[Effect of Kruppel-like factor 2 on the migration of human liver sinusoidal endothelial cells].

Objective: To investigate the effect and mechanism of Kruppel-like factor 2 (KLF2) on the migration of human liver sinusoidal endothelial cells (LSEC). Methods: Cultured human LSEC were infected with different lenti-viruses to overexpress or suppress KLF2 expression (LV5-KLF2 and LV3-shKLF2, respectively), the infection efficacies were examined by real-time PCR and Western blot analysis.Transwell migration assay was used to investigate the role of KLF2 on the migration of LSEC.The mRNA and protein expression of vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by real-time PCR and Western blot analysis, respectively.The expression and phosphorylation of Src, P38 MAPK, and P44/42 MAPK were detected by Western blot. Results: The up-regulation of KLF2 expression dramatically inhibited migration of treated LSEC, compared with LV5-NC and WT control cells, fewer LV5-KLF2 cells migrated to the lower side of the filter after 12 h [ (35.6±1.4), (71.3±2.4) and (69.3±1.6), P<0.001 for all comparisons]. In contrast, the down-regulation of KLF2 expression promoted the migration of LSEC, more LV3-KLF2 cells migrated to the lower side of the filter compared with the LV3-NC and WT control cells [(189.5±5.4), (83.4±2.5) and (82.2±3.4), P<0.001 for all comparisons]. Furthermore, up-regulation of KLF2 reduced the mRNA and protein expression level of VEGFR2, while down-regulation of KLF2 significantly increased its expression in LSEC.Additionally, up-regulation of KLF2 inhibited the phosphorylation of Src, P38 MAPK, and P44/42 MAPK pathway in LSEC, whereas down-regulation of KLF2 promoted the phosphorylation of those signaling pathway proteins. Conclusions: KLF2 may inhibit the migration of human LSEC through the Src/ MAPK signaling pathway.

Rupture of mitral chordae tendineae: adding to the list of hypertension complications.

BACKGROUND: Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated. METHODS: 494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included. RESULTS: Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p<0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p<0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p<0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p<0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively. CONCLUSIONS: There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.

Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max)). EXPERIMENTAL APPROACH: After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and Q(max), using the elastance-resistance model. Physically, E(max) reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance. KEY RESULTS: Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG. CONCLUSIONS AND IMPLICATIONS: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes.

Aminoguanidine prevents fructose-induced deterioration in left ventricular-arterial coupling in Wistar rats.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties. EXPERIMENTAL APPROACH: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature. KEY RESULTS: There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. CONCLUSIONS AND IMPLICATIONS: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.

Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetes.

BACKGROUND: Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. MATERIALS AND METHODS: The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. RESULTS: After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18.8% reduction of aortic characteristic impedance (P < 0.05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. CONCLUSIONS: Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall.

Arterial stiffening and cardiac hypertrophy in a new rat model of type 2 diabetes.

BACKGROUND: We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. METHODS: Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg(-1) of NA, 30 min before an intravenous injection of 50 mg kg(-1) STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. RESULTS: In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1.49 +/- 0.33 (mean +/- SD) to 1.95 +/- 0.28 mmHg s mL(-1) (P < 0.05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor (0.46 +/- 0.09 vs. 0.61 +/- 0.13, P < 0.05) and decreased wave transit time (25.8 +/- 3.8 vs. 20.6 +/- 2.8 ms, P < 0.05). Ratio of the left ventricular weight to body weight was also enhanced in the 8-week STZ-NA diabetic rats. CONCLUSION: The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration.

Relation of Chlamydia pneumoniae infection in Taiwan to angiographically demonstrated coronary artery disease and to the presence of acute myocardial infarction or unstable angina pectoris.

