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A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was successfully treated by mechanical off loading of the left ventricle. A nonpulsatile left-heart bypass was undertaken with an implantable centrifugal blood pump. Careful weaning resulted in device removal on the seventh day. Left and right ventricular function is sustained at 7 months. Widespread application of this method depends on the availability of an inexpensive user friendly blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.

Background: The AB-180 circulatory support system is a small, durable, efficient centrifugal pump with low thrombogenic potential. The device was designed to provide a fully implantable, left ventricular assist system for short-term support to address the issues of systemic anticoagulation, thrombus formation, infection, and cost., Methods: Extensive bench and animal studies were performed to validate the mechanical integrity of the device and its functionality as an implant., Results: These studies demonstrated anticoagulation requirements, established operating guidelines, incorporated safety systems, and demonstrated safety and efficacy., Conclusions: The AB-180 fulfills the stated goals on initial evaluation. A phase I human trial is underway.

Background: The Society of Thoracic Surgeons National Database Committee is committed to risk stratification and assessment as integral elements in the practice of cardiac operations. The National Cardiac Surgery Database was created to analyze data from subscribing institutions across the country. We analyzed the database for valve replacement procedures with and without coronary artery bypass grafting to determine trends in risk stratification., Methods: The database contains complete records of 86,580 patients who had valve replacement procedures at the participating institutions between 1986 and 1995, inclusive. The 1995 harvest of data was conducted in late 1996 and available for evaluation in 1997. These records were used to conduct an in-depth analysis of risk factors associated with valve replacement and to provide prediction of operative death by using regression analysis. Regression models were made for six subgroups., Results: Adverse patient risk factors, including diabetes, hypertension and reoperation, but not ventricular function, increased over time. There were trends with regard to increasing age of the various population subsets. The types of prostheses used remained similar over time, with more mechanical prostheses than bioprostheses used for both aortic and mitral valve replacement. There was a trend toward increased use of bioprostheses in aortic replacements and decreased use in mitral replacements between 1991 and 1995 than between 1986 and 1990. The mortality rate was determined by patient subset for primary operation and reoperation and by urgency status. The modeling showed that the predicted and observed mortality correlated for all age groups and within patient subsets., Conclusions: Risk modeling is a valuable tool for predicting the probability of operative death in any individual patient. This large, multiinstitutional database is capable of determining modern operative risk and should provide standards for acceptable care. The study illustrates the importance of risk stratification for early death both for the patient and the surgeon.

Various approaches to the calculation of medical risk are reviewed, including univariate analysis, additive methods, use of Bayes' theorem by The Society of Thoracic Surgeons, logistic regression, and neural networks. Strengths and weaknesses of the various approaches are evaluated. The use and importance of observed/expected ratios, the C statistic, and receiver operating curves are discussed. Specific requirements for the building of useful risk-calculation models are discussed, including the importance of the model set/test set method and the role of both numbers of patients and time frames in model building.

In summary, the National Database Committee's Audit and Validation Subcommittee is working to maximize the data completeness and quality of the STS National Database. Toward this end, we welcome your suggestions for improvement.

At the request of the Councils of The Society of Thoracic Surgeons (STS) and The American Association for Thoracic Surgery (AATS) the Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity "revisited" the "Guidelines" published in September 1988 [1-3]. The purpose of the review was to update and clarify definitions within the guidelines and to consider recommendations made by others [4, 5]. The variety of cardiac valvular procedures has expanded since 1988; therefore, in this document the term "operated valve" indicates prosthetic and bioprosthetic heart valves of all types: operated or repaired native valves and allograft and autograft valves. The term "operated valve" includes any cardiac valve altered by a surgeon during an operation. Much morbidity and mortality is a direct consequence of the interaction between the patient and operated valve(s), although patient variables (e.g., age, degree of coronary arterial disease, follow-up care) may be more responsible for outcomes than an operated valve. However, no set of guidelines can identify all possible patient factors that may affect morbidity and mortality. General agreement regarding the following definitions of terms and suggestions for reporting data do not preclude more detailed analyses or constructive recommendations and investigators are encouraged to identify relevant patient factors in addition to factors related to operated valves.

Background: In 1991, Allegheny General Hospital and Allegheny-Singer Research Institute purchased a centrifugal pump, then a 2-year-old technology, from Medtronic Bio-Medicus, as part of its research program for novel treatments of acute and chronic heart failure. During a 4-year development program, we then established and met goals of durability, performance, thromboresistance, and low cost., Methods: In vitro testing involved extensive hydraulic characterizations using Penn State mock loops. Calorimetry was used to determine efficiency. Durability studies used heated (37 degrees C) seawater for 28 to 45 days. In vivo studies used 46 sheep to test performance and engineering changes and to determine myocardial oxygen consumption, thromboresistance, and long-term durability. A left atrium-to-aorta circuit was used in all., Results: Hydraulic testing showed no preload sensitivity but moderate afterload sensitivity at all impeller speeds (2,000 to 6,000 rpm). The heat load was low, and overall efficiency was 13% to 15%. Bench durability studies showed no electrical malfunction of the stator or console without degradation of the biomaterials used. Acute in vitro studies showed a near-linear relationship of myocardial oxygen consumption and left ventricular stroke work, pump flow, and pump speed. At speeds of 2 to 3 L/min (50% bypass), left ventricular stroke work and myocardial oxygen consumption were decreased approximately 50%. Additionally, 5 animals have had implants for 28 to 154 days with no macroemboli or microemboli detected in any animal. Hematologic and biochemical studies became normal 3 to 7 days after implantation. Hemolysis was low at less than 10 mg/dL. Clinical costs of the device are estimated to be 80% less than those of currently available devices., Conclusions: We conclude that an old technology has been made into new technology by application of sound engineering design principles, microchips, and new biomaterials. Qualifying trails for a Food and Drug Agency investigational device exemption application are in progress.

New volume requirements for coronary artery bypass grafting are being imposed on cardiac surgeons by hospitals, managed care groups, and others. The rationale for this is unclear. The available literature as well as additional sources relating volume and outcomes in cardiac surgery were extensively reviewed and reexamined. There are no data to conclusively indicate that outcomes of cardiac operations are related to a specific minimum number of cases performed annually by a cardiac surgeon. Each cardiothoracic surgeon should participate in a national database that permits comparison of his or her outcomes on a risk-adjusted basis with other surgeons. Until conclusive data become available that link volume to outcome, volume should not be used as a criterion for credentialing of cardiac surgeons by hospitals, managed care groups, or others. Instead, each surgeon should be evaluated on his or her individual results.

