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Biomedical subjects

A M Scher

Publications and source records attributed to A M Scher.

At least 19 recordsLinked to original sources
PubMed2000

Absence of atherosclerosis in human intramyocardial coronary arteries: a neglected phenomenon.

Atherosclerosis is absent in human intramyocardial (buried) coronary arteries but atherosclerosis may be severe in superficial segments of the same vessels. The development of atherosclerosis has three phases: a plasma phase, a transfer phase and an intramural phase. The transfer phase involves the transfer of low-density lipoproteins and macrophages from the plasma into the arterial wall. Efficiency of transfer is low where plasma flow near the wall is rapid. Eddy currents caused by arterial branches produce low flow near the arterial wall. Plasma recalculates and moves slowly in these eddy currents and thus prolongs contact of LDL and macrophages with the wall, increasing the occurrence of atherosclerosis. Absence of atherosclerosis in buried vessels appears due to the effects of myocardial contraction on the transfer phase. Contraction of the myocardium surrounding buried arterial vessel compresses these vessels and moves the plasma, LDL and macrophages away from the wall. This will decrease transfer into the wall and act to prevent the development of atherosclerosis. Similar but less striking effects occur where bridges of myocardium cross arterial vessels. Possible applications to human disease are discussed briefly.

Arteriosclerosis↗
PubMed1995

Studies of the electrical activity of the ventricles and the origin of the QRS complex.

Historical events in the development of cardiac electrophysiology are described briefly. Observations before 1900 showed that electrical changes accompanied activity of muscle and nerve. Other studies showed that electrical activity of the heart produced voltage changes on the human torso. In 1903 Einthoven developed the string galvanometer which made measurement of electrocardiographic potentials much easier, more accurate and more common. The bases of understanding of arrhythmias were established by Lewis in the early 1900's. Soon thereafter Wilson devised practical and theoretical approaches to the human electrocardiogram which led to many further developments. Events before 1950 established the existence and mechanism of electrical activity in excitable cells. Studies of the origin of QRS began in about 1950, with studies of depolarization of the canine ventricle. Studies of the human ventricle followed. In the 70's it appeared possible to solve the electrocardiographic forward problem, prediction of electrocardiographic potentials from a knowledge of intracardiac events. That solution appeared possible because of new approaches to the associated physical and computational problems. Attempts to solve the forward problem at that time assumed that the cardiac generator (the boundary between resting and depolarized cells) was a uniform double layer generator. (The strength of the generator is constant everywhere along the boundary). Meanwhile physiologists and anatomists had worked out the mechanism of communication between cardiac cells. The cells are longer than they are wide, and each cell can depolarize contiguous cells. The connections between cells are predominantly at the ends of the cell and the longitudinal depolarization of a cardiac mass travels three times as fast as transverse depolarization. The generator is not uniform but is strongest parallel to the long axes of the cells. Many or most of those working in the field did not recognize the importance of the connections between cardiac cells in not only the pathway of excitation, but also the potentials produced as the cells depolarized. A number of experiments indicated that the uniform double layer assumption led to both qualitative and quantitative errors in prediction of fields generated by depolarization of cardiac muscle. These are reviewed. There are now alternatives to the uniform model which recognize the non-uniformity of the cardiac generators, particularly the axial model. The forward problem is unsolved but it appears possible that these newer models will make a solution possible.

Animals↗
PubMed1994

Validity of the uniform double layer in the solution of the ECG forward problem.

This study attempted to solve the electrocardiographic forward problem (ie, to predict body surface potential fields from pathways of depolarization). A perfused heart was suspended in a cylinder and surrounded with fluid of the conductivity of the lung. Computation of potential fields included conductivity and boundary effects and assumed a uniform double-layer source. Three instants (early, late, and mid QRS) during normal depolarization and one instant during a stimulated beat were studied. There was good qualitative agreement between recorded and predicted fields early and late in the QRS and during the stimulated beat, but there were quantitative differences. The cardiac generator was far stronger late in the QRS. In mid QRS, the agreement between recorded and predicted fields was very poor. To resolve questions raised in this study, potentials around a small volume of stimulated tissue were recorded and predicted. Recorded potentials were compared with potentials calculated (1) on the assumption that the cardiac generator is a uniform double layer and (2) on the assumption that all current flows along the long axes of the cardiac fibers. The recorded potentials compared most favorably with the second of these. These studies led to the opinion that the uniform double-layer assumption is inadequate for prediction of body surface potential fields from depolarization pathways. Other studies of the forward and inverse problem that assume a uniform double-layer source are considered to be successful and therefore disagree with this study's conclusion. It appears that the question needs further experimental study.

