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Biomedical subjects

C C Lang

Publications and source records attributed to C C Lang.

At least 19 recordsLinked to original sources
PubMed1998

Abnormalities of the QT interval in primary disorders of autonomic failure.

BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Aged↗
PubMed1998

Effect of CYP3A inhibition on vesnarinone metabolism in humans.

OBJECTIVE: To identify the cytochrome P450 (CYP) enzymes involved in the conversion of vesnarinone to it main primary metabolite OPC-18692 and to investigate the effect of CYP3A inhibition on the pharmacokinetics of vesnarinone in vivo. METHODS: Formation of the primary vesnarinone metabolite OPC-18692 was measured in microsomes from AHH-1 TK +/- cells heterologously expressing CYP1A1, CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, or CYP3A4. The pharmacokinetics of vesnarinone and OPC-18692 were defined for 12 health white men after oral administration of 60 mg vesnarinone before and after CYP3A inhibition, which was produced by pretreatment with erythromycin. CYP3A inhibition was verified with erythromycin breath test. RESULTS: In vitro, expressed CYP2E1 and CYP3A4 produced significant amounts of OPC-18692 with the higher formation rate observed by CYP3A4 (12.3 pmol/pmol VYP3A4 per 2 hours versus 1 pmol/pmol CYP2E1 per 2 hours). In vivo, the area under the concentration-time curve extrapolated to infinity (AUC[infinity]) of vesnarinone after pretreatment with erythromycin increased from 133 +/- 26 micrograms.hr/ml to 202 +/- 47 micrograms.hr/ml (p < 0.001), and the half-life increased from 36.5 +/- 9.6 hours to 46.2 +/- 9.2 hours (p < 0.01). Clearance decreased from 372 +/- 68 ml/min to 256 +/- 49 ml/min (p < 0.001). These changes in the disposition of vesnarinone were accompanied by a decrease in plasma concentration of the metabolite OPC-18692 so that the AUC(0-48) was reduced from 1311 +/- 513 micrograms.hr/ml to 850 +/- 148 micrograms.hr/ml (p < 0.001). The total amount of vesnarinone excreted in the urine up to 168 hours after administration increased after erythromycin pretreatment (p < 0.001). Although renal clearance did not change, OPC-18692 was not detectable in the urine. The erythromycin breath test showed significant inhibition after pretreatment with erythromycin (p < 0.001). CONCLUSIONS: CYP2E1 and CYP3A4 are involved in the phase I metabolism of vesnarinone. Inhibition of CYP3A activity in vivo increases the plasma concentration of vesnarinone and delays its elimination in humans so that monitoring of its plasma levels may be helpful in preventing concentration-related toxicity when CYP3A activity is impaired. Whether CYP3A induction and altered CYP2E1 activity may also change the in vivo disposition of vesnarinone remains to be determined.

Administration, Oral↗
PubMed1998

Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature.

OBJECTIVES: This study sought to define the local regulation of vascular tissue-type plasminogen activator (t-PA) release. BACKGROUND: The vascular endothelium, through the production of t-PA and plasminogen activator inhibitor (PAI-1), is an important regulator of fibrinolysis. Plasma t-PA levels increase in response to adrenergic stimulation; however, it is unclear whether this increase is the result of systemic reflex responses or direct effects on the vascular endothelium. METHODS: Forearm blood flow dose responses were generated to low doses of agonist infused directly into the brachial artery in 15 normotensive men (mean [+/-SE] age 28.9 +/- 2.2 years). Simultaneous arterial and venous blood samples were drawn at baseline and in response to the intraarterial administration of isoproterenol (400 ng/min), methacholine (8 microg/min) and sodium nitroprusside (SNP) (8 microg/min). PAI-1 and t-PA antigen levels were measured by enzyme-linked immunosorbent assay, and the net release across the forearm was calculated. RESULTS: Forearm plasma flow increased significantly from baseline (1.4 +/- 0.2 ml/100 ml per min) after administration of isoproterenol, methacholine and SNP (9.7 +/- 1.9, 8.7 +/- 1.9 and 6.7 +/- 1.1 ml/100 ml per min, respectively) (p < 0.001 by analysis of variance). Baseline net t-PA release (0.7 +/- 0.3 ng/100 ml per min) increased significantly after administration of isoproterenol (26.2 +/- 11.6 ng/100 ml per min, p = 0.005) and methacholine (15.3 +/- 5.5 ng/100 ml per min, p = 0.001) but not after administration of SNP (1.8 +/- 2.2 ng/100 ml per min, p = 0.84). There was no net release of PAI-1 across the vascular bed. CONCLUSIONS: Marked, rapid local t-PA release occurred in response to isoproterenol, a beta-adrenoceptor agonist, and methacholine, an endothelium-dependent nitric oxide agonist, in the human forearm. This effect was selective and independent of the effects of shear stress due to increased flow because SNP induced similar increases in forearm blood flow without affecting t-PA release. Vascular t-PA release may be a potentially valuable tool for evaluating endothelial function in diseases associated with increased risk of thrombosis.

