Search PubMed⌕ Search

Biomedical subjects

R Zelis

Publications and source records attributed to R Zelis.

At least 19 recordsLinked to original sources
PubMed1992

Endothelial function in chronic congestive heart failure.

There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. The hypothesis that an impairment of this mechanism is involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF) was tested. Acetylcholine and N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine, were infused in the brachial artery of healthy volunteer subjects (controls) and patients with severe CHF. The radial artery diameter was determined by a high-precision A-mode ultrasound device, using a 10 MHz probe. Forearm blood flow was calculated from vessel diameter and blood flow velocity measured simultaneously by Doppler. The blood flow response to acetylcholine was blunted in patients with CHF compared with that in control subjects. In contrast, the decrease in blood flow induced by L-NMMA was exaggerated in CHF, and the blood flow response to nitroglycerin was preserved. The changes in radial artery diameter induced by acetylcholine and L-NMMA were not significant in control subjects and CHF patients, but dilation of the radial artery by nitroglycerin was significantly reduced in CHF. The results demonstrate an impaired endothelium-dependent dilation of forearm resistance vessels in CHF, suggesting a reduced release of nitric oxide on stimulation. In contrast, the basal release of nitric oxide from endothelium of forearm resistance vessels is preserved or may even be enhanced, and may play an important compensatory role in chronic CHF by antagonizing neurohumoral vasoconstrictor forces in CHF.

Acetylcholine↗
PubMed1992

Regulation of tissue noradrenaline in the rat myocardial infarction model of chronic heart failure.

OBJECTIVE: The aim was to evaluate mechanisms regulating tissue noradrenaline in congestive heart failure. METHODS: Tissue noradrenaline was measured in the conscious post myocardial infarction rat model of congestive heart failure and in sham operated rats (1) under control conditions, (2) 6 h after inhibition of tyrosine hydroxylase by the intraperitoneal administration of alpha-methyl-para-tyrosine (AMPT) (100 mg.kg-1 every 2 h), (3) 6 h after AMPT with desipramine pretreatment (0.3 mg.kg-1), and (4) following exhaustive exercise after AMPT. Tissue noradrenaline was extracted with perchloric acid and measured by high performance liquid chromatography with electrochemical detection. RESULTS: In control animals without drug, tissue noradrenaline concentration was lower in the following tissues in the rats with myocardial infarction compared with the sham operated group: left and right ventricles, spleen, soleus and white gastrocnemius muscles, kidney cortex, and tail artery. After AMPT, tissue noradrenaline concentration in the sham operated group was significantly lower than control; in the myocardial infarction group the fall in noradrenaline was only significant in the kidney, and group differences were no longer present. In the sham operated animals, coadministration of desipramine with AMPT attenuated the fall in tissue noradrenaline caused by AMPT in the heart and spleen. With exercise to exhaustion, cardiac noradrenaline was lower in rats with myocardial infarction than in sham operated rats, but higher in the soleus muscle. CONCLUSIONS: These data suggest that tissue noradrenaline depletion in congestive heart failure is not isolated to the heart, and it occurs despite activation of mechanisms that might be operating to conserve neuronal noradrenaline. One mechanism may be reduced organ blood flow to retard diffusion of noradrenaline into the circulation. If this increases interstitial noradrenaline concentration, it would facilitate prejunctional alpha 2 receptor restraint on noradrenaline release. Metabolic coronary vasodilatation during exercise reverses this process, and makes the heart most susceptible to noradrenaline depletion in congestive heart failure.

Animals↗
PubMed1992

Comparison of norepinephrine and isoproterenol clearance in congestive heart failure.

Congestive heart failure (CHF) is accompanied by increased sympathetic nervous activity. Previous studies have demonstrated that plasma norepinephrine (NE), a marker of sympathetic nervous activity, is elevated in CHF due to increased NE spillover into the circulation and decreased NE clearance. In this study we compared the clearance of NE and isoproterenol (ISO) in eight CHF subjects (plasma NE 601 +/- 133 pg/ml), and in nine controls (plasma NE 285 +/- 53 pg/ml) by using steady-state infusions of tritiated NE ([3H]NE) and tritiated ISO ([3H]ISO). Because ISO is not a substrate of neuronal reuptake but is removed from the circulation in a way that is similar to NE after neuronal reuptake blockade with desipramine, ISO clearance may permit a gross estimation of non-neuronal uptake of circulating NE. The NE clearance was lower in CHF than in the control group (CHF 1.25 +/- 0.13, controls 2.04 +/- 0.22 l.min-1.m-2; P = 0.009). The ISO clearance was reduced similarly in CHF (CHF 0.90 +/- 0.09, controls 1.59 +/- 0.12 l.min-1.m-2; P less than 0.001). Because the ratio of ISO to NE clearance was similar in both groups, our findings suggest that a low cardiac output in CHF decreases the availability of circulating catecholamines to tissue elimination sites.