Reports of the association of Chlamydia pneumoniae (C. pneumoniae) infection with coronary artery disease (CAD) are scarce in the Oriental population. We therefore conducted a case-control study to explore this issue in Taiwan. There were 242 consecutive subjects (166 men and 76 women) who underwent cardiac catheterization at the National Taiwan University Hospital Cardiac Catheterization Laboratory. Patients with CAD (n = 156) had > or = 1 coronary artery lesion of > 50% diameter stenosis on angiography. Controls (n = 86) had no demonstrable CAD angiographically. Antibodies to C. pneumoniae were tested by using an enzyme-linked immunosorbent assay. The prevalence of antibodies to C. pneumoniae was as follows: immunoglobulin-G (IgG), 50% (122 of 242 patients); immunoglobulin-A (IgA), 72% (176 of 242 patients); and either IgG or IgA, 79% (192 of 242 patients ). The odds ratio (OR) for CAD with either IgG or IgA was 1.4 (95% confidence interval [CI] 0.7 to 2.7, p = 0.31). After adjusting for the known CAD risk factors, the OR decreased to 0.8 (95% CI 0.3 to 2.1, p = 0.60). The OR for unstable angina or acute myocardial infarction with the presence of either IgG or IgA was 0.5 (95% CI 0.2 to 1.1, p = 0.08) and 0.4 ( 95% CI 0.1 to 1.0, p = 0.049) after adjusting for other risk factors. These results suggest a high prevalence of C. pneumoniae infection in Taiwan. However, C. pneumoniae infection is not associated with angiographically documented CAD, and, in contrast, is a negative predictor for the development of acute coronary syndromes.

Hypotensive effects of captopril on physical properties of the arterial system in young and adult rats.

We determined the acute effects of the angiotension converting enzyme inhibitor captopril on the arterial mechanics in rats at different ages, based on the exponentially tapered T-tube model. Male Wistar-Kyoto rats aged 4 and 12 months were individually referred to as young (n = 8) and adult rats (n = 8) and were anesthetized and thoractomized. The pulsatile aortic pressure and flow signals before and after the administration of captopril (20 mg/kg, i.p.) were measured by a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. In each age group, captopril showed little change in basal heart rate as well as cardiac output. However, captopril produced a drop of 15% in mean aortic pressure in young and a fall of 12% in adult rats. In addition. captopril reduced total peripheral resistance by 21% in young and by 23% in adult animals. As for the pulsatile nature of the arterial system, captopril had increased wave transit time of the lower body circulation of 10% in young and of 12% in adult rats. By contrast, captopril reduced wave reflection factor by 22% in young and by 25% in adult animals. In conclusion, the converting enzyme inhibitor captopril has a stiffness-decreasing effect on Windkessel vessels and a dilated effect on resistance arterioles in either young or adult rats. No age dependence of vascular response and reflex tachycardia to captopril has been found in rats between 4 and 12 months.

Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study.

OBJECTIVES: The objective of this study was to assess the spatial distribution of atrial ectopic foci potentially triggering recurrent atrial tachyarrhythmias after electrical cardioversion of long-standing atrial fibrillation (AF). BACKGROUND: It remains unknown whether targeted ablation of atrial ectopic foci concentrated in the pulmonary veins is feasible in patients with long-standin

Possible involvement of protein kinase C in the induction of adipose differentiation-related protein by Sterol ester in RAW 264.7 macrophages.

The accumulation of lipid droplets in macrophages contributes to the formation of foam cells, an early event in atherosclerosis. It is, therefore, important to elucidate the mechanisms by which lipid droplets accumulate and are utilized. Sterol ester (SE)-laden RAW 264.7 macrophages accumulated lipid droplets in a time-dependent manner up to 16 h, which was enhanced by cotreatment with 0.1 microM phorbol 12-myristate 13-acetate (PMA). Inhibition of protein kinase C (PKC) activity by cotreatment with 0.3 microM calphostin C CAL for 16 h resulted in coalescence of small lipid droplets into large ones and increased accumulation of lipid droplets, although to a lesser extent than after PMA cotreatment. Immunostaining for adipose differentiation-related protein (ADRP) revealed a fluorescent rim at the surface of each medium to large lipid droplet. ADRP appearance correlated with lipid droplet accumulation and was regulated by PMA in a time-dependent manner. Induction of ADRP expression by PMA or CAL required SE, since ADRP levels in PMA- or CAL-treated non-SE-laden macrophages were comparable to those in untreated cells. Removal of SE from the incubation medium resulted in the concomitant dissolution of lipid droplets and down-regulation of ADRP. In conclusion, the above results suggest that ADRP may be an important protein in the regulation of lipid droplet metabolism in lipid-laden macrophages and that this regulation may be mediated by PKC activity.

Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.

1. In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identified as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10(-7) g kg(-1). The aim of this study was to determine whether liriodenine at its effective anti-arrhythmic dose of 10(-7) g kg(-1) had effects on the left ventricular (LV)-arterial coupling in Wistar rats. 2. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E(es)) and effective arterial volume elastance (E(a)), respectively. The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the optimality of energy transmission from the left ventricle to the arterial system. 3. Liriodenine at the dose of 10(-7) g kg(-1) showed no significant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (P(es)), E(a), E(es), and Q(load). 4. By contrast, liriodenine at the dose of 10(-6) g kg(-1) produced a significant fall of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in P(es). Moreover, liriodenine administration of 10(-6) g kg(-1) to rats significantly decreased E(es) by 8.5% and E(a) by 10.6%, but did not change Q(load). 5. We conclude that liriodenine at the dose of 10(-7) g kg(-1) has no effects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects on the efficiency of energy transferred from the left ventricle to the arterial system.

Effects of food restriction on systolic mechanical behavior of the ventricular pump in middle-aged and senescent rats.

Previous work from our laboratory has revealed that the intrinsic contractility of the left ventricle is depressed in rats at 24 months, and the ventricular internal resistance shows declines with age. The aim of this study was to determine whether food restriction (FR) delays the development of age-related changes in left ventricular (LV) contractility and internal resistance. Male Fischer 344 rats that began FR at the ages of 12 and 18 months were fed on alternate days for 6 months and compared with age-matched ad libitum (AL)-fed rats. Rats studied at the ages of 18 and 24 months were referred to as middle-aged and senescent rats, respectively, and were anesthetized and thoracotomized. We measured LV pressure and ascending aortic flow waves by using a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. The elastance-resistance model was used to generate Emax and Qmax to describe the physical properties of the left ventricle; Emax is the maximal systolic elastance to represent the myocardial contractility; Qmax is the theoretical maximal flow to be inversely related to the LV internal resistance. Neither age nor diet affected basal heart rate, LV end-systolic pressure, or cardiac output. Emax normalized to LV weight (Emaxn) exhibited a decline from 941.9+/-62.7 mmHg/ml-g to 690.2+/-57.5 mmHg/ml-g with age in AL-fed rats but not FR rats. Qmax showed an increase with age from 36.55+/-2.78 ml/s to 44.22+/-2.62 ml/s in AL-fed rats or from 36.01+/-2.09 ml/s to 43.52+/-2.74 ml/s in FR rats. There was no effect of diet on Qmax. In conclusion, FR prevents or delays the reduction in myocardial contractility that occurred between 18 and 24 months of age in AL rats. However, FR does not affect the age-related changes in ventricular internal resistance.

Reversal of deteriorated fractal behavior of heart rate variability by beta-blocker therapy in patients with advanced congestive heart failure.

