Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart-Liver Transplantation.

When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart-liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune-mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol- and indication-specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell-mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor-specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody-mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0-0.02; p < 0.0001), antibody-mediated rejection (OR 0.04, 95% CI 0-0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07-0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients.

Cardiac allograft remodeling after heart transplantation is associated with increased graft vasculopathy and mortality.

The aim of this study was to assess the patterns, predictors and outcomes of left ventricular remodeling after heart transplantation (HTX). Routine echocardiographic studies were performed and analyzed at 1 week, 1 year and 3-5 years after HTX in 134 recipients. At each study point the total cohort was divided into three subgroups based on determination of left ventricle mass and relative wall thickness: (1) NG-normal geometry (2) CR-concentric remodeling and (3) CH-concentric hypertrophy. Abnormal left ventricular geometry was found as early as 1 week after HTX in 85% of patients. Explosive mode of donor brain death was the most significant determinant of CH (OR 2.9, p = 0.01) at 1 week. CH at 1 week (OR 2.72, p = 0.01), increased body mass index (OR 1.1, p = 0.01) and cytomegalovirus viremia (OR - 4.06, p = 0.02) were predictors of CH at 1 year. CH of the cardiac allograft at 1 year was associated with increased mortality as compared to NG (RR 1.87, p = 0.03). CR (RR 1.73, p = 0.027) and CH (RR 2.04, p = 0.008) of the cardiac allograft at 1 year is associated with increased subsequent graft arteriosclerosis as compared to NG.

Is early anticoagulation with warfarin necessary after bioprosthetic aortic valve replacement?

OBJECTIVES: Freedom from anticoagulation is the principal advantage of bioprosthesis; however, the American Heart Association/American College of Cardiology and the American College of Chest Physicians guidelines recommend early anticoagulation with heparin, followed by warfarin for 3 months after bioprosthetic aortic valve replacement. We examined neurologic events within 90 days of bioprosthetic aortic valve replacement at our institution. METHODS: Between 1993 and 2000, 1151 patients underwent bioprosthetic aortic valve replacement with (641) or without (510) associated coronary artery bypass. By surgeon preference, 624 had early postoperative anticoagulation (AC+) and 527 did not (AC-). In the AC- group, 410 patients (78%) received antiplatelet therapy. Groups were similar with respect to gender (female, 36% AC+ vs 40% AC-, P = .21), hypertension (64% AC+ vs 61%, P = .27), and prior stroke (7.6% AC+ vs 8.5% AC-, P = .54). The AC+ group was slightly younger than the AC- group (median, 76 years vs 78 years, P = .006). RESULTS: Operative mortality was 4.1% with 43 (3.7%) cerebrovascular events within 90 days. Excluding 18 deficits apparent upon emergence from anesthesia, we found that postoperative cerebrovascular accident occurred in 2.4% of AC+ and 1.9% AC- patients. By multivariable analysis, the only predictor of operative mortality was hypertension ( P < .0001). Postoperative cerebrovascular accident was unrelated to warfarin use ( P = .32). The incidence of mediastinal bleeding requiring reexploration was similar (5.0% vs 7.4%), as were other bleeding complications in the first 90 days (1.1% vs 0.8%). No variables were predictive of bleeding by multivariate analysis. CONCLUSIONS: Although these data do not address the role of antiplatelet agents, early anticoagulation with warfarin after bioprosthetic aortic valve replacement did not appear to protect against neurologic events.

Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings.

BACKGROUND: Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. SUBJECTS AND METHODS: We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. RESULTS: Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. CONCLUSIONS: Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.

Effects of pentoxifylline on renal function and blood pressure in cardiac transplant recipients: a randomized trial.

