To study the tissue carnitine level in patients with chronic heart failure, we obtained biopsy specimens of the left ventricular papillary muscle from 8 patients with mitral valve disease undergoing valve replacement surgery. As a control group autopsy specimens from 7 patients without heart disease were obtained within 4 hours of death. The free carnitine level in the heart was significantly lower in patients with chronic heart failure than in the control group (412±142 nmol/g wet tissue vs 769±267; p<0.01, mean±SD). The long-chain acylcarnitine level was significantly higher in chronic heart failure than in the control group (532±169 nmol/g wet tissue vs 317±72; p<0.01). The total carnitine level in chronic heart failure was similar to that in the control group (1321±170 nmol/g wet tissue vs 1315±377) . These results show that in failing myocardium the fatty acid metabolism may be impaired, and administration of carnitine may be worth trying to treat chronic heart failure.

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We investigated the clinical and pathophysiologic characteristics in patients with vasospastic angina who developed syncope and/or experienced aborted sudden death (SD). Vasospastic angina was diagnosed using the methylergonovine test. Syncope was found in 32 (10.4%) patients among 309 who were admitted to our institute in a one-year period. The most frequent cause of syncope was ventricular tachycardia which was found in 10 (31.2%) of the 32 patients. The next important cause of syncope was vasospastic angina which was found in 7 patients (21.8%). Among the 7 patients with vasospastic angina who experienced one or more syncopal episodes, there were 3 patients with aborted SD, 3 with syncope and one with shock. Cardiovascular collapse was observed in 4. Interior wall ischemia was found in 5 and anterior wall ischemia in 2 during the methylergonovine test. None of the 7 patients had significant coronary stenosis. Two patients had no prodromal symptom such as chest pain. Our results suggest that coronary artery spasm may be one of the most frequent cardiovascular diseases that causes syncope which is not always accompanied by a prodromal symptom. Therefore, coronary spasm should be distinguished in patients with unexplained syncope or aborted SD.

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The clinical efficacy of combination therapy with mexiletine and propranolol was investigated in several centres. Twenty-four-hour Holter electrocardiograms were recorded and the severity of ventricular premature beats (VPBs) was assessed on the basis of the frequency of VPBs and according to the criteria of Lown. Forty-eight cases with VPBs received single treatment with mexiletine (300 mg/day). Single treatment with mexiletine was effective in 26 out of 48 cases (54%). Nineteen cases in which the single treatment with mexiletine was not sufficiently effective received combintion therapy with mexiletine (300 mg/day) and a low dose of propranolol (30 mg/day). After the combination therapy, significant decreases in the frequency of VPBs were found in 11 out of 19 cases (58%), and lowering of the severity of the grade was found in 4 cases (30.8%). Thirteen out of 19 cases given combination therapy changed to single treatment with propranolol. A change in treatment from combination therapy to single treatment with propranolol was assessed as "undesirable" in 8 out of 13 cases (61.5%). During single treatment with mexiletine, side effects were found in 1 out of 48 cases (2.1%), and during the combination therapy in 1 out of 19 cases (5.2%). Thus, combination therapy with mexiletine and a low dose of propranolol was shown to be useful for patients with VPBs.

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1) Captopril was orally administered in a dose of 12.5 mg to 12 patients with congestive heart failure to follow changes in its blood concentration and determine changes in clinical test values. 2) The blood concentration of captopril reached its peak in 2 h after medication, the mean value being 274 ng/ml and the half-life 3.16h. The T_max and T^1/2 were found to be extended as compared with those of normal humans and hypertensive patients that had been reported. No significant differences were noted between Group I of mild cases and Group II of serious cases. 3) Following administration of captopril, a rise in angiotensin I and renin activity and a reduction in aldosterone were noted. These were found to be correlated or inversely correlated with the changes in the blood concentration of captopril. Greater changes were noted in Group II than in Group I. All clinical test values in each group tended to return to the control value 6h after the administration.