Animals↗
PubMed1993

Dependence of cardiac filling pressure on cardiac output during rest and dynamic exercise in dogs.

At rest, central venous pressure (CVP) falls when cardiac output (CO) rises. This can be attributed to flow-dependent redistribution of blood volume from central to peripheral blood vessels. In contrast, CVP rises during dynamic exercise despite a rise in CO. Therefore peripheral circulatory changes during exercise must counteract the factors that lower CVP when CO rises during rest. Our objectives were to determine the importance of blood flow, the muscle pump, and reflexes on changes in ventricular filling pressure during dynamic exercise. In seven dogs with a surgically produced atrioventricular (AV) block, normal relationships between CO and CVP were established by AV-linked pacing (normal heart rates) during rest and exercise. Cardiac output was altered during rest and treadmill exercise (4 miles/h at 0, 10, or 20% grade) by changing ventricular pacing rate to establish curves relating delta CVP to delta CO. These curves were displaced rightward (higher CO) and upward (higher CVP) by exercise because of the muscle pump. Changing CO by pacing during rest and exercise revealed a constant slope for delta CVP/delta CO of -2.7 mmHg.l-1.min-1. Blockade of reflex vasoconstriction and venoconstriction with hexamethonium at rest and during mild exercise (to isolate effects of the muscle pump) did not alter these slopes or the displacement of the curves by exercise, although CVP was 4.3 mmHg lower at a given CO after blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Is rapid rise in vascular conductance at onset of dynamic exercise due to muscle pump?

We tested the hypothesis that rapid increases in muscle blood flow and vascular conductance (C) at onset of dynamic exercise are caused by the muscle pump. We measured arterial (AP) and central venous pressure (CVP) in nine awake dogs, eight with atrioventricular block, pacemakers, and ascending aortic flow probes for control of cardiac output (CO) (2 also had terminal aortic flow probes). One dog had only an iliac artery probe. At exercise onset (0 and 10% grade, 4 mph) C and CVP rose to early plateaus, and AP reached a nadir, all in 2-5 s. At 20% grade and 4 mph, C increased continuously after its initial sudden rise. Timing and magnitude of initial change in conductance (delta C) were independent of CO, AP, work rate (change in grade at constant speed), or autonomic function (blocked by hexamethonium). Speed of initial delta C and its independence from work rate and blood flow ruled out metabolic vasodilation as its cause; insensitivity to AP and autonomic blockade ruled out myogenic relaxation and sympathetic vasodilation as causes of sudden delta C. Sensitivity to contraction frequency (not work per se) implicates the muscle pump. When reflexes were blocked, a large secondary rise in C, presumably caused by metabolic vasodilation, began after 10 s of mild exercise. When reflexes were intact in mild exercise, C was lowered below its initial plateau by sympathetic vasoconstriction, which partially raised AP from its nadir toward its preexercise level. Our conclusion is that dynamic exercise has a large rapid effect on C that is not explained by known neural, metabolic, myogenic, or hydrostatic influences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Recovery of arterial pressure control after partial baroreceptor denervation in awake rabbits.

We examined recovery of control of heart rate (HR) and total peripheral resistance (TPR) by arterial baroreceptors after bilateral carotid sinus and aortic denervation or unilateral carotid sinus and aortic denervation in conscious rabbits. In one group of animals, HR responses to changes in mean arterial pressure (MAP) after injection of nitroglycerin or phenylephrine were measured in control studies and at 2, 5, 10, and 15 days after partial baroreceptor denervation. All denervation procedures increased MAP and HR at 2 and 5 days after denervation. Reflex sensitivity decreased to 57-67% of control on day 2 after denervation. HR responses recovered by day 10 after bilateral aortic or carotid sinus denervation; however, recovery following unilateral denervation was less complete. In a second group of animals, studied after implantation of aortic flowmeters, TPR changes following reduction in cardiac output by inferior vena caval occlusion were 49% of control responses on day 2 after denervation and returned close to control level on day 5. Controls of HR and TPR recovered substantially and were not significantly different from control 10 days after partial denervation. Recovery apparently occurred through the remaining arterial baroreceptors, possibly due to central reorganization of reflex pathways.

