Circadian Patterns of Myocardial Ischaemia and the Effects of Antianginal Drugs

Chronopathology of cardiovascular disease is now well documented. Silent myocardial ischaemia involves the same pathophysiological changes as conventional ischaemia. Early morning peaks in angina and myocardial ischaemia call for adequate timing of medication, β-blockers abolish the morning peak, and aspirin reduces morning infarctions. The effects of other antianginals on these phenomena are presently unknown.     

Twenty-Four-Hour Blood Pressure Control: An Intraarterial Review

Intraarterial blood pressure monitoring has shown the circadian rhythm of blood pressure control. Blood pressures tend to be highest in the morning before falling gradually during the day to a nadir at 3:00 a.m. There is a slight rise in the late afternoon that may correspond to patients' attendance at hospital for calibration of the equipment. There is a small rise in the blood pressure before awakening, and after arousal there is a rise in blood pressure to the peak level of the morning. In this article, we examine the effect of a variety of antihypertensive agents on this rhythm. In general, β-adrenoceptor blockers appear to have less effect on nocturnal blood pressure and surge in pressure after arousal, while vasodilators, particularly α-adrenoceptor blockers, have a pronounced effect. These findings indicate that the rise in blood pressure before awakening and the rapid rise upon arousal appear to be due to increased α-adrenoceptor activity.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low-28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low–28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Circadian and short-term regulation of blood pressure and heart rate in transgenic mice with cardiac overexpression of the beta1-adrenoceptor

Congestive heart failure is associated with a loss of circadian and short-term variability in blood pressure and heart rate. In order to assess the contribution of elevated cardiac sympathetic activity to the disturbed cardiovascular regulation, we monitored blood pressure and heart rate in mice with cardiac overexpression of the β₁-adrenoceptor prior to the development of overt heart failure. Telemetry transmitters for continuous monitoring of blood pressure and heart rate were implanted in 8 to 9-week-old wildtype and transgenic mice, derived from crosses of heterozygous transgenic (line β₁TG4) and wildtype mice. Cardiovascular circadian patterns were analyzed under baseline conditions and during treatment with propranolol (500 mg/L in drinking water). Short-term variability was assessed by spectral analysis of beat-to-beat data sampled for 30 min at four circadian times. Transgenic β₁TG4 mice showed an increase in 24 h heart rate, while blood pressure was not different from wildtype controls. Circadian patterns in blood pressure and heart were preserved in β₁TG4 mice. Addition of propranolol to the animals' drinking water led to a reduction in heart rate and its 24 h variation in both strains of mice. Short-term variability in blood pressure was not different between wildtype and β₁TG4 mice, but heart rate variability in the transgenic animals showed a rightward shift of the high-frequency component in the nocturnal activity period, suggesting an increase in respiratory frequency. In conclusion, the present study shows that both the circadian and the short-term regulation of blood pressure and heart rate are largely preserved in young, nonfailing β₁-transgenic mice. This finding suggests that the loss of blood pressure and heart rate variability observed in human congestive heart failure cannot be attributed solely to sympathetic overactivity but reflects the loss of adrenergic responsiveness to changes in the activity of the autonomic nervous system.     

Circadian Rhythm of Blood Pressure and Heart Rate in Cardiopathic Patients Before and After Heart Transplantation

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitor-ings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation. the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.     

Consistent Changes in the Circadian Rhythms of Blood Pressure and Atrial Natriuretic Peptide in Congestive Heart Failure

We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:OO h. The mean (±SEM) circadian mesors of ANP plasma levels were 13.4 ± 1.7 pmol/L in the control group, 28.6 ± 2.4 pmol/L in the group of 10 patients in class 11, and 81.5 ± 12 pmol/L in the group of 10 patients in class 111-IV. In normal subjects, plasma ANP concentration was highest at 04:OO h (21.5 ± 2.7 pmol/L) and lowest at 16:OO h (8.8 ± 2.4 pmol/L; p < 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.     

