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Biomedical subjects

J L Izzo

Publications and source records attributed to J L Izzo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Impact of angiotensin-converting enzyme inhibitor underdosing on rehospitalization rates in congestive heart failure.

In a retrospective, cohort design, clinical usage of digoxin, diuretic, and angiotensin-converting enzyme (ACE) inhibitor was assessed in all patients readmitted over a 36-month period for congestive heart failure (CHF) diagnostic-related group (DRG) 127. ACE inhibitor dose-response analysis used the discharge dose of ACE inhibitor, converted to enalapril-equivalent doses and adjusted for renal function. Principal end points were time-to-readmission and 90-day readmission rate. Of 314 total patients, digoxin was used in 72%, diuretic in 86%, and 67% received an ACE inhibitor. Only 22% of those on an ACE inhibitor received currently recommended doses of enalapril > or = 20 mg/day or equivalent, whereas 41% received enalapril < or = 5 mg/day. Time-to-readmission was increased by an ACE inhibitor (p = 0.002) but not digoxin or diuretic. An ACE inhibitor was the principal covariate of 90-day readmission rate (p <0.05). The readmission rate was not reduced with daily ACE inhibitor doses of < or = 5 mg enalapril, whereas daily doses of > or = 10 mg enalapril reduced 90-day readmission rates by 28% compared to those receiving diuretic or digoxin therapy (p <0.05). Using a dynamic model, the dose required to achieve 90% to 95% of the theoretical maximum ACE inhibitor effect exceeded 100 mg enalapril daily. Thus, CHF readmission rates are lower when daily ACE inhibitor doses exceed 5 mg enalapril or the equivalent daily, but are unaffected by digoxin or diuretic. Modeled maximum ACE inhibitor benefits require doses 8- to 10-fold higher than current usage patterns.

Aged↗
PubMed1998

Vasoreactivity in pre- and postmenopausal women: evaluation by pharmacodynamic modeling.

Postmenopausal women experience an increase in cardiovascular mortality and morbidity compared with their premenopausal counterparts. This study was undertaken to develop a pharmacodynamic model to determine whether vascular reactivity in postmenopausal women differed from that in premenopausal women. Eleven subjects in each group were recruited. Graded doses of norepinephrine and insulin were infused via the dorsal hand vein. Venous diameter was measured by ultrasound. Dosage and venous diameter were fit to a Hill-type pharmacodynamic model in which norepinephrine acts as a vasoconstrictor and insulin counteracts varying fractions of norepinephrine constriction. Fitted pharmacodynamic parameters for norepinephrine did not differ uniformly between groups, but at norepinephrine infusion rates between 14 and 46 ng/mL, postmenopausal women demonstrated increased norepinephrine-induced vasoconstriction. Also, the modeled maximal response to insulin (Emaxi) was greater in premenopausal women. By stepwise linear regression, maximal response to insulin was found to be related to menopausal status and diastolic blood pressure. Postmenopausal women showed differences in vasoreactivity that may have important implications in the pathogenesis of hypertension.

Aged↗
PubMed1998

Heparin attenuates norepinephrine-induced venoconstriction.

Reversal by heparin of norepinephrine-induced constriction of normal hand veins was studied. Venous size was measured using a linear variable differential transformer (LVDT) during infusions of saline, norepinephrine, insulin and norepinephrine, and graded doses of heparin with norepinephrine. Heparin reduced the venoconstrictive effects of norepinephrine (p < 0.01), with the effects beginning at 18.5 nmol/min (0.05 U/min) and reaching a maximum between 185 nmol/min and 1.85 mumol/min (0.5 and 5 U/min). Maximal heparin-induced venorelaxation correlated with the maximal insulin effect within individuals (r = 0.8, p < 0.01) and was unchanged by the addition of insulin. Methylene blue, a non-specific inhibitor of the nitric oxide cGMP cascade, reduced heparin-induced venorelaxation. In conclusion, heparin in either physiologic or pharmacologic concentration attenuated norepinephrine-induced venoconstriction. A common mechanism of venorelaxation by heparin and insulin is not excluded given the correlation and lack of additivity of maximum effects and their inhibition by methylene blue.

Adult↗
PubMed1997

Effects of cholesterol reduction on BP response to mental stress in patients with high cholesterol.

