Magnetic resonance imaging changes in a patient with migraine attack and transient global amnesia after cardiac catheterization.

The presence of magnetic resonance imaging (MRI) abnormalities in patients with transient global amnesia has been an interesting phenomenologic finding. Several theories surround the occurrence of this syndrome, but little is known about its true physiopathology. We present a case of transient global amnesia after cardiac catheterization associated with migraine headache and MRI changes compatible with an ischemic insult. A discussion on potential explanations for this finding is made, as well as a review of the pertinent literature.

C1q-deficiency is neuroprotective against hypoxic-ischemic brain injury in neonatal mice.

BACKGROUND AND PURPOSE: This study was undertaken to determine whether the initial component of the classical complement (C) activation pathway contributes to hypoxic-ischemic brain injury in neonatal mice. METHODS: Hypoxia-ischemia (HI) was produced in C1q(-/-) and wild-type (WT) neonatal mice. At 24 hours after HI, neonatal mouse reflex performance and cerebral infarct volume were assessed. Long-term outcomes were measured by water-maze performance and degree of cerebral atrophy at 7 to 8 weeks after HI. Activation of circulating neutrophils, and C1q, C3, and neutrophil deposition in brains were examined. RESULTS: C1q(-/-) mice were significantly protected against HI (mean+/-SE infarct volume in C1q(-/-) mice=17.3+/-5.5% versus 53.6+/-6.8% in WT mice; P<0.0001) and exhibited significantly less neurofunctional deficit compared with WT mice. Immunostaining revealed significantly greater deposition of C3 (and C1q) as well as granulocytes in the infarcted brains in WT mice compared with C1q(-/-) animals. Activation of circulating leukocytes was significantly decreased in C1q(-/-) mice compared with WT mice, which correlated strongly (r=0.7) with cerebral infarct volumes. CONCLUSIONS: Cerebral deposition of C1q and C3 after hypoxic-ischemic insult is associated with significantly greater neurologic damage in WT mice compared with C1q(-/-) mice, providing strong evidence that the classical C pathway contributes to the hypoxic-ischemic brain injury. Significantly decreased activation of circulating neutrophils associated with diminished local accumulation and attenuation of brain injury in C1q(-/-) mice suggests a potential cellular mechanism by which C1q mediates neurodegeneration in HI.

Evidence for C-reactive protein's role in (CRP) vascular disease: atherothrombosis, immuno-regulation and CRP.

For clinicians plasma C-reactive protein (CRP) levels are the only widely available tests that provide a tangible link between inflammation and atherosclerosis. New AHA/CDC joint guidelines from 2002-03 now include the measurement of CRP as a class IIa recommendation for stratifying patients with known cardiovascular disease (CVD) at a moderate (10-20%) 10-year event risk and a class IIb recommendation for patients without known CVD [1]. While the association of CRP and atherosclerosis is by now accepted, the molecular biology behind the association is evolving rapidly into a fascinating story. While some of the story remains obscure, this review aims to bridge the clinical and basic science and identify what is known about the role of this ancient molecule in atherosclerosis. The review covers CRP's interaction with atherosclerosis' major ingredients and cell types including the endothelium, monocytes and neutrophils, lipoproteins and the complement system. Taken together, the clinical and basic science leave the tantalizing impression that CRP has a fundamental role in atherogenesis, and hint at a more complex immunomodulatory effect which transforms the acute inflammatory response to vascular injury into the chronic inflammation seen in atherosclerosis.

Load dependence of cardiac output in biventricular pacing: right ventricular pressure overload in pigs.

BACKGROUND: The effect of biventricular pacing on stroke volume is believed to be dependent on right ventricular/left ventricular delay, but effects in individual patients are unpredictable. This variability may reflect relative right and left ventricular volume and/or pressure overloads. Accordingly, we tested the hypothesis that the relation of cardiac output to right ventricular/left ventricular delay is load dependent in a pig model of pulmonary stenosis. METHODS: After median sternotomy in 6 anesthetized, domestic pigs, complete heart block was induced by ethanol ablation. During epicardial, atrial tracking DDD biventricular pacing, atrioventricular delay was varied between 60 and 180 ms in 30-ms increments. Right ventricular/left ventricular delay was varied at each atrioventricular delay from +80 ms (right ventricle first) to -80 ms (left ventricle first) in 20-ms increments. Aortic flow, right ventricular pressure, peripheral arterial pressure, and electrocardiogram were measured in the control state and during pulmonary stenosis, created by tightening a snare around the pulmonary artery until cardiac output decreased by 50%. RESULTS: Atrioventricular and right ventricular/left ventricular delay had no effect on cardiac output during the control state, but during pulmonary stenosis there was a statistically significant (P =.0001, repeated-measures analysis of variance) right ventricular/left ventricular delay-related trend toward higher cardiac output with right ventricular pacing first. This effect was more pronounced when the optimal atrioventricular delay was determined first, resulting in a 20% increase in cardiac output when the optimal right ventricular/left ventricular delay was compared with simultaneous biventricular pacing. CONCLUSIONS: Optimized biventricular pacing in swine is associated with increased cardiac output during acute pulmonary stenosis, but not during the control state. Further studies are needed to determine whether specific types of right ventricular and left ventricular overload predictably affect the relation between right ventricular/left ventricular delay and cardiac output.

