Purification of cardiac myocytes from human heart biopsies for gene expression analysis.

The collection of gene expression data from human heart biopsies is important for understanding the cellular mechanisms of arrhythmias and diseases such as cardiac hypertrophy and heart failure. Many clinical and basic research laboratories conduct gene expression analysis using RNA from whole cardiac biopsies. This allows for the analysis of global changes in gene expression in areas of the heart, while eliminating the need for more complex and technically difficult single-cell isolation procedures (such as flow cytometry, laser capture microdissection, etc.) that require expensive equipment and specialized training. The abundance of fibroblasts and other cell types in whole biopsies, however, can complicate gene expression analysis and the interpretation of results. Therefore, we have designed a technique to quickly and easily purify cardiac myocytes from whole cardiac biopsies for RNA extraction. Human heart tissue samples were collected, and our purification method was compared with the standard nonpurification method. Cell imaging using acridine orange staining of the purified sample demonstrated that >98% of total RNA was contained within identifiable cardiac myocytes. Real-time RT-PCR was performed comparing nonpurified and purified samples for the expression of troponin T (myocyte marker), vimentin (fibroblast marker), and alpha-smooth muscle actin (smooth muscle marker). Troponin T expression was significantly increased, and vimentin and alpha-smooth muscle actin were significantly decreased in the purified sample (n = 8; P < 0.05). Extracted RNA was analyzed during each step of the purification, and no significant degradation occurred. These results demonstrate that this isolation method yields a more purified cardiac myocyte RNA sample suitable for downstream applications, such as real-time RT-PCR, and allows for more accurate gene expression changes in cardiac myocytes from heart biopsies.

Building a clinical program in a single institution.

A successful clinical program within either a single institution or a multi-institution complex requires the recruitment and retention of excellent faculty, a strong residency program, a successful, recognized research program, and leaders with administrative, organizational, and leadership skills.

Management of the atherosclerotic ascending aorta with endoaortic occlusion.

Application of an external cross-clamp to an atherosclerotic ascending aorta increases the risk of an embolic event and traumatic injury of the aorta. Currently, there are limited management options in these patients when the clinical situation requires cardiac arrest during an operation. We present our approach to these patients using the Heartport Endoaortic Clamp (Heartport, Redwood City, CA).

Aortic valve replacement in the elderly. Risk factors and long-term results.

OBJECTIVE: The current study was undertaken to determine long-term results of aortic valve replacement (AVR) in the elderly, to ascertain predictors of poor outcome, and to assess quality of life. SUMMARY BACKGROUND DATA: Aortic valve replacement is the procedure of choice for elderly patients with aortic valve disease. The number of patients aged 70 and older requiring AVR continues to increase. However, controversy exists as to whether surgery devoted to this subset reflect a cost-effective approach to attaining a meaningful quality of life. METHODS: This study reviews data on 247 patients aged 70 to 89 years who underwent isolated AVR between 1980 and 1995; there were 126 men (51%) and 121 women (49%). Follow-up was 97% complete (239/247 patients) for a total of 974.9 patient-years. Mean age was 76.2 +/- 4.8 years. Operative mortality and actuarial survival were determined. Patient age, gender, symptoms, associated diseases, prior conditions, New York Health Association class congestive heart failure, native valve disease, prosthetic valve type, preoperative catheterization data, and early postoperative conditions were analyzed as possible predictors of outcome. Functional recovery was evaluated using the SF-36 quality assessment tool. RESULTS: Operative mortality was 6.1% (15/247). Multivariate logistic regression showed that poor left ventricular function and preoperative pacemaker insertion were independent predictors of early mortality. After surgery, infection was predictive of early mortality. Overall actuarial survival at 1, 5, and 10 years was 89.5 +/- 2% (198 patients at risk), 69.3 +/- 3.4% (89 patients at risk), and 41.2 +/- 6% (13 patients at risk), respectively. Cox proportional hazards model showed that chronic obstructive pulmonary disease and urgency of operation were independent predictors of poor long-term survival. Postoperative renal failure also was predictive of poor outcome. Using the SF-36 quality assessment tool, elderly patients who underwent AVR scored comparably to their age-matched population norms in seven of eight dimensions of overall health. The exception is mental health. CONCLUSIONS: Aortic valve replacement in the elderly can be performed with acceptable mortality. Significant preoperative risk factors for early mortality include poor left ventricular function and preoperative pacemaker insertion. Predictors of late mortality include chronic obstructive pulmonary disease and urgency of operation. These results stress the importance of operating on the elderly with aortic valve disease; both long-term survival and functional recovery are excellent.

