Toshiharu Maruyama

Heart rate variability in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure

The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 +/- 12.6 ms, 43.7 +/- 15.4 ms, and 34.6 +/- 15.8 ms vs 65.6 +/- 16.7 ms, p less than 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 +/- 6.5 ms vs 44.2 +/- 11.0 ms, p less than 0.05) mean SD as compared to survivors: 49 +/- 7 ms in patients with mild ischemic heart disease, 48 +/- 15 ms in patients with severe ischemic heart disease, and 23 +/- 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p less than 0.05) than in those who survived (19.0 +/- 5.6 ms vs 40.0 +/- 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid Metabolites in Acute Myocardial Infarction

Abnormalities of arachidonic acid metabolism are implicated in spasm and thrombosis in coronary arteries. Therefore, arachidonic acid metabolites were examined in patients with acute myocardial infarction (AMI). Plasma levels of thromboxane B2 (TXB 2), 6-keto prostaglandin F1α (6KPGF1α), leukotriene B4 (LTB4), and slow reacting substance of anaphylaxis (SRS-A) composed of leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4), were measured in 19 AMI patients. Plasma levels of TXB2, LTB4, and SRS-A in systemic artery blood were significantly elevated during the acute stage (within twenty-four hours after the onset of chest pain) of AMI (TXB2, 0.36 ng/mL; LTB4, 0.75 ng/mL; and SRS-A [LTC4+LTD4+LTE 4], 0.96 ng/mL) compared with those of normal controls (TXB2, 0.18 ng/mL; LTB4, 0.44 ng/mL; and SRS-A [LTC4+LTD4+LTE 4], 0.31 ng/mL). These values decreased to near-normal control levels by one month after the AMI attack. The findings in this study suggest that abnormalities of arachidonic acid metabolism accompany, and may play a role in the pathogenesis of, AMI.

Differences in plasma β-endorphin and bradykinin levels between patients with painless or with painful myocardial ischemia

To verify whether plasma beta-endorphin and bradykinin affects the pathophysiology of myocardial ischemia and the perception of cardiac pain, 35 patients with coronary artery disease were subjected to treadmill testing and 48-hour Holter ECG monitoring to measure their pain thresholds. Patients were divided into two groups during exercise testing: group 1 (N = 19) who had ST segment depression, and group 2 (N = 16), who had chest pain. Both groups were then compared with 12 age-matched control subjects. Pain thresholds were measured after Holter ECG monitoring, and blood samples were drawn before and immediately after exercise. No statistical differences were noted between groups 1 and 2 with regard to the severity of myocardial ischemia as assessed by ST segment depression or exercise tolerance time. The frequency of the episodes of silent myocardial ischemia in group 1 was found to be significantly (p less than 0.05) higher than that in group 2. The duration of the episodes of silent myocardial ischemia in group 1 was 41.9 minutes (range 3 to 343 minutes), which was significantly (p less than 0.05) longer than that in group 2 (11.5 minutes; range 0 to 74). The pain threshold in group 1 was a statistically (p less than 0.05) higher value than that in group 2. Although the resting plasma beta-endorphin level in group 1 was not statistically significantly different from values in either group 2 or the control group, during exercise the plasma beta-endorphin levels in both group 1 and the control group were significantly (p less than 0.05) elevated in comparison with their resting levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.

Pathological Renal Findings of Chronic Renal Failure in a Patient with the E66Q Mutation in the α-galactosidase A Gene

A 66-year-old Japanese man was diagnosed with interstitial nephritis on a renal biopsy at 45 years of age and began to receive hemodialysis at 65 years of age. He was suspected of having Fabry disease as a result of a screening study for Fabry disease performed in hemodialysis patients. He had an E66Q mutation in the α-galactosidase A gene. We conducted an electron microscopic examination of a renal biopsy specimen obtained when the patient was diagnosed with chronic renal failure at 45 years of age in order to elucidate the pathogenicity of the E66Q mutation. Interestingly, an electron microscopic examination of the renal biopsy specimen indicated no characteristic findings of Fabry disease.

Aortic aneurysm as a complication of myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis

Abstract Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV) does not usually involve large vessels, such as the aorta. However, we experienced three cases having an aortic aneurysm as a complication of MPO-AAV with renal insufficiency. In one patient it involved the onset of descending aortic dissection during treatment for MPO-AAV; another two patients had an abdominal aortic aneurysm at the time of our diagnosis of MPO-AAV. Although we found no pathological evidence in our patients, MPO-AAV might result in large vessel inflammation. Therefore, we suggest that patients with MPO-AAV should be examined by computed tomography scan to check for the presence of an aortic aneurysm.