The use of autologous platelet-leukocyte gels to enhance the healing process in surgery, a review.

BACKGROUND: The therapeutic use of autologously prepared, platelet-leukocyte-enriched gel (PLG) is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. The effectiveness of this procedure lies in the delivery of a wide range of platelet growth factors mimicking the physiologic wound healing and reparative tissue processes. Despite an increase in PLG applications, the structures and kinetics of this autogenously derived biologic material have not been observed. METHODS: A review of the most recent literature was performed to evaluate the use of PLG in various surgical disciplines. RESULTS: The review showed that the application of PLG has been extended to various surgical disciplines including orthopedics, cardiac surgery, plastic and maxillofacial surgery, and recently also endoscopic surgery. CONCLUSION: This review demonstrates the usefulness of PLG in a wide range of clinical applications for improvement of healing after surgical procedures.

Reviewing the structural features of autologous platelet-leukocyte gel and suggestions for use in surgery.

The therapeutic use of autologously prepared platelet-leukocyte gel (PLG) is a relatively new technology which might stimulate and accelerate soft-tissue and bone healing. The effectiveness of this procedure lies in the exogenous delivery of a wide range of platelet growth factors, intentionally released from autologously prepared PLG. The rationale to employ this technique is to mimic physiological wound healing and reparative tissue processes. Despite an increase in clinical PLG applications, the structures and kinetics of this biological material have not been completely examined. Electron microscopic imaging was performed to evaluate platelet-leukocyte gel structures. Furthermore, directions for PLG application are presented, based on results from published articles in various surgical disciplines. In conclusion, PLG can be useful in a wide range of clinical applications to enhance healing following surgical procedures, since exogenous applied PLG releases instantly platelet growth factors, in the presence of leukocytic cells.

Preoperative therapy of low-dose aspirin in internal mammary artery bypass operations with and without low-dose aprotinin.

The effect of preoperative low-dose aspirin (1 mg/kg of body weight) and intraoperative low-dose aprotinin (2 million kallikrein inactivator units) treatment on perioperative blood loss and blood requirements in patients who undergo internal mammary artery bypass operations is unknown. Therefore, we retrospectively studied 75 matching patients who underwent internal mammary artery operations, and they were allocated to one of three groups: low-dose aspirin and aprotinin treatment (group 1, n = 25), low-dose aspirin treatment without aprotinin (group 2, n = 25), and neither aspirin nor aprotinin treatment (group 3, n = 25). Although the perioperative blood loss was similar, the blood requirements tended to be higher (p = 0.09) in the patients who were treated with aspirin (group 2) than in the control patients (group 3). When aprotinin was added to the priming solution in patients who were treated with aspirin (group 1), blood loss was significantly lower (p < 0.05) than that of group 2 patients but not of control patients. Blood requirements were significantly lower (p < 0.01) than those of patients in groups 2 and 3. Blood products were needed in 29%, 62%, and 75% of patients in groups 1, 2, and 3, respectively.

Combined superior-transseptal approach to the left atrium.

The combined superior-transseptal approach to the left atrium was used in 22 patients: to perform a mitral valve repair in 14 patients and mitral valve replacement in 8 patients. Mitral valve operation was combined with other cardiac procedures in 18 patients (82%) and was performed as a reoperation in 3 patients (14%). In all cases there was excellent exposure of the complete mitral annulus and subvalvar apparatus. There were no instances of postoperative bleeding, conduction defects, or intraatrial shunting related to the approach. The combined superior-transseptal approach to the left atrium is an excellent approach that can be used in most reoperations and primary procedures for isolated or combined mitral valve operations.

Systemic blood activation with open and closed venous reservoirs.

In 20 patients undergoing coronary artery bypass grafting, we studied prospectively systemic blood activation, blood loss, and the need for donor blood when using an extracorporeal circuit equipped at random with one of two different venous reservoirs. In 10 patients we used an open venous reservoir system (ORS) consisting of a hard shell venous reservoir with an integral cardiotomy filter, and in 10 patients we used a closed reservoir system consisting of a collapsible venous reservoir and separate cardiotomy reservoir. Concentrations of complement 3a, elastase, thromboxane B2, and fibrin degradation products showed a biphasic course, especially in ORS patients. During bypass, we observed a first peak of levels of complement 3a, thromboxane B2, fibrin degradation products, and elastase, which was higher in ORS patients than in patients with the closed system, because their blood continuously contacted the foreign materials of the filter and air in the open reservoir, which was avoided in the closed reservoir. Intensive blood-foreign material contact also caused the highest (p < 0.05) hemolysis in ORS patients. The larger amount of hemolytic products in ORS patients theoretically resulted in a temporary decrease in capacity of their Kupffer cells to clear endotoxin released after aortic declamping. This theory might explain the significantly (p < 0.01) higher second peak of activated products after declamping that was observed in ORS patients. Due to increased blood activation, the largest (p < 0.001) amount of shed blood loss, greatest (p < 0.05) need for colloid-crystalloid infusion, and largest (not significant) need for donor blood were found in ORS patients (0.8 +/- 0.4 versus 0.2 +/- 0.2 units of packed cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative predonation contributes to blood saving.