INTRODUCTION: The slope of the power spectrum in heart rate variability (HRV) reflects the fractal or scaling behavior in HR dynamics and recently was confirmed as an independent predictor of postmyocardial infarction survival. Whether or not the new measurement in HRV foresees the functional evolution in patients with advanced congestive heart failure treated by beta blockers is unclear. METHODS AND RESULTS: Sequential 24-hour Holter ECG recordings were obtained at baseline, and 1 and 3 months after addition of atenolol therapy for advanced congestive heart failure in 10 patients. The slope and intercept of the regression line of power-law behavior, the short- and intermediate-term of detrended fluctuated analysis (DFA), the approximate entropy (ApEn), and the standard frequency spectra of the 24-hour HRV were compared sequentially as well as with those in 12 age-matched normal controls. The results showed that the slope (-1.70 +/- 0.45 vs -1.22 +/- 0.21; P < 0.05) and the intercept (5.11 +/- 0.46 vs 5.62 +/- 0.24; P < 0.05) of the regression line of power-law behavior and the short-term DFA (for 4 to 11 beats) (0.78 +/- 0.18 vs 1.13 +/- 0.21; P < 0.05) increased after 3 months of atenolol treatment. However, the change in intermediate-term DFA (>11 beats) and ApEn was not apparent (1.24 +/- 0.21 vs 1.22 +/- 0.15 and 1.34 +/- 0.14 vs 1.36 +/- 0.11; both P > 0.05). The evolution of the slope or intercept of the regression line of the HRV power spectrum did not correlate with the echocardiographic or clinical cardiac function, or with the frequency spectral components of the HRV (P > 0.05). CONCLUSION: Additional beta-blocker therapy upregulated the fractal behavior control of the HRV in patients with advanced congestive heart failure. The improvement was independent of subjective and objective global cardiac performance.

Decreased autonomic nervous system activity as assessed by heart rate variability in patients with chronic tetraplegia.

OBJECTIVES: To assess the alterations of autonomic nervous functions and sympathovagal balance of the subjects with spinal cord injuries (SCIs) in different levels by heart rate variability analysis. DESIGN: Prospective, observational study. SETTING: All participants were recruited from the outpatient clinic from National Taiwan University Hospital, which is a tertiary referral center. PARTICIPANTS: Thirty-one patients with traumatic chronic complete SCI (more than 6 months): 14 with paraplegia (Group A), and 17 with tetraplegia (Group B). MAIN OUTCOME MEASURES: Heart rate variability assessed by 24-hour Holter monitoring. RESULTS: Two patients in Group A and 1 in Group B were excluded from final data analysis because of poor recording data. Two time domain variables, the standard deviation (SD) of all normal RR intervals (SDNN) and the mean of the SDs of all normal RR intervals for all 5-minute intervals (SDNNi), over 24 hours were decreased in Group B. All time domain variables, SDNN, SDNNi, root mean square of the successive normal RR interval difference (rMSSD), and the percentage of RR intervals differing >50msec from the preceding one (pNN50), were decreased during the nighttime recordings (all p < .05) in Group B. The very-low-frequency, low-frequency (LF), and high-frequency (HF) components of the power spectrum of the RR intervals were also decreased in Group B (p < .05), irrespective of the daytime and nighttime recordings. The LF-to-HF ratio did not differ significantly in these two groups, indicating the maintained sympathovagal balance in the chronic SCI patients. CONCLUSION: These findings suggested that the autonomic nervous system activity was depressed in the patients with chronic tetraplegia, but the autonomic nervous system still maintained homeostasis.

Age-related changes in pumping mechanical behavior of rat ventricle in terms of systolic elastance and resistance.

Both the maximal systolic elastance (Emax) and the theoretical maximal flow (Qmax) can quantify the systolic mechanical behavior of the ventricular pump. Physically, Emax can reflect the intrinsic contractility of the myocardium as an intact heart. The quantity in (Qmax is inversely related to the internal resistance of the left ventricle. How great the effects of age are on these Emax and Qmax has never been examined, however. This study was to determine the ventricular pumping mechanics in terms of the systolic elastance and resistance in male Fischer rats at 6, 12, 18, and 24 months of age. We measured left ventricular (LV) pressure and ascending aortic flow waves using a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. Those two parameters that characterize the systolic pumping mechanics of the left ventricle are obtained by making use of an elastance-resistance model. The basic hemodynamic condition in those animals with different ages is characterized by (i) no significant change in cardiac output and (ii) a decrease in basal heart rate, LV end-systolic pressure, as well as effective arterial volume elastance. Changes that take place in the left ventricle with age include a decline in Emax and an increase in Qmax especially at 24 months. These results demonstrate that the impaired intrinsic contractility of an aging heart may be compensated to some extent by the diminished ventricular internal resistance. Such compensation in aging rats may maintain normal blood flow essential for the metabolic needs of tissues and/or organs before heart dysfunction and failure occur.