High dose neostigmine treatment of malignant sinus tachycardia.

Sinus tachycardia caused by circulating catecholamines in the setting of congestive heart failure may impair systemic perfusion because of decreased diastolic filling time. We report the case of a patient with Wolff-Parkinson-White syndrome with angina and cardiogenic shock who improved dramatically following administration of neostigmine. Cardiac output, blood pressure, and stroke volume increased as heart rate was reduced. A previous attempt at heart rate control, in the same patient, using a low dose beta-antagonist, precipitated hemodynamic collapse. The remarkable recovery of our patient suggests that acetylcholinesterase inhibitors may warrant further investigation in patients with severe sinus tachycardia.

Cognitive outcome after coronary artery bypass: a one-year prospective study.

BACKGROUND: Cognitive deficits have been reported in patients after coronary artery bypass grafting, but the incidence of these deficits varies widely. We studied prospectively the incidence of cognitive change and whether the changes persisted over time. METHODS: Cognitive testing was done preoperatively and 1 month and 1 year postoperatively in 127 patients undergoing coronary artery bypass grafting. Tests were grouped into eight cognitive domains. A change of 0.5 standard deviation or more at 1 month and 1 year from patient's preoperative Z score was the outcome measure. RESULTS: We identified four main outcomes for each cognitive domain: no decline; decline and improvement; persistent decline; and late decline. Only 12% of patients showed no decline across all domains tested; 82% to 90% of patients had no decline in visual memory, psychomotor speed, motor speed, and executive function; 21% and 26% had decline and improvement in verbal memory and language; approximately 10% had persistent decline in the domains of verbal memory, visual memory, attention, and visuoconstruction; and 24% had late decline (between 1 month and 1 year) in visuoconstruction. CONCLUSIONS: This study establishes that the incidence of cognitive decline varies according to the cognitive domain studied and that some patients have persistent and late cognitive changes in specific domains after coronary artery bypass grafting.

Predictors of stroke risk in coronary artery bypass patients.

BACKGROUND: Stroke occurs after coronary artery bypass grafting with an incidence ranging between 0.8% and 5.2%. To identify factors associated with stroke, we prospectively examined a study cohort and tested findings in an independent validation sample. METHODS: The study cohort comprised 456 patients undergoing coronary artery bypass grafting only, and the validation sample comprised 1,298 patients. Stroke was detected postoperatively by the study team and confirmed by neurologic consultation and computed tomographic scanning. RESULTS: Five factors taken together were correlated with stroke: previous stroke, presence of carotid bruit, history of hypertension, increasing age, and history of diabetes mellitus. The only significant intraoperative factor was cardiopulmonary bypass time. Probabilities were calculated, and patients were placed into low, medium, and high stroke-risk groups. In the validation sample, this model was able to rank the majority of patients with stroke into the high-risk group. CONCLUSIONS: These five factors taken together can identify the risk of stroke in patients having coronary artery bypass grafting. Recognition of the high-risk group will aid studies on the mechanism and prevention of stroke by modification of surgical procedures or pharmacologic intervention.

Bioprosthetic versus mechanical prostheses for aortic valve replacement in the elderly.