The merits of reinfusing prebypass-removed autologous blood (intraoperative predonation) to salvage blood and improve postoperative hemostasis are still debated, specifically for patients at a higher risk for bleeding. To evaluate the effect of intraoperative predonation on the platelet count, blood hemoglobin content, and blood saving postoperatively, we retrospectively studied 100 matching patients. All patients underwent internal mammary artery bypass surgery resulting in a considerable blood loss postoperatively. Intraoperative predonation (800 ml), reinfusion of the residual volume of the extracorporeal circuit, autotransfusion of shed blood, and acceptance of normovolemic anemia postoperatively was the approach adopted in 50 patients (group 1). A similar blood salvage program, excluding intraoperative predonation, was carried out in the other 50 patients (group 2), and these served as the control group. The platelet counts and blood hemoglobin content were significantly higher postoperatively (p < 0.01) in the predonated patients than in the control patients. However, the net blood loss, the amount of retransfused shed blood, and the blood requirements postoperatively were significantly less (p < 0.01) in the predonated patients than in the control patients, whereas 65% of the predonated patients versus 10% of the control patients did not need any donor blood products. In conclusion, predonation reduces the postoperative blood loss and thereby importantly ameliorates the blood-saving effect of a blood salvage program after IMA procedures.

Noninvasive long-term follow-up after coarctation repair.

Thirty patients operated on for aortic coarctation while less than 3 years of age underwent magnetic resonance imaging, digital subtraction angiography, and bicycle exercise testing 14 to 33 years (mean, 22 years) after operation. Diameters of the aorta at the site of the anastomosis, of the distal arch, and of the aorta at the level of the diaphragm were measured in the images. Blood pressures were obtained from the right arm and leg before and after exercise. Patients were divided into three groups according to blood pressure data: group I, resting gradient less than 30 mm Hg and exercise gradient less than 50 mm Hg; group II, resting gradient less than 30 mm Hg and exercise gradient greater than 50 mm Hg; and group III, resting gradient 30 mm Hg or greater. A control group underwent the same test. The frequency of hypertensive patients was greater in groups II (58%) and III (100%) than in group I (20%). The anastomosis/descending aorta ratio seen in digital subtraction angiograms was smaller in group II and III patients. Exercise blood pressure gradient correlated significantly (r = -0.48; p = 0.009) with anastomosis/descending aorta ratio in digital subtraction angiograms but not in magnetic resonance images. Twenty of 30 patients (67%) had a significant anatomic narrowing at the site of the anastomosis. Blood pressure data correlated with diameters measured in digital subtraction angiograms but not with diameters measured in magnetic resonance images.

Low-dose aprotinin in internal mammary artery bypass operations contributes to important blood saving.

The effect on postoperative blood loss and blood use of blood-saving treatment with or without 280 mg of low-dose aprotinin (2 million kallikrein inactivator units) was studied in 200 consecutive patients undergoing either unilateral or bilateral internal mammary artery bypass grafting. Postoperative blood loss and total units of homologous blood products were similar in patients having either bypass procedure without aprotinin treatment. In patients given aprotinin, postoperative blood loss and use of homologous blood products were significantly lower (p < 0.05). The use of any donor blood product was prevented in 78% of the patients given aprotinin versus only 45% of patients treated without aprotinin. None of the aprotinin-treated patients underwent repeat thoracotomy for excessive bleeding; repeat thoracotomy was indicated in 8% of the patients having bilateral internal mammary artery grafting without aprotinin treatment. These results demonstrate that low-dose aprotinin reduces blood loss and blood use significantly and prevents excessive bleeding.

Similar hospital morbidity with the use of one or two internal thoracic arteries.