Background: Recent changes in health care financing have raised the specter of operation-specific, volume credentialing for cardiac surgeons. To meet this challenge, the leadership of The Society of Thoracic Surgeons formed an Ad Hoc Committee to study the question of the relationship of case volume to outcome. One product of the committee's work in this analysis of data from The Society of Thoracic Surgery National Cardiac Database., Methods: We examined data for all types of coronary artery bypass graft-only operations (n = 124,793) from more than 1,200 surgeons working in more than 600 hospitals for the years 1991 through 1993. All in-hospital and 30-day out-of-hospital mortality, both observed and expected as predicted by The Society of Thoracic Surgeons risk stratification method, was plotted against annualized group practice volume. Both patient-based and practice-based sampling techniques were used., Results: The data show that observed mortality ranged from 2.0% to 3.6% for practices of more than 100 cases through practices with more than 900 cases per year. Those practices with less than 100 cases (n = 18) had a mean mortality of 5%. Expected mortalities ranged from 2.4% to 3.9% and did not vary as a function of volume. No practice volume category had an observed/expected ratio of less than 0.8 and none had a ratio greater than 1.2, if annual volume was more than 100. Practices of less than 100 cases/year had an observed/expected ratio of 1.6% to 1.7%. There was great variation in observed and expected mortalities in the lower volume categories and less variation when volume was greater (more than 600 cases/year)., Conclusions: Although the data are practice-group-specific only, there was no clinically relevant correlation of volume to outcome except at extremely low annual volume (less than 100 cases per year). Variability of outcome was significant in lower volume practices (less than 600 cases/year) and varied little at more than 600 cases per year. There were no differences in expected mortality regardless of the size of the practice.

Since inception in 1990, The Society of Thoracic Surgeons (STS) National Cardiac Database has grown rapidly. More than 1,500 surgeons working in 706 hospitals have contributed more than one half million patient records. Geographic distribution of those participating is proportional to the number of centers performing heart surgery. The STS system is in use in all 49 states where centers are operating. There has been a significant decrease in length of stay for most patients having heart operations and a modest fall in coronary artery bypass grafting operative mortality from 3.7% to 3.3% over the past 3 years. Coronary artery bypass grafting case mix also is changing nationally as evidenced by a decline of 17% in the best-risk cases and concomitant increases in those with predicted risks of 5% to 10% and greater. New uses for local data in addition to self assessment and quality assurance include development of critical clinical pathways, support for managed-care group applications, and regional use. Minnesota has established a statewide STS system and Florida is soon to follow. The key to acceptance has been a peer-reviewed risk-stratification system that continues to be refined each year. Finally, a major effort will be made this year to increase the participation of general thoracic surgeons, particularly with respect to lung cancer.

Large multiinstitutional databases are excellent sources of information that provide clinically useful insight into the practice of cardiac surgery. Fully informed subscribers should be aware of the practical concerns associated with the management and interpretation of database results. During development of The Society of Thoracic Surgeons National Database, three such areas have become particularly important: the database population, the database quality, and the significance of results. Appreciation of the real and philosophical problems associated with these issues will allow for greater appreciation of the intricacies of the database and will enhance the users' ability to interpret information gained from the database.

The Society of Thoracic Surgeons' National Cardiac Database was used to determine the changes in preoperative characteristics and the predicted and observed risk of operative mortality of patients undergoing coronary artery bypass grafting during the decade of 1984 to 1993. During this period, the data show an increase of 2.5 years in age and decreases of 3% both in incidence of male patients and in incidence of first operation. There was little change in the percentages of urgent/emergent procedures or mean left ventricular ejection fraction. There was a significant 17.5% decrease in the proportion of lowest risk patients (0% to 2.5% predicted mortality) from 61.1% to 43.6%. Although no change in the next higher risk group (> 2.5% to 5.0% predicted mortality) occurred, the higher risk groups showed increases of 6.2%, 9.1%, 1.4%, and 1.1% for the > 5% to 10%, > 10% to 20%, > 20% to 30%, and > 30% to 50% risk groups, respectively. Over the past 2 years, there have been no significant changes in the distribution of the risk groups. These data will provide a base for comparison of future endeavors to lower complication rates and cost of coronary artery bypass graft operations.

Previous investigations with roller pumps and pneumatic pulsatile assist devices have demonstrated that nearly complete capture of normal left ventricular end-diastolic volume was necessary for appreciable reductions in oxygen consumption and stroke work. We tested the hypothesis that a centrifugal pump would decrease left ventricular stroke work and oxygen consumption as a function of pump flow. Ten sheep (35 to 50 kg) were instrumented and placed on left atrium-to-descending aorta bypass with a small, lightweight (112 g), implantable centrifugal pump. The relations between pump flow as a percent of cardiac output (% bypass), left ventricular stroke work, and oxygen consumption were studied. Left ventricular stroke work was calculated from the pressure-volume loops obtained with micromanometer and conductance catheters and was indexed per 100 g of left ventricular wet weight. Oxygen consumption was calculated from left main coronary artery blood flow and the arterial-coronary sinus oxygen content difference, normalized to 100 g of left ventricular wet weight and a heart rate of 100 beats/min. Measurements were made in stepwise increments of pump flow from zero to the maximum obtainable and then reversed in similar decrements. Analyses were made for 27 complete runs. Our data demonstrate that reductions in left ventricular stroke work and oxygen consumption were achieved from zero to maximal bypass. There was an approximate 66% and 50% reduction in left ventricular stroke work and oxygen consumption, respectively, at 60% bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term survival at our institution for postcardiotomy cardiogenic shock patients supported with the BioPump is 36% (29/80 patients). A heparin-coated extracorporeal membrane oxygenator (ECMO), first introduced in 1991, may reduce organ injury associated with cardiopulmonary bypass. The device can be employed rapidly because it connects directly to the cardiopulmonary bypass cannula. In an effort to improve our results in the treatment of postcardiotomy cardiogenic shock, we used ECMO in 21 patients with this syndrome and accompanying complications. The patients were divided into three groups: group 1, ECMO after coronary artery bypass grafting; group 2, ECMO after mitral valve operation; and group 3, ECMO after open heart operation with prolonged cardiac arrest. Survival in group 1 was 80% with 12 of 14 patients discharged to home. All three deaths were caused by cardiac failure. Bleeding complications in this group were moderate. There was no evidence of disseminated intravascular coagulation, and levels of fibrin split products remained within the normal range. Postoperative complications included stroke (2), renal failure (1), mediastinitis (1), and prolonged respiratory failure (6). Mortality in group 2 was 100%. The major problem limiting recovery was left ventricular distention secondary to inadequate left ventricular decompression. Mortality in group 3 was 100%; all 4 died of brain death. Extracorporeal membrane oxygenation without left ventricular drainage clearly is not effective in patients undergoing mitral valve operations as it does not effectively decompress the left ventricle, but it was highly effective in treating postcardiotomy cardiogenic shock in our coronary artery bypass grafting patients. Extracorporeal membrane oxygenation also proved to be safe as the patient-related complications of stroke, renal failure, and mediastinitis were low. Our preliminary success with heparin-coated ECMO now needs to be confirmed by studies from other centers with larger groups of patients.

Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS)

This report describes the development of the first known national surgical database designed for the practicing community cardiothoracic surgeon. Acceptance by members of The Society of Thoracic Surgeons has been gratifying. The number of patients on the system has grown from 116,109 at the end of 1991 to an anticipated 350,000 to 450,000 by the end of 1993. At the time of this report, 842 surgeons were participating, and more than 1,200 will be on the system by the end of 1993. A risk stratification system has been incorporated into the software, which predicts each patient's risk based on the individual surgeon's past experience. Trend analyses demonstrate a substantial increase in the number of patients at increased risk for perioperative death for coronary artery bypass operations over the past 5 years, while observed mortality has remained relatively constant. Programs are available for adult and congenital heart disease, lung cancer, and esophageal cancer, and modules for mediastinal tumors, pleural disorders, and benign pulmonary disease will soon be added. We anticipate that growth will continue as the need for practice profile data increases because of reimbursement issues.

The need for accurate risk assessment has become an indispensable element in the practice of cardiac surgery. The Society of Thoracic Surgeons National Cardiac Surgery Database allows subscribing institutions to perform sophisticated patient risk assessment using traditional statistical tools and a newly developed risk model of operative mortality. The database experience with isolated coronary artery bypass grafting has been studied most closely at this point and serves as the basis for this report. The approach to operative risk assessment is presented along with an analysis of important risk factors in the practice of coronary artery surgery from 1980 through 1990. The database contains records of 80,881 patients undergoing coronary artery bypass grafting in numerous institutions from 1980 through 1990. These records were used to conduct a detailed analysis of risk factors associated with coronary operations in this time interval and to present statistical methods used to formulate a risk equation that allows one to predict the probability of operative death. In the course of this decade, there were clearly defined trends showing a statistically significant increase in adverse patient risk factors. The risk model has proven to be a reliable tool for predicting the probability of operative death in an individual patient and may be valuable in both patient counseling and medical decision making. Large multi-institutional databases of this type are key ingredients of modern operative risk assessment. A database containing a broad national experience of this type can represent an aggregate experience that may well approximate a universally accepted standard of care.

The long-term advantages of internal mammary artery (IMA) conduits in coronary artery bypass graft (CABG) procedures are widely recognized, but the immediate short-term impact of IMA grafts is not well defined. The purpose of this study was to investigate the influence of IMA conduits on CABG operative mortality (OM). A retrospective study of two groups of patients undergoing isolated CABG was performed. Patients having at least one IMA graft (group 1) were compared with those with only venous conduits (group 2). The patient population was taken from The Society of Thoracic Surgeons National Cardiac Surgery Database, which contains a broad multi-institutional experience. A total of 38,578 registered patients undergoing isolated CABG from 1987 through 1991 were studied. Of these, 18,614 patients had at least one IMA conduit (group 1), whereas 19,964 had CABG using entirely venous conduits (group 2). The OM for group 1 was 2.0% (365/18,614), whereas the mortality was 4.5% (903/19,964) for group 2 (p < 0.005). Patient subgroups were examined to determine if the improved OM associated with IMA grafting was present in these patient subsets. The population was broken down according to age, sex, ejection fraction, extent of coronary disease, and operative priority. For each subset, univariate analysis showed that group 1 OM was significantly less (p < 0.005) than the OM for group 2. Numerous combinations of these patient parameters were also analyzed. Group 1 patients had a significant (p < 0.05) improvement in OM in each combination except for patients more than 70 years of age requiring reoperations.(ABSTRACT TRUNCATED AT 250 WORDS)

We retrospectively reviewed the 26-year National Institutes of Health experience with operative treatment of obstructive hypertrophic cardiomyopathy in pediatric patients. Operative criteria were either severe obstructive symptoms (New York Heart Association functional class III or IV) or sudden death. Seventeen patients underwent 19 open procedures, of which the present study is comprised. Complete follow-up was available 10.1 +/- 1.4 years (mean +/- standard error; range, 0.8 to 26.2 years) after operation. The mean ages at diagnosis and operation were 11.9 +/- 1.3 years (range, 1 to 17 years) and 14.8 +/- 0.7 years (range, 9 to 17 years), respectively. The preoperative intraventricular septum mean dimension was 23.2 +/- 1.3 mm (range, 11 to 36 mm). The left ventricular outflow tract gradient was 74 +/- 9 mm Hg (range, 20 to 175 mm Hg) at rest and 94 +/- 7 mm Hg (range, 55 to 175 mm Hg) with provocation. Fifteen patients (88%) underwent left ventricular myotomy and myectomy, and 2 underwent mitral valve replacement. Two patients who initially received left ventricular myotomy and myectomy later underwent mitral valve replacement. There were one perioperative death (6%) and five late sudden deaths (31%) at 3.8, 8.7, 9.6, 14.1, and 21 years postoperatively. Kaplan-Meier survival was 86% +/- 8% at 5 years and 77% +/- 12% at 10 years. After operation, the left ventricular outflow tract gradient decreased almost 80% to 21 +/- 15 mm Hg (p = 0.0001). In 8 patients, the left ventricular outflow tract gradient completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

Early investigations involving patient response to thyrotropin-releasing hormone during cardiac operations prompted researchers to consider that the cardiopulmonary bypass (CPB) procedure may affect this response. Results from several studies indicate that total T3 (active thyroid hormone) concentrations are significantly reduced during and after CPB (ie, the euthyroid sick syndrome). Inhibition of the monodeiodinase pathway during CPB, and subsequent inhibition of peripheral thyroxine to T3 conversion may partly explain these findings. These data prompted the investigation of intravenous T3 administration to patients undergoing CPB. Clinical trials to date have shown that intravenous T3 administered during or after CPB improves cardiac output and contractility. This article reviews the studies of thyroid hormone before, during, and after CPB operations.