BACKGROUND: The current success of cardiac transplantation is in part attributable to the development of effective immunosuppressive agents such as cyclosporine. However, concern remains regarding the potential for cyclosporine-induced nephrotoxicity. Animal studies and early reports of renal protective effects of pentoxifylline in bone marrow transplant recipients prompted a randomized trial in cardiac transplant recipients. METHODS: Twenty-nine patients were randomized to receive pentoxifylline 400 mg p.o. t.i.d. or matching placebo for 1 year after cardiac transplantation. Renal function was assessed preoperatively and at 1, 6, and 12 months postoperatively. Glomerular filtration rate and renal plasma flow were measured with iothalamate and para-aminohippurate, respectively. Serum creatinine was also measured. Ambulatory blood pressure monitoring after withdrawal of antihypertensives for 3 days was performed 12 months postoperatively. RESULTS: Twenty-seven patients completed the study. Glomerular filtration rate rose between 1 and 6 months after transplantation, presumably due to the reduction in goal cyclosporine level in that period, and then fell modestly between 6 and 12 months, presumably due to ongoing nephrotoxic effects of cyclosporine. No difference in glomerular filtration rate or creatinine was seen between pentoxifylline and placebo groups at any interval. Renal plasma flow increased modestly between baseline and 6 months in the pentoxifylline group, but not in the placebo group, and then fell between 6 and 12 months. Serum creatinine increased between baseline and 6 months in both groups, apparently due to increased body weight. Results of 18-hr ambulatory blood pressure monitoring obtained 1 year after transplantation was not different between groups. CONCLUSIONS: Renal function declines only modestly in the first year after cardiac transplantation. Pentoxifylline did not attenuate this process and had no effect on blood pressure. The modest decline in renal function may be related to current immunosuppressive strategies.

Time to reperfusion and other procedural characteristics of emergency coronary artery bypass surgery after unsuccessful coronary angioplasty.

A databank search was performed and 148 consecutive patients (mean age 59.5 +/- 10.4 years) were identified who underwent emergency coronary artery bypass surgery at the Mayo Clinic between November 20, 1979, and February 12, 1992, immediately after unsuccessful coronary angioplasty. At the end of the angioplasty procedure, there was no anterograde coronary blood flow in the treated artery in 54%, ongoing chest pain in 78%, and hemodynamic compromise requiring intravenous vasopressor therapy in 25% of patients; 127 patients (86%) had at least 1 of these adverse characteristics. After leaving the catheterization laboratory, the median time to arrival in the operating room was 12 minutes. Median time from arrival in the operating room to initiation of cardiopulmonary bypass was 86 minutes, to administration of cardioplegia was 98 minutes, and to removal of the aortic cross-clamp was 135 minutes. In-hospital mortality was 11%, and 18% developed nonfatal Q-wave myocardial infarction. Thus, significant time is required to achieve surgical reperfusion after unsuccessful coronary angioplasty.

Surgical issues in lung transplantation: options, donor selection, graft preservation, and airway healing.

To present an overview of the surgical issues in lung transplantation, including the historical context and the rationale for choosing a particular procedure for a specific patient, we reviewed and summarized the current medical literature and our personal experience. Several surgical options are available, including single lung transplantation; double lung transplantation; heart-lung transplantation; bilateral, sequential single lung transplantation; and (recently) single lobe transplantation. Although single lung transplantation is preferred for maximal use of the available organs, bilateral lung transplantation is necessary for septic lung diseases and may be appropriate for pulmonary hypertension and bullous emphysema. Heart-lung transplantation is performed for Eisenmenger's syndrome and for primary pulmonary hypertension with severe right ventricular failure. General factors for consideration in assessment of compatibility of the donor and potential recipient include ABO blood group, height (the donor should be within +/- 20% of the recipient's height), and length of the lungs (determined on an anteroposterior chest roentgenogram). Graft preservation and minimal duration of ischemia are important. Complications associated with airway healing are related to ischemia of the donor bronchus. We have addressed the issue of donor bronchial ischemia by direct revascularization of the donor bronchial arteries with use of the recipient's internal thoracic artery. Currently, lung transplantation offers a realistic therapeutic option to patients with end-stage pulmonary parenchymal or vascular disease.

Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases.

