Poor quality teaching in lay person CPR courses.

Recent studies have found that poor cardiopulmonary resuscitation (CPR) is commonly performed in resuscitation attempts, both by health professionals and lay people. One of the contributing factors to poor performance of CPR may be poor initial teaching. This study was conducted to investigate the quality of 14 CPR courses complying with New Zealand Qualifications Authority standards, which includes formal assessment of CPR. While courses taught by the large first aid training organisations in New Zealand had a student to manikin ratio of around 3:1, courses taught by smaller providers had a ratio of over 4:1. During the 4h course, only 20+/-2 min were spent demonstrating CPR, and 26+/-4 min were spent with students practising CPR. The assessment of adult, child and infant CPR took on average less than 2.5 min in total. Importantly, in the majority of courses (71%), certification was granted when the CPR technique was performed incorrectly, with both compression depth and compression place being corrected only 57% of the time. Courses only discussed the importance of early defibrillation 57% of the time, and provided limited information on symptoms of acute coronary syndromes. In light of these observations it is suggested that the current style of teaching is unlikely to result in students being able to perform adequate CPR if required in the community.

Augmentation of endothelial function following exercise training is associated with increased L-arginine transport in human heart failure.

We have reported previously a decrease in the clearance of the NO (nitric oxide) precursor L-arginine in the forearm circulation of CHF (congestive heart failure) patients, suggesting a potential rate-limiting mechanism contributing to the common finding of endothelial dysfunction in CHF. Given data that show exercise training augments endothelial function in CHF, the aim of the present study was to investigate whether these improvements were due to an increase in L-arginine transport. Measures of L-arginine transport, endothelial function and exercise capacity were repeated before and after 8 weeks of "usual living" or exercise training in 21 CHF patients [NYHA (New York Heart Association) class II/III]. Exercise capacity (6-min walk test) increased following exercise training (496+/-21 to 561+/-17 m; P=0.005), whereas the control group demonstrated no change [488+/-18 to 484+/-21 m; P=ns (not significant)]. Basal FBF (forearm blood flow) remained stable following exercise training (2.68+/-0.55 to 2.46+/-0.32 ml.min(-1).100 ml(-1) of tissue) and "usual living" (2.16+/-0.37 to 2.91+/-0.55 min(-1).100 ml(-1) of tissue). FBF responses to ACh (acetylcholine) increased following exercise by 49.6+/-17.7% (area under curve; P=0.01) demonstrating augmented endothelial function. FBF responses to SNP (sodium nitroprusside) were also improved following exercise training (30.8+/-8.2%; P=0.02). There was no change in vascular function in the "usual living" group. The clearance of L-arginine was significantly increased following involvement in the exercise programme (69.4+/-7.8 to 101.0+/-9.5 ml/min; P=0.04), whereas there was no change in the "usual living" group (78.4+/-17.5 to 81.0+/-14.9 ml/min; P=ns). In conclusion, the augmentation in endothelial function observed following exercise may be due, in part, to an increase in the transport of L-arginine in CHF patients.

Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects.

BACKGROUND: Impaired endothelium-dependent NO-mediated vasodilation is a key feature of essential hypertension and may precede the increase in blood pressure. We investigated whether transport of the NO precursor L-arginine is related to decreased endothelial function. METHODS AND RESULTS: Radiotracer kinetics ([3H]L-arginine) were used to measure forearm and peripheral blood mononuclear cell arginine uptake in hypertensive subjects (n=12) and in 2 groups of healthy volunteers with (n=15) and without (n=15) a family history of hypertension. In conjunction, forearm blood flow responses to acetylcholine and sodium nitroprusside were measured before and after a supplemental intra-arterial infusion of L-arginine. In vivo and in vitro measures of L-arginine transport were substantially reduced in the essential hypertension and positive family history groups compared with the negative family history group; however, no difference was detected in peripheral blood mononuclear cell mRNA or protein expression levels for the cationic amino acid transporter CAT-1. Plasma concentrations of L-arginine and N(G),N(G')-dimethylarginine (ADMA) did not differ between groups. L-arginine supplementation improved the response to acetylcholine only in subjects with essential hypertension and positive family history. CONCLUSIONS: Similar to their hypertensive counterparts, normotensive individuals at high risk for the development of hypertension are characterized by impaired L-arginine transport, which may represent the link between a defective L-arginine/NO pathway and the onset of essential hypertension. The observed transport defect is not due to apparent alterations in CAT-1 expression or elevated endogenous ADMA.

beta-Adrenoceptor-mediated, nitric-oxide-dependent vasodilatation is abnormal in early hypertension: restoration by L-arginine.

