Cardiac Rupture Complicating Hemorrhagic Infarction after Intracoronary Thrombolysis

An 80-year-old woman with acute myocardial infarct intracoronary thrombolysis by a large dose of urokinase four hours after the onset of chest pain. Despite the patient having no chest pain after intracoronary thrombolysis and her general condition being stable, she died suddenly on the 4th hospital day. Autopsy revealed hemopericardium due to cardiac rupture, which occurred at the center of the transmural hemorrhagic infarction of the anteroseptal wall. The massive hemorrhagic infarction was promoted by reperfusion from thrombolytic therapy. She had also classic risk factors for cardiac rupture, such as hypertension, senility, female gender, and first acute myocardial infarct. Therefore, the present case demonstrated that hemorrhagic infarction increased the incidence of cardiac rupture.     

Development of in vivo tissue-engineered autologous tissue-covered stents (biocovered stents)

Biocovered stents, which are stents covered with autologous membranous tissues, were developed by applying a novel concept based on in vivo tissue engineering. Balloon-expandable stents crimped on silicone rods as a mold (diameter: 2 mm) were embedded into dorsal subcutaneous pouches in rabbits. After 1 month, the struts of the stents were fully encapsulated with membranous connective tissues formed around the silicone rods. Upon removing the silicone rod, stents covered with tubular connective tissues, in which the struts were completely impregnated, were obtained as biocovered stents. These tissues were composed mainly of collagen and fibroblasts and had a thickness of less than approximately 200 μm with an excellent high burst strength of approximately 1000 mmHg. The luminal surface of the tissues was extremely flat and smooth. The stents could be mounted on balloon catheters with a hand crimping tool and could be expanded by inflation with little damage to the tissues. It is anticipated that these novel stents may greatly enhance early normal vascular reconstruction with high reliability, thereby reducing the rate of in-stent restenosis.     

Histopathological Study of Aorto-Coronary Bypass Grafts With Special Reference to Fibrin Deposits on Grafted Saphenous Veins

A histopathological study was performed on 36 patients (60 grafts) who had undergone aorto-coronary bypass graft (ACBG) surgery 0 to 99 months prior to death. The following pathologic changes were found: 1) The thickness of diffuse intimal proliferation in the ACBG progressed with time from graft surgery to death. 2) The media became atrophic and the adventitia was increased slightly in thickness. 3) Fibrin deposits were found in 20 patients on/in the intimal thickenings of the vein graft walls and 7 patients showed incorporated fibrin in the thickened intima even one month after surgery. 4) Atherosclerosis, identified as intimal foam cell accumulation or frank plaques, was seen in only 3 patients 4 years after surgery. Fi-brointimal proliferation occurred with relatively greater frequency in patients with fibrin deposits (P< 0.001). Although it is well known that mural thrombi in vein grafts manifest fibrointimal proliferation, our results suggest that fibrin deposits might be responsible for intimal thickening even one month after graft surgery. Acta Pathol Jpn 39: 425 432, 1989.     

Effect of the mono- and tetra-sialogangliosides, GM1 and GQ1b, on long-term potentiation in the CA1 hippocampal neurons of the guinea pig

 Effects of the mono- and tetra-sialogangliosides, GM1 and GQ1b, on long-term potentiation (LTP) were investigated in the CA1 neurons of guinea-pig hippocampal slices. The magnitude of LTP induced by a strong tetanus (100 Hz, 100 pulses) was not significantly affected by application of either ganglioside. In contrast, when LTP was induced by a weak tetanus (100 Hz, 4 pulses), a significantly greater LTP was induced in the presence of either ganglioside. Similarly, when slices were incubated in low-Ca²⁺ (1.0–1.1 mM) medium for more than 2 h, the LTP was usually small or absent, but showed a significant increase in amplitude of population spike (A-PS) when the slices were incubated with either GM1 or GQ1b (4–5 μg/ml). In addition, the application of GQ1b (4 μg/ml) reversed the blocking effect of an NMDA-receptor antagonist, APP-5 (10 μM), on the induction of LTP and resulted in forming LTP. Based on these findings, we conclude that GM1 and GQ1b exert positive modulatory effects on the induction of LTP in hippocampal CA1 neurons and suggest that GM1 and GQ1b may participate in the induction of LTP as donors of Ca²⁺ ions. Received: 21 April 1998 / Accepted: 5 May 1998     

Advanced hepatocellular carcinoma with response to lenvatinib after atezolizumab plus bevacizumab

Rationale:Various treatments are available for treating hepatocellular carcinoma (HCC). The immune checkpoint inhibitor combination of atezolizumab plus bevacizumab was recently approved for the treatment of unresectable HCC, but there are few reports on the failure of the combination treatment. Here, we present a case of unresectable HCC with adrenal metastasis that was eventually operated on after lenvatinib (LEN) treatment that followed failed treatment with atezolizumab plus bevacizumab.Patient concerns:A 68-year-old man was diagnosed with non-alcoholic steatohepatitis-based HCC with adrenal metastasis.Diagnosis:Cirrhosis was classified as Child-Pugh score of 5. HCC was diagnosed as Barcelona Clinic Liver Cancer stage C.Interventions:We initiated treatment with atezolizumab plus bevacizumab. Liver dysfunction appeared 2 days after the first administration but was improved by intravenous rehydration and did not appear after the second course. The HCC shrank, but the adrenal metastasis grew bigger after the fourth course, so we changed the therapy to LEN. After HCC and adrenal metastasis were necrotic by LEN, conversion surgery was performed.Outcomes:After successful conversion therapy, the general condition of the patient was good, and has been carefully followed for 4 months to date without any evidence of further recurrences.Lessons:This case showed that even if atezolizumab plus bevacizumab is not effective, multidisciplinary treatment such as LEN and conversion surgery is possible. Given the efficacy of LEN after atezolizumab plus bevacizumab, it is important to consider that there is a possibility of cure even when first-line treatment is not effective for a patient with unresectable HCC.     

