In vivo and in vitro measurements of the relationship of human squamous carcinomas to herpes simplex virus tumor-associated antigens.

An additional 244 unfiltered sera have now been studied in a series of controlled, coded tests to determine the relationship of squamous carcinomas of the head and neck and cervix to the presence of complement-fixing antibodies to herpesvirus-tumor-associated antigens (HSV-TAA) in both tumor-bearing and cured patients. Ninety % of sera from patients with squamous carcinomas had antibodies to HSV-TAA, in contrast to 11% of sera from patients with nonsquamous cancers and 4% of sera from noraml individuals. The temporal relationship of Stage 1 laryngeal carcinomas suggests that HSV-TAA appearance precedes the immune defects. An in vitro correlate of the previously demonstrated specific delayed hypersensitivity reactions in controlled skin tests of squamous carcinoma patients with HSV-TAA is reported. In leukocyte migration inhibition tests, the migration indices after incubation with HSV-TAA of peripheral blood leukocytes from patients with squamous carcinoma (x = 0.847) were in definite contrast to migration indices seen for normal leukocytes (x = 1.037) and patients with nonsquamous solid cancers (x = 1.03). Thus, these polypeptides elicit both humoral antibody response and cell-mediated reactivity.

Acute endocarditis in drug addicts: surgical treatment for multiple valve infection.

In 72 drug abusers surgically treated for acute infective endocarditis, 14 patients (19%) required surgical procedures on two valves. The predominant infecting organisms were Staphylococcus aureus and Pseudomonas aeruginosa (29%). In contrast to single valve infection, congestive heart failure was the most common operative indication (86%, p less than 0.05) and was uniformly present when both left-sided valves were involved. Surgery was performed 20 +/- 13 days after initiation of antibiotic therapy, yet 7 of the 14 patients had perivalvular abscess formation. In nine patients with solely left-sided infection, aortic and mitral valve replacements were performed. In five patients with bilateral infection, partial or complete tricuspid valvectomy was performed in conjunction with one aortic and four mitral valve replacements. Tricuspid valve competence was reestablished by valve insertion or anuloplasty in two patients, and these patients experienced less perioperative heart failure than did those with tricuspid excision alone. There was no early (less than 30 day) mortality. However, long-term follow-up revealed a reoperative incidence of 21% and a 36% late mortality rate due to prosthetic valve infection with or without dehiscence at 3 to 18 months (mean 7.2 +/- 6) after the initial operation. These late infectious complications were not related to infecting organism or prosthetic material in the tricuspid anulus, but did occur in four (57%) of seven patients with intracardiac abscess. The data indicate that multiple valve infection does not preclude successful early surgical therapy, maintaining tricuspid competence may be hemodynamically preferable, and reinfection in this addict population increases late mortality.

Outcome of coronary artery bypass grafting in black persons.

Relatively little attention has been given to coronary artery disease in black persons in the United States. During 31 months, 73 consecutive black patients drawn from an urban working class inner city population who had undergone coronary artery bypass grafting were studied. In the total series of elective and emergency operations, 3 patients (4%) died within the first 30 days and 3 more died by the end of the first year of follow-up. Functional capacity was assessed by interviews and a questionnaire in a subset (n = 39) at least 6 months after operation. Although 79% of the patients felt that the operation had resulted in improvement of symptoms, half of them continued to report angina. Only one-third of the patients were working in the period immediately before the operation; 13% were working postoperatively. Coronary artery bypass grafting had an acceptable mortality risk in these patients, although the functional outcome was disappointing.

Pulsatile reperfusion does not modify global myocardial ischemic injury.

