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K S Channer

Publications and source records attributed to K S Channer.

At least 19 recordsLinked to original sources
PubMed2002

Testosterone acts as a coronary vasodilator by a calcium antagonistic action.

T acts as a vasodilator in vitro and in vivo. Supplemental T therapy in humans with angina improves symptoms and reduces objective measures of ischemia. In left anterior descending coronary arteries taken from adult male Wistar rats, T abolishes 100+/-4.2% of calcium-dependent contraction induced by potassium chloride, 82.3+/-6.1% of the mostly calcium-dependent contraction induced by prostaglandin-F-2-alpha, but only 45.3+/-3.4% of the contraction induced by phorbol-12,13-dibutyrate (PDBu) in the presence of extracellular calcium, and 54.5+/-4.5% of the contraction induced by PDBu in the absence of extracellular calcium. These findings suggest that T is primarily inhibiting the calcium-dependent elements of vascular contraction.

Animals↗
PubMed2001

Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction.

BACKGROUND: Glycoprotein (GP) VI plays a crucial role in platelet activation and aggregation. We investigated whether polymorphic variation at the GP VI locus confers an increased risk of myocardial infarction (MI). METHODS AND RESULTS: Coding and 5' and 3' non-coding regions of the GP VI gene were analyzed by polymerase chain reaction and conformation sensitive gel electrophoresis in 21 healthy subjects. Ten dimorphisms, 5 of which predicted amino acid substitutions (T13254C, A19871G, A21908G, A22630T, C22644A), were identified. Two core haplotypes involving 7 dimorphisms (C10781A and G10873A and all those predicting amino acid substitutions) were apparent. The contribution of the T13254C dimorphism, which predicted the substitution of serine 219 by proline, to risk of MI was assessed in 525 patients with acute MI and 474 controls, all aged <75 years. The allelic odds ratio (OR) for MI associated with the 13254C allele was 1.16 (95% CI, 0.91 to 1.46; P=0.23). Compared with corresponding control subgroups, the 13254CC genotype was more common among cases who were female (OR, 4.52; 95% CI, 1.23 to 16.64; P=0.029), nonsmokers (OR, 2.50; 95% CI, 0.98 to 6.38; P=0.048), aged >/=60 years (OR, 6.48; 95% CI, 1.47 to 28.45; P=0.009) or carried the beta-fibrinogen -148T allele associated with increased fibrinogen levels (OR, 10.49; 95% CI, 1.32 to 83.42; P=0.02). In logistic regression analysis that took other cardiovascular risk factors into account, the interactions of GP VI genotype with age (P=0.005) and beta-fibrinogen genotype (P=0.035) remained significant. CONCLUSIONS: The GP VI 13254CC genotype increases the risk of MI, particularly in older individuals, and the interaction of the GP VI 13254C allele with other candidate risk alleles may accentuate this risk.

Aged↗
PubMed2001

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction.

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.

Aged↗
PubMed2001

The -1185 A/G and -1051 G/A dimorphisms in the von Willebrand factor gene promoter and risk of myocardial infarction.

Elevated plasma von Willebrand factor (VWF) levels are associated with coronary artery disease, although the precise mechanism for this is unclear. Recently, four linked dimorphisms in the VWF gene promoter were demonstrated to influence plasma VWF level. We conducted a case-control study of 525 acute myocardial infarction (MI) cases and 451 control subjects, all aged < or = 75 years, to assess the potential contribution of two of these dimorphisms (-1185 G/A and -1051 A/G) to the risk of MI. The frequency of the -1185A/-1051G haplotype, associated with elevated VWF levels, was similar in the case and control groups, yielding a haplotypic odds ratio for MI of 0.93 (95% CI 0.77, 1.12, P = 0.43), and there was no significant association between the -1185A/-1051G haplotype and the risk of MI in any subgroup analysed. We therefore conclude that possession of the -1185A/-1051G haplotype does not confer an increased risk for MI.

Aged↗
PubMed2001

Gender differences in the vasomotor effects of different steroid hormones in rat pulmonary and coronary arteries.

It is well recognised that oestrogens possess vasodilatory properties, and similar responses to testosterone have been demonstrated. However, vasomotor effects of other steroid hormones have not been well described. Direct comparisons of the relative vasoactivity of different steroid hormones in different vascular beds in male and female genders have not been made. Coronary and pulmonary arteries from adult Wistar rats were mounted in a wire myograph, loaded to 100 and 17 mmHg respectively, maximally pre-contracted with 1 x 10(-4) M prostaglandin-F-2-alpha, and dose response curves to 1 x 10(-6) to 1 x 10(-3) or 3 x 10(-3) M of 17 beta-oestradiol, testosterone, progesterone, and cortisol dissolved in water were constructed. Addition of each steroid hormone caused acute, dose dependent dilatation in coronary and pulmonary vessels. In coronary arteries the order of activity was testosterone > progesterone > 17 beta-oestradiol > cortisol, p < 0.001. In pulmonary arteries, the order of activity was progesterone > testosterone > cortisol > 17 beta-oestradiol, p < 0.001. Pulmonary arteries from male animals were more sensitive to the effects of testosterone than those from female animals, p = 0.003, whereas coronary arteries from female animals were more sensitive to the effects of 17 beta-oestradiol than those from male animals, p < 0.001. We have demonstrated significant differences in the in vitro vasomotor effects of different steroid hormones in two distinct vascular beds. Gender differences in vasomotor responses to steroid hormones may play a role in the aetiology of vasospastic diseases.

