our hospital for investigation of cerebellar infarction, thought to have been caused by cardiac thromboembolism. We assumed that the cardiac thromboembolism had occurred as a late complication of a percutaneous transvenous mitral commissurotomy (PTMC) performed 7 years earlier. An echocardiogram and thoracic computed tomography revealed a protruding thrombus in the left atrium and an emergency operation was performed. The protruding thrombus was found to originate from the scar that penetrated into the intra-atrial muscular septum caused by the PTMC. After removing the thrombus, the scar was covered with normal endothelium and the mitral valve was replaced with a 27-mm St. Jude Medical prosthetic valve. We think that the thromboembolism was caused by mitral valve restenosis, atrial fibrillation, and endothelial injury in the interatrial septum during PTMC. Therefore, long-term follow-up and appropriate medication is recommended after PTMC, since restenosis and thrombosis are likely to occur.

Aortic Pseudoaneurysm due to Simple Vertebral Compression Fracture Treated with Conservative Management

Blunt aortic injures are rarely associated with minimal trauma. We present a 78-year-old man with an aortic pseudoaneurysm resulting from a simple vertebral compression fracture, which was conservatively managed. He was diagnosed with a compression fracture from a minor fall 10 days previously, and fortuitously he visited the hospital after which follow-up computed tomography (CT) for previous multiple aortic surgeries was performed. The enhanced CT revealed a pseudoaneurysm on the abdominal aorta, which was bleeding from a pinhole perforation. He was conservatively treated and follow-up CT 9 months later revealed that the pseudoaneurysm had disappeared.

Angiotensin II, as well as 5-hydroxytriptamine, is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus

Diabetes mellitus (DM) is an important risk factor for adverse outcomes of coronary artery bypass grafting. The bypass grafts harvested from patients with DM tend to go into spasm after their implantation into the coronary circulation. To clarify the contribution of 5-hydroxytriptamine (5-HT) and angiotensin II (AngII) in the bypass graft spasm, we examined the contractile reactivity to 5-HT or AngII of isolated human endothelium-denuded saphenous vein (SV) harvested from DM and non-DM patients. The 5-HT-induced constriction of the SV was significantly augmented in the DM group than in the non-DM group, which is similar to our previous report. AngII-induced constriction of the SV was also significantly augmented in the DM group than the non-DM group. Especially in the non-DM group, the AngII-induced maximal vasoconstriction was markedly lower than the 5-HT-induced one. Meanwhile, the increasing rates of AngII-induced vasoconstriction in the DM group to the non-DM group were significantly greater than those of 5-HT-induced vasoconstriction. These results indicate that 5-HT is a potent inducer of SV graft spasm in both DM and non-DM patients, while AngII is a potent inducer of SV graft spasm only in patients with DM. Furthermore, the protein level of AngII AT1 receptor (AT1R), but not the protein level of 5-HT2A receptor, in the membrane fraction of the SV smooth muscle cells of DM patients was significantly increased as compared with that of the non-DM patients. These results suggest that the mechanism for hyperreactivity to AngII in the SV from DM patients is due to, at least in part, the increase in the amount of AT1R on membrane of the SV smooth muscle cells.