Circadian Rhythm of Blood Pressure in Congestive Heart Failure and Effects of ACE Inhibitors

In 33 patients with heart failure (NYHA 11-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:OO to 22:OO h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 ± 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 ± 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p < 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 ± 0.1 mmol/L) reached statistical significance (p < 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 ± 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

Circadian time-qualified tolerance intervals for ambulatory blood pressure monitoring in the diagnosis of hypertension

The large-amplitude circadian pattern in blood pressure of healthy subjects of both genders suggests that the constant threshold currently used to diagnose hypertension should be replaced by a time-specified reference limit reflecting the mostly predictable blood pressure variability during the 24 h. Accordingly, we derived circadian time-specified reference standards for blood pressure as a function of gender. We studied 743 normotensive Caucasian volunteers (400 men and 343 women), 45.7 ± 16.5 (mean ± SD) years of age. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual in order to avoid differences among subjects in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each gender separately. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data and, therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results reflect expected changes in the tolerance limits as a function of gender and circadian sampling time, as well as upper blood pressure limits below the thresholds currently used for diagnosing hypertension, especially for women. The use of these time-dependent tolerance limits for the computation of a hyperbaric index as a measure of blood pressure excess has already been shown to provide a reproducible and high-sensitivity test for the diagnosis of hypertension, which can also be used to evaluate treatment efficacy.     

Circadian Time-Qualified Tolerance Intervals for Ambulatory Blood Pressure Monitoring in the Diagnosis of Hypertension

The large-amplitude circadian pattern in blood pressure of healthy subjects of both genders suggests that the constant threshold currently used to diagnose hypertension should be replaced by a time-specified reference limit reflecting the mostly predictable blood pressure variability during the 24 h. Accordingly, we derived circadian time-specified reference standards for blood pressure as a function of gender. We studied 743 normotensive Caucasian volunteers (400 men and 343 women), 45.7 ± 16.5 (mean ± SD) years of age. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual in order to avoid differences among subjects in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each gender separately. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data and, therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results reflect expected changes in the tolerance limits as a function of gender and circadian sampling time, as well as upper blood pressure limits below the thresholds currently used for diagnosing hypertension, especially for women. The use of these time-dependent tolerance limits for the computation of a hyperbaric index as a measure of blood pressure excess has already been shown to provide a reproducible and high-sensitivity test for the diagnosis of hypertension, which can also be used to evaluate treatment efficacy.     

24-Hour Variation in the Reactivity of Rate-Pressure-Product to Everyday Physical Activity in Patients Attending a Hypertension Clinic

The exercise-related response of the rate-pressure-product (RPP) is a prognostic marker of autonomic imbalance, cardiovascular mortality, and silent myocardial ischemia in hypertension. In view of the well-known 24 h variation in out-of-hospital sudden cardiac events, our aim was to investigate whether the reactivity of RPP to everyday physical activities varies over the 24 h. Ambulatory measurements of systolic blood pressure (BP) and heart rate were recorded every 20 min for 24 h in 440 diurnally active patients attending a hypertension clinic. Wrist activity counts were summed over the 15 min that preceded a BP measurement. An RPP reactivity index was derived for each of twelve 2 h data bins by regressing the change in RPP against the change in logged activity counts. The RPP showed 24 h variation (p?<?0.0005), with a peak of 11,004 (95% CI?=?10,757 to 11,250) beat?·?min^?1?·?mmHg occurring at 10:00 h (2 h after mean wake-time). The overall 24 h mean of RPP reactivity was 477 beat?·?min^?1?·?mmHg?·?logged activity counts^?1 (95% CI?=?426 to 529). The largest increase in RPP reactivity occurred within the first 2 h after waking (p?<?0.0005). There were no subsequent significant differences in RPP reactivity up to 14 h after waking. The lowest RPP reactivity was found 18–20 h after waking, with a peak-to-trough variation of 593 beat?·?min^?1?·?mmHg?·?logged activity counts^?1 (95% CI?=?394 to 791, p?<?0.0005). Although this variation was not moderated by BP status, age, or sex, less variability in RPP reactivity was found for the medicated individuals during the waking hours. These data suggest that under conditions of normal living, the reactivity of RPP to a given change in physical activity increases markedly during the first 2 h after waking from nocturnal sleep, the time when out-of-hospital sudden cardiac events are also most common. Therefore, these data add weight to the notion that reactivity of RPP to physical activity could be a prognostic marker of autonomic imbalance and cardiovascular mortality, although more research is needed to assess the specific prognostic value of 24 h ambulatory measurements of RPP and physical activity.     