OBJECTIVE: To describe a clinicopathologic study of a large group of congenitally bicuspid aortic valves surgically excised at a single institution. MATERIAL AND METHODS: The medical charts and bicuspid valves from patients undergoing aortic valve replacement at Mayo Clinic Rochester between 1991 and 1996 were retrospectively reviewed. RESULTS: The age of the 542 patients ranged from 1 to 86 years (mean, 61), and 372 (69%) were men. Among these, 409 (75%) had pure aortic stenosis (AS), 73 (13%) had pure aortic insufficiency (regurgitation) (AI), 53 (10%) had combined AS and AI, and 7 (1%) had normal function. The mean age was higher for those with AS than AI (65 versus 46 years; P < 0.001), whereas the male-to-female ratio was higher for AI than AS (17.3:1 versus 1.7:1; P < 0.001). The two cusps were not equal in size in 95%, and a raphe was present in 76% (67% typical, 9% atypical). Raphal position was described in 315 and was between the right and left cusps in 270 (86%). Raphal absence occurred more often in valves with equal-sized cusps than unequal (33% versus 14%; P = 0.005). Moderate to severe calcification affected valves with AS more frequently than AI (99% versus 41%; P < 0.001). In contrast, annular dilatation was associated with AI more than AS (48% versus 11%; P < 0.001). Acquired commissural fusion involved valves with combined AS and AI more often than the other functional states (31% versus 14%; P = 0.002). Sixteen patients (age range, 18 to 78 years; 13 men) had infective endocarditis (6 active, 10 healed), including 10 with AI (9 men), 3 with AS plus AI, 2 with AS, and 1 with normal function but embolization. CONCLUSION: Functionally, the most common fate of congenitally bicuspid aortic valves was calcific stenosis with or without regurgitation (85%). Because approximately 4 million US citizens have bicuspid valves and because valve replacement is currently the only treatment of symptomatic AS, this disorder will continue to affect health-care costs.

Genetic expression of endothelial nitric oxide synthase in human atrial myocardium.

OBJECTIVE: To investigate the expression of endothelial nitric oxide synthase (eNOS) in human cardiac tissues. DESIGN: We attempted to determine the genetic expression and localization of eNOS in normal human atrial tissue. MATERIAL AND METHODS: In normal human right atrial tissues from five donors during cardiac transplantation, eNOS expression and localization were assessed by using Northern blot analysis, in situ hybridization, and immunohistochemical staining. RESULTS: Northern blot analysis and in situ hybridization demonstrated that eNOS messenger RNA is present in cardiomyocytes. Positive immunohistochemical staining was observed in the cytoplasm of cardiomyocytes. CONCLUSION: These studies show for the first time the genetic expression and distribution of eNOS in human atrial myocardium and suggest that the eNOS mediated paracrine and autocrine pathway may participate in the control of myocardial function in humans.

Calcified bicuspid aortic valve mass prolapsing into the left main coronary artery.

We report a case of a mobile calcific mass on the aortic valve that prolapsed into the left main coronary artery of a 51-year-old man. This case and a review of the literature suggest that calcific embolization to coronary arteries is a rare but possibly underrecognized complication of calcified degenerative or bicuspid aortic valves. This potentially catastrophic complication of calcified aortic valves needs to be suspected and recognized in clinical practice.

Cardiac transplantation for end-stage congenital heart defects: the Mayo Clinic experience. Mayo Cardiothoracic Transplant Team.

OBJECTIVE: To review the outcome of cardiac transplantation undertaken in patients with congenital heart defects. MATERIAL AND METHODS: Between November 1991 and March 1998 at our institution, cardiac transplantation was performed in 16 patients with congenital heart disease (age range, 3 to 57 years; mean, 26.1). Preoperative diagnoses included univentricular heart (N = 4); complete transposition of the great arteries (N = 3); Ebstein's anomaly (N = 2); tetralogy of Fallot (N = 2); levotransposition (N = 2); dextrocardia, corrected transposition, ventricular and atrial septal defects, and pulmonary stenosis (N = 1); double-outlet right ventricle (N = 1); and hypertrophic obstructive cardiomyopathy (N = 1). All patients had undergone from one to five previous palliative operations. RESULTS: Four patients required permanent pacemaker implantation during the first month postoperatively because of bradycardia; more than 2 years later, another patient required a permanent pacemaker because of sick sinus syndrome. In addition, one patient had an automatic implantable cardioverter-defibrillator. Three patients required reconstruction of cardiovascular structures with use of prosthetic material (Teflon patches or donor tissue) at the time of cardiac transplantation. Actuarial 1-, 2-, and 5-year survival was 86.2 +/- 9.1%. During the first year after transplantation, two deaths occurred--one at 41 days of putative vascular rejection and the second at 60 days of severe cellular rejection. All other patients are alive and functionally rehabilitated; the mean follow-up period has been 26.1 months (range, 2 to 89.6). CONCLUSION: Cardiac transplantation for patients with congenital heart disease can be accomplished with a low perioperative mortality and an excellent medium-term survival despite the challenges presented by the technical difficulties during invasive diagnostic procedures and at operation and the need for adherence to long-term multiple-drug therapy in this patient population.

