Eiji Murakami

Hemodynamic effects of dibutyryl cyclic AMP in congestive heart failure.

To evaluate the hemodynamic effects of dibutyryl cyclic AMP (DBcAMP) in congestive heart failure (CHF), right-sided cardiac catheterization was performed in 11 patients with CHF, and hemodynamic variables were investigated before and after infusion of various doses of DBcAMP at a rate of 0.025 to 0.2 mg/kg/min (mean 0.14 +/- 0.077 [standard deviation]). DBcAMP reduced total systemic vascular resistance index from 3,171 +/- 1,158 to 1,880 +/- 554 dynes s cm-5 X m2 (mean +/- standard deviation) and pulmonary arterial end-diastolic pressure from 23 +/- 13 to 20 +/- 11 mm Hg, and increased cardiac index from 2.24 +/- 0.60 to 3.41 +/- 1.02 liters/min/m2. Mean arterial blood pressure decreased from 91 +/- 14 to 84 +/- 13 mm Hg, and heart rate increased from 91 +/- 16 to 99 +/- 13 beats/min. The increase in cardiac index was accompanied by a proportional decrease in total systemic vascular resistance index in all patients except 1. In 8 patients the decrease in pulmonary arterial end-diastolic pressure was accompanied by an increase or no change in the left ventricular stroke work index. In 6 patients, DBcAMP was given in incremental doses of 0.05, 0.1, and 0.2 mg/kg/min every 20 minutes, and 5 of 6 patients tolerated the full dose and showed dose-related hemodynamic changes for the incremental doses of DBcAMP. These data suggest that DBcAMP has powerful vasodilating effects on resistance vessels in patients with CHF; hence, it can be a useful vasodilating agent for treatment of CHF.

Effects of LDL apheresis on restenosis after angioplasty

We performed long-term maintenance LDL apheresis therapy on patients with hypercholesterolemia after undergoing PTCA, and investigated the therapeutic effects of reducing serum cholesterol, LDL-cholesterol and Lp(a). LDL apheresis significantly reduced serum lipids and was an efficacious therapy in the prevention of recurrent stenosis after PTCA.

Myocardial tissue characterization by magnetic resonance imaging in Fabry's disease

6. Louie EK, Maron BJ. Apical hypertrophic cardiomyopathy: clinical and two-dimensional echocardiographic assessment. Ann Intern Med 198’7;106:663. Kereiakes DJ, Anderson DJ, Crouse L, Chatterjee K. Apical hypertrophic cardiomyopathy. AM HEART J 1983;10:855. Kaufman L, Crooks L, Sheldon P, Hricak H, Hee 67:251. Higgins CB, Kaufman L, Crooks LE. Magnetic resonance imaging of the cardiovascular system. AM HEART J 1985; 109~136. Friedman BJ, Waters J, Kwan L, De Maria AN. Comparison of magnetic resonance imaging and echocardiography in determination of cardiac dimensions in normal subjects. J Am Co11 Cardiol 1985;5:1369. Higgins CB, Byrd II BF, Stark D, et al. Magnetic resonance imaging in hypertrophic cardiomyopathy. Am J Cardiol 1985;55:1121.

Effects of some radical scavengers on reperfusion-induced arrhythmias in the canine heart

SummaryIn this study, using electron spin resonance (ESR), we investigated the relation at the time of reperfusion between free radicals originating from the mitochondria of the canine myocardium and arrhythmias induced by reperfusion as well as the effect of radical scavengers on both. The left anterior descending artery was ligated just below the first diagonal branch and then reperfused for 10 minutes in 48 adult mongrel dogs. The dogs were divided into six groups consisting of: 1) control group administered no radical scavengers (n=8), 2) SOD group (n=6) receiving superoxide dismutase (15,000 U/kg), 3) SOD+CAT group (n=6) receiving SOD (15,000 U/kg) and catalase (45,000 U/kg), 4) L-SOD group (n=6) receiving liposomal-encapsulated SOD (30,000 U/kg), 5) CV-3611 (2-O-octadecylascorbic acid) group (n=8) receiving CV-3611 (10 mg/kg), and 6) CoQ10 group (n=6) receiving coenzyme Q10 (10 mg/kg). SOD, SOD+CAT, L-SOD, CV-3611, and CoQ10 were administered into the left atrium prior to reperfusion. The second lead of the electrocardiogram was continuously monitored during the experiment. The following results were obtained. 1) The relative intensity (RI) of the electron spin resonance signal of the mitochondria of the reperfused portion of the myocardium was smaller (p<0.025) in the SOD, SOD+CAT, L-SOD, CoQ10 groups (1.08±0.36, 0.92±0.19, 0.91±0.11, and 0.81 ±0.09, respectively) than in the control group (1.70±0.20). 2) Effects of radical scavengers on ventricular arrhythmias: The disappearance time was (p<0.025) shorted in the SOD, SOD+CAT, L-SOD, and CoQ10 groups (82±16, 86±10, 82 ±19, and 131±63 sec, respectively) as compared to the control group (304±71 sec). Also, SOD, SOD+CAT, L-SOD, and CoQ10 reduced the number of episodes of ventricular tachycardia (VT) and total ventricular premature contractions compared to that of the controls, and also significantly shortened the maximum VT duration. In addition, the time in normal sinus rhythm was prolonged. 3) RI and the time for disappearance of ventricular arrhythmias were positively correlated (r=0.7827, p<0.05). The above results suggest that the administration of various kinds of radical scavengers such as SOD can limit the development of reperfusion arrhythmias, and that the generation of free radicals in the mitochondria of the myocardium is suppressed by these interventions, resulting in attenuation of cellular injury and preservation of mitochondrial function.

