Early detection of acute allograft rejection in rat heart transplantation: flowcytometric monitoring of interleukin 2 receptor expression on CD8 positive lymphocytes.

To assess the usefulness of flowcytometric monitoring in the early detection of acute allograft rejection, we studied surface markers of graft infiltrating lymphocytes, coronary sinus blood lymphocytes and peripheral blood lymphocytes after rat heart transplantation. Fisher rats served as donors and Lewis rats as recipients. Among recipients that received no immunosuppression, grafts were removed 2 days after transplantation (Ongoing Rejection Group: n = 7) and on the day of terminal rejection (Rejection Group: n = 7). The Immunosuppression Group (n = 7) was treated with cyclosporine A at a dose of 3 mg/kg/day intramuscularly for 14 days. The following two color analyses were studied: OX8 (anti-CD8) with OX39 (anti-interleukin 2 receptor; IL2R), W3/25 (anti-CD4) with OX39, W3/25 with OX8. Histological grading demonstrated no significant difference between the Ongoing Rejection Group and the Immunosuppression Group, which showed mild rejection (1.29 +/- 0.27 versus 1.14 +/- 0.24). The proportion of CD8(+)IL2R(+) graft infiltrating lymphocytes showed a more significant increase in the Ongoing Rejection Group than in the Immunosuppression Group (32.1 +/- 3.05 versus 20.6 +/- 9.02; p &#60; 0.01). The proportion of CD8(+) IL2R(+) coronary sinus blood lymphocytes also showed significant increase in the Ongoing Rejection Group compared with the Immunosuppression Group (4.63 +/- 1.91 versus 2.52 +/- 1.60; p &#60; 0.05). These results suggest that this technique can detect acute allograft rejection earlier than endomyocardial biopsy, before the phase in which histological findings become evident.</p

Angiogenesis Is Enhanced in Ischemic Canine Myocardium by Transmyocardial Laser Revascularization 11This study was supported in part by a research grant from CardioGenesis Corporation, Sunnyvale, California.

AbstractObjectives. This study sought to test whether transmyocardial laser revascularization (TMLR) stimulates angiogenesis in an animal model of chronic ischemia.Background. TMLR relieves angina and may also improve blood flow in patients who are not candidates for traditional therapies. The mechanisms of these benefits are not fully defined.Methods. Ischemia was created in 14 dogs by proximal left anterior descending coronary ameroid constrictors. TMLR was performed in the anterior wall (∼1 channel/cm2) of seven dogs; the remaining dogs served as the ischemic control group. Myocardial blood flow was measured (colored microspheres) at rest and during chemical stress (adenosine) in the acute setting and after 2 months.Results. TMLR did not influence blood flow in the acute setting. After 2 months, resting blood flow increased comparably in the anterior wall in both groups to ∼80% of normal. However, the TMLR-treated dogs demonstrated an ∼40% increase in blood flow capacity during stress in the ischemic territory compared with untreated dogs (left anterior descending coronary artery/left circumflex coronary artery flow 0.53 ± 0.16 in the control group vs. 0.73 ± 0.08 in TMLR animals, p < 0.05). Vascular proliferation, assessed by bromodeoxyuridine incorporation and proliferating cell nuclear antigen positivity in endothelial and smooth muscle cells was about four times greater in the TMLR group than in the control group (p < 0.001). The density of vessels with at least one smooth muscle cell layer was ∼1.4 times greater in the myocardium surrounding the TMLR channel remnants than in control ischemic tissue (p < 0.001).Conclusions. In this canine model of chronic ischemia, TMLR significantly enhances angiogenesis as evidenced by the increased number of vessels lined with smooth muscle cells, markedly increased vascular proliferation and increased blood flow capacity during stress

Effect of left atrial plication for the giant left atrium on left ventricular function.

Left atrial plication (LAP) following Kawazoe's method was performed on eight patients with mitral valve stenosis associated with a giant left atrium. To investigate the effect of LAP particularly on left ventricular function, the preoperative and postoperative left ventricular function in these patients were compared. The data were also compared to that of the non-left atrial plication (non-LAP) group with left atrial dimension of 60 mm or over. In the LAP group, there were significant differences between preoperative and postoperative data in the following parameters; New York Heart Association (NYHA) class, cardiothoracic ratio, mean pulmonary arterial pressure (PAP), left ventricular end-diastolic pressure (LVEDP), left atrial dimension, stroke volume index, ejection fraction and cardiac index. On the contrary, in the non-LAP group, there were significant differences between preoperative and post-operative data in the following two factors; NYHA class and PAP. The size of the left atrium in the non-LAP group remained unchanged over the course of long-term follow-up. Despite severe clinical symptoms and severely reduced cardiac function of the patients in the LAP group, cardiac function in all patients improved satisfactorily. This suggests that left atrial plication has a considerably beneficial effect on left ventricular function, and therefore, may be recommended for patients with a giant left atrium.</p

Effects of Modified Ultrafiltration on Coagulation as Measured by the Thromboelastograph

Hemodilution during cardiopulmonary bypass (CPB) continues to be a cause of morbidity associated with coagulation dysfunction, bleeding, and allogeneic blood transfusion. Clot formation and strength have been shown to impact bleeding and transfusions. Strategies to reduce hemodilution may be negated based on the course of the cardiac procedure itself. Modified ultrafiltration (MUF) is commonly used in pediatric cardiac surgery; however, it is not well accepted in adult surgery. This study aimed to evaluate clot formation and strength, bleeding, and transfusions in adult subjects undergoing MUF. Nineteen subjects having primary coronary artery bypass, aortic, or mitral valve surgeries were recruited and randomized to having MUF (n = 10) or no-MUF (n = 9) performed after the termination of CPB. Five time points for data collection were designated: T1, baseline/induction; T2, termination CPB; T3, post-MUF; T4, post-protamine; T5, 24 hours postoperative. Subjects randomized to MUF had 1505 ± 15.8 mL of effluent removed, and no-MUF subjects had the CPB remnants processed with a cell salvage device. There was no statistical difference seen in 24-hour chest tube output, thromboelastograph values, or allogeneic transfusions at any time point between MUF and no-MUF subjects. There was a significant difference between MUF and no-MUF in the number of autologous cell salvage units processed (1.3 ± .48 vs. 2.9 ± .78, p = .0013) and end of procedure net fluid balance (+2003 ± 1211 vs. +4194 ± 1276 mL, p = .001), respectively. Estimated plasma loss from the cell salvage device was 477.6 mL greater in the no-MUF group. In primary adult cardiac procedures, MUF did not change coagulation values as measured by thromboelastography, number of allogeneic unit transfusions, or chest tube output at 24 hours postoperatively. There was a significant difference in autologous cell salvage units processed and end of procedure net fluid balance that benefited MUF subjects