Impaired endothelium-dependent vascular relaxation has been reported in patients with high cholesterol (HC), but the systemic effects of elevated cholesterol on blood pressure (BP) and BP reactivity to stress have not been studied. We examined the BP response to a standard mental arithmetic test (MAT) in 37 healthy, normotensive HC subjects and 33 normal cholesterol controls (NC). Both groups had similar age, body mass index, and gender distribution. HC had slightly higher systolic BP at baseline (122 v 118 mm Hg, P < .05) than NC and systolic BP response during MAT was significantly higher in HC compared to NC (18 +/- 8 v 10 +/- 5 mm Hg, P < .05). Maximal changes in systolic BP were significantly correlated with cholesterol (R = 0.41, P < .001), whereas heart rate and diastolic BP changes were unrelated to serum cholesterol. To confirm that BP reactivity was dependent on cholesterol, MAT was repeated after treatment with 20 mg/day of lovastatin, a hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, for 6 weeks using a cross-over design in 26 HC subjects. Lovastatin significantly altered lipid profiles (-26% total cholesterol, +8% HDL, -34% LDL). A small decrease in systolic BP at baseline (-3 mm Hg, P = NS) and significantly lower systolic BP (-8 mm Hg, P < .05) during MAT was observed after the treatment with lovastatin. In conclusion, patients with high cholesterol had an exaggerated systolic BP response to MAT. Decreased BP reactivity during HMG-CoA reductase inhibitor therapy suggests that lowering cholesterol may have a role in the overall control of BP.

Adult↗
PubMed1997

Changing the infection control paradigm from off-line to real time: the experience at Millard Fillmore Health System.

In 1993, several departments at Millard Fillmore Health System joined efforts to initiate a new approach to infection control. The main emphasis of this program is to move infection control to a real-time mode to manage patient outcomes daily. The principal objective was to decrease the number of nosocomial infections by 10%, with a particular emphasis on surgical-site infections. Besides real-time surveillance, we are critically evaluating several aspects of the management of nosocomial infections. High-level computer support has been the frame-work upon which this program was built. We have microcomputers that are linked directly to microbiology, pharmacy, billing, and admissions, downloading data several times daily. An expert software system merges all of the data, and from this we can target patients for real-time interventions. The computer system allows all inpatients to be screened for either infection control or antibiotic management interventions on a daily basis, with minimal time being spent on data collection and maximal efforts devoted to interventions at the bedside. Additionally, the infection management program will assist in maintaining the extraordinarily low expenditures on antimicrobial agents. During 1993, the Millard Fillmore Health System spent $924,884 on antibiotics, an amount approximately 50% that of comparably sized hospitals.

Anti-Bacterial Agents↗
PubMed1997

Moderately obese, insulin-resistant women exhibit abnormal vascular reactivity to stress.

To define the hemodynamic implications of insulin resistance (IR), we compared 10 normotensive, insulin-resistant women who had abnormal glucose tolerance tests with 10 age-matched healthy normotensive women with normal glucose tolerance tests with respect to mental arithmetic and handgrip responses. Hemodynamic variables obtained at baseline and during stress included heart rate, blood pressure, cardiac output, and systemic vascular resistance. The IR group weighed more (84 versus 66 kg). Screening BP was similar (123/72 versus 120/68 mm Hg, P=NS) between groups although baseline diastolic BP at testing day was higher in the IR group than control group (75 versus 65 mm Hg, P<.05). The IR group showed a significantly greater increase in systolic (18% versus 10%, P<.O1) and diastolic (24% versus 12%, P<.01) blood pressure responses to mental stress than the control group. During mental stress, the control group demonstrated increased cardiac output (1.4 L/min) and decreased systemic vascular resistance (-120 dyne x s x cm[-5]), whereas IR subjects demonstrated increased systemic vascular resistance (119 dyne x s x cm(-5); group difference, P<.02) with only a small increase in cardiac output (0.5 L/min). Handgrip also caused a greater increase in systemic vascular resistance in the IR group (252 versus 64 dyne x s x cm(-5), P<.05), with a correspondingly greater increase in blood pressure than control subjects. Baseline blood pressure was correlated with weight (r=.41, P<.02) and stress blood pressure with fasting insulin (r=.51, P<.001) and glucose-to-insulin ratio (r= -.55, P<.001). We conclude that insulin resistance is associated with an exaggerated blood pressure response to stress; an enhanced vasoconstriction to stress may mediate this response. This hyperreactivity may be a marker for future hypertension in obese, normotensive, hyperinsulinemic individuals.

Adult↗
PubMed1995

Vascular reactivity in patients with peripheral vascular disease.

Noninvasive techniques have been used to demonstrate a specific pattern of impaired vasoactive response in the normal brachial artery of patients with clinical atherosclerosis. This is a physiologic reflection of the systemic nature of atherosclerosis and may be useful as a marker for identifying patients with preclinical atherosclerotic disease.