The purpose of this study was to determine if the combination of a mechanical and bioprosthetic valve in the aortic and mitral positions influences late morbidity and mortality when compared with patients who had dual mechanical or dual bioprosthetic valves inserted. We reviewed the course of 89 hospital survivors of combined aortic and mitral valve replacement. The mean postoperative follow-up interval was 6.6 years, with a total follow-up of 583 years (98% complete). At 12 months after operation, mean functional class decreased from 3.1 to 1.7 (p < 0.05) and mean cardiac index increased from 2.1 to 2.5 L.min-1.m-2 (p < 0.05). Actuarial survival for the 89 patients (exclusive of < 30-day or in-hospital mortality, 14%) was 70%, 51%, and 33% at 5, 10, and 15 years. Freedom from reoperation was 93%, 78%, and 68%, and freedom from combined thromboembolism and anticoagulant-related hemorrhage was 82%, 60%, and 50%. These results show that there was no difference in overall survival in patients with dual mechanical valves, dual bioprosthetic valves, or a combination of both types at 15 years. There was, however, a lower reoperation rate in the group with dual mechanical valves as compared with the group with dual bioprosthetic valves (p < 0.05 at 10 years) or with a combination of valves (p < 0.05 at 15 years). The higher the number of mechanical valves the higher the combined risk of thromboembolism and anticoagulant-related hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine what influence various combinations of mechanical and bioprosthetic valves in the aortic, mitral, and tricuspid positions had on late morbidity and mortality of 40 hospital survivors of triple-valve replacement. At operation the patients ranged in age from 27 to 69 years; 73% were women. The mean postoperative follow-up interval was 8.3 years, with a total follow-up of 331 years (100% complete). At 12 months after operation, functional class decreased from 3.3 to 1.6 (p < 0.05), cardiac index increased from 2.0 to 2.6 L.min-1 x m-2 (p < 0.05), and pulmonary artery pressures decreased from 59/27 to 40/17 mm Hg (p < 0.05). There were no differences in preoperative variables between groups. Actuarial survival for the 40 patients (exclusive of 30-day or in-hospital mortality, which was 31%) was 78% and 74% at 5 and 10 years. At the same milestones, freedom from reoperation was 96% and 54%, freedom from combined thromboembolism and anticoagulant-related hemorrhage was 68% and 56%, and freedom from all late valve-related morbidity and mortality was 64% and 25%. Comparison of the patients with two or more mechanical prostheses with the patients having two or more bioprostheses indicated no significant differences in actuarial freedom from late death, thromboembolic events, or anticoagulant-related hemorrhage. However the actuarial freedom from reoperation in the groups with two or more mechanical valves was lower than that of the groups with two or more bioprosthetic valves (0/10 versus 13/30; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.

The effectiveness of the calcium antagonist nicardipine in protecting the ischemic myocardium was evaluated using the hemodynamic recovery of isolated working rat hearts subjected to hyperkalemic cardiac arrest followed by ischemia at 37.5 degrees C and 10 degrees C. Rat hearts (n = 51) received 20 mL of cardioplegia and were subjected to 27 minutes of ischemia at 37.5 degrees C. Group A (control) did not receive nicardipine. Groups B through F received nicardipine in the cardioplegia with total doses ranging from 2 micrograms to 6 micrograms. Group A had 46% survival of ischemia, whereas groups C (3 micrograms) and D (4 micrograms) had survival rates of 88% and 100%, respectively (p less than 0.05). The recovery of aortic flow after ischemia was 35% in group A, compared with 76% in group B (2 micrograms) and 81% in group D (p less than 0.05). Group A had 49% postischemic recovery of cardiac output, whereas groups B and D had 82% and 85% recovery (p less than 0.05). The postischemic recovery of stroke volume was 48% in group A compared with 84% in group B, 87% in group D, and 73% in group E (5 micrograms) (p less than 0.05). Additional rats were exposed to 210 minutes of ischemia (n = 41) or 240 minutes of ischemia (n = 56) at 10 degrees C. Control groups did not receive nicardipine, whereas treatment groups received nicardipine in the cardioplegia with total doses ranging from 1.4 micrograms to 6.4 micrograms. There were no significant differences in the survival of ischemia or the recovery of function after ischemia at 10 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine the effects of triiodothyronine (T3) on postischemic left ventricular performance and high-energy phosphate content in a severe injury model. Isolated working rat hearts (n = 63) received 20 mL of hyperkalemic NIH No. 1 cardioplegia and were subjected to 20 minutes of ischemia at 37 degrees C. Treated hearts were reperfused with T3-supplemented modified Krebs-Henseleit buffer. Control hearts did not receive T3 supplementation. All treated hearts (n = 44) performed work after ischemia, whereas 26% (5/19) of the control hearts were not able to perform any left ventricular work after ischemia. Comparisons with preischemic values demonstrated significant progressive hemodynamic recovery with increasing concentrations of T3 (0, 0.06, 0.15, and 0.60 ng/mL) with concomitant recovery of left ventricular stroke work index (63%, 72%, 89% [p less than 0.05], and 99% [p less than 0.05], respectively). There were corresponding increases in recovery of aortic flow, systolic pressure, cardiac index, and stroke volume index (p less than 0.05). There were no significant changes in coronary sinus flow or heart rate in any group compared with preischemic values. Comparisons of postischemic high-energy phosphate concentrations also demonstrated no change between treated and untreated groups (p greater than 0.05). We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery with no change in postischemic high-energy phosphate concentrations.