Adult↗
PubMed1998

The effect of mivacurium pretreatment on intra-ocular pressure changes induced by suxamethonium.

Forty patients without eye disease, undergoing elective nonophthalmic surgery, were studied in a double-blind, randomised, placebo-controlled study evaluating the efficacy of mivacurium pretreatment in attenuating the rise in intra-ocular pressure in response to suxamethonium administration, laryngoscopy and intubation. The patients were randomly allocated to receive either mivacurium 0.02 mg.kg-1 or normal saline as pretreatment 3 min before a rapid sequence induction technique using alfentanil, propofol and suxamethonium. Suxamethonium induced a significant increase in intra-ocular pressure in the control group but not in the mivacurium pretreatment group (mean (SEM) increase = 3.5 (1.2) mmHg vs. 0.4 (0.8) mmHg, p < 0.05). There was a decrease in intra-ocular pressure in both groups after laryngoscopy and intubation with no significant difference between the two groups. These results show that mivacurium pretreatment is effective in preventing the increase in intra-ocular pressure after suxamethonium administration.

Adolescent↗
PubMed1997

Normalization of acquired QT prolongation in humans by intravenous potassium.

BACKGROUND: QT interval prolongation and dispersion have been implicated in serious arrhythmias in congestive heart failure (CHF) and the congenital and drug-induced long-QT syndromes (LQTS). In a subset of the congenital LQTS, infusion of potassium can correct QT abnormalities, consistent with in vitro increases in outward currents such as I(Kr) or I(Kl) when extracellular potassium concentration ([K+]o) is increased. Furthermore, increasing [K+]o decreases the potency of I(Kr)-blocking drugs in vitro. The purpose of this study was to test the hypothesis that increasing [K+]o corrects QT abnormalities in CHF and in subjects treated with quinidine. METHODS AND RESULTS: KCl (maximum, 40 mEq) was infused into (1) 12 healthy subjects treated with quinidine sulfate (5 doses of 300 mg/5 h) or placebo and (2) 8 CHF patients and age-matched normal control subjects. Mean [K+] increased from 4 to 4.2 mEq/L to 4.7 to 5.2 mEq/L. Potassium infusion significantly reversed QTUc prolongation, especially in the precordial leads (quinidine, 590+/-79 to 479+/-35 [+/-SD] ms(1/2), P<.001; CHF, 521+/-110 to 431+/-47 ms(1/2), P<.05). There was no effect in either control group. Similarly, potassium decreased QTUc dispersion (quinidine, 210+/-62 to 130+/-75 ms(1/2), P<.01; CHF, 132+/-68 to 84+/-35 ms(1/2), P=.07) and was without effect in the control subjects. QT morphological abnormalities, including U waves and bifid T waves, were reversed by potassium. CONCLUSIONS: Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.

Adult↗
PubMed1997

Effect of sympathoinhibition on exercise performance in patients with heart failure.