The hospital morbidity and mortality of 100 patients operated with two internal thoracic arteries with or without additional vein grafts (BITA group) were compared with a matched group of 100 patients operated with one left internal thoracic artery (ITA) on the anterior descending artery with additional vein grafts (LITA control group). In each study group, 3% of the patients had diabetes mellitus. There was no statistical significant difference in hospital mortality (1% versus 0%), perioperative myocardial infarction (5% versus 1%), low cardiac output (3% versus 5%), rethoracotomy (1% versus 0%), lung complications (13% versus 13%), wound complications (8% versus 8%), other cardiac complications (26% versus 16%), other noncardiac complications (1% versus 4%), median duration of stay in the intensive care unit (1 versus 1 day), and mean duration of stay in the hospital (10.4 versus 10.8 days) between the groups. Logistic regression analysis showed that the number of ITAs used was not a predictor of complications. Thus, there is no difference between the BITA and LITA control group in hospital mortality and morbidity (in patients with a low incidence of diabetes). If an improvement in cardiac event-free and reoperation-free survival is to be expected, the use of both ITAs can be continued in similar patients.

Systemic blood activation during and after autotransfusion.

To evaluate the extent of shed blood activation in two autotransfusion systems and the effect of circulating blood activation upon autotransfusion, we performed a prospective study in 18 patients undergoing internal mammary artery bypass operation and a control group of 10 patients. The autotransfusion systems were from Sorin (n = 9) consisting of a hard shell reservoir with a filter having a small contact area (0.32 m2), and from Dideco (n = 9) consisting of a hard shell reservoir with a filter having a larger contact area (4.64 m2). We found high concentrations of thromboxane, fibrinogen degradation products, complement split product C3a, and elastase in the shed blood and, with the exception of C3a, in the circulating blood of autotransfused patients. There was no such activation in control patients. The degree of the systemic inflammatory reaction was determined by the type of autotransfusion system and by the amount of infused shed blood. The Dideco system provoked more inflammatory response than did the Sorin. This was reflected by the larger shed blood loss during autotransfusion in the Dideco patients than in Sorin patients, resulting in infusion of more shed blood (means, 737 mL versus 566 mL; not significant). After autotransfusion, Dideco patients shed significantly more blood than did Sorin or control patients (p < 0.05). Dideco patients also needed more colloid/crystalloid solution per 24 hours than Sorin patients (p < 0.05). This became clinically relevant only after infusion of more than 800 mL of shed blood (p < 0.001): hemodilution indicated the need for packed cells in 4 Dideco patients and in 1 Sorin patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Postcardiotomy shock: clinical evaluation of the BVS 5000 Biventricular Support System.

This prospective trial evaluated the safety and efficacy of a new pulsatile, temporary ventricular assist device, the BVS 5000. Patients were eligible for treatment if they were hemodynamically unstable despite maximal pharmacologic and intraaortic balloon pump therapy, were free of concomitant complications, and were less than 6 hours from the first attempt to separate from cardiopulmonary bypass. Fifty-five postcardiotomy patients were enrolled; 31 met all selection criteria and the remainder failed to meet criteria (n = 15) or were not successfully supported (n = 9). The BVS 5000 effectively restored hemodynamics: Mean arterial pressure increased (77.1 +/- 8.0 mm Hg on-support versus 50.1 +/- 15.3 mm Hg presupport; p = 0.0001). Cardiac index increased (2.3 +/- 0.3 L.min-1.m-2 on-support versus 1.6 +/- 0.6 L.min-1.m-2 presupport; p = 0.0013). Left ventricular filling pressure decreased (11.9 +/- 4.5 mm Hg on-support versus 23.8 +/- 8.7 mm Hg presupport; p = 0.0030). The most frequent complication was bleeding in 42 patients (76%). Of the patients meeting all criteria, 17 (55%) were weaned from support and 9 (29%) were discharged. Survival was significantly influenced by presupport cardiac arrest events. Survival among patients not experiencing arrest was 47%. Eight patients are long-term survivors and were asymptomatic in New York Heart Association class I or II at 1-year follow-up. The BVS 5000 restored hemodynamics, permitted myocardial recovery, and improved survival in a group of patients who would have otherwise died.

Does it make sense to use two internal thoracic arteries?

Retrospectively, the first 143 patients who were operated on with bilateral internal thoracic arteries (BITA group) were matched with 143 patients operated on with only one left internal thoracic artery anastomosed on the left anterior descending artery and additional vein grafts (LITA group) and followed up for a maximum of 8 years. At 5 years follow-up there were no significant differences in event-free survival between the groups. After 8 years, the overall survival was 96% and 92% (not significant [NS]), cardiac survival 99% and 97% (NS), angina-free cardiac survival 51% and 35% (NS), infarction-free cardiac survival 95% and 78% (NS), reintervention-free cardiac survival 87% and 88% (NS), and all cardiac event-free survival 49% and 31% (NS) for the BITA and LITA groups, respectively. The incidence of late pulmonary, wound, and other complications was comparable. Cox proportional hazards analysis showed that a higher left ventricular end-diastolic pressure and female sex were predictors of recurrent angina and late cardiac events. During this intermediate-term follow-up, the use of one or two internal thoracic arteries was of no value in predicting angina-free or cardiac event-free survival.