Aged↗
PubMed1992

Arterial dilatory reserve in congestive heart failure.

AIM: The purpose of this study was to determine whether there are abnormalities in flow-mediated large vessel relaxation in patients with congestive heart failure (CHF). METHODS: The radial arterial diameter and flow responses upon the release of 10 min of forearm arterial occlusion (reactive hyperemia) were measured with ultrasound and Doppler devices. RESULTS: In patients with CHF there was a 26% reduction in peak blood flow (P = 0.09) compared to age-matched controls. However, the increase in arterial diameter that followed the peak blood flow was reduced by 49% in CHF (P < 0.01). CONCLUSIONS: The causes of the abnormal flow-mediated large artery relaxation in CHF are unclear; both structural and endothelial abnormalities may contribute.

Blood Flow Velocity↗
PubMed1991

Time-constant adaptations in heart failure.

The circulatory compensatory mechanisms designed to cope quickly with physiological stress (e.g. sympathetic nervous system and the Frank-Starling mechanism) are less effective when there is chronic pathological stress, such as congestive heart failure (CHF). Other mechanisms come into play that operate over a longer time (e.g. activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and physiological deconditioning). Changes in blood vessels and skeletal muscle metabolism that result from inadequate delivery of oxygenated blood to working muscles belong to the group of mechanisms that develop slowly. When CHF therapy is successful, the abnormalities produced by this latter group of mechanisms will improve, but slowly. The concept that compensatory mechanisms have either short or long time constants for activation and reversal may explain why exercise tolerance improves much later than haemodynamics, which can be reversed acutely with vasodilator therapy.

Adaptation, Physiological↗
PubMed1991

Baroreflex and atrial natriuretic factor concentration correlate with myocardial infarct size and predict early death in rabbits: implications for drug studies.

The severity of myocardial infarction (MI) and its functional consequences are difficult to assess in small animals. We searched for criteria to achieve such an assessment in rabbits 1 week after MI. Thirteen large mongrel rabbits (3-4 kg) were anesthetized with pentobarbitone for ligating a branch of the circumflex coronary artery and 7 rabbits were subject to a sham operation without ligation. All sham-operated rabbits and 12 MI animals survived for 1 week, when blood was obtained for biochemical analyses and the baroreflex was tested. Six animals survived to the third week (survivors) and six died earlier (nonsurvivors). The MI size, measured immediately after death, was 42 +/- 3% of the left ventricular mass in nonsurvivors and 20 +/- 7% in survivors. The plasma atrial natriuretic factor (ANF) concentration was correlated linearly with MI size (r = 0.77) over the whole range of infarct sizes and, like the MI size itself, was associated with the risk of early death (critical limit: 80 pM). Plasma renin activity and catecholamines yielded less prognostic information. The baroreflex control of the heart rate (tested using phenylephrine and nitroprusside) of nonsurvivors was severely impaired and the slopes correlated with MI size (r = 0.90 for phenylephrine and r = 0.67 for nitroprusside). The plasma ANF concentration and the baroreflex both accurately reflected MI size and also correctly classified 11/12 rabbits into survivors and nonsurvivors. An ANF- and baroreflex-based stratification of animals for future studies on therapeutic interventions after MI will reduce the number of animals required by at least 65%, making such studies far more feasible than in the past.

Animals↗
PubMed1991

Norepinephrine clearance is increased during acute hypoxemia in humans.

Acute hypoxemia leads to activation of the sympathetic nervous system (SNS), yet adrenergic vasoconstriction does not occur and venous plasma norepinephrine (NE) fails to rise as expected. To examine whether this dissociation between SNS tone and plasma NE is due to altered metabolism of NE, we measured arterial NE kinetics ([3H]NE infusion technique) and sympathetic nervous outflow to muscle (peroneal microneurography) during 25-30 min of hypoxemia (spontaneous breathing, mean O2 saturation 74%) in six healthy young men. During hypoxemia, muscle sympathetic nervous activity (MSNA) rose significantly from 12.2 +/- 3.3 to 18.6 +/- 3.5 bursts/min, and the total amplitude increased from 123 +/- 36 to 255 +/- 50 mm/min. NE spillover, an index of NE release at the sympathetic nerve terminals, rose from 1.66 +/- 0.30 to 2.33 +/- 0.40 nmol.min-1.m-2 (P = 0.014). However, NE clearance increased also from 0.99 +/- 0.05 to 1.19 +/- 0.11 l.min-1.m-2 (P = 0.014), and arterial NE rose from 281 +/- 50 to 339 +/- 64 pg/ml (P = 0.023). Hypoxemia resulted in a significant rise in forearm blood flow and a decrease in forearm vascular resistance. The fact that skin blood flow and vascular resistance did not change implies that forearm vasodilation was localized to skeletal muscle. Our results suggest that during acute hypoxemia in humans the SNS is activated but the rise in plasma NE is attenuated because NE clearance is increased.

