Omke E. Teebken

Ischemic preconditioning prior to myocardial protection with cold blood cardioplegia in coronary surgery

OBJECTIVE Encouraging results on myocardial preconditioning in experimental models of infarction, stunning or prolonged ischemia raise the question whether preconditioning techniques may enhance conventional cardioplegic protection used for routine coronary surgery. METHODS A prospective clinical trial was conducted to investigate the effect of additional ischemic normothermic preconditioning prior to cardioplegic arrest applying cold blood cardioplegia in patients scheduled for routine coronary surgery (3 vessel disease, left ventricular ejection fraction > 50%). Two cross clamp periods of 5 min with the hearts beating in sinus rhythm were applied followed by 10 min of reperfusion, each (n = 7, group I). Inducing moderate hypothermia cold blood cardioplegia was delivered antegradely. In control groups, cold intermittent blood cardioplegia (n = 7, group II) was used alone. Coronary sinus effluents were analyzed for release of creatine kinase (CK), CK-MB, lactate, and troponin T at 1, 3, 6, 9, and 12 h. In addition, postoperative catecholamine requirements were monitored. RESULTS The procedure was tolerated well, and no perioperative myocardial infarction in any of the groups studied occurred. Concentrations of lactate tended to be higher in group I, but this difference was not significant. In addition, no significant differences for concentrations of CK, CK-MB, and troponin T were found. Following ischemic preconditioning an increased dosage of dopamine was required within the first 12 h postoperatively (group I: 2.63 +/- 1.44 microg/kg/min, group II: 0.89 +/- 1.06 microg/kg/min). CONCLUSIONS Combining ischemic preconditioning and cardioplegic protection with cold blood cardioplegia does not appear to ameliorate myocardial protection when compared to cardioplegic protection applying cold blood cardioplegia alone. Inversely, contractile function seemed to be impaired when applying this protocol of ischemic preconditioning.

Thoracic computed tomography prior to redo coronary surgery

OBJECTIVE Median resternotomy in coronary redo surgery represents a specific risk for injury of adjacent retrosternal structures. Aiming at improved preoperative evaluation of retrosternal structures, computed tomography (CT) techniques were routinely applied in redo cases. METHODS Of 99 patients undergoing coronary reoperations since April 93, thoracic CT scans were retrospectively analyzed for retrosternal vicinity of cardiovascular structures, condition of the ascending aorta and structural abnormalities of the sternum. RESULTS The minimal median distance between the posterior sternum surface and the anterior aortic wall was measured at 1.9 +/- 0.9 cm, whereas the mean closest distance to the anterior right ventricular wall was 0.4 +/- 0.5 cm. In 28 cases, the distance between sternum and aorta was smaller than or equal to 1 cm. No measurable distance between the sternum and the right ventricle was noted in 41 patients. Calcification of the ascending aorta became obvious 56 times. With respect to potential injury of the ascending aorta or the right ventricle, a safe reentry by resternotomy was facilitated in all cases. However, following complete sawing, the innominate vein became injured during retrosternal dissection in two cases. Preventive femoral vessel exposure was not performed and urgent femoral cannulation (n = 1) was infrequent. CONCLUSIONS Thoracic CT scanning prior to redo coronary surgery allows for detailed assessment of retrosternal relations and facilitates reopening of the sternum. Preventive femoral vessel exposure and lateral thoracotomies may be avoidable in many cases.

Differentiated corticosteroid production and regeneration after selective transplantation of cultured and noncultured adrenocortical cells in the adrenalectomized rat.

