Search PubMed⌕ Search

Biomedical subjects

M A Creager

Publications and source records attributed to M A Creager.

125 records · Page 7Linked to original sources
PubMed1985

Haemodynamic and neurohumoral response to exercise in patients with congestive heart failure treated with captopril.

The contribution of the renin-angiotensin system to the cardiovascular response to exercise was studied in 12 patients with congestive heart failure. The haemodynamic effects of captopril were measured at rest and during supine bicycle exercise. After captopril administration, resting systemic vascular resistance fell by 26.6% and mean blood pressure by 16.7% and cardiac index increased by 19.7%. During exercise, captopril decreased systemic vascular resistance by 25.6% and mean blood pressure by 8.2% and increased cardiac index by 24.4%. Pulmonary wedge pressure fell by 25% at rest but was not altered by captopril during exercise. Pretreatment plasma renin activity increased from 13.4(16.0) ng/ml/hr (10.3(12.3) mmol/l/hr) at rest to 20.0(27.8) ng/ml/hr (15.4(21.4) mmol/l/hr) during exercise. Pretreatment plasma noradrenaline concentration increased from 659(433) pg/ml (39(25.6) nmol/l) at rest to 2622(1486) pg/ml during exercise (155(88) nmol/l). Captopril favourably alters systemic vascular resistance and cardiac index during exercise in patients with congestive heart failure. This may reflect inhibition of the increased activity of the renin-angiotensin system during exercise in these patients and a subsequent reduction in systemic vasoconstriction.

Adult↗
PubMed1985

Beta adrenergic-mediated vasodilator response to insulin in the human forearm.

Insulin, in doses sufficient to cause systemic hypoglycemia, decreases vascular resistance; however, a vasoactive effect of insulin in humans, in the absence of hypoglycemia, is unknown. Venous occlusion strain gauge plethysmography was utilized to determine forearm blood flow (FBF) and forearm vascular resistance (FVR) during incremental intra-arterial infusion of insulin (0.1, 0.5 and 1.0 mU/kg/min) in seven normal subjects. With the increasing doses of insulin, FBF increased 55, 76 and 145% and FVR decreased 30, 42 and 58%, respectively. Systemic glucose concentration decreased only during the highest dose insulin infusion. In eight subjects who received insulin during euglycemic glucose clamping, FVR also decreased. Therefore, it was demonstrated that insulin dilates the forearm vasculature in the absence of hypoglycemia. In order to determine whether the vasodilatory effect of insulin was mediated by the sympathetic nervous system, plasma levels of epinephrine and norepinephrine were measured. During the incremental insulin infusions, norepinephrine levels did not change, but epinephrine concentration increased during the 1.0 mU/kg/min infusion when hypoglycemia developed. Furthermore, 21 subjects were pretreated with intra-arterial phentolamine, propranolol or the combination of phentolamine and propranolol. Phentolamine did not potentiate the fall in FVR during insulin administration; however, propranolol attenuated or completely inhibited the changes in FBF and FVR. During combined alpha and beta adrenergic blockade, insulin increased FBF and decreased FVR only during the higher dose insulin infusions. It is concluded that insulin causes forearm vasodilation primarily via a beta adrenergic mechanism. In addition, at the higher doses used in this study, insulin may decrease FVR directly or by a mechanism other than adrenergic stimulation.

Adult↗
PubMed1984

Redistribution of regional blood flow following angiotensin-converting enzyme inhibition. Comparison of normal subjects and patients with heart failure.

The systemic and regional circulatory effects of angiotensin-converting enzyme inhibition were investigated in 30 normal subjects and in 36 patients with severe congestive heart failure. Regional blood flow was measured in individual patient groups. Cardiac index rose and systemic vascular resistance fell in normal subjects after angiotensin-converting enzyme inhibition. In the patients with heart failure, a similar rise in cardiac index and fall in systemic resistance occurred. In addition, right and left ventricular filling pressures decreased. The fall in systemic vascular resistance correlated with plasma renin activity (r = 0.57, p less than or equal to 0.001). Of the regional circulations investigated in normal subjects, only forearm blood flow increased after angiotensin-converting enzyme inhibition. Although over-all there was no change in renal or coronary blood flow, coronary flow dramatically increased in some patients and the increase in flow correlated with plasma renin activity (r = 0.939, p less than or equal to 0.001). In patients with heart failure, forearm, splanchnic, and coronary flow were unaffected by angiotensin-converting enzyme inhibition, whereas renal blood flow estimated from para-aminohippurate clearance increased 60 percent and accounted for 50 percent of the increase in cardiac output seen in these patients. Thus, redistribution of flow occurs in congestive heart failure with a significant reduction in the fraction flow to the kidneys when compared with normal flow. The contribution of the renin-angiotensin system to the regulation of regional blood flow is different in normal subjects and in patients with heart failure. Angiotensin-converting enzyme inhibition augments skeletal flow in normal subjects whereas it increases renal blood flow in patients with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Nifedipine-induced fingertip vasodilation in patients with Raynaud's phenomenon.

The effect of nifedipine on fingertip hemodynamics was studied in 10 patients with Raynaud's phenomenon. Fingertip blood flow (FBF) was determined in a 20 degrees C environment by venous occlusion air plethysmography and fingertip vascular resistance (FVR) was calculated from the mean blood pressure and the FBF. Nifedipine, administered as a 10 mg sublingual dose, increased FBF in 8 of the 10 patients. FVR for the 10 patients decreased 40% from 40.7 +/- 10.8 to 24.2 +/- 6.1 U (p less than 0.05). Seven of the 10 patients were followed in a crossover placebo-controlled clinical trial. The frequency and severity of Raynaud's phenomenon was less in all seven patients when taking nifedipine as compared to placebo. Nifedipine-induced fingertip vasodilation may contribute to clinical improvement in some patients with Raynaud's phenomenon.

Adult↗
PubMed1984

Effect of renin-angiotensin system on limb circulation in normal subjects.

It is not known whether the renin-angiotensin-aldosterone (RAA) system contributes to the regulation of the limb circulation in normal human beings. Accordingly, the effect of the angiotensin converting-enzyme inhibitor, captopril, on forearm vascular resistance (FVR) and forearm venous volume (FVV) was studied in nine normal subjects during states of both sodium loading and sodium depletion. All subjects were studied in the supine position and during 60 degrees head-up tilt. By analysis of variance, the combined intervention of sodium depletion and converting-enzyme inhibition was responsible for a decrease in both FVR and mean blood pressure (BP). In sodium-depleted subjects, converting-enzyme inhibition decreased supine mean BP 7.0% and supine FVR 22.8% but did not change FVV. Neither the fall in BP nor the fall in FVR, however, was significantly augmented by tilting from a supine to upright posture. In sodium-loaded subjects, captopril did not alter BP, FVR, or FVV in recumbent or upright positions. Therefore, the RAA system contributes to the maintenance of blood pressure and limb vascular resistance only in sodium-depleted subjects. Limb venous capacitance in normal subjects is not regulated by the RAA system.

Adult↗
PubMed1983

Efficacy and safety of verapamil in patients with angina pectoris after 1 year of continuous, high-dose therapy.

The long-term efficacy and safety of high-dose verapamil therapy (480 mg/day) was assessed in 26 patients with chronic stable angina pectoris during a 3-phase protocol: Phase 1--an initial, 6-week placebo-controlled, double-blind crossover assessment; Phase 2--an open label, 1-year follow-up; and Phase 3--a final drug withdrawal and rechallenge 10-week study. Three patients withdrew during Phase 2 (1 had hepatitis and 2 underwent coronary bypass surgery). Adverse effects during Phase 2 were mild, consisting of constipation (6 patients) and prolongation of the P-R interval (5 patients); however, no patient required alteration of the 480 mg/day dosage. At the end of Phase 2, 10 patients underwent the Phase 3 study, commencing with a 2-week period in which verapamil was either tapered gradually or abruptly discontinued. This was followed by an 8-week double-blind, placebo-controlled crossover rechallenge study with verapamil. The clinical and exercise responses to verapamil compared with placebo were similar during the Phase 3 protocol and the initial Phase 1 study (treadmill time increased by 55% and anginal attacks per week decreased by 63% during Phase 3, compared with a 28% increase and a 42% decrease, respectively, during Phase 1, p = not significant [NS]). Withdrawal of verapamil produced a similar return of anginal symptoms whether the drug was abruptly discontinued or its administration tapered. No patient had unstable angina pectoris or acute myocardial infarction. These investigations demonstrate that verapamil is safe and effective when evaluated after 1 year of continuous therapy using a dosage of 480 mg/day. There is no evidence of drug tachyphylaxis, nor does verapamil appear to cause an abrupt withdrawal syndrome in patients with chronic stable angina pectoris.

Adult↗
PubMed1983

Nifedipine as a therapeutic modality for Raynaud's phenomenon.

Eight patients with Raynaud's phenomenon were entered into a double-blind crossover study of nifedipine versus placebo, with 7 patients undergoing finger plethysmography before and after sublingual nifedipine administration. While receiving nifedipine, all patients reported decreased frequency and severity of attacks, and 4 of 5 had digital ulcer healing. Total finger blood flow increased 5 of 6 patients after treatment with sublingual nifedipine. This preliminary study indicates that nifedipine may be a useful agent for treatment of digital vasospasm.

Adult↗
PubMed1983

Treatment of chronic orthostatic hypotension with ergotamine.

The acute and chronic effects of ergotamine were examined in four patients with chronic orthostatic hypotension. Chronic oral administration of ergotamine tartrate produced significant increases in standing blood pressure and marked clinical improvement, without appreciable recumbent hypertension. The blood pressure increases were not associated with significant changes in plasma norepinephrine or plasma renin activity. No major toxicity was observed at doses of 2-6 mg/day over treatment periods of 3-18 months. Hemodynamic studies on the effects of i.v. ergotamine tartrate (0.25-0.50 mg) revealed that the ergotamine-induced increase in blood pressure in the supine position was associated with an increase in total peripheral resistance (from 1616 +/- 165 to 2574 +/- 583 U) without a change in cardiac output. During 45-60 degrees upright tilt, ergotamine increased both total peripheral resistance (1801 +/- 296 to 3262 +/- 1107 U) and cardiac output (2.42 +/- 0.46 to 3.34 +/- 0.54 l/min). Forearm plethysmographic studies revealed decreased forearm blood flow and venous volume and increased vascular resistance with ergotamine. The orthostatic hypotensives had more platelet alpha-receptors (390 +/- 31 receptors/cell) than the control subjects (234 +/- 17 receptors/cell). The increased receptor level was associated with abnormally low circulating levels of norepinephrine and increased pressor responsiveness to infused norepinephrine in three of the four patients. Chronic ergotamine therapy appeared to reduce platelet alpha-receptor number to normal. The results indicate that ergotamine is of value in certain patients with chronic orthostatic hypotension and that the blood pressure effects are related to vasoconstriction in both arterial and venous beds.

Adult↗
PubMed1982

Determinants of clinical response and survival in patients with congestive heart failure treated with captopril.

The efficacy of chronic ambulatory captopril (CPT) therapy was evaluated over an 18-month period in 36 patients with refractory chronic congestive heart failure (CHF) by cardiac catheterization, treadmill exercise, nuclear scintigraphy, echocardiography, and symptomatology. Clinical improvement to New York Heart Association functional class I or class II was observed in 63% of the patients (20 of 32) after 2 months of treatment; this amelioration of CHF symptoms was sustained in 63% of the patients (10 of 16) at 18 months. Exercise tolerance increased in 64% of the patients (16 of 25) at early follow-up and in 79% (11 of 14) at late follow-up. Univariate analysis revealed that the pre- and post-CPT stroke work indices (SWI) and the post-CPT cardiac index related to favorable long-term clinical response. Fourteen CHF patients (39%) died during the 18-month follow-up. Univariate analysis revealed that the pretreatment SWI, right atrial pressure, plasma norepinephrine concentration, and echocardiographic shortening fraction were significant predictors of mortality. Multivariate analysis indicated that the SWI was the principal determinant of survival: the 18-month cumulative survival rate for CHF patients with a SWI less than 32 gm . m/m2 was 44% compared to 88% when the SWI was greater than 32 gm . m/m2. Thus, CPT results in sustained symptomatic and functional improvements in patients with advanced CHF, but the mortality remains high and is primarily related to the severity of cardiac dysfunction.

Acute Kidney Injury↗
PubMed1982

Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure.

The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril and teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 +/- 240 to 1,715 +/- 170 dynes . s . cm-5 (p less than 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 +/- 8 to 86 +/- 5 mm Hg, p less than 0.001) and left ventricular filling pressure (30 +/- 2 to 21 +/- 2 mm Hg, p less than 0.001). Coronary sinus thermodilution blood flow paralleled perfusion pressure but did not significantly vary overall (160 +/- 20 to 133 +/- 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 +/- 8.8 to 41.3 +/- 7.9 g l m/m2, p less than 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 +/- 1.0 to 10.4 +/- 1.0 ml/10 ml, NS) or calculated myocardial oxygen consumption (16.4 +/- 1.9 to 13.9 /- 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 +/- 703 to 7,087 +/- 514 beats . mm Hg, p less than 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 +/- 3 to 26 +/- 6, p less than 0.05), reflecting greater left ventricular work without increased oxygen demand. Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.

Aged↗
PubMed1982

The effect of angiotensin converting enzyme inhibition of coronary blood flow and hemodynamics in patients without coronary artery disease.

We examined the role of the renin-angiotensin system in the regulation of systemic and coronary vascular tone by studying the effect of converting enzyme inhibition by teprotide on systemic and coronary hemodynamic parameters in 14 normal patients undergoing routine cardiac catheterization. Serial hemodynamic measurements were made before and up to 30 minutes after 1 mg/kg of intravenous teprotide. A significant rise in cardiac index and stroke volume index occurred with a fall in systemic vascular resistance. The increase in cardiac index was related to the level of resting plasma renin activity. Blood pressure, pulmonary artery and left ventricular end-diastolic pressures remained unchanged. Coronary sinus thermodilution blood flow also showed no significant change; however, some patients demonstrated dramatic increase in flow. The change in blood flow was highly correlated with the resting plasma renin activity (r = 0.939 P less than 0.001). The change in coronary vascular resistance and myocardial oxygen consumption were likewise related to the resting plasma renin level. Converting enzyme inhibition produces significant systemic hemodynamic changes in normal patients which implies that the renin-angiotensin system is important in normal cardiovascular homeostasis. The direct relationship between plasma renin activity and coronary blood flow suggests that the renin-angiotensin system may play an important role in coronary vasomotor regulation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Peripheral arterial and venous responses to acetylstrophanthidin in patients with acute myocardial infarction.

The peripheral arterial and venous responses to rapidly active acetylstrophanthidin (rather than the much slower digitalis) were studied in patients with acute myocardial infarction without congestive heart failure. In eight control patients placebo did not change mean blood pressure (BP), calf blood flow (CBF), calf vascular resistance (CVR), or calf venous volume (CVV). Seventeen patients received 10 mg IV acetylstrophanthidin. In these patients BP increased 5.3%, CBF decreased 18.2%, and CVR increased 29.2%. Venous capacitance was not changed. Acetylstrophanthidin induced no significant change in cardiac output, systemic vascular, resistance, pulmonary capillary wedge pressure, or right atrial pressure. In patients with acute myocardial infarction not complicated by congestive heart failure, digitalis may promote limb vasoconstriction and increase blood pressure, but it does not adversely affect cardiac function.

Electrocardiography↗
PubMed1982

Regional circulatory response to converting-enzyme inhibition in congestive heart failure.

1 To determine the distribution of flow, the regional haemodynamic response to 100 mg of captopril was determined in 36 patients with refractory cardiac heart failure. Measurements included forearm blood flow by venous occlusion plethysmography (eight patients), splanchnic blood flow by indocyanine green clearance (10 patients), and coronary blood flow by thermodilution (12 patients). 2 Cardiac index significantly rose in one hour (1.9 +/- 0.1 to 2.2 +/- 0.1 1/m/m2, p less than 0.01) while forearm blood flow rose slightly (2.9 +/- 0.8 to 3.2 +/- 0.3 ml/100 ml/min). Renal blood flow rose significantly by 30% (344 +/- 48 to 533 +/- 82 ml/min, p less than 0.02). Despite a fall in rate pressure product (8.8 +/- 0.7 to 7.1 +/- 0.5 mm Hg bt x 10(3), p less than 0.02), coronary blood flow did not significantly change (160 +/- 20 to 133 +/- 12 ml/min), indicating an improved supply-demand relationship. 3 External myocardial efficiency improved (19 +/- 3 to 26 +/- 6%, p less than 0.05). Coronary blood flow is unaffected and converting-enzyme inhibitor improves myocardial efficiency. This strategic reduction in vascular impedence distinguishes converting-enzyme inhibitors as a unique class of vasodilators in the treatment of coronary heart failure.

Aged↗
PubMed1981

Angiotensin inhibition in severe heart failure: acute central and limb hemodynamic effects of captopril with observations on sustained oral therapy.

The systemic, pulmonary, and limb circulatory responses to the angiotensin-converting enzyme inhibitor, captopril, were determined in 10 patients with severe, chronic heart failure. Immediate effects include sustained reductions in arterial pressure and pulmonary capillary wedge pressure and improvement in cardiac output, as reported with other vasodilator drugs. Calf vascular resistance did not change despite substantial lowering of total systemic vascular resistance, indicating that arteriolar dilatation occurred on a selective basis. Transient reduction in mean right atrial pressure paralleled slight calf venodilatation, but effects upon the resistance vasculature predominated. Plasma renin activity and norepinephrine concentrations increased after therapy in the acute phase as plasma aldosterone levels consistently fell. During maintenance oral treatment over 7 to 15 months (median, 11.5 months), patients displayed symptomatic benefit, improved functional capacity, and greater exercise tolerance. No major adverse reactions developed. These findings suggest that angiotensin converting enzyme inhibition with captopril in congestive heart failure patients improved cardiocirculatory function through selective arteriolar dilatation. The reordering of regional blood flow which appears to result from release of angiotensin-mediated vasoconstriction, as well as the suppression of aldosterone, may underlie the prolonged benefit observed in these patients. This oral vasodilator appears to represent an effective adjunct for the treatment of advanced, chronic heart failure refractory to conventional measures.

Administration, Oral↗
PubMed1981

Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure.

The acute effects of the angiotensin converting-enzyme inhibitor captopril on regional blood flow, renal hemodynamics and sodium excretion were studied in 12 patients with severe congestive heart failure. Converting-enzyme inhibition decreased systemic vascular resistance by 27% and increased cardiac index by 16%. Estimated hepatic blood flow decreased 17%, but renal blood flow increased 60%. The ratio of renal-systemic blood flow increased from 0.10 +/- 0.01 to 0.14 +/- 0.02 (p = 0.031). Although renal plasma flow increased from 202.8 +/- 28.8 to 323.7 +/- 42.7 ml/min (p less than 0.008), the glomerular filtration rate did not change significantly from the mean pretreatment value of 82.1 +/- 12.3 ml/min. The filtration fraction decreased from 41.3 +/- 3.8% to 33.4 +/- 4.5% (p = 0.050), while urinary sodium excretion doubled, from 34.5 +/- 9.6 to 68.2 +/- 19.6 muEq/min. The plasma renin activity increased from 12.6 +/- 5.0 to 29.9 +/- 8.4 ng/ml/hr (p = 0.030) as plasma aldosterone concentration decreased from 30.5 +/- 6.5 to 11.3 4/- 1.2 ng/dl (p = 0.010) and norepinephrine concentrations decreased from 774 +/- 105 to 618 +/- 85 pg/ml (p = 0.020). We conclude that converting-enzyme inhibition reverses renal vasoconstriction in congestive heart failure and redistributes regional blood flow. The natriuresis may be mediated by one or more of the following: improved renal plasma flow, reduction in filtration fraction, suppression of hyperaldosteronism, and lowering of circulatory catecholamine concentrations.

Acute Disease↗
PubMedDate not supplied

Medical management of peripheral arterial disease.

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.

Cardiovascular Diseases↗