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Biomedical subjects

E D Frohlich

Publications and source records attributed to E D Frohlich.

At least 145 records · Page 8Linked to original sources
PubMed1991

Is reversal of left ventricular hypertrophy in hypertension beneficial?

The left ventricle increases its mass and wall thickness in hypertension as a result of the progressive increase in hemodynamic overload offered by increasing arterial blood pressure and total peripheral resistance. However, evidence is increasing that nonhemodynamic factors may also be important in the development of left ventricular hypertrophy (LVH). This LVH resulting from hypertensive disease conveys an independent risk of premature cardiovascular morbidity and mortality. The specific mechanisms accounting for this increased risk are not known with assurance, although several mechanisms are under active study; they include more prominently ventricular dysrhythmias and myocardial ischemia. It is possible to diminish the increased left ventricular mass with pharmacological agents, although currently it is not known whether this reversal also diminishes the risk associated with LVH. Therefore, at the present time the best means for preventing the risk of LVH is to prevent its development in the first place, and this seems to be preventable through control of arterial blood pressure at the earliest stages of hypertension. Risk may also be diminished in patients with existing LVH who are receiving digitalis or diuretics or who have chronic fluid- and electrolyte-disturbing diseases. Under these circumstances, the careful use and selection of antihypertensive therapy and control of electrolyte balance no doubt will prevent unnecessary morbidity and mortality.

Adaptation, Physiological↗
PubMed1991

Cardiac and aortic effects of angiotensin converting enzyme inhibitors.

The effects of six angiotensin converting enzyme inhibitors (captopril, CGS-16617, cilazapril, enalapril, utibapril, and quinapril) on cardiovascular structure, systemic hemodynamics, left ventricular end-diastolic pressure, left ventricular pumping ability, and aortic distensibility were assessed in male normotensive Wistar-Kyoto and spontaneously hypertensive rats 16-19 weeks of age. Rats (10 in each group) were treated for 3 weeks with drugs or control diluents administered daily by gavage. The agents, in general, had similar hemodynamic effects, although these effects on cardiac mass were variable; some agents reduced left ventricular mass and some produced no change. These effects occurred in hypertrophied as well as nonhypertrophied chambers. Furthermore, changes in left ventricular pumping ability were not necessarily related to the ability of these agents to change left ventricular mass; this dissociation in performance was neither related to change in structure nor to changes in aortic distensibility. Thus, even within a same class of antihypertensive agents (i.e., angiotensin converting enzyme inhibitors), similarly induced hemodynamic alterations were associated with inconsistent changes in left ventricular pumping ability or aortic distensibility regardless of whether the structure was hypertrophied before therapy. These dissociated responses in cardiovascular structure and function may be related to pharmacodynamic or pharmacokinetic differences; alternatively, they also may be related to these differences in action on local myocytic renin-angiotensin systems or in intramyocytic biological responses.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

The heart in hypertension: a 1991 overview.

Left ventricular hypertrophy may be considered the result of an interaction of a myriad of factors, including hemodynamic overload; age, race, and gender of the patient; the stage of hypertensive disease; and other coexisting diseases. This concept is similar to the multifactorial "mosaic of hypertension" described by Page. In addition, the increased left ventricular mass in hypertension may reflect the disposition of collagen tissue and the participation of a myriad of myocytic growth factors, as well as drug therapy. The resultant left ventricular hypertrophy confers increased cardiovascular risk that is independent of the height of arterial pressure. The mechanisms that account for that risk are not yet well understood but include reduced adaptive myocardial reserve, enhanced predisposition to cardiac dysrhythmias and cardiac failure, accelerated atherosclerosis, and reduced (absolute and relative) coronary flow and flow reserve, as well as other possibilities. At present much work is directed to the demonstration of pharmacological reversal of hypertrophy. However, even with that demonstration of reduced cardiac mass with therapy, it will be necessary to show improved risk at the reduced mass that is independent of the reduction of arterial pressure as well as of the effects of those drugs on cardiac rhythm, flow, metabolism, and direct effects on the cardiac myocyte itself.

Animals↗
PubMed1991

The heart in hypertension.

