Delayed retroperitoneal haematoma after failed lumbar plexus block.
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Publications and source records attributed to D T Hsu.
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We describe the clinical course, echocardiography, angiography, and histopathology of a female infant with pulmonary atresia and intact ventricular septum (PA/IVS) with complete coronary ostial atresia and right ventricle-dependent coronary circulation who survived for 7 weeks after palliative surgery. The patient expired from myocardial insufficiency while waiting for a donor heart. Postmortem examination demonstrated atretic coronary ostia, ventricular sinusoids, and myocardial infarctions of various ages. This report suggests that neonates with PA/IVS who have this extreme form of coronary abnormality may potentially be managed medically and surgically until cardiac transplantation is available.
Corticotropin-releasing hormone (CRH) coordinates multiple aspects of the stress response. Recently, CRH mRNA has been identified in two regions of the thalamus: the posterior nuclear group (Po), and a region located at the interface of the central medial and ventral posteromedial nucleus (parvicellular part) (CM-VPMpc). Previous studies demonstrated that in both regions CRH mRNA increases following 1 h of restraint stress, suggesting involvement of thalamic CRH in processing somatosensory and visceral information related to stress. The current study was proposed to further understand the effects of repeated and acute restraint stress on levels of thalamic CRH mRNA. Adult male rats were assigned to one of four groups in a 2 (repeated stress, no repeated) x2 (acute, no acute) design. Brain sections were processed for CRH mRNA in situ hybridization. ANOVA revealed no main effects of acute or repeated stress in either thalamic region. However, significant interactions between acute and repeated stress for levels of CRH mRNA were found for both regions of the thalamus. Compared to the no stress condition, acute restraint significantly increased CRH mRNA in the Po (39%) and the CM-VPMpc (32%). Repeated restraint did not alter baseline CRH mRNA levels, but blocked the acute restraint-induced effects. Thus, while acute stress increases levels of thalamic CRH mRNA, repeated exposure to the same stressor is without effect and prevents the acute response. These findings add to data establishing a role for thalamic CRH in the stress response and suggest a mechanism that may underlie habituation to repeated stress exposure.
Corticotropin-releasing hormone (CRH) mediates endocrine, behavioral, and autonomic responses to stress. In addition to binding to two receptor subtypes, CRH binds to a CRH-binding protein (CRH-BP). While CRH-BP is hypothesized to play a role in regulating levels of free CRH and modulating the stress response, the effects of stressors on brain CRH-BP are relatively unexplored. The present study determined effects of acute and repeated restraint on CRH-BP mRNA in basolateral amygdala (BLA) and dorsal hippocampus (DH), brain regions involved in fear and motivation. Using in situ hybridization, we found that a single acute period of restraint significantly increased CRH-BP mRNA in BLA by 20% but had no effect in DH. Repeated restraint had no effect on basal levels of CRH-BP mRNA in BLA or DH. Importantly, repeated restraint blocked the effects of acute restraint in the BLA. These results demonstrate differential effects of acute and repeated restraint on CRH-BP mRNA.
Corticotropin-releasing hormone plays a critical role in mediating the stress response. Brain circuits hypothesized to mediate stress include the thalamus, which plays a pivotal role in distributing sensory information to cortical and subcortical structures. In situ hybridization revealed neurons containing corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group and the central medial nucleus of the thalamus, which interfaces with the ventral posteromedial nucleus (parvicellular part). These regions are of interest because they process somatosensory and visceral information. In the first experiment, the effect of acute stress on thalamic corticotropin-releasing hormone messenger RNA levels was assessed. Rats restrained for 1 h and killed 1 h later were found to have increased corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group. The time course of these changes was examined in a second experiment in which rats were killed immediately or 3 h after restraint. While no changes occurred in the thalamus immediately after restraint, 3 h after restraint, increases in corticotropin-releasing hormone messenger RNA occurred in both the posterior thalamic nuclear group and the central medial-ventral posteromedial nucleus (parvicellular part) of the thalamus. A different pattern of activation was observed in the paraventricular nucleus of the hypothalamus with increased corticotropin-releasing hormone messenger RNA immediately after restraint, but not 1 or 3 h later. In addition to the stress-induced changes, a prominent decrease in baseline thalamic corticotropin-releasing hormone messenger RNA was observed from 1000 to 1300 h. These results show that the thalamus contains corticotropin-releasing hormone messenger RNA that increases after restraint stress, indicating a role for thalamic corticotropin-releasing hormone systems in the stress response. Stress-induced changes in thalamic corticotropin-releasing hormone messenger RNA expression appears to be regulated differently than that in the paraventricular nucleus of the hypothalamus, and may be influenced by diurnal mechanisms.
