Naoto Aoki

Possible prevention of postangioplasty restenosis by ascorbic acid

In this preliminary study to assess the possibility of using ascorbic acid to prevent post-percutaneous transluminal coronary angiography (PTCA) restenosis, the incidence of restenosis was significantly less in 50 patients receiving 500 mg/day of oral ascorbic acid than in 51 control patients. Thus, ascorbic acid, a potent natural antioxidant, appeared to be possibly effective in attenuating post-PTCA restenosis.

Comparison of protective effects of preinfarction angina pectoris in acute myocardial infarction treated by thrombolysis versus by primary coronary angioplasty with stenting

The protective effects of preinfarction angina were evaluated in acute myocardial infarction (AMI) treated by primary percutaneous transluminal coronary angioplasty (PTCA) and stenting. We studied 613 patients with AMI. Group 1 (n = 306) was treated by conventional medical therapies and coronary thrombolysis and group 2 (n = 307) was treated by primary PTCA supported by stenting. Each group was subdivided into those with and without preinfarction angina within 24 hours before the onset of AMI. There was no significant difference in clinical characteristics between the subgroups of groups 1 and 2. In group 1, there were differences between patients with preinfarction angina (n = 84) and those without (n = 222) in in-hospital mortality (11% vs 18%), pump failure (Killip classes 3 and 4) (11% vs 21%, p <0.05), left ventricular ejection fraction at discharge (52 +/- 13% vs 48 +/- 14%, p <0.05), and peak creatine kinase (2,106 +/- 1,637 vs 2,764 +/- 2,154 U/L, p <0.02). In group 2, however, there was no significant difference between those with preinfarction angina (n = 82) and those without (n = 225) in mortality (6% vs 6%), pump failure (12% vs 12%), left ventricular ejection fraction (50 +/- 13% vs 50 +/- 13%) and peak creatine kinase (3,285 +/- 2,306 vs 3,291 +/- 2,262 U/L). Multivariate analysis indicated that preinfarction angina was an independent determinant of in-hospital death and pump failure in group 1, but not in group 2. We conclude that the protective effects of preinfarction angina in AMI are not evident in those treated by primary PTCA and stenting, possibly because of the overwhelming protective effects of complete coronary revascularization provided by primary PTCA and stenting.

Superoxide dismutase activity as a predictor of myocardial reperfusion and salvage in acute myocardial infarction

We attempted to predict successful myocardial reperfusion and salvage in acute myocardial infarction (AMI) by using measurements of plasma superoxide dismutase (SOD), a plasma free-radical scavenger, activity. Forty-nine patients with AMI were studied within 6 hours of symptoms onset. In group 1 (n = 26), primary percutaneous transluminal coronary angioplasty (PTCA) was undertaken, and plasma SOD activity was measured for 8 hours by the nitrite method. Left ventricular (LV) angiography was assessed before and 3 months after PTCA by computer LV contraction analysis. In group 2 (n = 23), TPA was infused intravenously over a 60-minute period, and plasma SOD activity was measured before and immediately after TPA infusion. In group 1, occluded coronary arteries were successfully dilated in 24 of 26 patients, and plasma SOD activity increased from 3.20 +/- 0.17 microns/ml to 4.66 +/- 0.29 microns/ml at 1 hour after PTCA (p < 0.001), returning to the basal level by 8 hours after PTCA. Plasma SOD activity did not significantly change patients with unsuccessful PTCA or those with the no-reflow phenomenon. The maximal increase in plasma SOD activity was significantly correlated with the grade of improvement in LV contraction (r = 0.852, p < 0.001). In group 2, the sensitivity and specificity of predicting coronary recanalization was 86% and 89%, respectively. In conclusion, myocardial reperfusion and salvage in AMI can be predicted by changes in plasma SOD activity.

Instability of coronary lesions in unstable angina assessed by C-reactive protein values following coronary interventions

The instability of coronary lesions was evaluated in 30 patients with stable angina and 60 patients with unstable angina. The grade of instability of coronary lesions as predicted by the increases in C-reactive protein induced by PTCA and/or stenting was closely correlated with Braunwalds classification of unstable angina.