BACKGROUND: It is unknown whether beta-adrenoceptor-mediated vasodilatation is altered in early hypertension and whether it can be modulated by L-arginine. METHODS AND DESIGN: We measured changes in forearm blood flow by plethysmography in response to acetylcholine (9 and 37 microg/min), sodium nitroprusside (200 and 800 ng/min) and the beta-receptor agonist, isoproterenol (50 and 200 ng/min) in 12 patients with essential hypertension (group EH) and in healthy volunteers with (group PFH; n = 14) and without (group NFH; n = 14) a family history of essential hypertension, before and during concomitant infusion of L-arginine (10 micromol/min). In five individuals from each group, infusion of acetylcholine and isoproterenol was repeated during the concurrent blockade of nitric oxide synthesis by N-monomethyl-L-arginine (L-NMMA; 4 micromol/min). RESULTS: The response to acetylcholine was reduced in groups EH and PFH compared with group NFH (both P < 0.05), whereas the vasodilator effects of isoproterenol and sodium nitroprusside were similar in all three groups. Acetylcholine- and isoproterenol-induced vasodilatation did not change during infusion of the nitric oxide precursor, L-arginine, in group NFH, but were significantly enhanced by L-arginine in groups PFH and EH [forearm blood flow before and after isoproterenol 200 ng/min: group PFH 11.8 +/- 1.02 and 13.3 +/- 1.08 ml/min, respectively (P < 0.05); group EH: 11.3 +/- 1.57 and 14.9 +/- 1.91 ml/min, respectively (P < 0.01)]. Co-infusion of L-NMMA blunted the response to acetylcholine and isoproterenol in group NFH (P < 0.05), but did not significantly modify vasodilatation in groups PFH and EH. CONCLUSIONS: Although beta-adrenergic vasodilatation seemed to be unaltered in early hypertension, L-arginine enhanced the response to isoproterenol, whereas concomitant inhibition of nitric oxide synthase by L-NMMA had no significant effect. These findings suggest that the nitric oxide component of isoproterenol-mediated vasodilatation is impaired in early hypertension and possibly compensated by increased beta-adrenoceptor responsiveness of smooth muscle cells. In this setting, supplementation of the nitric oxide precursor, L-arginine, enhances the vasodilator response to beta-adrenergic stimulation.

An age-related decline in endothelial function is not associated with alterations in L-arginine transport in humans.

OBJECTIVES: Endothelial dysfunction is established in aged individuals; however, the mechanism(s) are not fully elucidated. We have previously identified l-arginine transport as a potential rate-limiting factor in nitric oxide (NO) production in heart-failure patients, characterized with endothelial dysfunction. We therefore aimed to investigate whether the age-related decline in endothelial function is due to reduced transport of the NO precursor, L-arginine. METHODS: Thirty-seven healthy males aged between 19 and 69 were recruited. Throughout 40 min of intra-arterial (i.a.) infusion of [3H]L-arginine (100 nCi/min), venous blood samples were withdrawn for the determination of L-arginine clearance. Venous occlusion plethysmography was then used to record the forearm blood flow responses to i.a. infusions of acetylcholine (ACh; 9.25 and 37 microg/min) and sodium nitroprusside (SNP; 2 and 8 microg/min). RESULTS: While ACh-induced vasodilation decreased with age (37 microg/min; young 15.87 +/- 1.30, middle-aged 9.59 +/- 1.33, older 10.42 +/- 1.12 ml/min per 100 ml tissue; P = 0.001), there was no change in forearm [3H]L-arginine clearance (young 126.08 +/- 19.05, middle-aged 122.47 +/- 20.96, older 126.56 +/- 19.56 ml/min; NS). Further [3H]L-arginine uptake studies in isolated peripheral blood mononuclear cells supported our in vivo findings, demonstrating no difference in [3H]L-arginine transport across the age spectrum. CONCLUSIONS: The present study excludes the hypothesis of impaired L-arginine transport as a potential mechanism for the age-related decline in endothelial function.

In vivo and in vitro evidence for ACh-stimulated L-arginine uptake.

Whereas L-arginine is clearly recognized as the precursor for nitric oxide synthesis, and its entry into endothelial cells via system y(+) transport is established, few data exist regarding the acute regulation of this transport process. We specifically investigated the effect of ACh and isoprenaline (Iso) on L-arginine uptake in the human forearm and in cultured bovine aortic endothelial cells (BAEC). Sixteen healthy males were studied. During a steady-state intra-arterial infusion of [(3)H]L-arginine (100 nCi/min), the effects of ACh (9.25 and 37 microg/min), Iso (25-50 and 200 microg/min), and sodium nitroprusside (SNP) (1-2 and 8 microg/min) on forearm plasma flow (FPF), L-[(3)H]arginine uptake, and L-[(3)H]citrulline release were determined. In parallel experiments, the effects of ACh, Iso, and SNP on L-[(3)H]arginine uptake were studied in BAEC. L-Arginine uptake was inversely related to FPF (r = -0.50; P < 0.005). At a similar FPF (ACh 56.82 +/- 9.25, Iso 58.49 +/- 5.56, SNP 57.92 +/- 4.96 ml/min; P = ns), intra-arterial ACh significantly increased forearm uptake of L-[(3)H]arginine (54,655 +/- 8,018 dpm/min), compared with that observed with either Iso (40,517.23 +/- 6,841 dpm/min; P = 0.01) or SNP (36,816 +/- 4,650 dpm/min; P = 0.011). This was associated with increased ACh-induced L-[(3)H]citrulline release compared with Iso and SNP (P = 0.046). Similarly, in BAEC, ACh significantly increased L-[(3)H]arginine uptake compared with control, Iso, or SNP (ACh 12.0 x 10(7) +/- 1.83 x 10(7) vs. control 6.67 x 10(7) +/- 1.16 x 10(7) vs. Iso 7.35 x 10(7) +/- 1.63 x 10(7) vs. SNP 6.01 x 10(7) +/- 1.11 x 10(7) fmol.min(-1).mg(-1) at 300 micromol/l L-arginine; P = 0.043). Taken together, these data indicate that ACh stimulates L-arginine uptake in cultured endothelial cells and in human forearm circulation, indicating the potential for acute modulation of endothelial L-arginine uptake.