Circadian Rhythm of Blood Pressure and Heart Rate in Healthy Persons and Kidney Transplant Patients: Correlations with Activity

Fourteen diurnally active (07: 00–22: 39 h) normotensive healthy control subjects and 14 kidney transplant patients were studied by ambulatory blood pressure monitoring and wrist actigraphy simultaneously during one 24-h period. In the control group, circadian rhythms in systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure, heart rate (HR), and wrist activity were documented by cosinor analysis with comparable afternoon peak times. In contrast, circadian rhythms with afternoon acrophases were detected only in HR and wrist activity in the patient group. The correlation of wrist activity with HR in controls and patients was comparable. Wrist activity and blood pressure were associated (r = 0.65 DBP and 0.54 SBP; p < 0.05) in controls, while in patients the relationship was weak or absent (r ranging from 0.02 SBP to 0.22 DBP). In 6 of 14 patients, BP and wrist activity were negatively correlated, reflecting the existence of nocturnal hypertension. In eight others, the correlation was small but positive. The 24-h pattern in BP and wrist activity in controls was comparably phased; however, this was not the case for the transplant patients, indicating the day-night pattern in blood pressure in this group is strongly dependent on pathologic phenomena rather than activity level and pattern.     

Circadian Rhythm of Cardiac Output, Peripheral Vascular Resistance, and Related Variables by a Beat-to-Beat Monitoring

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.     

侧脑室注射硫化氢对大鼠血压和呼吸的调节作用

目的 探讨中枢硫化氢（H2S）对正常大鼠平均动脉血压的调节及其机制.方法 将微量H2S饱和盐溶液一次性和连续注射入麻醉大鼠侧脑室（ICV）,观察注药后血压、心率和呼吸的变化.结果 ICV一次性注射不同剂量的H2S饱和盐溶液后可引起血压先急剧降低而后迅速升高,心率减慢,呼吸幅度增加和呼吸频率减慢,并存在显著的剂量和时间依赖关系.ICV连续注射H2S可显著升高血压,但对心率和呼吸没有影响.ICV注射一次性注射K＋-ATP通道开放剂Pinacidil可显著的降低血压,但心率和呼吸没有显著变化;ICV一次性注射K＋-ATP通道阻断剂glibenclamide对血压、心率和呼吸没有显著的影响;但预先ICV注射glibenclamide可阻断H2S的降低血压和减慢心率的作用,对呼吸没有影响.预先静脉注射酚妥拉明对血压没有明显的影响,却显著抑制ICV给予H2S产生的升高血压减慢心率效应.结论 本工作提示H2S是调节心血管活动的一个重要的中枢活性因子,其降低血压的效应是通过K＋-ATP通道和影响呼吸有关系,而升压效应是通过激活交感神经的活性.     

Circadian pacemaker function and entrainment during maturation of transgenic hypertensive TGR(mREN2)27 and Sprague-Dawley rats

TGR(mREN2)27 (TGR) transgenic rats develop hypertension due to the mouse mRen-2 gene inserted in their genome. At 5 weeks of age, the blood pressure of TGR rats starts rising, until a maximum is reached at 10 weeks of age. Adult TGR rats show peak values of blood pressure (BP) during the light phase, while heart rate (HR) and motor activity (MA) peak at night. In the present experiment, we evaluated the evolution of circadian rhythms in motor activity, heart rate, and blood pressure of TGR and Sprague-Dawley (SD) rats under 12h light-dark cycles (LD 12:12). Results confirmed that the blood pressure of TGR rats starts to increase at 5 weeks of age, reaching a plateau by the 11th week. Parallel to the increase in blood pressure levels, there was a decrease in the period length of the blood pressure rhythm, a delay in the onset of the alpha phase of the blood pressure rhythm with respect to that of motor activity and heart rate, and a decrease in heart rate levels. In all of the variables studied, the alpha phase of SD rats always started before darkness, whereas that of TGR rats started after lights off. In general, heart rate and motor activity levels of TGR rats were higher than those of SD rats. The amplitude of the circadian rhythms studied was greater in TGR rats than in SD rats. The present results suggest that the different evolution of circadian rhythms in TGR and SD rats might be due to differences in the functioning of the entrainment pathway or the circadian clock itself, which can be detected in young rats and that are probably caused by the expression of the mouse transgene. (Chronobiology International, 18(4), 627-640, 2001)     

