Mitsuhiro Hirata

Early and late stroke after mitral valve replacement with a mechanical prosthesis: risk factor analysis of a 24-year experience

OBJECTIVE We evaluated risk factors for mortality and stroke after mechanical mitral valve replacement between May 1977 and December 2001. METHODS Early and late mortality and stroke were assessed. Potential predictors of mortality and stroke were entered into a Cox proportional hazards model. Actuarial survival and freedom from stroke were determined by a log-rank test. RESULTS Mitral valve replacement was performed in 812 patients. Concomitant procedures included left atrial appendage closure in 493 (61%) patients, tricuspid annuloplasty-replacement in 348 (43%) patients, maze procedure in 185 (23%) patients, plication of the left atrium in 148 (18%) patients, and other procedures in 151 (19%) patients. Five-year actuarial survival was 91.1% +/- 2.3%. Freedom from stroke at 8 years was significantly better in patients with sinus rhythm versus atrial fibrillation (P <.001). Ninety-nine percent of patients with mitral valve replacement combined with a maze procedure were free from stroke, whereas only 89% of patients with mitral valve replacement alone were free from stroke at 8 years after surgical intervention. Seventy-two patients had late stroke; sixty-five patients (90%) were in atrial fibrillation, and 47 (65%) patients had the left atrial appendage closed. Multivariate analysis showed that late atrial fibrillation (odds ratio, 3.39; 95% confidence interval, 1.72-6.67; P =.0001) and omission of the maze procedure (odds ratio, 3.40; 95% confidence interval, 1.14-10.14; P =.003) were the significant risk factors for late stroke. CONCLUSIONS Persistent atrial fibrillation was the most significant risk factor for late stroke after mechanical mitral valve replacement. Restoration of sinus rhythm with a maze procedure nearly eliminated the risk of late stroke, whereas neither closure of the left atrial appendage nor therapeutic anticoagulation prevented this complication.

Serum amylase level on admission in the diagnosis of blunt injury to the pancreas: its significance and limitations.

OBJECTIVE The objective of this study was to elucidate the significance and limitations of serum amylase levels in the diagnosis of blunt injury to the pancreas. SUMMARY BACKGROUND DATA Several recently published reports of analyses of patients with blunt abdominal trauma have indicated that determination of the serum amylase level on admission seemed to be of little value in the diagnosis of acute injury to the pancreas. Few previous reports have described clearly the significance and the limitations of the serum amylase level in diagnosing injury to the pancreas. METHODS Retrospective analysis of 73 patients with blunt injury to the pancreas during 16-year period from February 1980 to January 1996 was performed. The factors analyzed in the current study included age, gender, time elapsed from injury to admission, hypotension on admission, type of injury to the pancreas, intra-abdominal- and intracranial-associated injuries, and death. RESULTS The serum amylase level was found to be abnormal in all patients admitted more than 3 hours after trauma. Various comparisons between patients with elevated (n = 61, 83.6%) and nonelevated (n = 12, 16.4%) serum amylase levels showed the statistical significance solely of the time elapsed from injury to admission (7 +/- 1.5 hours vs. 1.3 +/- 0.2 hour, p < 0.001). The major factor that influences the serum amylase level on admission appeared to be the time elapsed from injury to admission. Determination of the serum amylase level is not diagnostic within 3 hours or fewer after trauma, irrespective of the type of injury. CONCLUSIONS To avoid failure in the detection of pancreatic injury, the authors advocate determination of serum amylase levels more than 3 hours after trauma.

Characteristics of pancreatic injury in children: A comparison with such injury in adults

A retrospective study of eight pediatric patients (under 15 years of age) who had pancreatic injuries was undertaken. Comparisons were made with 59 adult patients who sustained pancreatic injuries over the same 15-year period. All the pediatric injuries and 96.6% of the adult resulted from blunt abdominal trauma. Bicycle accidents (children, 75.0%; adults, 0%; P < .001) and automobile accidents (children, 0%; adults, 61.0%; P < .01) were the most common causes of pancreatic injury in the two groups. There was no significant difference in the incidence of abdominal pain or peritoneal irritation between the groups. However, abdominal pain in the adults was poorly localized. Isolated pancreatic injuries were noted in 62.5% of the pediatric patients and in 15.3% of the adult patients (P < .05). Associated intraabdominal injuries were present in 25.0% of the children and in 69.5% of the adults (P < .05). The duodenum was injured in two (25.0%) pediatric patients and in 10 (16.9%) adult patients. Whereas the duodenal injuries in pediatric patients were intramural hematomas without perforation in both cases, all but one of these injuries in adults were perforations or transections (P < .05). There was a significant difference in the type of pancreatic injury between the two groups (P < .05). Surgery was performed in 12.5% of the pediatric cases and in 78.0% of the adult cases (P < .01). There were no deaths among the pediatric patients, but 8.5% of the adults died in the hospital. The difference with respect to clinical course might be related to the differences in cause of injury.

Pancreatographic classification of pancreatic ductal injuries caused by blunt injury to the pancreas.