Animals↗
PubMed1991

Baroreflex-induced vasoconstriction in active skeletal muscle of conscious dogs.

We investigated the magnitude of baroreflex-mediated vasoconstriction in the hindlimbs of six conscious dogs at rest and during four levels of treadmill exercise ranging in intensity from mild (2 mph, 0% grade) to heavy (6 mph, 10% grade). Dogs were instrumented with vascular occluders on both common carotid arteries, an electromagnetic flow probe and vascular occluder on the terminal aorta, and a catheter in a branch of the femoral artery; aortic baroreceptors were intact. The responses to a 2-min carotid occlusion were observed at rest and after 3-5 min of exercise at each work rate. The increases in mean arterial pressure during carotid occlusion were similar at rest and at each level of exercise (26 +/- 4 to 35 +/- 3 mmHg; no significant difference). At rest, carotid occlusion caused only a small but significant decrease in terminal aortic vascular conductance (TAC) (-0.89 +/- 0.21 ml.min-1.mmHg-1, P less than 0.05). During mild exercise, baseline terminal aortic blood flow (TAQ) and TAC increased, and the reduction in TAC during carotid occlusion exceeded that observed at rest (-1.85 +/- 0.42 ml.min-1.mmHg-1, P less than 0.05). As exercise intensity increased, the magnitude of the reduction in TAC during carotid occlusion increased linearly with the baseline TAQ. At the highest work rate, approximately 59% of the increase in mean arterial pressure during carotid occlusion was due to the large decrease in TAC (-6.35 +/- 0.50 ml.min-1.mmHg-1). We conclude that the vasoconstriction of active skeletal muscle during the pressor response to bilateral carotid occlusion increased with exercise intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Time course of recovery of arterial pressure control after carotid denervation.

We examined the recovery of arterial pressure control after carotid sinus baroreceptor denervation in conscious dogs with atrioventricular block. Strength of control was assessed by measuring changes in peripheral resistance and atrial rate after step changes in cardiac output. One day after carotid denervation, arterial pressure was significantly elevated (+13.7 mmHg), and the strength of control of peripheral resistance and atrial rate were significantly decreased to 46.1 and 36.6% of control, respectively. Over 4-7 days, the strength of control of both peripheral resistance and atrial rate and the mean arterial pressure returned to the levels observed before denervation. After carotid denervation, the pressor response to bilateral carotid artery occlusion was abolished, and thus the recovery of arterial pressure control was not caused by inadequate carotid denervation or regeneration of carotid baroreceptors. The recovery of arterial pressure control after carotid denervation is probably caused by an increase in the reflex responses to pressure changes at the aortic baroreceptors and may reflect plasticity within the baroreflex pathway.

Animals↗
PubMed1990

Pulsatile pressure can prevent rapid baroreflex resetting.

In a previous study [Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H673-H678, 1988] we demonstrated that baroreflex responses decay (reset) to increased static sinus pressures, but with increased pulsatile pressure, responses are maintained. To determine more conclusively whether pulsatile pressure prevents rapid baroreflex resetting in this study we examined resetting as shifts of the baroreflex (sinus pressure-arterial pressure) curve. In seven anesthesized rabbits the left sinus was vascularly isolated and conditioned for 5 min to static or pulsatile pressures of 60, 100, or 140 mmHg mean pressure, 0 or 35-40 mmHg pulse pressure. The baroreflex curve was then determined by stepwise changing sinus pressure from 40 to 160 mmHg in 20-mmHg increments. Threshold, midpoint, and saturation sinus pressures shifted 25-39% with static conditioning pressures but did not shift significantly with pulsatile pressures. Also, the baroreflex responses to step increases in static sinus pressure decayed, as resetting occurred, but did not decay with pulsatile sinus pressure increases. Thus the baroreflex rapidly resets with static pressures, but there is minimal, if any, resetting with pulsatile pressures.

Animals↗
PubMed1990

Baroreflex attenuates pressor response to graded muscle ischemia in exercising dogs.