Obstruction of the reconstructed aortic arch, or the neoaortic arch, is now known to be an important factor increasing mortality after the Norwood operation for hypoplastic left heart syndrome. Transcatheter balloon angioplasty has been shown to provide effective relief of both native aortic coarctation and obstructions of the aortic arch occurring subsequent to therapeutic intervention. We sought to determine the outcomes of balloon angioplasty used as an initial treatment for obstruction of the neoaortic arch occurring after the Norwood operation. We gathered the characteristics of 58 patients with such obstruction from 8 institutions, noting procedural factors and outcomes of initial balloon dilation. Obstruction occurred at a median interval of 4 months, with a range from 1.5 months to 6.3 years, after a Norwood operation. Ventricular dysfunction was present before dilation in 13 patients. Mean peak to peak systolic pressure gradients were acutely reduced from 31+/-20 mm Hg to 6+/-9 mmHg (p<0.001), with outcome subjectively judged to be successful in 89%. Three patients with pre-existing ventricular dysfunction died within 48 hours of dilation. There were 10 additional deaths during the period of follow-up, with Kaplan Meier estimates of survival after intervention of 87% at 1 month, 77% at 12 months, and 72% after 15 months. In addition, 9 patients required re-intervention during the period of follow-up, with Kaplan Meier estimates of freedom from re-intervention after dilation of 87% at 6 months, 78% at 12 months and 74% after 18 months. Although transcatheter dilation of neoaortic arch obstructions after Norwood operation is successful, there is a high risk of re-intervention and ongoing mortality in this subgroup of patients. Close follow-up is recommended.
Percutaneous access of the right internal jugular vein for coronary sinus cannulation in pediatric patients undergoing electrophysiologic studies may be technically difficult. We report the use of an ultrasound-guided technique for obtaining jugular venous access. Forty-five pediatric patients who underwent electrophysiologic study were analyzed. Access was obtained in 100 % of the patients using this technique with no major complications. Ultrasound guidance for access of the internal jugular vein for coronary sinus cannulation during electrophysiologic studies in pediatric patients, may increase the success rate and prevent the development of complications.
Serial echocardiographic measurements of the annulus and sinus were obtained in children before the Ross operation, and early and late postoperatively. Values were compared with normal standards for the aorta and pulmonary artery (PA). There was no significant difference between PA annulus measurements before surgery and the corresponding autograft immediately afterward (1.73 +/- 0.60 cm preoperatively; 1. 63 +/- 0.58 cm postoperatively, p = NS). Late after surgery the mean annulus diameter was enlarged compared with the normal aorta (DeltaZ 1.9 +/- 2.4), but remained relatively unchanged compared with the normal PA (DeltaZ 0.7 +/- 1.1, p <0.01). In contrast, the autograft sinus was dilated early after surgery (1.83 +/- 0.58 cm preoperatively; 2.18 +/- 0.73 cm postoperatively, p <0.01). Mean sinus Z score further increased compared with both the aorta (DeltaZ 1.3 +/- 1.7) and PA (DeltaZ 1.3 +/- 1.6). Use of standard PA measurements may be important in the assessment of autograft enlargement. Minimal change in autograft Z scores over time suggests that annulus enlargement is mainly due to somatic growth. In contrast, the autograft sinus showed an immediate and continued disproportionate increase in size over time, suggesting that sinus enlargement is largely due to passive dilation.
Endomyocardial biopsy (EMB) is usually performed from the femoral veins in infants and small children. This requires the use of a long vascular sheath to direct a bioptome to the ventricular septum. We describe a technique of EMB in this population that obviates the need for the use of a long vascular sheath. A 5 Fr 0.038" internal diameter, no-sideholes Cobra catheter (Cook, Bloomington, IN) introduced via a 5 Fr short sheath was used to direct a 3 Fr, 60-cm-length Cook bioptome to the ventricular septum. From January 1998 to August 1999, this technique was used 22 times in seven patients for EMB (median, age 13 months; range, 1-72 months). Indications for EMB in this group were posttransplantation surveillance (21 times) and evaluation for cardiomyopathy/myocarditis (1). Median number of EMB specimens obtained per procedure was 6 (range, 5-9). There was one pneumopericardium seen post-EMB with this technique without hemodynamic embarrassment. EMB in infants and small children can be performed successfully, safely, and repeatedly from the femoral veins without the need for a long sheath.
