During cardiac surgery, ischemia-reperfusion injury (IRI) is thought to be a major factor in intraoperative myocardial damage. Coronary endothelial cells have been thought to play an important role in the pathogenesis of cardiac IRI. Release of nitric oxide (NO) from coronary endothelial cells is impaired following myocardial ischemia, and this may contribute to the vulnerability of the coronary circulation to thrombus-formation and vasospasm. Several experimental studies have found that NO has a cardioprotective effect in myocardial IRI. In this regard, attempts have been made to supplement NO production exogenously during reperfusion, when endogenous NO release from endothelial cells may be diminished. In a blood-reperfused heart model, L-arginine acts cardioprotectively via 2 primary possible mechanisms: (1) by blocking both neutrophil aggregation and neutrophil adherence, and (2) by scavenging oxygen-derived free-radicals. On the other hand, in a non-blood reperfused heart model, the optimal concentration of L-arginine may be low and protection may be due to 2 additional mechanisms: (3) direct coronary vasodilatation and (4) reduced oxygen demand due to vasodilatation-induced hypotension. Other studies have suggested that NO exacerbates IRI and that NO synthase (NOS) inhibitors act cardioprotectively. It has also been suggested that the pharmacological effectiveness of inhibiting NO production may be due to the prevention of peroxinitrite formation from NO and superoxide during reperfusion. This review summarizes the current understanding of the role of NO in IRI.

Neutrophil activation and oxygen-derived free radical formation have been implicated in cardiac ischemia-reperfusion injury. To elucidate the mechanism of ischemia-reperfusion injury, we thus determined the effect of the nitric oxide (NO) precursor L-arginine on the free radical injury of cultured cardiomyocytes which were obtained from patients undergoing corrective surgery for tetralogy of Fallot. Free radicals were generated from hypoxanthine via xanthine oxidase, and the cellular changes were determined microscopically. All concentrations of L-arginine (0.5 to 3 mM) prolonged the myocyte survival time compared to the control group, with 0.5 mM L-arginine increasing the survival time to the greatest extent. Cellular susceptibility to free radical injury was the lowest with 0.5 mM L-arginine. Further experiments were performed with 0.5 mM L-arginine plus 100 mM or 1000 mM of the NO synthase (NOS) inhibitor NG-nitro-L-arginine methylester (L-NAME) to determine whether or not the effects of L-arginine are mediated through the NO pathway. The survival time for the cells treated with a concentration of L-NAME was shorter than for the cells treated with 0.5 mM L-arginine alone. These results suggest that L-arginine acts through the NO-dependent pathway. In conclusion, our findings thus confirmed the quenching effects of NO on free radical injury in cultured cardiomyocytes.

The release of nitric oxide (NO) from coronary endothelial cells is impaired following reperfusion; however, several experimental studies have found that it exerts a cardioprotective effect during myocardial ischemia-reperfusion. Thus, attempts have been made to supplement NO production exogenously during reperfusion when endogenous NO release may be diminished. Conversely, other studies suggest that NO exacerbates reperfusion injury by inducing the production of peroxynitrite. NO has also been reported to provide beneficial effects as a selective pulmonary vasodilator to relieve pulmonary hypertension. A loss of NO-mediated relaxation caused by the dysfunction of endothelial cells is characteristic of intimal hyperplasia, and nitrosovasodilators have proven efficient against atherosclerotic coronary heart disease, which may be attributable to their antiplatelet effects as well as to vasodilation. Furthermore, protamine sulfate, which is rich in L-arginine, is thought to augment NO production by supplying exogenous L-arginine, or to act on endothelial cell receptors to stimulate the production of NO. This review summarizes the current role of NO in cardiac surgery.

Salivary gland-type mixed tumor primarily arising in the lung is extremely rare. We report here a case of this type of tumor that occurred in the periphery of S4 of the right middle lobe in a 74-year-old man. Light-microscopically, this lung tumor, 15x9mm in size, exhibited almost the same features as those of mixed tumor of the salivary gland intermingled with chondromyxoid stroma, glandular component, solid growth pattern of myoepithelial components and well-developed cartilage formation, exhibiting a sharp margin. Immunohistochemical study revealed that the glandular components in the tumor was positive for thyroid transcription factor-1, TTF-1, a marker of epithelial cells of the thyroid as well as the lung. Furthermore, surface lining cells of the glandular components and luminal contents were positive for surfactant apoprotein A, PE-10, used as a marker of type II alveolar epithelial cells. These findings clearly demonstrate for the first time that glandular epithelial cells in the present salivary gland-type mixed tumor exhibited differentiation toward type II alveolar epithelial cells.

Tepid retrograde cardioplegia resulted in an accumulation of toxic metabolites. The addition of antegrade vein graft infusions at a flow rate of 100 ml/min resulted in a washout of these metabolites. A flow rate of 200 ml/min further improved this washout and resulted in improved ventricular function. An integrated approach to myocardial protection using a flow rate of 200 ml/min may improve the results of coronary bypass surgery.