Christian Hagl

Replacing the ascending aorta and aortic valve for acute prosthetic valve endocarditis: is using prosthetic material contraindicated?

BACKGROUND The use of prosthetic material (rather than a homograft) for ascending aorta/aortic valve replacement (Bentall procedure) in cases of acute prosthetic valve endocarditis is controversial. We report favorable results using this technique almost exclusively (a homograft was used in only 3 patients with hematological problems) during a 12-year interval. METHODS Twenty-eight patients (55 +/- 14 years; 22 male) underwent a Bentall procedure for acute prosthetic valve endocarditis between 1988 and 2000. Twenty-five patients had undergone previous aortic valve replacement (1 with concomitant mitral valve replacement, 4 with coronary artery bypass grafting), and 3 had had a previous Bentall operation. The median interval between initial surgery and reoperation was 13 months (range, 1 to 106). Sixty-eight percent of operations were urgent or emergencies. Ninety-three percent of patients had significant aortic regurgitation; complete annuloaortic dehiscence occurred in 71%, and in 57%, an abscess was found. Causative organisms were identified in 25 of 28 patients: Staphylococcus epidermidis (9), Staphylococcus aureus (7), Streptococcus viridans (6), Pseudomonas (2), and Legionella (1). RESULTS Twenty-three patients had mechanical and 5 had biological valves implanted during the Bentall procedure. Hypothermic circulatory arrest was used in 64%. Hospital mortality was 11%: there was one intraoperative death, and two before discharge (one cardiac, one sepsis). Eighty-nine percent survived without stroke. During follow-up (median, 44.5 months; complete in 92%), 1 patient died of recurrent endocarditis at 4 months. CONCLUSIONS These results indicate that prosthetic root replacement may be superior to use of a homograft for acute aortic prosthetic valve endocarditis, with only a 4% incidence of recurrent endocarditis and reoperation.

Acute type B aortic dissection: surgical therapy

BACKGROUND Surgery for acute type B aortic dissection is associated with significant mortality. We report the results for 34 consecutive patients who underwent urgent surgery because they met criteria for operation during the acute phase (< 14 days) of acute type B dissection. METHODS The average patient age was 64 (32 to 88) years. Indications for surgery were persistent pain (12), threatened exsanguination (18), malperfusion (renal [3], limb [3]), rapid aortic enlargement (4), and uncontrolled hypertension (1). The mean interval from onset of pain to operation was 7 (1 to 14) days. Resection included the proximal descending aorta in 32, the distal aortic arch in 10, extension to the diaphragm in 10, and involved a thoracoabdominal procedure in 3. Surgical techniques included hypothermic circulatory arrest (16 [47%]), distal bypass, monitoring of somatosensory-evoked potentials, sequential intercostal sacrifice (average, 5.6 pairs), cerebrospinal fluid drainage, and steroid administration. RESULTS There was no hospital mortality. Important complications occurred in 16 patients (47%): 10 respiratory requiring tracheostomy, six infectious, four dialysis, two myocardial infarctions, and two neurologic (one transient stroke, one paraplegia). Mean intensive care unit and hospital stays were 10 (3 to 32) and 35 (7 to 107) days. Survival at 5 and 10 years was 80% and 57%, respectively (mean follow-up, 5.8 years). CONCLUSIONS Patients meeting criteria for urgent surgery have a low perioperative risk for mortality and paraplegia, and are relatively free from long-term aorta-related complications. These findings warrant consideration of earlier surgery for appropriate patients with acute type B aortic dissection.

Involvement of apoptosis in neurological injury after hypothermic circulatory arrest: a new target for therapeutic intervention?