Pulmonary arteriovenous malformations (PAVMs) can occur following caval to pulmonary artery connection, Glenn and/or Fontan procedure, leading to severe cyanosis and exercise intolerance. It is unknown whether these abnormalities regress or persist following heart transplantation (HTx). Twenty patients with failed Fontan or Glenn procedures were screened for PAVMs prior to HTx by contrast echocardiography, selective pulmonary angiography, and pulmonary venous desaturation. Age at transplant, diagnosis, previous operations, time from Glenn to transplant, systemic oxygenation, hemoglobin level, and ventricular function were determined. The clinical course after HTx was characterized in three patients with significant PAVMs. Indications for HTx were exercise intolerance and severe cyanosis in one patient, and cyanosis and ventricular dysfunction in two. Pre-HTx, mean systemic saturation was 67%; mean pulmonary venous wedge saturation was 81%. Post-HTx, oxygen saturations were normal (> 96%) at 14, 40, and 180 days. Contrast echocardiography, performed 1 month to 3.3 yrs after HTx, showed no intrapulmonary shunting in two patients and minimal shunting in one. One patient suffered an embolic stroke from right-to-left shunting post-HTx. All patients are alive and well 35, 71, and 73 months post-HTx. In patients with single ventricle physiology, PAVMs are not an absolute contraindication to HTx. Heart-lung transplant may not be required for these patients.
OBJECTIVE: Inhibition of inducible nitric oxide synthase (nitric oxide II) activity has been proposed as a method to attenuate capillary leak and edema during rejection of heterotopically transplanted rat hearts. Myocardial edema has previously been implicated in diastolic dysfunction during allograft rejection. Accordingly, we tested the hypothesis that inducible nitric oxide synthase inhibition with aminoguanidine would alleviate left ventricular stiffening and myocardial edema formation in 4-day heterotopic rat heart allografts. METHODS: Passive left ventricular filling was studied in American Cancer Institute Lewis rats receiving heterotopic heart transplants receiving either aminoguanidine, a selective nitric oxide synthase inhibitor (n = 6); dexamethasone (1 mg. kg(-1). d(-1) administered subcutaneously) for 4 days after transplantation (n = 6); or intravenous saline solution (n = 6). American Cancer Institute-to-American Cancer Institute isografts (n = 6) were used as controls. RESULTS: Serum nitrite/nitrate levels in the aminoguanidine group (18 +/- 3 mmol/L) and dexamethasone group (22 +/- 4 mmol/L) were reduced versus the intravenous saline group (144 +/- 36 mmol/L [SEM]) to levels seen in controls (25 +/- 9 mmol/L). Left ventricular volume at 15 mm Hg for the aminoguanidine group was increased versus that for the intravenous saline solution group, similar to that for controls, and reduced versus dexamethasone-treated animals. Myocardial water content for the aminoguanidine-treated animals (78.3% +/- 0.4%) was similar to those of intravenous saline-treated animals (78.0% +/- 0. 3%) but greater than those of controls (77.1% +/- 0.2%) and dexamethasone-treated animals (76.7% +/- 0.3%). CONCLUSIONS: Nitric oxide II inhibition with aminoguanidine minimizes the reduction in left ventricular filling that is seen with allograft rejection through a mechanism that is not associated with attenuation of myocardial edema.
BACKGROUND: Advances in surgical and medical management have greatly improved long-term survival rates in patients with congenital heart disease (CHD). As these patients reach adulthood, myocardial dysfunction can occur, leading to cardiac transplantation. METHODS AND RESULTS: We reviewed the pretransplantation and posttransplantation courses of 24 patients >18 years old (mean age, 26 years; range, 18 to 56 years) with CHD who received a transplant between January 1985 and September 1998. The relation between preoperative and perioperative risk factors for complications and death was assessed. Single ventricle was the pretransplantation diagnosis for 12 patients (50%), and d-transposition of the great vessels was the diagnosis for 4 patients (16%). Twenty-two patients had a mean of 2 previous operations. At cardiac transplantation, additional surgical procedures were required to correct extracardiac lesions in 18 patients (75%). Refractory heart failure was present in 22 patients, significant cyanosis was present in 7, and protein-losing enteropathy was present in 4. There were 5 early deaths due to bleeding (n=3) and infection (n=2). The Kaplan-Meier survival rate after cardiac transplantation was 79% at 1 year and 60% at 5 years. No anatomic or surgical risk factor was predictive of death. The outcome of patients with CHD who received a transplant was compared with that for patients without CHD (n=788). Mean bypass and ischemic times were significantly longer in patients with CHD than in patients without CHD. Survival rates after transplantation did not differ significantly between patients with and those without CHD (P=0.83). CONCLUSIONS: Successful cardiac transplantation is obtainable in adults with complex CHD, with an outcome similar to that of patients without CHD. A detailed assessment of cardiac anatomy and careful surgical planning are essential to the pretransplantation and posttransplantation management of these patients.