BACKGROUND: Many centers advocate bioprosthetic valves in the elderly to avoid anticoagulation, in particular when patient survival is less than the expected valve durability. Because expected survival in the elderly is increasing and age-specific risk of anticoagulation in the elderly is not known, we examined valve- and anticoagulation-related morbidity in elderly patients after aortic valve replacement (AVR) with bioprostheses or mechanical prostheses. METHODS AND RESULTS: Between January 1980 and June 1994, 211 patients age > or = 70 years underwent isolated AVR; there were 109 men (52%) and 102 women (48%). Mean age was 75.9 +/- 4.8 years. Aortic stenosis was present in 194 (92%) patients. Bioprostheses were used in 145 (69%) and mechanical prostheses were used in 66 (31%). Chronic anticoagulation was maintained in all patients with a mechanical valve and in 18 patients (12%) with a bioprosthetic valve. Follow-up data were obtained for 98% (194 of 197) of hospital survivors at a mean follow-up of 3.8 years. Operative mortality was 6.6%; survival at 3 and 5 years was 75.3 +/- 3% and 64.6 +/- 4%, respectively. There was no significant difference in operative or late mortality between patient groups. Rates of freedom from thromboembolic events, endocarditis and anticoagulant-related hemorrhage for bioprosthetic and mechanical valve patients were similar. Prosthetic failure was identified in three bioprosthetic valves (2%); furthermore, the 4 patients in the series who required reoperation had received bioprostheses at the first operation. CONCLUSIONS: In conclusion, (1) elderly patients undergoing isolated AVR can be managed with either mechanical or bioprosthetic valves with similar early and late risk, as long as there are no specific contraindications to anticoagulation; (2) anticoagulation-related risk of hemorrhage is low in this group of elderly patients; and (3) the low but significant risk of reoperation following the use of bioprostheses suggests that mechanical valves may be underused in the elderly.

Cardiopulmonary bypass as an adjunct to pulmonary surgery.

Although performance of concomitant open heart and pulmonary operations has been described, there is general reluctance to perform pulmonary procedures in patients receiving cardiopulmonary bypass (CPB). Reasons for this include fear of excess bleeding caused by systemic heparinization, limited exposure afforded by median sternolomy, and alterations in the immune system caused by CPB that might lead to dissemination of lung cancer or infection. We have used CPB to facilitate operations on the lung in four patients who did not require concomitant cardiac surgery. In each case, lesions involving central pulmonary vessels precluded safe operation by conventional techniques. There were no complications related to the use of CPB. We believe that CPB can be a valuable adjunct in the surgical treatment of selected tumors and vascular malformations that involve large or central pulmonary vessels.

Valve replacement in patients with endocarditis and acute neurologic deficit.

BACKGROUND: Acute neurologic deficits occur in up to 40% of patients with left heart endocarditis. Appropriate evaluation and management of patients with acute neurologic dysfunction who require valve operations for endocarditis remain controversial. This retrospective review was undertaken to develop recommendations for the evaluation and treatment of these challenging patients. METHODS: From 1983 to 1995, 247 patients underwent operations for left heart native valve endocarditis at the Johns Hopkins Hospital. From a review of medical and pathology records, 34 patients (14%) with preoperative neurologic deficits were identified. Data on these 34 patients were recorded and analyzed. RESULTS: Causes of neurologic dysfunction included embolic cerebrovascular accident (n = 23, 68%), embolic cerebrovascular accident with hemorrhage (n = 4, 12%), ruptured mycotic aneurysm (n = 3, 9%), transient ischemic attack (n = 2, 6%), and meningitis (n = 2, 6%). Preoperative diagnostic studies included computed tomography (32 patients), magnetic resonance imaging (11 patients), cerebral angiogram (14 patients), and lumbar puncture (2 patients). Computed tomography demonstrated structural lesions in 29 of 32 patients; in only 1 patient did magnetic resonance imaging reveal a lesion not already seen on computed tomography. Of 14 patients having cerebral angiograms, 7 had a mycotic aneurysm. Three mycotic aneurysms had ruptured, and these were clipped before cardiac operations. The mean interval from onset of neurologic deficit to cardiac operation was 22.2 +/- 2.8 days for all patients and 22.1 +/- 3.0 days for those with embolic cerebrovascular accident. The hospital mortality rate was 6%. New or worse neurologic deficits occurred in 2 patients (6%). CONCLUSIONS: Neurologic deficits are common in patients with endocarditis referred for cardiac operations. Despite substantial preoperative morbidity, most of these patients do well if the operation can be delayed for 2 to 3 weeks. Computed tomography scan is the preoperative imaging technique of choice, as routine magnetic resonance imaging and cerebral angiogram are unrewarding. Cerebral angiogram is indicated only if computed tomography reveals hemorrhage.