Knowledge concerning the functional and structural changes of the heart in hypertension has increased remarkably over the past three decades. These changes may not at all be the same as with other diseases associated with increased afterload since the etiology, pathophysiological mechanisms, and other associated diseases are very different. Hemodynamic alterations associated with hypertension have a major role in the adaptive cardiac changes; but recent knowledge indicates that they are not exclusive. Nonhemodynamic factors are also very important; they not only include the now-accepted demographic considerations of age, race, gender and associated diseases but also consider newly discovered growth factors as well as prior and present therapy. The heart that provides a physiological adaptation to the increasing overload produced by disease in order to stem the tide from eventual cardiac failure also confers an independent risk of premature cardiovascular morbidity and mortality. It is too early to infer that reversal of the LVH reverses this risk. But, even if this does occur, mechanisms other than only LVH reversal must be considered. Therefore, at this time, the implications and consequences of reversed LVH has yet to be demonstrated.

Animals↗
PubMed1990

Dissociation of changes in cardiovascular mass and performance with angiotensin-converting enzyme inhibitors in Wistar-Kyoto and spontaneously hypertensive rats.

The effects of angiotensin-converting enzyme inhibitors on cardiovascular mass and function were measured in three groups of 22 week old male Wistar-Kyoto normotensive and spontaneously hypertensive rats treated with CGS-16617, cilazapril or quinapril. Left ventricular performance was assessed by electromagnetic flow meter during rapid whole blood infusion before and after arterial pressure and increased abruptly with aortic snare; aortic distensibility also was assessed in vitro. The systemic hemodynamic effects of these three agents were similar, yet their structural effects varied. Although left ventricular and aortic masses diminished and right ventricular mass remained unchanged (with all three agents) in the spontaneously hypertensive rats, CGS-11617 and cilazapril also reduced left ventricular mass in the normotensive Wistar-Kyoto rats without changing aortic mass. All three agents improved aortic distensibility whether or not mass was decreased. Left ventricular structural changes were associated with variable changes in pumping ability. These data show that reduced mass associated with angiotensin-converting enzyme inhibitor treatment was not consistent in ventricles and aorta, that a dissociation exists between structural and functional changes and that reduction of cardiac mass alone does not relate to changes in chamber mass or in function. Thus, biologic and pharmacodynamic differences exist among angiotensin-converting enzyme inhibitors as well as between classes of antihypertensive agents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Hemodynamic effects of calcitonin gene-related peptide in spontaneously hypertensive rats.

Systemic and regional hemodynamic effects of intravenously injected calcitonin gene-related peptide (CGRP), 220 and 650 pmol, were compared in nine Wistar-Kyoto (WKY) and nine spontaneously hypertensive rats (SHR). CGRP (higher dose) reduced mean arterial pressure (from 135 +/- 2 to 83 +/- 2 and from 179 +/- 4 to 116 +/- 3 mmHg; P less than 0.01, each, in WKY and SHR, respectively) through a fall (-38 +/- 4 and -40 +/- 3%; P less than 0.01) in total peripheral resistance associated with an unchanged cardiac output and an increased heart rate. The decreases in arterial pressure and total peripheral resistance were not different between these two strains. Of particular significance were the highly selective reductions in organ vascular resistances, being greatest in the cutaneous (-78 +/- 3 and -67 +/- 4%) and gastric (-80 +/- 3 and -84 +/- 2%) circulations in WKY and SHR, respectively (P less than 0.01). Reduction in coronary, cerebral, and hepatic vascular resistances, although significant (P less than 0.05, at least), were only moderately reduced compared with the two former circulations. These effects were similar in WKY and SHR and demonstrate that CGRP is a highly selective and potent natural vasodilating peptide that has the most striking effects in skin and stomach, suggesting possible modulator functions in regulating certain regional hemodynamics.

Animals↗
PubMed1990

Hemodynamic differences between black patients and white patients with essential hypertension. State of the art lecture.

Physiological studies reported from our laboratory over the past several years have been reviewed and support epidemiological reports indicating that hypertensive cardiac and vascular disease runs a more severe course in the black patient. Although comparison of systemic hemodynamics failed to demonstrate that, for any level of arterial pressure, the magnitude of total peripheral resistance (which is the hemodynamic hallmark of hypertensive disease) differed between black patients and white patients, there are more subtle differences that were ascertained. Thus, although intravascular (plasma) volume contracts as arterial pressure and total peripheral resistance increase in both racial groups, this relation may differ quantitatively. At least in some black patients (43%), intravascular volume may be more expanded; in these patients, this relation is less closely correlated with the renopressor system (i.e., plasma renin activity). Moreover, these studies indicated that, at any level of arterial pressure, cardiac (left ventricular mass and posterior wall thickness) and renal hemodynamic involvement is more severe in the black patient. These findings point to important differences that operate in black patients and white patients with essential hypertension. With further study, these findings may be translated into more specific antihypertensive therapeutic implications for patients of both racial groups with essential hypertension.

Black People↗
PubMed1990

Sympathectomy fails to reveal prominent vasodilation by atrial natriuretic factor.

Reflex activation of the sympathetic nervous system may conceal direct vasodilatory actions of atrial natriuretic factor and mediate atrial natriuretic factor-induced increases in total peripheral resistance. We determined whether peripheral sympathectomy would enhance the hypotensive actions of atrial natriuretic factor and convert the increase in total peripheral resistance to peripheral vasodilation. Sympathectomized rats studied included 1) conscious rats treated with 6-hydroxydopamine alone (partially sympathectomized) and 2) conscious anephric rats sympathectomized with adrenal demedullation and 6-hydroxydopamine (totally sympathectomized), with vascular tone returned to levels of sham-operated (control) rats with norepinephrine infusion. Sympathectomized rats and appropriate control rats received rat atrial natriuretic factor infusion (0.5 microgram/kg/min) or vehicle for 1 hour. Atrial natriuretic factor infusion lowered mean arterial pressure and increased hematocrit in control rats but not in partially sympathectomized rats. Changes in cardiac output and total peripheral resistance were not significantly different between control and partially sympathectomized rats. In totally sympathectomized rats, atrial natriuretic factor lowered mean arterial pressure more than in control rats; changes in cardiac output were nearly identical in both groups, but there were no changes in total peripheral resistance from control levels in the totally sympathectomized group. Changes in plasma volume and central venous pressure were similar in totally sympathectomized rats and control rats. These findings suggest that reflex sympathetic activity largely mediated atrial natriuretic factor-induced increases in total peripheral resistance but failed to reveal an atrial natriuretic factor-mediated sustained vasodilation in the absence of sympathetic reflexes. Furthermore, atrial natriuretic factor decreased cardiac output, central venous pressure, and plasma volume independent of the sympathetic nervous system.

Adrenal Medulla↗
PubMed1990

One-year longitudinal study of a no-smoking policy in a medical institution.

Smoking and health are increasingly understood to be incompatible. To evaluate, prospectively and retrospectively, the attitudes of employees, staff physicians, and patients of a medical institution, a questionnaire was administered before and after implementation of a no-smoking policy. Of many questions, select ones reviewed here focused on the following concerns: (1) how tobacco smoke affects employees and patients, (2) employee acceptance of a no-smoking policy before and after its implementation, and (3) the consequences of the policy on employee smokers. Open-ended questions about smoking were constructed by a committee comprised of clinicians, investigators, and administrators. The questionnaire was given to 2,000 randomly selected patients and the institution's entire staff of 4,200 employees and 225 staff physicians. Data were obtained on three occasions: six months before, six months after, and one year after the implementation of the no-smoking policy. The majority of patients, employees, and physicians indicated that the smoke of others bothered them and ranked the following as most offensive: smell, eye irritation, provocation of sinus problems, coughing, and headache. Approximately 80 percent of employees and patients favored the policy before its inception; and employees increasingly favored it through the year after its implementation with a favorable attitude increasing by nearly 10 percentage points. One year after implementation, 80 percent of patients were in favor of the policy. In the final survey, 74 percent of respondents indicated the policy had helped them. One year after policy implementation, employee smoking was reduced significantly from 22 to 14 percent; and of those employees who continued to smoke, 81 percent smoked less than eight cigarettes per day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Left ventricular hypertrophy: an independent factor of risk.

Left ventricular hypertrophy imposes a definite risk of increased cardiovascular morbidity and mortality. This increased risk is independent of other risks (including that of hypertension). The precise mechanism or mechanisms that account for this risk are not known, although several possible factors have been identified. A variety of antihypertensive agents have been shown to decrease the mass of hypertrophied left ventricle, although some may also diminish the mass of the normal ventricle. No study to date has demonstrated improvement in the risk from LVH with so-called reversal of LVH with pharmacologic agents.

Cardiomegaly↗
PubMed1990

Stress and hypertension.