BACKGROUND: In patients with heart failure, excessive sympathetic activation during exercise could interfere with exercise performance by impairing arteriolar dilation in working muscle and by adversely altering skeletal muscle metabolic behavior. To test this hypothesis, we examined the effect of sympathoinhibition with clonidine, a central sympatholytic agent, on skeletal muscle blood flow and metabolism in patients with heart failure. METHODS AND RESULTS: Swan-Ganz and femoral venous catheters were inserted in 20 patients with chronic heart failure and exercise intolerance (peak exercise VO2 = 9.3 +/- 1.4 [SEM] mL.min-1.kg-1). Central hemodynamic measurements, leg blood flow determined by thermodilution, and systemic and leg metabolic parameters were measured during maximal treadmill exercise before and 2 hours after clonidine 2 micrograms/kg IV (n = 15) or 0.9% normal saline (n = 5). During-control exercise before the administration of clonidine, leg blood flow increased from 0.3 +/- 0.1 to 1.8 +/- 0.2 L/min and plasma norepinephrine increased from 485 +/- 61 to 2155 +/- 186 pg/mL (both P < .01). Treatment with clonidine markedly suppressed norepinephrine levels during exercise (matched peak exercise workload: control, 2137 +/- 187 versus clonidine, 1430 +/- 161 pg/mL), increased leg blood flow (control, 1.8 +/- 0.2 versus clonidine, 2.3 +/- 0.4 L/min), reduced systemic oxygen consumption (control, 1002 +/- 70 versus clonidine, 966 +/- 68 mL/min), reduced pulmonary artery lactate concentration (control, 3.2 +/- 0.3 versus clonidine, 2.6 +/- 0.2 mEq/L), and decreased minute ventilation (control, 39.7 +/- 2.1 versus clonidine, 34.9 +/- 2.4 L/min) (all P < .05). CONCLUSIONS: These findings suggest that sympathetic activation during exercise reduces leg blood flow, increases muscle glycolysis, and decreases muscle efficiency in patients with heart failure.

Cardiomyopathy, Dilated↗
PubMed1997

Vasodilation in black Americans: attenuated nitric oxide-mediated responses.

BACKGROUND: Attenuated vasodilation in response to the intra-arterial administration of the beta-adrenergic agonist isoproterenol (INN, isoprenaline), an endothelium-independent vasodilator, has previously been observed in normotensive black Americans. To determine whether this reflected a more generalized attenuation of responses to vasodilators, we compared forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilator sodium nitroprusside in young normotensive black men and white men. METHODS: Forearm blood flow responses to the intra-arterial administration of isoproterenol (10 to 400 ng/min), methacholine (0.25 to 8 micrograms/min), and sodium nitroprusside (0.25 to 8 micrograms/min) were measured with use of venous occlusion plethysmography in 11 normotensive black men (mean +/- SE age, 30.5 +/- 2.2 years) and nine normotensive white men (mean age, 28.0 +/- 3.2 years). RESULTS: Baseline characteristics, including baseline forearm blood flow, were similar in the black and the white subjects. Vasodilation in response to isoproterenol, sodium nitroprusside, and methacholine was significantly attenuated in black subjects, resulting respectively in a 3.7-fold, 3.6-fold, and 5.0-fold increase in forearm blood flow in black subjects and a 7.5-fold, 5.2-fold, and 6.9-fold increase in forearm blood flow in white subjects (ANOVA; isoproterenol, p < 0.0001; sodium nitroprusside, p < 0.0001; methacholine, p = 0.01). CONCLUSIONS: Our finding of attenuated nitric oxide-mediated vasodilation in response to methacholine and sodium nitroprusside in healthy black American men suggests that attenuated vasodilation in black subjects is a relatively generalized phenomenon, resulting in attenuated responses to multiple vasodilators that act through different receptor- and nonreceptor-mediated mechanisms.

Adrenergic beta-Agonists↗
PubMed1997

Diagnosing left ventricular dysfunction after myocardial infarction: the Dundee algorithm.