Disturbance of Circadian Rhythms in Analgosedated Intensive Care Unit Patients with and without Craniocerebral Injury

Melatonin, cortisol, heart rate, blood pressure, spontaneous motor activity, and body temperature follow stable circadian rhythms in healthy individuals. These circadian rhythms may be influenced or impaired by the loss of external zeitgebers during analgosedation, critical illness, continuous therapeutic intervention in the intensive care unit (ICU), and cerebral injury. This prospective, observational, clinical study examined 24 critically ill analgo‐sedated patients, 13 patients following surgery, trauma, or acute respiratory distress (ICU), and 11 patients with acute severe brain injury following trauma or cerebral hemorrhage (CCI). Blood samples for the determination of melatonin and cortisol were obtained from each patient at 2 h intervals for 24 h beginning at 18:00 h on day 1 and ending 16:00 h on day 2. Blood pressure, heart rate, body temperature, and spontaneous motor activity were monitored continuously. Level of sedation was assessed using the Ramsey Sedation Scale. The severity of illness was assessed using the APACHE‐II‐score. The time series data were analyzed by rhythm analysis with the Chronos‐Fit program, using partial Fourier series with up to six harmonics. The 24 h profiles of all parameters from both groups of patients were greatly disturbed/abolished compared to the well‐known rhythmic 24 h patterns in healthy controls. These rhythm disturbances were more pronounced in patients with brain injury. The results of this study provide evidence for a pronounced disturbance of the physiological temporal organization in ICU patients. The relative contribution of analgosedation and/or brain injury, however, is a point of future investigation.     

Time domain baroreflex sensitivity assessment by joint analysis of spontaneous SBP and RR series

The sequences technique is frequently used for time domain assessment of the arterial-cardiac baroreceptor reflex sensitivity (BRS). The BRS is estimated by the slope between systolic blood pressure and RR interval values in baroreflex sequences (BSs) and an overall estimate is obtained by slope averaging. However, only 25% of all beats are in BSs with 60% of those located in 3-beat length segments. Also, in cases of BSs absence (usually associated with poor BRS function), the BRS cannot be quantified.Here, baroreflex events (BEs) are introduced and used with global/total slope estimators to improve BRS assessment. The performance of the novel method is evaluated using the EuroBaVar dataset. The events technique benefits from a higher number of beats: 50% of all beats are in BEs with more than 70% exceeding 3-beat length. It always provides a BRS estimate, even when BSs cannot be identified. When BSs are available, estimates from BEs and BSs are highly correlated. The estimates from BEs for the cases without BSs are lower than the estimates for the remaining cases, indicating poorer BRS function. The events technique also offers superior ability to discriminate lying from standing position in the EuroBaVar dataset (23/23 versus 18/23 for the sequences technique).     

Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol,lipid peroxidation,antioxidant status and aortic histology in cholesterol-fed rabbits

