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Background Ischemic mitral regurgitation (IMR) is common in ischemic heart disease and results in poor prognosis. However, the exact mechanism of IMR has not been fully elucidated. Hypothesis Quantitation of the mitral tetrahedron using three-dimentianl (3D) echocardiography is capable of evaluating the geometric determinants and mechanisms of IMR. Methods Forty patients with a history of ST-elevation myocardial infarction at least 6 months earlier were studied. Parameters of mitral deformation and global left ventricular (LV) function and shape were evaluated by 2-dimensional echocardiography. The effective regurgitant orifice (ERO) of IMR was obtained by the quantitative continuous-wave Doppler technique. Three-dimensional (3D) echocardiography was applied to assess the mitral tetrahedron. Results Mitral valvular tenting area (P

Background We compared the haemodynamic and metabolic effects of acetyl-L-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) in streptozotocin-induced diabetes in male Wistar rats. Materials and methods Diabetes was induced by a single tail vein injection of 55 mg kg )1 streptozotocin. The diabetic animals daily treated with either acetyl-L-carnitine (150 mg kg )1 in drinking water) or oxfenicine (150 mg kg )1 by oral gavage) for 8 weeks,were compared with the untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. Results Oxfenicine, but not acetyl-L-carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl-L-carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl-L-carnitine may attenuate the diabetes-induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA ⁄TBARS content in plasma and aortic walls in diabetes. Acetyl-L-carnitine therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Conclusion Acetyl-L-carnitine, but not oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived MDA ⁄TBARS in the rats with insulin deficiency.

Background and purpose: Our team previously demonstrated that diabetes induces a deterioration in vascular dynamics, in parallel with the enhanced formation of advanced glycation end products. The aim of this study was to determine whether prevention of the arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen. Experimental approach: Diabetes was induced in rats by a single tail vein injection with 55 mg·kg -1 steptozotocin (STZ). After induction of hyperglycaemia, animals were treated for 8 weeks with pyridoxamine (1 g·L -1 in drinking water) and compared with the age-matched untreated diabetic controls. Pulse wave reflection along the vasculature was derived using the impulse response function of the filtered aortic input impedance spectra. Keyresults: Treatment of this experimental diabetes with pyridoxamine resulted in a significant increase in wave transit time and a decrease in wave reflection factor, indicating that pyridoxamine attenuates the diabetes-induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, pyridoxamine therapy ameliorated the diabetes-related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Glycation-derived modification of aortic collagen was also found to be attenuated by administration of pyridoxamine to the STZ-induced diabetic rats. Conclusions and implications: Pyridoxamine imparts significant protection against the diabetes-induced deterioration in pulsatile arterial load imposed on the heart, at least partly through inhibition of the formation of advanced glycation end products and their accumulation on aortic collagen of the STZ-treated rats. British Journal of Pharmacology (2009) 157, 1419–1426; doi:10.1111/j.1476-5381.2009.00309.x

Background Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. Materials and methods A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene were genotyped. Results In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT1R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT1R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. Conclusions Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

Background Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ- and NA-treated animals, using modern spectral estimation technique. Design An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4- and 8-week STZ-NA rats with anaesthesia. The power of low-frequency and high-frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed-loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low-frequency band. Results Compared with the age-matched controls, both the 4- and 8-week STZ-NA diabetic rats had significantly decreased low-frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0·451 ± 0·060 and 0·484 ± 0·056 vs. 1·196 ± 0·064 ms mmHg−1, P

To study the association of renin gene polymorphism with essential hypertension in the Chinese population, 86 hypertensive and 107 normotensive subjects were enrolled from an epidemiologic survey. Leukocyte DNA was extracted and digested with Hind III and Bgl I restriction enzymes. Southern hybridization was done with digoxigenin-incorporated renin gene probes generated by polymerase chain reaction. The restriction fragments were detected by anti-digoxigenin antibody and enzyme methods. Two Hind III polymorphysms of the renin gene (8.7 kb and 6.2 kb) were identified. The allele frequences were 129(75%) and 43(25%), respectively, in hypertensives; they were 139(65%) and 75(35%), respectively, in normotensives (chi2 = 4.074, p = 0.044). The genotypes of 8.7/8.7,8.7/6.2 and 6.2/6.2 were significantly different between hypertensives and normotensives, being 45(52%), 39(45%), 2(3%) and 48(45%), 43(40%), and 16(15%), respectively (chi2 = 9.002, p = 0.11). The Bgl I polymorphism did not show a difference between hypertensives and normotensives. Thus, we conclude that the renin gene Hind III polymorphysm is associated with hypertension in this Chinese population.

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65 mg kg−1 STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50 mg kg−1) and compared with the age-matched untreated diabetic controls. After exposure to AG, the STZ-diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (τ), from 20.4±0.6 to 24.7±0.5 ms (P

In recent studies, aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that can prevent the age-related aortic stiffening and cardiac hypertrophy. The aim of this study was to determine whether AG had effects on the left ventricular (LV)-arterial coupling in aged Fisher 344 rats in terms of the ventricular and arterial chamber properties. Normotensive rats were treated from 18 to 24 months with AG (1 g l(-1) in drinking water) and compared with a control group. 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 (Ees) and effective arterial volume elastance (Ea), respectively. The optimal afterload (Qload) determined by the ratio of Ea to Ees was used to measure the efficiency of mechanical energy transferred from the left ventricle to the arterial system. In comparison with the 6-month-old rats, the 24-month-old animals had decreased Ees, at 567.4 +/- 26.7 vs 639.0 +/- 20.7 mmHg ml(-1), decreased Ea, at 411.5 +/- 18.6 vs 577.9 +/- 15.7 mmHg ml(-1), and decreased Q(load), at 0.9428 +/- 0.0024 vs 0.9962 +/- 0.0014. Treatment with AG for 6 months did not significantly affect Ees; however, when normalized to LV weight (i.e., Eesn = Ees/LV weight), Eesn showed a significant rise of 22.8%, suggesting that AG may retard the aging process on the intrinsic contractility of the left ventricle. On the other hand, the decrease in Ea in aging rats was prevented by AG, as reflected in the increase of 19.7% in this variable (P < 0.05). The 24-month-old treated rats also exhibited a significant rise of 21.6% in Ea/Ees, causing an increase of 5.2% in Qload (P < 0.05). We conclude that in healthy older Fisher 344 rats without diabetes, long-term treatment with AG may improve both the arterial and ventricular function and optimize the matching condition for the left ventricular-arterial coupling.

We determined the effects of long-term treatment with aminoguanidine (AG), an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in aged Fisher 344 rats, using the aortic impedance analysis. Normotensive rats were treated from 18 to 24 months with AG (1 g/l−1 in drinking water) and compared with a control group. Pulsatile aortic pressure and flow signals were measured and then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. With no alteration in body weight, rats treated with AG had decreased heart weight compared with the aged untreated controls. AG did not affect arterial blood pressure; however, the age-related increase in total peripheral resistance was prevented by AG. AG retarded the age-related decline in aortic distensibility, as evidenced by a reduction of 25.2% in aortic characteristic impedance and an increase of 28.1% in wave transit time. Meanwhile, the increase in wave reflection factor in aging rats was reduced by 32.3% by AG. Both the increased wave transit time and the decreased wave reflection factor suggest that AG may prevent the age-related augmentation in systolic loading condition for the left ventricle coupled to the arterial system. We conclude that long-term treatment with AG may impart significant protection against aortic stiffening and cardiac hypertrophy in aged Fisher 344 rats. British Journal of Pharmacology (2003) 140, 107–114. doi:10.1038/sj.bjp.0705410