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Biomedical subjects

R Zelis

Publications and source records attributed to R Zelis.

At least 55 records · Page 3Linked to original sources
PubMed1989

Characteristics of flow-mediated brachial artery vasodilation in human subjects.

In an effort to determine whether arterial conductance vessels dilate in response to increased blood flow stimuli, brachial artery area (cm2) and diameter (cm) were derived by simultaneous measurement of forearm blood flow (ml/min.100 ml) and brachial artery blood flow velocity (cm/sec) following the release of arterial occlusion. Measurements were made at rest and at the time of maximal flow after the release of graded periods of forearm arterial occlusion (20 seconds to 10 minutes). These studies showed a graded large vessel dilation following occlusions of up to 1 minute (baseline diameter, 0.33 +/- 0.01; after 1 minute occlusion, 0.45 +/- 0.02 cm; p less than 0.05) after which time diameter plateaued (after 10 minutes of occlusion, 0.48 +/- 0.02 cm). In addition, the time course of diameter and flow changes after 3 minutes of arterial occlusion were examined. Flow was maximal at 5 seconds but diameter was maximal at 15-30 seconds after release. Furthermore, the half time for the return of diameter to baseline was longer than that for blood flow. We also measured the diameter after forearm heating (42 degrees C) and noted a substantial increase in diameter (before heating, 0.32 +/- 0.01; after heating, 0.39 +/- 0.02 cm; p less than 0.05). Finally, we applied pressure to the venous side of arteriovenous fistulae in five hemodialysis patients. This maneuver was associated with large reductions in forearm blood flow (baseline flow, 63.3 +/- 10.6; venous compression flow, 36.0 +/- 4.4 ml/min.100 ml; p less than 0.05) and a decrease in brachial artery size (baseline diameter, 0.63 +/- 0.07; venous compression diameter, 0.58 +/- 0.06 cm; p less than 0.05). We conclude that 1) the human brachial artery size changes in response to changes in blood flow, and 2) the maximal dilation occurs after maximal flow is noted. Although alternate explanations are possible for each of our observations, our results are most consistent with a flow-mediated, localized vasodilating process.

Adult↗
PubMed1989

Recent insights into the calcium channels.

Calcium channels play a central role in the regulation of intracellular calcium (Ca2+) concentration, and their function is subject to control by voltage-regulated, receptor-regulated, or voltage- and receptor-regulated mechanisms. Three types of calcium channels have been described. These are the T (transient or "fast"), the N (neuronal), and the L (long lasting or "slow") channels. The L channels appear to be heterogeneous and have different properties in different tissues. Intracellular calcium-ion concentration can be increased by three types of receptor mechanisms. In the heart, L channels can be phosphorylated by a cyclic AMP-dependent protein kinase after beta 1-adrenergic receptor stimulation. In vascular smooth muscle, the postjunctional alpha 2-adrenergic receptor is coupled to a Ca2+ channel by a G protein; receptor stimulation facilitates calcium influx. This channel might be a form of L channel. A third receptor mechanism, especially active in vascular smooth muscle, is typified by the alpha 1-adrenergic receptor that, when stimulated, will activate phospholipase C. This leads to an increase in intracellular inositol trisphosphate (IP3), which is an intracellular messenger that can induce calcium release from the sarcoplasmic reticulum. Thus, release of norepinephrine from sympathetic nerves in the cardiovascular system stimulates the heart and vessels to contract by increasing Ca2+; however, the mechanism by which this occurs is different, depending on whether the noradrenergic agonist interacts with beta 1-, alpha 2-, or alpha 1-adrenergic receptors.

Calcium↗
PubMed1989

The peripheral circulation.

In severe congestive heart failure, exercise capacity is reduced. This is not directly due to reduced ventricular function. We present evidence in this article that peripheral vascular abnormalities are important in determining exercise capacity. We believe the vascular abnormalities noted in heart failure may be related to both sodium retention and deconditioning. Moreover, we propose that in severe heart failure this vascular response may be protective.

Blood Circulation↗
PubMed1988

Regional blood flow in congestive heart failure: concept of compensatory mechanisms with short and long time constants.