The relationships between stress and hypertension have been evaluated extensively. Acutely, stress has been shown to increase blood pressure by increasing cardiac output and the heart rate without affecting total peripheral resistance. Acute stress has been found to increase levels of catecholamines, cortisol, vasopressin, endorphins and aldosterone, which may in part explain the increase in blood pressure. However, a primary role for the activation of the sympathetic nervous system has recently been suggested in several studies. Studies in the rat are beginning to determine specific central nervous system pathways which transform stressful stimuli into signals triggering a cardiovascular response without direct cortical participation. Furthermore, acute stress reduces renal sodium excretion, which contributes to an increase in blood pressure. Several studies suggest that prolonged stress may predispose people and animals to prolonged hypertension and certain populations are at risk for the development of stress-induced hypertension. It is likely that prolonged stress-induced hypertension is the result of neurohormonal trophic factors which cause vascular hypertrophy or atherosclerosis. Because stress can affect measurement of blood pressure due to the phenomenon of 'white-coat hypertension', ambulatory blood pressure monitoring is emerging as an important feature in the evaluation of patients with hypertension. Finally, relaxation techniques are being used increasingly in the treatment of patients with hypertension.

Animals↗
PubMed1989

Clinical and physiologic significance of local tissue renin-angiotensin systems.

Increasing and compelling evidence continues to amass that favors the existence of local tissue renin-angiotensin systems. All renin-angiotensin system components have been demonstrated in kidney, brain, arteries, adrenals, and other organs. Favoring its clinical importance are direct demonstration of its components in tissues; dissociation between hemodynamic and structural effects of renin-angiotensin system inhibition; evidence for local modulating roles with other humoral, autocrine/paracrine, and growth factors; and the effects of renin-angiotensin system inhibitors in patients who are anephric or have low plasma renin activity. Evidence will be presented demonstrating the hemodynamic/structural dissociation of pharmacologic agents that reduce cardiac mass in spontaneously hypertensive rats with left ventricular hypertrophy. Although centrally active adrenolytic agents, angiotensin-converting enzyme inhibitors, and calcium antagonists all reduce cardiac mass, their structural and cardiac functional effects differ greatly. Even within the angiotensin-converting enzyme inhibitor group their effects vary: improving, impairing, or not changing the Frank-Starling relationships. It is postulated that there is great variability of cardiac intramyocytic penetration of the pharmacologic agents and of their local intracellular effects on mitogenesis. The implications for cardiac function and therapy are vast.

Animals↗
PubMed1989

Ventricular performance in spontaneously hypertensive rats (SHR) with reduced cardiac mass.

This study was designed to investigate the effect of 4 weeks of captopril treatment on cardiac mass and performance in spontaneously hypertensive rats (SHR). Left (LV) and right (RV) ventricular mass of SHR and normotensive WKY rats was reduced (p less than 0.01). Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) in the treated SHR and WKY were reduced; cardiac (CI) and stroke (SI) indices remained unaltered in SHR but increased in WKY. Ventricular performance (i.e., cardiac pumping ability), assessed by rapid blood infusion, did not differ between untreated SHR and WKY, and between treated and untreated WKY rats. However, the ventricular performance curves for the treated SHR shifted down and to the right from the untreated SHR (p less than 0.01). Moreover, when MAP of treated SHR (with regressed LV mass) was elevated to their pretreatment levels, cardiac performance curves shifted further rightward and downward. In contrast, the performance curves of treated WKY whose MAP was also elevated to the level of untreated WKY were no different from those of untreated WKY. These data demonstrate that captopril treatment (at doses used in this study) reduced MAP in SHR through decreased TPRI while decreasing biventricular mass. Furthermore, the cardiac-pumping ability of previously hypertrophied SHR hearts was reduced, suggesting that certain antihypertensive agents that diminish cardiac mass could produce impaired cardiac function when called upon to increase performance (e.g., when MAP is suddenly raised).

Animals↗
PubMed1989

Life's quality: a major consideration in health care delivery--especially with hypertensive diseases.

The purposes of this paper are severalfold: a) to avoid a cloak of product inference; b) to focus attention on the need to keep patients on long-term (antihypertensive) therapy with as few side effects as possible; c) to acknowledge certain arguments relating to side effects, some of which have engendered concern among respected authorities in the field; d) to underscore the validity of current health care preoccupations relating to cost containment and cost effectiveness; and e) to question the wisdom of certain governments around the world in suggesting that low-cost antihypertensive medications that are already available should be used in preference to newer and more costly drugs no matter what the theoretical or clinical justification.

Antihypertensive Agents↗