An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation.

BACKGROUND: Aprotinin is a serine protease inhibitor used extensively in cardiac operations to reduce postoperative bleeding. It has also been used in trials aimed at reducing the systemic inflammatory response to cardiopulmonary bypass. It remains unclear whether the anti-inflammatory action of aprotinin is related to its general ability to suppress leukocyte activation or whether aprotinin can exercise effects during the leukocyte-endothelial cell adhesion cascade. METHODS: We used intravital microscopy to study the 3 main stages of the adhesion cascade (leukocyte rolling, firm adhesion, and extravasation) within the mesenteric microcirculation of rats. This in vivo technique allows leukocyte recruitment to be viewed directly through the transparent mesentery of anesthetized animals. RESULTS: Aprotinin, given by continuous infusion at a clinically relevant dose, exerted no effect on the rolling or firm adhesion responses toward local chemoattractant N -formyl-methyl-leucyl-phenylalanine but significantly inhibited extravasation of leukocytes (73% at 40 minutes, P =.04) into surrounding tissues. In parallel in vitro experiments, aprotinin (used at 200, 800, and 1600 kIU/mL) dose dependently inhibited neutrophil transmigration through cultured endothelial cells in response to 3 different chemoattractants: N -formyl-methyl-leucyl-phenylalanine (P <.001 at 800 and 1600 kIU/mL), interleukin 8 (P <.05 at 200 kIU/mL and P <.001 at 800 and 1600 kIU/mL), and platelet-activating factor (P <.05 at 1600 kIU/mL). CONCLUSIONS: Our studies have therefore revealed a novel anti-inflammatory mechanism of aprotinin operating at the level of leukocyte extravasation. These findings may be relevant in the prevention of systemic inflammation after cardiopulmonary bypass through the use of protease inhibitors.

Recurrent arterial embolization from a metastatic germ cell tumor invading the left atrium.

Arterial embolization of a malignant tumor is extremely rare. We report an unusual case of a young adult man who presented with acute lower limb ischemia and a mass in the right lung and left atrium. These clinical manifestations were the result of metastases and embolization from a germ cell tumor and were the first indication of malignancy in this patient. The importance of appropriate investigations in the subsequent treatment is stressed.

A literature review of cardiopulmonary bypass models for rats.

Cardiopulmonary bypass (CPB) has improved a great deal since its first applications in the early 1950s. If improvements are to be continued, a preclinical model of CPB for small animals is desirable, mainly because of convenience of equipment and low costs. We review the different models of CPB for rats that have been designed, discuss their characteristics and points where improvements may be made. We give suggestions and requirements for a new up-to-date model that could be a useful tool in continued research on the pathophysiology and therapeutic strategies of CPB.

Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass.

Cardiopulmonary bypass is often followed by pulmonary dysfunction as assessed by measuring the alveolar-arterial oxygenation gradient, intrapulmonary shunt, degree of pulmonary edema, pulmonary compliance, and pulmonary vascular resistance. It is also regarded as a risk factor for development of acute respiratory distress syndrome. On the other hand, cardiopulmonary bypass is associated with a whole body inflammatory response, which involves activation of complement, leukocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and oxygen free radicals. Leukocyte adhesion to microvascular endothelium, leukocyte extravasation, and tissue damage are the final steps. Although the inflammatory response to cardiopulmonary bypass often remains at subclinical levels, it can also lead to major organ dysfunction and multiple organ failure. This review article summarizes the recent literature on the molecular and cellular mechanisms involved in the phenomenon of pulmonary dysfunction after cardiopulmonary bypass. It also summarizes reports on the prevalence and mortality of acute respiratory distress syndrome after cardiac surgery.

Outcome of coronary endarterectomy: a case-control study.

BACKGROUND: Despite early reports showing a high incidence of postoperative morbidity and mortality, coronary endarterectomy continues to be used as an adjunct to coronary artery bypass grafting, particularly in diffusely diseased coronary arteries. The changing nature of patients and improvements in modern cardiac surgery call for a reevaluation of the role of coronary endarterectomy. METHODS: Data from the 56 patients, who underwent coronary endarterectomy in our institution between January 1993 and August 1996, were reviewed retrospectively and compared with a control group of 56 patients matched for age, sex, LV function, and angina class. In the endarterectomy group, there were 47 men and nine women, with a mean age of 59.6 years. The mean follow-up time was 21 months. Indications for operation were angina in 45 (80.3%), angina with signs or symptoms of cardiac failure in 3 (5.4%), and prognosis in 8 (14.3%) asymptomatic patients. RESULTS: Fifty (89%) patients had one, four (7.2%) had two, and 2 (3.6%) patients had three coronary arteries endarterectomized. Of these 64 endarterectomies, 33 (51.5%) involved the right coronary artery, 20 (31.3%) the left anterior descending artery, and 11 (17.2%) branches of the circumflex artery. There were three (5.4%) nonfatal myocardial infarctions in the endarterectomy group, but none in the control group (p>0.05). Two patients (3.6%) in the endarterectomy group, but none in the control group, died within the first 30 days (p>0.05). Actuarial survival and incidence of recurrent angina were similar in the two groups. CONCLUSIONS: In current cardiac surgical practice, coronary endarterectomy displays satisfactory rates of postoperative morbidity and medium term results in selected groups of patients.