BACKGROUND This study was undertaken to evaluate the role of apoptosis in neurological injury after hypothermic circulatory arrest (HCA). METHODS Twenty-one pigs (27 to 31 kg) underwent 90 minutes of HCA at 20 degrees C and were electively sacrificed at 6, 24, 48, and 72 hours, and at 7, 10, and 12 days after HCA, and compared with unoperated controls. In addition, 3 animals that had HCA at 10 degrees C, and 3 treated with cyclosporine A (CsA) in conjunction with HCA at 20 degrees C, were examined 72 hours after HCA. After selective perfusion and cryopreservation, all brains were examined to visualize apoptotic DNA fragmentation and chromatin condensation on the same cryosection of the hippocampus: fluorescent in situ end labeling (ISEL) was combined with staining with a nucleic acid-binding cyanine dye (YOYO). RESULTS In addition to apoptosis, which was seen at a significantly higher level (p = 0.05) after HCA than in controls, two other characteristic degenerative morphological cell types (not seen in controls) were characterized after HCA. Cell death began 6 hours after HCA and reached its peak at 72 hours, but continued for at least 7 days. Compared with the standard protocol at 20 degrees C, HCA at 10 degrees C and CsA treatment both significantly reduced overall cell death after HCA, but not apoptosis. CONCLUSIONS The data establish that significant neuronal apoptosis occurs as a consequence of HCA, but at 20 degrees C, other pathways of cell death, probably including necrosis, predominate. Although preliminary results suggest that the neuroprotective effects of lower temperature and of CsA are not a consequence of blockade of apoptotic pathways, inhibition of apoptosis nevertheless seems promising as a strategy to protect the brain from the subtle neurological injury that is associated with prolonged HCA at clinically relevant temperatures.

Cyclosporine A as a potential neuroprotective agent: a study of prolonged hypothermic circulatory arrest in a chronic porcine model

OBJECTIVE To assess whether Cyclosporine A (CsA) or cycloheximide (CHX) can reduce ischemia-induced neurological damage by blocking apoptotic pathways, we assessed their effects on cerebral recovery in a chronic animal model of hypothermic circulatory arrest (HCA). METHODS Twenty-eight pigs (28-33 kg) underwent 90 min of HCA at 20 degrees C. In this blinded study, animals were randomized to placebo (n=12), 5 mg/kg CsA (n=8), given intravenously before and subcutaneously for 7 days after HCA, or a single dose of 1 mg/kg CHX (n=8), given after weaning from cardiopulmonary bypass. Hemodynamics, intracranial pressure (ICP) and neurophysiological data (EEG, SSEP) were assessed for 3 h after HCA; early behavioral recovery was scored, and neurological/behavioral evaluation (9=normal) was carried out daily until elective sacrifice on postoperative day (POD) 7. Brains were selectively perfused and evaluated histopathologically for apoptosis. RESULTS Basic hemodynamic data revealed no differences between CsA or CHX and control groups. ICP was significantly lower throughout rewarming (P=0.009) and reperfusion (P=0.05) in the CsA group. EEG recovery 3 h after HCA was observed in four of eight CsA animals but in only 1 of 12 controls (P=0.11) and one of eight CHX animals; cortical SSEP recovery also seemed faster in CsA animals, but failed to reach significance. Some early recovery scores were significantly better in the CsA group, and daily behavioral scores were consistently and significantly higher in the CsA-treated animals from POD1 through POD4. CONCLUSIONS The data indicate that treatment with Cyclosporine A but not cycloheximide has a positive effect on cerebral recovery following HCA. Whether CsA results in inhibition of neuronal apoptosis, and/or inhibits release of cytokines and thereby reduces postischemic cerebral edema remains to be elucidated. The neuroprotective effect of CsA, if confirmed in further studies, would make its clinical application conceivable.

Impact of high intracranial pressure on neurophysiological recovery and behavior in a chronic porcine model of hypothermic circulatory arrest

OBJECTIVE This review was undertaken to determine whether high intracranial pressure (ICP) during reperfusion after hypothermic circulatory arrest (HCA) correlates with evidence of suboptimal cerebral protection in a chronic porcine model. METHODS In concurrent studies of cerebral protection, 48 control pigs (24-31 kg) underwent 90 min of HCA at 20 degrees C using a strictly standardized protocol. Hemodynamic measurements, ICP and neurophysiological data (EEG, SSEP) were assessed before HCA and until 3 h postoperatively. ICP was measured using a Codman microtip catheter inserted directly into brain parenchyma. Neurological/behavioral evaluation (9=full recovery) was carried out daily through postoperative day (POD) 3. RESULTS There were no significant hemodynamic or metabolic differences between individual animals. ICP (mmHg) increased significantly for the first 3 h after HCA: from baseline levels of 6.2+/-2.1 to 10+/-2.6 at 1 h, 11+/-3.2 at 2 h and 10+/-3.6 mmHg at 3 h; P<0.001 for the trend. EEG recovery 3 h after HCA was observed in 13 animals (27%), and correlated with lower ICP during reperfusion (P<0.001): with each 1 mmHg increase in ICP at 3 h, the odds of early EEG recovery decreased by a factor of 0.72. Lower ICP during reperfusion was also significantly associated with higher behavioral scores on POD 1 and 2, P<0.001. CONCLUSIONS A significant rise in ICP may help explain the prolonged obtundation and confusion often seen clinically after HCA. If these small but consistent increases in ICP contribute to rather than reflect ischemic neuronal damage, simple maneuvers to reduce ICP may improve cerebral recovery after HCA.

