Hirokazu Nagayoshi

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)

Usefulness of plasma beta-endorphin level, pain threshold and autonomic function in assessing silent myocardial ischemia in patients with and without diabetes mellitus

The differences between diabetic and nondiabetic patients with silent myocardial ischemia were investigated. Based on the results of previous exercise testing, a total of 110 patients (15 diabetic and 95 nondiabetic) with exercise-induced myocardial ischemia were divided into the following 3 groups: 15 diabetics with silent myocardial ischemia, 49 nondiabetics with silent myocardial ischemia, and 46 nondiabetics with anginal symptoms. All patients underwent treadmill exercise testing and 24-hour ambulatory electrocardiographic recording. Before and during exercise, blood samples from the antecubital vein were obtained to determine the plasma beta-endorphin levels, and the pain threshold of each patient was measured with the electrical skin stimulation test. Furthermore, with regard to the ambulatory electrocardiographic recording, the mean of the SDs of all normal sinus RR intervals during successive 5-minute recording periods over 24 hours was analyzed and considered as an index of the autonomic function. The plasma beta-endorphin level during exercise was significantly greater in nondiabetic patients with silent ischemia than in diabetic ones. The SD mean was significantly less in the diabetic group than in the 2 nondiabetic ones. The findings suggest that the role of beta endorphin in diabetic patients with silent myocardial ischemia may be less significant than in nondiabetic ones; therefore, a diabetic neuropathy that affects the autonomic pain fibers that innervate the heart may be involved in the mechanism of silent myocardial ischemia in diabetics.

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.

The Effects of Orally Administered Atenolol on the Coronary Hemodynamics and Prostaglandin Metabolism in Angina Pectoris Patients

The effects of oral atenolol on coronary hemodynamics and prostaglandin metabolism have been investigated in 8 chronic stable angina pectoris patients who underwent the supine bicycle ergometer. At rest, atenolol taken orally reduced the pressure-rate product significantly (P < 0.05) but did not significantly affect the coronary sinus blood flow or the coronary sinus pressure. During exercise, atenolol also reduced the pressure-rate product signifi cantly (P < 0.05) but did not significantly affect the coronary sinus blood flow, the coronary sinus pressure, or the coronary vascular resistance. Atenolol also did not signif icantly affect the thromboxane B2/6-keto prostaglandin F1α ratio in the arterial blood before and after exercise but did reduce this ratio in the coronary sinus blood by 15% from 1.9 ±1.1 to 1.5 ±0.46 (P < 0.10) after exercise. These results indicate that atenolol taken orally does not significantly depress the coronary hemodynamics. However, the effects of atenolol on the prostaglandin metabo lism could not be clearly determined.

Significant usefulness of heart rate variabilities by ambulatory electrocardiographic monitoring in diabetes mellitus, congestive heart failure and ischemic heart disease

ホルター心電図より求めた心拍数変動の指標のうちSD, LF, HFを用いて糖尿病, うつ血性心不全, 虚血性心疾患の3群の重症度について検討した.その結果, 糖尿病群で自律神経障害を有している群のSD, LF, HFともに, 有していない症例に比べて有意に低値であった.うっ血性心不全群ではNYHA4群のLF, HFともにNYHA2群に比べて低値であった.また死亡群のSDは生存群に比べて有意に低値であり, 治療により非代償期から代償期になるに従いSDは上昇した.虚血性心疾患群では死亡群のSDは生存群に比べて低値で, 生存群でも多枝障害で左室機能の低下群 (EF<50%) のLF, HFともに低値であったが有意差はなかった.SD<20ms, SD<30msの信頼度はsensitivity, specificityは30から100%であった.なお健常者3名の高圧環境 (41気圧) 4日目ではLF, HFともに心拍数に比べて著明に変動した.以上よりSD, LF, HFとも各種病態の異常を反映しており, 予後を判定する際有用であるが, 必ずしも自律神経の異常のみでは説明できない可能性がある.