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To evaluate the diagnostic value of an exercise-induced increase in R-wave amplitude (RWA) for detecting coronary artery disease (CAD), treadmill testing using the modified Bruce protocol was performed on a CASE 11 computerized system (Marquette) in 10 healthy young men, 35 patients (pts) with CAD, 22 subjects with normal coronary arteries, and 11 pts with aortic or mitral regurgitation. Based on the analysis of the patterns of serial changes in RWA in lead V₅, we proposed new RWA criteria for detecting CAD . (1) During exercise, RWA increases in stage 1 and subsequently increases further or remains unchanged. (2) During exercise. RWA decreases in the early phase of exercise and subsequently increases. (3) In the recovery period, RWA shows a gradual and excessive increase. A combination of the above RWA criteria showed a sensitivity, specificity and accuracy of an equal value of 86%. We conclude that an exercise-induced RWA increase is a useful indicator for detecting CAD, especially when taking the patterns of serial changes into consideration, and that the abnormal RWA increase may be related to an increase in left ventricular (LV) end-diastolic volume due to exercise-induced LV dysfunction.

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In order to clarify the role of platelets as a factor aggravating cerebral ischemia, an experimental model of ischemia was investigated using thrombocytopenic rats. In addition, the prostacyclin derivative (OP-41483) and the thromboxane A₂ synthetase inhibitor (OKY-046), both of which inhibit platelet aggregation, were tested for possible beneficial effects on cerebral ischemia. Cerebral ischemia was produced in spontaneously hypertensive male rats using bilateral common carotid artery ligation (BLCL). Thrombocytopenia was produced with an antiplatelet antiserum which reduced the platelet count to less than 6×10⁴/μl by 24h. OP-41483 was administered four times hourly (500ng/kg ×4, i.p.), beginning 1h prior to BLCL. Similarly. OKY-046 was injected four times hourly (10mg/kg ×4, i.p.). Brain metabolites such as ATP, lactate and pyruvate and water content were determined after 3h of cerebral ischemia. Brain levels of ATP in the ischemic rats with thrombocytopenia were higher than those of the ischemic rats without thrombocytopenia. In addition, thrombocytopenia reduced the increase of lactate and water content in the ischemic brain. Animals treated with OP-41483 also maintained higher levels of ATP and lower levels of lactate and water compared to animals given a vehicle. OKY-046 significantly reduced brain water content, but had no effect on the ischemic alteration of brain metabolite levels. These results indicate that platelets play an important role in the progression of metabolic change during ischemia.

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The mechanism and prognostic implications of Q wave regression following transmural acute myocardial infarction (AMI) were assessed in 54 patients. Of these subjects, 14 lost their Q waves. Exercise myocardial thallium-201 (²⁰¹Tl) scintigraphy and two-dimensional echocardiography were performed before the patients were discharged from hospital. Two-dimensional echocardiography and electrocardiography were simultaneously repeated about 18 months after AMI. Both the relative ²⁰¹Tl activity in the infarcted area and the improvement of echocardiographic wall motion index were higher in patients who had lost their Q waves than in those with retained Q waves (70±14% vs 58±13%, p<0.01; 5.2±3.0 vs 2.0±3.4, p<0.01. respectively). The prevalence of post-infarction angina pectoris was significantly higher in the former (29% vs 0%, p<0.01). We concluded that remnants of viable myocardial muscle might be responsible for Q wave regression following transmural acute myocardial infarction, and the prevalence of post-infarction angina pectoris was high among these patients.