Apoptotic cell death in the hippocampus due to prolonged hypothermic circulatory arrest: comparison of cyclosporine A and cycloheximide on neuron survival.

OBJECTIVE To determine whether cyclosporine A (CsA) or cycloheximide (CHX) can reduce neuronal apoptosis in the hippocampus in a chronic animal model of hypothermic circulatory arrest (HCA). METHODS Twenty-eight pigs (28-33 kg) underwent 90 min of HCA at 20 degrees C. In a blinded study, animals were randomized to placebo (n=12), 5 mg/kg CsA (n=8), or 1 mg/kg CHX (n=8). After elective sacrifice 7 days postoperatively, brains were perfusion-fixed and the left hippocampus was examined for evidence of neuronal cell death. An in situ double-labeling method was used on cryosections to unequivocally identify apoptotic nuclei by the simultaneous visualization of DNA fragmentation and apoptotic chromatin condensation. Sections were also examined by immunocytochemistry for upregulation of the pro-apoptotic proteins Bax, activated caspase 3, and glyceraldehyde-3-phosphate dehydrogenase. RESULTS Apoptotic nuclear degradation was clearly present in the CA1, CA2 and CA3 subregions of the hippocampus after HCA. However, there was also morphological evidence for an accompanying necrotic-like cell death. There was no significant difference between the number of apoptotic nuclei observed in CSA-treated animals, mean value 4.4+/-1.63 SEM or CHX-treated animals, mean value 4.0+/-1.92 SEM, and age-matched control HCA pigs, mean value 4.85+/-1.69 SEM, (P>0.10). CONCLUSIONS The data clearly demonstrate apoptotic cell death in pigs after HCA by simultaneously demonstrating in situ end labeling (TUNEL reaction) and apoptotic chromatin condensation using a nucleic acid-binding dye. Since CsA shows promising neuroprotective effects in behavioral studies, and since the peak of HCA-induced apoptosis occurs earlier than 7 days, further studies will be required to determine whether CsA can improve neuronal survival in the first few days after HCA. CHX was not effective in reducing apoptosis in this model.

Is aortic surgery using hypothermic circulatory arrest in octogenarians justifiable

OBJECTIVE This study was undertaken to analyze the risk of mortality and neurological complications after aortic surgery requiring hypothermic circulatory arrest (HCA) in octogenarians. METHODS All patients of >80 years at the time of aortic surgery requiring HCA since 1988 were examined. Of 51 patients, 23 were male; the median age was 83. Twenty-six (51%) had proximal repair; the arch was replaced in eight (16%), and 17 (33%) had descending aorta repair. Eleven (22%) were emergencies. Multivariate analysis was carried out to determine the risk factors for in-hospital mortality and/or stroke (adverse outcome) using variables with P<0.1 after univariate analysis. RESULTS The hospital mortality was 16%. Five patients suffered strokes (9.8%): only one survived >6 months, and three died before discharge. The overall adverse outcome was 22%, but elective operation was associated with much better results, with an adverse outcome of only 3.6% after operations via a median sternotomy. Adverse outcome was strikingly higher with more distal resections via a left thoracotomy: 47 vs. 8.8% for ascending aorta/arch resections (P=0.003). Emergency operation via a lateral thoracotomy was associated with a prohibitively high adverse outcome. Twenty-nine patients (73%) had temporary neurological dysfunction (TND). Multivariate analysis revealed emergency operation (P=0.01; odds ratio (OR), 10.6) and operations via a lateral thoracotomy (P=0.008; OR, 11) as independent preoperative predictors of adverse outcome. The overall survival was 66% at 2 years and 39% at 5 years, compared with 85 and 52% among age- and sex-matched controls. CONCLUSIONS Aortic surgery utilizing HCA in octogenarians can be performed with an acceptable risk of mortality and stroke. From the evidence in this study, it seems that elective aneurysm repair via a median sternotomy can be undertaken for the usual indications, even in octogenarians. However, the enhanced vulnerability of the brain in the elderly is reflected by a high early mortality following stroke, and a high incidence of TND. Emergency operations increase the possibility of adverse outcome dramatically, and patients who require a lateral thoracotomy are at significantly higher risk than those operated via a median sternotomy.