In an attempt to arbitrate the reputed clinical efficacy of pulsatile flow during reperfusion in minimizing ischemic injury, 32 mongrel dogs supported by normothermic cardiopulmonary bypass were subjected to 30 minutes (Groups IC and IP) or 60 minutes (Groups IIC and IIP) of global myocardial ischemia. The effect of pulsatile flow (P) initiated during 30 minutes of reperfusion on the recovery of myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content (MWC) was compared to the effect of linear reperfusion (C) in another group of animals. ATP stores, which significantly decreased to 43% and 53% of preischemic levels (Groups IC and IP, respectively, p less than 0.01) and 36% and 31% of control values (Groups IIC and IIP, respectively. p less than 0.001), did not increase with either pulsatile or linear reperfusion. CP stores, depleted 97% during ischemia in all groups, returned to preischemic levels regardless of the mode of reperfusion flow. Coronary blood flow measured 30 minutes after aortic unclamping was not significantly different from control flow in any group. MWC significantly decreased during ischemia from 80.5% +/- 0.8% to 76.5% +/- 1.1% in Group IC and from 81.8% +/- 1.2% to 76.8% +/- 0.8% in Groups IP (p less than 0.05) and returned to preischemic levels with reperfusion. However, following 60 minutes of ischemia, pulsatile reperfusion prevented the significant increase in MWC that accrued after linear reperfusion (80.7% +/- 1.5% to 84.0% +/- 0.7%, p less than 0.05). These data indicate that pulsatile reperfusion initiated after an ischemic injury that results in a 50% or greater depletion of myocardial ATP stores does not restore myocardial nucleotide levels or enhance coronary blood flow, although the pathological increase in MWC may be avoided.

Coronary flow reserve after ischemia and reperfusion of the isolated heart. Divergent results with crystalloid versus blood perfusion.

Mechanical function and coronary hemodynamics were assessed in 73 isolated rabbit hearts randomly subjected to 0, 10, 20, 30, or 45 minutes of 37 degrees C global ischemia and 45 minutes of reperfusion in either a modified Krebs buffer or homologous blood-perfused Langendorff mode (n = 7 to 9 hearts per group). Isovolumic developed pressure, resting coronary flow, and response to endothelium-dependent (bradykinin) and -independent (nitroglycerin) agonists were quantitated at defined preload and heart rate. Perfusate did not influence systolic performance, which was impaired after 30 minutes of ischemia and fell to 64% to 72% of preischemic values after 45 minutes of ischemia (p < 0.05). However, basal coronary flow was at least sixfold greater in crystalloid-perfused hearts. Moreover, coronary hyperemia (p < 0.05) persisted for Krebs-perfused hearts subjected to all but the longest ischemic interval. After equilibration, all postischemic blood-perfused hearts had basal flow unchanged from before ischemia. Bradykinin and nitroglycerin induced similar increases in coronary flow for each group before and after each ischemia interval. However, the magnitude of this increase was greater in blood-perfused hearts (p < 0.01) and was not attenuated by the ischemic times encompassed in this protocol. In contrast, endothelium-dependent and -independent coronary flow reserve was abolished after 20 minutes of ischemia or longer in Krebs-perfused hearts. These data suggest that the unphysiologic resting flow patterns of crystalloid-perfused isolated hearts obfuscate interpretation of the interaction between coronary flow reserve and ischemic injury.

Beneficial metabolic effect of nucleoside augmentation on reperfusion injury following cardioplegic arrest.

Restoration of coronary flow after hyperkalemic cardioplegic arrest (HCA) is associated with a unique metabolic reperfusion injury (RI) manifested by declining nucleotide stores despite their end-ischemic preservation. Prevention of this RI by exogenous provision of adenosine with or without inhibition of adenosine's major catabolic enzyme was assessed in 27 dogs subjected to 60 minutes of HCA. The effect of aortic root infusion of 40 mg/kg of adenosine in addition to adenosine deaminase inhibition by 10 mg/kg of EHNA (group 2) initiated during 60 minutes of reperfusion on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores and coronary blood flow (CBF) were compared to animals having adenosine infusion alone (group 3) or controls (group 1). Although ATP levels were preserved at the end of HCA in all groups, adenosine infusion with or without EHNA prevented the significant 23 percent decline in ATP stores incurred during unmodified reperfusion (p less than 0.01, group 1). The CP stores decreased (p less than 0.05, all groups) during arrest, but were restored to preischemic levels during reperfusion. When measured 60 minutes after aortic unclamping, CBF was 312 percent of preischemic flow in group 3 (p less than 0.01), only 170 percent in group 2 (p less than 0.05), and unchanged in controls (group 1). The data indicate that provision of adenosine as a nucleotide precursor prevents the metabolic RI following HCA. In addition, inhibition of adenosine catabolism is not necessary for this salutary effect, nor is adenosine's efficacy solely mediated by augmentation of CBF.