Syngeneic transplantation of adrenocytes was investigated in Lewis rats in regard to differentiated hormone secretion and cortex regeneration after bilateral adrenalectomy as an alternative to steroid substitution. Methods. Purified cell suspensions of glomerulosa (density 1.061±0.001 g/ml) and fasciculata (density 1.034±0.003 g/ml) cells were obtained by density gradient separation and were transplanted under the kidney capsule either immediately or after a 29-day culture period. Animals were killed after transplantation of cultured glomerulosa (CG-Tx) or cultured fasciculata cells (CF-Tx), noncultured glomerulosa cells (G-Tx) or non-cultured fasciculata cells (F-Tx), or both cell types (GF-Tx) for morphological studies after 30, 120, and 360 days. Plasma samples were drawn for measurement of corticosterone and aldosterone as well as 24 hr-urine for sodium and potassium levels at day 3, 30, 120, and 360 after transplantation. Results. In primary culture fasciculata cell number remained stationary although glomerulosa cell number increased to almost 10-fold. Vital cortex cells were demonstrated in each explanted graft by histochemistry but only group G-Tx, CG-Tx, and GF-Tx (purified cell suspensions of zona glomerulosa and fasciculata) showed neocortex-like structures. We found plasma (urine) corticosterone to decrease from preoperatively 256–304 ng/ml (226–239 ng/day) in untreated animals to levels about half as high 3 days after transplantation, increasing to normal values in all study groups 30 days after treatment (data given as range). Plasma aldosterone concentrations, 150–180 pg/ml in untreated rats, decreased to nondetectable levels for 1 week after bilateral adrenalectomy. At day 30 group GF-Tx, G-Tx, and CG-Tx showed comparable aldosterone plasma concentrations (104–122 pg/ml); however, levels in F-Tx and CF-Tx were 19–49 pg/ml, and did not increase significantly within the observation period. Conclusions. Cells derived from the zona glomerulosa maintain viability, produce both aldosterone and corticosterone, and regenerate a neocortex with cells that histologically resemble both zona glomerulosa and fasciculata cells. They are therefor suitable for adrenocortical transplantation. In contrast, cells derived from the zona fasciculata maintain viability, but do not regenerate zona glomerulosa and do not produce aldosterone. These results suggest that the cell migration model, in which zona glomerulosa cells can acquire the phenotype of zona fasciculata cells as they can migrate centripetaly, is more likely the correct explanation of adrenocortical zonation.

Enzymatic properties of transplanted glomerulosa cells.

Abstract. There are several theories about the physiologic regeneration of adrenals and maintenance of physiologic steroid secretion after subtotal loss of adrenal cortical cells. According to the cell migration theory, adrenocytes from the zona glomerulosa migrate centripetally toward the medulla. This theory is opposed by the zonal theory according to which each zone resplenishes its cells independently. What these theories have in common is that they are based on data from the intact adrenal gland. We transplanted purified glomerulosa cells under the kidney’s capsule of Lewis rats. The tissue was removed 30, 60, 90, and 150 days after transplantation to investigate the presence of two specific enzymes that are responsible for the secretion of aldosterone and corticosterone. Cytochrome p-450as is specific for glomerulosa cells producing aldosterone, and cytochrome p-45011β is specific for fasciculata cells producing corticosterone. After sequencing the genetic code of these enzymes it became possible to demonstrate expression of the enzymes by in situ hybridization. The transplanted glomerulosa cells turned their enzymatic property to fasciculata cells expressing cytochrome p-45011β. Our results suggest that glomerulosa cells are able to take over the physiologic function of a whole adrenal cortex in the absence of fasciculata cells, and that they are sufficient to maintain the function of the adrenal cortex.

Early Neurologic Outcome after Bovine Pericardium versus Venous Patch Angioplasty in 599 Patients Undergoing Carotid Endarterectomy

Bovine pericardium was compared to great saphenous vein patch angioplasty regarding the neurologic events after carotid endarterectomy (CEA) with or without concomitant cardiac surgery (CS). From January 1996 to December 2007, 599 patients undergoing CEA (259 with concomitant CS) were enrolled; 456 patients were treated with the great saphenous vein (GSV group) and 143 were treated with bovine pericardium (BP group). Neurologic outcome and Rankin score (RS) were recorded after 24 hours and 30 days. We found comparable rates of neurologic complications (transient ischemic attack, stroke) between the two groups. Thirty-day mortality was 4% (17 of 456 patients) in the GSV group and 0% in the BP group (p = .12). None of the patients died as a consequence of a fatal stroke. Preoperative RS was a prognostic factor for postoperative neurologic deterioration (p = .001). Early neurologic outcome was comparable for the two types of patch material. Preoperative RS predicted postoperative neurologic deterioration.