Thirty-day mortality and long-term survival following surgery for prosthetic endocarditis: a study from the UK heart valve registry.

OBJECTIVE: To assess the 30-day mortality, long-term survival and freedom from reoperation following surgery for prosthetic endocarditis (PVE). METHOD: A retrospective analysis of data from the UK Heart Valve Registry of 322 patients who had undergone single mechanical/bioprosthetic valve replacement for PVE between 1 January 1986 and 31 December 1996. The mean age was 54.9 +/- 12.8 years and 213 (66.1%) were males. There were 170 aortic and 152 mitral valve implantations. Eighty-five (26%) of the infected valves were bioprosthetic and 237 (74%) were mechanical. Of the new prostheses implanted 53 (17%) were bioprosthetic and 269 (83%) were mechanical. Of those with infected bioprostheses, 50 (15.2%) had mechanical valves at redo surgery, whilst 219 (68.3%) of infected mechanical prostheses were re-replaced by mechanical prostheses. The follow-up was 98% complete with a total of 1084.9 patient years. RESULTS: The 30-day mortality was 63 (19.9%; 95%CI 15.9-24.7%). There were 85 late deaths. One, 5 and 10 year survival rates were 67.1% (61.6-72.0%), 55.0% (49.0-60.7%) and 37.6% (27.9-47.2%), respectively. Age was the only significant determinant of 30-day mortality (P = 0.04). Age (P = 0.001) and explanting of infected bioprosthesis and replacement by mechanical valve (P = 0.04) determined long-term survival (P = 0.001). The incidence of re-reoperation was 9.9%. Freedom from reoperation for PVE was 88.4, 87.3 and 87.3% at 1, 5 and 10 years, respectively. Explanting of bioprosthesis and replacement by mechanical valve (P < 0.001) and reoperation within 60 days of native valve replacement (P = 0.02) were determinants of reoperation for PVE. Freedom from death or reoperation was 61.1, 50.6 and 34.2% at 1, 5 and 10 years, respectively. Age (P = 0.003), explanting of bioprosthesis and replacement by mechanical valve (P = 0.002) and the period between prosthetic re-replacement (P = 0.04) determined freedom from death or reoperation. CONCLUSION: Operation for PVE carries a high 30-day mortality and reduced long-term survival. There is no evidence that type of prosthesis used for re-reoperation determines survival or freedom from re-reoperation.

Tricuspid valve replacement: UK Heart Valve Registry mid-term results comparing mechanical and biological prostheses.

BACKGROUND: Little is known of time-related outcome and comparative performance of biological and mechanical prostheses following tricuspid valve replacement (TVR). METHODS: A retrospective UK Heart Valve Registry study (Jan 1, 1986 to June 30, 1997) identified 425 patients who underwent TVR. Two-hundred twenty-five (52.9%) received biological and 200 (47.1%) received mechanical valves. One-hundred sixty (38%), 158, and 76 had isolated, double, and triple valve replacements, respectively. The follow-up was 96% complete with a total of 1,585 patient-years. RESULTS: Thirty-day mortality for TVR was 17.3% (73 deaths). One-, 5-, and 10-year survival rates were 72.2%, 59.9%, and 42.9%, respectively. Year of operation (p = 0.04), age (p = 0.04), and number of valves implanted (p = 0.0 3) predicted overall mortality. Age (p<0.001) and year of operation (p = 0.002) predicted overall survival. Thirty-day mortality for biological and mechanical prostheses was 18.8% and 15.6%, respectively. One-, 5-, and 10-year survival rates were 70.5%, 61.5%, and 47.7% for biological and 74.0%, 57.9%, and 33.9% for mechanical prostheses, respectively. Freedom from reoperation at 1 and 10 years was 98.7% and 97.4%. Freedom from death or reoperation was 71.2% at 1 year and 41.9% at 10 years. None of the above outcomes was significantly different between the type of valve prostheses. CONCLUSIONS: TVR carries a high 30-day mortality and a poor longer term survival. No superiority could be identified for biological or mechanical prostheses in the tricuspid position for either survival or reoperation.