With physiologic stress to the cardiovascular system, some circulatory compensatory mechanisms are designed to restore homeostasis quickly (e.g., sympathetic nervous system activation and the Frank-Starling mechanism). These compensatory mechanisms are not nearly as effective when there is a chronic pathologic stress such as congestive heart failure (CHF). In this circumstance, other mechanisms that operate with longer time constants come into play (e.g., activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and deconditioning). The most successful chronic drug therapies of CHF are those that are designed to reverse the latter group of compensatory mechanisms, a process that is slow. It takes especially long to reverse those CHF-induced changes in blood vessels and skeletal muscle metabolism that are activated to cope with inadequate delivery of oxygenated blood to working muscles. The concept that compensatory mechanisms have either short or long time constants for activation, effectiveness and reversal may help explain why the improvement in exercise tolerance with effective heart failure therapy lags behind hemodynamic improvement.

Adaptation, Physiological↗
PubMed1988

Vascular sympathetic nerve function in congestive heart failure.

To determine if intrinsic abnormalities of sympathetic nerve function might contribute to enhanced vascular tone in congestive heart failure, chronic myocardial infarction (infarct) was produced in rats by coronary artery ligation 9 to 10 months previously for comparison with animals subjected to sham operation (sham). The excised pulmonary artery, preincubated with 3H-norepinephrine (NE) was superfused, and stimulated electrically at 2, 4, 8 and 16 Hz. The nonnormalized data at each frequency for electrically evoked 3H overflow in excess of basal outflow was similar in sham and infarct vessels (difference not significant); however, the shape of the frequency-response curves was different. The 3H overflow/pulse from sham vessels was constant between 2 and 16 Hz; however, for the infarct vessels there was a significant reduction (p less than 0.05) at the highest frequency (16 Hz). Because of an 18.4% lower peak 3H overflow at 16 Hz (difference not significant), the infarct frequency-response curve shifted significantly (4 and 8 Hz, p less than 0.025 and p less than 0.01) to the left when data were expressed as a percent of peak percent 3H overflow, suggesting an increased sensitivity of the system. These data suggest that an intrinsic vascular sympathetic nerve abnormality is not a major cause of the increased plasma NE in congestive heart failure; increased nerve activity or decreased clearance of NE may be more important.

Animals↗
PubMed1988

Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation.

The effects of changes in central cardiovascular function on peripheral vasodilation were investigated. Strain gauge plethysmography was used to measure the maximal blood flow response following release of forearm arterial occlusion and the peak reactive hyperemic blood flow response (ml/min.100 ml) before and twice after orthotopic heart transplantation in 10 subjects with severe congestive heart failure. The 2 posttransplantation studies were done before hospital discharge (mean 18 days after transplantation) and again after discharge (mean 114 days after transplantation). Transplantation led to a significant but delayed increase in maximal vasodilation (reactive hyperemic blood flow: pretransplant 21 +/- 3; predischarge 25 +/- 2; postdischarge 43 +/- 5) and a concurrent significant reduction in minimal forearm resistance. Although the improvement in peripheral vasodilator function may be linked to improvement in cardiac function, this linkage is not direct, nor is it immediate. If the normalization of maximal metabolic blood flow is related to resumption of normal physical activity postdischarge, then much of the basic abnormality in vasodilator capacity in congestive heart failure may be related to physical deconditioning.

Adult↗
PubMed1988

Abnormalities in systemic norepinephrine kinetics in human congestive heart failure.

A high venous plasma norepinephrine (NE) level is a predictor of poor prognosis in congestive heart failure (CHF). To evaluate the mechanisms responsible for the high plasma NE in CHF, NE kinetics were studied in 19 patients with CHF and 18 normal subjects during a 90-min steady-state intravenous infusion of tracer [3H]NE of high specific activity. Venous plasma NE between 70 and 90 min of infusion was significantly higher in the CHF patients (CHF, 634, and normal, 247 pg/ml; P less than 0.001). The following equations were used: NE clearance = [3H]NE infusion rate (dpm/min)/plasma [3H]NE (dpm/l), and NE spillover = [3H]NE infusion rate (dpm/min)/[3H]NE specific activity (dpm/nmol). In CHF, a decreased clearance and an increased spillover contributed nearly equally to the high plasma NE (NE clearance: CHF, 0.99; normal, 1.48 l.min-1.m-2; P less than 0.001; NE spillover: CHF, 3.60; normal, 2.08 nmol.min-1.m-2; P less than 0.001). These data document that both NE clearance and NE spillover are abnormal in CHF, and they raise the new possibility that the factors responsible for the reduced NE clearance could be related to the factors linking a high plasma NE with early mortality.

