Muneyasu Saito

ENDOTHELIAL CELL INJURY IN VENULE AND CAPILLARY INDUCED BY CONTRAST ULTRASONOGRAPHY

The aim of the present study was to test the hypothesis that microvascular endothelial cells (EC) are subject to the bioeffects induced by contrast ultrasound (US) because of their proximity to the circulating microbubbles. We examined EC injury in each microvessel section (arteriole, capillary or venule) in rat mesenteries among the following five groups: three controls (sham operation, microbubble injection alone, US exposure with saline injection), and two contrast-US groups (US exposure at a 1-Hz or 30-Hz frame rate with microbubble injection). Propidium iodide (PI), a fluorescent indicator of cell injury, was employed to visualize impaired EC. PI-positive nuclei were equally few among the three controls. Contrast-US increased PI-positive cells in capillaries (1-Hz frame rate, 2.4 +/- 2.2 cells per 0.1-mm vessel length, p = 0.09; 30-Hz frame rate, 4.3 +/- 1.8 cells, p < 0.01) and in venules (1-Hz frame rate, 4.1 +/- 2.5 cells, p < 0.05; 30-Hz frame rate, 13.8 +/- 3.6 cells, p < 0.01) compared with sham operation (0.10 +/- 0.22 cells). The finding indicates that diagnostic contrast US potentially causes EC injury, particularly in venules and capillaries.

Usefulness of extracorporeal membrane oxygenation for treatment of fulminant myocarditis and circulatory collapse

Prognosis for fulminant myocarditis with cardiogenic shock refractory to conventional therapy is poor. This report describes mechanical circulatory support with extracorporeal membrane oxygenation as an effective alternative for treating fulminant myocarditis with circulatory collapse.

Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction

Objective: To compare the effects of nicorandil (a hybrid ATP sensitive potassium channel (K+ATP channel) opener/nitric oxide donor) with those of isosorbide dinitrate (ISDN) on myocardial microcirculation and cardiac function in patients with acute myocardial infarction (AMI) who had undergone reperfusion treatment by direct balloon angioplasty. Design: Double blind randomised study. Patients: 60 patients with AMI in Killip class I. Interventions: Patients were assigned into two treatment groups: a nicorandil group (n  =  30) and an ISDN group (n  =  30). Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission and was administered directly to the treated coronary artery immediately after angioplasty. Results: Compared with ISDN, nicorandil more frequently caused recovery of ST segment elevation just after reperfusion (15 of 27 (55.5%) in the nicorandil group v 5 of 26 (19.2%) in the ISDN group, p  =  0.006). The nicorandil group had higher values of averaged peak velocity 40 minutes after reperfusion (mean (SD) 24.8 (13.3) cm/s v 16.0 (11.1) cm/s, p  =  0.045) and higher values of regional wall motion of the infarcted area three weeks after onset of AMI (–1.78 (1.11) v –2.50 (1.04) SD/chord, p  =  0.046). Conclusions: A combination of nicorandil drip infusion starting before reperfusion and intracoronary injection immediately after reperfusion is more effective than a similarly performed infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI area. The nicorandil regimen resulted in better left ventricular regional wall motion.

Transient rise in serum interleukin-8 concentration during acute myocardial infarction.

OBJECTIVE--To determine whether interleukin-8 (IL-8, a potent activator of neutrophils) is involved in tissue injury during ischaemia and reperfusion in patients with acute myocardial infarction. SETTING--Teaching hospital. SUBJECTS--Five consecutive patients with acute Q-wave myocardial infarction, two patients with stable angina who underwent elective percutaneous transluminal coronary angioplasty, and 10 normal controls. MAIN OUTCOME MEASURE--Serum IL-8 concentration measured by enzyme linked immunosorbent assay (ELISA) over time (every four, eight or 12 hours for 36-72 hours). RESULTS--All five patients with acute myocardial infarction had a transient but significant rise in serum IL-8 concentration (13-1100 ng/l) within 22 hours after the onset of symptoms, whereas IL-8 was not detected in any of the samples from patients with angina pectoris or normal controls. One patient who died of pump failure and two patients who had mild congestive heart failure showed the highest values (1100, 920, and 190 ng/l respectively). CONCLUSIONS--Serum IL-8 concentration showed a transient rise during the very early phase of acute myocardial infarction. In combination with several recent lines of evidence indicating the importance of injurious activities of neutrophils as a cause of tissue damage in acute myocardial infarction and the potent stimulation of neutrophils by IL-8, these results strongly suggest that IL-8 is important in the development of myocardial injury in acute myocardial infarction.