BACKGROUND In the treatment of patients with pancreatic injury, the focus of attention is usually on main ductal injuries. METHODS To develop a classification system for pancreatic ductal injuries, we retrospectively analyzed blunt pancreatic injuries in 40 patients. We assessed the relationships between findings on pancreatography (36 endoscopic retrograde procedures and 4 transduodenal procedures), the treatment modality, and the clinical course. RESULTS Patients with class 1 injuries (radiographically normal ducts, n = 13) could be treated nonsurgically without major complications. Patients with class 2 injuries (branch injuries, n = 7), in whom contrast medium from ductal branches did not leak from the pancreatic parenchyma (class 2a, n = 3), could be treated nonsurgically. Patients with leaks into the retroperitoneal space (class 2b, n = 4) required at least a drainage laparotomy. Patients with class 3 injuries (main duct injuries, n = 20), including two patients in whom conservative treatment resulted in severe complications, required laparotomy. CONCLUSION This classification system for pancreatic ductal injuries may facilitate the selection of appropriate therapeutic modalities for patients with blunt pancreatic injury.

Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice

It is known that the neural system plays a fundamental role in neovascularization. A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in the central and peripheral neuronal systems. However, it remains to be elucidated the role of CGRP in angiogenesis during ischemia. The present study examined whether endogenous CGRP released from neuronal systems facilitates revascularization in response to ischemia using CGRP knockout mice (CGRP-/-). CGRP-/- or their wild-type littermates (CGRP+/+) were subjected to unilateral hindlimb ischemia. CGRP-/- exhibited impaired blood flow recovery from ischemia and decreased capillary density expressed in terms of the number of CD-31-positive cells in the ischemic tissues compared with CGRP+/+. In vivo microscopic studies showed that the functional capillary density in CGRP-/- was reduced. Hindlimb ischemia increased the expression of pro-CGRP mRNA and of CGRP protein in the lumbar dorsal root ganglia. Lack of CGRP decreased mRNA expression of growth factors, including CD31, vascular endothelial growth factor-A, basic fibroblast growth factor, and transforming growth factor-β, in the ischemic limb tissue. The application of CGRP enhanced the mRNA expression of CD31 and VEGF-A in human umbilical vein endothelial cells (HUVECs) and fibroblasts. Subcutaneous infusion of CGRP8-37, a CGRP antagonist, using miniosmotic pumps delayed angiogenesis and reduced the expression of proangiogenic growth factors during hindlimb ischemia. These results indicate that endogenous CGRP facilitates angiogenesis in response to ischemia. Targeting CGRP may provide a promising approach for controlling angiogenesis related to pathophysiological conditions.

The role of angiography in the assessment of blunt liver injury.

Angiography and therapeutic embolism (TE) were studied retrospectively in cases of blunt liver injury with regard to their indications and usefulness. The management of patients fell into three groups distinguished by the clinical evidence of the severity of the liver injuries. The most severe 42 cases (39.6 per cent) were managed surgically and promptly, the least severe 38 cases were not subjected to angiography and the intermediate group (26 cases; 24.5 per cent) underwent angiography and 12/26 cases underwent TE. However, haemodynamic stability on admission was not significantly different between these groups. In addition, all patients who underwent angiography and TE had more severe parenchymal injury on imaging studies while their haemodynamic instability was not identified on admission. Angiography and TE for blunt liver injury were most strongly indicated in patients with good haemodynamic responses to intravenous fluid administration during the acute phase and/or in cases of severe parenchymal injury on imaging.

Large-volume intraoperative peritoneal lavage with an assistant device for treatment of peritonitis caused by blunt traumatic rupture of the small bowel

The benefits of large-volume intraoperative peritoneal lavage (IOPL), with an assistant lavage device, were evaluated retrospectively in 114 patients with peritonitis caused by blunt traumatic rupture of the small bowel. Postoperative complications caused by infection were a major problem after rupture of the small bowel (46 of 114, 39.4%). Both prolongation of the interval between injury and laparotomy and rupture of the lower part of the small bowel were risk factors for postoperative complications caused by infection. Large-volume IOPL (25.2 +/- 2.1 L) with an assistant lavage device reduced the rate of complications caused by infection from 30 of 58 (51.8%) to 15 of 56 (26.8%). The volume used for IOPL was closely related to the occurrence of postoperative complications resulting from infection. No complications from infection occurred in patients who received lavage with of 28.3 +/- 2.7 L of saline, whereas complications occurred in those patients treated with a smaller volume of lavage fluid (18.0 +/- 2.5 L). Large-volume IOPL should be considered in patients with blunt rupture of the small bowel who are at risk for infection, and the assistant device for IOPL may be useful for such treatment.

VEGFR1-positive macrophages facilitate liver repair and sinusoidal reconstruction after hepatic ischemia/reperfusion injury.