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Comparative long-term performance characteristics of mechanical valves and bioprosthetic valves were analyzed retrospectively for patients who had undergone isolated mitral valve replacement from 1967 to 1988. Two hundred ninety-one patients received either mechanical (n=97) or bioprosthetic (n.=194) valves. The cumulative follow-up was 1, 609 patient-years (mean 6.3±3.8 years, ranging from 0.6 to 20.2 years, 98.9% complete follow-up). The actuarial survival rate, including hospital deaths, at 10 years was 72±12% for mechanical and 74±4% for bioprosthetic valve recipients. The rates of freedom from thromboembolism, structural valve failure, prosthetic valve endocarditis, prosthetic valve endocarditis, reoperation, and overall valve-related complications at 10 years were 87±5%, 100%, 91±3%, 100%, and 79±8% for mechanical valve recipients and 85±3%, 77±5% (p<0.001), 85±13%, 71±5% (p<0.001), and 52±5% (p<0.001) for bioprosthetic valve recipients, respectively. Thromboembolism occurred at a similar incidence in two types of valves (2.0±0.7 vs. 2.2±0.4%/pt-yr). Structural valve failure, reoperations, and overall valve-related events occurred more frequently in the bioprostheses recipients (0 vs. 2.0±0.4%/pt-yr; p<0.001, 0.3±0.3 vs. 2.9±0.5%/pt-yr; p<0.001, 2, 5±0.8 vs. 5.6±0.7%/pt-yr; p<0.005, respectively). There was no mortality at the time of redo-operation. These results show that bioprostheses in the mitral position exhibit small benefits of antithrombogenesis and prominent disadvantage of poor durability requiring reoperation.

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Acute effects of oral isosorbide dinitrate on exercise capacity were evaluated in 14 patients with chronic heart disease measuring the anaerobic threshold and left ventricular function during exercise. A symptom-limited exercise test was performed on a bicycle ergometer with work rates increased by 1W every 6 seconds. Left ventricular function was continuously monitored with a computerized cadmium telluride detector following the intravenous injection of technetium-labeled red blood cells. Thirty minutes after the control exercise test, patients were given isosorbide dinitrate, 5 mg orally. The second exercise test was performed 30 min later. Isosorbide dinitrate improved the anaerobic threshold from 715.4±172.9 to 774.9±173.5 ml/min (p<0.01) and ejection fraction at peak exercise from 36.7±11.6 to 39.9±12.3% (p<0.05). However, there was no significant change in maximum work rate or peak oxygen uptake. Those patients for whom isosorbide dinitrate resulted in a 10% or greater improvement in the anaerobic threshold had both higher pre-treatment ejection fractions and greater increases in peak exercise ejection fraction following isosorbide dinitrate. Measurements of the anaerobic threshold and left ventricular function during exercise may be useful in the evaluation of the efficacy of vasodilators in cardiac patients.

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We designed experiments to investigate the roles of endogenous prostaglandins (PG) for the rapid proliferation of vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR). Both the basal and arachionate-stimulated vasodepressor PG generations were significantly enhanced in the VSMC of SHR when they were at the 1st or 2nd passage. Conversely, the generating capacity was significantly lowered in the VSMC of SHR when the cells reached the 4th or older generation. Based on the (³H)thymidine uptake and doubling time of VSMC, the decline of PG generating capacity seen in the VSMC of SHR was markedly associated with the increased VSMC growth. Indeed, the stimulation of endogenous vasodepressor PG by arachidonate produced a decrease in (³H)thymidine uptake in the VSMC of Wistar-Kyoto rats, whereas the dose was not sufficient to retard the uptake in SHR. On the other hand, the PG synthesis inhibition by indomethacin, a cyclooxygenase inhibitor, significantly enhanced the uptake by the VSMC of SHR. Thus, these data indicate that the impaired vasodepressor PG system is at least partly responsible for the rapid VSMC growth in SHR.

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Transient hypertrophic cardiomyopathy has been described in human infants of diabetic mothers. The purpose of this study was twofold: first, to document the features of cardiac hypertrophy in newborns of female rats with streptozotocin-induced diabetes and second, to investigate the natural history of this cardiomyopathy. Marked asymmetrical septal hypertrophy with hypertrophy of myocytes was observed in newborns of diabetic female rats, whether or not the mothers received daily administration of NPH insulin. The abnormal cardiac morphology was no longer apparent 4 weeks after birth. Thus, in this model, the asymmetrical septal hypertrophy was secondary and was not a manifestation of genetically transmitted hypertrophic cardiomyopathy.

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A case of native valve endocarditis due to Acinetobacter calcoaceticus in a patient with dental caries is presented. The aortic, mitral and tricuspid valves were affected and showed vegetation by echocardiography in the affected valves. In spite of a good response to antibiotic therapy, multiple embolisms resulted in the patient's death. An autopsy confirmed the vegetation, which was calcified and contained no bacteria.

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