Plasma adenosine concentration during and after dynamic exercise in patients with chronic heart failure

The purpose of this study was to evaluate the changes of plasma adenosine concentration by dynamic exercise in patients with chronic heart failure. We studied six patients with chronic heart failure (heart failure group) and six normal subjects (normal group). A symptom-limited ramp exercise test was performed with subjects sitting upright on a bicycle ergometer. The first exercise test was performed to determine the anaerobic threshold. The second exercise test was performed 2 days thereafter, and blood samples for assay of adenosine, lactate, and norepinephrine were taken from the antecubital vein at rest, during, and after exercise. In the heart failure group, VO2 at anaerobic threshold and peak exercise was significantly lower than that in the normal group, whereas there was no difference in respiratory quotient at peak exercise between the two groups. There was a significant increase in the plasma adenosine level from the point before anaerobic threshold to 10 minute after exercise in the normal group, whereas a mild increase in plasma adenosine level was observed only 15 minute after exercise in the heart failure group. The change of plasma adenosine was significantly smaller in the heart failure group (p<0.05). There was a significant relationship between plasma adenosine and lactate levels (r=0.42, n=48,p<0.01). These findings indicate that production of adenosine is decreased in patients with chronic heart failure, and vasodilation of exercising muscle induced by adenosine might be impaired during exercise.

981-50 Contribution of Skeletal Muscle Fatigue versus Dyspnea to Exercise Intolerance in Chronic Heart Failure

Background and Purpose Decreased exercise capacity is a major clinical problem in patients with chronic heart failure (CHF) and is associated with skeletal muscle fatigue and/or dyspnea. To study the factors contributing to the exercise limitation of CHF, we observed the oxygenation of both working skeletal and respiratory muscles during exercise. Method Thirteen subjects, 6 normal subjects and 7 patients with CHF, were studied. Using near-infrared (NIR) spectroscopy, relative changes in oxygenated Hb and Mb (oxy Hb/Mb) and deoxygenated Hb and Mb (deoxy Hb/Mb) contents in both vastus lateralis and serratus anterior muscles were monitored simultaneously during incremental maximal supine bicycle exercise (ramp protocol, 15 w/min, 50 cycle/min). Anaerobic threshold (AT) by respiratory gas analysis (VAT) was obtained using the V-slope method, and AT in the vastus lateralis (MAT) and the serratus anterior (RAT) muscles were determined by points obtained from deoxy Hb/Mb ≥ oxy Hb/Mb in each muscle. Results (1) In total subjects, VO2 at VAT was 10.1xa0±xa02.41xa0ml/min/kg (mean ± SD), VO2 at RAT 8.1xa0±xa01.80 and VO2 at MAT 7.0xa0±xa02.74 (VAT vs RAT pxa0lxa00.01, VAT vs MAT pxa0lxa00.01, RAT vs MAT Pxa0lxa00.05). (2) In all of the subjects, there was significant correlation between VO2 at VAT and that at MAT (rxa0=xa00.608, pxa0lxa00.05), while there was no significant correlation between VO2 at VAT and that at RAT. The relations between VO2 at MAT and that at RAT are shown on the graph. Download : Download high-res image (85KB) Download : Download full-size image (3) Comparisons between patients with CHF and normal subjects. Download : Download high-res image (104KB) Download : Download full-size image Conclusions During exercise, the oxygenation profile of exercising skeletal muscle is similar to that of respiratory muscle, but the former shows anaerobic metabolism at an earlier stage of exercise than the latter. This phenomenon is more prominent in patients with CHF.