Hemodynamic pathogenesis of ischemic hepatic injury following cardiogenic shock/resuscitation.

Post-ischemic hepatic injury is observed commonly following cardiogenic or hypovolemic shock. We evaluated the putative roles of the alpha-adrenergic sympathetic nervous system and the renin-angiotensin axis in the pathogenesis of hepatic injury following cardiogenic shock. Previous studies have characterized the hepatic hemodynamic response to shock, while the relationship of these hemodynamic changes to ischemic hepatic injury has not been defined. Sustained (4 h) periods of pericardial tamponade (after mild hemorrhage) followed by 2 h of resuscitation generated a reproducible model of cardiogenic shock and consequent post-ischemic hepatic injury in anesthetized pigs. In a separate group of pigs, the alpha-adrenergic component of the sympathetic nervous system was ablated with phenoxybenzamine or, in other groups, the renin-angiotensin axis was ablated by either prior nephrectomy or, separately, by confirmed angiotensin converting enzyme inhibition with teprotide. The hepatic injury response in each case was reevaluated. Compared to sham-shocked pigs, those subjected to tamponade alone manifested selective splanchnic vasospasm and consequent biochemical and histological evidence of classic post-ischemic liver injury (centrilobular necrosis involving about a third of each hepatic lobule). These manifestations of splanchnic vasospasm and the consequent ischemic injury were not ameliorated by confirmed alpha-adrenergic blockade, but significantly attenuated by either method of prior ablation of the renin-angiotensin axis. This model of sustained cardiogenic shock and resuscitation generates the manifestations of ischemic hepatic injury associated with selective splanchnic vasospasm, findings consistent with previous, short-term, hemodynamic studies. The major mediator of this response, and the consequent hepatic injury, is the selective hypersensitivity of the mesenteric vasculature to the renin-angiotensin axis.

The fate of a patent carotid artery contralateral to an occlusion.

The finding of carotid stenosis contralateral to a carotid occlusion is becoming more frequent. While the neurologic outcomes in this patient population have been described, the rate of disease progression measured by duplex examination and the eventual need for carotid endarterectomy has not been described. In this study, a computerized database of carotid duplex examinations was reviewed and clinical data were obtained from clinic records. From 9124 studies 117 patients were identified. Thirty patients had previous carotid surgery on the patent side and were excluded. Of 87 patients 33 required carotid endarterectomy on the patent side. The rate of disease progression and/or the performance of a carotid endarterectomy by life-table analysis was 85.9% over 8 years. There were 10 neurologic events during the follow-up period. Patients with carotid stenosis and contralateral occlusion are at significant risk for disease progression. Follow-up should be more frequent and of longer duration in this patient population. A significant number of patients with carotid artery occlusion will require a carotid endarterectomy of the patent contralateral carotid.

Timing of computed tomography in acute diverticulitis.

PURPOSE: The purpose of this study was to evaluate the use and timing of computed tomography in the treatment of patients with acute left-sided diverticulitis. METHODS: We reviewed our four-year experience of 47 patients with the diagnosis of acute diverticulitis. We have evaluated the benefits of admission vs. delayed computed tomography in patients with this diagnosis. RESULTS: Of the 47 patients, 17 were diagnosed on clinical grounds alone, treated, and released. Thirty patients had their clinical diagnoses of diverticulitis evaluated with either computed tomographic scan (26) or laparotomy (4). Eleven of those 30 (36 percent) patients were found to have normal computed tomographic scans, indicating inaccurate clinical diagnosis, and all patients who underwent laparotomy had the pathologic diagnosis of diverticulitis. Six of the 47 patients had abscesses, but only 2 were identified at the time of admission. The remaining four abscesses were identified on delayed computed tomographic scans after failure of medical therapy. Thirty-seven hospital days were used by patients with inaccurate diagnoses before their computed tomographic scans. Analysis of cost revealed that a computed tomographic scan for all 47 patients would have cost less than the expense of admission for just the 11 patients who had normal computed tomographic scans. CONCLUSION: Routine admission computed tomographic scan for patients with acute diverticulitis leads to more accurate diagnosis, earlier identification of complications, and possible decreased hospital costs.

Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor alpha in endothelium.

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor alpha (TNF-alpha) in vitro. TNF-alpha upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-alpha was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-alpha. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-alpha to induce ICAM-1 expression in endothelium in vitro.

Leptin regulates proinflammatory immune responses.

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.

Delayed presentation of 50 years after a World War II vascular injury with intraoperative localization by duplex ultrasound of a traumatic false aneurysm.

A case of delayed presentation of a traumatic false aneurysm in the left arm 50 years after penetrating injury sustained during World War II is described. The original injury resulted in brachial artery occlusion and complete median nerve palsy. The false aneurysm presented with a spontaneous, contained rupture. Surgical repair was performed after duplex ultrasound localization of the lesion to a small collateral artery lateral to the elbow, thereby avoiding dissection in the densely scarred tissue plains in the antecubital fossa. Duplex ultrasound was also used intraoperatively to facilitate localization of the aneurysm neck and to confirm absence of flow in the sac after repair. A brief historical review of traumatic false aneurysms caused by combat injuries, is provided. The progress in the treatment of such injuries gained by wartime experience is reviewed.