Plasma Soluble P-Selectin in Acute Myocardial Infarction: Effects of Coronary Recanalization Therapy:

P-selectin is translocated from platelets and endothelial cells to initiate the first step in a sequence of events leading to the adherence of leukocytes, possibly inducing reperfu sion injury and the no-reflow phenomenon in acute myocardial infarction (AMI). This study was undertaken to investigate plasma P-selectin in AMI patients undergoing coronary recanalization therapy. A total of 40 patients were studied: 20 patients with AMI who underwent coronary recanalization by direct percutaneous transluminal coronary angioplasty (PTCA), 10 patients with AMI who underwent thrombolytic therapy by tissue-type plasminogen activator (TPA), and 10 patients with stable angina pectoris who underwent elective PTCA. Blood samples were obtained from systemic arteries before and immediately after PTCA or thrombolytic therapy. Plasma-soluble P-selectin was measured by enzyme immunoassay. Plasma P-selectin was significantly higher in AMI than in stable angina pectoris (176.6 ± 12.9 ng/mL vs 91.4 ± 9.5 ng/mL, p<0.001). Plasma P-selectin did not change significantly as a result of elective PTCA in patients with stable angina (from 91.4 ± 9.5 ng/mL to 87.9 ± 7.9 ng/mL). Plasma P-selectin was decreased by direct PTCA in all of the 20 patients with AMI (from 176.2 ±17.7 ng/mL to 141.7 ±12.6 ng/mL; p<0.001, paired t-test), whereas it was increased by thrombolysis using TPA in nine of the 10 AMI patients (from 177.4 ±17.2 ng/mL to 248.8 ±17.3 ng/mL, p<0.005). Increased P-selectin activity in AMI appeared to be attenuated by direct PTCA, but augmented by thrombolysis, possibly due to direct stimulatory effects of TPA on P-selectin expression. This may lead to less favorable results in salvaging the ischemic myocardium by thrombolytic than mechanical coronary recanalization therapy in AMI.

Prediction of coronary artery lesions in unstable angina by iodine 123 beta-methyl iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, single photon emission computed tomography at rest.

Iodine 123 beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP), a beta-methyl- branched fatty acid analogue, has been proven by experimental studies to reveal abnor malities in fatty-acid-related metabolism. This study was undertaken to validate the accuracy and limitations of 123I-BMIPP imaging at rest in detecting myocardial metabolic abnormalities and predicting coronary lesions in unstable angina (UA). One hundred UA patients without prior myocardial infarction were studied. 123I-BMIPP and thallium 201 chloride (201TlCl) imaging with single photon emission computed tomography (SPECT) and coronary and left ventricular cineangiography (LVC) were performed 1 week after the last episode of angina. There was reduced uptake of 123I-BMIPP imaging in 70 patients, reduced uptake of 201TICI in 41, and abnormal LVC contraction in 49 patients. There were significant increases in severity scores of 123I-BMIPP imaging along with increases in the number of stenosed coronary arteries and the severity of stenosis in indi vidual coronary arteries. There was a significant reduction in 123I-BMIPP severity scores 1 month after percutaneous transluminal coronary angioplasty (p<0.01) and a significant correlation between the severity scores of 123I-BMIPP and LVC (r=0. 579, p<0.001). Overall rates of sensitivity and specificity in detecting significant coronary stenosis by 123I-BMIPP imaging were 74% and 86%, respectively, whereas rates of sensitivity and specificity in detecting significant coronary stenosis by 201TlCl were 31% and 91%, respec tively. 123I-BMIPP sensitivity increases to 86% if only advanced coronary stenosis of >90% is included. In conclusion, 123I-BMIPP myocardial imaging is an effective method of predicting coronary artery lesions of UA patients without provocative test.

Local treatment with an antithrombotic drug reduces thrombus size in coronary and peripheral thrombosed arteries.

SummarySince the treatment of thrombotic disease by antithrombotic drugs may be associated with bleeding complications, a local delivery technique for administration of the drug may be useful. The efficacy of low-dose local delivery of an antithrombotic drug on thrombosis was investigated in 73 dogs. The antithrombotic drug (heparin, 25U/kg, antithrombin: argatroban, 0.05mg/kg, or defibrinogenating agent: batroxobin, 0.05U/kg) was infused locally to a 1-h-old thrombus, and no drug was given in controls. The effect of the local delivery on the thrombus was evaluated. Low- and high-dose systemic drug delivery was also evaluated. The mean reduction in thrombotic coronary stenosis observed by angiography was 30.3% with argatroban, 22% with heparin, and 20.8% with batroxobin (P < 0.005 vs controls). Systemic delivery of low-dose heparin or argatroban did not induce any change in thrombus size. With high-dose systemic drug delivery (heparin 250 U/kg, argatroban 0.5 mg/kg), the mean reduction of thrombotic stenosis was 15.2% with heparin and 32.8% with argatroban (P < 0.005 vs controls). In iliac arterial thrombosis, after local delivery of the drugs, the mean reduction of thrombotic stenosis observed by angiography was 24.4% in the argatroban group, and 19.2% in the heparin group (P < 0.05 vs controls, respectively). With high-dose systemic heparin delivery, the mean reduction of the thrombotic stenosis was 13.2% (P < 0.01 vs control). Angioscopy also demonstrated a similar trend. The high-dose drug delivery reduced systemic coagulability. Thus, local delivery of an antithrombotic agent can reduce the thrombus size in the coronary and iliac arteries without having any significant influence on coagulability.