Oxygen-derived free radicals have been implicated in myocardial ischemia-reperfusion injury. It has been proposed that deferoxamine, an iron chelator, improves myocardial preservation by reducing the iron-catalyzed production of the hydroxyl radical. The objectives of this study were to define the appropriate timing of iron chelation therapy and the dose-response properties of deferoxamine. Isolated working rat hearts were subjected to 25 minutes of normothermic global ischemia. Deferoxamine was given as pretreatment (n = 39; doses of 10 or 30 mg/kg), added to cardioplegic solution (n = 43; doses 0.46 to 1.90 mmol/L), or administered upon reperfusion (n = 52; doses 0.15 to 0.76 mmol/L) and compared with saline controls (n = 25). Deferoxamine pretreatment improved survival at each dose from a control value of 44% to 71% and 72% (p less than 0.05), respectively. A cardioplegia dose of 0.46 mmol/L improved survival from 48% to 75%. Higher doses reduced survival and implied a toxic effect. Reperfusion therapy did not alter survival. Regardless of time of administration, deferoxamine did not improve ventricular function or adenosine triphosphate levels. Deferoxamine given as pretreatment 1 hour before ischemia at doses of 30 mg/kg, and perhaps as low as 10 mg/kg, significantly improved survival. The addition of deferoxamine to cardioplegic solution was safe and may be protective at approximately 0.50 mmol/L; however, toxicity should be considered at concentrations greater than 0.76 mmol/L. These data support the postulate that iron catalysis is involved in the production of oxygen-derived free radicals during ischemia-reperfusion injury. We conclude that pretreatment before ischemia is an important component of iron chelation therapy in myocardial preservation.

Lodoxamide tromethamine, an orphan antiallergy drug, inhibits degranulation of mast cells that reside in the myocardium and inhibits xanthine oxidase located in myocytes and predominantly in the vascular endothelium. The hypothesis evaluated was that lodoxamide tromethamine would attenuate oxygen free radical damage. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing 0, 1, 10, 100, or 1,000 mumol/L lodoxamide tromethamine at 37 degrees and 24 degrees C with ischemic times of 22 and 93 minutes, respectively. These ischemic intervals yielded 50% survival and 50% return of function in untreated hearts. Lodoxamide treatment alone at the onset of reperfusion was also studied. Performance end points were aortic flow, pressure, and coronary flow. Biochemical analyses included serotonin collected from coronary effluent as a marker of mast cell degranulation, uric acid for xanthine oxidase inhibition, myocardial adenosine triphosphate, and carbonyl group concentrations. Performance data demonstrated that lodoxamide was beneficial in a log-linear dose response when given continuously at both temperatures. Percent of preischemic values for untreated and maximal responses at 1,000 mumol/L of lodoxamide were as follows: a mortality of 50% in nontreated hearts versus 0%; aortic flow, 47% to 94% (37 degrees C), 46% to 86% (24 degrees C); cardiac output, 60% to 98% (37 degrees C), 58% to 97% (24 degrees C); adenosine triphosphate, 59% to 90% (37 degrees C), 48% to 65% (24 degrees C). Serotonin was undetectable from any hearts. Uric acid concentrations and carbonyl group content did not change with increasing dose. Lodoxamide demonstrated no benefit when given only during reperfusion, suggesting injury occurred at times other than reperfusion.

The purpose of this prospective study was to define the effect of cardiopulmonary bypass on the concentrations of thyroid hormones and metabolites. Blood samples were obtained from 14 patients preoperatively, at specific times throughout cardiopulmonary bypass, and serially to 24 hours postoperatively. Thyroid-stimulating hormone, thyroid-binding globulin, total thyroxine, triiodothyronine (T3), and reverse T3, an inactive metabolite of thyroxine, were measured by radioimmunoassay. Free T3 was assayed by equilibrium dialysis. Values of total T3 and free T3, the active hormone, were significantly depressed (75% and 50%, respectively) up to 24 hours after bypass (p less than 0.05). Reverse T3 demonstrated a greater than fourfold rise at 8 and 24 hours postoperatively (p less than 0.05). Thyroid-binding globulin was decreased at all sampling times (p less than 0.05). Thyroid-stimulating hormone, thyroxine, and free thyroxine levels remained within normal ranges at all sampling times. These results indicate that cardiopulmonary bypass simulates the "euthyroid sick syndrome" as seen in severely burned patients and critically ill patients, which is characterized by depression of T3 and free T3 concentrations with a concomitant increase in reverse T3 levels and normal concentrations of thyroid-stimulating hormone, thyroxine, and free thyroxine. The hemodynamic effects of primary hypothyroidism are well established. These data provide further support for investigational trials of intravenous administration of T3 in the prevention or treatment of low cardiac output syndrome after cardiopulmonary bypass.

Previous nuclear magnetic resonance studies in this laboratory have shown a beneficial biochemical effect of antegrade cerebroplegia (CP-A) during hypothermic circulatory arrest. This study compared CP-A with other methods of cerebral protection during hypothermic circulatory arrest to assess the clinical utility of this technique. Twenty-three sheep were divided into four groups: systemic hypothermia alone (SYST) and systemic hypothermia combined with external cranial cooling (EXTNL), retrograde cerebroplegia (CP-R), or CP-A. Cardiopulmonary bypass was started, and the sheep were cooled to 15 degrees C and subjected to 2 hours of circulatory arrest. Cardiopulmonary bypass was restarted, and the animals were rewarmed and weaned from cardiopulmonary bypass. Serial neurological examinations were performed and hourly scores assigned until the animals were extubated. Postanesthetic neurological scores improved in all groups throughout the 6-hour recovery period except the CP-R group. The improvement over time for these scores was similar for the EXTNL and CP-A groups and significantly better than for the SYST or CP-R groups (p = 0.004). The CP-A group had 5 of 7 animals with deficit-free survival despite the similarity in recovery of baseline brainstem function. We conclude that both antegrade infusion of cerebroplegia and external cranial cooling confer distinct cerebroprotective effects after a protracted period of hypothermic circulatory arrest when compared with the other methods studied.

Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.