Efficacy of crystalloid cardioplegic solutions in patients undergoing myocardial revascularization. Effect of infusion route and regional wall motion on preservation of adenine nucleotide stores.

The effect of varying the mode of cardioplegic delivery and the presence of regional wall motion abnormalities on myocardial protection by crystalloid cardioplegic solutions was assessed in 68 patients undergoing coronary artery bypass grafting. Serial transmural biopsy specimens from the left ventricular apex were assayed for adenosine triphosphate. All patients had more than 75% stenosis of the left anterior descending coronary artery. They were prospectively randomized into Groups I and II to receive (I) all cardioplegic solution infused via the aortic root or (II) reinfusions of cardioplegic solution given both centrally and through the completed distal left anterior descending anastomosis. Patients were also stratified as to the presence of normal (N) or impaired (Ab) apicoanterior regional wall motion. Inadequate delivery of cardioplegia during ischemia in Group I was manifested by a 41% (p less than 0.01) depletion of adenosine triphosphate stores in abnormally contracting myocardium distal to the left anterior descending stenosis that was not repleted after restoration of coronary flow and a 27% (p less than 0.05) decline in ATP stores during reperfusion in myocardium with normal preoperative wall motion. In contrast, nucleotide stores were preserved at preischemic levels throughout ischemia and reperfusion in Group II regardless of preoperative wall motion. Preservation of ATP did not correlate with duration of ischemia, highest recorded septal temperature, or volume of cardioplegic solution infused. Two patients in each group had a new perioperative infarction. However, 38% of patients in Group IAb required transient inotropic support versus 5% in Group IIAb (p less than 0.05). These data emphasize that reinfusion of cardioplegic solutions distal to coronary obstructions is mandatory for optimal myocardial protection during coronary revascularization.

Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Afterload independence and sensitivity to inotropic state.

Previous studies suggest that the relationship between end-diastolic volume and stroke work calculated as the area of the pressure-volume work loop is linear, afterload independent, and sensitive to the inotropic state. The correlation of myocardial oxygen consumption with this stroke work could provide an integrated measure of cardiac performance and metabolism to assess perturbations induced by ischemia or pathologic loading conditions. Fourteen canine hearts instrumented for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during progressive volume infusion on right heart bypass (1.5 to 3.5 L/min in 250 ml/min increments). Data acquisition both in the control state and during continuous infusion of calcium chloride (0.03 mEq/kg/min, n = 7) to increase contractility or phenylephrine (2 micrograms/kg/min, n = 7) to alter afterload facilitated the construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least-squares regression analysis. The cardiac mechanics assessment for this group of dogs confirmed a highly linear (mean r = 0.984) work versus preload relationship that was unaffected by changes in afterload but sensitive to increased contractility (71% increase in slope). The myocardial energetics correlation was also linear (mean r = 0.939) and demonstrated an increased oxygen utilization characteristic of the higher inotropic state produced by calcium chloride infusion (0.047 +/- 0.003 versus 0.070 +/- 0.008 ml oxygen/beat/100 gm left ventricular weight, p = 0.008). Although phenylephrine administration produced variable perturbations of myocardial oxygen consumption, the energetics relationship for this subgroup was not statistically altered by changes in afterload. The features of this cardiac energetics assessment suggest its value as a biological marker to evaluate the postischemic, hypertrophied, or failing heart.

Preloading history influences pressure-volume-derived indices of myocardial contractility in the ejecting canine left ventricle.

