Angiographically demonstrable coronary artery spasm could be provoked repeatedly by giving intracoronary or intravenous injections of histamine to miniature swine with experimentally induced atherosclerotic lesions of the coronary artery. The spasm induced in this way subsided either spontaneously or after the administration of nitroglycerin and was prevented by a calcium antagonist or an agent that blocks histamine H1 receptors. This model, which suggests that atherosclerotic changes may be one of the primary factors in the occurrence of coronary artery spasm, should facilitate studies on the pathogenesis of this condition.

The purpose of this study was to determine whether oxygenation in localized working muscle depended on the muscle activity and on the lactic acidosis level. Seven healthy male subjects underwent the five 6-min cycling exercises with work rates of 50 watts (25.0 +/- 5.0% VO2max), 100 watts (36.6 +/- 6.2% VO2max), 150 watts (50.6 +/- 7.7% VO2max), 200 watts (67.8 + 6.9% VO2max), and 250 watts (82.9 +/- 7.5% VO2max) while gas exchange parameters and blood lactate concentration (BL) were measured. We also measured oxygenated hemoglobin and myoglobin concentration (oxy-Hb/Mb) with continuous-wave near infrared spectroscopy (NIR) and surface myoelectric activity with surface electrodes (EMG). The NIR probe and electrodes were positioned on the vastus lateralis muscle of the right leg. The relative change in oxy-Hb/Mb was estimated by regarding oxy-Hb/Mb in the resting condition as 100% and that obtained during thigh occlusion as 0%. The mean values of oxy-Hb/Mb and integrated EMG (iEMG) were determined from 5'30" to 6'00" at each work rate. The percentage of oxy-Hb/Mb was sustained at the first two work rates corresponding to 25.0 +/- 5.0 and 36.6 +/- 6.2% VO2max and decreased slightly at 150 watts corresponding to 50.6 +/- 7.7% VO2max, which was followed by a linear decrease at 200 and 250 watts corresponding to 67.8 +/- 6.9 and 82.9 +/- 7.5% VO2max. The iEMG, however, was increased slowly at 25.0 +/- 5.0 to 50.6 +/- 7.7% VO2max, and a rapid increment of the iEMG occurred at 67.8 +/- 6.9 and 82.9 +/- 7.5% VO2max. BL was sustained at 25.0 +/- 5.0 to 50.6 +/- 7.7% VO2max and increased linearly at 67.8 +/- 6.9 and 82.9 +/- 7.5% VO2max. There was a significant negative correlation for each subject between the percentage of oxy-Hb/Mb and iEMG (r = -0.947 to -0.993), between the percentage of oxy-Hb/Mb and BL (r = -0.890 to -0.982), and between the percentage of oxy-Hb/Mb and VO2 (r = -0.929 to -0.994) These results indicated that oxygenated hemoglobin/myoglobin concentration measured with NIR reflected the muscle activity and the lactic acidosis.

