Kazuo Takahara

Effect of Low Dose Aspirin on Augmented Piasminogen Activator Inhibitor Type 1 Activity in Patients with Permanent Pacemakers

To clarify the activity states of coagulation and fibrinolysis in patients with a permanent pacemaker, we studied 29 patients more than 4 months after operation. They were divided into a single pacemaker lead group (S, n = 14) and a double lead group (D, n = 15). Prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, tissue‐type plasminogen activator (tPA) activity, plasminogen activator inhibitor type‐1 (PAI‐1) activity, and platelet aggregation were measured and compared to those in an age‐matched control group (C, n ‐ 7). The effects of low dose aspirin (81 mg/day) in the patients (n = 21) were also studied 2 weeks after administration. PAI‐1 activity in groups S and D was significantly higher than that in the group C (53.5 ± 36.5, 86.8 ± 59.2 ng/ mL vs 19.4 ± 7.2 ng/mL; P < 0.01 and P < 0.005). Platelet aggregation induced by collagen was slightly higher in groups S and D than group C. Other parameters were not significantly different. In the patients, low dose aspirin significantly suppressed collagen induced platelet aggregation (71.8 ± 20.3% vs 41.7 ± 28.3%; P < 0.005), but not PAI‐1 activity. tPA activity was increased significantly by the low dose aspirin administration (3.94 ± 1.85 ng/mL vs 2.48 ± 1.19 ng/mL; P < 0.005). Thus, PAI‐1 activity in patients with a permanent pacemaker is elevated, and the activity is not suppressed by low dose aspirin unlike the platelet aggregation.

Effects of Nisoldipine on Cytosolic Calcium, Platelet Aggregation, and Coagulation/Fibrinolysis in Patients with Coronary Artery Disease

The effect of nisoldipine, a dihydropyridine Ca2+ antagonist, on the platelet cytosolic Ca 2+ concentration ( [Ca2+] i), platelet aggregation, and various coagulation and fibri nolysis parameters was assessed in normotensive patients with coronary artery disease (CAD). Eleven patients with angiographically confirmed CAD (4 men, 7 women aged 67.3 ±5.4 years) were administered nisoldipine at 10 mg/day for two weeks. The [Ca2+]i was determined by use of fura2-loaded platelets, platelet aggregation was measured with an aggregometer, and coagulation/fibrinolysis parameters were measured by standard methods. Nisoldipine did not significantly affect blood pressure or heart rate. However, the [Ca2+] decreased significantly (P<0.05) and platelet aggregation was also signifi cantly inhibited. Plasma D-dimer levels decreased significantly (P<0.01). Thus, nisol dipine not only suppressed platelet activation but also affected the coagulation system, suggesting that it is not only a vasodilator and platelet inhibitor but also an antithrom botic agent.

Determination of baroreceptor-stroke volume reflex sensitivity by power spectral analysis: a quantitative probe of baroreceptor-cardiac reflex.

Baroreceptor‐cardiac reflex, which consists of baroreceptor‐induced chronotropic and inotropic actions, is a very useful index of cardiac sympathovagal balance. Baroreceptor‐heart rate reflex sensitivity, which reflects baroreceptor‐induced chronotropic action, has been used as a marker of baroreceptor‐cardiac reflex. However, it cannot be used in patients with chronotropic incompetence and/or implanted cardiac pacemaker. We hypothesized that baroreceptor‐stroke volume (SV) reflex sensitivity, which reflects baroreceptor‐induced inotropic action, may also be a useful method for measurement of baroreceptor‐cardiac reflex, similar to the baroreceptor‐heart rate reflex sensitivity. To test this hypothesis, we measured baroreceptor‐SV reflex sensitivity expressed as ratio of low frequency (LF) power to total power of SV fluctuation (LF/TPsv: %/mmHg) by spectral analysis of mean blood pressure and SV fluctuations, the gain in low‐frequency band between two signals in supine and 60° upright positions, and compared these values to baroreceptor‐heart rate reflex sensitivity in 14 healthy subjects. Baroreceptor‐SV reflex sensitivity correlated significantly with baroreceptor‐heart rate reflex sensitivity (r = 0.73, p < 0.0001). In addition, baroreceptor‐SV reflex sensitivity correlated significantly and positively with high frequency (HF) power (r = 0.57, p < 0.005) and negatively with LF/HF ratio (r = − 0.57, p < 0.005) in power spectral analysis of R‐R interval variability. Moreover, baroreceptor‐SV reflex sensitivity in LF/TPSV correlated positively with the R‐R interval (r = 0.70, p < 0.0001) and negatively with diastolic blood pressure (r = − 0.50, p < 0.01). We conclude that baroreceptor‐SV reflex sensitivity in LF/TPSV can be used as a quantitative probe of baroreceptor‐cardiac reflex, similar to the baroreceptor‐heart rate reflex sensitivity in healthy subjects, and it may enable us to estimate inotropic aspect in baroreceptor‐cardiac reflex in patients with chronotropic incompetence and/or implanted pacemaker.