Adult↗
PubMed1988

Sympathetic tone affects human limb vascular resistance during a maximal metabolic stimulus.

To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilation, peak forearm blood flow (ml.min-1.100 ml-1) was measured plethysmographically in 18 volunteers after the release of 10 min of arterial occlusion (the peak reactive hyperemic blood flow response, RHBF) both before and after a stimulus to induce heightened sympathetic tone. The stimulus was the application of ice to the forehead for 90 s just before and during RHBF measurements. Mean arterial cuff blood pressure (MAP; mmHg) was calculated, and corresponding resistance (R; mmHg.ml-1.min.100 ml) was derived from blood pressure divided by RHBF. During ice application, blood pressure rose (pre 92 vs. post 115 ml/mmHg; P less than 0.05), peak RHBF was unchanged (pre 38.8 vs. post 36.4 ml.min-1.100 ml-1; not significant), but R during the maximal metabolic stimulus rose (pre 2.5 vs. post 3.2 mmHg.ml-1.min.100 ml; P less than 0.05). To examine the effects of heightened sympathetic tone on conduit vessels, simultaneous measurements of maximal metabolic blood flow (RHBF) and brachial artery Doppler velocity (V, cm/s) were conducted (n = 5) with and without ice applied to the forehead. Velocity rose by 70% as flow remained constant. Thus brachial artery area (area = flow/velocity) and diameter decreased substantially (20% decrease in diameter). The increase in R noted with ice was due to an alpha-mediated response, since the increase in R was blocked by oral prazosin (n = 6) and was unaffected by maneuvers to alter myogenic tone (n = 5). We conclude that maximal metabolic vasodilation can be counteracted to some extent by the effects of heightened sympathetic tone. Moreover, some of the interaction between these two opposing influences takes place at the arterial level.

Adult↗
PubMed1988

Glycogen concentrations and endurance capacity of rats with chronic heart failure.

The endurance capacities of rats with myocardial infarctions (MI) and of rats having undergone sham operations (SHAM) were tested during a submaximal exercise regimen that consisted of swimming to exhaustion. During this test, a decrement in the endurance capacity of the MI rat was demonstrated as the SHAM rat swam 25% longer than the MI rat (65 +/- 4 vs. 52 +/- 4 min). Glycogen concentrations were measured in the liver and the white gastrocnemius, plantaris, and soleus muscles of SHAM and MI rats that were randomly divided into four subgroups, which consisted of resting control, swim to exhaustion, swim to exhaustion + 24 h recovery, and swim to exhaustion + 24 h recovery + a second swim to exhaustion. The results demonstrated that the glycogen concentrations found in the liver, white gastrocnemius, plantaris, and soleus muscles of the SHAM and MI rats belonging to the resting control groups were similar. After swimming to exhaustion the glycogen concentrations in these tissues were significantly reduced compared with those found in the resting control groups of rats, and after 24 h of recovery the glycogen concentrations in these tissues were again similar to those found in the resting control groups of rats. Since the magnitude of the glycogen depletion in the liver and the white gastrocnemius, plantaris, and soleus muscles was similar in the SHAM and MI rats and because the SHAM rats consistently swam for longer periods of time in each of the experimental groups, it would be logical to assume that the rates of glycogen utilization for the various tissues may have been greater in the MI rat during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1988

The peripheral distribution of cardiac output in heart failure.

There are two sets of compensatory mechanisms activated when the heart fails: cardiac mechanisms that try to maintain a normal cardiac output and peripheral circulatory mechanisms that try to maintain blood pressure to perfuse the heart and the brain. The latter are most important during the stress of exercise. During exercise, two patterns of responses are noted: 1) blood vessels supplying active skeletal muscle fail to dilate normally, and 2) blood vessels supplying other visceral organs constrict excessively. The inability of skeletal muscle resistance vessels to dilate normally to a metabolic stimulus is related to sodium and water accumulation in the vessels and to a deconditioning response. These effects probably are at the small artery level. This results in an abnormal metabolic response to exercise. Vasoconstriction in visceral organs is related to neurogenic (sympathetic adrenergic) and humoral (angiotensin, norepinephrine, and vasopressin) mechanisms. The peripheral sympathetic nervous system is the primary determinant of the high plasma norepinephrine levels seen in heart failure. The role of the sympathetic nervous system is to provide for acute vasoconstriction and the renin-angiotensin system is to provide for chronic visceral vasoconstriction. These circulatory mechanisms operate most effectively over different time frames that are either short (sympathetic nervous system), intermediate (renin-angiotensin system), or long (deconditioning, vascular stiffness). When treatment is successful these systems return to normal over similar time frames.