Increase in total plasma homocysteine concentration after cardiac transplantation.

OBJECTIVE: To determine whether plasma homocysteine concentrations are increased in patients after cardiac transplantation. DESIGN: Total plasma homocysteine concentration was measured in 44 consecutive patients before and at 3, 6, and 12 months after orthotopic heart transplantation between June 1, 1988, and Oct. 15, 1992, and the data were analyzed statistically. RESULTS: Mean homocysteine concentrations (normal range, 4 to 17 mumol/L) increased 70% from 12.5 mumol/L before cardiac transplantation to 21.2 mumol/L (P < 0.002) 3 months after transplantation, at which time the concentrations were above normal in 14 of 26 patients (54%). Homocysteine concentrations remained elevated 6 and 12 months after transplantation (20.4 and 22.6 mumol/L, respectively) but did not increase further. Mean concentrations of plasma folic acid and vitamin B12, cofactors in homocysteine metabolism, decreased 20% and 49%, respectively, within 3 months after transplantation (11.6 to 9.3 micrograms/L [P = 0.04] and 584 to 295 ng/L [P = 0.01]). The mean glomerular filtration rate decreased 25% during this same interval (81 to 61 mL/min; P = 0.0001). Linear regression analysis revealed an association between the increase in homocysteine concentration and the folic acid concentration that approached statistical significance (P = 0.07); we found no statistically significant correlates of the increase in homocysteine concentration. CONCLUSION: The homocysteine concentration increases in most patients within 3 months after cardiac transplantation to levels previously associated with premature atherosclerotic coronary artery disease, and it remains increased for at least 1 year. Further investigation into the mechanism for the increase in homocysteine concentration and the relationship between homocysteine and coronary artery disease after transplantation is warranted.

Neuroendocrine and behavioral effects of high-dose anabolic steroid administration in male normal volunteers.

OBJECTIVE: Despite widespread abuse of anabolic-androgenic steroids (AAS), the endocrine effects of supraphysiologic doses of these compounds remain unclear. We administered the AAS methyltestosterone (MT) to 20 normal volunteers in an in-patient setting, examined its effects on levels of pituitary-gonadal, -thyroid, and -adrenal hormones, and examined potential relationships between endocrine changes and MT-induced psychological symptoms. METHOD: Subjects received MT (three days of 40 mg/day, then three days of 240 mg/day) or placebo in a fixed sequence with neither subjects nor raters aware of order. Samples were obtained at the ends of the baseline, high-dose MT and withdrawal phases. Potential relationships between hormonal changes and visual analog scale measured mood changes were examined. RESULTS: Significant decreases in plasma levels of gonadotropins, gonadal steroids, sex hormone binding globulin, free T3 and T4, and thyroid binding globulin (Bonferroni t, p<0.01 for each) were seen during high-dose MT; free thyroxine and TSH increased during high-dose MT, with TSH increases reaching significance during withdrawal. No significant changes in pituitary-adrenal hormones were observed. Changes in free thyroxine significantly correlated with changes in aggressiveness (anger, violent feelings, irritability) (r=0.5,p=0.02) and changes in total testosterone correlated significantly with changes in cognitive cluster symptoms (forgetfulness, distractibility) (r=0.52,p=0.02). Hormonal changes did not correlate with plasma MT levels. CONCLUSIONS: Acute high-dose MT administration acutely suppresses the reproductive axis and significantly impacts thyroid axis balance without a consistent effect on pituitary-adrenal hormones. Mood and behavioral effects observed during AAS use may in part reflect secondary hormonal changes.

Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls.

BACKGROUND: GABA receptor-modifying neurosteroids may play a role in premenstrual syndrome (PMS). The peripheral benzodiazepine receptor (PBR) both regulates the formation of neurosteroids and is, in animals, regulated by ovarian steroids. Alterations in PBR density have been observed in association with several psychiatric disorders. METHODS: We examined the effects of gonadal steroids on lymphocytic PBR density in nine women with prospectively confirmed PMS and nine controls. PBR densities were measured during three pharmacologically controlled conditions: gonadotropin releasing hormone agonist (Lupron)-induced hypogonadism, Lupron plus estradiol, and Lupron plus progesterone replacement. Blood samples were obtained after six weeks of Lupron alone and after 3-4 weeks of estradiol and progesterone replacement. RESULTS: No significant hormone state-related changes in PBR density were observed (ANOVA-R: phase-F(2,32)=1.5, P=0.2). Despite mood symptom development in the subjects with PMS, PBR density did not differ in women with PMS compared to controls across hormonal states (ANOVA-R: F(1,16)=0.6, P=0.4). CONCLUSIONS: PBR densities are not altered in women with PMS and are not changed significantly by selective gonadal steroid administration. Changes in PBR density would not appear to underlie the differential sensitivity to the mood destabilizing effects of ovarian steroids in PMS.

Histologic comparison of experimental coronary artery bypass grafts. Similarity of in situ and free internal mammary artery grafts.

This study compares patency and histologic structure of in situ internal mammary artery grafts, free internal mammary artery grafts, stripped, free internal mammary artery grafts, and stripped, free superficial femoral artery grafts (a muscular artery model) in a canine model of coronary artery bypass. Twenty-four adult mongrel dogs underwent bypass of the circumflex coronary artery with one of the above grafts. Three months postoperatively, graft patency was assessed by angiogram, and postmortem specimens were studied by intraluminal injection of a dilute barium solution proximal to the graft. Proximal, mid, and distal segments of each graft were examined microscopically. In situ internal mammary artery grafts and free internal mammary artery grafts were not significantly different in regard to patency, vascular wall cellular structure, or perfusion of the vasa vasorum. The stripped, free internal mammary artery group had a higher incidence of thrombosis, intimal thickening, and medial injury than the pedicled (in situ and free internal mammary artery) grafts. This difference may be due to early vascular wall ischemia as a result of poor early perfusion of the vasa vasorum. The stripped, free superficial femoral artery grafts were all patent, but all had adventitial injury.

Ischemia of the interventricular septum. A mechanism of right ventricular failure during mechanical left ventricular assist.

Right ventricular failure has been noted in up to 25% of patients requiring a left ventricular assist device. Altered septal motion or function is one proposed mechanism of right ventricular failure during left heart bypass. We studied the effect of regional ischemia and reperfusion of the interventricular septum on right ventricular function during complete left heart bypass. In six calves the septal perforating branches of the proximal left anterior descending coronary artery were isolated for intermittent occlusion. Complete left heart bypass was established with a Pierce-Donachy left ventricular assist device. Right and left ventricular function were studied with two-dimensional echocardiography and with intraventricular pressure monitors. Establishment of left heart bypass did not significantly affect right ventricular developed pressure, right ventricular end-diastolic area, or right ventricular fractional change in area. Left heart bypass significantly (p less than 0.001) decreased percent systolic septal wall thickening. Septal ischemia during left heart bypass resulted in a decrease in right ventricular developed pressure (p = 0.09), significant increase in right ventricular end-diastolic area (p = 0.002) and significant decrease in right ventricular fractional change in area (p less than 0.001), and a further decrease in interventricular septal wall thickening (p = 0.016). The interventricular septum became thin with flattening of its normal contour. Septal reperfusion resulted in right ventricular recovery with significant improvement in all factors (p less than 0.02). Similar results were documented during a second episode of septal ischemia with recovery after septal reperfusion. In some cases, septal ischemia may be an important factor in the development of right ventricular failure during left heart bypass.