Large-scale trials of angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) suggest that the benefits are greatest in patients with left ventricular (LV) dysfunction. However, early evaluation of LV function in all patients after AMI by current methods can be difficult due to a lack of resources and skilled personnel. Thus a clinical algorithm that could be used at the bedside to reliably identify patients with a left ventricular ejection fraction (LVEF) < or = 40% would be helpful as an occasional alternative to echocardiography. We have devised such an algorithm based on the presence of one of: (i) clinical signs of heart failure; (ii) an index Q-wave anterior myocardial infarction; (iii) lack of thrombolytic therapy when there is a history of two or more previous myocardial infarctions and a CK rise > 1000 U/l. We tested this new algorithm prospectively in the coronary care units of two hospitals (one UK and one USA). In the UK centre, the sensitivity and specificity of the algorithm at identifying patients with a LVEF < or = 40% were 82% and 72%, respectively. In the US centre, the sensitivity of the algorithm was 91% and the specificity 78% at identifying patients with LV dysfunction. We have validated a simple clinical algorithm which can be used at the bedside for identifying patients who would benefit from an ACE inhibitor after AMI.

Aged↗
PubMed1997

Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure.

The purpose of this study was to determine whether skeletal muscle atrophy limits the maximal exercise capacity of stable ambulatory patients with heart failure. Body composition and maximal exercise capacity were measured in 100 stable ambulatory patients with heart failure. Body composition was assessed by using dual-energy X-ray absorption. Peak exercise oxygen consumption (VO2peak) and the anaerobic threshold were measured by using a Naughton treadmill protocol and a Medical Graphics CardioO2 System. VO2peak averaged 13.4 +/- 3.3 ml.min-1.kg-1 or 43 +/- 12% of normal. Lean body mass averaged 52.9 +/- 10.5 kg and leg lean mass 16.5 +/- 3.6 kg. Leg lean mass correlated linearly with VO2peak (r = 0.68, P < 0.01), suggesting that exercise performance is influences by skeletal muscle mass. However, lean body mass was comparable to levels noted in 1,584 normal control subjects, suggesting no decrease in muscle mass. Leg muscle mass was comparable to levels noted in 34 normal control subjects, further supporting this conclusion. These findings suggest that exercise intolerance in stable ambulatory patients with heart failure is not due to skeletal muscle atrophy.

Adult↗
PubMed1997

Prostaglandin production contributes to exercise-induced vasodilation in heart failure.

Endothelial release of prostaglandins may contribute to exercise-induced skeletal muscle arteriolar vasodilation in patients with heart failure. To test this hypothesis, we examined the effect of indomethacin on leg circulation and metabolism in eight chronic heart failure patients, aged 55 +/- 4 yr. Central hemodynamics and leg blood flow, determined by thermodilution, and leg metabolic parameters were measured during maximum treadmill exercise before and 2 h after oral administration of indomethacin (75 mg). Leg release of 6-ketoprostaglandin F1alpha was also measured. During control exercise, leg blood flow increased from 0.34 +/- 0.03 to 1. 99 +/- 0.19 l/min (P < 0.001), leg O2 consumption from 13.6 +/- 1.8 to 164.5 +/- 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 +/- 8.5 to 267.4 +/- 35.8 pg/min (P < 0.001). Indomethacin suppressed release of prostaglandin F1alpha (P < 0.001) throughout exercise and decreased leg blood flow during exercise (P < 0.05). This was associated with a corresponding decrease in leg O2 consumption (P < 0.05) and a higher level of femoral venous lactate at peak exercise (P < 0.01). These data suggest that release of vasodilatory prostaglandins contributes to skeletal muscle arteriolar vasodilation in patients with heart failure.

Cyclooxygenase Inhibitors↗
PubMed1997

Blunted blood pressure response to central sympathoinhibition in normotensive blacks: increased importance of nonsympathetic factors in blood pressure maintenance in blacks.

