Takanobu Tomaru

Prediction of acute coronary syndromes by percutaneous coronary angioscopy in patients with stable angina.

To pinpoint the link between plaque characteristics and acute coronary syndromes, we performed a 12-month prospective follow-up study in 157 patients with stable angina pectoris in whom regular coronary plaques were observed by percutaneous coronary angioscopy. Acute coronary syndromes occurred more frequently in patients with yellow plaque than in those with white plaques (11 of 39 vs 4 of 118; p = 0.00021). Moreover, the syndromes occurred more frequently in patients with glistening yellow plaques than in those with nonglistening yellow plaques (9 of 13 vs 2 of 26; p = 0.00026). Thrombus arising from the ruptured identical plaques was confirmed by angioscopy as the culprit lesion of the syndromes. The results indicate that acute coronary syndromes occur frequently and in a short time in patients with glistening yellow plaques and that angioscopy but not angiography is feasible for prediction of the syndromes.

Angiogenic therapy of acute myocardial infarction by intrapericardial injection of basic fibroblast growth factor and heparin sulfate: An experimental study

To examine whether angiogenesis and myocardial salvage occur, 30 micrograms basic fibroblast growth factor (bFGF) and 3 mg heparin sulfate (HS) were injected through the right atrium into the pericardial cavity by a thin needle-tipped catheter in a canine model of acute myocardial infarction. One month later infarcted weight/left ventricle weight was 24% +/- 5.2%, 25% +/- 4.0%, 18% +/- 2.4%, and 10% +/- 1.8% (mean + SE) in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Vascular number in the infarcted area of the outer layer was 13 +/- 3.3, 20 +/- 2.2, 47 +/- 8.3, and 136 +/- 26.3/200 x 200 microns2 in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Thus the vascular number was the largest in the bFGF plus HS group. The vascular number was larger in the subepicardial than in the subendocardial infarcted areas. Vessels directed from the epicardium toward the subepicardial infarcted area were also observed. The transcatheter intrapericardial injection of bFGF plus HS caused angiogenesis and myocardial salvage. This method might bring about a selective therapeutic and preventive modality of myocardial infarction irrespective of coronary anatomy and contraindications for coronary interventions and surgery.

Percutaneous coronary angioscopy in patients with ischemic heart disease

Percutaneous transluminal coronary angioscopy was performed during routine coronary angiography in seven patients and during PTCA in one patient with ischemic heart disease. A flexible fiberscope with an external diameter of 1.4 mm was introduced through an 8F or 9F guiding catheter used for PTCA into the coronary arteries. Warmed saline solution (15 to 20 ml) was injected through the guiding catheter into the coronary arteries for replacement of blood. Twenty-one of the 31 coronary segments were visualized and photographed on color cinefilms. The lumen of the atherosclerotic segment showed narrowing with smooth surface or with spiral folds. PTCA caused dilatation of the stenosed segment with scattered thin thrombi. These findings indicate the usefulness of angioscopy to observe luminal changes in the coronary arteries of patients with ischemic heart disease.

Fiberoptic observation of thrombosis and thrombolysis in isolated human coronary arteries

Coronary arteries isolated from cadavers autopsied within 7 hours after death were perfused with canine arterial blood, and the processes of thrombus formation at the segments stenosed with atheroma and the thrombolytic effects of urokinase were investigated by angioscopy. Ten minutes of blood perfusion caused thin mural thrombi localized at the stenotic or nonstenotic segments. During 30 minutes of blood perfusion, the thin mural thrombi of the outlet or inlet of the segment grew into a doughnut-shaped thrombus. Also, the thin mural thrombi in the stenotic segment grew into a streamer-like thrombus and drifted downstream. These thrombi grew in size with increasing perfusion time and finally obstructed the stenotic segment. Globular thrombi close to the outlet also were formed in a few preparations. Unlike the thrombi at the stenotic segment, the mural thrombi in the nonstenotic segments did not grow into massive thrombi. The thrombi were reduced in size within 10 minutes of perfusion with 320 U/ml or more of urokinase. During thrombolysis, sandstorm-like dispersion of the blood cells occurred, small fragments detached from the mother thrombus and flew downstream, or the fibrin core of the thrombus was exposed. The results indicate the usefulness of angioscopy for the dynamic and serial investigation of thrombosis and thrombolysis.

