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University of Wisconsin solution has provided excellent myocardial preservation. However, the high potassium content of the currently available University of Wisconsin solution has been implicated in coronary artery endothelial damage. We placed 16 neonatal (age 1 to 3 days) Duroc piglet hearts on an isolated nonworking perfusion circuit. Endothelium-dependent and endothelium-independent vasodilation were tested by measuring coronary blood flow after intracoronary infusion of bradykinin (10-6 mol/L) and nitroprusside (10–6 mol/L), respectively. In addition, nitric oxide levels were measured after bradykinin infusion. The hearts were then arrested blindly with either a modified University of Wisconsin solution (group 1; n = 8, K+ = 25 mEq/L) or standard University of Wisconsin solution (group 2; n = 8, K+ = 129 mEq/L) by infusion of cardioplegic solution every 20 minutes for a total of 2 hours. After bradykinin infusion, the mean coronary blood flow increased by 237.1% ± 14.0% of baseline valves before arrest and by 232.8% ± 16.0% after arrest in group 1 ( p = not significant). As in the first group, the mean coronary blood flow in group 2 increased by 231.1% ± 13.7% before arrest; however, the increase in mean coronary blood flow after arrest was significantly attenuated (163.3% ± 12.8%, p < 0.01). The loss of endothelium-dependent coronary blood flow response in group 2 correlated with a decreased capacity to release nitric oxide after arrest (prearrest 8.25 ± 2.30 nmol/min per gram versus postarrest –2.46 ± 2.29 nmol/min per gram, p < 0.01). Endothelium-independent vasodilatory response revealed no significant difference between groups before and after arrest. These results suggest that the low-potassium University of Wisconsin solution provides superior protection of the endothelium by preserving the endothelium-dependent vasodilatory response to nitric oxide release. (J Thorac Cardiovasc Surg 1996;112:103-10)

Commercially available cardioplegia delivery systems now allow for antegrade (aortic root, coronary ostia, saphenous vein graft) perfusion to occur either sequentially or simultaneous with retrograde (coronary sinus) perfusion. This study was designed to compare the total flow and local distribution of sequential versus simultaneous antegrade/retrograde cardioplegia delivery. Methods: Explanted human hearts diagnosed with idiopathic cardiomyopathy underwent a cold cardioplegic arrest and bicaval cardiectomy. Thirty-seven degree centigrade blood cardioplegia containing colored microspheres was then delivered antegrade (red color) at a pressure of 80 mmHg or retrograde (blue color) at a pressure of 40 mmHg. In the sequential group (n = 6), cardioplegia was delivered antegrade and then retrograde for 2 minutes, respectively. For the simultaneous group (n = 6), cardioplegia was delivered both antegrade and retrograde for 2 minutes. The ventricular myocardium was then sampled at 12 representative sites to determine regional cardioplegic flow. Results: Mean total cardioplegia delivery/minute was 0.69 ± 0.62 mL/g per minute for sequential cardioplegia, and 0.46 ± 0.19 mL/g per minute for simultaneous cardioplegia (p > 0.05, NS). At the 12 ventricular sites sampled, mean regional cardioplegic flow (mL/g per min) was in general slightly greater for sequential delivery. However, this was not statistically significant (p > 0.05, NS). Conclusion: The data suggest that there may be a slight advantage in total cardioplegia delivery and regional cardioplegia delivery when using sequential rather than simultaneous cardioplegia delivery. However, this difference was not statistically significant and is likely not of clinical significance. Therefore, we would recommend using either sequential or simultaneous antegrade/retrograde cardioplegia based upon whichever technique facilitates the conduct of the individual operation.

This study introduces a model for intracoronary gene transfer in murine cardiac isografts using adenovirus vectors. This approach may offer an opportunity to modulate alloreactivity after cardiac transplantation. Donor hearts were infected via the coronary arteries with a volume of 10 9 plaque-forming units per milliliter of a recombinant adenovirus containing the β-galactosidase–encoding gene (Ad.CMVLacZ). In a control group, 200 μl of normal saline solution was infused. The grafts were stored in 4º C cold saline solution for 15 minutes, then transplanted heterotopically into syngeneic hosts (B10.BR). The grafts were harvested at 3, 7, 15, or 30 days (n = 5 for each group) after transplantation, and β-galactosidase activity was assessed by histochemical staining (X-gal). All grafts were functioning when harvested. X-gal staining pattern was nonuniform with positive staining appearing in epicardial, myocardial, and endocardial cells, as well as in the vessel walls. The cells permissive to infection consisted predominantly of myocardial cells. The mean total numbers of β-gal–positive staining cells per slice were 68.7 ± 27.3 in the 3-day group, 330.4 ± 53.8 in the 7-day group, 151.3 ± 48.0 in the 15-day group, and 39.9 ± 10.8 in the 30-day group, thus peaking in the 7-day group (p < 0.05). Control isografts (n = 5), retrieved at day 30, revealed no staining activity. In conclusion, our model demonstrates that intracoronary gene transfer to the transplanted murine cardiac grafts is feasible at the time of harvest. Adenovirus-mediated gene transfer produces widespread gene expression which, though perhaps transient, does not adversely affect myocardial structure or function. This technology may allow modification of graft immunogenicity in the future through the production of therapeutic proteins sufficient to modulate local immune responses. (J THORAC CARDIOVASC SURG 1996;111:246-52)