SUMMARY Twenty-four-hour ambulatory ECG recording was performed in 26 patients with variant angina to evaluate the diurnal distribution of ST-segment elevation in relation to chest pain and the incidence of arrhythmias during the episodes. During a recording period of 52 days, 364 ST-segment elevations of 1 mm or greater were observed and 79% were asymptomatic. ST-segment elevation frequently occurred between 0:00 and 9:00 hours (72%) and most frequently between 5:00 and 6:00 hours (13%). Only a few episodes occurred between 10:00 and 18:00 hours. Premature atrial contractions, premature ventricular contractions (PVCs), ventricular tachycardia (VT) and complete atrioventricular block occurred during 12% of the episodes and were more common during painful episodes (32%) than during painless ones (6%). However, VT and severe forms of PVCs (couplets and bigeminy) appeared eight times during painless episodes and nine times during painful ones. Arrhythmias occurred more frequently when the elevated ST segment started to return or was returning to the control level (n = 38) than when the ST segment was rising (n = 8). The incidence of arrhythmias was lower when the daily frequency of ischemic episodes was high. This study shows that episodes of asymptomatic coronary artery spasm predominantly occur early in the morning as symptomatic episodes; complex dysrhythmias appear during the asymptomatic episodes; arrhythmias occur predominantly during a "reperfusion period;" and more arrhythmias accompany infrequent daily episodes of ischemia than frequent ones.IN PATIENTS with variant angina, anginal attacks occur more frequently at midnight or early in the morning, and arrhythmias, including life-threatening ones, are common during the attack. 1-3 To our knowledge, however, no quantitative data have been reported on the diurnal distribution of ischemic episodes, such as chest pain and ECG changes, in variant angina except for a preliminary report by Kuroiwa,4 which showed a higher frequency of recurrent ST-segment elevations early in the morning. It is important to clarify the diurnal distribution of the episodes for the evaluation of pathophysiology of variant angina as well as for treatment.ST-segment elevation without pain has been observed in variant angina and recently proved to be due to coronary vascular spasm resulting, like painful STsegment elevations, in myocardial ischemia.5-7 Twenty-four-hour ambulatory ECG monitoring is a good tool for evaluating ST-segment elevation in variant angina, especially that without chest pain,2' 8.9 and can also be used to evaluate arrhythmias during the episodes.In the present study, we studied the diurnal distribution of ischemic episodes with or without chest pain and the incidence of arrhythmias during the episodes using 24-hour ambulatory ECG recordings. Materials and Methods Twenty-six consecutive patients with variant angina admitted to our clinic from June 1976 to December 1981 were studied. Twenty-five were males and one was female, ages 44-72 years old. None of these patie...

Carbocyclic thromboxane A2 [2#(Z),3a-(1E,3R*i3 3-hydrox ctenylfbicyclo[3.1.1]hept-2-yl-5hepte-noic acidi, a stable analog of thromboxane A2, has been tested for its physiologic properties. Carbocyclic thromboxane A2 is a potent coronary vasoconstrictor, stimulating coronary vascular smooth muscle at concentrations as low as 29 pM. At 1-5 ,M it is also an inhibitor of arachidonic-acid-and endoperoxideinduced aggregation of platelets. At 200 nM it stimulated the release of lysosomal hydrolases from large granule fractions of liver homogenate. It inhibited thromboxane synthesis in platelets, although it did not inhibit synthesis of prostacyclin in ram seminal vesicles. Thus, carbocyclic thromboxane A2, a molecule closely related to thromboxane A2, separates coronary vasoconstrictor from platelet-aggregating activity. The constrictor activity predominates in vivo; carbocyclic thromboxane A2 induces coronary vasoconstriction leading to myocardial ischemia and sudden death in rabbits in the absence of pulmonary or coronary thrombosis.

To study the effects of magnesium (Mg2+) on human coronary arteries and to compare those effects with those of diltiazem and nitroglycerin, we measured the tension of ring segments from isolated human coronary arteries obtained at autopsy within 5 hours after death. Precontracted segments with 3 x 10(-6) M prostaglandin F2 alpha were studied after adding cumulative concentrations of these agents (1.0-8.0 mM, 10(-9)-10(-5) M, and 10(-10)-10(-6) M, respectively). Mg2+ significantly inhibited the tonic contraction compared with the time-matched controls at 1.0 and 2.0 mM (48.7 +/- 5.6% vs. 88.6 +/- 2.2%, p less than 0.01, 36.2 +/- 6.1% vs. 78.9 +/- 3.0%, p less than 0.01, respectively). 1.0 and 2.0 mM Mg2+ did not suppress, but actually increased, the amplitude of periodic contraction, but 8.0 mM Mg2+ reduced the amplitude compared with the controls (6.6 +/- 5.2% vs. 73.3 +/- 10.7%, p less than 0.01). Diltiazem at a concentration of 10(-5) M moderately inhibited the tonic contraction, and reduced the amplitude of periodic contraction almost completely. Nitroglycerin reduced the tonic contraction almost completely at a concentration of 10(-6) M but did not reduce the amplitude of periodic contraction at any concentration. We conclude that 1.0 and 2.0 mM Mg2+ inhibits the tonic contraction and that 8.0 mM Mg2+ inhibits the periodic as well as the tonic contraction of isolated human coronary arteries. Diltiazem inhibits the periodic contraction, whereas nitroglycerin suppresses tonic contraction without affecting the periodic contraction.