Graded reductions in hindlimb perfusion in dogs exercising at 2 miles/h (0% grade) elicited reflex pressor responses by what is referred to as the "muscle chemoreflex." To determine the extent to which arterial baroreceptor reflexes oppose the muscle chemoreflex, we elicited pressor responses to muscle ischemia before and after chronic surgical denervation of the arterial baroreceptors. The muscle chemoreflex showed a threshold beyond which systemic pressure rose approximately 3 mmHg for each 1-mmHg decrease in hindlimb perfusion pressure when the arterial baroreceptors were intact. Arterial baroreceptor denervation approximately doubled the pressor responses, i.e., systemic pressure rose by approximately 6 mmHg for each 1-mmHg fall in hindlimb perfusion pressure, without alteration in threshold. We conclude that during mild dynamic exercise, the arterial baroreflexes oppose the pressor response to graded reductions in hindlimb perfusion, reducing it by approximately 50%. When unopposed by the arterial baroreflexes the muscle chemoreflex exhibits a gain (ratio of change in systemic pressure to change in hindlimb perfusion pressure) of approximately -6; thus this reflex can correct by 85% the decrease in muscle perfusion pressure caused by partial vascular occlusion.

Animals↗
PubMed1989

Effects of steps in cardiac output and arterial pressure in awake dogs with AV block.

In awake dogs with atrioventricular block, we examined the responses in total peripheral resistance and atrial rate to square-wave changes in mean arterial pressure or cardiac output. We compared the responses 2-3 min after a step change with the responses 19-20 min after a step. With resetting of arterial pressure control, the compensatory responses should decrease as the baroreceptors reset to the prevailing pressure. With step changes in mean arterial pressure or cardiac output, the responses in both peripheral resistance and atrial rate increased from minutes 2-3 to minutes 19-20. The responses in peripheral resistance also increased in animals studied after bilateral vagal block. All of the above changes were significant in the majority of cases. In another experiment, the animals were "conditioned" by 20 min at imposed high or low pressure. When control was returned to the animal after conditioning at high pressure, arterial pressure was not significantly different (P greater than 0.05) from the initial control levels. When control was returned after conditioning at low pressure, arterial pressure was significantly greater (P less than 0.05) than during the initial control period. These results indicate an absence of resetting of the entire arterial pressure control system.

Animals↗
PubMed1989

Cardiovascular control by arterial and cardiopulmonary baroreceptors in awake dogs with atrioventricular block.

We studied reflex responses to pressure changes at arterial and cardiopulmonary baroreceptors in five awake dogs with atrioventricular block before and after baroreceptor denervation. We changed ventricular pacing rate and blood volume to vary cardiac output and arterial (MAP) and central venous pressure (CVP). We determined peripheral resistance (TPR) and atrial rate (HRA) as responses. In the intact animal, regression analysis showed an average relationship across dogs of TPR = 169-0.69 MAP-1.952 CVP + error. Correlation (r) between observed and predicted TPR was 0.83. For HRA, regression indicated HRA = 291.66-2.319 MAP + 8.144 CVP + error (r = 0.899). TPR and MAP are percent of control at 90 beats/min; CVP is in mmHg; HRA, in beats/min. Although its coefficient is smaller, MAP explains approximately 69% of the variation in TPR. After arterial baroreceptor denervation, effects of MAP on TPR were insignificant and the coefficient for CVP increased. Subsequent vagal block eliminated all reflex responses. Effects from the two receptor sites sum linearly. They act cooperatively with changes in blood volume, but oppose one another with cardiac output changes.

Animals↗
PubMed1988

Pulsatile sinus pressure changes evoke sustained baroreflex responses in awake dogs.

A modified Stephenson-Donald preparation was used to control pressure in an isolated carotid sinus in conscious dogs with all other arterial baroreceptors denervated. Sinus pressure was changed from preisolation control levels to either an elevated static or an elevated pulsatile pressure for 5 min. These sinus pressure changes evoked similar initial decreases in arterial pressure. The elevated static sinus pressure (150 or 175 mmHg) caused an initial depressor response of -32.7 +/- 5.5 mmHg, which then decayed rapidly. Five minutes after the change in sinus pressure, the depressor response was abolished, as arterial pressure returned to control pressure. This decay of the response would be expected if resetting occurred. In contrast, when the sinus was exposed to elevated pulsatile pressures (125 or 150 mmHg mean, 50 mmHg pulse pressure) depressor responses were sustained throughout the sinus pressure change (-23.2 +/- 5.3 mmHg initial, -29.0 +/- 4.8 mmHg at 5 min; P greater than 0.4). These results demonstrate that while the reflex responses rapidly reset to elevated static sinus pressures, elevated pulsatile pressures elicit sustained reflex responses.

Animals↗
PubMed1988

Arterial pressure control after chronic carotid sinus denervation.