Five hundred twenty-five patients with hypertrophic cardiomyopathy underwent left ventricular myotomy and myectomy (LVMM) from 1960 to 1990. Four hundred ninety-six had nonregurgitant trileaflet aortic valves before LVMM. In 19 (4%) of these patients, aortic regurgitation developed after LVMM. Age of the 19 patients ranged from 10 to 58 years (mean age, 35 +/- 3 [+/- standard error of the mean]]. Seven were male and 12, female. Five patients underwent LVMM followed immediately by aortic valve replacement or valvuloplasty. Aortic regurgitation developed in 14 patients at a later date. The average New York Heart Association functional class improved from 3.2 +/- 0.1 to 1.3 +/- 0.1 (p less than 0.05, Student's t test) after operation. The average peak systolic left ventricular outflow tract gradient at rest and with provocation decreased from 65 +/- 8 to 14 +/- 5 mm Hg (p less than 0.05) and 108 +/- 9 to 45 +/- 7 mm Hg (p less than 0.05), respectively, 6 to 8 months after operation. Aortic regurgitation occurred in 7 of the 14 patients at 6 months or less after operation, and 3 required operative repair. In the other 7 patients, aortic regurgitation developed 3 years or more after LVMM, and 3 of them also required operative repair. All 12 patients in whom aortic regurgitation developed at operation or within 6 months postoperatively had either a very small aortic annulus (less than or equal to 21 mm, 5 patients), a low mitral-septal contact lesion (greater than or equal to 35 mm below the aortic annulus, 3 patients), or both (4 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

This study compares results of a second left ventricular myotomy and myectomy (M + M) with those of mitral valve replacement (MVR) as reoperative procedures for persistent left ventricular outflow obstruction after M + M in hypertrophic cardiomyopathy. Comparison of the second M + M group (n = 12) with the MVR group (n = 11) disclosed significant difference (p less than 0.05) in mean age at the initial operation (29 +/- 11 years versus 40 +/- 8 years), interval between operations (46 +/- 57 months versus 18 +/- 13 months), and age at reoperation (33 +/- 10 years versus 42 +/- 8 years); and insignificant differences in mean preoperative functional class, cardiac index, left ventricular outflow gradients at rest or with provocation, and hospital mortality at reoperation (2/12 versus 1/11). At 6 months after reoperation, comparison of results of a second M + M with MVR showed that mean functional class, cardiac index, and left ventricular outflow gradient at rest were similarly improved, but the outflow gradient with provocation was significantly higher in the second M + M group (57 +/- 44 mm Hg versus 14 +/- 9 mm Hg, p less than 0.05). Total follow-up was 108 patient-years (100% complete) with an average of 5.9 years per patient in the second M + M group and 3.4 years per patient in the MVR group. Actuarial survival, including hospital mortality, at 3 and 5 years was 83% and 76%, respectively, after the second M + M, which was similar to 92% and 77% after MVR.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of magnesium ion and its relation to the calcium concentration of cardioplegic solutions was reexamined in this study. Isolated rat hearts were used with an oxygenated modified Krebs-Henseleit bicarbonate buffer as perfusion medium. The hearts were arrested for 20 minutes at 37 degrees C or 90 minutes at 24 degrees C. Treatment groups received one dose of nine possible cardioplegic solutions containing magnesium (0, 1.2, or 15 mmol/L) and calcium (0.05, 1.5, or 4.5 mmol/L). Ninety-six percent of the 75 magnesium-treated hearts recovered, regardless of the calcium concentration, in contrast to a 52% recovery rate in the 69 hearts that did not receive magnesium. The addition of 15 mmol/L Mg2+ to a cardioplegic solution containing no magnesium but 0.05 mmol/L Ca2+ significantly increased (p less than 0.01) the percent recovery of the following parameters of cardiac function: systolic pressure, 74% to 93% (37 degrees C), 64% to 98% (24 degrees C); cardiac output, 76% to 101% (37 degrees C), 71% to 102% (24 degrees C); stroke work, 64% to 104% (37 degrees C), 52% to 99% (24 degrees C); and adenosine triphosphate level, 75% to 83% (37 degrees C), 58% to 90% (24 degrees C). There were significant reductions (p less than 0.03) in percent recovery (37 degrees C and 24 degrees C) of cardiac output, stroke work, and adenosine triphosphate level in the groups that contained 0 or 15 mmol/L Mg2+ as the calcium concentration was increased from 0.05 to 4.5 mmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty-one patients, aged 1 to 18 years, having aortic valvotomy for congenital valvar aortic stenosis between 1956 and 1986 were followed up. The average age at operation was 11.5 years, with an operative mortality of 3.9%. The aortic valve gradient decreased from a mean preoperative value of 91 mm Hg to 27 mm Hg postoperatively. Current follow-up was 90% and averaged 16.8 years. Late cardiac mortality was 17.6%, with actuarial survival of 93.7% at 10 and 15 years, 81.8% at 20 and 25 years, and 70.9% at 28 years. Nineteen patients required reoperation (39%) at a mean of 17.7 years postoperatively, with a reoperation-free survival of 98% at 10 years. The reoperation rate accelerated in the following decade to 3.3% per year. Ten patients without reoperation were evaluated by continuous-wave Doppler echocardiography. The mean gradient was 21.6 mm Hg, and 90% had mild to moderate aortic insufficiency. This study confirms the efficacy of valvotomy in this age group and suggests that long-term survival and time to reoperation may be longer than previously reported.

Prostaglandin E2 (PGE2) has been shown to a clear role in the suppression of immune responses after burn and trauma injury. This probably results from inhibition of interleukin-2 production. This study examined the effects of PGE2 in vivo on the survival of solid-organ allografts and in vitro on the rat allogeneic mixed lymphocyte response. Administration of 16,16-dimethyl prostaglandin E2 (DMPGE2), a stable analogue of PGE2, significantly prolonged the survival of heterotopic cardiac allografts from ACI to LBN rats: 10.4 +/- 1.7 days versus 5.7 +/- 1.1 days (mean +/- standard error of the mean) (p less than or equal to 0.001). In 1 animal, DMPGE2 apparently led to the induction of long-term tolerance. Mixed lymphocyte cultures using splenocytes from naive LBN and ACI rats to which DMPGE2 was added showed a dose-dependent suppression of the mixed lymphocyte response with concentrations as low as 1 x 10(-7) mol/L. Splenocytes harvested from treated animals with functioning but histologically rejecting hearts demonstrated a marked decrease in mixed lymphocyte response to donor (ACI) stimulators compared with naive LBN controls (3,804 +/- 603 versus 27,395 +/- 2,668 cpm, n = 4), but maintained a normal response to third-party (Wistar Furth) stimulators. We conclude that DMPGE2 suppressed solid-organ allograft rejection, inhibited the allogeneic mixed lymphocyte response, and induced donor-specific in vitro hyporesponsiveness.