Right Bundle Branch Block in Acute Myocardial Infarction Treated by Primary Coronary Angioplasty and Stenting

Patients with right bundle branch block (RBBB) in acute myocardial infarction (AMI) have a significantly higher mortality rate even with the advent of thrombolytic therapy. This study was undertaken to assess the impact of primary percutaneous transluminal coronary angioplasty (PTCA) and stenting on the outcome of patients with RBBB in AMI. A total of 600 patients with AMI who underwent primary PTCA and stenting (rate: 61%) <12 hours of onset were studied. A 12-lead ECG was obtained at least every 6 hours. Serial creatine kinase was measured, and left ventricular ejection fraction was obtained during the hospital stay. Among 600 patients with AMI, 94 patients (15.7%) had RBBB; it was persistent in 31 (33%) and transient in 63 (67%). In-hospital mortality rate was 7.3% in patients without RBBB, 7.9% in transient RBBB, and 25.8% in persistent RBBB (p<0.02). The incidence of heart failure was 26.5% in those without RBBB, 34.9% in transient RBBB, and 58.1% in persistent RBBB (p<0.001). There was no significant difference among these 3 groups in ventricular arrhythmias and complete atrioventricular block. Peak creatine kinase was 3,214 ±2,293 U/L in those without RBBB, 4,558 ±3,316 U/L in transient RBBB (p<0.001), and 5,635 ±3,920 U/L in persistent RBBB (p<0.001). Left ventricular ejection fraction was 50 ±11% in those without RBBB, 47 ±11% in transient RBBB (p<0.05), and 42 ±13% in persistent RBBB (p<0.001). Patients with AMI treated by primary PTCA and stenting had an increased incidence of transient RBBB, especially following reperfusion therapy, although the clinical outcome was similar to that of those without RBBB. In contrast, there was no satisfactory improvement in clinical outcomes in those with persistent RBBB.

Coronary blood flow in evolving myocardial infarction preceded by preinfarction angina: a critical reevaluation of preconditioning effects in clinical cases.

This study was undertaken to reevaluate the protective effects of preinfarction (pre-MI) angina in acute MI. The mechanisms involved in the apparent protective effects of pre-MI angina have been presumed to be preconditioning effects as defined by experimental studies. The phenom enon, has not, however, been observed in diabetic and/or elderly patients or in those treated by primary percutaneous coronary intervention (PCI). A total of 202 patients with anterior wall MI without a history of MI who underwent primary PCI with coronary balloon dilation and stenting (rate: 50%) < 6 hours after onset were studied. Patients included 59 with pre-MI angina (group 1) and 143 without pre-MI angina (group 2). The infarct-related coronary artery was patent on admission in 46% of group 1 and 31 % of group 2 (p = 0.045). Thrombolysis in Myocardial Infarction (TIMI) 1-2 flow was significantly more frequent in group 1 (29%) than in group 2 (11%, p = 0.005) on admission. Among risk factors, clinical background, coronary anatomy, and clinical outcome, the only significant predictor of pre-MI angina was a patent infarct-related coronary artery on admission (odds ratio: 2.39, p=0.015). There was no signif icant difference in left ventricular ejection fraction, peak creatine kinase, or the incidences of heart failure and in-hospital/follow-up deaths between these groups. In conclusion, the findings suggest that the protective effects reported in MI with pre-MI angina treated by thrombolysis are due to more fragile thrombotic occlusion, which can be more easily recanalized by throm bolysis, whereas the beneficial effects are not evident in those treated by primary PCI.

Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter

SummaryThe efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissuetype plasminogen activator (t-PA; Tisokinase, 50 000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30 000U/kg), was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.