Diabetes and evidence of atherosclerosis are major risk factors for adverse outcome after elective thoracic aortic surgery

BACKGROUND To predict risk after elective repair of ascending aorta and aortic arch aneurysms, we studied 464 consecutive patients. METHODS Adverse outcome (stroke or hospital death) was analyzed in 372 patients who underwent proximal repair and 92 patients who underwent aortic arch replacement from 1986 to the present. Preoperative risk factors with a P value less than.2 in a univariate analysis were entered into a multivariate model, and an equation incorporating independent risk factors was derived separately for proximal aorta and arch surgery. RESULTS Age more than 65 years (P =.04), diabetes (P =.02), cause (P =.01), and prolonged total cerebral protection time (duration of hypothermic circulatory arrest and selective cerebral perfusion, P =.001) were significant univariate risk factors for elective proximal aortic repair. Diabetes (P =.005, odds ratio 5.1), atherosclerosis (P =.003, odds ratio 4.0), and dissection (P =.048, odds ratio 2.5) were independent factors. For elective arch surgery, female sex (P =.07), age more than 65 years (P =.04), coronary artery disease (P =.02), diabetes (P =.06), cause (P =.07), and prolonged total cerebral protection time (P =.025) were univariate risk factors. Female sex (P =.05, odds ratio 4.7), coronary artery disease (P =.02, odds ratio 6.5), diabetes (P =.13, odds ratio 4.0), and total cerebral protection time (P =.03, odds ratio 1.02/min) were independent factors. To calculate risk of adverse outcome (P), enter 1 if factor is present, 0 if absent, and estimate total cerebral protection time (in minutes). [equation: see text]. CONCLUSION In this large series of patients, the presence of diabetes and manifestations of atherosclerosis emerge as extremely important risk factors for adverse outcome after ascending aorta or arch surgery, displacing age. Multivariate equations derived from these data allow more precise calculation of risk for each individual contemplating elective surgery.

A comparison of complete blood replacement with varying hematocrit levels on neurological recovery in a porcine model of profound hypothermic (<5°C) circulatory arrest

Profound hypothermia (<5 degrees C) may afford better neurological protection after circulatory arrest; however, there are theoretical concerns related to microcirculatory sludging of blood components at these ultra-low temperatures. We hypothesized that at temperatures <5 degrees C, complete blood replacement results in superior neurological outcome. Twelve Yorkshire pigs (30 kg) underwent thoracotomy, cardiopulmonary bypass (CPB), and were randomly assigned to one of three target hematocrits during circulatory arrest: 0%, 5%, 15%. Hextend (6% hetastarch in a balanced electrolyte vehicle) was used for the CPB prime and as an exchange fluid. Animals were cooled to a temperature <5 degrees C, underwent 1-h circulatory arrest, and were warmed to 35 degrees C with administration of blood to increase the hematocrit to >25% before separation from CPB. The primary outcome, peak postoperative neurobehavioral score, was compared between groups. The 0% group (mean +/- SD) had significantly (P: < 0.02) better neurobehavioral scores than the 5% and 15% groups (6.0 +/- 2.9 vs 1.3 +/- 1.0 and 1.5 +/- 0.6) respectively. Other variables (e.g., intracranial pressure) were similar between groups. In a porcine model of profound hypothermia (<5 degrees C) and circulatory arrest, complete blood replacement resulted in superior neurological outcome. This finding suggests that at ultralow temperatures, the presence of some blood component (e.g., erythrocytes, leukocytes) may be deleterious.