Infantile hypertrophic pyloric stenosis: long-term audit from a general surgical unit.

This article describes a 22 year experience of a general surgical unit in the treatment of infantile hypertrophic pyloric stenosis (IHPS). The hospital course of 229 IHPS patients is reviewed. The male:female ratio was 3.6:1, median age 6 weeks (range 2-26 weeks) with a positive family history in 8.3%. The diagnosis of IHPS was established clinically by palpation of a "pyloric tumour" during a pre operative test meal/clinical examination in 92.6%; in the remainder, the diagnosis was made radiologically. Ramstedt's pyloromyotomy was performed within 5 days of admission in 74% of patients and within 10 days of admission in 89%. The median post-operative hospital stay was 10 days (range 3-60 days). Wound morbidity occurred in 10.0% wound infection (7.3%) and wound dehiscence (2.6%). However, wound morbidity was reduced in the second half of the series, partly by greater utililisation of non-absorbable suture in place of chromic catgut for wound closure. Mucosal penetration was suspected in 14.8% of cases. Repeat pyloromyotomy was necessary in 1.3%. One baby died (0.4%)- this was in the early part of the series and was directly attributable to fluid and electrolyte disorder. We conclude that Ramstedt's pyloromyotomy for infantile hypertrophic pyloric stenosis can be performed with acceptable morbidity and minimal mortality in a general surgical unit.

Neurologic injury in cardiac surgical patients with a history of stroke.

BACKGROUND: Controversy still exists as to whether patients with previous stroke are at increased risk for neurologic complications after heart operations. METHODS: We performed a prospective analysis of 1,000 consecutive patients undergoing cardiac operations requiring cardiopulmonary bypass, without hypothermic circulatory arrest. Of the 1,000 patients, 71 had previously documented stroke (study group); 2 control patients with no history of stroke were selected for each of these patients (control group, n = 142). There were no significant differences between the study and control patients with respect to established risk factors for neurologic complications. RESULTS: Compared with controls, study patients took longer to awaken (12.6 +/- 10.9 versus 3.5 +/- 2.1 hours; p < 0.0001) and longer to extubate (29.5 +/- 29.3 versus 9.1 +/- 5.2 hours; p < 0.001), and had a greater incidence of reintubation (7 of 71, 9.9% versus 2 of 142, 1.4%; p < 0.01) and postoperative confusion (26 of 71, 36.6% versus 7 of 142, 4.9%; p < 0.001). There was a higher incidence of focal neurologic deficit among study patients (31 of 71, 43.7% versus 2 of 142, 1.4%; p < 0.001). These deficits included new stroke (6 of 71, 8.5%) as well as the reappearance of previous deficits (19 of 71, 26.8%) or worsening of previous deficits (6 of 71, 8.5%), without new abnormalities on head computed tomography or magnetic resonance imaging. Study patients with neurologic deficit had longer cardiopulmonary bypass times than did study patients without deficit (146 +/- 48.5 versus 110 +/- 43.3 minutes; p < 0.001). The 30-day mortality rate was greater in study patients than in controls (5 of 71, 7% versus 1 of 142, 0.7%; p < 0.02), with four deaths among the 6 study patients with a new stroke (66.7%). CONCLUSION: This analysis identifies a group of patients at high risk for neurologic sequelae and confirms the vulnerability of the previously injured brain to cardiopulmonary bypass, as evidenced by reappearance or exacerbation of focal deficits in such patients.

