Paricalcitol aggravates perivascular fibrosis in rats with renal insufficiency and low calcitriol

Cardiovascular complications are a major problem in chronic renal failure. We examined the effects of plasma calcium, phosphate, parathyroid hormone (PTH), and calcitriol on cardiac morphology in 5/6 nephrectomized rats. Fifteen weeks after nephrectomy rats were given a control diet, high-calcium or -phosphorus diet, or given paricalcitol treatment for 12 weeks. Sham-operated rats were on a control diet. Blood pressure, plasma phosphate, and PTH were increased, while the creatinine clearance was reduced in remnant kidney rats. Phosphate and PTH were further elevated by the high-phosphate diet but suppressed by the high-calcium diet, while paricalcitol reduced PTH without influencing phosphate or calcium. The high-calcium diet increased, while the high-phosphate diet reduced plasma calcium. Plasma calcitriol was significantly reduced in other remnant kidney groups, but further decreased after paricalcitol. Cardiac perivascular fibrosis and connective tissue growth factor were significantly increased in the remnant kidney groups, and further increased in paricalcitol-treated rats. Hence, regardless of the calcium, phosphate, or PTH levels, cardiac perivascular fibrosis and connective tissue growth factor increase in rats with renal insufficiency in association with low calcitriol. Possible explanations are that aggravated perivascular fibrosis after paricalcitol in renal insufficiency may be due to further suppression of calcitriol, or to a direct effect of the vitamin D analog.     

Heart rate variability and occurrence of ventricular arrhythmias during balloon occlusion of a major coronary artery

Experimental studies suggest that autonomic mechanisms are important in the genesis of ischemia-induced malignant ventricular arrhythmias, but the role of the autonomic nervous system in human arrhythmogenesis is not well known. To assess whether heart rate variability (HRV) predicts the occurrence of ventricular arrhythmias during acute coronary artery occlusion, we performed continuous electrocardiographic, heart rate, and blood pressure recordings before and during a 2-minute balloon occlusion of a stenotic coronary artery in 252 patients with no baseline ventricular premature complexes (VPCs). The ranges of nonspecific responses in heart rate and blood pressure were determined by analyzing a control group of 19 patients with no ischemia during a 2-minute balloon inflation in a totally occluded coronary artery. Balloon occlusion of a coronary artery was stopped because of complex, i.e., bigeminal or repetitive, VPCs in 14 patients, and solitary (<5) VPCs were observed in an additional 19 patients. During coronary occlusion, HRV increased (p <0.001) and heart rate decreased (p <0.05) in patients with no VPCs, whereas an opposite tendency to reduction in HRV (p = 0.08) was observed in patients with complex VPCs. Complex VPCs were observed in 5 (42%) of the 12 patients with a significant coronary occlusion-induced decrease in HRV, in 7 (3.5%) of 200 patients with no change in HRV, but in none of the 40 patients with a significant increase in HRV (p <0.001). Baseline HRV did not predict the occurrence of VPCs during coronary occlusion. Logistic regression analysis identified the decrease in HRV (p <0.001) to be the only independent predictor of complex VPCs. In conclusion, coronary occlusion-induced increase in HRV seems to protect against occurrence of complex ventricular arrhythmias during the early phase of abrupt coronary occlusion, suggesting that vagal activation may modify the outcome of acute coronary events in patients with coronary artery disease.     