Enhanced sympathetic reactivity may predispose blacks to the development of hypertension and may occur because of increased sympathetic stimulation and/or attenuated sympathoinhibition. A potential site for such attenuated sympathetic inhibition may be at the level of central alpha2-adrenergic receptors, which play an important role in the feedback inhibition of norepinephrine release. We used cumulative doses (1, 2, and 3 microg/kg I.V.) of the centrally acting alpha2-adrenergic agonist clonidine to measure the sensitivity of alpha2-adrenoceptor-mediated sympathoinhibition and the resultant hypotensive response in 8 normotensive blacks and 10 normotensive whites. Sympathetic activity was determined by radioisotope dilution methodology. Basal norepinephrine spillover was similar in blacks (0.80+/-0.14 microg/min) and whites (0.73+/-0.19 microg/min, P=NS) and after clonidine decreased significantly in both blacks (0.21+/-0.07 microg/min, P<.0001) and whites (0.24+/-0.06 microg/min, P<.0001), with no difference between the groups (P=NS). Despite this similar degree of sympathoinhibition, the hypotensive response to clonidine was markedly blunted in blacks, such that mean arterial pressure decreased by only 10% in blacks but by 21% in whites (P<.0001). The smaller blood pressure decrement after clonidine in normotensive blacks, in the face of an equal degree of sympathoinhibition, suggests that even when sympathetic tone is decreased to the same level in blacks and whites, normotensive blacks have less reduction in blood pressure than whites, implying that nonadrenergic mechanisms contribute more to blood pressure maintenance in blacks than whites. Whether a similar interethnic difference in response to sympathoinhibition occurs in hypertensive patients is as yet unknown.

Adult↗
PubMed1997

Sympathoinhibitory response to clonidine is blunted in patients with heart failure.

To determine whether alpha2-adrenergic-mediated sympathoinhibition was altered in chronic heart failure, sympathoinhibitory sensitivity was assessed using the alpha2-adrenergic agonist clonidine in 7 patients with heart failure and in 10 healthy control subjects. Basal norepinephrine spillover was significantly higher in patients with heart failure (1.3+/-0.3 microg/min) than in control subjects (0.7+/-0.1 microg/min, P=.05). Compared with control subjects, the decrement in norepinephrine spillover to cumulative doses of clonidine (1, 2, and 3 microg/kg administered intravenously) was significantly less in patients with heart failure (P<.05). Blood pressure also tended to decrease less in patients with heart failure (P=.06). The doses of clonidine required to produce a 10% decrease in blood pressure and a 25% decrease in norepinephrine spillover were significantly higher in heart failure (P<.01 and P=.05, respectively). Thus, although clonidine lowers norepinephrine spillover significantly in patients with heart failure, such patients are less sensitive to clonidine than healthy control subjects. This difference in sensitivity suggests that doses of clonidine provide effective sympathoinhibition will need to be selected for studies that will evaluate the potential therapeutic effect of clonidine in heart failure.

Adrenergic alpha-Agonists↗
PubMed1997

Treatment of subclinical fluid retention in patients with symptomatic heart failure: effect on exercise performance.

BACKGROUND: Patients with heart failure frequently have elevated intracardiac diastolic pressures but no clinical evidence of excess fluid retention. We speculated that such pressure elevations may indicate subclinical fluid retention and that removal of this fluid could improve exercise intolerance. METHODS: To test this hypothesis, we studied 10 patients with right atrial pressure > or = 8 mm Hg but without rales, edema, or apparent jugular venous distension. Right-sided heart catheterization was performed, after which patients underwent maximal treadmill cardiopulmonary testing. Patients were then hospitalized and underwent maximal diuresis, after which exercise was repeated. RESULTS: Before diuresis, right atrial pressure averaged 16 +/- 5 mm Hg (+/-standard deviation), pulmonary capillary wedge pressure 30 +/- 6 mm Hg, and peak exercise Vo2 11.2 +/- 2.3 ml/min/ kg. Patients underwent diuresis of 4.5 +/- 2.2 kg over 4 +/- 2 days to a resting right atrial pressure of 6 +/- 4 and wedge pressure of 19 +/- 7 mm Hg. After diuresis, all patients reported overall symptomatic improvement. Maximal exercise duration increased significantly from 9.2 +/- 4.2 to 12.5 +/- 4.7 minutes. At matched peak workloads, significant improvements were also seen in minute ventilation (45 +/- 12 to 35 +/- 9 L/min), lactate levels (42 +/- 16 to 29 +/- 9 mg/dl), and Borg dyspnea scores (15 +/- 3 to 12 +/- 4) (all p < 0.05). CONCLUSIONS: Invasive hemodynamic monitoring allows the identification of excess fluid retention in patients with heart failure when there are no clinical signs of fluid overload. Removal of this subclinical excess fluid improves exercise performance and exertional dyspnea.