The dependency of indices of myocardial contractility on the immediate preloading protocol was assessed in 14 pentobarbital anesthetized open-chest dogs. An intracavitary micromanometer and epicardially placed ultrasonic dimension transducers allowed acquisition of dynamic left ventricular pressure-volume relationships while varying preload on right heart bypass. A resting cardiac output of 75 ml/kg/min was either increased twofold or reduced to zero flow over a 20-second interval. Linear regression analysis of the mechanical parameters permitted construction of the end-systolic pressure-volume relationship, rate of pressure rise-end-diastolic volume relationship, and the preload recruitable stroke work relationship. The slopes of the end-systolic pressure-volume relationship and rate of pressure rate-end-diastolic volume relationship were significantly higher when measured during volume depletion than during volume expansion (17.2 +/- 1.3 versus 8.5 +/- 0.8 mm Hg/ml and 205 +/- 14 versus 126 +/- 11 mm Hg/sec/ml, p less than 0.001, respectively). This finding was also evident when data analysis was confined to the initial 10 seconds of the loading interval. Nonlinear regression analysis of pooled data from both preloading protocols revealed curvilinear characteristics for each relationship. In contrast, the slope of the preload recruitable stroke work relationship was lower as a result of volume unloading (16.8 +/- 2.0 versus 22.8 +/- 1.7 mJ/beat/100 gm left ventricle/ml, p less than 0.01) and was independent of loading protocol when data analysis was confined to the initial 10-second acquisition period. Furthermore, second-order regression analysis of the pooled data showed no curvilinearity. These findings emphasize the importance of both the timing and method of varying cardiac preload in the determination of intrinsic myocardial contractility and suggest that the preload recruitable stroke work relationship may be a more linear contractile index that is less affected by preloading history over brief intervals.

Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Effect of unprotected and protected global ischemia.

Previous studies noted augmented postischemic myocardial oxygen consumption as a subtle indicator of ischemic injury in the isovolumically contracting left ventricle. The present study was done to determine if the linear relationship between oxygen utilization and stroke work present in the ejecting heart would facilitate compartmentalization of this increased oxygen consumption into resting and working metabolic demands. Therefore, 18 canine hearts instructed for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during incremental volume infusion while undergoing right heart bypass. Data acquisition before and after either 20 minutes of 37 degrees C global ischemia or 2 hours of 20 degrees C cardioplegic arrest allowed construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least squares regression analysis. Although contractility was depressed 48% (p less than 0.01) after unprotected ischemia and was unchanged after cardioplegic arrest, neither group demonstrated a change in the efficiency of converting consumed oxygen to external mechanical work. In contrast, in both groups the oxygen utilization for unloaded contraction was comparably augmented by 21% and 16% (p less than 0.05), despite the varying ischemic conditions and disparate preservation of contractile function. These data suggest a highly linear correlation between oxygen consumption and external mechanical work that persists after ischemia and discriminates the components of postischemic energetic derangements. This model may be useful in the development and assessment of specific myoprotective strategies.

Assessment of the intrinsic contractile state within an area of myocardium.

Afterload independent, inotropic state sensitive indices of regional function were sought in 31 canine hearts instrumented with piezoelectric crystals to depict trapezoidal areas in the left anterior descending and circumflex arterial beds. Control and postinterventional end-systolic pressure versus regional length and area relationships and regional stroke work versus end-diastolic length and area relationships were inscribed during incremental volume loading on right heart bypass. Hearts were randomized to undergo afterload variation with phenylephrine infusion, contractility augmentation by calcium chloride, or 20 minutes of ischemia in the region of the left anterior descending artery with 30 minutes of reperfusion. All relationships were linear before and after each intervention (mean r = 0.726 to 0.974). The slopes of each correlation were interpreted to quantify intrinsic regional contractility, and all were afterload insensitive (unaffected by phenylephrine). Regional stroke work versus end-diastolic area and length relationships were depressed 55% and 62%, respectively, after ischemia (p less than 0.001 each), whereas neither end-systolic pressure versus regional area nor regional length was significantly altered. Calcium chloride increased regional stroke work versus area 45% in both arterial beds, but significantly increased the other indices only in the left anterior descending and not the left circumflex region. Unlike previous studies of global contractility, correlation of end-systolic events alone did not reliably discriminate perturbations in regional function. The superiority of regional stroke work versus end-diastolic area may be due to incorporating pressure-area changes during the entire cardiac cycle and obviating variability owing to crystal orientation inexactly parallel to fiber shortening.

Optimal intraoperative protection of myocardium distal to coronary stenoses.