Thalidomide as replacement for steroids in immunosuppression after lung transplantation.

Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation.

Neutrophils are important mediators of reperfusion injury, and suppression of neutrophil function or numbers can reduce reperfusion injury and improve long-term organ preservation in transplantation. NPC 15669, a leumedin, is a novel compound that prevents recruitment of neutrophils at inflammatory foci by inhibiting CD11b/CD18 adhesion molecule expression. NPC 15669 was used to inhibit neutrophil adhesion during reperfusion of isolated rabbit lungs after 12 and 24 hours of cold storage. Lungs (New Zealand White male rabbits, 2 to 3 kg) were flushed with 4 degrees C Euro-Collins (EC) solution, harvested en bloc, stored under various study conditions, and reperfused for 3 hours with fresh whole blood at 37 degrees C in an isolated perfusion system at constant flow and an inspired oxygen fraction of 1. Four groups (n = 6 each) were studied. Group I underwent immediate whole blood reperfusion. Group II were stored for 12 hours in 4 degrees C EC solution before reperfusion. Group III were stored for 12 hours in 4 degrees C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg whole body weight). Group IV were stored for 24 hours in 4 degrees C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg). Pulmonary artery and peak airway pressures were significantly lower and compliance higher in groups III and IV lungs after 3 hours of reperfusion (p < 0.05) compared with group I. Group I and III lungs had significantly less edema than group II (p < 0.05). The arterial partial pressure of oxygen was similar in all stored groups (II to IV).(ABSTRACT TRUNCATED AT 250 WORDS)

Humoral pulmonary vasoregulation in conscious dogs after left lung autotransplantation.

We investigated the roles of cyclooxygenase metabolites, arginine vasopressin (AVP) and angiotensin II (ANG II), as mediators of the chronic increase in pulmonary vascular resistance associated with left lung autotransplantation (LLA) in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs 2- to 5-wk post-LLA and in sham-operated control conscious dogs. LLA resulted in a marked shift (P < 0.01) in the LP-Q relationship as reflected by an approximate doubling of the pulmonary vascular pressure gradient at each common value of left pulmonary blood flow compared with the control group. Cyclooxygenase pathway inhibition (indomethacin) and AVP V1-receptor block had no effect on the LP-Q relationship post-LLA. Angiotensin-converting enzyme inhibition (captopril) also failed to reverse the increase in pulmonary vascular resistance post-LLA. Because captopril has the dual effect of inhibiting the production of ANG II and the degradation of bradykinin, additional studies utilizing a selective ANG II receptor antagonist were performed. ANG II receptor block (saralasin) significantly altered the LP-Q relationship post-LLA to cause active pulmonary vasodilation (P < 0.01). Thus, the chronic increase in pulmonary vascular resistance post-LLA is not mediated by metabolites of the cyclooxygenase pathway or AVP V1-receptor activation. A significant component of the increase in pulmonary vascular resistance resulting from LLA is mediated by ANG II. The differential responses to captopril and saralasin may imply a pulmonary vasoregulatory role for bradykinin post-LLA.

Neutrophil adhesion molecule expression during cardiopulmonary bypass with bubble and membrane oxygenators.

