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Biomedical subjects

E D Frohlich

Publications and source records attributed to E D Frohlich.

At least 109 records · Page 6Linked to original sources
PubMed1994

Preserved cardiac performance with reduced left ventricular mass in conscious exercising spontaneously hypertensive rats.

OBJECTIVES: To investigate whether cardiovascular performance can be modified beneficially with left ventricular hypertrophy reversal and whether the associated sudden afterload increases may adversely affect overall cardiac performance. METHODS: We studied cardiovascular performance with thermodilution techniques at rest and during maximal treadmill exercise after 3 weeks' treatment with the angiotensin converting enzyme inhibitor quinapril (3 mg/kg per day) in 19 male spontaneously hypertensive rats (SHR) aged 20 weeks. RESULTS: Left ventricular mass was reduced significantly, without impairment of exercise performance, demonstrating that left ventricular hypertrophy reversal benefited or at least did not hinder cardiovascular adaptation to physiologic exercise in the SHR. Moreover, decreasing the afterload did not further improve the performance after the reversal of left ventricular hypertrophy.

Animals↗
PubMed1993

Hypertension in the elderly: age- and disease-related complications and therapeutic implications.

Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an "aging process" on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of "muted" hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.

Aged↗
PubMed1993

Different ATP effects on natriuretic peptide receptor subtypes in LLC-PK1 and NIH-3T3 cells.

We have observed different ATP interactions in two guanylate cyclase (GC)-coupled natriuretic peptide (NP) receptor subtypes, designated NPR-A and NPR-B. The NPR-A is selectively expressed by LLC-PK1 epithelial cells and the NPR-B by NIH-3T3 fibroblast cells. In LLC-PK1 membranes, ATP-Mg2+ potentiated ANP-stimulated GC activity (ANP-s-GC). In contrast, in NIH-3T3 membranes, ATP-Mg2+ inhibited ANP-s-GC but enhanced CNP-stimulated GC activity (CNP-s GC). ATP in the presence of Mn2+ inhibited LLC-PK1 and NIH-3T3 membrane ANP-s-GC and CNP-s-GC. These are the first data suggesting that the ATP-Mg2+ produces different effects between membrane NPR-A and -B subtypes. We have also demonstrated that GC of NPR-B is sensitive to methylene blue.

3T3 Cells↗
PubMed1993

Biochemical components and myocardial performance after reversal of left ventricular hypertrophy in spontaneously hypertensive rats.

OBJECTIVE: This study was undertaken to determine the biochemical and left ventricular functional changes associated with reversal of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). DESIGN: Male SHR and normotensive Wistar-Kyoto (WKY) rats, aged 19 weeks, were treated for 3 weeks with vehicle, amlodipine (10 mg/kg), benazepril (10 mg/kg) or the combination of both agents (4 mg/kg amlodipine and 4 mg/kg benazepril). Left ventricular function was assessed while blood was infused rapidly, at pharmacologically reduced and pretreatment mean arterial pressure (MAP). RESULTS: All treatments reduced MAP and left ventricular mass significantly in SHR. Myocardial protein, RNA and myocardial collagen content were reduced proportionately in all treatment groups in SHR, but not in WKY rats. DNA remained unchanged in all groups. Increased right ventricular mass was produced by amlodipine in both SHR and WKY rats (SHR +11.3%; WKY +9.8%), but this was prevented by cotreatment with benazepril. Right ventricular protein and collagen increased significantly with amlodipine in SHR but not WKY rats, and there were no changes in right ventricular RNA and DNA contents in either strain. Amlodipine improved, benazepril impaired and the combination of both agents maintained left ventricular pumping ability when pressure was increased abruptly to pretreatment levels in WKY rats. In contrast, when afterload was increased abruptly in SHR to pretreatment levels, neither amlodipine nor benazepril affected pumping ability, although it was enhanced by the combination. CONCLUSIONS: These data demonstrate that amlodipine, benazepril and their combination reduced left ventricular mass in SHR. This reversal of LVH was associated with proportional reductions in mycotic protein, RNA and collagen, but not DNA. Therefore, it seems unlikely that LVH reversal with these agents was associated with increased fibrous tissue or impaired left ventricular performance. Finally, addition of the angiotensin converting enzyme inhibitor prevents the increase in right ventricular mass produced by the calcium antagonist.

Amlodipine↗
PubMed1993

Relationship between dietary sodium intake, hemodynamics, and cardiac mass in SHR and WKY rats.

To study the effects of sodium intake on circulatory homeostasis and cardiac structure, changes in cardiac mass, systemic hemodynamics, and organ blood flows were determined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats after 10 wk of controlled dietary intake of low sodium (0.01%), standard sodium (0.44%), and high sodium (2 levels: 1.44 and 4%). Systemic and regional hemodynamics were measured in conscious rats using the radioactive microsphere reference method. The various dietary sodium manipulations did not cause any changes in systemic and regional hemodynamics in the WKY rats. In contrast, the high-sodium diets increased arterial pressure and total peripheral resistance progressively in the SHR rats while decreasing cardiac index, heart rate, and organ blood flows to heart, kidneys, and splanchnic area. The higher sodium intake (4%) increased total and left ventricular mass index in both the SHR and the WKY rats even though hemodynamics of the WKY rats remained unchanged. These data indicate that the high-sodium diet, in addition to producing general vasoconstriction and exacerbation of hypertension, increased cardiac mass further in SHR rats; it also increased cardiac mass in the WKY rats independent of arterial pressure changes, suggesting that high sodium intake may be an independent pathogenetic factor for the development of cardiac hypertrophy.

Aging↗
PubMed1993

Glomerular hemodynamics in aortocaval fistula rats: role of renin-angiotensin system.

To investigate intrarenal hemodynamics of aortocaval, arteriovenous (AV)-fistula rats and the effect of angiotensin-converting-enzyme (ACE) inhibition, micropuncture studies were obtained before and after administration of quinapril (100 micrograms.kg-1 x min-1), an ACE inhibitor. AV fistula produced by needle multipuncture was characterized by elevated left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and increased left and right ventricular weights. Effective renal plasma flow was lower in AV-fistula rats, and single-nephron glomerular filtration rate (SNGFR) and plasma flow (SNPF) were reduced. Single-nephron filtration faction (SNFF), stop-flow pressure, and glomerular pressure (PG) were increased. The lower SNGFR and SNPF and higher PG and SNFF were associated with higher afferent and efferent arteriolar resistances (RA and RE) and lower ultrafiltration coefficient (Kf). LVEDP correlated positively with with RA, RE, and SNFF (all P < 0.01) and negatively with SNGFR (P < 0.05) and SNPF (P < 0.01). After quinapril these variables returned toward normal. Thus this method for producing AV fistula was useful in creating mild and moderately severe cardiac failure (CHF). Intrarenal hemodynamics of AV were characterized by increased PG and SNFF and lower SNGFR and SNPF associated with increased RA and RE and lower Kf and SNPF correlated and with severity of CHF. Restoration of intrarenal hemodynamics to or toward normal with quinapril supports an important pathophysiological role of renin-angiotensin system in this CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Calcium antagonists as cardioprotective agents.

The potential role that calcium antagonists play toward enhancing cardioprotection is discussed, while recognizing that they are much more heterogeneous than other classes of antihypertensive or antianginal agents. Similarities and differences between the mechanisms of action and clinical effects of individual drugs are discussed. Among these is the ability of some of them to reduce left ventricular hypertrophy rapidly while simultaneously and uniquely increasing right ventricular wall thickness. Although the clinical importance of this as a potential cardioprotective effect is undetermined, the renal protective effect of some calcium antagonists is discussed in detail.

Calcium Channel Blockers↗
PubMed1992

Hemodynamic and metabolic effects of intravenous clentiazem in hypertensive patients.