Metabolic evidence of improved delivery of cardioplegic solutions by adjuvant use of nitroglycerin (NTG) and reinfusing these solutions distal to an obstructed coronary artery was sought in 40 dogs subjected to cold cardioplegic arrest. The left anterior descending coronary artery was occluded prior to initiating arrest by intra-aortic root infusion. Cardioplegic solution was reinfused with the left anterior descending occluded throughout ischemia (Group I), or with this artery reopened, to simulate a completed distal anastomosis (Group II). Serial biopsy specimens of the left ventricular apex were assayed for adenosine triphosphate and creatine phosphate, while specimens from the posterior left ventricular wall served as controls. Regional myocardial temperatures were recorded throughout ischemia. Half of the hearts in each group received 300 micrograms of nitroglycerin in the cardioplegic solution. Adenosine triphosphate was preserved in myocardium distal to a patent coronary artery whether nitroglycerin was added to the cardioplegic solution or not (control, control + NTG). Moreover, nitroglycerin did not prevent the 26% to 34% (p less than 0.05) decline in adenosine triphosphate levels when the left anterior descending remained obstructed throughout ischemia (Group I, I + NTG). However, opening the left anterior descending for reinfusion of cardioplegic solution allowed adenosine triphosphate to be preserved at end-ischemia (Group II, II + NTG). In addition, the metabolic reperfusion injury manifested by a 37% (p less than 0.01) decline in adenosine triphosphate levels after aortic unclamping (Group II) was obviated when nitroglycerin was added to the cardioplegic solution delivered in this manner (II + NTG). The depletion of cardioplegic solution stores during ischemia was more severe in the experimental groups than in controls (p less than 0.05). These metabolic changes did not correlate with regional myocardial temperature gradients. The data indicate that myocardium jeopardized by coronary stenoses can be preserved as well as myocardium supplied by a patent coronary artery by adjuvant use of nitroglycerin and varying the mode of delivery of the cardioplegic solution.

Platelet deposition after surgically induced myocardial ischemia. An etiologic factor for reperfusion injury.

Despite meticulous adherence to presently known principles of myocardial preservation, reperfusion after aortic cross-clamping results in a unique injury manifested by decreasing high-energy phosphate levels and increased coronary resistance. We hypothesize that platelet deposition into the coronary microvasculature is a major factor in reperfusion injury. To differentiate platelet deposition due to subendocardial hemorrhage from deposition due to vascular entrapment, we infused 111In-labeled platelets together with 51Cr-labeled erythrocytes into 15 dogs that were on normothermic bypass and subjected to 60 minutes of global ischemia followed by 30 minutes of reperfusion. Platelet deposition is indicated only when the proportion of platelets to erythrocytes in tissue exceeds that measured by peripheral blood. Myocardial biopsy specimens were obtained after 10 minutes of bypass, 120 minutes of continuous bypass (Group I), and at the end of reperfusion after global ischemia (Group II). In five dogs (Group III), dipyridamole (1 mg/kg), an antiplatelet activation agent, was administered in the preischemic period. Platelet deposition was expressed as the number of radioactive-labeled platelets deposited per gram of tissue. Bypass for 120 minutes resulted in only a minimal increase in platelet deposition. However, normothermic ischemia followed by reperfusion resulted in over a twofold increase in platelet deposition compared to controls. Pretreatment with dipyridamole appeared to avoid platelet deposition. These data indicate that platelet deposition in the coronary microcirculation following surgically induced myocardial ischemia may be associated with reperfusion injury and that antiplatelet drugs after this sequence.

Developmental changes in reperfusion injury. A comparison of intracellular cation accumulation in the newborn, neonatal, and adult heart.

Intracellular sodium and calcium accumulation were measured after 30 and 40 minutes of ischemia and 30 minutes of reperfusion in newborn (0 to 7 day), neonatal, (14 to 21 day), and adult (4 to 6 month) New Zealand white rabbit heart preparations. Newborn hearts showed twofold and threefold elevations of calcium when exposed to 30 and 40 minutes of ischemia and reperfusion, respectively, whereas sodium increase was noted only in the 40 minute group. Conversely, adult hearts exhibited sodium elevation if exposed to ischemia for 30 minutes and calcium accumulation occurred only after 40 minutes of ischemia. There was no significant alteration in intracellular sodium and calcium levels after ischemic intervals of 30 and 40 minutes in the neonate. These studies demonstrate that the immature newborn heart is the most susceptible and the neonatal heart is the least susceptible to injury sustained by ischemia followed by reperfusion. These differences in susceptibility to ischemia may be due to age-dependent alterations of intramembrane ionic pumps and channels.