Enhancement of arterial thrombolysis with native tissue type plasminogen activator by pretreatment with heparin or batroxobin: An angioscopic study

The enhancement of canine arterial thrombolysis with native tissue type plasminogen activator (nt-PA) obtained from human-derived normal cells by pretreatment with heparin or the defibrinogenating agent, batroxobin, was evaluated with angioscopy. The nt-PA, 0.25 mg/kg, was infused intravenously to lyse 1-hour-old thrombus (eight thrombosed arteries without medication, seven with nt-PA alone, seven with nt-PA and heparin, and seven with nt-PA plus batroxobin). Angioscopy provided a cross-sectional view of the vessel lumen with clear visualization of the thrombus. Thirty minutes after nt-PA infusion, the percent luminal obstruction decreased from 74 to 61 in nt-PA alone (p less than .025), from 77 to 37 in nt-PA plus heparin (p less than .005), and from 79 to 25 in nt-PA plus batroxobin (p less than .005). Fifteen minutes after drug infusion, plasma fibrinogen levels decreased to 89% of preinfusion value in nt-PA alone, to 84% in nt-PA plus heparin, and to less than 5% in nt-PA plus batroxobin. Thus rapid infusion of nt-PA alone provided slight thrombolytic effects. However, heparin and batroxobin showed marked enhancement of thrombolytic effects of nt-PA.

Comparison of ablation efficacy of excimer, pulsed-dye, and holmium-YAG lasers relevant to shock waves

Ablation efficacy of pulsed lasers on human arterial tissue and associated shock waves have been investigated by means of excimer laser at 308 nm, pulsed-dye laser at 480 nm, and holmium-YAG laser at 2.1 microns. A multifiber catheter was used for lasing at 420 mjoules/pulse with holmium-YAG, 18.9 mjoules/pulse with excimer, and 100 mjoules/pulse with pulsed-dye laser. Ablation efficiency (ablated volume/energy) was greatest with pulsed-dye laser in blood and excimer laser in saline solution. There was selectivity for atheroma with pulsed-dye laser (ablation efficiency in atheroma versus normal tissue, 58 versus 27 x 10(-2) mm3/joule in blood; p less than 0.005) and holmium-YAG laser (12.6 versus 5.6 x 10(-2) mm3/joule in blood; p less than 0.001). Ablation efficiency of pulsed-dye laser was enhanced by blood (0.58 in blood versus 0.17 mm3/joules in saline for atheroma; p less than 0.005). Shock waves were correlated with ablation efficiency (r = 0.63 and 0.74 for pulsed-dye laser and holmium-YAG laser, respectively). There was neither selectivity for atheroma nor influence of blood medium with excimer laser. Only holmium-YAG laser could ablate tissue at a distance from the target in the blood medium. Histologic findings showed that all lasers could create smooth-edged craters with minimal coagulation necrosis. In conclusion, laser irradiation with holmium-YAG and pulsed-dye lasers could selectively ablate atheromatous tissue with minimal thermal injury, whereas excimer laser could not. Ablation efficiency was correlated with shock waves. Efficiency of pulsed-dye laser was enhanced by blood.

Eicosapentaenoic acid inhibits vasopressin-activated Ca2+ influx and cell proliferation in rat aortic smooth muscle cell lines

The purpose of this study was to clarify how eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, modulates the vascular action of vasopressin in rat aortic smooth muscle cell lines. The effects of EPA on Ca2+ mobilization and DNA synthesis elicited by vasopressin were investigated and compared to those of Ca2+ channel blocking agents, by means of Ca2+ measurements and the incorporation of [3H]thymidine. Patch-clamp techniques were also employed. Vasopressin (100 nM) elicited an initial peak of intracellular Ca2+ ([Ca2+]i), followed by a sustained phase due to Ca2+ entry. Nifedipine or nicardipine (1 microM), a potent L-type Ca2+ channel blocker, partly inhibited the sustained phase, but La3+ completely abolished it. EPA (10 microM) also inhibited it even in the presence of nicardipine. Under voltage-clamp conditions with CsCl-internal solution, depolarizing pulses positive to -30 mV from a holding potential of -40 mV elicited a slow inward current. The inward current was blocked by La3+, nicardipine, and nifedipine (1 microM), suggesting that the inward current mainly consisted of the voltage-dependent L-type Ca2+ channel (ICa.L). EPA (1-30 microM) also inhibited ICa.L in a concentration-dependent manner. The inhibitory effect of EPA was observed at concentrations higher than 1 microM, and its half-maximal inhibitory concentration (IC50) was 7.6 microM. Vasopressin induced a long-lasting inward current at a holding potential of -40 mV. The vasopressin-induced current was considered as a non-selective cation current (Icat) with a reversal potential of approximately +0 mV. Both nifedipine and nicardipine (10 microM) failed to inhibit it significantly, but La3+ completely abolished Icat. EPA also inhibited vasopressin-induced Icat in a concentration-dependent manner; its IC50 value was 5.9 microM. Vasopressin (100 nM) stimulated [3H]thymidine incorporation. Exclusion of extracellular Ca2+ with EGTA or La3+ markedly inhibited it. EPA (3-30 microM) also inhibited the incorporation induced by vasopressin, while nifedipine and nicardipine (1 microM) only partly inhibited it. These results suggested that EPA, unlike nifedipine and nicardipine, inhibited vasopressin-induced Ca2+-entry and proliferation in rat vascular smooth muscle cells, where the inhibitory effects of EPA on Icat as well as ICa.L might be involved. Thus, EPA would exert hypotensive and antiatherosclerotic effects.