Impact of chronic infection with chlamydia pneumoniae on incidence of cardiac allograft vasculopathy.

Chronic infection with Chlamydia pneumoniae (CP) is associated with development of coronary disease. However, little information exists concerning CP infection and impact on posttransplant cardiac allograft vasculopathy (CAV). A total of 202 patients were investigated 5.5+/-3.1 years after cardiac transplantation (46.5+/-11.0 years; 169 male, 33 female). Assessment of CAV was performed by annual coronary angiograms. Chlamydia serology (IgG/IgA) was performed using micro-immunofluorescence. Statistics comprised analysis of variance and Kaplan-Meier analysis. A total of 152 patients were CAV positive. Elevated titers were present in 45% (IgG) and 72.8% (IgA) of patients. Generally, serostatus was not associated with development of CAV when evaluated over the total postoperative interval. However, after month 14 there was a significant trend toward lower actuarial freedom from CAV in patients with elevated IgA titers. CP seems not to play a significant role in the development of CAV early after heart transplantation but might be a predicting risk factor after the first postoperative year.

Ovine blood: establishment of a list of reference values relevant for blood coagulation in sheep.

Ovine animal models are widely used to conduct preclinical studies, e.g., to evaluate cardiovascular prostheses intended to be applied in man. However, although analyzed in many of those studies, information about ovine blood reference values is scanty. The aim of this study is to establish a reference list of ovine blood parameters relevant for blood coagulation. A cohort of 47 mature ewes was evaluated. Parameters comprised the following: cells and cellular components—platelet, red, and white cell counts (including subsets), hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), and MCH concentration (MCHC); global tests of coagulation—prothrombin time (Quick’s time) and activated partial thromboplastin time (aPTT); and parameters relevant for blood coagulation—fibrinogen, antithrombin (AT), and von Willebrand Factor. After explorative data analysis, a list of ovine reference values was established. Interestingly, a comparison with human reference values revealed some interspecies differences between sheep and man, i.e., much higher ovine ranges for some cell counts (neutrophils, lymphocytes, basophils, eosinophils, and platelets) but lower values for some other parameters (Hb, HCT, MCV, MCH, AT, and Quick’s test). We established a reference list of ovine blood count and blood coagulation parameters. Because of some peculiarities of the ovine blood, this list may have implications for the interpretation of experimental data.

Transplantation of H-2Kb-transgenic adrenocortical cells in the mouse having undergone an adrenalectomy: functional and morphological aspects.