Hemodilution and whole body oxygen balance during normothermic cardiopulmonary bypass in dogs.

OBJECTIVE: The purpose of this study was to determine the minimum hematocrit value that can support whole body oxygen consumption during normothermic cardiopulmonary bypass. The effect of hemodilution on peripheral resistance, whole body oxygen delivery, and oxygen consumption was determined over a range of hematocrit values. METHODS: Measurements were obtained during 38 degrees C cardiopulmonary bypass with progressive normovolemic hemodilution (hematocrit value 40% to 9%) in nine dogs. Dextran 70 (6%) was used as a diluent. Anesthesia consisted of high-dose fentanyl and midazolam. A mean arterial pressure of 60 mm Hg was maintained throughout cardiopulmonary bypass via increases in pump flow. RESULTS: Progressive hemodilution was associated with a decreasing total peripheral resistance. During normothermic cardiopulmonary bypass with a whole blood prime, the whole body oxygen consumption approximated values previously reported in dogs under nonbypass conditions. Oxygen delivery and whole body oxygen uptake were maintained between a hematocrit value of 39% and 25%. Significant decreases for both were seen when the hematocrit value was reduced to 18% and below. CONCLUSIONS: A hematocrit level greater than 18% was needed to maintain systemic oxygen delivery and consumption during warm cardiopulmonary bypass. The critical hematocrit value may be higher under bypass than nonbypass conditions because the flow increases that are practical during cardiopulmonary bypass do not approximate those seen in response to hemodilution of the intact circulation. Finally, the critical hematocrit value for the body may be higher than that required for the brain during warm cardiopulmonary bypass.

Transmission of invasive aspergillosis from a subclinically infected donor to three different organ transplant recipients.

OBJECTIVE: To describe a cluster of donor-transmitted cases of invasive aspergillosis. DESIGN: Case series of epidemiologically linked cases of invasive aspergillosis. SETTING: Two tertiary care centers with solid-organ transplant programs. PATIENTS: Two kidney recipients, one heart recipient, and the single donor. MEASUREMENTS: Routine clinical, microbiological, and pathologic investigation as dictated for patient care. Epidemiologic analysis to establish linkage among cases. RESULTS: Three allografts (two kidneys and a heart) from a single donor transmitted invasive aspergillosis to the recipients. Three weeks after transplantation, the two kidney recipients had fever and urine cultures positive for Aspergillus fumigatus. The infected kidneys had multiple Aspergillus abscesses and had to be removed to cure the patients. The heart recipient had a negative workup when a diagnosis of aspergillosis was made for the kidney recipients but presented three months later with aspergillus endocarditis with hematogenous spread to the eyes and to the skin. Treatment included eye surgery, aortic valve replacement, and antifungal therapy; control of infection ensued. The donor was intensely immunosuppressed (17 days post-liver transplantation with death from intracerebral bleeding) but had no clinical or autopsy evidence of aspergillosis. Donor tracheal secretions obtained at the time of organ harvest later grew A fumigatus. CONCLUSION: Expanded criteria for organ donation have to be balanced against infectious risk to organ recipients. A fumigatus can be transmitted from a subclinically infected donor to solid-organ transplant recipients.

A prospective, randomized comparison of cerebral venous oxygen saturation during normothermic and hypothermic cardiopulmonary bypass.