Adult↗
PubMed1996

Hemodynamic exercise testing. A valuable tool in the selection of cardiac transplantation candidates.

BACKGROUND: Peak exercise oxygen consumption (Vo2), a noninvasive index of peak exercise cardiac output (CO), is widely used to select candidates for heart transplantation. However, peak exercise Vo2 can be influenced by noncardiac factors such as deconditioning, motivation, or body composition and may yield misleading prognostic information. Direct measurement of the CO response to exercise may avoid this problem and more accurately predict prognosis. METHODS AND RESULTS: Hemodynamic and ventilatory responses to maximal treadmill exercise were measured in 185 ambulatory patients with chronic heart failure who had been referred for cardiac transplantation (mean left ventricular ejection fraction, 22 +/- 7%; mean peak Vo2, 12.9 +/- 3.0 mL. min-1.kg-1). CO response to exercise was normal in 83 patients and reduced in 102. By univariate analysis, patients with normal CO responses had a better 1-year survival rate (95%) than did those with reduced CO responses (72%) (P < .0001). Survival in patients with peak Vo2 of > 14 mL.min-1.kg-1 (88%) was not different from that of patients with peak Vo2 of < or = 14 mL.min-1.kg-1 (79%) (P = NS). However, survival was worse in patients with peak Vo2 of < or = 10 mL.min-1.kg-1 (52%) versus those with peak Vo2 of > 10 mL.min-1.kg-1 (89%) (P < .0001). By Cox regression analysis, exercise CO response was the strongest independent predictor of survival (risk ratio, 4.3), with peak Vo2 dichotomized at 10 mL. min-1.kg-1 (risk ratio, 3.3) as the only other independent predictor. Patients with reduced CO responses and peak Vo2 of < or = 10 mL.min-1.kg-1 had an extremely poor 1-year survival rate (38%). CONCLUSIONS: Both CO response to exercise and peak exercise Vo2 provide valuable independent prognostic information in ambulatory patients with heart failure. These variables should be used in combination to select potential heart transplantation candidates.

Analysis of Variance↗
PubMed1996

Diagnostic value of B-type natriuretic peptide concentrations in patients with acute myocardial infarction.

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide.

Adult↗
PubMed1996

Angiotensin converting enzyme inhibition and sympathetic activity in healthy subjects.

BACKGROUND: One suggested mechanism for the reduction in mortality rates resulting from the use of angiotensin converting enzyme inhibitors in congestive heart failure is the inhibition of the angiotensin II-mediated norepinephrine release. Direct evidence for this mechanism is lacking in humans. SUBJECTS AND METHODS: We examined the effects of captopril, 25 mg three times a day, or matched placebo for 7 days on sympathetic activity during a 10 mEq/day sodium diet in seven healthy male subjects aged 30 +/- 3 (SEM) years. A tritiated norepinephrine radioisotope dilution technique was used to measure sympathetic activity, both at rest and during isometric handgrip exercise. RESULTS: Captopril blunted the increase in mean arterial pressure during isometric handgrip exercise (placebo, from 81 +/- 4 to 112 +/- 2 mm Hg; captopril, from 78 +/- 3 to 101 +/- 2 mm Hg; p < 0.01). However, the increase in systemic norepinephrine spillover during isometric handgrip exercise was not blunted by captopril. Captopril had no effect on resting mean arterial pressure or systemic norepinephrine spillover. CONCLUSIONS: Captopril did not attenuate baseline or static exercise-stimulated sympathetic activity in healthy subjects. These findings would indicate that angiotensin converting enzyme inhibition does not decrease sympathetic activity at rest or during the stimulus of isometric handgrip exercise.

Adult↗