An unusual aorto-pulmonary communication secondary to syphilitic aortitis.

With the advent of antibiotics syphilis and its complications appear to have been declining as an important cause of cardiovascular disease. We describe a patient with an unusual aorto-pulmonary communication secondary to syphilitic aortitis. The case illustrates the difficulty in defining the anatomy of this rare association preoperatively. The reason for the rarity of this manifestation is discussed and finally doubt is cast upon the assumption that cardiovascular syphilis is of only historical interest.

Significance of plasma fibrinogen in coronary arterial disease: marker or causative risk factor for arterial thrombosis?

The relationship between fibrinogen and severity of disease was measured in patients with coronary arterial disease (n = 301) prior to surgical coronary revascularisation. Platelet reactivity (shear-induced haemostasis) was measured from non-anticoagulated blood, in vitro. Coagulation was assessed by the clotting time of flowing native blood (dynamic) and by the conventional (stagnant) tube tests. Significantly enhanced platelet reactivity to shear-stress was observed when patients with one-vessel disease were compared to those with two- or three-vessel disease (P = 0.003). Neither coagulation nor fibrinogen were significantly related to the severity of disease. Furthermore, patients who had myocardial infarction (n = 144) showed enhanced platelet reactivity (P = 0.02) as compared to those who had not (n = 157). Again, neither coagulation nor fibrinogen discriminated between these groups of patients. Relationship between plasma fibrinogen and platelet reactivity was also investigated in vitro. Identical blood samples with normal (220-280 mg/dl) and elevated plasma fibrinogen (approximately 500 mg/dl) were compared by measuring platelet reactivity and coagulation from native blood and platelet aggregation in whole blood. The in vitro studies suggested that plasma fibrinogen and platelet reactivity are inversely associated. Furthermore, increased fibrinogen prolonged dynamic coagulation. These findings do not support the assertion that elevated plasma fibrinogen is a true causative factor for coronary arterial disease and arterial thrombosis.

High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation.

BACKGROUND: A unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions. METHODS AND RESULTS: Two hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p less than 0.0001 versus less than 0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; less than 0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction. CONCLUSIONS: It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.

Preoperative hemostatic activity and excessive bleeding after cardiopulmonary bypass.

The rationale for predicting the risk of excessive postoperative bleeding by assessing the hemostatic status of a patient before cardiopulmonary bypass was investigated. A novel, rapid, overall test (hemostatometry) consisting of a physiologically relevant test of platelet function (shear-induced hemostasis) and coagulation was performed using nonanticoagulated blood and compared with the routine coagulation screen. Two hundred five patients undergoing elective coronary revascularization were studied 3 to 4 days before operation. Forty-nine bled excessively for nonsurgical reasons; none were predicted by the routine coagulation tests. Using a stepwise discriminant analysis, hemostatometry correctly predicted 31 of 49 (63%). Thirty of 156 predicted as bleeders by hemostatometry did not bleed. Thus, preoperative hemostatometry predicted 77% of the true outcome. The false predictions suggest, however, that certain bleeding abnormalities probably acquired during cardiopulmonary bypass cannot be predicted. These findings do not justify the routine use of preoperative tests in assessing the bleeding risk in patients undergoing cardiopulmonary bypass.

Extensive endocardial resection for recurrent ventricular tachyarrhythmias.

Twenty-two consecutive patients underwent elective map-guided extensive endocardial resection (EER) for recurrent ventricular tachyarrhythmias (VT) of whom 20 were male. The ages ranged from 43 to 74 years (mean 57). All arrhythmias were ischaemic in origin. The mean ejection fraction was 29%. The presenting arrhythmias were ventricular tachycardia in 14, ventricular fibrillation (VF) alone in 1 and ventricular tachycardia and VF in 7. Useful additional intraoperative mapping was obtained in 19 patients. Under cardioplegic arrest, the scarred left (22) and where indicated right (4) ventricular endocardium was extensively resected. Resection of scarred papillary muscles was avoided and where indicated, localised cryoablation was performed: 21/22 had concomitant aneurysmectomy and/or coronary artery bypass grafting. There was 1 (4.5%) operative death. All survivors (95.5%) underwent postoperative electrophysiological studies at around 1 week. None had inducible arrhythmias. There were 3 (13.5%) late cardiac deaths, all due to primary cardiac failure without recurrence of arrhythmia. Of 17 (77%) long-term survivors, 16 (94%) are VT-free on no anti-arrhythmic medication at a mean follow-up of 37.2 months. One developed a new arrhythmia at 1 year which is controlled on medication. EER offers a high rate of success in ablating VT in association with a low operative mortality and good prospect of VT-free long-term survival.