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Biomedical subjects

W W Parmley

Publications and source records attributed to W W Parmley.

At least 55 records · Page 3Linked to original sources
PubMed1999

Reunion.

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Education, Medical↗
PubMed1999

Influence of felodipine on left ventricular hypertrophy and systolic function in orthotopic heart transplant recipients: possible interaction with cyclosporine medication.

BACKGROUND: Concentric left ventricular (LV) hypertrophy develops early in orthotopic heart transplant (OHT) recipients. To compare the effects of a calcium channel blocker, felodipine, versus diuretics on LV hypertrophy and LV systolic function repeated magnetic resonance imaging studies were performed in OHT recipients. Cyclosporine levels and neurohormones were also measured to explore potential interactions with treatment. METHODS: Twenty-two patients were randomized at baseline (2 months after OHT) to receive felodipine or diuretic treatment. Before and after 4 months of treatment (n = 19), LV dimensions and LV mass (Simpson's rule) were measured. The relationship between circumferential fiber shortening (two-shell cylindrical model) and end-systolic wall stress was used as a measure of load-independent LV contractility. Neurohormones were measured at the beginning and end of the treatment period, and cyclosporine levels and blood pressures were additionally measured during treatment. RESULTS: At baseline, the felodipine and diuretic groups did not differ in LV mass, wall stress, and fiber shortening. During felodipine treatment LV mass decreased (p < 0.01) and tended to increase during diuretics treatment (p = 0.06). Afterload-corrected fiber shortening did not change during felodipine treatment, but decreased (p < 0.01) with diuretics. Changes in LV mass were positively correlated with cyclosporine levels (r = 0.70) in the diuretics group, but not in the felodipine group. CONCLUSIONS: In OHT recipients during diuretic treatment, progression of LV hypertrophy occurs in relation to cyclosporine plasma levels and is accompanied by impairment of systolic contractile function. Felodipine induces regression of LV hypertrophy, while systolic contractile function is preserved. During felodipine treatment, regression of LV hypertrophy is unrelated to cyclosporine levels. Thus, felodipine seems to attenuate the hypertrophic effect of cyclosporine on transplanted hearts.

Analysis of Variance↗
PubMed1999

Effects of L-arginine on atherogenesis and endothelial dysfunction due to secondhand smoke.

Secondhand smoke (SHS) and hypercholesterolemia increase cardiovascular risk. We hypothesized that L-arginine, the precursor of nitric oxide (NO), might protect against atherogenesis and endothelial dysfunction caused by SHS. The effects of L-arginine supplementation (2.25% solution ad libitum) and SHS (smoking chambers for 10 weeks) were examined in 32 hypercholesterolemic rabbits. Eight normal rabbits served as controls. Acetylcholine- and nitroglycerin-induced vasorelaxation was assessed in aortic rings precontracted with norepinephrine. Hypercholesterolemia increased intimal lesion area (P=0.012), reduced endothelium-dependent relaxation (P=0.009), and reduced basal (P=0.005) and stimulated (P<0.0005) production of NOs. SHS increased intimal lesion area (P=0. 01) norepinephrine-induced contraction (P=0.001) and reduced endothelium-dependent relaxation (P=0.02). SHS-induced increase in norepinephrine contraction was abolished by the inhibition of NO synthase and removal of endothelium. L-Arginine improved endothelium-dependent relaxation (P=0.001) and attenuated SHS-induced endothelial dysfunction (P=0.007) and atherogenesis (P=0. 001). Basal production of nitrogen oxides correlated inversely with intimal lesion area (r=-0.66; P<0.0005) and stimulated production of NOs correlated with endothelium-dependent relaxation (r=-0.66; P<0. 001). SHS causes endothelial dysfunction and increased adrenergic responsiveness and atherogenesis in hypercholesterolemic rabbits. Chronic dietary supplementation with the NO precursor L-arginine mitigates these effects. The adverse vascular consequences of SHS appear to be mediated via deleterious effects on endothelial function.

Animals↗
PubMed1998

Evolution of angiotensin-converting enzyme inhibition in hypertension, heart failure, and vascular protection.

Over 100 years of scientific investigation has established that angiotensin-converting enzyme (ACE) plays an important role in both the renin-angiotensin system and the kinin-kallekrein system. ACE inhibitors--which stem the production of angiotensin II, a potent vasoconstrictor--have proved to be useful agents in the management of hypertension, in the prevention and treatment of heart failure, and in the improvement of endothelial function. Generally, ACE inhibitors are as efficacious as beta blockers and thiazide diuretics in reducing blood pressure and also induce regression of left ventricular hypertrophy. Many trials-including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), the Veteran's Administration Cooperative Vasodilator-Heart Failure Trial (V-HeFT I), the Studies of Left Ventricular Dysfunction (SOLVD), and the Survival and Ventricular Enlargement (SAVE) trial--have demonstrated the ability of ACE inhibitors to reduce mortality within a wide range of heart failure, from asymptomatic left ventricular dysfunction to severe heart failure. The SAVE trial specifically evaluated the effects on post-myocardial infarction mortality and remodeling and found that ACE inhibitors were effective in reducing both. Further studies are assessing the potential additional antiatherosclerotic aspects of ACE inhibitors. Initial research indicates a reversal of endothelial dysfunction in atherosclerotic animals, and subsequent clinical trials, including the Trial on Reversing ENdothelial Dysfunction (TREND), support the likelihood of a similar effect in humans. Beneficial effects in hypertension or heart failure may also be gained with other interruptors of the renin-angiotensin system, such as angiotensin receptor blockers. Results from studies assessing these receptor blockers will bring greater understanding to the mechanism of action of ACE inhibitors.

Angiotensin Receptor Antagonists↗
PubMed1998

Ventricular fibrillation-induced intracellular Ca2+ overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation.

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]i overload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i overload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]i overload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.

Animals↗
PubMed1998

In-utero and neonatal exposure to secondhand smoke causes vascular dysfunction in newborn rats.

OBJECTIVES: We sought to determine the effects of secondhand smoke (SHS) exposure on vascular reactivity in newborn and infant rats. BACKGROUND: Secondhand smoke exposure increases cardiovascular risk. Secondhand smoke-induced endothelial dysfunction has been demonstrated in older teenagers and young adults. We have previously shown in adult rabbits that SHS induces atherogenesis and endothelial dysfunction. The effects of SHS on vascular function in the offspring of SHS-exposed mothers and in infants are unknown. METHODS: In this study the effects of in-utero (21 days) and neonatal (28 days) exposure to SHS were examined in 80 rats, 4 weeks of age, in a 2-by-2 design study. Rats were exposed to sidestream smoke in smoking chambers. Aortic rings were excised and isometric force responses to phenylephrine, acetylcholine, A23187 and nitroglycerin were studied in organ baths. RESULTS: Neonatal SHS exposure reduced animal weight (p=0.009). In-utero exposure increased the sensitivity (decreased the EC50) of aortic rings to phenylephrine (p < 0.0005), as did neonatal exposure (p=0.01). Maximal contraction to phenylephrine was reduced by in-utero exposure (p=0.04). In-utero SHS exposure reduced maximal endothelium-dependent relaxation to acetylcholine (p=0.04) and increased the EC50 (p=0.05), suggesting impaired sensitivity to acetylcholine. In-utero exposure decreased the sensitivity (increased the EC50) to the endothelium-independent vasodilator nitroglycerin (p=0.003). CONCLUSIONS: Secondhand smoke has detrimental effects on vascular smooth muscle function in the newborn.

Acetylcholine↗
PubMed1998

Is CPR the answer?

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Academic Medical Centers↗