BACKGROUND A new model of cellular adrenocortical transplantation after bilateral adrenalectomy in the mouse was established. This model was used to study the effects of the expression of the transgenic MHC class I molecule H-2K(b) (Kb) on graft survival and morphologic features, corticosterone secretion, and the possibility of tolerance induction in the recipient. METHOD A single cell suspension of purified adrenocortical cells was grafted under the kidney capsule of B10.Br (H-2k) mice having adrenalectomies. Syngeneic, fully MHC-mismatched, and MHC class I-incompatible Kb-transgenic mice served as donor strains. To analyze graft function, urinary excretion and serum levels of corticosterone were monitored over 100 days. Tolerance induction in the graft recipients of Kb-transgenic and third party skin grafts was tested on day 50 after adrenocortical transplantation. Histological sections of the adrenocortical grafts were obtained on day 100. RESULTS Recipients of syngeneic and Kb-transgenic grafts displayed pretransplant corticosterone levels on days 20, 50, and 100 and ACTH-stimulated serum corticosterone levels similar to those of controls on day 100 after adrenocortical transplantation. In contrast, in recipients of fully MHC-mismatched grafts, corticosterone excretion was significantly reduced. In this group, 4 of 7 mice did not survive. Syngeneic skin grafts survived indefinitely in recipients of syngeneic and Kb-transgenic adrenocortical grafts, whereas Kb-transgenic and fully MHC-mismatched skin grafts were acutely rejected. Tissue sections of the adrenocortical grafts revealed vascularized cell conglomerates in syngeneic and Kb-transgenic grafts without infiltrations of mononuclear cells. Furthermore, a differentiation similar to adrenocortical organization was partly found. CONCLUSION In conclusion, a model of cellular adrenocortical transplantation was established. The results show that syngeneic transplantation resulted in physiological corticosterone levels early after transplantation, whereas fully MHC-incompatible grafts were rejected. Recipients of Kb-transgenic grafts showed unimpaired adrenocortical function, but did not tolerize toward Kb-transgenic skin grafts. Possible mechanisms include a local immunomodulatory effect of glucocorticoids secreted by the graft and a low immunogenicity of the relatively small numbers of transplanted cells.

Pancreatic metastasis of a pleuropulmonary blastoma in an adult

Pleuropulmonary blastoma (PPB) is a rare dysontogenetic tumor that usually develops in the first decade of life and has been recognized as a distinct clinico-pathological entity different from the ordinary pulmonary blastoma of adulthood. Since the tumor grows aggressively and tends to metastasize early, physicians have to be aware of late onset of symptoms and uncommon manifestations. We report a case of PPB in a young adult and its recurrence in the pancreas after primary surgical treatment and adjuvant chemotherapy. Keeping in mind the moderate prognosis of PPB in children, accurate assessment and treatment of PPB require a team approach of oncology, radiology and surgery to establish new therapeutic guidelines in the future.

Adrenomedullin Is Associated With Surgical Trauma and Impaired Renal Function in Vascular Surgery Patients.

Background: Patients undergoing vascular surgery are prone to perioperative organ injury because of both higher prevalence of cardiovascular risk factors and the extent of surgery. Early detection of organ failure is essential to facilitate appropriate medical care. Midregional pro-adrenomedullin (MR-proADM) has been investigated in acute medical care settings to guide clinical decision-making regarding patient pathways and to identify patients prone to imminent cardiovascular or inflammatory complications. In this study, we evaluated the impact of perioperative MR-proADM levels as an early marker of perioperative cardiovascular and inflammatory stress reactions and kidney injury. Methods: The study was conducted as a monocentric, prospective, noninterventional trial at Hannover Medical School, Germany. A total of 454 consecutive patients who underwent open vascular surgery were followed from the day prior to until 30 days after surgery. The composite primary end point was defined as the occurrence of major adverse cardiac events (MACEs), acute kidney injury (AKI), or systemic inflammatory response syndrome (SIRS). Measurements were correlated with both medical history and postoperative MACE, AKI, or SIRS using univariate and multivariate regression analysis. Results: One hundred thirty-nine (31%) of the patients reached the primary end point within the study interval. Midregional pro-adrenomedullin change was associated with the combined primary end point and with the intensity of surgical trauma. Midregional pro-adrenomedullin change was increased in patients reaching the secondary end points, SIRS (optimal cutoff: 0.2 nmol/L) and AKI (optimal cutoff: 0.7 nmol/L), but not in patients with MACEs. Conclusion: Increased levels of MR-proADM within the perioperative setting (1) were linked to the invasiveness of surgery and (2) identified patients with ongoing loss of renal function. Increased MR-proADM levels may therefore identify a subgroup of patients prone to excessive cardiovascular stress but did not directly correlate with adverse cardiac events. Consistently low levels of MR-proADM may identify a subgroup of patients with acceptable low risk to guide discharge from high-density care units.