Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period.

BACKGROUND: Intrinsic cardiac nerve activity (ICNA) and skin nerve activity (SKNA) are both associated with cardiac arrhythmias in dogs. OBJECTIVE: The purpose of this study was to test the hypothesis that ICNA and SKNA correlate with postoperative cardiac arrhythmias in humans. METHODS: Eleven patients (mean age 60 ± 13 years; 4 women) were enrolled in this study. Electrical signals were simultaneously recorded from electrocardiogram (ECG) patch electrodes on the chest wall and from 2 temporary pacing wires placed during open heart surgery on the left atrial epicardial fat pad. The signals were filtered to display SKNA and ICNA. Premature atrial contractions (PACs) and premature ventricular contractions were determined manually. The SKNA and ICNA of the first 300 minutes of each patient were calculated minute by minute to determine baseline average amplitudes of nerve activities and to determine their correlation with arrhythmia burden. RESULTS: We processed 1365 ± 973 minutes of recording per patient. Low-amplitude SKNA and ICNA were present at all time, while the burst discharges were observed much less frequently. Both SKNA and burst ICNA were significantly associated with the onset of PACs and premature ventricular contractions. Baseline average ICNA (aICNA), but not average SKNA, had a significant association with PAC burden. The correlation coefficient (r) between aICNA and PAC burden was 0.78 (P < .01). A patient with the greatest aICNA developed postoperative atrial fibrillation. CONCLUSION: ICNA and SKNA can be recorded from human patients in the postoperative period. The baseline magnitude of ICNA correlates with PAC burden and development of postoperative atrial fibrillation.

Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram.

BACKGROUND: Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE: The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS: We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 ± 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS: In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 ± 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION: SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone.

Long-term results with cryopreserved arterial allografts (CPAs) in the treatment of graft or primary arterial infections.

OBJECTIVE: Our purpose was to evaluate our results with CPAs in patients with infected grafts or primary arterial infection with emphasis on long-term durability of these grafts. METHODS: To evaluate the long-term durability of CPAs, clinical outcomes were analyzed following their use for either graft or primary arterial infections at a single institution over a 9-y period (2000-2009). The 30-d mortality rate, 90-d mortality rate, and the cause of early mortality were determined in each case. Among those surviving 90 d, the grafts were evaluated for subsequent failure. RESULTS: From 2000 through 2009, 51 patients with either infected prosthetic grafts (35) or primary arterial infections (15) received CPAs. One patient had infection of a previously placed thoracic allograft. Forty-three graft infections involved either the thoracic or abdominal aorta. Eleven patients presented with fulminant sepsis with systemic inflammatory response syndrome (SIRS), seven of whom died postoperatively. Eight patients presented with aorto-enteric, esophageal, or bronchial fistulae with infected prosthetic grafts. The 30-d mortality rate was 25.5% (11 deaths) seven of which occurred in patients with SIRS. The 90-d mortality rate was 41.4%. There were 10 graft failures, seven occurring in patients with aorto-enteric or bronchial fistulae all of whom had recurrent hemorrhage. The other three graft failures were due to anastomotic hemorrhage in the early postoperative period. Among those surviving 90 d, the mean follow-up was 46.4 mo (range 1-112 mo). No aneurysmal degeneration of the CPAs was noted. Only one subsequent allograft graft failure was noted among those surviving more than 90 d. CONCLUSIONS: CPAs are a suitable option in dealing with cardiovascular infections. Patients with enteric or bronchial fistulae are a difficult group to treat perhaps because of ongoing contamination of the allograft. The operative mortalities are largely determined by patient comorbidities (SIRS). Subsequent degeneration or infection of the CPAs is rare.

Sensor to detect endothelialization on an active coronary stent.

BACKGROUND: A serious complication with drug-eluting coronary stents is late thrombosis, caused by exposed stent struts not covered by endothelial cells in the healing process. Real-time detection of this healing process could guide physicians for more individualized anti-platelet therapy. Here we present work towards developing a sensor to detect this healing process. Sensors on several stent struts could give information about the heterogeneity of healing across the stent. METHODS: A piezoelectric microcantilever was insulated with parylene and demonstrated as an endothelialization detector for incorporation within an active coronary stent. After initial characterization, endothelial cells were plated onto the cantilever surface. After they attached to the surface, they caused an increase in mass, and thus a decrease in the resonant frequencies of the cantilever. This shift was then detected electrically with an LCR meter. The self-sensing, self-actuating cantilever does not require an external, optical detection system, thus allowing for implanted applications. RESULTS: A cell density of 1300 cells/mm2 on the cantilever surface is detected. CONCLUSIONS: We have developed a self-actuating, self-sensing device for detecting the presence of endothelial cells on a surface. The device is biocompatible and functions reliably in ionic liquids, making it appropriate for implantable applications. This sensor can be placed along the struts of a coronary stent to detect when the struts have been covered with a layer of endothelial cells and are no longer available surfaces for clot formation. Anti-platelet therapy can be adjusted in real-time with respect to a patient's level of healing and hemorrhaging risks.