Liver repair after acute liver injury is characterized by hepatocyte proliferation, removal of necrotic tissue, and restoration of hepatocellular and hepatic microvascular architecture. Macrophage recruitment is essential for liver tissue repair and recovery from injury; however, the underlying mechanisms are unclear. Signaling through vascular endothelial growth factor receptor 1 (VEGFR1) is suggested to play a role in macrophage migration and angiogenesis. The aim of the present study was to examine the role of VEGFR1 in liver repair and sinusoidal reconstruction after hepatic ischemia/reperfusion (I/R). VEGFR1 tyrosine kinase knockout mice (VEGFR1 TK-/- mice) and wild-type (WT) mice were subjected to hepatic warm I/R, and the processes of liver repair and sinusoidal reconstruction were examined. Compared with WT mice, VEGFR1 TK-/- mice exhibited delayed liver repair after hepatic I/R. VEGFR1-expressing macrophages recruited to the injured liver showed reduced expression of epidermal growth factor (EGF). VEGFR1 TK-/- mice also showed evidence of sustained sinusoidal functional and structural damage, and reduced expression of pro-angiogenic factors. Treatment of VEGFR1 TK-/- mice with EGF attenuated hepatoceullar and sinusoidal injury during hepatic I/R. VEGFR1 TK-/- bone marrow (BM) chimeric mice showed impaired liver repair and sinusoidal reconstruction, and reduced recruitment of VEGFR1-expressing macrophages to the injured liver. VEGFR1-macrophages recruited to the liver during hepatic I/R contribute to liver repair and sinusoidal reconstruction. VEGFR1 activation is a potential therapeutic strategy for promoting liver repair and sinusoidal restoration after acute liver injury.

Blockade of bradykinin B2 receptor suppresses acute pancreatitis induced by obstruction of the pancreaticobiliary duct in rats

The involvement of bradykinin (BK) B2 receptor in acute pancreatitis induced by pancreaticobiliary duct ligation was investigated in rats. The activities of amylase and lipase in the serum, the water content of the pancreas, and vacuolization of the acinar cells were significantly increased 2 h after obstruction of the duct in Sprague‐Dawley rats. Elevated serum amylase activity, increased pancreatic oedema, and damage of the pancreatic tissue were significantly less marked in plasma kininogen‐deficient, B/N‐Katholiek rats than in the normal strain, B/N‐Kitasato rats 2 h after the ligation. Obstruction of the pancreaticobiliary duct augmented the level of (1‐5)‐BK (Arg1‐Pro2‐Pro3‐Gly4‐Phe5), a stable BK metabolite, in the blood from 73.0±21.7 pg ml−1 at 0 h to 149.8±38.0 pg ml−1 at 2 h after the induction of pancreatitis in SD rats. Administration of a BK B2 receptor antagonist, FR173657 (100 mg kg−1, p.o.) or Hoe140 (100 nmol kg−1, s.c.), reduced the elevation of amylase and lipase activities in the serum and of pancreatic water content in a dose‐dependent manner. The effective attenuation of oedema formation and vacuolization by the antagonists was also confirmed light‐microscopically. In contrast, treatment with gabexate mesilate or indomethacin did not cause significant suppression of the pancreatitis. These findings suggest a possible involvement of kinin B2 receptor in the present pancreatitis model. Furthermore, they point to the potential usefulness of the B2 receptor in clinical acute pancreatitis.

Leukotriene B4 type-1 receptor signaling promotes liver repair after hepatic ischemia/reperfusion injury through the enhancement of macrophage recruitment

Recruited macrophages play a critical role in liver repair after acute liver injury. Leukotriene B4 (LTB4) is a potent chemoattractant for macrophages. In this study, we investigated the role of LTB4 receptor type 1 (BLT1) in liver repair during hepatic ischemia/reperfusion (I/R) injury. BLT1‐knockout mice (BLT1‐/‐) or their wild‐type counterparts (WT) were subjected to partial hepatic I/R. Compared with WT, BLT1‐/‐ exhibited delayed liver repair and hepatocyte proliferation accompanied by a 70% reduction in the recruitment of macrophages and a 70–80% attenuation in hepatic expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1). Disruption of BLT1 signaling also reduced the expression of EGF by 67% on recruited macrophages expressing VEGFR1 in the injured liver. Treatment of WT mice with an EGF‐neutralizing antibody delayed liver repair and reduced macrophage recruitment, compared with control immunoglobulin G (IgG). BLT1 signaling enhanced the expression of VEGF, VEGFR1, and EGF in isolated peritoneal macrophages in vitro. These results indicate that BLT1 signaling plays a role in liver repair after hepatic I/R through enhanced expression of EGF in recruited macrophages and that the development of a specific agonist for BLT1 could be useful for liver recovery from acute liver injury.—Ohkubo, H., Ito, Y., Minamino, T., Mishima, T., Hirata, M., Hosono, K., Shibuya, M., Yokomizo, T., Shimizu, T., Watanabe, M., Majima, M., Leukotriene B4 type‐1 receptor signaling promotes liver repair after hepatic ischemia/reperfusion injury through the enhancement of macrophage recruitment. FASEB J. 27, 3132–3143 (2013). www.fasebj.org