BACKGROUND: To minimize decreases in left ventricular (LV) compliance immediately after rat heart transplantation, we tested several different methods of myocardial protection. MATERIALS AND METHODS: Five groups of ACI rat hearts (n = 6 each) were arrested by coronary perfusion with 5 ml of UW (University of Wisconsin), UW-BDM (UW with 2,3-butanedione monoxime), CU (Columbia University), or CU-BDM solution or by LV injection of potassium chloride and Ringer's lactate immersion (KCl/RL). After abdominal isografting and blood reperfusion for 15 min, transplanted hearts (TxH) were arrested and excised. Diastolic LV pressure-volume curves (LVPVCs) were correlated with myocardial water content (MWC). Native hearts (NH) were arrested identically to TxH and maintained at 4 degrees C by immersion. LVPVCs were measured at 15-min intervals for 90 min. RESULTS: In three of four pressure intervals at Time 0, normalized LV volume (LVV) was smaller (P < 0.05, ANOVA) in KCl/RL native hearts than in the four perfusion groups. LVV decreased significantly in NH after 45-75 min; LVV decreased similarly with time in all groups. In TxH, postarrest LVVs were higher with UW-BDM, CU-BDM, and CU than with UW or KCl/RL (P < 0.05, ANOVA). Expressing LVV of TxH as a percentage of NH, UW-BDM, CU, and CU-BDM provided qualitatively better diastolic properties than KCl/RL and UW. CONCLUSIONS: Thus rat LVPVCs can be improved after heart transplantation with alternative strategies of myocardial protection. KCl arrest decreases LV filling volume in this model and should be avoided.
BACKGROUND: Recent studies found that edema, histology, and left ventricular diastolic compliance exhibit quantitative relationships in rats. Edema due to low osmolarity coronary perfusates increases myocardial water content and histologic edema score and decreases left ventricular filling. The present study examined effects of perfusate osmolarity and chemical composition on rat hearts. METHODS: Arrested American Cancer Institute (ACI) rat hearts (4 degrees C) were perfused with different cardioplegia solutions, including Plegisol (289 mOsm/L), dilute Plegisol (172 mOsm/L), Stanford solution (409 mOsm/L), and University of Wisconsin solution (315 mOsm/L). Controls had blood perfusion (310 mOsm/L). Postmortem left ventricular pressure-volume curves and myocardial water content were measured. After glutaraldehyde or formalin fixation, dehydration, and paraffin embedding, edema was graded subjectively. RESULTS: Myocardial water content reflected perfusate osmolarity, being lowest in Stanford and University of Wisconsin solutions (p<0.05 versus other groups) and highest in dilute Plegisol (p<0.05). Left ventricular filling volumes were smallest in dilute Plegisol and Plegisol (p<0.05). Osmolarity was not a major determinant of myocardial edema grade, which was highest with University of Wisconsin solution and dilute Plegisol (p<0.05 versus other groups). CONCLUSIONS: Perfusate osmolarity determined myocardial water content and left ventricular filling volume. However, perfusate chemical composition influenced the histologic appearance of edema. Pathologic grading of edema can be influenced by factors other than osmolarity alone.
BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a well-known complication of immunosuppression associated with solid organ transplantation. The clinical course of PT-LPDs is unpredictable; some patients experience regression of all lesions with a reduction in immunosuppression, whereas other patients, despite chemotherapy, radiation therapy, or surgery, rapidly die of their disease. In this study, the authors attempted to establish whether the previously described morphologic and molecular genetic categories of PT-LPD--plasmacytic hyperplasia (PH), polymorphic PT-LPD (polymorphic), and malignant lymphoma/multiple myeloma (ML/MM)--are clinically relevant and helpful in predicting the clinical outcome of patients who develop these lesions. METHODS: To determine the clinical significance of the morphologic and molecular genetic categories of PT-LPDs, the clinical characteristics of 32 solid organ transplant recipients (26 heart, 5 kidney, and 1 lung), including age, time from transplantation to development of PT-LPD, stage of disease, and clinical outcome, were compared with the morphologic and molecular genetic features of the 41 PT-LPDs that they developed (15 PH in 12 patients, 19 polymorphic in 16 patients, and 7 ML/MM in 6 patients). Clinical outcome was defined by the following categories: 1) regression (after a reduction in immunosuppression) and surgical resolution (by surgical excision, with or without a reduction in immunosuppression); 2) medical resolution (by chemotherapy and/or radiation therapy); and 3) no response. RESULTS: Although there was no difference in the time from transplantation to PT-LPD development among patients belonging to the three morphologic and molecular genetic categories, there was a significant difference in patient age at the time of PT-LPD development (P < 0.0098). Younger patients developed PH (mean age of 19 years), whereas older patients developed polymorphic PT-LPD (mean age of 35 years) and ML/MM (mean age of 56 years). Patients with PH presented with lower stages of disease (Stages I-II) than patients with ML/MM (P < 0.0004). Furthermore, there was a statistically significant trend between morphologic and molecular genetic category and clinical outcome, with decreased likelihood that lesions categorized as PH, polymorphic, or ML/MM would regress with a reduction in immunosuppression or be resolved by surgery, whereas those classified as ML/MM were more likely to exhibit no response to aggressive clinical intervention (P < 0.00006). Furthermore, no patients with PH died, whereas 20% with polymorphic PT-LPD and 67% with ML/MM died as a direct result of their PT-LPDs. CONCLUSIONS: This study strongly suggests that classification of PT-LPDs into the morphologic and molecular genetic categories PH, polymorphic, PT-LPD and ML/MM is clinically relevant.
High densities of nerve cells containing corticotropin-releasing hormone (CRH) are located in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) of the hypothalamus. These brain regions play an important role in activating autonomic, behavioral, and endocrine responses to stress. This study was conducted to provide needed information concerning the acute effects of stress on CeA and PVN CRH mRNA expression. Rats were exposed to restraint stress for 1 h and brains collected after a 1-h post-stress interval. CRH mRNA expression occurring in the CeA and PVN was examined using in situ hybridization techniques. Densitometric analysis revealed that acute restraint stress produced significant increases in CRH mRNA levels in the PVN and in the rostral CeA region. In addition, the area in the rostral CeA encompassing high CRH mRNA signals increased significantly after stress. Results provide clear evidence that CRH neurons in the CeA and PVN exhibit rapid increases in CRH mRNA expression after exposure to stress.
BACKGROUND: Although myocardial edema is known to impair diastolic filling of the left ventricle, the interrelation of edema, histologic condition, and function has not been quantitated sufficiently for extrapolation to studies of multifactorial influences on diastolic properties. METHODS: Accordingly, ACI rat hearts arrested at 4 degrees C underwent coronary artery perfusion with a cardioplegia solution that was either unaltered (288 mOsm/L, P288 group, n = 6), diluted (144 mOsm/L, P144 group, n = 6), or concentrated (380 mOsm/L, P380 group, n = 6). Postmortem left ventricular pressure-volume curves and myocardial water content were measured. Myocardial samples were fixed in varying dilutions of glutaraldehyde. After dehydration and paraffin embedding, edema was graded subjectively (0 to 5), and myocardial interstitial spaces were determined by use of a semiquantitative method. RESULTS: Mean normalized left ventricular filling volume at 20 mm Hg filling pressure in the P144 group, 189 +/- 16 microliters (SEM), was reduced versus both the P288 (278 +/- 26 microliters) and the P380 (332 +/- 18 microliters) groups (p < 0.05, ANOVA). Mean myocardial water content in the P144 group, 80.7% +/- 1%, was increased versus the P380 (76.7% +/- 0.4%, p < 0.05) but not versus the P288 group (78.4% +/- 0.8%). In hearts preserved with 2.5% glutaraldehyde, mean edema grade and interstitial space in the P144 group (4.0 +/- 0.3) were increased versus the P380 (1.8 +/- 0.3, p < 0.05) but not the P288 group (2.7 +/- 0.5). Derived linear regressions relate water content to filling volume and histologic condition. CONCLUSIONS: Coronary perfusate osmolarity is thus associated with predictable changes in myocardial water content, left ventricular filling volume, and edema. These correlations allow definition of new hypotheses for the study of cardiac allograft rejection in patients and experimental animals.
BACKGROUND: Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture. METHODS: Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals. RESULTS: On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5. CONCLUSIONS: Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.