Differentiation between transmural perioperative myocardial infarction and subendocardial injury after coronary artery bypass grafting using biochemical tests, elaborated by cluster and discriminant analysis.

The aim of this study is to differentiate between transmural perioperative myocardial infarction (T-PMI) and subendocardial perioperative myocardial injury (S-PMI) as a complication of coronary artery bypass grafting (CABG). Seventy-three patients undergoing CABG were followed post operatively by measuring troponin T, CK-MB isoenzyme mass concentration (CK-MB mass), creatine kinase MB isoenzyme activity (CK-MB activity), creatine kinase (CK), alpha hydroxybutyrate dehydrogenase (HBD), and aspartate aminotransferase (AST) at five sampling times. Lacking a proper definition of the gold standard for the diagnosis of perioperative myocardial infarction, a statistical procedure was used. Supported by the cluster analysis method of Ward, patients were assigned to a patient group with a perioperative myocardial infarction (PMI) or a patient group without a PMI (non-PMI) as a confirmation of interpretation of the biochemical results. Using the results of electrocardiogram (ECG) and echocardiography, the PMI patient group was split into a T-PMI patient group and a S-PMI patient group. With discriminant analysis, two canonic discriminant functions were drawn up to differentiate between patients suffering from a T-PMI or S-PMI and non-PMI patients.

Influence of mammary artery as a bypass vessel on the results of seven biochemical assays after coronary artery bypass surgery.

We compared the changes in troponin T, creatine MB isoenzyme mass concentration (CK-MB mass), creatine kinase MB isoenzyme activity (CK-MB activity), creatine kinase (CK), alpha-hydroxybutyrate dehydrogenase (HBD), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) concentrations after coronary artery grafting with saphenous vein grafts, without or in combination with uni- or bilateral internal mammary artery(ies) as bypass vessels in 73 patients. An increase in CK concentration after surgery was highest for the bilateral internal mammary artery bypass patient group and lowest for the group who received only saphenous vein grafts. We present 90th percentile values for the seven tests.

Autotransfusion of shed blood contributes additionally to blood saving in patients receiving aprotinin (2 million KIU).

Aprotinin decreases the hemoglobin content of shed blood significantly and thereby could potentially reduce the contribution of autotransfusion of shed blood to the blood-saving program. In part 1, by means of a prospective randomized study, we evaluated the effect of autotransfusion (AT) of shed blood on the reduction and avoidance of donor blood requirements in 40 matched patients undergoing internal mammary artery bypass (IMA) surgery and treatment with low-dose aprotinin (2 million KIU). Twenty patients (Group 1) received AT with a hard shell cardiotomy reservoir; twenty patients (Group 2, control) did not receive AT. In part 2, we studied at random the hemoglobin and total-protein content of shed blood in 10 patients of group 2 and in 10 IMA patients not receiving aprotinin. Retransfused patients required 0.1 +/- 0.3 units of donor blood versus 0.8 +/- 0.2 units in non-retransfused patients (not significant). The use of any blood product was avoided in 95% and 80% of the patients, respectively (not significant). Patients receiving aprotinin lost 50% less (P < 0.05) hemoglobin (62 g) and total-protein (28 g) in their drainage system than patients not receiving aprotinin. It was calculated that autotransfusion of about 530 ml of shed blood in aprotinin-treated patients, is equivalent to 0.4 units of homologous packed cells. In conclusion, autotransfusion of shed blood may contribute to blood saving in IMA patients treated with aprotinin, which reduces the shed blood hemoglobin and total protein content by 50%.

An anatomical variation of the right gastroepiploic artery that excludes its use as a pedicled coronary bypass graft.

In an attempt to perform complete coronary revascularization with only arterial conduits in a 44 year-old male, both internal mammary arteries and the right gastroepiploic artery were harvested. The right gastroepiploic artery, however, showed an anatomical variation that excluded its use as a pedicled graft.

The Monostrut prosthetic valve. Predictors for valve-related events during an eight years' experience.