Fiberoptic angioscopy of cardiac chambers, valves, and great vessels using a guiding balloon catheter in dogs

The applicability of fiberoptic angioscopy with a guiding balloon catheter to observe the cardiac chambers, valves and the great vessels was examined in anesthetized dogs. A No. 11 French guiding balloon catheter (balloon diameter 50 French) was introduced through either the right jugular vein or the right femoral vein into the right heart, and then a fiberscope (4.3 French in diameter) was introduced through the catheter into the right heart in 10 dogs. The balloon was inflated with air and gently pushed against the luminal surface, warm saline was infused through the catheter to displace the blood, and the luminal surfaces were photographed on 16 mm color cinefilms. Pulmonary angioscopy was also performed in these dogs. Similarly, the guiding catheter and fiberscope were introduced through the right common carotid artery into the left ventricle for observation of the luminal changes in the other 10 dogs. The luminal surfaces of the superior vena cava, right atrium, right ventricle, and pulmonary artery could be observed in all dogs. The trabeculae of the left ventricle, contracting and relaxing synchronously with the cardiac beat, could also be observed in all dogs. However, observations of the tricuspid valve, aortic valve, papillary muscle, and chordae were successful in only some dogs. Postmortem examinations revealed no obvious endocardial or intimal damage. The results indicate the applicability and safety of angioscopy guided by a balloon catheter for observations of the luminal changes in the cardiac chambers and great vessels.

Modification of atrioventricular conduction using a combined laser-electrode catheter.

Ablation of the AV junction is an accepted technique for the management of selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be safe and effective for AV junction ablation in most patients, but the need for firm tissue contact may make it less effective for ventricular tachycardia and certain ectopic atrial tachycardias. Laser energy can also be delivered through a catheter, and thus it may be an attractive alternative energy source for ablation. A new laser‐electrode catheter was developed for modification of conduction through the AV node as a model for ablation of an arrhythmia substrate. A window for delivery of continuous‐wave Nd:YAG laser energy was placed between the two electrodes of a bipolar electrode catheter. In vitro studies using a matrix of power versus time were performed to determine the energy that would create lesions of the appropriate size in vivo. Using this information, advanced AV block was successfully created in 16 of 17 dogs (94%) with the laser‐electrode catheter. Advanced AV block was successfully created in all four dogs in the chronic study, and it persisted for 1‐24 weeks of follow‐up until sacrifice of the animals. Histologic examination demonstrated discrete thermal damage at the AV junction with no instances of septal perforation in the acute studies or progressive necrosis in chronically maintained dogs. Advanced AV block may be produced consistently and safely in dogs using a combined laser‐electrode catheter.

Percutaneous intracardiac surgery with cardioscopic guidance

The feasibility of a novel catheter system of percutaneous transluminal cardiomyotomy and valvulotomy was examined in anesthetized dogs. The system was composed of a guiding balloon catheter, a cardioscope, and a pair of scissors with or without guide wire at the distal tip. The system without guide wire was introduced into the left ventricle, the balloon was inflated and was pushed against the endocardial surface. After confirmation by cardioscopy, the targeted tissues were incised by the scissors. By these maneuvers, the trabeculae, papillary muscles, and chordae were incised or transected in 7, 6, and 6 of 7 dogs, respectively. The system without guide wire was advanced to the aortic root, the guide wire was introduced into the left ventricle to prevent dislocation of the catheter system, the balloon was manipulated against the aortic cusp and the cusp was successfully incised with cardioscopic guidance in all five dogs. The results indicate that percutaneous transluminal cardiomyotomy and valvulotomy can be performed with cardioscopic guidance.