Kenryo K. Minezaki

Expression of cytokine-induced neutrophil chemoattractant in rat cardiac myocytes.

Accumulation and adhesion of leukocytes to cardiac myocytes play important roles in the pathogenesis of inflammation-mediated myocardial injury such as ischaemia/reperfusion and myocarditis. The involvement of leukocyte chemotactic factors has been speculated in these processes. We investigated the expression of cytokine-induced neutrophil chemoattractant (CINC) in rat cardiac myocytes. CINC is a rat equivalent of human interleukin-8. On exposure to interleukin-1 alpha (IL-1 alpha), cultured neonatal rat cardiac myocytes released appreciable levels of CINC both dose- and time-dependently. Tumor necrosis factor-alpha and lipopolysaccharide also significantly increased CINC accumulation in the culture supernatant. CINC mRNA expression was not observed in unstimulated myocytes, however, the expression was markedly induced by exposure to IL-1 alpha with a peak elevation at 3 h. Potent chemotactic activity for neutrophils was detected in the supernatant of cultured rat cardiac myocytes by stimulation with IL-1 alpha. This IL-1 alpha-induced chemotactic activity was significantly inhibited by polyclonal anti-CINC antiserum. Addition of dexamethasone, genistein, actinomycin D or cycloheximide significantly suppressed the IL-1 alpha-induced CINC accumulation. Under hypoxia (95%N2 + 5%CO2), CINC accumulation was increased in a time-dependent manner, and reoxygenation after hypoxia further intensified CINC accumulation. This hypoxia reoxygenation-induced CINC expression was significantly inhibited by pretreatment with dexamethasone. In conclusion, inflammatory stimuli induce the expression of CINC in rat cardiac myocytes, which may lead to myocardial injury via accumulation and activation of neutrophils.

Effect of Mitral Valvuloplasty in Mitral Stenosis on Coagulation Activity

We investigated the plasma levels of molecular markers for the status of thrombin generation and fibrinolysis in patients with mitral stenosis before and after percutaneous mitral valvuloplasty. Our results show that percutaneous mitral valvuloplasty results in decreased coagulation activity, suggesting that percutaneous mitral valvuloplasty is also useful for prevention of systemic embolism in patients with mitral stenosis.

The Demonstration of Dmpo Superoxide Adduct upon Reperfusion Using a Low Non-Toxic Concentration

Experiments were conducted in an attempt to circumvent the problem associated with the use of a high concentration of the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which has been suggested to have serious toxic effects on tissue. A low concentration of DMPO (10 mM) was used to detect the free radical generation in hearts with ischemia/reperfusion insult. In the effluent immediately after reperfusion, DMPO-OOH, a superoxide spin adduct of DMPO, was obtained. DMPO in that concentration range did not interfere at all with the left ventricular (LV) function during the control perfusion period. Even after reperfusion, LV function was not depressed any more than that occurring in hearts without DMPO, whereas DMPO of the conventional concentration (100 mM) markedly depressed the ventricular function. Enzyme leakage from hearts also supported non-toxicity finding of DMPO at 10 mM; confirming that the DMPO superoxide adduct is real evidence of the generation of superoxide upon reperfusion and is not attributed to an artificial generation due to the cytotoxicity of DMPO.

The detection of technical failures in perfused heart with ischemia and reperfusion by epicardial NADH fluorescence

SummaryThis study documents the value of continuous observation of nicotinamide adenine dinucleotide (NADH) fluorescence (NADH-F). NADH-F monitoring is used to identify ischemic regions for the recognition of minor technical failures associated with ischemia and reperfusion experiments in the isolated perfused heart system. The visualization of NADH-F is possible by simply irradiating the heart with ultraviolet light. Rat hearts, in the working-heart mode, were subjected to occlusion/reperfusion of the left coronary artery, and analyzed. The perfusate was filtered through a 5 µm pore membrane. Out of 281 hearts which were judged to be free of technical failures by conventional physiological indices (heart rate >200/min, cardiac output >34 ml/min, and coronary flow 9–14 ml/min), 43 (15%) disclosed an abnormal NADH-F area prior to the coronary intervention. During coronary intervention, 29 technical failures were detected as indicated by sparse NADH-F distribution with occlusion, delayed disappearance of NADH-F upon reperfusion, or the exhibition of an abnormal NADH-F region unassociated with the coronary artery supply area. These technical failures are not detectable without the use of NADH-F, although the actual number of failures detected may depend on the skill of the operator. We recommend NADH-F monitoring for any preparations which do not contain hemoglobin, since NADH-F is an intrinsic probe for ischemia and is easily applicable to a variety of experiments.

Impact of an Influenza Pandemic on the Mortality of Congestive Heart Failure in Older Japanese: The 1998 Japanese Influenza Pandemic

dent in all activities of daily living (ADLs), with serum sodium within normal values. Two months later he was again admitted with the same manifestations of delirium, dependent in activities of daily living (ADLs), and with important hyponatremia after interruption of corticosteroid medication. Reintroduction of corticosteroid medications produced marked improvement in his metabolic, mental, and functional status.

The failure of radical scavengers to attenuate the incidence of reperfusion arrhythmias despite improvement of cardiac function

SummaryWe studied the concomitant effects of scavengers of reactive oxygen species (ROS) on both cardiac function and the incidence of arrhythmias. Isolated rat heart was perfused with a working mode paced at 300 beats/min. The left coronary artery was occluded for 5, 7, 15, or 60 min and reperfused thereafter for 30 min. Superoxide dismutase and catalase were infused from 5 min prior to reperfusion to the end of reperfusion in the scavenger treatment group. In the 60-min ischemia group with scavenger treatment, the cardiac output was significantly higher than that in the untreated group at both 10 and 30 min of reperfusion (P < 0.01). In the 15-min ischemia group with scavenger treatment, the cardiac output showed a tendency toward a higher value than that in the untreated group. The incidence of reperfusion arrhythmias occurring after a short ischemic time (5, 7, or 15 min) were similar in the scavenger treated and untreated groups; but, with a preceding ischemia of 60 min, the incidence of ventricular tachycardia was higher in the scavenger treated group than in the untreated group (P < 0.02). In conclusion, scavengers improved contractile dysfunction but did not attenuate the incidence of arrhythmias.