Hoang S. Tran

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome

BACKGROUND Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fishers exact test, and multivariate regression were performed with statistical significance P </=0.05. RESULTS Fifty-five consecutive patients between 14 and 62 years of age were admitted in a 1-year period and underwent 64 diagnostic and therapeutic procedures. Fourteen (22%) postoperative infections and 18 (28%) complications other than infection, with an overall mortality of 11%, were documented. Total preoperative white blood cell count ([WBC] P <0.01), preoperative percent lymphocyte count (P <0.01), absolute postoperative CD4 lymphocyte count (P <0.01), and postoperative plasma viral load (P <0.0001) are associated with mortality. Multivariate regression indicated that postoperative percent CD4 lymphocyte count is an independent predictor of both postoperative infection and other complications (P <0.05, R = 0.848, power = 0.9911), while the decrement in percent CD4 lymphocyte count is an independent predictor of postoperative complications other than infection (P <0.05, R = 0.596, power = 0.7838). CONCLUSIONS In accordance with the medical literature for clinical outcome in HIV-infected and AIDS patients, both immune cell counts and HIV-1 RNA counts were found to associate with postoperative mortality. However, the postoperative and decrement in percent CD4 lymphocyte proved to be the independent predictors of postoperative complications.

Prostacyclin is neither sufficient alone nor necessary to cause pulmonary dysfunction: results from infusions of prostacyclin and antiprostacyclin antibody in porcine septic shock.

ObjectiveThis study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock. DesignExperimental. SettingLaboratory. SubjectsTwenty-three anesthetized adult swine. IntervensionsSwine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL·kg−1·hr−1 and increased to 4.0 mL·kg−1·hr−1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion. Measurements and Main Results Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased Pao2, as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p < .05). Thromboxane B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p < .05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups. ConclusionsProstacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.

Transmyocardial Laser Revascularization: Current Status

Transmyocardial laser revascularization (TMLR) has been widely evaluated for treatment of the ischemic myocardium either in conjunction with coronary artery bypass grafting or as sole therapy. Clinically, it has shown significant improvement for angina symptoms, but the mechanism by which this modality works is unknown at this time. The original premise on which transmyocardial revascularization was established depended on its ability to essentially generate channels that would directly carry blood from the ventricle into the ischemic myocardium. This theory, however, has not been substantiated, so other mechanisms have been postulated. This article gives a historical perspective on the advent of transmyocardial revascularization and the many animal and human studies that have paved the way for its clinical use. Current controversies are examined, along with the new advances in laser technology and where the future of TMLR is headed.Transmyocardial laser revascularization (TMLR) has been widely evaluated for treatment of the ischemic myocardium either in conjunction with coronary artery bypass grafting or as sole therapy. Clinically, it has shown significant improvement for angina symptoms, but the mechanism by which this modality works is unknown at this time. The original premise on which transmyocardial revascularization was established depended on its ability to essentially generate channels that would directly carry blood from the ventricle into the ischemic myocardium. This theory, however, has not been substantiated, so other mechanisms have been postulated. This article gives a historical perspective on the advent of transmyocardial revascularization and the many animal and human studies that have paved the way for its clinical use. Current controversies are examined, along with the new advances in laser technology and where the future of TMLR is headed.

Site-specific immunosuppression: mechanisms of cellular immunosuppression that are operative at local and systemic levels.

The cellular mechanisms by which topical cyclosporine A (tCsA) induces site-specific immunosuppression were investigated. Experiments were designed to elucidate how cyclosporine A (CsA) suppresses activated immunocytes in animals that are undergoing local alloactivation and concomitant tCsA immune suppression. Lewis rats received dual Lewis x Brown Norway rat skin allografts; the rats were treated with systemic CsA (sCsA) at 8 mg/kg/day for 10 days after grafting and then tCsA and vehicle thereafter. CsA added to mixed lymphocyte reactions 24 hours after culture initiation modeled the local effects of CsA on alloactivated immunocytes, and tCsA in conjunction with limited sCsA prolonged local skin allograft survival. CsA inhibited both antigen-specific and nonspecific activated alloresponses of immunocytes from animals that had received allografts and that underwent limited sCsA treatment only in a dose-dependent manner. When tCsA had been applied, immunocyte responses to a nonspecific antigen were extremely CsA-resistant as compared with those induced by antigen-specific suppression. However, this nonspecific alloresponse was fully suppressible with the use of elevated CsA doses (66 microg/mL); thus alloresponding immunocytes were significantly more sensitive to CsA if they were challenged with the donor antigen and preexposed to limited sCsA followed by tCsA in vivo.

The cardiovascular hemodynamics and leukotriene kinetics during prostacyclin and anti-prostacyclin antibody infusions in septic shock.