Cross Spectral Analysis in Assessment of Baroreflex Gain in Patients with Coronary Artery Disease

Background: Interest in determination of baroreflex sensitivity in clinical practice is growing because of its prognostic information in patients with heart disease. The purpose of the present study was to assess the feasibility of cross spectral analysis in the determination of baroreflex gain from spontaneous RR interval and systolic pressure fluctuations, and to compare the results to the traditional pharmacological method in patients with coronary artery disease. Methods: We measured the gain and time lag between RR interval and systolic pressure variabilities in the frequency domain, and compared baroreflex indexes obtained by this technique with standard phenylephrine tests in 32 patients with coronary artery disease. Results: Cross spectral analysis by fast Fourier transform techniques yielded acceptable (> 0.5) coherence between systolic pressure and RR interval in the mid- (0.07–0.15 Hz) and in the respiratory-frequency (0.15–0.40 Hz) band fluctuations in 30 patients (94%), with mean coherences of 0.69 and 0.74. The mean phase difference in the mid-frequency band was greater than in the respiratory-frequency band (?83 vs ?23 degrees, P < 0.001), suggesting that the mid-frequency fluctuations of RR intervals followed nearly 2 seconds after pressure changes, while respiratory-frequency fluctuations of RR intervals occurred nearly concomitantly with systolic pressure. The mean baroreflex slope derived from the bolus phenylephrine technique was 6.2 ms/mmHg (range 1.6–16.0), 5 patients had an abnormally low (< 3 ms/mmHg) baroreflex sensitivity. Baroreflex gain determined by cross spectral analysis from the mid-frequency band correlated significantly (r = 0.60, P < 0.001, n = 27) with the baroreflex gain determined by the phenylephrine test, while the correlation in the respiratory-frequency band was not significant (r = 0.35, P = 0.09, n = 26). Conclusions: Baroreflex slopes derived from cross spectral techniques provide reliable (but not perfect) information regarding baroreflex gain derived from the classic phenylephrine technique, even in patients with depressed baroreflex responses. Cross correlation calculation of spontaneous baroreflex slopes should be limited to data in the mid-frequency range, where the slopes are likely to reflect simple baroreflex physiology.     

Vagal Cardiac Activity in Essential Hypertension: The Effects of Metoprolol and Ramipril

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both β-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1–2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.     

Abnormal hepatocystin caused by truncating PRKCSH mutations leads to autosomal dominant polycystic liver disease

Mutations in protein kinase C substrate 80K-H (PRKCSH), encoding for the protein hepatocystin, cause autosomal dominant polycystic liver disease (PCLD), which is clinically characterized by the presence of multiple liver cysts. PCLD has been documented in families from Europe (Netherlands, Belgium, Finland) as well as from the United States. In this article, we report results from extensive mutational analysis of the PRKCSH gene in a group of 14 PCLD families and 65 singleton cases of Dutch and Finnish descent with multiple simple liver cysts. We identified PRKCSH mutations in 12 families and in 3 sporadic cases. In 8 of 10 Finnish families we detected the 1437+2delTG splice-site mutation. In Dutch families, we found 2 other mutations that affect correct splicing of PRKCSH: 292+1 G>C (2 families) and 1338-2 A>G (1 family). In another Dutch family, we detected a novel deletion (374-375delAG) in exon 6, predicting an abnormal shortened protein. Investigation of the carrier haplotypes identified a common founder chromosome in unrelated individuals in each of the 3 identified splice-site mutations. In 2 Finnish families with dominantly inherited PCLD, and in 62 of 65 sporadic cases with multiple simple liver cysts, we failed to demonstrate any PRKCSH mutation. This corroborates the notion that autosomal dominant PCLD is genetically heterogeneous. In conclusion, we propose that, on the basis of our results, genetic screening for PRKCSH gene mutations should be limited to patients either with a positive family history for PCLD or who have severe polycystic liver disease.     

Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinically evident cardiovascular disease

Equilibrium radionuclide angiocardiography was performed on 19 men and 17 women with insulin-dependent diabetes mellitus (IDDM) and on 24 men and 15 women with noninsulin-dependent diabetes mellitus (NIDDM) and on 24 male and 24 female control subjects aged 46 to 67 years. All were without clinically evident cardiovascular disease. No significant differences were found in left ventricular (LV) ejection fraction at rest between men with IDDM (56 +/- 1%; mean +/- standard error of the mean) or NIDDM (58 +/- 1%) and control men (58 +/- 1%), whereas LV ejection fraction was higher in women with IDDM (63 +/- 1%; p less than 0.01) and NIDDM (64 +/- 2%; p less than 0.01) than in control women (58 +/- 1%). An abnormal LV ejection fraction response to dynamic exercise (an increase of less than 5% units or a decrease) was observed in 1 control man (4%), in 8 men with IDDM (42%, p less than 0.01) and in 10 men with NIDDM (42%, p less than 0.01). The respective figures were 4 (17%) for control women, 7 (44%, difference not significant) for women with IDDM and 10 (71%, p less than 0.01) for women with NIDDM. Abnormal LV ejection fraction response to exercise in diabetic patients was not related to the metabolic control of diabetes, presence of microangiopathy or abnormalities in the autonomic nervous function. Myocardial perfusion scintigraphy performed in 18 diabetic patients in whom LV ejection fraction decreased during exercise showed a reversible perfusion defect in only 5 (28%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diabetes and haemodynamic reactions to acute coronary occlusion

BACKGROUND: The risk of early sudden death before hospital admission is higher in diabetic than non-diabetic men with acute myocardial infarction and autonomic nervous activity may modify the clinical outcome of abrupt coronary occlusion. Since diabetes mellitus may interfere with autonomic and myocardial function, we decided to study whether diabetes alters autonomic and haemodynamic responses to acute coronary occlusion. METHODS: We analyzed the changes in heart rate, heart rate variability and blood pressure, and the occurrence of ventricular ectopy during a 2-min coronary occlusion in 238 non-diabetic and 32 diabetic patients referred for single vessel coronary angioplasty. The ranges of non-specific responses were determined by analyzing a control group of 19 patients with no ischaemia during a 2-min balloon inflation in a totally occluded coronary artery. RESULTS: Diabetic patients were more often (p<0.05) female, but there were no significant differences in the occluded vessel or incidence of ST changes or chest pain during coronary occlusion between the groups. Incidence of significant heart rate reactions and ventricular arrhythmias was comparable in both groups. Systolic blood pressure decreased (p=0.01) in the diabetic patients during coronary occlusion, but did not change significantly in the non-diabetic group. Coronary occlusion caused more often (34% vs. 14%, p<0.01) a significant decrease in blood pressure in diabetic patients. Logistic regression models developed to analyze the significance of diabetes while controlling for baseline variables and signs of ischaemia identified diabetes to be an independent predictor of hypotensive reactions (odds ratio [OR] 2.9, 95% confidence intervals 1.1-7.8, p<0.05), while female gender and high short-term heart rate variability were other independent predictors of hypotensive reactions. CONCLUSIONS: Diabetic patients often develop significant hypotension during the early phase of acute coronary occlusion. This abnormality may be related to diabetic cardiomyopathy and impairment of baroreflex-mediated regulation of circulation. Predisposition to hypotension may contribute to the observed differences in the clinical presentation and outcome of acute coronary events.     

社区空巢老人孤独感现状及影响因素分析

目的:了解社区空巢老人孤独感现状并探讨其相关影响因素。方法:2019年1月—2019年7月采用便利抽样法选取重庆市6个主城区的385名社区空巢老人为调查对象,采用一般资料调查表、UCLA孤独量表(UCLA)、阿森斯失眠量表(AIS)及社会支持评定量表(SSRS)对其进行调查并统计分析。结果:385名社区空巢老人孤独感得分为(39.65±7.36)分,中等及以上水平孤独感者占78.45%。多元线性回归分析发现,独居、月收入较低、睡眠障碍是社区空巢老人孤独感的危险因素,参加体育锻炼、饲养宠物、社会支持水平较高是社区空巢老人孤独感的保护因素。结论:社区空巢老人孤独感水平较高,社区工作人员应针对孤独感的主要影响因素制定切实可行的干预措施,从而降低其孤独感,改善空巢老人的生活质量。