To determine the hemodynamic and certain metabolic effects of clentiazem, a diltiazem congener, 10 untreated essential hypertensive patients were given the calcium antagonist in 3 successive doses totaling 1.0 mg/kg intravenously. Mean arterial pressure and total peripheral resistance progressively declined from 121 +/- 3 mm Hg and 47 +/- 2 U (mean) to 110 +/- 3 mm Hg and 33 +/- 1 U, respectively (p less than 0.05); heart rate remained unchanged. Cardiac output increased as a result of augmented cardiopulmonary volume (p less than 0.05) produced by peripheral venoconstriction and norepinephrine release (from 258 +/- 41 to 319 +/- 42 pg/ml; p less than 0.01). Surprisingly, there was an immediate reduction in plasma aldosterone (10.4 +/- 1.2 to 6.5 +/- 1.0 ng/dl; p less than 0.01), serum potassium (4.3 +/- 0.1 to 3.6 +/- 0.1 mEq/dl; p less than 0.001) and calcium (9.5 +/- 0.1 to 8.8 +/- 0.1 mg/dl; p less than 0.001) concentrations, whereas epinephrine increased (21.2 +/- 3.3 to 45.8 +/- 5.9 pg/ml; p less than 0.002). Previous studies with diltiazem, conducted similarly, did not show these changes. Therefore, clentiazem reduced mean arterial pressure through a decrease in total peripheral resistance, and released epinephrine was associated with intracellular potassium influx (urinary potassium did not change). The inhibited aldosterone release was not compensated by altered renal blood flow, glomerular filtration or increased plasma renin activity. These findings underscore the concept that calcium antagonists are a remarkably heterogeneous antihypertensive group.

Aged↗
PubMed1992

Academic pursuits in the multispecialty clinic.

Although usually viewed as institutions that provide excellence in health care delivery, the larger multispecialty clinics must also be considered as major national academic resources. The professional staffs at multispecialty clinics not only have provided important contributions scientifically but have also made a major clinical impact on overall health care delivery. This issue is dedicated to the founding physicians of Alton Ochsner Medical Foundation and, in particular, to Alton Ochsner who provided the guiding inspiration in a continuing quest to achieve these academic goals.

Academic Medical Centers↗
PubMed1992

Current issues in hypertension. Old questions with new answers and new questions.

Hypertension is a systemic vascular disease that makes its mark upon the "target organs"--heart, brain, and kidneys--through the hemodynamic hallmark of the disease, a progressively increasing vascular resistance to the forward flow of blood. The effect of pressure overload upon the heart is one of concentric hypertrophy of the left ventricle that is, in turn, associated with an independent risk of morbidity and mortality. Reduction of arterial pressure reverses the risk associated with the elevated arterial pressure and also diminishes the risk from hemorrhagic and thrombotic strokes. Why the risk of the interaction of hypertensive and atherosclerotic diseases can be reduced on the brain but not as impressively on the heart remains to be learned, but certain recent lines of clinical and experimental evidence point to some answers. The issue as to why, in the face of increasing numbers of patients receiving the benefits of therapy, there is an alarming increase in patients with end-stage renal disease defies more imagination and study. Thus, many of the old questions seem to be achieving some meaningful answers; but associated with these new answers we are confronted with new questions.

Antihypertensive Agents↗
PubMed1992

Cardiovascular mass and ventricular function after celiprolol in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: The effects of a new beta 1 adrenergic receptor blocking agent with beta 2 receptor agonistic properties on cardiovascular mass, left ventricular function, and aortic distensibility were studied in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. METHODS: 20 male SHR and 20 male WKY rats (10 treated and 10 untreated) aged 22 weeks were studied after three weeks of treatment. Cardiovascular mass was measured and left ventricular function was assessed using electromagnetic flowmetry while rapidly infusing whole blood at pharmacologically reduced mean arterial pressure and at pretreatment arterial pressure levels. Aortic distensibility was assessed by obtaining pressure-volume relationships in isolated aortic segments. RESULTS: Mean arterial pressure was reduced without changing cardiac output in SHR (p less than 0.01); it remained unchanged in WKY despite reduced cardiac output. Most noteworthy, and like no other agent studied to date, celiprolol significantly reduced both left and right ventricular as well as aortic mass in both WKY and SHR. Despite these similar mass reductions, celiprolol improved left ventricular function (p less than 0.01) and aortic distensibility (p less than 0.05) only in the SHR, a function maintained even when mean arterial pressure was increased abruptly to pretreatment levels. CONCLUSIONS: Unlike other beta receptor blockers (or any other agent studied in the SHR), celiprolol was effective in reducing mass of right and left ventricles and of aorta; decreasing mean arterial pressure through a fall in total peripheral resistance; and improving left ventricular function and aortic distensibility in the SHR. In contrast, while these structural changes were also produced in WKY, they were not associated with similar functional responses. These findings provide further support for the thesis of a structural and haemodynamic dissociation in antihypertensive therapy.

Adrenergic beta-Antagonists↗