Influence of coronary artery disease risk factors on baroreflex sensitivity in the elderly.

Abstract.In this study, we assessed whether baroreflex sensitivity (BRS) is influenced by risk factors of cardiovascular disease. Subjects of this study were 95 elderly people (40 males and 55 females; mean age ± SD, 66.6±1.6 years) who underwent a medical check-up. BRS was determined as the gain of transfer function in baroreflex arc by spectral analysis of mean blood pressure and R-R interval variabilities in low-frequency band (0.04–0.15 Hz). Gender-related differences in BRS and relationships between BRS and various risk factors of cardiovascular disease were investigated. The value of BRS was significantly higher in males [10.7±3.7 (SD) ms/mmHg] than in females [9.0±4.0 ms/mmHg, p< 0.05]. However, this gender-related difference disappeared when other variables were taken into account in the multivariate model. Multiple regression analyses showed independent inverse relationships between BRS and heart rate [b=–0.016±0.004 (SE) bpm, β=–0.39], and between BRS and platelet count [b=–0.002±0.001 × 103/µl, β=–0.22]. Our results indicated that BRS is inversely related to platelet count in the elderly population. The precise mechanism of this correlation is unknown, but platelet factors released from platelet aggregates can potentially influence vascular function and modify BRS, or there is a common underlying determinant responsible for the covariation.

Low-dose Aspirin Inhibits Cardiac Sympathetic Activation and Vagal Withdrawal Response to Morning Rising

Abstract: Aspirin is known to interfere with platelet function and can protect individuals at risk of sudden death. However, this property of aspirin is less defined for cardiac autonomic activity. We assessed pulse rate variability by spectral analysis and measured plasma eicosanoid levels before and after administration of 81-mg aspirin to 12 healthy subjects over a 60-degree head-up tilt test in the morning. In upright posture, low-dose aspirin decreased both the normalized unit value of low-frequency (normalized LF) power (mean ± SD, 82.5 ± 4.5 vs. 77.5 ± 6.5 nu, P = 0.01) and LF/HF ratio (6.0 ± 2.1 vs. 4.7 ± 2.7, P = 0.02) and augmented the normalized unit value of high-frequency power (15.0 ± 4.4 vs. 19.8 ± 6.4 nu, P = 0.004). It simultaneously upregulated plasma 6-keto-PGF1&agr; level (13.4 ± 6.8 vs. 19.7 ± 12.8 pg/mL, P = 0.04) and inhibited plasma thromboxane B2 (TXB2) level (11.6 ± 7.3 vs. 6.3 ± 4.2 pg/mL, P = 0.003). In the upright posture, both before and after aspirin, there was a significant direct correlation between plasma TXB2 levels and the normalized LF power (r = 0.42, P = 0.04) as well as between the plasma TXB2/6-keto-PGF1&agr; ratio and the normalized LF power (r = 0.50, P = 0.01). Administration of low-dose aspirin in healthy people inhibits cardiac sympathetic activation and vagal withdrawal response to morning rising through an alternation of the TXA2/PGI2 balance.