All postoperative complications, including transient ischaemic attacks (TIA) and cerebrovascular accidents (CVA) of 259 patients, in whom a total of 301 Monostrut tilting-disc valves were implanted between January 1985 and December 1991 were evaluated retrospectively. The follow-up was maximally 8 years, with a mean of 3.5 years, and totaled 914 patient-years. In this study we found no mechanical deterioration of the Monostrut valve and demonstrated the elimination of valve thrombosis in patients receiving adequate anticoagulation. The actuarial probability of being free of thrombo-embolism was 94.7% +/- 1.7% and free of anticoagulant related hemorrhage 95.4% +/- 1.5% at 8-years. In comparison with earlier reports by others, our findings show a lower ratio of thromboembolic and hemorrhagic events. We demonstrated a correlation (p < 0.05) between thrombo-embolic and hemorrhagic complications. In addition, a lower incidence of CVA's (0.22 per 100 patient-years), but a higher incidence of TIA's (0.66 per 100 patient-years) in comparison with the general Dutch population was found. At eight years follow-up, all patients were in Class I or II of the New York Heart Association Classification. Although the overall valve related event-free survival at eight years was only 47.9%, 93.5% of the patient were satisfied with their operative result. Predictive factors for late mortality were the occurrence of paravalvular leakage (p < 0.01), the age of the patient at the time of operation (p < 0.01) and the number of diseases coronary arteries (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of a blood conservation program including low-dose aprotinin in routine myocardial revascularization.

OBJECTIVES: We attempted to analyze the efficacy and safety of an extensive blood saving program applied in a large cohort of patients. MEASURES: Blood saving included reinfusion of intraoperative predonated blood, aprotinin (2 million KIU) in the prime solution, reinfusion of any residual volume, postoperative acceptance of normovolemic anemia (hematocrit > or = 25%) and autotransfusion of shed blood. SETTING, EXPERIMENTAL DESIGN AND PATIENTS: In our general hospital with a heart surgery service (1150 cases/year), we studied the records of 527 non-selected consecutive patients, who were prospectively treated with this program being applied in primary myocardial revascularization between. RESULTS: We avoided the use of donor blood in 86.9% of the patients requiring a mean of 0.2+/-0.01 unit of donor blood per patient. No repeat thoracotomy for bleeding was needed in any patient. Univariate analysis revealed that female gender, a low level of hematocrit, high age, a small stature, weight, body surface area, and red cell volume prebypass significantly (p<0.001) were correlated to treatment with donor blood. Multiple regression showed that a small red cell volume and a low prebypass hematocrit were the most (p<0.0001) significant predictors for the use of donor blood. Observing a low incidence of morbidity (myocardial infarction, gastrointestinal, neurological thromboembolic, renal and wound complications), the safety of this program seems to be emphasized. CONCLUSIONS: Extensive blood saving including low-dose aprotinin reduced effectively and safely the need for donor blood in a large cohort of patients.

Blood loss and use of blood in internal mammary artery and saphenous vein bypass grafting with and without adding a single, low-dose of aprotinin (2 million units) to the pump prime.

In comparison with saphenous vein bypass grafting (SVG) without a pleurotomy, internal mammary artery (IMA) bypass surgery might enhance more blood loss by the intrathoracic wound and a wide opened pleura. Low-dose aprotinin (Trasylol) reduces blood loss and consequently, the use of homologous blood. We studied the blood loss and blood requirements peri-operatively in 70 patients, who underwent either SVG-(n = 35) or IMA-surgery (n = 35) without aprotinin and another 70 patients who underwent SVG- (n = 35) or IMA-surgery (n = 35) with a single dose of aprotinin, added to the pump prime. We also determined the hemoglobin and total protein content of the shed blood. Without aprotinin administration, the mean intra-operative and post-operative blood loss was significantly less (p < 0.01) in SVG-patients, than in IMA-patients. We observed no statistical differences in the mean blood requirements between SVG- and IMA-surgery (1.2 units and 1.6 units). The use of any homologous blood product was similarly averted in 39% of the SVG-patients, and in 48% of the IMA-patients. Treatment with aprotinin significantly lessened (p < 0.01) the mean intra-operative blood loss only in IMA-patients. Post-operative blood loss was diminished with 45% in IMA-patients and 33% in SVG-patients, being significantly less (p < 0.01) after SVG, than after IMA-surgery. Blood requirements were significantly lowered (p < 0.01): a total mean of 0.2 units in SVG- and 0.6 units in IMA-patients (NS). Any homologous blood product was prevented in 78% of the IMA-patients and in 87% of the SVG-patients (NS). The mean loss of hemoglobin and total protein per 100 ml of shed blood was similar in IMA-, and SVG-patients with or without aprotinin, although aprotinin diminished the total amounts in both groups with 50% (p < 0.01).