Cardiac Output↗
PubMed1987

Enhanced metabolic vasodilation secondary to diuretic therapy in decompensated congestive heart failure secondary to coronary artery disease.

Since sodium and water retention have been implicated as major factors limiting maximal metabolic vasodilation in congestive heart failure (CHF), the effect of rigorous diuresis on maximal vasodilatory capacity was studied systematically in 9 subjects hospitalized with decompensated CHF. Peak reactive hyperemic blood flow, measured by strain-gauge plethysmography, was used as an index of maximal vasodilatory capacity. After 24 hours of diuresis and a 2.2-kg weight loss, maximal flow increased from 19.9 to 26.1 ml/min X 100 ml (p less than 0.05). Despite a further 1.4-kg weight loss between 24 and 48 hours, maximal blood flow increased no more (26.1 to 25.8 ml/min X 100 ml). Since blood pressure did not change significantly, minimal forearm resistance and maximal conductance showed similar improvements. It is unlikely that vasoconstrictor hormone changes could account for this effect since a marked decrease in plasma norepinephrine occurred in only 2 of 8 subjects and plasma renin activity decreased in only 1 subject. As a group there was no significant change in norepinephrine level, which remained substantially above normal (1,525 to 1,148 pg/ml), or in plasma renin activity (12.3 to 18.9 ng/ml/hour). Because the improvement in vasodilator capacity reached a plateau by 24 hours despite continued diuresis, and because peak reactive hyperemic blood flow was still 32% below normal, it is suggested that a second mechanism besides sodium and water retention is responsible for a significant portion of the impaired peripheral vasodilation in CHF.

Aged↗
PubMed1987

Cardiac receptors affect regional flow during acute infarction in conscious rats.

This study was conducted to determine if cardiac receptors have a role in the control of the regional circulations during small acute myocardial infarction in the conscious rat. Cardiocirculatory dynamics and cardiac output distribution (microspheres) were measured in conscious rats 24 and 48 h after surgery for left main coronary artery ligation or the sham procedure. Data from animals without treatment were compared to data from animals treated to induce chemical cardiac denervation (85% phenol applied to the supraventricular surface of the heart and the root of the great vessels). The results suggest that neurogenic vasopressor stimuli originating from the heart contribute to changes in peripheral resistance secondary to small, acute, experimentally induced myocardial infarction in the conscious rat.

Animals↗
PubMed1987

Halothane selectively attenuates alpha 2-adrenoceptor mediated vasoconstriction, in vivo and in vitro.

The mechanism by which halothane interferes with catecholamine-induced vasoconstriction was examined, utilizing specific agonists at postjunctional alpha 1- and alpha 2-adrenoceptors on vascular smooth muscle. Stimulation of either adrenoceptor subtype normally produces vasoconstriction. Two experimental models of drug-induced vasoconstriction were used: in vivo blood pressure response in pithed rats, and in vitro isometric tension development in canine saphenous vein rings. These models were then utilized to examine the anti-vasoconstriction properties of halothane. In vivo, halothane (1 MAC) produced a significant depression in the vascular response to azepexole (an alpha 2-adrenoceptor agonist), but halothane did not alter vasoconstriction by phenylephrine (an alpha 1-adrenoceptor agonist). Halothane caused a 24% reduction of maximal response (P less than 0.0001) to azepexole in pithed rats, and a 3.2-fold rightward shift of the log dose-response curve (P less than 0.0001). Similarly, in vitro, halothane significantly attenuated alpha 2- but not alpha 1-adrenoceptor responsiveness. Halothane (4%) depressed maximal vein contraction to azepexole by 26% (P less than 0.0001), and shifted the log concentration-response curve 2.4-fold to the right (P less than 0.0001). The observed selective interference with alpha 2-mediated vasoconstriction by halothane is unlikely to represent drug antagonism at the receptor level. Our observations may suggest, indirectly, that halothane interferes with Ca+2 entry into vascular smooth muscle. The phenomenon of selective anti-vasoconstriction at alpha 2-adrenoceptors by halothane may explain why alpha 1-adrenergic agonists often appear to retain their vasopressor activity during halothane anesthesia. The mechanism of halothane-induced vasodilation thus includes attenuation of alpha 2- but not alpha 1-adrenergic vasoconstriction; this further demonstrates the multifactorial nature of halothane-induced vasodilation.