Amyotrophic lateral sclerosis with a 'pseudo-infarction' pattern on the electrocardiograph. A case report.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease involving both the upper and lower motor neurons in the brain stem and spinal cord. Although it is well known that various central nervous system disorders can produce a 'pseudo-infarction' pattern on the electrocardiogram, there have been no reports of this particular pattern in ALS patients. This report concerns an ALS patient who presented with an ECG pattern of S-T elevation followed by biphasic T and inverted T without any detectable myocardial abnormality. Data from the present case suggest that this pattern may be an inherent characteristic of ALS.

Expression pattern in a modified equalized kidney cDNA library of hypertensive rat.

BACKGROUND: Genes with important functions and rarely expressed would probably more easily be cloned from a modified equalized kidney cDNA library for further investigation. METHODS: A kidney cDNA library of a spontaneously hypertensive rat was synthesized by a modified equalization method. Inserts of random clones were amplified by PCR and sequenced. Sequences were compared against a nonredundant database in GenBank. The cDNA profile was compared with an expression profile of a mouse renal proximal tubule cDNA library. Seven clones were analyzed by Northern blot analysis. The cDNA ends of two novel genes were amplified by PCR, sequenced and analyzed. RESULTS: 336 cDNA clones were analyzed and grouped into 323 species of transcript with 77 species similar to previously reported genes. Northern blot analysis identified one kidney-specific, one rarely expressed and lung-specific, and another relatively testis-specific gene. Two novel genes were cloned. One was 4.1 kb in length and encoded a 390-amino acid zinc-finger protein. Another was 2.5 kb and encoded a 474-amino acid protein of unknown function. Compared with the expression profile of a mouse renal proximal tubule cDNA library, this kidney library had a lower proportion of ribosomal genes and had a greater proportion of genes for signal transduction and DNA or RNA binding. CONCLUSIONS: Rare or novel genes could be more easily isolated from this library for molecular study of hypertension and renal pathophysiology.

Impaired vascular dynamics in normotensive diabetic rats induced by streptozotocin: tapered T-tube model analysis.

This study is to explore the changes of arterial mechanical properties in streptozotocin (STZ)-diabetic rats, based on the exponentially tapered T-tube model. Rats given STZ 65 mg kg(-1)i.v. are compared with untreated weight- and age-matched controls. A high-fidelity pressure sensor and electromagnetic flow probe measured pulsatile pressure and flow waves in the ascending aorta, respectively. Diabetic rats exhibit isobaric vasodilatation that is characterized by an increase in cardiac output and no significant changes in aortic pressure. Total peripheral resistance of diabetic rats is lower than that of weight- and age-matched controls. Diabetic rats have higher total peripheral compliance (2.86+/-0.70 microl mm Hg(-1)) than do weight- (1.77+/-0.34 microl mm Hg(-1)) and age-matched (1.87+/-0.69 microl mm Hg(-1)) controls. Aortic characteristic impedance is reduced from 0.017+/-0.003 mm Hg min kg ml(-1)in weight- and 0.020+/-0.004 mm Hg min kg ml(-1)in age-matched controls to 0.010+/-0.004 mm Hg min kg ml(-1)in diabetic rats. Moreover, diabetic rats show shorter wave transit time in lower body circulation (17.86+/-1.91 ms) than do weight- (20.45+/-1.91) and age-matched (23.05+/-2.04 ms) controls. Under isobaric vasodilatation, the decreased resistance and increased compliance in peripheral circulation suggest that the contractile dysfunction of the smooth muscle cells may occur in resistance arterioles in diabetes. With unaltered aortic pressure, an impairment in aortic distensibility of STZ-diabetic rats is manifest on the reduced wave transit time rather than on the diminished aortic characteristic impedance.