This study evaluated whether or not prostacyclin (PGI2) was necessary or sufficient by itself in a pathophysiologic concentration to mediate the cardiovascular dysfunction of septic shock. Anesthetized adult swine received anesthesia only (ANESTHESIA CONTROL, n = 6); graded Aeromonas hydrophila, 10(10)/mL, infusion at 0.2 mL/kg/h that increased to 4.0 mL/kg/h over 3 h (SEPTIC SHOCK CONTROL, n = 6); pathophysiologic prostacyclin infusion to match septic shock control plasma levels without bacteremia (PGI2 INFUSION, n = 6), or graded Aeromonas hydrophila plus anti-prostacyclin antibody infusion (ANTI-PGI2-Ab INFUSION, n = 5). This graded porcine bacteremia model was 100% lethal after 4 h. Cardiovascular hemodynamics, arterial blood gases, and plasma levels of arachidonate metabolites were measured at baseline and hourly over a 4-h period. The results showed that PGI2 was not a necessary mediator of impaired cardiovascular hemodynamics in graded bacteremia, as anti-PGI2 antibody infusion did not improve the cardiac index, systemic vascular resistance, or peripheral oxygen balance in septic animals. Also, PGI2 was not sufficient alone to cause the cardiovascular dysfunction of sepsis, as pathophysiologic infusion of PGI2 did not reproduce such changes in normal animals. PGI2 blockade during bacteremia significantly increased LTC4D4E4, and LTB4 whereas PGI2 infusion suppressed LTC4D4E4 concentration, suggesting that endogenous PGI2 may blunt leukotriene release during septic shock. These results indicate a complex dynamic equilibrium among prostacyclin and leukotrienes in septic shock.

A Novel Technique in a Sheep Model for Evaluating Prosthetic Heart Valve Performance

There have been many various animal studies to evaluate the structural integrity and antithrombogenicity of prosthetic heart valves. We were interested in developing a novel sheep model to study the thrombogenicity of mechanical heart valves placed into the systemic circulation but without the need for cardiac bypass. Also, we wanted to minimize the risk of paraplegia from complete thoracic aortic clamping. Six sheep underwent left lateral thoracotomy for placement of a mechanical heart valve in parallel with the descending thoracic aorta. A valved conduit with a dacron tube graft sutured to the back end was fashioned. Employing partial aortic occlusion with a side-biting clamp, the proximal and distal ends were anastomosed in an end-to-side fashion. Once flow was confirmed through the graft, the native aorta was occulded with umbilical tape. The sheep received no postoperative anticoagulation. The median operative time and estimated blood loss (EBL) was 170 min and 250 cc, respectively. Patency of the valved conduits was confirmed during the initial procedure, and there was no incidence of paraplegia postoperatively. Two animals expired shortly after extubation and at necropsy the valved conduits were patent with preserved valve function. The four survivors were sacrificed a median of 37 days postoperatively. Prior to euthanasia, the valved conduits were evaluated in situ with ultrasound. In all cases, the valves had clot formation at the hinges, which prevented active movement of the leaflets. This novel in vivo technique provides an alternative in testing the thrombogenicity of prosthetic heart valves without cardiac bypass or the risk of paraplegia in an animal that is extremely sensitive to complete aortic cross-clamp.There have been many various animal studies to evaluate the structural integrity and antithrombogenicity of prosthetic heart valves. We were interested in developing a novel sheep model to study the thrombogenicity of mechanical heart valves placed into the systemic circulation but without the need for cardiac bypass. Also, we wanted to minimize the risk ofparaplegia from complete thoracic aortic clamping. Six sheep underwent left lateral thoracotomy for placement of a mechanical heart valve in parallel with the descending thoracic aorta. A valved conduit with a dacron tube graft sutured to the back end was fashioned. Employing partial aortic occlusion with a side-biting clamp, the proximal and distal ends were anastomosed in an end-to-side fashion. Once flow was confirmed through the graft, the native aorta was occulded with umbilical tape. The sheep received no postoperative anticoagulation. The median operative time and estimated blood loss (EBL) was 170 min and 250 cc, respectively. Patency of the valved conduits was confirmed during the initial procedure, and there was no incidence of paraplegia postoperatively. Two animals expired shortly after extubation and at necropsy the valved conduits were patent with preserved valve function. The four survivors were sacrificed a median of 37 days postoperatively. Prior to euthanasia, the valved conduits were evaluated in situ with ultrasound. In all cases, the valves had clot formation at the hinges, which prevented active movement of the leaflets. This novel in vivo technique provides an alternative in testing the thrombogenicity of prosthetic heart valves without cardiac bypass or the risk of paraplegia in an animal that is extremely sensitive to complete aortic cross-clamp.

Surface Modifications of Mechanical Heart Valves

For more than four decades, the advent of prosthetic heart valves has revolutionized the treatment of cardiac valvular dysfunctions. Compared to patients with dysfunctional cardiac valves who did not undergo valve replacement, patients who did have cardiac valve replacement operations for severe valve disease have increased survival, enhanced cardiovascular function, and improved quality of life (1,2). More than 80 models of prosthetic heart valves have been introduced and used globally, and more than 60,000 cardiac valve replacement surgeries are performed annually in the United States alone (3).