Gender dimorphisms in progenitor and stem cell function in cardiovascular disease.

Differences in cardiovascular disease outcomes between men and women have long been recognized and attributed, in part, to gender and sex steroids. Gender dimorphisms also exist with respect to the roles of progenitor and stem cells in post-ischemic myocardial and endothelial repair and regeneration. Understanding how these cells are influenced by donor gender and the recipient hormonal milieu may enable researchers to further account for the gender-related disparities in clinical outcomes as well as utilize the beneficial effects of these hormones to optimize transplanted cell function and survival. This review discusses (1) the cardiovascular effects of sex steroids (specifically estradiol and testosterone); (2) the therapeutic potentials of endothelial progenitor cells, mesenchymal stem cells, and embryonic stem cells; and (3) the direct effect of sex steroids on these cell types.

Proinflammatory cytokine effects on mesenchymal stem cell therapy for the ischemic heart.

Mesenchymal stem cells (MSCs) hold great promise for improving myocardial recovery after ischemia. The cardiothoracic surgeon is uniquely positioned to be at the forefront of any clinical application of this therapy. As such, a basic understanding of stem cells and the cytokines that affect stem cell function will be an essential component of the surgeon's ever-expanding knowledge base. This review provides: (1) a general overview of stem cells and MSCs in particular, (2) critically analyzes several cytokines known to alter MSC function, and (3) discusses methods to manipulate cytokine-activated MSCs to improve MSC function for potential clinical application.

MEK mediates the novel cross talk between TNFR2 and TGF-EGFR in enhancing vascular endothelial growth factor (VEGF) secretion from human mesenchymal stem cells.

BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) may mediate their beneficial effects by paracrine mechanisms. Recently, we reported that tumor necrosis factor-alpha (TNF-alpha) increased the release of vascular endothelial growth factor (VEGF) from human MSCs and augmented transforming growth factor-alpha (TGF-alpha)-stimulated VEGF secretion. However, it is unknown whether TNF-alpha stimulates VEGF production via TNF receptor 1 (TNFR1) or 2 (TNFR2) and the mechanism by which TNF-alpha augments TGF-alpha (a ligand of epidermal growth factor receptor, EGFR) stimulated VEGF production. We hypothesized that the ablation of TNFR2 would decrease TNF-alpha-stimulated and/or TGF-alpha- stimulated VEGF production via MEK-dependent mechanisms. METHODS: MSCs transfected with TNFR1, TNFR2, or GAPDH siRNA were stimulated with TNF-alpha and/or TGF-alpha for 24 h. VEGF levels in the supernatant were determined by enzyme-linked immunosorbent assay (ELISA). A Western blot analysis was performed to measure the activation of MEK and ERK and the expression of TNFR1 and TNFR2. RESULTS: TNF-alpha or TGF-alpha increased VEGF secretion in cells transfected with GAPDH or TNFR1 siRNA. The combination of TNF-alpha and TGF-alpha increased VEGF production. TNF-alpha and/or TGF-alpha stimulation increased phospho-MEK and phospho-ERK in cells transfected with TNFR1 siRNA. Conversely, the effects of TNF-alpha and/or TGF-alpha on MSC VEGF production were significantly decreased, and MEK/ERK activation was negated in cells transfected TNFR2 siRNA. CONCLUSION: TNFR2 plays a vital role in the effects of TNF-alpha and TGF-alpha on MSC VEGF production. The activation of MEK was implicated in this novel cross talk between TNFR2 and TGF-alpha-EGFR in regulating the production of VEGF in human MSCs.

Pseudoaneurysm formation in a subset of patients with small intestinal submucosa biologic patches after carotid endarterectomy.

BACKGROUND: The carotid artery is frequently patched after carotid endarterectomy (CEA) to minimize the risks of early postoperative thrombosis and late recurrent stenosis. The small intestinal submucosa (SIS) patch is a biologic vascular patch derived from porcine small intestine. It is composed primarily of cell-free collagen and other extracellular matrix constituents that act as a scaffold for host cell deposition. METHODS: In May 2001, we began an investigational trial of SIS patches in 76 patients undergoing patch angioplasty of the carotid artery after CEA. RESULTS: No adverse events related to the patches were observed in the first 69 patients implanted with an SIS patch. However, in late 2002, seven patients were found to have asymptomatic pseudoaneurysms (PSA) by duplex imaging < or =10 weeks after their CEAs. The trial was immediately suspended. The PSAs were treated by surgical resection with vein grafting in two patients and placement of covered endoluminal stents in four patients. One patient is being followed as the PSA is small and has remained stable. Histopathologic examination of the SIS patch explanted from one of the surgically treated patients demonstrated the presence of actin-positive myofibroblasts or smooth muscle cells. Extensive mechanical testing of the SIS material from the two material lots associated with PSAs demonstrated thinner and more variable physical characteristics compared with control device lots. CONCLUSIONS: Biologic patches that undergo active remodeling in the carotid artery require greater thickness than was anticipated to decrease wall stress and suture hole elongation. Patches exceeding this minimum thickness will be required to ensure the safety of new SIS patch designs for vascular operations.