Low-dose atorvastatin therapy does not augment endothelial function in active hypercholesterolaemic males.

AIMS: As statin therapy has been demonstrated to augment endothelial function in sedentary hypercholesterolaemia (HC), we aimed to investigate the effects of atorvastatin therapy on endothelial function in physically active, HC men. METHOD AND RESULTS: Eleven physically active, HC males were recruited. Endothelial function [forearm blood flow response to brachial artery infusion of acetylcholine (Ach)] was assessed twice in each subject following atorvastatin or no therapy in a randomized crossover design. In addition, endothelial function was compared with an active, normolipidaemic control group (C). Atorvastatin therapy reduced total and LDL cholesterol, but had no effect on basal blood flow or endothelial function (peak ACh mean difference +/- standard error 0.75 +/- 1.75 ml min(-1) per 100 ml tissue) [95% confidence interval (CI) -3.1, 4.6]. In addition, there was no difference in endothelial function between the HC and C groups (-1.14 +/- 2.60 ml min(-1) per 100 ml tissue; CI -6.53, 4.25). CONCLUSION: Statin therapy in HC patients with normal endothelial function does not augment endothelial function.

Reduced myocardial and systemic L-arginine uptake in heart failure.

Altered nitric oxide (NO) bioavailability has been ascribed an important role in the pathophysiology of congestive heart failure (CHF). In the peripheral vasculature, we recently demonstrated a depression of L-arginine transport in association with pharmacological evidence of reduced endothelial function. In contrast, increased myocardial NO generation has been proposed to account for a component of the reduced myocardial contractility in CHF, although this remains controversial. We determined the whole body clearance rate and cardiac fractional extraction of L-arginine during a steady-state intravenous infusion of [3H]L-arginine (300 nCi/min) in 9 healthy control subjects and 7 patients with moderate to severe CHF. In patients with CHF, there was a 30% reduction in the transcardiac extraction of [3H]L-arginine compared with controls (P<0.05), which was accompanied by a trend toward reduced [3H]L-citrulline release (P=0.06). In conjunction, the systemic clearance rate of [3H]L-arginine was significantly lower in patients with CHF (778+/-148 versus 1278+/-144 mL/min, P<0.05). In association with these biochemical indices, we observed a 38% reduction (P<0.05) in the mRNA expression of the cationic amino acid transporter CAT-1 in ventricular myocardial samples from patients with CHF compared with healthy unused donor myocardium, whereas myocardial NOS enzymatic activity and NOS protein were unchanged. These data indicate the presence of a significant reduction in the myocardial uptake of L-arginine in patients with CHF. Furthermore, this abnormality seems to be part of a systemic downregulation of L-arginine transport.

Exercise training increases arterial compliance in patients with congestive heart failure.

Systemic arterial compliance (SAC) makes an important contribution to cardiac afterload, and thus is a significant determinant of left ventricular work. Previous studies have suggested that arterial compliance may be reduced in patients with congestive heart failure (CHF), and that SAC is increased after a 4-week exercise training programme in healthy, sedentary individuals. The present study aimed to investigate the effects of an 8-week exercise training programme on arterial mechanical properties, left ventricular performance and quality of life in CHF patients. A total of 21 patients with NYHA class II or III CHF (mean+/-S.D. age 55+/-13 years) were randomly allocated to either an 8-week exercise training group or a "usual lifestyle" control group. SAC, as determined non-invasively using applanation tonometry and Doppler aortic velocimetry, increased from 0.57+/-0.11 to 0.77+/-0.14 arbitrary compliance units (mean+/-S.E.M.; P=0.01) in the exercise group, while no change occurred in the control group. Left ventricular structure and function was assessed by echocardiography, and these parameters were unchanged over the 8-week study period. Exercise training significantly increased exercise capacity, measured by a 6-min walking test (474+/-27 to 547+/-34 m; P=0.008). Quality of life, as assessed using the Minnesota Living with Heart Failure Evaluation, demonstrated a decrease in heart failure symptoms from 46+/-7 to 24+/-5 units (P=0.01) following the exercise training programme. These data show that exercise training improves SAC in patients with CHF. The accompanying improvement in exercise capacity may be due, in part, to an improvement in arterial function.