Reactive oxygen metabolites and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of atherosclerosis. Amlodipine, a unique third-generation dihydropyridine-type calcium channel blocker, seems to exert atheroprotective effects through its antioxidant properties related to its chemical structure and independent of its calcium channel-blocking effect. In this study, the interactions of amlodipine with major cellular antioxidants were investigated in order to elucidate the mechanisms underlying its atheroprotective effects. New Zealand white male rabbits were fed regular chow (group 1), chow with 1% cholesterol (group 2), regular chow plus 5 mg/kg/day amlodipine per os (group 3) and 1% cholesterol plus amlodipine (group 4) for 8 weeks. Total cholesterol, malondialdehyde (MDA) and vitamin E concentrations and catalase and superoxide dismutase (SOD) activities were determined in blood drawn before and after the experimental period. Aortic tissue was examined for atherosclerotic changes and aortic total cholesterol, MDA, catalase and SOD were determined. At the end of the 8-week treatment period, serum total cholesterol and plasma MDA were elevated in groups 2 and 4. In group 2, serum vitamin E and plasma SOD diminished (p < 0.05) and catalase increased (p < 0.05). In group 4, SOD activity increased at the end of treatment. MDA levels were lower and plasma SOD activities were higher in group 4 than in group 2. Aortic tissue investigations revealed higher total cholesterol and MDA concentrations and catalase activities in group 2 than in group 4, and the highest tissue SOD activity was recorded in group 4 (p < 0.05 for all comparisons). Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group 2. Histopathological alterations related to atherogenesis were less in group 4 than in group 2. Amlodipine seems to exert atheroprotective effects by reducing aortic cholesterol accumulation and blood and aortic lipid peroxidation, enhancing SOD activity both in blood and aortic tissue and suppressing the consumption of vitamin E. On the other hand, the suppression of catalase activity in blood and the aorta interferes with the drug's well-known antioxidant effects.     

The Effects of a Therapy Dog on the Blood Pressure and Heart Rate of Older Residents in a Nursing Home

The aim of the present project was to investigate whether repeated visits by a therapy dog to nursing homes might affect the older residents’ systolic blood pressure and heart rate. A secondary aim was to investigate and compare effects (differences in responses) in older people with high and normal systolic blood pressure. The project consisted of two consecutive studies; the dog study (two researchers and a therapy dog with a handler visited the residents at three nursing homes, n = 13), and the control study (the two researchers alone visited the residents at three different nursing homes, n = 13). The studies were divided into three periods; period 1 (weeks 1–2), period 2 (weeks 3–4), and period 3 (weeks 5–6) and included two visits per week. The dog and her handler visited during periods 2 and 3 in the dog study. Participants’ heart rate and blood pressure were measured at 0 and 20 minutes at each visit. The data were analyzed using Friedman's two- way analysis of Variance by Rank with post-hoc analysis using Wilcoxon signed-rank tests with a Bonferroni correction, and also with the Mann-Whitney U test for independent samples. In the dog study, participants’ heart rate decreased significantly (p = 0.006) from period 1 to period 3. Participants with an initial systolic blood pressure ≥ 130 mmHg had a significant decrease in both systolic blood pressure (p = 0.009) and heart rate (p = 0.009). In the control study, participants’ heart rate and systolic blood pressure did not change significantly. The participants in the dog study had a significantly lower systolic blood pressure during period 3 (p = 0.016) compared with those in the control study. In conclusion, repeated visits by a therapy dog–handler team decreased the older adults’ heart rate, and for those with high initial systolic blood pressure, blood pressure also decreased. In addition, systolic blood pressure decreased significantly in the dog group when compared with the control group.     

A Pilot Study on the Effects of Heart Rate Variability Biofeedback in Patients with Depression and in Healthy Subjects

Decreased vagal activity and increased sympathetic arousal have been proposed as major contributors to the increased risk of cardiovascular mortality in patients with depression. It was aim of the present study to assess the feasibility of using heart rate variability (HRV) biofeedback to treat moderate to severe depression. This was an open-label study in which 14 patients with different degrees of depression (13 f, 1 m) aged 30 years (18–47; median; range) and 12 healthy volunteers attended 6 sessions of HRV biofeedback over two weeks. Another 12 healthy subjects were observed under an active control condition. At follow up BDI was found significantly decreased (BDI 6; 2–20; median 25%–75% quartile) as compared to baseline conditions (BDI 22;15–29) in patients with depression. In addition, depressed patients had reduced anxiety, decreased heart rate and increased HRV after conduction of biofeedback (p < 0.05). By contrast, no changes were noted in healthy subjects receiving biofeedback nor in normal controls. In conclusion, HRV biofeedback appears to be a useful adjunct for the treatment of depression, associated with increases in HRV.