Recent reports have described cerebral venous oxygen desaturation during and after rewarming from hypothermic cardiopulmonary bypass. Additionally, patients undergoing normothermic cardiopulmonary bypass may be at higher risk for neurologic injury. This study was designed to determine whether patients undergoing normothermic cardiopulmonary bypass are at increased risk for sustained cerebral desaturation. Fifty-two patients undergoing first-time coronary artery bypass grafting were randomized to receive normothermic (37 degrees C, n = 26) or hypothermic (27 degrees C, n = 26) cardiopulmonary bypass. The anesthetic was standardized and alpha-stat pH management was used. A 4F oximetric catheter was placed in the jugular bulb and cerebral venous and radial arterial blood were sampled. Oxygen partial pressure and saturation were measured at six intervals from cerebral venous blood and from radial arterial blood. Patients receiving normothermic cardiopulmonary bypass had lesser values of oxygen partial pressure and saturation in cerebral venous blood than patients subjected to hypothermia during the first 40 minutes of bypass. Cerebral venous desaturation (oxygen saturation in cerebral venous blood of 50% or less) was observed in 54% of patients in the normothermic group and 12% of patients in the hypothermic group during cardiopulmonary bypass. In the normothermic group, cerebral desaturation occurred primarily in early bypass (14 of 26). The three episodes of desaturation in the hypothermic group occurred during rewarming. During cardiopulmonary bypass, the arteriovenous oxygen content difference was greater in the normothermic group than in that in the hypothermic group, suggesting higher oxygen consumption. Differences in glucose utilization during early cardiopulmonary bypass between the groups was also detected. One patient in the hypothermic group had an embolic stroke and subsequently died. There were no other perioperative strokes or deaths in the study population. The present study demonstrates that patients undergoing normothermic cardiopulmonary bypass are at greater risk for cerebral desaturation. Because it is a global assessment, cerebral venous oxygen saturation may be insensitive to focal ischemic events. It remains to be seen whether these differences in cerebral physiologic states translate into differences in clinical outcome.

Aortic valve replacement in patients aged eighty years and older: early and long-term results.

UNLABELLED: We have studied 322 patients, 80 years of age or older, who underwent aortic valve replacement between June 1971 and December 1992. Two hundred six patients (64%) have had surgery since the end of 1985. Their mean age was 82.7 years (range 80 to 92 years). One hundred seventy-one (53%) were male and most (86%) were in New York Heart Association class III-IV. Fifty-seven patients (18%) required admission to the coronary care unit before the operation. One hundred seventy-nine patients (56%) underwent an urgent or emergency operation. Known cerebrovascular disease was present in 77 (24% of patients), aortic stenosis in 79%, aortic incompetence in 9%, and combined stenosis and incompetence in 12%. Associated procedures included bypass grafting in 139 (43%), mitral valve replacement/repair in 20 (6%), tricuspid valve repair in 6 (2%), and aortic annular enlargement in 38 (12%). Thirty patients (9.3%) were undergoing reoperation. Hospital mortality was 44 of 322 (13.7%). The median hospital stay was 11 days. On univariate analysis, significant predictors of hospital mortality were female sex, preoperative rest pain, New York Heart Association class III-IV, admission to the coronary care unit, heart failure, mitral valve disease, emergency/urgent operation, chronic obstructive pulmonary disease, bypass grafting, valve size, peripheral vascular disease, and ejection fraction less than 0.35. On multivariate analysis the most important independent predictors of operative mortality were female gender (p = 0.0001), renal impairment (p = 0.001), bypass grafting (p = 0.005), ejection fraction less than 0.35 (p = 0.01), and chronic obstructive pulmonary disease (p = 0.028). Age and year of operation did not influence mortality. Five-year survivals for all patients and for operative survivors were 60.2% +/- 3.2% and 70.3% +/- 3.4%, respectively. On univariate analysis, factors that adversely affected long-term survival were coronary bypass grafting (p = 0.007), more than two comorbidities (p = 0.02), male gender (p = 0.04), and ejection fraction less than 0.35 (p = 0.04). On multivariate analysis, no factor was consistently significant for long-term survival. At most recent clinical follow-up 85% were angina free and 82% were in class I-II. At least 92% of patients, both at 1 year and at most recent clinical follow-up, believed they had significantly benefited from the operation: CONCLUSION: Risk factors for aortic valve replacement in octogenarians include female gender, unstable symptoms, poor ejection fraction, renal impairment, and bypass grafting. However, despite a hospital mortality higher than that reported for younger patients, the outlook for operative survivors is excellent, with good relief of symptoms and an expected survival normal for this particular age group. If possible, aortic valve replacement should be done before development of unstable symptoms.