Long-term prognosis of patients with acute myocardial infarction: Is mortality and mortidity as low as the incidence of ischemic heart disease in Japan?

Long-term prognosis of hospital survivors with myocardial infarction (MI) was investigated to assess the validity of previous reports on the low incidence of ischemic heart disease in Japan. Among 686 patients with acute MI, 115 (16.8%) died during hospitalization and eight were lost to follow-up. The cumulative mortality rate of the 563 hospital survivors was 6.2% in the first year, 12.0% in the third year, and 19.1% in the fifth year, with cardiac death accounting for 63% of the deaths. Cumulative rates for recurrent MI were 4.4% in the first year, 11.0% in the third year, and 13.2% in the fifth year. Parameters influencing long-term mortality rates obtained by stepwise discriminant analysis were arteriosclerosis-related factors, presence of congestive heart failure at admission, age, and presence of previous MI, while parameters influencing the recurrence of MI were congestive heart failure, arteriosclerosis-related factors, and ischemic findings at discharge. Our findings indicate that the prognosis for patients with MI is far better in Japan than in Western countries and support the previous reports on the low incidence of ischemic heart disease in Japan, while factors influencing the prognosis are similar to those previously reported.

Comparison of clinical features of non-Q wave and Q wave myocardial infarction

The clinical spectrum and outcome of 119 patients with acute non-Q wave myocardial infarction (NQMI) were studied, in comparison with those of 354 patients with acute Q wave myocardial infarction (QMI). The patients with NQMI had a significantly higher incidence of preinfarction angina (73% vs 63%), previous myocardial infarction (43% vs 22%), multivessel disease (73% vs 51%), postinfarction angina (55% vs 21%), and recurrent myocardial infarction during follow-up for an average of 25 months (17% vs 8%). NQMI patients also had a lower rate of complication of pump failure and smaller infarct size estimated by peak creating phosphokinase (CPK) levels (1361 +/- 1243 vs 2711 +/- 1684 IU/L) than those with QMI. There was no difference in in-hospital mortality between the two groups (17% vs 17%). However, death due to cardiac rupture was exclusively noted in the QMI group. The present study suggests that NQMI is more unstable than QMI in the clinical course.

Effects of right ventricular ischemia on left ventricular geometry and the end-diastolic pressure-volume relationship in the dog.

We studied the effects of right ventricular ischemia on left ventricular three-dimensional geometry and the end-diastolic pressure-volume relationship in 16 open-chest dogs before and after pericardiectomy. Left ventricular volume was calculated from three internal dimensions measured with ultrasonic crystals. In one group of eight dogs, right coronary artery (RCA) occlusion for 2 min with the pericardium intact reduced aortic flow by 24 +/- 9% (p less than .001) and septal-lateral dimension by 8 +/- 5% (p less than .01), without changing anterior-posterior and apical-basal dimensions. However, parameters of left ventricular systolic function (aortic flow, left ventricular systolic pressure, peak dP/dt, and mean percent systolic shortening) were similar to those observed at a comparable level of left ventricular end-diastolic volume during inferior vena caval occlusion. In the other group of eight dogs, during RCA occlusion before pericardiectomy the left ventricular end-diastolic pressure-volume relationship determined during rapid blood transfusion shifted leftward and upward significantly from the preocclusion relationship. After pericardiectomy, RCA occlusion caused less significant changes in aortic flow and septal-lateral dimension as well as in the left ventricular end-diastolic pressure-volume relationship. We concluded that right ventricular ischemia causes a leftward shift of the interventricular septum in end-diastole and an alteration of the left ventricular end-diastolic pressure-volume relationship without changing left ventricular myocardial performance. These changes are enhanced by the intact pericardium.