Adult↗
PubMed1991

Norepinephrine response to exercise of rats with a chronic myocardial infarction.

Plasma and tissue norepinephrine (NE) concentrations were determined at rest and after 45 min of swimming in rats with a surgically induced myocardial infarction (MI) and in rats having undergone a sham operation (SHAM). The MI rats had moderate-sized infarcts and demonstrated decreases in maximal O2 uptake (VO2max) that are consistent with the contention that the animals possessed a significant amount of left ventricular (LV) dysfunction and chronic heart failure (CHF). Plasma NE concentrations measured at rest were not significantly different between the SHAM and MI groups of rats, although a strong trend was found for the plasma NE concentrations to be elevated in the MI group. The plasma NE responses to 45 min of swimming at the same absolute submaximal workload were similar in the two groups of rats in light of the fact that the MI group of rats exercised at a greater percentage of their VO2max when compared with their SHAM counterparts. Exercise produced significant reductions in the NE concentrations of the diaphragm, vastus lateralis, red portion of the gastrocnemius, plantaris, and vastus intermedius muscles for both the SHAM and MI groups of rats. In addition, the NE concentrations measured in both the soleus and red portion of the gastrocnemius muscle were significantly greater in the MI rats when compared with their SHAM counterparts for both rest and exercise conditions. The results from the present study support the hypothesis that the sympathetic response to exercise is either unchanged or attenuated in MI rats that have a significant amount of LV dysfunction and CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Pericardial-fluid complement: normal values.

Reports of low pericardial-fluid complement levels in systemic lupus erythematosus and rheumatoid arthritis have been difficult to interpret, as few data are available to describe complement concentrations in patients without pericardial disease. The authors therefore determined normal values under standardized conditions of collection, storage, and assay. The normal ranges for pericardial-fluid C3, C4, and total hemolytic complement were 35-127 mg/dl, 6.3-23 mg/dl, and 1.9-9.1 CH50 units, respectively. Storage at -20 C resulted in a 50% reduction in values. Hence, storage at -70 C is recommended. As the level of pericardial-fluid total hemolytic complement is normally low, caution is needed in interpreting its apparent reduction in various immunologic diseases.

Complement C3↗
PubMed1979

Cardiovascular response to acute aquatic and treadmill exercise in the untrained rat.

The cardiovascular effects of acute aquatic (AE) and treadmill (TE) exercise were determined in untrained adult male Sprague-Dawley rats. Animals were exercised to exhaustion or for a maximum of 5 min with either exercise mode and data collected during the last minute of exercise were compared to preexercise rest data. Heart rate and cardiac output increased only with TE; arterial pressure remained stable during both protocols. Regional blood flow was determined by the radioactive microsphere technique. Coronary flow increased only with TE. Skeletal muscle flow, determined in six muscle groups, increased more with TE (97 to 587%) than with AE (-44 to 260%) (flow in the quadriceps group decreased during AE). Flow to the skin and splanchnic regions decreased; cerebral flow increased in both groups. Blood gas data suggest lactic acidosis and hyperventilation only with TE. These data indicate that 1) the cardiovascular effects of acute, exhaustive bouts of AE and TE in the rat are not comparable, and 2) the hemodynamic changes occurring with exhaustive TE in rat, as in man, involve a shunting of blood to the regions of demand and away from the nonessential circulations.

Abdomen↗
PubMed1979

Cage size and exercise affects infarct size in rat after coronary artery cauterization.

Left coronary occlusion in the rat was performed by cornary artery cauterization. A small amount of myocardial damage at the site of occlusion was noted, and myocardial infarction occurred in the distal distribution of the obstructed coronary. The effects of cage size and level of physical activity on estimated infarct size (as measured by creatine kinase depletion) 48 h after occlusion were determined. Isolation in small cages and moderate treadmill exercise resulted in an approximate doubling of the amount of infarction when compared to grouping of rats in large cages. Mild exercise did not increase infarct size. Total urinary catecholamines in normal rats placed in small cages for 48 h were elevated when compared to unconfined rats in larger cages. Cornary artery occlusion by cauterization is an easily performed technique. Cage size and level of activity (and their effects on sympathoadrenal function) are important independent determinations of infarct extent after coronary occlusion in the rat.

Animals↗
PubMed1979

Pericardial effusions in sarcoidosis.

A case of sarcoid pericarditis is presented. The associated pericardial effusion was a transudate with a low complement level. Investigating the prevalence of pericardial effusions in sarcoid by echocardiography, we found small effusions in 19 percent of 48 consecutive patients with sarcoid. Additionally, ten previously reported cases of symptomatic parietal pericardial sarcoid are reviewed.

Female↗