The neutrophil-mediated tissue injury associated with cardiopulmonary bypass (CPB) is thought to require the interaction of specific neutrophil and endothelial adhesion molecules. In this study, the effects of CPB on the expression of neutrophil CD11b and CD18 (the components of the Mac-1 adhesion molecule) were examined; the effects of membrane versus bubble oxygenators on the expression of neutrophil CD11b and CD18 were compared; and the plasma levels of the intercellular adhesion molecule-1 (cICAM-1), an inducible endothelial adhesion molecule, were measured. In addition, the time courses of complement activation and neutrophil granule release were measured to determine their temporal relationship to the expression of the neutrophil adhesion molecule. Fifteen adult patients underwent procedures requiring cardiopulmonary bypass; hollow-fiber membrane oxygenators were used in 8 (group M) and bubble oxygenators were used in 7 (group B). Blood samples were drawn before, during, and after CPB for determination of the expression of neutrophil CD11b and CD18 (immunofluorescent flow cytometry), and the plasma cICAM-1, elastase, lactoferrin (enzyme-linked immunoabsorbent assay), and plasma C3a (radioimmunoassay) levels. CPB caused an immediate and sustained increase in the neutrophil CD11b and CD18 expression in both groups; after 60 minutes of CPB, CD11b expression had increased by 116.9% +/- 19.1% in group B and by 79.3% +/- 8.5% in group M (p = 0.78). Over the same period, CD18 expression increased by 97.2% +/- 17.9% in group B and by 72.4% +/- 16.8% in group M (p = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin-coated bypass circuits reduce pulmonary injury.

Heparin coating of the extracorporeal circuit not only reduces heparin requirements during cardiac operations but also may reduce organ injury associated with cardiopulmonary bypass (CPB). To examine this possibility, pulmonary injury and neutrophil adhesion molecule expression after CPB were studied in pigs undergoing CPB with a standard extracorporeal circuit (group S, n = 6) or a heparin-coated CPB circuit (Carmeda BioActive Surface) (group HC, n = 6). Pigs received heparin sodium (300 U/kg intravenously) and then underwent 90 minutes of hypothermic (28 degrees C) CPB using membrane oxygenators, followed by 2 hours of observation. Blood samples were obtained for determination of neutrophil number and expression of the neutrophil adhesion molecule subunit CD18 (by immunofluorescence flow cytometry). The CPB-associated injury was less in group HC. Two hours after CPB, the arterial oxygen tension group was higher in group HC (597.2 +/- 31.2 versus 220.5 +/- 42.3 mm Hg; p < 0.0001), the pulmonary vascular resistance was lower in these animals (408.6 +/- 69.4 versus 1,159.8 +/- 202.4 dyne.s.cm-5; p = 0.02), and the static compliance was higher in group HC (66.4 +/- 5.4 versus 39.8 +/- 5.8 mL/mm Hg; p = 0.004). After 60 minutes of CPB, both groups had similar increases in expression of the neutrophil adhesion molecule subunit CD18 (29.4% +/- 19.5% versus 26.0% +/- 24.4%, group S and group HC, respectively) and similar decreases in neutrophil counts (6,056 +/- 1,285 to 2,453 +/- 979 cells/microL versus 6,010 +/- 1,748 to 3,197 +/- 1,225 cells/microL, group S and group HC, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Centrifugal ventricular assist device for support of the failing heart after cardiac surgery.

OBJECTIVE: To determine the morbidity and mortality associated with use of centrifugal ventricular assist devices for postcardiotomy cardiogenic shock and to determine factors that might influence outcome and thus, aid in patient selection. DESIGN: A retrospective study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: During a 6-yr period, a total of 7,385 adult patients underwent cardiac operations requiring cardiopulmonary bypass. Myocardial protection consisted of single-dose cold crystalloid cardioplegia and continuous topical hypothermia by saline lavage. A total of 72 (1%) patients developed postcardiotomy cardiogenic shock. Of 72 patients, 28 met the institutional criteria and were placed on centrifugal ventricular assist devices. INTERVENTIONS: Twenty-eight adult patients with postcardiotomy cardiogenic shock were supported with centrifugal ventricular assist devices. MEASUREMENTS AND MAIN RESULTS: A total of 15 patients received left ventricular assist devices, five received right ventricular assist devices, and eight received both right and left ventricular assist devices. Mean age of ventricular assistance patients was 50.8 +/- 12.9 yrs (range 22 to 72), and mean duration of ventricular assistance was 2.8 +/- 2.5 days (range 4 hrs to 10 days; median 2 days). Twenty-five complications occurred in 16 patients and included bleeding (13), tamponade (2), systemic embolism (6), seizures (2), and sepsis (2). Nine patients required reexploration for bleeding or tamponade. Nine (32%) of 28 patients were discharged from the hospital. Ventricular assistance for cardiac failure after transplantation was associated with improved survival (p < .10), while age > 50 yrs and postoperative tamponade each showed trends toward association with mortality (p = .10). Survival was not predicted by gender, weight, time on cardiopulmonary bypass, aortic cross-clamp time, urgency of operation, or preoperative congestive heart failure. At 27 +/- 20 months follow-up, all survivors were alive and New York Heart Association functional class I or II. CONCLUSIONS: These results document a low incidence of ventricular assist device use in a surgical practice that employs a relatively simple method of myocardial protection. When postcardiotomy ventricular assistance was necessary, a centrifugal pump was used and successful outcome and satisfactory long-term results were possible in nearly one third of patients. Ventricular assistance for cardiac failure after transplantation was associated with improved survival. Older age is a relative contraindication to mechanical ventricular assistance.