This report analyzes 118 prosthetic heart valves obtained from 97 patients at reoperation (96) or at postmortem examination (22). The number obtained from the mitral, aortic, and tricuspid positions were 78, 32, and 8, respectively. Duration of implant ranged from one day to 12.3 years. Valves showing the least long-term wear were the Starr-Edwards metal strut-silicone bell and the Björk-Shiley. Moderate long-term durability was provided by the Beall and Starr-Edwards cloth-covered composite-seat prostheses while short-term durability was given by Hancock and Carpentier valves. Reoperation for valve-related causes was performed for 46 of 47 Beall valves, which demonstrated stenosis, hemolysis, and incompetence from component wear, 6 of 27 Björk-Shiley prostheses for valve thrombosis or thromboembolism or both, and 11 of 17 porcine prostheses because of calcification (4) or cusp perforation or rupture. Analyses of wear and fatigue of mechanical valves demonstrated that use of ultrahard materials (pyrolyte carbon, titanium, stellite 21) provided superior durability in contrast to polymeric solids or fabrics with poor abrasion and impact characteristics. Further, cloth and disc wear were evident as early as 0.5 year after implant and appeared to be complete by 4 years. Completeness of healing after 24 months was not related to the type of fabric material used or its construction. This study suggests that mechanical valves made from hard materials have long durability when properly implanted and require fastidious prophylaxis against infection and thromboembolism. The findings of early cusp perforation or rupture in the aortic position and leaflet calcification, stiffening, or disruption in the mitral position for porcine prostheses suggest that frequent and careful examinations of patients with these prostheses are required to detect early signs of stenosis or incompetence and that early reoperation is required before catastrophic valve failure necessitates emergency prosthetic valve replacement.

Review of our experience with multiple valve replacement over a 6-year-period revealed a recent marked reduction in operative risk. Operative mortality for 62 patients operated on before 1974 was 34%; for 44 patients operated on since 1974, mortality was only 11%. In both groups, mortality was clearly related to the preoperative cardiac functional status. Several recent technical advances including myocardial protection by topical hypothermia, shortened perfusion time, and the intraaortic balloon pump may all have contributed to the reduced operative risk.

Sixty-four dogs were placed on normothermic total cardiopulmonary bypass, and global ischemia was induced for 1 hour during which continuous infusions (240 ml per hour) (N = 39) or bolus injections (150 to 200 ml every 30 minutes) (N = 23) into the proximal aortic root were performed. The control groups (N = 26) had infusion or injection of normal saline solution, normal saline solution + 25 mEq/L of potassium chloride, or Normosol-R pH 7.4. The cardioplegic solution (N = 15) contained 25 mEq/L of potassium chloride in Normosol-R pH 7.4, 0.25 mg/ml of lidocaine, 500 mg/dl of glucose, and 1.8 microU/ml of insulin. The nifedipine group (N = 23) had infusion or injection of 0.167 to 0.2 microgram/ml of nifedipine in saline solution, Normosol-R pH 7.4, or the cardioplegic solution. Left ventricular performance was assessed by phasic and mean measurements of left ventricular peak and end-diastolic pressures and its first derivative, left and right atrial pressures, and ascending aortic blood flow. Calculations of stroke work index and total peripheral resistance were performed. Morphological examinations, and light and electron microscopic examinations of heart slices were done. The results demonstrated a consistent superiority of the nifedipine group in terms of performance after bypass compared with the cardioplegic or control group. Normal preischemic stroke work indices and Sarnoff curves were present 2 hours after bypass for the nifedipine-treated groups. The cardioplegic solution was ineffective when given continuously but gave modest protection when given as a bolus injection. It is concluded that the concept of the efficacy of calcium blockade during ischemia and the initial reperfusion period for enhanced myocardial protection is valid.

Previous animal studies and a preliminary clinical trial of the addition of nifedipine to cardioplegic solution demonstrated salutary effects in terms of postischemic performance. This report examines the combined results of extended clinical trials conducted in two centers: Barnes Hospital, St. Louis, and Allegheny General Hospital, Pittsburgh. From an open-heart population of 4,777 patients, 205 highest-risk persons were selected for study. One hundred seventy of them were given nifedipine in cardioplegic solution. The remaining 35 served as controls to compare with 39 treated patients in the randomized subset of 74. Thirty-eight percent were women; the average age was 61 +/- 1 year; and most were in New York Heart Association Class IV. One-third had valve replacement, one-quarter had coronary artery bypass grafting (CABG), and 37% had valve, CABG, and other procedures in combination. Characteristically, these patients had a 50% increase in end-diastolic volumes, low cardiac indexes (1.7 +/- 1 L/min/m2), and low left ventricular stroke work indexes (22 +/- 2 gm-m/m2). Average cross-clamp time was 77 minutes. At Allegheny, an extracellular hyperkalemic solution was used to deliver an average dose of 407 +/- 22 micrograms per patient. At Barnes, a low-sodium hyperkalemic solution was used; the average dose was 476 +/- 22 micrograms. The results of hemodynamic studies in the randomized subset demonstrated approximately a twofold greater improvement in the treated group in cardiac index, stroke volume, left ventricular stroke work index, and pulmonary vascular resistance immediately after bypass. The incidence of acute low cardiac output death was 4% versus 11% in the nontreated group. The hospital survivorship for all treated patients was 84%. It is concluded that the addition of a calcium antagonist, nifedipine, reduced the incidence of acute global cardiac failure in the immediate postoperative interval.

A calf model for reproducible, prosthetic tricuspid valve endocarditis was developed using Staphylococcus aureus. The course of late prosthetic valve endocarditis was characterized as a fulminant disease when untreated with antibiotics. The earliest sign of a colonized valve prosthesis was an elevation of body temperature, which correlated with occurrence of positive blood cultures. The dose required to colonize an endothelialized tricuspid prosthetic valve in the calf model was 10(7) to 10(8) S. aureus organisms. In the model for late prosthetic valve endocarditis, silver-allantoin-heparin (SAH) treatment of the prosthetic valve gave no protection from inoculums of 10(8) S. aureus injected 60 days after operation. SAH treatment may be beneficial in early stages of prosthetic valve endocarditis, but this requires further study. Simultaneous cultures from the right atrium, the right ventricle, and the aorta of 2 animals showed that there was a 1,000- to 10,000-fold decrease in the bacterial titers across the combined pulmonary and systemic capillary beds. Bacterial titers drawn from the jugular vein had a 46% false negative result, and positive cultures from the external jugular vein showed only 1.3 S. aureus organisms per milliliter of blood. These bacteriological findings point out the risks of depending on sampling from the peripheral venous system when culturing for right heart endocarditis.