Developmental changes in reperfusion injury. Comparison of intracellular ion accumulation in ischemic and cardioplegic arrest.

Developmental differences in ischemic and potassium cardioplegic arrest were evaluated in newborn (birth to 7 day old) and adult (6 to 12 month old) New Zealand white rabbit hearts isolated and perfused by Langendorff's method. An extracellular space washout technique was used to measure intracellular sodium and calcium in the two age groups after ischemia alone, after normothermic and hypothermic cardioplegia, and after cardioplegia with reperfusion. Although the intracellular ionic contents of nonreperfused adult hearts after 30 and 40 minutes of ischemia were identical, there was a twofold elevation in intracellular sodium level after 40 minutes of ischemia in the newborn hearts. Adult hearts arrested by normothermic potassium cardioplegia demonstrated no alteration in the intracellular ionic content, whereas in the newborn hearts, potassium cardioplegia produced excess intracellular calcium loading before reperfusion, which was greater than that occurring with ischemia alone. When hypothermia (12 degrees C) was combined with cardioplegic arrest, a prereperfusion influx of sodium and calcium was not observed in the newborn hearts, and ionic reperfusion injury was blunted in both newborn and adult hearts. These studies demonstrate that the newborn heart is more susceptible than the adult to both ischemia and cardioplegia. This may be due to age-dependent differences in transmembrane passive diffusion, sodium/calcium exchange, or calcium slow channel properties and suggests alternative myocardial protective strategies for the newborn infant.

The efficacy of blood cardioplegia is not due to oxygen delivery.

Twenty-seven canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work and myocardial oxygen consumption during incremental volume loading on right heart bypass before and 30 minutes after 2 hours of cardioplegic arrest at 10 degrees C. Three cardioplegic solutions were used: Hematocrit values were 17.0% (group I), 8.2% (group II), and 0% (group III). In all groups the slope of the linear stroke work versus end-diastolic volume relationship, a measure of contractility, was unchanged after ischemic arrest. However, the myocardial oxygen consumption for basal metabolism was increased an average of 25.5% after arrest with plasma (group III). Since the plasma concentration in all three groups was identical, and the oxygen available to the hearts during ischemia was the same in groups II and III, the efficacy of blood-based cardioplegic solutions cannot be attributed to a plasma component or to the greater oxygen-carrying capacity of the red blood cell. Future studies should attempt to identify the salutory entity of the red cell responsible for preservation of myocardial oxygen consumption efficiency.

Prospective evaluation of malignant neoplasms in cardiac transplant recipients uniformly treated with prophylactic antilymphocyte globulin.

Although there is convincing evidence that prophylactic administration of high doses of the monoclonal antibody OKT3 predisposes patients to an increased prevalence of early posttransplantation malignancy, particularly posttransplantation lymphoproliferative disease, it is indeterminate whether polyclonal antilymphocyte globulin poses a similar hazard. We reviewed the outcome of 112 consecutive cardiac transplant recipients who received uniform immunosuppression, including induction therapy with antilymphocyte globulin, and were prospectively followed-up for a median duration of 41.5 months (range 1 to 81 months). No patients had posttransplantation lymphoproliferative disease. Nine malignant neoplasms (8%) were detected from 6 to 70 months after transplantation. Four patients with cutaneous neoplasms were alive and well at the time this article was written. Three patients died of disseminated adenocarcinoma 6 months, 17 months, and 60 months after transplantation. One patient was undergoing treatment of Kaposi's sarcoma at the time this article was written, and another was undergoing treatment of transitional bladder cell carcinoma. Actuarial survival for all patients was 88% at 1 year and 79% at 5 years. Moderate doses of induction antilymphocyte globulin may facilitate rapid reduction of maintenance cyclosporine and steroid doses, thereby decreasing the duration of intense immunosuppression and lowering the risk of posttransplantation lymphoproliferative disease. Testing this hypothesis would require the development of reliable and reproducible in vivo assays to prospectively assess immune status.

Blood conservation in coronary artery surgery.