Adrenergic alpha-Agonists↗
PubMed1987

A 30-day forearm work protocol increases maximal forearm blood flow.

To evaluate the local circulatory changes that accompany chronic localized work, we studied the effects of a 4-wk handgrip work protocol on maximal forearm work-related blood flow (ml X min-1 X 100 ml-1) in the nondominant forearms of six normal subjects. The reactive hyperemic blood flow response (RHBF) was also evaluated pre- and posttraining in both forearms of each subject to determine whether maximal vasodilatory capacity would be enhanced. In addition, maximal O2 consumption (VO2max) was measured. We found that chronic handgrip work led to an increase in work-related blood flow (before, 22.4; after, 32.1; P less than 0.05); a drop in work-related minimal resistance (R) (before, 6.4; after, 4.1; P less than 0.05). RHBF rose in the chronically exercised extremity by 30% (before, 33.5; after, 43.7; P less than 0.05) as minimal R fell (before, 3.2; after, 2.2; P less than 0.05). RHBF and R in the unstimulated dominant forearm remained unchanged (blood flow: before, 33.5; after, 31.0; NS; R before, 3.2; after, 3.2; NS). VO2max (ml X kg-1 X min-1) did not change (before, 35.7; after, 34.0). These findings show that localized skeletal muscle forearm work is associated with a localized increase in vasodilation (RHBF). Thus the vascular system appears to be an independent integral partner in the training process.

Adult↗
PubMed1987

Acute regional vascular effects of intravenous captopril in a rat model of myocardial infarction and failure.

The effects of i.v. captopril on regional blood flow (radioactive microspheres, 15 +/- 5 micron), hemodynamics and maximal oxygen consumption were evaluated in conscious rats with congestive heart failure due to large myocardial infarction (n = 9, infarct size 39.5 +/- 2% of left ventricle) and compared to data obtained from rats subjected to sham surgical procedures (n = 8). In both groups data were obtained at rest and during submaximal treadmill exercise during alternate infusion of captopril and saline. In the congestive heart failure group captopril reduced systemic vascular resistance, mean arterial pressure and left ventricular systolic pressure (P less than .05 each). Blood flow to the renal, gastrointestinal and coronary circulations was reduced in the heart failure group treated with saline vehicle. Flow to the renal and gastrointestinal beds of heart failure animals was enhanced to values similar to those observed in sham animals during captopril treatment. Left ventricular coronary flow was also increased significantly by captopril in both sham and heart failure animals. The most prominent effects of captopril occurred in the renal circulation of the heart failure group in which blood flow increased by 55%. Blood flow to skeletal muscle and skin was unchanged by captopril both in sham and heart failure animals at rest and during exercise. Maximal oxygen consumption was not affected by captopril treatment. Thus, captopril induced a differential pattern of vasodilation with the greatest effect in the renal bed and a less intensive effect in the gastrointestinal and coronary beds. The unchanged flow to skeletal muscle may explain the failure of captopril to improve exercise capacity after short-term administration.

Animals↗
PubMed1987

Norepinephrine kinetics during orthostatic stress in congestive heart failure.

To evaluate the determinants of the plasma norepinephrine (NE) response to orthostatic stress, NE kinetics were measured during steady-state infusion of [3H]NE of high-specific activity for two consecutive 90-minute periods; the first was supine, and the second was during 60 degrees head-up tilt. In 6 normal subjects, plasma NE increased from 242 to 570 pg/ml, and NE clearance decreased from 1.43 to 1.00 l/min X M2. In 6 patients with congestive heart failure, there was no significant change in plasma NE during orthostatic stress. This has been interpreted previously to indicate that there was little activation of the baroreflex arc. In fact, NE clearance decreased from 1.08 to 0.79 l/min X M2; however, there was a decrease in NE spillover from 4.04 to 2.88 nmol/min X M2. A reduction of organ blood flow with tilt could be responsible for the reduced NE clearance by both groups, but the mechanism for the reduction in NE spillover with tilt in congestive heart failure is unclear.

Adult↗