Intramyocardial pH was assessed as a potential marker for clinical evaluation and treatment of acute rejection following cardiac transplantation. Fifteen cats underwent forty operative procedures. Following intra-abdominal heterotopic heart transplantation, serial laparotomies were performed in the early (days 0 to 2), intermediate (days 5 to 7), and late (days 7 to 16) postoperative periods. Rejection was assessed by serial clinical examinations, ECG analyses, B-mode echocardiography, histological and ultrastructural analyses, and measurements of interstitial myocardial pH. Intramyocardial pH was measured by a new miniature (0.6 X 3.0 mm) fiberoptic pH transducer. At confirmed rejection, concomitant laparotomy and thoracotomy were performed and pH sensors were implanted in both native (anatomical) and graft hearts. Nine animals at rejection were given methylprednisolone and changes in graft and native heart pH were measured. The pH during absence of rejection, mild acute rejection, and severe acute rejection averaged 7.430 +/- 0.019, 7.233 +/- 0.040 (p less than .02), and 6.860 +/- 0.066 (p less than .02), respectively (mean +/- standard error of the mean). A progressive decline in pH was noted in each heart. In animals receiving steroids, graft heart pH increased over 90 minutes from 6.852 +/- 0.065 to 7.043 +/- 0.077 (p less than .05). Although pH decline may be secondary to either inflammatory or ischemic etiology, histological and ultrastructural analyses demonstrate a predominant inflammatory response with progressive mononuclear cell infiltration, interstitial edema, vascular wall edema, infiltration by polymorphonuclear neutrophil leukocytes, vacuolation of sarcoplasmic reticulum, and disarray of myocytes associated with falling pH. Degree of pH change correlated closely with degree of histological rejection, presence of ECG voltage decline, and change in wall thickness by ultrasound.

Mitral valve replacement has been performed in patients with obstructive hypertrophic cardiomyopathy if: (1) the interventricular septum is smaller than 18 mm in the region of usual resection; (2) atypical septal morphology is encountered; (3) a previous left ventricular myomectomy has been performed but residual major obstruction and symptoms persist; or (4) intrinsic mitral valve disease exists. Since 1983, mitral valve replacement has been performed in 58 patients with obstructive HCM only. Thirty-three female patients (mean age, 47.9 years) and 25 men (mean age, 45.7 years) met criteria 1 through 3 for mitral valve replacement. Patients with intrinsic mitral valve disease (criterion 4) were omitted from this study. All patients were in New York Heart Association functional class III or IV and had failed optimal medical therapy. Low-profile mechanical prostheses and bioprostheses were implanted, and the early mortality (less than 30 days or in the hospital) was 8.6% (5/58). Six patients (11.3%) died late, 3 suddenly of probably arrhythmia, 2 of respiratory failure, and 1 of an anticoagulant-related complication. After mitral valve replacement, 40 (83%) of 48 patients surviving operation and returning for evaluation were in functional class I or II, whereas 8 patients were in functional class III. Hemodynamic data obtained 6 months postoperatively showed that pulmonary artery wedge pressure was normal (13.7 +/- 4 mm Hg [+/- standard deviation]), left ventricular end-diastolic pressure had decreased (10.9 +/- 3.4 mm Hg), cardiac index was maintained (2.6 +/- 0.6 L/min/m2), and resting and provoked gradients were unremarkable. Mean follow-up was 24.2 months, actuarial survival was 86% at 3 years, and survival free from thromboembolism, anticoagulant-related complication, reoperation, and congestive heart failure for the same interval was 68%. Complications such as ventricular septal defect and complete heart block are avoided in patients undergoing mitral valve replacement, but device-related and cardiac-related complications can add to the morbidity and mortality in these patients in the long term.

The effect of amiodarone on the ischemic-reperfusion injury was tested in an isolated working preparation, using hypertrophied rat heart at 37 degrees C. Constant filling and afterload pressures and similar heart rates were used. Hearts from spontaneously hypertensive rats (N = 78) had thirty minutes of ischemia. Each received a 12-ml injection, by aortic root infusion, of amiodarone in normal saline or of normal saline alone at 37 degrees C at the onset of ischemia. Heart rate, aortic output, coronary sinus output, atrial pressure, and aortic pressure were recorded before and after global ischemia under steady-state conditions. Dose-response studies were performed at concentrations of 0.01 to 1.0 mg/ml. At every dose administered, amiodarone was found to significantly ameliorate the deleterious effects of global ischemia. The maximal benefit of amiodarone (70 +/- 4.6% recovery of function [mean +/- standard error of the mean], p less than 0.01) was found to be 0.25 mg (0.021 mg/ml), or 0.11 mg/g wet heart weight. Improvement in survival (return of aortic output and heart rate following ischemia) with all doses of amiodarone was statistically significant (p less than 0.002). Decreased recovery of function following global ischemia when doses were greater than 0.25 mg may have been secondary to the known negative inotropic effects of the drug. The mechanisms for the protective effects of amiodarone may be coronary vasodilatation, antiarrhythmic stabilization, or inhibition of calcium flux at the slow channel.

An experience based on 1,211 patients has shown aspiration needle biopsy to be a valuable technique for diagnosing bronchogenic carcinoma and other localized intrathoracic lesions that are beyond the reach of the fiberoptic bronchoscope. In 896 patients with malignant intrathoracic neoplasm, the aspirate demonstrated malignant cells in 96%. A false cytological diagnosis of carcinoma occured in 2 patients, for a true positive rate of 99%. However, the true negative rate was only 87%. In 77% of 31 immunosuppressed patients, the causative agent of a focal infectious process was diagnosed. Pneumothorax was the only notable complication, occuring in 24% of patients, with 14% requiring chest tube drainage. The procedure is relatively simple and rapid, generally causes little patient discomfort, and can be performed in virtually any hospital.