Reverse CPR: a pilot study of CPR in the prone position.

BACKGROUND: Cardiopulmonary resuscitation (CPR), as described in 1960, remains the cornerstone of therapy for cardiopulmonary arrest. Recent case reports have described CPR in the prone position. We hypothesized rhythmic back pressure on a patient in the prone position with sternal counter-pressure (termed reverse CPR here) would increase intra-thoracic pressure and in turn systolic blood pressure (SBP) during cardiac arrest versus standard CPR. METHODS AND RESULTS: Six patients from Columbia Presbyterian Medical Center's Cardiac and Medical Intensive Care Units (CICU and MICU) were enrolled. Eligible patients had suffered circulatory arrest and failed standard CPR for at least 30 min. After enrollment the patients received 15 additional min of standard CPR and then reverse CPR for 15 min. The study's primary endpoint, mean SBP, significantly improved from 48 mmHg during standard CPR to 72 mmHg during reverse CPR (mean improvement=23+/-14 mmHg). Mean calculated mean arterial pressure (MAP) was also improved significantly from 32 mmHg during standard CPR to 46 mmHg during reverse CPR (mean improvement=14+/-11 mmHg). The mean diastolic blood pressure (DBP) improved from 24 mmHg during standard to 34 mmHg during reverse CPR (mean improvement=10+/-12 mmHg). This difference did not meet statistical significance. No patients had return of spontaneous circulation. CONCLUSIONS: Reverse CPR generates higher mean SBP and higher mean MAP during circulatory arrest than standard CPR. These novel findings justify further research into this technique.

Transcriptional control of cardiac allograft vasculopathy by early growth response gene-1 (Egr-1).

Expression of the zinc finger transcription factor early growth response gene-1 (Egr-1) is triggered rapidly after mechanical vascular injury or after a precipitous drop in ambient oxygen, whereupon it induces the expression of diverse gene families to elicit a pathological response. Initially characterized as an early response transcriptional activator, the role of Egr-1 in more chronic forms of vascular injury remains to be defined. Studies were designed to examine whether Egr-1 induction may serve as a causal link between early preservation injury and delayed vascular consequences, such as coronary allograft vasculopathy (CAV). The preservation and transplantation of heterotopic murine cardiac allografts strongly induce Egr-1 expression, leading to increased expression of its downstream target genes, such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet-derived growth factor A chain. Expression of these Egr-1-inducible gene targets is virtually obliterated in homozygous Egr-1-null donor allografts, which also exhibit attenuated parenchymal rejection and reduced CAV as long as 60 days. Congruous data are observed by treating donor hearts with a phosphorothioate antisense oligodeoxyribonucleotide directed against Egr-1 before organ harvest, which blocks subsequent expression of Egr-1 mRNA and protein and suppresses the late development of CAV. These data indicate that Egr-1 induction represents a central effector mechanism in the development of chronic rejection characterized by CAV. Blocking the expression of this proximal transcription factor solely at the time of organ harvest elicits beneficial delayed consequences for the cardiac allograft.

Suppression of murine cardiac allograft arteriopathy by long-term blockade of CD40-CD154 interactions.

BACKGROUND: The interaction between CD40 on antigen-presenting cells and CD40L on T cells is critical in allograft rejection. CD154 blockade suppresses allograft rejection, but the role of this pathway in allograft vasculopathy remains obscure. METHODS AND RESULTS: A vascularized murine heterotopic cardiac transplant model was used to test whether perioperative CD154 blockade suppresses allograft vasculopathy or whether long-term CD154 blockade is required to suppress allograft vasculopathy. Perioperative CD154 blockade consisted of MR1 given on days -1, 1, and 3; long-term blockade consisted of MR1 given on days -1, 1, and 3 and continued twice weekly for 8 weeks. Allografts treated with perioperative or long-term CD154 blockade survived indefinitely. Perioperative and long-term treatment with control antibody (Ha4/8) resulted in uniform early rejection. Perioperative CD154 blockade transiently reduced early T-cell and macrophage infiltration in parallel with a transient reduction in endothelial adhesion receptor expression. Although perioperative CD154 blockade prevented allograft failure, it did not reduce allograft vasculopathy; mean neointimal cross-sectional area in perioperative MR1-treated and Ha4/8-treated recipients was 43+/-7% and 50+/-12%, respectively (P=NS). In contrast, mean neointimal cross-sectional area in long-term, MR1-treated recipients was 19+/-3% (P<0.001 versus perioperative MR1). Long-term CD154 blockade also suppressed endothelial E-selectin, P-selectin, and intracellular adhesion molecule-1 expression and improved graft function 3.5-fold versus control (P<0.05). CONCLUSIONS: These data show that perioperative CD154 blockade mitigates acute rejection but long-term CD154 blockade may result in decreased allograft endothelial activation and is required to suppress allograft arteriopathy.