Adult↗
PubMed1995

Insulin attenuates norepinephrine-induced venoconstriction. An ultrasonographic study.

To directly assess insulin-related venomotor changes objectively and quantitatively, we used a modified ultrasonographic technique to measure venous diameter. Ten healthy men and women were studied by use of an Acuson 128 XP ultrasonograph with a linear 7.5-MHz ultrasonographic transducer (sensitivity, +/- 0.1 mm). Venous diameter was measured with the arm kept at 30 degrees elevation and with a pneumatic cuff above the elbow inflated at 40 mm Hg for the last 2 minutes of each 5-minute observation period. Norepinephrine was infused at incremental concentrations of 12.5, 25, 50, and 100 ng/min (75, 150, 300, and 600 pmol/min, respectively) for 5 minutes each. Maximal venoconstriction was achieved by the dose of 100 ng/min norepinephrine, which was then combined with insulin doses of 8, 16, 24, and 32 microU/min (60, 120, 180, and 230 fmol/min, respectively) for 5 minutes each. In six different subjects, methylene blue, an inhibitor of guanylate cyclase, was infused simultaneously with 32 microU/min insulin and 100 ng/min norepinephrine. Mean resting diameter of the vein (1.8 +/- 0.6 mm [mean +/- SD]) increased (to 3.0 +/- 1.0 mm) after cuff inflation. Incremental doses of norepinephrine caused highly reproducible dose-dependent decrease in venous diameter (to 1.8 +/- 0.6 mm, P < .001). Incremental doses of insulin, when combined with the maximum dose of norepinephrine, caused highly reproducible dose-dependent increases in mean venous diameter (P < .001) compared with norepinephrine alone. Methylene blue, which had no independent effect on venous diameter, inhibited the venodilator effect of insulin (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Preservation of renal function by percutaneous renal angioplasty in high-risk elderly patients: short-term outcome.

In 17 elderly patients, 19 angioplasties (17 nonostial, 2 ostial) were performed to treat acute decreases in renal function caused by high-grade renal artery stenosis in patients considered to be high-risk surgical candidates. Seventeen angioplasties (percutaneous transluminal renal angioplasty, PTRA) were technically successful and 7 patients showed improved renal function, as reflected by a fall in mean serum creatinine from 566 to 180 mumol/l (6.4 to 2.1 mg/dl). Four others had stabilization of function and 3 out of 4 with acute oliguria improved. Complications included femoral hematoma (4), minor peripheral embolism (3), renal artery thrombosis (1) renal artery dissection (1). One fatal complication was thrombosis of the aortic bifurcation due to catheterization. Four other patients died of cardiovascular causes unrelated to PTRA. Eleven patients experienced stabilization or improvement in renal function, but five out of six PTRA failures required maintenance hemodialysis and died in the hospital. Percutaneous transluminal angioplasty may offer the best change of favorable outcome in selected severely ill elderly patients with uremia, hypertension and renal artery stenosis.

Aged↗
PubMed1990

Effect of postural stimulation on systemic hemodynamics and sympathetic nervous activity in systemic hypertension.

The contributions of the carotid sinus and cardiopulmonary baroreflexes to the interindividual variation in sympathetic nervous system activation caused by postural adaptation were indirectly assessed in 68 mild hypertensive subjects. Supine and upright plasma norepinephrine (NE), blood pressure (cuff) and cardiac output (acetylene rebreathing) were measured. Mean arterial pressure (MAP), carotid sinus pressure, stroke volume and systemic vascular resistance were calculated. Stroke volume was assumed to be proportional to the degree of stretch of cardiac mechanoreceptors, carotid sinus MAP was assumed to be proportional to carotid sinus stretch and plasma NE to reflect sympathetic nervous activity. Plasma NE correlated inversely with stroke volume (r = -0.62, p less than 10(-14] and estimated carotid sinus MAP (r = -0.33, p less than 0.0002) and positively with systemic vascular resistance (r = 0.59, p less than 10(-10]. Holding systemic vascular resistance constant by partial regression, the inverse relation between plasma NE and stroke volume remained (partial r = -0.36, p less than 0.02). Multiple linear regression yielded the equation: plasma NE (pg/ml) = 720 + 4.3 age - 5.1 stroke volume (ml) - 1.0 carotid sinus MAP (mm Hg). Substituting mean supine and upright values for stroke volume and carotid sinus MAP in this equation, it can be roughly estimated that changes in stroke volume account for as much as 60% of the postural variation in plasma NE in hypertensives, whereas only 15% of this variation is caused by changes in carotid sinus pressure. These findings suggest that cardiopulmonary baroreflexes are primary activators of the sympathetic nervous system during postural adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Hemodynamics of seasonal adaptation.