Intravenous sotalol decreases transthoracic cardioversion energy requirement for chronic atrial fibrillation in humans: assessment of the electrophysiological effects by biatrial basket electrodes.

OBJECTIVES: This study was undertaken to assess the effects of sotalol on the transthoracic cardioversion energy requirement for chronic atrial fibrillation (AF) and on the atrial electrograms during AF recorded by two basket electrodes. BACKGROUND: The effects of sotalol infusion on transthoracic electrical cardioversion for chronic atrial fibrillation in humans have not been well investigated. METHODS: We included 18 patients with persistent AF for more than three months. Atrial electrograms were recorded by two basket electrodes positioned in each atrium respectively. Transthoracic cardioversion was performed before and after sotalol 1.5 mg/kg i.v. infusion. RESULTS: In the 14 patients whose AF could be terminated by cardioversion before sotalol infusion, the atrial defibrillation energy was significantly reduced after sotalol infusion (236 +/- 74 jules [J] vs. 186 +/- 77 J; p < 0.01). Atrial fibrillation was refractory to cardioversion in four patients at baseline and was converted to sinus rhythm by cardioversion after sotalol infusion in two of them. We further divided the patients into two groups. Group A consisted of 10 patients in whom the energy requirement was decreased by sotalol while group B consisted of eight patients in whom the energy requirement was not decreased. The mean A-A (atrial local electrogram) intervals during AF were significantly increased after sotalol infusion in both groups, but the increment of A-A interval was significantly larger in group A than it was in group B patients (36 +/- 13 ms vs. 22 +/- 8 ms for the right atrium; 19 +/- 7 ms vs. 9 +/- 7 ms for the left atrium; both p < 0.05). The spatial and temporal dispersions of A-A intervals were not significantly changed after sotalol infusion in both atria in both groups. CONCLUSIONS: Sotalol decreases the atrial defibrillation energy requirement by increasing atrial refractoriness but not by decreasing the dispersion of refractoriness.

Role of desmin filaments in chicken cardiac myofibrillogenesis.

Desmin filaments are muscle-specific intermediate filaments located at the periphery of the Z-discs, and they have been postulated to play a critical role in the lateral registration of myofibrils. Previous studies suggest that intermediate filaments may be involved in titin assembly during the early stages of myofibrillogenesis. In order to investigate the putative function of desmin filaments in myofibrillogenesis, rabbit anti-desmin antibodies were introduced into cultured cardiomyocytes by electroporation to perturb the normal function of desmin filaments. Changes in the assembly of several sarcomeric proteins were examined by immunofluorescence. In cardiomyocytes incorporated with normal rabbit serum, staining for alpha-actinin and muscle actin displayed the typical Z-line and I-band patterns, respectively, while staining for titin with monoclonal anti-titin A12 antibody, which labels a titin epitope at the A-I junction, showed the periodic doublet staining pattern. Staining for C-protein gave an amorphous pattern in early cultures and identified A-band doublets in older cultures. In contrast, in cardiomyocytes incorporated with anti-desmin antibodies, alpha-actinin was found in disoriented Z-discs and the myofibrils became fragmented, forming mini-sarcomeres. In addition, titin was not organized into the typical A-band doublet, but appeared to be aggregated. Muscle actin staining was especially weak and appeared in tiny clusters. Moreover, in all ages of cardiomyocytes tested, C-protein remained in the disassembled form. The present data suggest the essential role of desmin in myofibril assembly.