A majority of trauma-related deep venous thromboses resolve prior to discharge.

Post-traumatic DVTs present unique challenges in patient populations with specific high-risk injury patterns. Duplex ultrasound (US) can be used to assess evolution of DVTs and may guide treatment for high-risk patients. We hypothesized that many DVTs resolve during the initial admission. Weekly duplex US are ordered on all trauma inpatients regardless of prior DVT at our facility. We reviewed US and outcomes data on all patients with lower extremity DVTs at our Level I trauma center from January 2012-December 2021. 392 patients were diagnosed with lower extremity DVT by US. 261 (67%) patients received follow-up US with a mean time to repeat US of 6 days. Of these, 91 (35%) patients experienced DVT resolution prior to the first follow-up US, and 141 (54%) patients experienced resolution prior to discharge. Mean time to resolution was 10 days. Over 50% of DVTs resolve before discharge and are detected by US. Further studies and post-discharge follow-up are needed to determine if patients with resolved DVTs can be managed without therapeutic anticoagulation.

Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury.

Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 10(6)/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2-8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury.

Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium.

Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use microarray and proteomic analyses to identify pathways modulated by LV-aortic banding (AOB) and RV-pulmonary artery banding (PAB) in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta [LV-AOB; n = 6]. RV-PAB was achieved by banding the pulmonary artery (n = 6). Controls (n = 6 each) were sham-manipulated. After 4 (LV-AOB) and 6 (RV-PAB) wk recovery, the hearts were removed and matched RNA and proteins samples were isolated for microarray and proteomic analysis. Microarray and proteomic data demonstrate that in LV-AOB there is increased transcript expression levels for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium, and protein kinase-A signaling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also an increased transcript expression levels for cardiac oxidative phosphorylation but increased protein expression levels for structural constituents of muscle, cardiac muscle tissue development, and calcium handling. These results identify divergent transcript and protein expression profiles in LV-AOB and RV-PAB and provide new insight into the biological basis of ventricular specific hypertrophy. The identification of these pathways should allow for the development of specific therapeutic interventions for targeted treatment and amelioration of LV-AOB and RV-PAB to ameliorate morbidity and mortality.

Microarray and proteomic analysis of the cardioprotective effects of cold blood cardioplegia in the mature and aged male and female.

Recently we have shown that the cardioprotection afforded by cardioplegia is modulated by age and gender and is significantly decreased in the aged female. In this report we use microarray and proteomic analyses to identify transcriptomic and proteomic alterations affecting cardioprotection using cold blood cardioplegia in the mature and aged male and female heart. Mature and aged male and female New Zealand White rabbits were used for in situ blood perfused cardiopulmonary bypass. Control hearts received 30 min sham ischemia and 120 min sham reperfusion. Global ischemia (GI) hearts received 30 min of GI achieved by cross-clamping of the aorta. Cardioplegia (CP) hearts received cold blood cardioplegia prior to GI. Following 30 min of GI the hearts were reperfused for 120 min and then used for RNA and protein isolation. Microarray and proteomic analyses were performed. Functional enrichment analysis showed that mitochondrial dysfunction, oxidative phosphorylation and calcium signaling pathways were significantly enriched in all experimental groups. Glycolysis/gluconeogenesis and the pentose phosphate pathway were significantly changed in the aged male only (P < 0.05), while glyoxylate/dicarboxylate metabolism was significant in the aged female only (P < 0.05). Our data show that specific pathways associated with the mitochondrion modulate cardioprotection with CP in the aged and specifically in the aged female. The alteration of these pathways significantly contributes to decreased myocardial functional recovery and myonecrosis following ischemia and may be modulated to allow for enhanced cardioprotection in the aged and specifically in the aged female.

Preliminary biomarkers for identification of human ascending thoracic aortic aneurysm.

BACKGROUND: Human ascending thoracic aortic aneurysms (ATAAs) are life threatening and constitute a leading cause of mortality in the United States. Previously, we demonstrated that collagens α2(V) and α1(XI) mRNA and protein expression levels are significantly increased in ATAAs. METHODS AND RESULTS: In this report, the authors extended these preliminary studies using high-throughput proteomic analysis to identify additional biomarkers for use in whole blood real-time RT-PCR analysis to allow for the identification of ATAAs before dissection or rupture. Human ATAA samples were obtained from male and female patients aged 65 ± 14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of ATAAs using qRT-PCR analysis of whole blood. Analysis of 41 samples (19 small, 13 medium-sized, and 9 large ATAAs) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with ATAA of ≥4.0 cm (P<0.001, sensitivity 0.79, CI=0.62 to 0.91; specificity 1.00, 95% CI=0.42 to 1.00). CONCLUSION: A preliminary transcript biomarker panel for the identification of ATAAs using whole blood qRT-PCR analysis in men and women is presented.