Shigeki Yanagida

Angioscopic coronary macromorphology in patients with acute coronary disorders.

To investigate the pathogenesis of acute coronary disorders and to clarify what type of plaque precedes these disorders, percutaneous transluminal coronary angioscopy, by means of a new angioscope, was carried out during catheterisation in 100 consecutive patients anatomically suitable for such investigations. The quality of the angioscopic image was good enough for analysis in 84 patients (14 with acute myocardial infarction [within 8 h of onset], 16 with recent myocardial infarction [3 days-2 months since onset], 24 with old myocardial infarctions, 10 with unstable angina, and 20 with stable angina). Thrombi were observed in most patients with acute coronary disorders (all 14 with acute myocardial infarction, 9 of 10 with unstable angina). Occlusive thrombi were more common in patients with acute myocardial infarction than in those with unstable angina (11 [79%] vs 1 [10%]; p less than 0.001), whereas mural (non-occlusive) thrombi were more common in the unstable angina than in the acute myocardial infarction group (8 [80%] vs 3 [21%]; p less than 0.001). Xanthomatous ulcerated plaques or ragged irregular surfaces were seen in patients with acute coronary disorders and in those with recent myocardial infarction. Xanthomatous plaques were more common in patients with acute coronary disorders (50%) than in those with stable angina (15%) or old myocardial infarction (8%). By contrast white and smooth plaques were seen in cases of stable angina and old myocardial infarction. Angioscopy could display the intracoronary lumen more precisely than could coronary arteriography. This angioscopic study suggested that, although a thrombus overlying a rupture in the lining of the plaque was common in both unstable angina and acute myocardial infarction, the character of the thrombus may differ between these disorders, and lipid-rich xanthomatous plaque may precede rupture.

Differential extractability of creatine phosphate and ATP from cardiac muscle with ethanol and perchloric acid solution

To compare the extractability of creatine phosphate with that of ATP by alcohol extraction, both compounds were extracted from normal perfused rat heart tissues by using various stepwise concentrations of ethanol and 0.4 M HClO4. Powdered samples (6-15 mg wet wt) from the freeze-clamped tissues were homogenized in 2 ml of the ethanol solutions. After centrifugation, the supernatant was removed; each centrifuged sediment was rehomogenized with 2 ml of 0.4 M HClO4 and centrifuged. The supernatant was neutralized with 0.4 m KHCO3. The same powdered samples were directly homogenized with 2 ml of 0.4 M HClO4 and treated in the same manner. Only a small amount of ATP in the tissues was extracted by an 85% or higher concentration of ethanol. Further, about 13% of the tissue ATP was not extractable by the subsequent perchloric acid extraction. In contrast to ATP, creatine phosphate in the tissues was partially extracted by 95% ethanol and nearly all of the tissue creatine phosphate was extracted by 70% ethanol. The total creatine phosphate obtained by 70% ethanol and by subsequent perchloric acid extraction was significantly higher than that obtained by direct perchloric acid extraction. From these results, it was concluded that the extractability of creatine phosphate in the tissue by alcohol extraction is clearly different from that of ATP. Additionally, the stepwise extraction is recommended as a useful method for the extraction of energy metabolites in perfused rat heart tissue.

Severe, short-term food restriction improves cardiac function following ischemia/reperfusion in perfused rat hearts

The purpose of this study was to clarify the characteristics of improved ischemic tolerance induced by severe, short-term food restriction in isolated, perfused rat hearts. Male Wistar (8 week-old) rats were given a food intake equivalent to a 70% reduction on the food intake of ad-libitum fed rats for 11 days (FR group and AL group, respectively). After this period, hearts were isolated and perfused in the Langendorff mode, and subjected to 20 min of global ischemia followed by 30 min of reperfusion. Although the coronary flow rate in the FR group (63.0 ± 3.1 ml/min/g dry weight) was higher than that in the AL group (47.1 ± 1.3 ml/min/g dry weight) during preischemic perfusion, the lactate release into the coronary effluent and absolute values of +dP/dt and −dP/dt in the FR group (2422 ± 161 and −1282 ± 51) were inversely lower than in the AL group (2971 ± 156 and −1538 ± 74, respectively). An increase in ischemic contracture was suppressed in the FR group. Following reperfusion, cardiac function, high-energy phosphate content, and intracellular pH, as measured by 31P-nuclear magnetic resonance spectroscopy, had recovered to a much greater degree in the FR group than in the AL group. The serum T3 level was significantly lower in the FR group (2.7 ± 0.1 pg/ml) than in the AL group (3.6 ± 0.1 pg/ml), and the levels of triglycerides, free fatty acids, insulin, and glucose were also significantly lower in the FR group than in the AL group. The protein expressions of myocyte enhancer factor 2A, Na+, K+-ATPase, and phospholamban in the cardiac tissue were higher in the FR group than in the AL group. These results suggested that severe, short-term food restriction improves ischemic tolerance in rat hearts via altered expression of functional proteins induced by low serum T3 levels, decreased coronary conductance, and change in metabolic flux.

Continuous inhibition of poly(ADP-ribose) polymerase does not reduce reperfusion injury in isolated rat heart.

Abstract: Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 &mgr;M) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis.