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Biomedical subjects

E D Frohlich

Publications and source records attributed to E D Frohlich.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Changes in cardiovascular mass, left ventricular pumping ability and aortic distensibility after calcium antagonists in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVES: To determine the effects of different dihydropyridine calcium antagonists on cardiovascular mass and function in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: The rats were treated daily for 3 weeks with nitrendipine (20 mg/kg), nifedipine (30 mg/kg), nisoldipine (6 mg/kg) or their vehicles. At the conclusion of that period left ventricular pumping ability and aortic distensibility were determined, and the aortic, cardiac and left and right ventricular masses. RESULTS: Each drug reduced arterial pressure in both rat strains; each decreased left ventricular mass in SHR but not in WKY rats. All three agents increased right ventricular mass in WKY rats; only nisoldipine did so in SHR. Each compound improved left ventricular pumping ability in WKY rats, maintaining function even when pressure was abruptly increased to pretreatment levels. In contrast, although all three calcium antagonists improved cardiac performance in SHR at the pharmacologically reduced pressures, pumping ability was not maintained when pressure was increased to pretreatment levels in nisoldipine-treated SHR. All three agents improved aortic distensibility in both strains, but only in SHR was reduced aortic mass demonstrated. CONCLUSIONS: These data not only continue to demonstrate a functional/structural dissociation associated with antihypertensive therapy, but also suggest subtle functional and structural effects that differ even within the same class of calcium antagonists.

Animals↗
PubMed1992

Quinaprilat increases total body vascular compliance in rats with myocardial infarction.

To test whether quinaprilat, a new angiotensin-converting enzyme (ACE) inhibitor, has any venous effect, we measured its immediate effects on mean circulatory filling pressure (MCFP), intravascular volume, and total body vascular (i.e., venous) compliance in conscious rats with healed myocardial infarction induced by coronary artery ligation. MCFP was determined by inflating a right atrial balloon to arrest the circulation instantly and temporarily. Total body vascular compliance was derived from total circulatory pressure-volume relationships as determined by series measurements of MCFP with different intravascular volume status. In 8 rats with mean infarct size of 26 +/- 4%, 30-min infusion of quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous pressures (MAP, CVP) by 8 and 0.7 mm Hg, respectively (p less than 0.02); heart rate (HR), MCFP, hematocrit, and blood volume remained unchanged. As compared with control vehicle infusion, quinaprilat increased total body vascular compliance (2.09 +/- 0.12 vs. 2.69 +/- 0.23 ml/kg/mm Hg; p less than 0.05) and decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs. 28.53 +/- 2.55 ml/kg; p less than 0.02). These data suggest that quinaprilat produces possible venodilation through improved total body vascular compliance, thereby reducing cardiac preload in this rat model of myocardial infarction.

Animals↗
PubMed1992

ANF does not increase total body venous compliance in conscious rats with myocardial infarction.

To test the hypothesis that atrial natriuretic factor (ANF) increases total body venous compliance through venodilation and thereby reduces cardiac preload, we compared the systemic hemodynamic effects of ANF (99-126) with the venodilator nitroglycerin in conscious rats with myocardial infarction (mean infarct size 25%) induced by coronary artery ligation 3 wk previously. A 30-min ANF infusion (0.5 microgram.kg-1.min-1) decreased mean arterial pressure, central venous pressure, and blood volume by 11 mmHg, 0.8 mmHg, and 3 ml/kg, respectively (P less than 0.02). Nitroglycerin (10 micrograms.kg-1.min-1) similarly reduced arterial and venous pressures (7 and 0.6 mmHg; P less than 0.02) but increased blood volume by 2 ml/kg (P less than 0.05). Both ANF and nitroglycerin reduced mean circulatory filling pressure (MCFP) by 1 mmHg (P less than 0.05). Compared with vehicle infusion, nitroglycerin increased total body vascular compliance as derived from serial MCFP measurements taken during 10% blood volume changes (2.09 +/- 0.12 vs. 2.76 +/- 0.32 ml.kg-1.mmHg-1; P less than 0.05) and reduced extrapolated unstressed volume (34.96 +/- 1.10 vs. 23.79 +/- 3.80 ml/kg; P less than 0.02). In contrast, ANF had no effect on either measurement. These data suggest that ANF and nitroglycerin reduced cardiac filling pressure through different mechanisms; the lack of effects of ANF on total body venous compliance and unstressed volume does not support its venodilating effect in these rats postmyocardial infarction.

Animals↗
PubMed1992

Effects of alpha 1-adrenergic blockade on intrarenal hemodynamics in heart failure rats.

To investigate intrarenal hemodynamics and effects of alpha 1-adrenergic blockade on glomerular functions in congestive heart failure (CHF), micropuncture studies were performed before and after intravenous injection of terazosin (1 microgram/100 g body wt iv) in eight myocardial infarction (MI) and in nine sham-operated rats after intraperitoneal injection of Inactin (70 mg/kg). CHF was characterized by elevated left ventricular end-diastolic pressure and increased total heart weight. In CHF rats, single nephron glomerular filtration rate (SNGFR), single nephron plasma flow (SNPF), and ultrafiltration coefficient (Kf) were decreased compared with sham-operated rats (SNGFR, 21.9 +/- 1.6 vs. 39.2 +/- 2.9 nl.min-1.g-1, P less than 0.01; SNPF, 66.6 +/- 6.1 vs. 133.8 +/- 10.5 nl.min-1.g-1, P less than 0.01; Kf, 0.019 +/- 0.001 vs. 0.041 +/- 0.004 nl.s-1.mmHg-1.g-1, P less than 0.01). Single nephron filtration fraction (SNFF), glomerular pressure (Pg), and efferent arteriolar resistance (Re) were higher in the CHF-MI rats than in the sham-operated rats (SNFF, 33.4 +/- 1.3 vs. 27.7 +/- 1.0, P less than 0.05; Pg, 60.2 +/- 1.6 vs. 53.3 +/- 0.8 mmHg, P less than 0.01; Re, 3.92 +/- 0.66 vs. 1.62 +/- 0.15 x 10(10) dyn.s.cm-5.g, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

Obesity hypertension. Converting enzyme inhibitors and calcium antagonists.

Exogenous obesity is characterized hemodynamically by expanded intravascular (plasma) volume associated with an increased cardiopulmonary volume and cardiac output. In contrast, essential hypertension is related to an increased total peripheral resistance that is more or less uniformly distributed throughout the component organ circulations associated with a contracted plasma volume in proportion to the height of arterial pressure. Thus, both cardiac output and total peripheral resistance are elevated in obesity hypertension, and both impose a load on the left ventricle, resulting in both a volume and a pressure overload left ventricular hypertrophy. Although renal vascular resistance is not as increased as it is in lean hypertensive patients, these patients are subjected to hyperfiltration and proteinuria. Additionally, these hemodynamic alterations coexist with carbohydrate intolerance, hyperinsulinemia, hyperlipidemia, and hyperuricemia. With weight reduction and associated pressure reduction, the hemodynamic and metabolic changes reverse toward normal. However, should this not be achievable, the angiotensin converting enzyme inhibitors and calcium antagonists provide rational physiological approaches to drug therapy. With these agents pressure reduction is achieved through a fall in vascular resistance without intravascular volume expansion, and this is associated with reduced left ventricular mass and preserved cardiac and renal function, and without exacerbation of preexisting metabolic perturbations. Hence, these two classes of antihypertensive agents may provide a rational and physiological means for reversing the pathophysiological alterations of hypertensive disease in those obese patients in whom weight control is not possible.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Quinaprilat increases total body vascular compliance in rats with myocardial infarction.

To test whether quinaprilat, a new angiotensin converting enzyme inhibitor, has any venous effect, its immediate effects were measured on mean circulatory filling pressure (MCFP), intravascular volume and total body vascular (i.e., venous) compliance in conscious rats with mild congestive heart failure induced by coronary artery ligation. MCFP was determined by inflating a right atrial balloon to arrest the circulation instantly and temporarily. Total body vascular compliance was derived from total circulatory pressure-volume relationships as determined by series measurements of MCFP with different intravascular volume status. In 8 rats with mean infarct size of 26 +/- 4%, 30-minute infusion of quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous pressures by 8 mmHg and 0.7 mmHg, respectively (P less than 0.02); heart rate, MCFP, hematocrit and blood volume remained unchanged. Compared with control vehicle infusion, quinaprilat increased the total body vascular compliance (2.09 +/- 0.12 vs 2.69 +/- 0.23 ml/kg/mmHg; P less than 0.05) and decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs 28.53 +/- 2.55 ml/kg; P less than 0.02). These data suggest that quinaprilat produces possible venodilation through immediately improved total body vascular compliance thereby reducing cardiac preload in this rat model of chronic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Hemodynamic comparison of two nifedipine formulations in patients with essential hypertension.

The hemodynamic and humoral effects and trough-to-peak 24-hour blood pressure responses of 2 nifedipine formulations, capsules and continuous-release once-daily formulation tablets, were evaluated in 10 patients with mild to moderate essential hypertension. Both formulations reduced mean arterial pressure similarly from 120 +/- 3 (baseline) to 107 +/- 2 (p less than 0.005) and 105 +/- 2 mm Hg (p less than 0.005) and total peripheral resistance index from 65 +/- 9 (baseline) to 47 +/- 4 (p less than 0.05) and 45 +/- 3 U/m2 (p less than 0.05), respectively. Renal, splanchnic and total forearm (including skin and skeletal muscle) blood flows were maintained or even increased slightly associated with reductions in regional vascular resistances. Decreases in renal, total forearm and skeletal muscle resistances were significant (p less than 0.05) with the capsules, but the decrease was only significant in renal resistance with the long-acting tablets. Intravascular volume did not expand with reduction in arterial pressure. This antihypertensive effect was not related to baseline plasma renin activity levels or age. Nifedipine tablets provided a better control of mean arterial pressure (66%) than did capsules (44%).

Capsules↗
PubMed1991

Hemodynamic effects of celiprolol in essential hypertension.