This study examines the control of arterial blood pressure in conscious, instrumented dogs with atrioventricular block before and greater than or equal to 9 days after carotid sinus baroreceptor denervation. Strength of reflex control of blood pressure was quantitated by measuring the changes in peripheral resistance and atrial rate after square wave changes in cardiac output. Surprisingly, nine or more days after carotid denervation, the strength of baroreflex control of peripheral resistance and atrial rate were not different (P greater than 0.05) from the values before denervation. This was not due to a change in the base-line levels of arterial pressure, atrial rate, cardiac output, or peripheral resistance. Bilateral vagal block after carotid denervation removed reflex effects from remaining baroreceptors and virtually eliminated changes in peripheral resistance in response to changes in arterial pressure. Therefore, the compensatory responses observed after carotid denervation were mediated by the remaining baroreceptors. Thus, after chronic carotid sinus denervation, there is no decrease in the strength of baroreflex control of peripheral resistance or heart rate.

Animals↗
PubMed1987

Does inadequate oxygen delivery trigger pressor response to muscle hypoperfusion during exercise?

In dogs running on a treadmill at 2 or 4 mph or 4 mph plus 10% incline, graded reductions in hindlimb perfusion reflexly elicited pressor responses. To test the idea that systemic arterial pressure (SAP) is raised by accumulation in muscle of a nerve-activating "pressor substance" release when O2 delivery becomes inadequate, arterial O2 content (CaO2) was reduced 29.1% by carbon monoxide (CO) inhalation before repeating exercise at 2 mph. We reasoned that the pressor substance, or related substances, should appear in femoral venous blood and be correlated to SAP. [K+] behaved inappropriately as a signal to raise SAP, i.e., when flow was reduced, SAP rose markedly with little or no change in [K+]. SAP was well correlated to pH and [lactate] over the three work loads. Compared with the same work load with normal CaO2, CO shifted the relation between SAP and terminal aortic flow rightward 0.30 l/min (34.5%) and the relation between SAP and PO2 leftward 7.7 mmHg. CO did not affect the relation of SAP to terminal aortic O2 delivery, hindlimb O2 uptake index, pH, or [lactate]. Thus pressor responses are apparently generated when O2 delivery falls below some critical level causing accumulation of a pressor substance the release of which is linked to a metabolic event that precipitates lactate accumulation.

Animals↗
PubMed1986

The nature of the exercise stimulus.

The two foremost hypotheses concerning the nature of the exercise stimulus are: Central Command. Centrally generated signals activate in parallel cardiovascular and skeletal muscle motor systems; Muscle Chemoreflex. Chemosensitive nerves within the skeletal muscle detect local accumulations of metabolites which reflect disparities between muscle blood flow and metabolism. The focus is mainly on the second hypothesis. The neurophysiological basis for this reflex is well established. Accumulations of metabolites within ischemic muscle reflexly trigger pressor responses that are abolished by blockade of sensory nerves from muscle. However, such blockade does not abolish circulatory responses to static or mild dynamic exercise. To assess the importance of muscle chemoreflexes, stepwise partial occlusions of the terminal aorta were made in exercising dogs. The rise in arterial pressure was related to reductions in terminal aortic flow and arterial pressure below the occluder. In mild exercise sensitivity of the reflex was low until flow was substantially reduced to a threshold. In heavier exercise sensitivity of the reflex was high (no threshold) and could provide a tonically active exercise stimulus. The nature of the metabolic signal is unknown. The pressor response was most closely related to femoral venous lactate concentration and unrelated to femoral venous K+ or PO2.

Animals↗
PubMed1985

The control of atrial contraction by ventriculo-atrial pacing in the dog with AV block.

Atrial contraction in dogs with atrioventricular (AV) block was controlled by multiple atrial stimuli delivered during ventricular diastole. Acute hemodynamic changes were assessed. At a ventricular rate of 60 bpm, the spontaneous atrial rate averaged 83, and atrial cannon waves were frequent. When the atria were given two stimuli at an interval of 500 ms during ventricular diastole, the cannon waves were eliminated completely, and a fall in mean central venous pressure and a rise in systemic blood pressure were found. At a pacing rate of 90 bpm, similar changes in the cannon waves, mean central venous pressure, and systemic blood pressure were found when two atrial stimuli followed ventricular stimulation. Ventriculo-atrial multiple pacing may be useful in both clinical and experimental AV block.

Animals↗