To investigate the possibility that seasonal adaptation requires significant hemodynamic changes, 5 normotensive and 21 mildly hypertensive subjects were followed through 4 seasons for changes in systemic hemodynamics and sympathetic nervous activity. In the upright position wintertime blood pressures increased by 3% (P = NS) over summer values whereas cardiac output and stroke volume decreased by 18% and 21%, respectively (P less than .0017 for each). Similarly, wintertime upright heart rate increased by 7% (P less than .017) with larger parallel increases in systemic vascular resistance (+24%, P less than .0017) and plasma norepinephrine (+26%, P less than .017). The supine values followed similar trends but the magnitude of changes was about 50% less than the corresponding upright values. Thus, in the northern US, wintertime vasoconstriction is related to increased sympathetic nervous activity and decreased cardiac output. When these reciprocal changes are proportional, blood pressure remains constant.

Adaptation, Physiological↗
PubMed1989

Potassium homeostasis during angiotensin-converting enzyme inhibition with enalapril.

The effect of angiotensin-converting enzyme (ACE) inhibition on renal and extrarenal potassium (K) regulation was examined. Six healthy men were studied in double-blinded crossover fashion on placebo or enalapril, 80 mg/day. On day 4, the subjects were given an intravenous infusion of KCl and on day 5 an oral dose of 10% NH4Cl. Treatment with enalapril decreased plasma aldosterone and increased plasma renin activity (PRA), epinephrine and norepinephrine, but did not affect serum glucose, plasma insulin or basal plasma K. Maximal increases in plasma K during K infusion or NH4Cl ingestion were similar during enalapril and placebo treatment. With enalapril treatment urinary K excretion was unchanged following K loading but moderately reduced following NH4Cl loading. We conclude that ACE inhibition does not acutely impair K homeostasis in men with normal renal function.

Adult↗
PubMed1989

Humoral effect of norepinephrine on renin release in humans.

We compared the effects of infused norepinephrine (NE) to another alpha-adrenergic agonist, phenylephrine, in order to understand better the influence of circulating NE on plasma renin activity (PRA) in man. In matched groups of normotensive men, NE (80 ng/min/kg) or phenylephrine (800 ng/min/kg) raised blood pressure by 15 to 20 mm Hg and caused reflex decreases in heart rate of 8 to 10 beats per minute. Infused phenylephrine suppressed PRA by about 15%, whereas NE increased PRA by about 40% (P less than .02). This differential effect of alpha-agonists on PRA defines an important humoral effect of NE, which should be considered to be a "cardiovascular hormone."

Blood Pressure↗
PubMed1989

Sympathoadrenal activity, catecholamines, and the pathogenesis of vasculopathic hypertensive target-organ damage.

In addition to the heart, the kidneys, eyes, and brain are the target organs of concern in people with hypertension. This review examines the evidence that damage to these organs can be grouped under the basic heading of hypertensive vasculopathy. The pathogenesis of hypertensive vasculopathy is incompletely understood, but probably involves both mechanical and humoral factors. The sympathoadrenal system and catecholamines have several potentially deleterious effects on large and small blood vessels and may promote thrombotic events. The hypothesis is put forward that norepinephrine is a major contributor to hypertensive vasculopathy and an overlooked cardiovascular risk factor. Choosing the optimal antihypertensive drugs may require considering the impact of the drugs on the sympathoadrenal system.

Adrenal Glands↗
PubMed1989

Influence of cadaveric organ source on delayed renal allograft function.

From 1984 to 1987, 110 locally retrieved cadaveric kidneys were transplanted into 108 local recipients, including 50 kidneys from multiple-organ retrieval (MOR) procedures and 60 from kidney-only (KO) donors. Conventional multiple organ retrieval technique, iced Euro-Collins storage, and cyclosporine-prednisone immunosuppression were employed. Delayed graft function (DGF), defined as dialysis dependence after transplantation, was twice as high in the MOR allografts as in the KO allografts, 46% vs. 22%, P less than 0.01. DGF was associated with longer hospitalization postoperatively and reduced eventual allograft function. The greater concordance of DGF in allograft pairs from the MOR group (25% vs. 7% in the KO group) and the increased incidence of DGF when more complex forms of MOR were used (40% with liver or heart retrieval, 55% with liver and heart retrieval) suggested that retrieval-related factors influenced allograft function. DGF in the MOR allografts was unrelated to other differences in donor, preservation, or recipient characteristics in the comparative groups. Unrecognized warm ischemia during conventional MOR is a plausible cause of DGF in kidneys from multiple-organ donors.

Adult↗