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A prospective randomized trial comparing retrograde warm blood cardioplegia with cold oxygenated crystalloid cardioplegia in coronary bypass patients at Emory University revealed an increased risk of adverse neurological events in the warm group (4.5% vs 1.4%, p < 0.005). Multivariant analysis found four variables to be independent predictors of adverse neurological outcome: congestive heart failure (p = 0.002); age (p = 0.002); aortic cross-clamp time (p = 0.02); and randomization to the warm group (p = 0.026). In Toronto, a prospective randomized trial compared antegrade warm blood cardioplegia with antegrade cold blood cardioplegia. Compared to the Emory trial, the Toronto series contained fewer female patients (16% vs 25%), fewer patients older than age 70 (16% vs 30%), and fewer redo operations (4% vs 14%). The other prominent differences between the Emory series and the Toronto series were: extensive use of retrograde cardioplegia in the Emory series; mild hypothermia in the warm group in the Toronto series; and elevated serum glucose in the warm group in the Emory series. The Toronto series showed no difference in adverse neurological events comparing cold versus warm cardioplegia groups. A comparison of these two series suggests that mild hypothermia in the Toronto series, elevated glucose in the Emory series, or the use of retrograde cardioplegia may be operative in the elevated incidence of adverse neurological events seen in the Emory series in addition to a relatively larger number of high-risk patients (female, elderly, and redo) in the Emory series.

Retrograde techniques for the administration of cardioplegia solutions are of interest because of their relative practical convenience, and because of the possibility that they provide better delivery to myocardial regions jeopardized by coronary stenosis than can be achieved with traditional antegrade techniques. This study was designed to test the following three hypotheses about how the distribution of cardioplegia by retrograde techniques might be optimized: (1) venting an occluded coronary artery improves the distribution of cardioplegia to the myocardial region originally supplied by it; (2) increasing the coronary sinus perfusion pressure makes the distribution of cardioplegia through the myocardium more uniform; and (3) increasing the driving pressure, as achieved by increasing the coronary sinus perfusion pressure or occluding a left coronary artery, improves the distribution of flow to the right ventricular free wall and interventricular septum. Tracer microspheres infused retrogradely with cardioplegia solution into canine hearts in vitro showed that the distribution of flow through the coronary sinus is consistently and significantly nonuniform, and is not significantly altered by coronary arterial occlusion and venting, or by increases in coronary sinus perfusion pressure.

The effects of different cardioplegia temperatures on myocardial protection with continuous aerobic blood cardioplegia were studied in a canine model of acute regional injury after left anterior descending coronary artery occlusion and subsequent revascularization. Twenty-five animals underwent 90 minutes of occlusion followed by revascularization during 60 minutes of electromechanical arrest with continuous retrograde blood cardioplegia delivered at one of three temperatures: 18 degrees C (n = 8), 28 degrees C (n = 8), and 37 degrees C (n = 9). Left ventricular protection was assessed in a right heart bypass model in terms of the left ventricular pressure-volume relationships, myocardial oxygen consumption, regional myocardial blood flow, adenosine trisphosphate concentration, and water content. The preload recruitable stroke work relationship at 90 minutes after reperfusion was better in the 18 degrees C and 28 degrees C groups than that in the 37 degrees C group (18 degrees C, 85 +/- 14 erg x 10(3)/mL; 28 degrees C, 77 +/- 17 erg x 10(3)/mL; 37 degrees C, 58 +/- 13 erg x 10(3)/mL; p < 0.05). The maximum elastance and stress-strain relationships showed there were no significant differences between the groups at 90 minutes. The myocardial oxygen consumption was greatest in the 37 degrees C group during the first hour after reperfusion (18 degrees C, 5.4 +/- 1.4 mL O2.min-1.100 g-1; 28 degrees C, 4.7 +/- 1.1 mL O2.min-1.100 g-1; 37 degrees C, 6.3 +/- 1.6 mL O2.min-1.100 g-1; p < 0.05). The regional myocardial blood flow, adenosine triphosphate concentration, and myocardial water content were similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Three murine hybridomas (TMMR-1-3) were developed by repeated immunizations of mice with four different human osteosarcoma cell lines in an alternating sequence of inoculations. The monoclonal antibodies were screened for reactivities to cultured cell lines and tissue sections of osteosarcomas using flow cytometry and immunohistochemical techniques. TMMR-2 is a highly specific antibody (IgG1) that reacted with all 14 osteosarcoma tumors and eight human osteosarcoma cell lines tested, including the established human osteosarcoma cell lines HOS and Saos-2. Benign neoplastic cells from two osteoblastomas, osteoblasts from regions of reparative osteoid formation and neonatal new bone, are also reactive with TMMR-2. TMMR-1 has mesenchymal specificity while TMMR-3, although reactive with osseous differentiated cells, also reacted with mitotic cells of all cell types. Characterization of antigen structure by Western immunoblotting revealed that TMMR-2 reacted with a 100 degrees C heat labile mercaptoethanol-sensitive Mr 26,000 protein, and TMMR-3 recognized a mercaptoethanol-resistant Mr 97,000 protein whereas TMMR-1 reacted with a series of bands from 65,000 to 85,000 molecular weight, all of which were mercaptoethanol sensitive. TMMR-1 and TMMR-2 monoclonal antibodies showed complement-independent inhibition of [3H]thymidine incorporation into DNA, but did not exhibit cytotoxic activity. The results suggest that TMMR-2 is a specific antibody that recognizes an osteoblast/osteocyte surface antigen present in normal, reactive, and neoplastic disorders of bone. The inhibitory effects on DNA synthesis in cultured osteosarcoma cells by TMMR-2 indicate an important cell growth/proliferation role of this surface antigen. These monoclonal antibodies, in combination with other known antibodies, can be used to characterize mesenchymal cell surface antigenic structure and differentiation.