Plasma D-Dimer Levels Can Provide Useful Diagnostic Information on Acute Vertebral Compression Fractures in Patients with Low Back Pain in the Emergency Room.

BACKGROUND: Patients with acute vertebral compression fractures (aVCFs) are frequently transferred to an emergency department by ambulance. The most useful imaging modality is magnetic resonance imaging (MRI); however, which patients should be prioritized for MRI evaluation may be unclear. The aim of this study was to evaluate plasma D-dimer levels as a biomarker for aVCFs. METHODS: This retrospective cohort study included patients with low back pain in the emergency department between November 2017 and October 2020. Patients with infections, patients with coagulation disorders, and patients without D-dimer level measurements were excluded. The presence of an aVCF was detected with MRI. Blood samples were collected for routine blood tests. The predictive factors for aVCFs were evaluated with univariate and multivariable logistic regression analyses. RESULTS: Overall, 191 consecutive MRI evaluations were ordered. After exclusions, 101 patients were reviewed. Based on MRI, 65 (64.4%) patients were diagnosed with aVCF. The presence of aVCF was significantly correlated with age (odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.018-1.191), an old vertebral compression fracture (OR = 3.290, 95% CI 1.342-8.075), hemoglobin (OR = 0.699, 95% CI 0.535-0.912), and D-dimer levels (OR = 1.829, 95% CI 1.260-2.656). Results from a multivariable logistic regression analysis showed that D-dimer levels (OR = 1.642, 95% CI 1.188-2.228) remained a significant risk factor for the presence of aVCFs after adjustment for potential confounders. CONCLUSIONS: Plasma D-dimer levels can provide useful diagnostic information about whether an aVCF is present.

Vascular occlusion in a previously unaffected territory after treatment with intravenous plasminogen activator: illustrative case.

BACKGROUND: Intravenous tissue plasminogen activator (IV t-PA) is effective for the treatment of distal artery occlusion. However, after the use of IV t-PA, vascular occlusion in unaffected territories may occur. Early recurrent ischemic stroke (ERIS) is defined as the occurrence of new neurological symptoms that suggest the involvement of initially unaffected vascular territories after intravenous thrombolysis (IVT). The authors reviewed the cases of ERIS that occurred within 24 hours after treatment with IVT. OBSERVATIONS: A 75-year-old woman with occlusion in the M2 segment of the left middle cerebral artery (MCA) was treated with IV t-PA. However, 360 minutes later, the patient presented with occlusion in the M1 distal segment of the contralateral side, the right MCA, which was recanalized by endovascular treatment. Her modified Rankin Scale score was 4; however, aphasia was not observed. She was transferred to a rehabilitation hospital after 3 months. LESSONS: ERIS is an extremely rare but catastrophic event. The underlying mechanism of ERIS most likely involves the disintegration and subsequent scattering of a preexisting intracardiac thrombus. Hence, caution must be used when managing not only hemorrhagic complications but also ischemic complications after IV t-PA. Endovascular management may be the only effective treatment for this type of large vessel occlusion.

Carotid Free-Floating Thrombus in a Stent 6 Months After Carotid Artery Stenting.

BACKGROUND: Carotid free-floating thrombus (CFFT) is defined as a blood clot attached to the arterial wall with surrounding blood flow at its distal component. Although rare, it is a clinically significant cause of embolic stroke. CFFT within a stent has not been previously reported. CASE DESCRIPTION: We report a 64-year-old man who underwent carotid artery stenting for asymptomatic right carotid artery stenosis. Six months after carotid artery stenting, he was admitted to the emergency department 1 hour after onset of left hemiparesis and dysarthria. His National Institutes of Health Stroke Scale score was 10. His medical history was notable for hypertension, chronic renal insufficiency, and type 2 diabetes mellitus. Carotid ultrasonography showed a dumbbell-shaped CFFT attached to the carotid stent that was moving in synchrony with his heartbeat. CFFT removal was performed via an endovascular approach with manual suction using a Luer Lock syringe. The CFFT was completely removed without residual stenosis. Histologic examination suggested plaque rupture associated with a lipid-rich necrotic core. CONCLUSIONS: Carotid plaque formation and plaque rupture can occur within a carotid stent and present as a CFFT.

Preischemic infusion of alpha-human atrial natriuretic peptide elicits myoprotective effects against ischemia reperfusion in isolated rat hearts.

Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP) is a newly developed drug for the treatment of heart failure. However, effects of carperitide on susceptibility to ischemia reperfusion injury are left to be determined. Isolated rat hearts were subjected to Langendorff perfusion. Six hearts received 0.1 microM of carperitide for 10 min, 6 hearts received 1 mM of a NO synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min before the infusion of carperitide, 6 hearts received 0.02 microM of a PKC synthetase inhibitor chelerythrine chloride for 5 min before the infusion of carperitide, 6 hearts received 100 microM of a selective mitochondrial ATP-sensitive potassium (KATP) channel blocker 5-dehydroxydecanoate (5HD) before the infusion of carperitide, 6 hearts received 10 microM of a soluble guanylate cyclase inhibitor methylene blue for 5 min before the infusion of carperitide, and 6 hearts served as a control with no drug infusion. All hearts were then subjected to 20 min of global ischemia followed by 120 min of reperfusion. Left ventricular pressures and coronary flow were measured throughout the experiment and infarct size was detected at the end of experiment. Both plasma and tissue cGMP levels were also determined. The results showed: (1) Carperitide significantly reduced infarct size compared to control (26.1 +/- 2.8 vs. 42.7 +/- 2.3%, carperitide vs. control, p < 0.05). This effect was reversed by L-NAME, chelerythrine and 5HD, but not methylene blue. (2) Plasma cGMP levels were increased in carperitide-treated group. This effect was reversed by L-NAME (0.16 +/- 0.03 vs. 1.04 +/- 0.09* vs. 0.28 +/- 0.02 nmol/L, control vs. carperitide vs. L-NAME, *p < 0.01 vs. control). We conclude that preischemic infusion of carperitide exerts cardioprotective effects possibly through NO-PKC dependent pathway followed by mitochondrial KATP channel activation.

Repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone elicits cardioprotective effects in the failing heart after myocardial infarction.

Beta-adrenergic (BA) signaling including cAMP-protein kinase A (PKA) pathway has been implicated in the mechanism of ischemic preconditioning (IPC). However, effect of IPC on the failing heart, in which BA signaling is supposed to be altered, is left to be determined. To assess a role of BA signaling in IPC, levels of beta2-adrenergic receptor (B2AR) mRNA were quantified by real time RT-PCR, and in vivo intracardiac function was evaluated in post-MI heart. The effect of IPC on post-MI heart was then determined with an isolated heart perfusion system. Finally, cardioprotective effect of repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone (30 microM), which is known to increase myocardial cAMP levels, was evaluated with/without PKA inhibitor H-89 (2 microM). B2AR mRNA levels in post-MI heart were significantly reduced compared to non-MI heart. IPC was not effective in post-MI heart. Repetitive preischemic infusion of olprinone increased peak developed pressure (94.6 +/- 6.3 vs. 62.8 +/- 4.9%, OLP vs. control, p < 0.05) and decreased infect size (15.2 +/- 0.4 vs. 33.5 +/- 2.5%, OLP vs. control, p < 0.01). These effects were abolished by H-89. These results may indicate that repetitive preischemic infusion of olprinone mimics IPC through cAMP-PKA pathway in post-MI heart, and that BA signaling plays a crucial role in IPC response.

[Preischemic infusion of alpha-human atrial natriuretic peptide elicits myoprotection through a nitric oxide-dependent mechanism].

OBJECTIVES: Alpha-human atrial natriuretic peptide (alpha-hANP) has been used to treat patients with heart failure due to its natriuretic and vasodilatory activities. Recent reports have suggested that alpha-hANP generates nitric oxide (NO) that is known to be involved in myoprotective mechanisms. In this study, the effects of preischemic infusion of alpha-hANP against reperfusion injury were evaluated. METHODS: Isolated rat (Sprague-Dawley rat, age 8-10 weeks, weight 260-340 g) hearts were subjected to Langendorff perfusion with buffered Krebs-Henseleit solution and were divided into three groups: Six hearts were treated with 0.1 microM of alpha-hANP for 10 min (Group H), six hearts with 1 mM of a NO synthetase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) for 5 min before alpha-hANP (Group L), and six hearts served as the controls with no interventions (Group C). All groups were then subjected to 20 min of global ischemia followed by 120 min of reperfusion. Left ventricular pressures and coronary flow were measured throughout the experiment and infarct size was evaluated at the end of the experiments. RESULTS: Treatment with alpha-hANP significantly reduced infarct size as compared to control hearts whereas pretreatment with L-NAME almost reversed the preventive effect (Group C = 42.7 +/- 2.3%, Group H = 26.1 +/- 2.8% *, Group L = 39.0 +/- 1.6%; * p < 0.01 vs Group C). There were no significant differences in left ventricular pressure and coronary flow between the three groups. CONCLUSIONS: Preischemic infusion of alpha-hANP may provide myoprotective effects against postischemic reperfusion, possibly through a NO-dependent mechanism.

Oral hypoglycemic sulfonylurea glimepiride preserves the myoprotective effects of ischemic preconditioning.

BACKGROUND: To investigate whether the sulfonylurea glimepiride affects the myoprotective effects of ischemic preconditioning (IPC), isolated rabbit hearts were perfused with Krebs-Henseleit solution. METHODS: Eight hearts underwent IPC consisting of two cycles of 5 min global ischemia and reperfusion. Six hearts received a 5-min infusion of 10 microM glimepiride, six hearts received a 5-min infusion of 50 microM glimepiride, and seven hearts received a 5-min infusion of 10 microM glibenclamide before IPC. Seven hearts received a 5-min infusion of the selective mitochondrial K(ATP) channel opener diazoxide (50 microM). Other hearts received a 5-min infusion of 10 microM glimepiride (n = 6), 50 microM glimepiride (n = 6), or 10 microM glibenclamide (n = 7) before diazoxide. Seven hearts served as a control. All groups then were subjected to 1 h of regional ischemia, followed by 1 h of reperfusion. LV pressures, monophasic action potential duration (APD(50)), and infarct size were measured. RESULTS: Both IPC and diazoxide significantly prolonged APD(50) and preserved diastolic function at 60 min of reperfusion compared to control. In addition, both groups reduced infarct size compared to control. Glibenclamide, but not glimepiride reversed these effects. CONCLUSION: Glimepiride offers less cardiovascular effects than glibenclamide, possibly due to its lower affinity for the mitochondrial K(ATP) channels.

HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals.

BACKGROUND: The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. METHODS: In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. RESULTS: Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%). CONCLUSIONS: The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation.