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In coronary artery bypass surgery, arterial grafts result in improved patency rates. However, these grafts frequently fail due to spasm. Papaverine has been used to prevent graft spasm, but its effect is short-lived. Botulinum toxin inhibits muscle contraction for about three months. We investigated the usefulness of botulinum toxin in preventing arterial grafts spasm in vitro. Samples of abdominal aorta from male Wistar rats were cut into 2 mm rings and treated with various doses of botulinum toxin or papaverine for 30 min. All rings were stimulated with KCl and noradrenaline. Tension was recorded using myography. We compared constriction caused by noradrenaline or KCl in rings treated with botulinum toxin, or papaverine, or physiological salt solution (PSS) (control). In the presence of KCl and noradrenaline, almost all concentrations of botulinum toxin completely inhibited arterial contraction when compared with controls. Spasm prevention was lost after 60 min in rings with papaverine but persisted for 120 min in rings with botulinum toxin. In the histological examination, arterial wall structure was not destroyed by botulinum toxin. Botulinum toxin prevented arterial graft spasm in vitro and had a longer lasting effect than papaverine, with no toxic effect on the artery.

The effect of once daily low-dose carvedilol on circadian variations of blood pressure (BP) was studied in Japanese patients with mild or moderate essential hypertension. Thirty-one patients were admitted to hospital whose BP was 150/90 mm Hg/day or greater and they participated in the study. After a placebo period of 1 week, 5 or 10 mg carvedilol was given once daily in the morning for 3 to 7 days, and if BP reduction was not sufficient, the dose was increased to 20 mg daily. The blood pressure variation was monitored before and 1, 2, 4, 6, 8, 10, 12, and 24 h after administration of the drug on the last day of placebo and final dose of carvedilol. Of the 31 cases receiving carvedilol once daily, cumulative effectiveness (13 mm Hg reduction in mean BP) was 48.4 at 10 mg/day and 54.8 at 20 mg/day. Both systolic and diastolic pressures decreased significantly and heart rate decreased slightly. There was no significant difference between the standard deviations of BP on the last days of the control period and the carvedilol treatment. The difference between maximum and minimum BP during the day was not significant between the two periods. Circadian variations of heart rate were also not significantly different for the two periods. This indicates that carvedilol did not have any effect on circadian variations of BP and heart rate. The present study also suggests that low-dose carvedilol once daily may be effective in the treatment of hypertension.

Abstract: It has been reported that serum lipoprotein(a) (Lp[a]) levels in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) were significantly higher than in patients without restenosis. In this study, we evaluated the preventive effect of LDL apheresis on restenosis after PTCA in patients with hypercholesterolemia. For 10 patients who had shown a serum cholesterol level of more than 220 mg/dl despite treatment with antihypercholesterolemic drugs, LDL apheresis was conducted every 2 weeks after a successful PTCA until restenosis could be checked. In 4 patients, LDL apheresis was conducted for 2 years. LDL apheresis significantly reduced serum cholesterol from 248 ± 22 mg/dl to 135 ± 26 mg/dl and Lp(a) from 42 ± 34 mg/dl to 21 ± 16 mg/dl. The average degree of stenosis in the 11 lesions undergoing PTCA was 92 ± 6% before PTCA, 35 ± 10% immediately after PTCA, and 38 ± 19% at 3 to 4 months after PTCA. Restenosis was observed in only 1 lesion. In 4 patients who received LDL apheresis for 2 years, restenosis did not occur in any of the 4 lesions treated. We concluded that LDL apheresis was an efficacious therapy to prevent restenosis after PTCA in patients with hypercholesterolemia.

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.

In ordcr furthcr to identify thc prcvalcncc of anti-rcccptor autoantibodics in thc scra of paticnts with dilated cardiomyopathy (DCM), we attcmptcd to dctcct autoantibodics against a scrics of G-protcin-coupled cardiovascular receptors in a wcll-defined population of DCM paticnts from Japan. Pcptidcs corresponding to the sequences of thc sccond cxtraccllular loops of thc human P,and P2 adrcnoccptors, a, adrcnoccptors, M2 muscarinic acctylcholinc rcccptors and angiotcnsin 11-1 (ATI) rcccptors wcrc used as antigens in an cnzymc imrnunoassay to scrccn the scra from patients with DCM (n = 28). Ninc scra from patients with DCM (32%) and 2 scra from hcalthy subjects (9%) rccognizcd thc PI adrcnoccptor pcptidc. Tcn scra from paticnts (36%) and 3 scra from hcalthy subjects (I 3%)) rccognizcd the M2 rcccptor pcptidc. Thirty-six pcr ccnt of the patients with autoantibody against thc PI adrcnoccptor had autoantibody against thc M2 rcccptor. Howcvcr, no significantly high frequencies of autoantibodies against the P2 adrcnoccptor, a, adrcnoccptor and AT1 rcccptor wcrc found in DCM patients. Our results dcmonstratc that a subgroup of paticnts with DCM have a spccific spcctrum of autoantibodics which arc spccifically dircctcd against thc second cxtraccllular loops of thc PI adrcnoccptors and M2 muscarinic rcccptors rather than othcr cardiovascular rcccptors.

Summary In 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.

This study was performed to find the optimal dose of carvedilol, in terms of efficacy and safety, in Japanese patients with mild to moderate essential hypertension. 134 patients with blood pressure > 160/95mm Hg after a 4-week placebo run-in period were initially given carvedilol 5mg once daily. The dose was increased to 10 and 20mg at 4-weekly intervals if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks’ administration, the average blood pressure was significantly (p < 0.001) reduced from 170/101 to 150/91mm Hg. The hypotensive activity of carvedilol 5mg was mild, but sufficient hypotensive effect was observed in 65% of patients receiving up to 20 mg/day. No significant postural changes in blood pressure were observed. Although heart rate was significantly decreased (77 to 66 beats/min, p < 0.001), no patient was judged to have bradycardia. Side effects occurred in 5.2% of patients. Carvedilol 10 to 20mg once daily is considered to be an effective and safe treatment for essential hypertension.

An experimental model of early-stage cardiomyopathy was created by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of eitherβ1-adrenoceptors or M2-muscarinic receptors. Thirty male rabbits were used and divided into three groups: a control group (n=10), a group immunized with the peptide corresponding to theβ1-adrenoceptor (β1group) (n=10) and a group immunized with the peptide corresponding to the M2-muscarinic receptor (M2 group) (n=10). In the sera from both groups of immunized rabbits high-titres of anti-peptide antibodies were found throughout the study period but not in the sera from control rabbits or in the preimmune sera of immunized rabbits. No significant cross-reaction with peptides other than those used for immunization was found. The myocardial receptor density of both immunized groups displayed a strong trend toward receptor up-regulation. This was significant in theβ1group but not in the M2 group. Both groups of immunized rabbits displayed significantly enlarged ventricles and thinner walls, as compared with the control group. However, in contrast to theβ1group, which showed enlarged cavities in both left and right ventricles, the M2 group was mainly affected in the right ventricles. Moreover, morphological examinations of the hearts of rabbits from both immunized groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules in the sarcoplasm and the myofibrils. One of the six control rabbit hearts which were examined showed mild degenerative changes in the myocardium and scant mononuclear cell infiltration. However, when all the control rabbit hearts were examined by electron microscopy, no significant alterations were found. These results suggest that immunization by peptides, corresponding to the target sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy induces morphological changes in the heart similar to those found in the human disease.

The heating rate and the volume dilatation of nitrobenzene have been measured between 8° and 11°C. and the refractive index between 7° and 20°C. The density of nitrobenzene is d204=1.2030, and the refractive index for Haline is given by the equation. n_c=1.555030–0.000455 t. The heating curve of carbon bisulphide has been measured between -100° and -85°C.No arrest in the heating curves, no distinct change of the slope in the dilatation curve and no distinct change in the value of the refractive index have been observed within the range of the observed temperatures. Two layers in liquid carbon bisulphide at -90°C. could not be observed.None of these results proves the existence of the two modifications of the liquid nitrobenzene and carbon bisulphide such as suggested by Wolfke and Mazur.

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.

• A 62-year-old man had an acute, transient, flaccid paraplegia. Examination showed a primary cardiac tumor with emboli to major branches of the aorta. A myxoma was removed from the left atrium, and normal function returned. Left atrial myxoma should be suspected as a cause for embolism to the CNS.