Pulmonary vascular beta-adrenoreceptor activity in conscious dogs after left lung autotransplantation.

Our objective was to determine whether chronic denervation associated with left lung autotransplantation (LLA) results in an alteration in sympathetic beta-adrenoreceptor regulation of the pulmonary circulation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 2-4 wk post-LLA and in sham-operated control conscious dogs. We tested the hypothesis that endogenous sympathetic beta-adrenoreceptor activation via circulating catecholamines acted to attenuate the chronic increase in pulmonary vascular resistance post-LLA. Administration of the sympathetic beta-adrenoreceptor antagonist propranolol had no significant effect on the LPQ relationship post-LLA. We also tested the hypothesis that pulmonary vascular reactivity to sympathetic beta-adrenoreceptor activation would be increased post-LLA. The thromboxane analogue U-46619 was used to acutely preconstrict (P < 0.01) the pulmonary circulation in control dogs; this preconstriction shifted the LPQ relationship to the same position measured post-LLA. Under these conditions, cumulative doses of the beta-adrenoreceptor agonist isoproterenol caused pulmonary vasodilation (P < 0.01) in the control group but had no effect post-LLA. However, after acute preconstriction with U-46619, the pulmonary vasodilator response (P < 0.01) to isoproterenol post-LLA was not significantly different from that in the control group. These differential responses to isoproterenol with and without acute preconstriction indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is mediated by passive nonvasoactive mechanisms. Moreover, sympathetic beta-adrenoreceptor reactivity of the pulmonary circulation is not enhanced by chronic denervation resulting from the LLA procedure.

Superior cerebral protection with profound hypothermia during circulatory arrest.

The optimal temperature for cerebral protection during hypothermic circulatory arrest is not known. This study was undertaken to test the hypothesis that deeper levels of cerebral hypothermia (< 10 degrees C) confer better protection against neurologic injury during prolonged hypothermic circulatory arrest ("colder is better"). Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass via femoral artery and femoral/external jugular vein. Using surface and core cooling, tympanic membrane temperature was lowered to 18 degrees to 20 degrees C (deep hypothermia, n = 6) or 5 degrees to 7 degrees C (profound hypothermia, n = 6). After 2 hours of hypothermic circulatory arrest, animals were rewarmed to 35 degrees to 37 degrees C on cardiopulmonary bypass. All were mechanically ventilated and monitored in an intensive care unit setting for 20 hours. Neurologic assessment was performed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0% to 100%, where 0 = normal and 100% = brain dead. After 72 hours, animals were sacrificed and examined histologically for neurologic injury. Histologic injury scores were assigned to each animal (range, 0 [normal] to 100 [severe injury]). At the end of the observation period, profoundly hypothermic animals had better neurologic function (neurodeficit score, 5.7% +/- 4.0%) compared with deeply hypothermic animals (neurodeficit score, 41% +/- 9.3%; p < 0.006). Every animal had histologic evidence of neurologic injury, but profoundly hypothermic animals had significantly less injury (histologic injury score, 19.2 +/- 1.2 versus 48.3 +/- 1.5; p < 0.0001).