Further ST Elevation at Reperfusion by Direct Percutaneous Transluminal Coronary Angioplasty Predicts Poor Recovery of Left Ventricular Systolic Function in Anterior Wall AMI

Some patients with acute myocardial infarction (AMI) develop further ST elevation at reperfusion by percutaneous transluminal coronary angioplasty (PTCA). This study reports the ST deviation at reperfusion by direct PTCA in relation to the clinical factors and the recovery of left ventricular (LV) systolic function. Fifty-two patients with anterior wall AMI were treated with direct PTCA. They were classified into the following 3 groups according to the change in ST elevation at reperfusion: increase of > or = 20% (ST reelevation); reduction of > or = 20% (ST resolution); and the other (ST no change). Angina pectoris preceding AMI occurred less often in the ST reelevation group (ST reelevation group, 38%; ST no change group, 81%; ST resolution group, 70%; p < 0.05). Recovery of LV ejection fraction during the first month after direct PTCA was significantly poor in the ST reelevation group in contrast to the ST resolution group (ST reelevation group, -6.3 +/- 13%; ST no change group, 18 +/- 20%; ST resolution group, 45 +/- 29%; p < 0.0001). The change in ST elevation at reperfusion was an index predicting the recovery of LV systolic function in the reperfusion by direct PTCA.

Classification of non-Q-wave myocardial infarction according to electrocardiographic changes.

The characteristics of 93 patients in whom electrocardiographic recordings were obtained within 12 hours of the onset of non-Q-wave myocardial infarction were studied. Patients were divided into the three groups according to what electrocardiographic changes were seen. Forty nine patients had ST segment depression, 35 had ST segment elevation, and nine had T wave changes. Patients with ST segment depression had a higher rate of pump failure and multivessel disease than the other two groups. There were no significant differences in peak serum creatine kinase activity among the three groups. Twelve of 13 patients who died of non-Q-wave myocardial infarction in hospital had ST segment depression. Furthermore nine of them had attacks of non-Q-wave myocardial infarction with severe ST segment depression in many leads. At necropsy five of six patients who had shown severe ST segment depressions in many leads at the onset of non-Q-wave myocardial infarction were found to have circumferential subendocardial lesions with triple vessel disease. This study suggests there are electrocardiographic subtypes of non-Q-wave myocardial infarction that are associated with specific patient characteristics.

Nicorandil and leukocyte activation.

Nicorandil, a hybrid compound of an ATP-sensitive potassium (KATP) channel opener and a nitric oxide donor, has been reported to preserve microvascular integrity in patients with reperfused myocardial infarction. The aim of the current study was to test the hypothesis that nicorandil suppresses activation of polymorphonuclear leukocytes (PMNLs), resulting in reduction of PMNL migration into tissue upon ischemia/reperfusion. Nicorandil, along with the mitochondrial KATP channel opener diazoxide and the nitric oxide donors nitroglycerin and isosorbide dinitrate, suppressed pseudopod projection in human PMNLs treated with 10−9M N-formyl-methionyl-leucyl-phenylalanine (FMLP) and subjected to shear stress (5 dyn/cm2) with a cone-and-plate shear device. Suppression by nicorandil and diazoxide was reversed by KATP channel blockers, 5 hydroxydecanoate and glibenclamide. FMLP-induced increase of [Ca2+]in in PMNLs was suppressed by nicorandil and diazoxide, and 5 hydroxy-decanoate and glibenclamide reversed this suppression. Results of reverse transcription polymerase chain reaction with rat PMNL mRNA indicated the presence of mRNAs of Kir6.2 and Kir6.1 but not mRNAs of sulfonylurea receptor 1 or 2. Isosorbide dinitrate, diazoxide, and nicorandil reduced leukocyte migration and microvascular obstruction in reperfused ischemic tissue of rat mesenteric microcirculation. In conclusion, nicorandil attenuates ischemia/reperfusion-induced PMNL activation via donation of nitric oxide and K channel–related cascade.