BACKGROUND: Most patients undergoing coronary artery bypass surgery receive homologous blood transfusions despite the availability of multiple pharmacologic and blood salvage conservation strategies. METHODS: The efficacy of defining strict transfusion criteria as the sole blood conservation strategy was adjudicated prospectively by comparing homologous blood product usage in 314 consecutive patients undergoing isolated primary coronary artery bypass surgery (group 2) with a retrospective group of 947 consecutive patients undergoing the same procedure but transfused without protocol (group 1). RESULTS: The incidence of red cell transfusion and plasma transfusion decreased from 40.5% to 25.8% and 23.8% to 13.4% in groups 1 and 2, respectively (p < 0.001). The percentage of patients receiving no homologous blood products increased from 47.6% in group 1 to 68.5% in group 2 (p < 0.001). Decreasing body weight and preoperative hematocrit were found to be highly significant predictors of the need for red blood cell transfusion (p < 0.001). Significant postoperative determinants included intensive care unit and hospital length of stay and reoperation for bleeding (p < 0.001 each). CONCLUSIONS: Because major determinant of homologous blood transfusion during coronary bypass surgery is the predictable and unavoidable dilution of a small red cell mass that occurs when instituting cardiopulmonary bypass, adherence to defined transfusion criteria alone is a simple, safe, and effective strategy for decreasing blood product utilization.

Compartmentalizing chemomechanical transduction in the ejecting heart.

The efficiency of transferring the total energy generated by ventricular contraction (pressure-volume area, PVA) to external work (EW) and internal work (IW) and the myocardial oxygen consumption (MVO2) at zero PVA were determined during volume loading on right heart bypass before and after a 50% augmentation (CaCl2, 0.03 mEq/kg/min, n = 7) or depression (20 minutes of 37 degrees C ischemia with 30 minutes of reperfusion, n = 7) of the contractile state. An increased EW efficiency (64% +/- 7% vs. 81% +/- 6%, p less than 0.01) with reciprocally decreased IW efficiency (36% +/- 7% vs. 19% +/- 6%, p less than 0.01) occurs with calcium chloride-augmented contractility. A reversible ischemia and reperfusion insult has the converse effect on these relative efficiencies (EW, 73% +/- 4% vs. 49% +/- 4%; IW, 27% +/- 4% vs. 51% +/- 4%; each p less than 0.01). Calcium chloride increases the oxygen requirements of both basal metabolism (28 +/- 2 vs. 67 +/- 9 ml O2/beat/100 gm LV, p less than 0.01) and fiber shortening (11 +/- 5 vs. 62 +/- 11 ml O2/beat/100 gm LV, p less than 0.01). The postischemic heart has a decreased oxygen need for shortening (20 +/- 2 vs. 3 +/- 4 ml O2/beat/100 gm LV, p less than 0.01), paralleling the depressed inotropic state. This new model of compartmentalized chemomechanical transduction may allow specific modulation of the energetic derangements attendant to the surgically treated heart.

Induction of cardioplegia with blood and crystalloid potassium solutions during prolonged aortic cross-clamping.

Recent controversy concerns the proper vehicle for delivery of potassium cardioplegia. In the present study, adult dogs supported by cardiopulmonary bypass were subjected to 2 hours of multidose, hypothermic potassium cardioplegic arrest with 30 minutes of reperfusion with either autologous blood or crystalloid solution as the cardioplegic vehicle. Preservation of myocardial high-energy nucleotide stores was assessed by serial left ventricular biopsies assayed for adenosine triphosphate (ATP) and creatine phosphate. Preischemic and postischemic ventricular function was assessed by the use of an isovolumic intraventricular balloon. ATP stores were equally maintained at preischemic levels after ischemia and reperfusion by both autologous blood and crystalloid solution. Although creatine phosphate stores significantly declined (P less than 0.01, both groups) after 2 hours of arrest, reperfusion allowed equal restoration of preischemic levels. Maximum first derivative of left ventricular pressure and measured velocity were not depressed by either mode of protection. Similarly, myocardial compliance, as assessed by length-tension curves, showed no change following either autologous blood or crystalloid solution. The data show equal and significant myocardial protection by multidose, hypothermic potassium cardioplegia when both delivery vehicles were used.