Animals↗
PubMed2001

Current management of symptomatic atrial fibrillation.

Atrial fibrillation (AF) is the commonest arrhythmia. It presents in distinct patterns of paroxysmal, persistent and chronic AF, and patient management aims differ according to the pattern. In paroxysmal AF, drug treatment with beta-blockers, class Ic and class III agents reduce the frequency and duration of episodes. In persistent AF (recent onset, non-paroxysmal), early cardioversion with either pharmacological agents or by direct current (DC) cardioversion should be actively considered, in those patients who are suitable. Patients most likely to cardiovert and remain in sinus rhythm include those with duration of AF of <1 year, an acute reversible cause, left atrial diameter <50 mm and good left ventricular function on echocardiography. Recent data show that maintenance of sinus rhythm after successful cardioversion is enhanced by the use of class III drugs including amiodarone and dofetilide. In chronic or permanent AF, management is aimed at controlling the ventricular rate response with combinations of digoxin, beta-blockers and calcium antagonists with atrio-ventricular nodal activity (diltiazem and verapamil). There is some debate about the prognostic significance of AF. Certainly AF is associated with an excess mortality but this is largely accounted for by its association with serious intrinsic heart disease and the thrombo-embolic complications of the arrhythmia. Atrial fibrillation is a common default arrhythmia for the sick heart.

Adrenergic beta-Antagonists↗
PubMed2001

Effect of cigarette smoking on levels of bioavailable testosterone in healthy men.

The effect of smoking on androgen levels is important given the recent interest in the link between low levels of androgens and the development of cardiovascular disease. Numerous studies examining the effects of cigarette smoking on the levels of total and free testosterone have reported conflicting findings, but there has been no accurate assessment of the effects of cigarette smoking on the levels of bioavailable testosterone [not bound to sex hormone-binding globulin (SHBG)]. We attempted to determine whether smoking affects the level of bioavailable testosterone. We undertook a case-control study of 25 healthy male smokers and 25 healthy never-smokers, matched by age and body mass index. Early morning levels of total, free and bioavailable testosterone, 17beta-oestradiol, SHBG and cotinine were determined and compared between the two groups. Levels of total (18.5+/-4.6 nM versus 15.1+/-4.9 nM, P=0.01) and free testosterone (462+/-91 pM versus 402+/-93 pM, P=0.03) were found to be higher in smokers compared with non-smokers respectively, as was SHBG (34.1+/-12.8 versus 28.1+/-9.0 nM, P=0.06). There were no significant differences in the levels of bioavailable testosterone (3.78+/-1.59 versus 3.51+/-1.26 nM, P=0.49) or 17beta-oestradiol (44.5+/-11.4 versus 42.3+/-11.5 pM, P=0.50) between smokers and non-smokers respectively. These data suggest that cigarette smoking has no significant effect on the biologically active fraction of testosterone, but may influence the levels of total and free testosterone through changes in the levels of SHBG.

Adolescent↗
PubMed2000

Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Experimental studies suggest that androgens induce coronary vasodilatation. We performed this pilot project to examine the clinical effects of long-term low-dose androgens in men with angina. METHODS AND RESULTS: Forty-six men with stable angina completed a 2-week, single-blind placebo run-in, followed by double-blind randomization to 5 mg testosterone daily by transdermal patch or matching placebo for 12 weeks, in addition to their current medication. Time to 1-mm ST-segment depression on treadmill exercise testing and hormone levels were measured and quality of life was assessed by SF-36 at baseline and after 4 and 12 weeks of treatment. Active treatment resulted in a 2-fold increase in androgen levels and an increase in time to 1-mm ST-segment depression from (mean+/-SEM) 309+/-27 seconds at baseline to 343+/-26 seconds after 4 weeks and to 361+/-22 seconds after 12 weeks. This change was statistically significant compared with that seen in the placebo group (from 266+/-25 seconds at baseline to 284+/-23 seconds after 4 weeks and to 292+/-24 seconds after 12 weeks; P:=0.02 between the 2 groups by ANCOVA). The magnitude of the response was greater in those with lower baseline levels of bioavailable testosterone (r=-0. 455, P:<0.05). There were no significant changes in prostate specific antigen, hemoglobin, lipids, or coagulation profiles during the study. There were significant improvements in pain perception (P:=0.026) and role limitation resulting from physical problems (P:=0.024) in the testosterone-treated group. CONCLUSIONS: Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia.

Administration, Cutaneous↗