The immediate and short-term (2 week) hemodynamic and humoral effects of the beta-1 antagonist, beta-2 agonist, celiprolol, were compared with those of more prolonged atenolol therapy in 12 patients with essential hypertension. Celiprolol produced an immediate dose-dependent decrease in mean arterial pressure (113 +/- 3 to 102 +/- 2 mm Hg; p less than 0.001) and total peripheral resistance (49 +/- 3 to 38 +/- 1 U/m2; p less than 0.005) that was associated with an increased heart rate (67 +/- 1 to 73 +/- 2 beats/min; p less than 0.01) and cardiac index (2,347 +/- 129 to 2,708 +/- 111 ml/min/m2; p less than 0.01). Both celiprolol and atenolol reduced mean arterial pressure with short-term treatment (p less than 0.01); this was associated with a reduced total peripheral resistance with celiprolol (from 24 +/- 1 to 21 +/- 1 U/m2; p less than 0.02) and was not observed with atenolol. Moreover, in contrast with atenolol, celiprolol did not change heart rate or stroke and cardiac indexes. Splanchnic and forearm vascular resistances decreased with celiprolol (p less than 0.05) but not with atenolol; neither beta-blocking drug altered renal blood flow. These results demonstrate that the hemodynamic effects of celiprolol were strikingly different from atenolol; celiprolol reduced arterial pressure and total peripheral and certain vascular resistances without altering heart rate, cardiac index or regional blood flows. These effects may be explained by celiprolol's cardiac beta-1 receptor inhibitory and peripheral beta-2 receptor agonistic effects.

Adrenergic beta-Antagonists↗
PubMed1991

Left ventricular hypertrophy: dissociation of structural and functional effects by therapy.

The heart is one of the major target organs that becomes secondarily involved with the unrelenting and progressive vascular disease of essential hypertension. As a result of this increasing afterload that is imposed upon the left ventricle, the ventricular chamber adapts structurally and functionally. Structural changes involve an increase in muscle mass that is achieved through left ventricular hypertrophy (in a manner similar to the arteriolar changes demonstrated by increased thickening). Unless antihypertensive therapy is interdicted in this disease process, left ventricular failure will ensue as the major cardiac hemodynamic consequence. Left ventricular hypertrophy is also associated with a risk that is independent of the pressure overload and hemodynamic risk. Although antihypertensive therapy will reduce from the hemodynamic alterations, only recently have epidemiological findings suggested that the independent risk of LVH may be reduced with pharmacological therapy. There are no data available to indicate just which agents may reduce the risk from LVH; but relatively recent studies seem to indicate that while all agents may reduce LVH with prolonged therapy only certain classes of agents will do so independent of their hemodynamic factors. Some of these agents, however, may impair cardiac function if arterial pressure is increased abruptly following therapeutic reduction of cardiac mass. Other agents may preserve normal function--or even may improve function. Among those classes of antihypertensive agents that reduce cardiac mass at least in part due to nonhemodynamic factors, are the angiotensin converting enzyme inhibitors, the calcium antagonists, and most adrenergic inhibitors. Evidence will be presented demonstrating the hemodynamic/structural dissociation of those pharmacological agents that reduce cardiac mass with short-term treatment in spontaneously hypertensive rats with left ventricular hypertrophy. Although centrally active adrenolytic, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists all reduce cardiac mass, their structural and cardiac functional effects differ greatly. Even within the ACE inhibitor group their effects vary--improving, impairing, or not changing the Frank-Starling relationships following reduction in left ventricular mass. We postulate great variability of cardiac intramyocytic penetrance of the pharmacological agents and their local intracellular effects on mitogenesis of the ventricular myocyte. The implications on cardiac function and therapy have vast potential. Therefore, current investigative areas involving new concepts of molecular biology of the cardiac myocyte may provide great promise to the quest of unraveling some of the newly postulated questions: What is the role of ionized intracellular calcium? Do the local renin-angiotensin systems in the cardiac and vascular myocyte participate in the development and regression of hypertrophy?(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Vasodilatory beta-blockers: systemic and regional hemodynamic effects.

The systemic and regional hemodynamic alterations in hypertension and of the beta-adrenergic receptor inhibiting agents are reviewed. Hemodynamically, hypertension may be regarded as persistent elevation of arterial pressure associated with increased total peripheral resistance. In early or mild essential hypertension, however, increased total peripheral resistance may not readily be recognized because of the overriding effect of increased cardiac output. Clearly, the hemodynamics of blood pressure control are complex, and the mechanisms of antihypertensive agents must be used appropriately. The early beta-blockers reduced heart rate and cardiac output immediately after intravenous administration without immediately reducing arterial pressure, and calculated total peripheral resistance was increased. With prolonged oral treatment, arterial pressure decreased while maintaining a reduced heart rate and cardiac output. Total peripheral resistance, however, remained elevated. Recent beta-blockers, such as celiprolol, provide an improved physiologic response by instantly reducing arterial pressure and total peripheral resistance without reducing heart rate or cardiac output or expanding intravascular volume.

Administration, Oral↗