Late gadolinium enhancement in cardiac amyloidosis: attributable both to interstitial amyloid deposition and subendocardial fibrosis caused by ischemia

Gadolinium contrast agents used for late gadolinium enhancement (LGE) distribute in the extracellular space. Global diffuse myocardial LGE pronounced in the subendocardial layers is common in cardiac amyloidosis. However, the pathophysiological basis of these findings has not been sufficiently explained. A 64-year-old man was admitted to our hospital with leg edema and nocturnal dyspnea. Bence Jones protein was positive in the urine, and an endomyocardial and skin biopsy showed light-chain (AL) amyloidosis. He died of ventricular fibrillation 3 months later. 9 days before death, the patient was examined by cardiac magnetic resonance (CMR) imaging on a 3-T system. We acquired LGE data at 2, 5, 10, and 20 min after the injection of gadolinium contrast agents, with a fixed inversion time of 350 ms. Myocardial LGE developed sequentially. The myocardium was diffusely enhanced at 2 min, except for the subendocardium, but LGE had extended to almost the entire left ventricle at 5 min and predominantly localized to the subendocardial region at 10 and 20 min. An autopsy revealed massive and diffused amyloid deposits in perimyocytes throughout the myocardium. Old and recent ischemic findings, such as replacement fibrosis and coagulative myocyte necrosis, were evident in the subendocardium. In the intramural coronary arteries, mild amyloid deposits were present within the subepicardial to the mid layer of the left ventricle, but no stenotic lesions were evident. However, capillaries were obstructed by amyloid deposits in the subendocardium. In conclusion, the late phase of dynamic LGE (at 10 and 20 min) visualized in the subendocardium corresponded to the interstitial amyloid deposition and subendocardial fibrosis caused by ischemia in our patient.     

Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents

Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.     

Partial Left Ventriculectomy for Patients with Ischemic Cardiomyopathy

BACKGROUND: Partial left ventriculectomy (PLV) has been performed in patients with dilated cardiomyopathy (DCM), but improved myocardial energetics may make PLV useful also for ischemic cardiomyopathy (ICM) unamenable to conventional treatment. METHODS: Of 262 patients undergoing PLV, 94 patients with ICM as the underlying pathology were analyzed and compared with 168 patients with DCM. RESULTS: ICM patients were older (57.3 years vs 50.9 years, p = 0.0001) and heavier (69.7 kg vs 65.9 kg, p = 0.039) than those with DCM, but ventricular end-diastolic and end-systolic dimensions were similar with comparably depressed fractional shortening (16% vs 15%, p = 0.294) and equally severe functional limitation [New York Heart Association (NYHA) Class 3.7 vs 3.6, p = 0.734]. A majority of patients in both groups underwent lateral PLV (76% vs 74%, p = 0.883) with myocardium excised between papillary muscles and simultaneous mitral valvuloplasty (41% vs 74%, p < 0.0001). Because ICM patients required coronary artery bypass grafting (CABG) more frequently (79% vs 0.6%, p < 0.0001), operation was more extensive in terms of bypass time (74 minutes vs 47 minutes, p < 0.0001), percentage requiring cardiac arrest (43% vs 19%, p < 0.0001), and arrest duration (34 minutes vs 28 minutes, p = 0.280), but all had similar resection and postoperative ventricular dimensions. Nonetheless, ICM patients required shorter intensive care unit (ICU) time (4.4 days vs 5.9 days, p = 0.048) and similar postoperative hospital stays, resulting in similar hospital survival rates (69% vs 71%, p = 0.778) and functional capacity in long-term follow-up. CONCLUSIONS: Results suggest that PLV can be performed in patients with ICM with comparable risks and benefits as in DCM. Relative efficacy of CABG and mitral repair as compared to volume reduction remains to be studied.     

A novel ganglioside, 9-O-acetyl GD1b, is recognized by serum antibodies in Guillain-Barré syndrome

A hitherto undescribed ganglioside was detected in a crude ganglioside fraction of bovine brain using an IgM M-protein binding to Ga1β 1,3Ga1NAc residue. We purified and identified it as 9-O-acetyl GD1b based on results of alkali treatment that yielded GD1b and results of fast atom bombardment-mass and gas chromatography-mass spectrometries. 9-O-acetyl GD1b was also found to be present in human peripheral nerve tissue. The reactivities of the serum antibodies from patients with Guillain-Barré syndrome to 9-O-acetyl GD1b, GD1b, and GM1 were determined by ELISA and TLC immunostaining. Nineteen of 85 serum samples from Guillain-Barré syndrome patients had antibodies that bound to 9-O-acetyl GD1b: 14 of the positive samples also reacted with GM1 and GD1b, three reacted with GM1 but not with GD1b, one with GD1b but not with GM1, and one with neither GM1 nor GD1b. These results show that a subset of patients with Guillain-Barré syndrome had antibodies that react with 9-O-acetyl GD1b; therefore, this ganglioside can serve as a target antigen against the antibodies present in Guillain-Barré syndrome.