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J E Parrillo

Publications and source records attributed to J E Parrillo.

At least 19 recordsLinked to original sources
PubMed2001

Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death.

BACKGROUND: Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. METHODS AND RESULTS: Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly. CONCLUSIONS: Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.

Acetylcholine↗
PubMed2001

Endothelial- and nitric oxide-dependent effects on oxidative metabolism of intact artery.

Oxidative metabolism and its possible modulation by nitric oxide (NO) was examined in endothelial-intact and endothelial-denuded segments of porcine carotid arteries. Endothelial-intact arteries displayed appropriate NO-mediated vasorelaxation to acetylcholine (ACh). Endothelial-denuded arteries demonstrated absent vasorelaxation to ACh stimulation and depressed contractile responsiveness to K(+) depolarization, which was normalized by inhibition of NO synthesis by N(omega)-nitro-L-arginine methylester (L-NAME). Confirmation that carotid arteries continued to produce NO despite removal of the endothelium was indicated by detection of NO metabolites in the incubation medium bathing the arteries. O(2) consumption and the oxidation of glucose and fatty acid were depressed in endothelial-denuded arteries. Depression of O(2) consumption and glucose oxidation was completely reversed by treatment with L-NAME. We conclude that endogenous NO produced by non-endothelial vascular cells depresses contractility, O(2) consumption, and oxidation of energy substrates in vascular smooth muscle. The endothelium may play a role in oxidative metabolism of vascular smooth muscle possibly by modulating the effects of NO produced by other cells of the vessel wall, or by other factors.

Acetylcholine↗
PubMed2001

Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography.

A small animal model of sepsis that reproduces the vasodilation, hypotension, increased cardiac output, and response to treatment seen in patients with septic shock would be useful for studies of pathophysiology and treatment, but no current models replicate all of these features. Mice were made septic by cecal ligation and puncture and resuscitated with fluids and antibiotics every 6 h. Blood pressure was measured in anesthetized mice with manometric catheters, and echocardiography was performed in these animals every 6 h. Survival in treated septic mice was improved compared with untreated mice (44% versus 0%, p < 0.01). In control mice, heart rate (HR, 420 +/- 31 beats/min), mean arterial pressure (Pa, 100 +/- 8 mm Hg), stroke volume (SV, 26 +/- 4 microl), and cardiac output (12.5 +/- 6.6 ml/min) were unchanged over 48 h. In septic mice Pa was significantly decreased (102 +/- 14 to 65 +/- 19 mm Hg, p < 0.02), starting at 12 h. HR and cardiac output increased significantly (HR, 407 +/- 70 to 524 +/- 76 beats/min, cardiac output, 11.6 +/- 2.0 to 17.1 +/- 1.5 ml/min, p < 0.01). SV (24 +/- 5 microl) remained constant. This fluid-resuscitated, antibiotic-treated model replicates the mortality, hypotension, and hyperdynamic state seen in clinical sepsis. Precise determination of serial hemodynamics in this model may be useful to elucidate pathophysiologic mechanisms and to evaluate new therapies for septic shock.

Animals↗
PubMed2001

Assessing coronary blood flow dynamics with the TIMI frame count method: comparison with simultaneous intracoronary Doppler and ultrasound.

This study compared the TIMI frame count (TFC), which has been proposed as a method for quantifying coronary blood flow, with coronary flow and microvascular function measured with intracoronary Doppler and intracoronary ultrasound. Coronary blood flow volume was calculated from coronary blood velocity (by intracoronary Doppler) and lumen area (by intracoronary ultrasound) in the LAD in 46 post-heart transplant patients at baseline and after intracoronary adenosine. TFC correlated significantly with average peak coronary blood velocity (r = -0.42; P = 0.004) and coronary lumen area (r = 0.39; P = 0.008), but not with coronary blood flow volume (r = -0.01; P = 0.96) or the coronary flow reserve response to adenosine (r = 0.09; P = 0.58). In conclusion, TFC is a simple method of assessing coronary blood velocity but not volumetric flow. While TFC does not predict coronary flow reserve, as a measure of velocity it does provide an assessment of basal microvascular tone, information that is complementary to that afforded by flow reserve measurements.

Adult↗
PubMed2001

Evidence of transcellular permeability pathway in microvessels.

We used video fluorescence microscopy of the vascular bed in the cremaster muscle of rat and mouse to study the transfer of plasmalemma vesicles (caveolae) across the microvessel barrier in situ. The water-soluble styryl pyridinium dye RH414, which adsorbs to and fluoresces at the membrane-water interface, was used as a marker for vesicular traffic through endothelial cells. Fluorescein isothiocyanate (FITC), similar in molecular size to the styryl pyridinium probe, was used to mark for dye transfer by the paracellular pathway. Transcellular dye flux was determined by comparing the fluorescence intensities of RH414 and FITC on either side of the vessel wall (i.e., in microvessel lumen and in muscle tissue at various distances from the microvessel wall). We observed that RH414 accumulated in the interstitium more rapidly than FITC. We next studied the role of the 60-kDa albumin-binding glycoprotein gp60, hypothesized to activate transcellular permeability, in stimulating the transcellular vesicle traffic. Introduction of anti-gp60 antibody into the microvessel to cross-link and activate gp60 markedly increased the transvascular flux of RH414. Control isotype-matched antibody had no effect on the RH414 flux. The sterol-binding agent filipin, which disassembles caveolae, inhibited the RH414 flux induced by gp60 cross-linking. The transfer of styryl pyridinium dyes in intact microvessels suggests that plasmalemmal membrane traffic across the skeletal muscle microvessel barrier is a constitutively active process. The results indicate that the gp60-dependent pathway is important in regulating endothelial permeability in situ via a transcellular mechanism.

Animals↗
PubMed2001

The contemporary management of acute myocardial infarction.

The contemporary management of acute myocardial infarction continues to evolve rapidly. The ultimate goal of therapy is timely, complete, and sustained myocardial reperfusion. There is a powerful time-dependent effect on mortality, and thus the balance between the time and likelihood of maximal reperfusion is crucial in deciding whether to use primary percutaneous balloon angioplasty or thrombolysis as the initial reperfusion strategy. Newer thrombolytic agents allow for equivalent coronary reperfusion compared with the standard accelerated alteplase (tPA) regimen with the advantage of easier dosing regimens. Low molecular weight heparin has been shown to be superior to unfractionated heparin and likely will be the standard of care in the near future. The use of glycoprotein IIb/IIIa inhibitors has been shown to decrease the short- and long-term complication rates in patients with acute coronary syndromes treated medically and with percutaneous coronary interventions; however, the choice of the optimal agent and dosing regimen in various clinical settings remains controversial. Combination therapy with low-dose fibrinolytics, glycoprotein IIb/IIIa inhibitors, and low molecular weight heparin, with or without subsequent early planned percutaneous coronary interventions, may provide the optimal strategy for maximal coronary reperfusion, but the results of large, randomized mortality trials currently underway need to be analyzed. Risk stratification will continue to play a major role in determining which patients should receive a specific therapy. The care of the patient with an acute myocardial infarction will continue to be a challenge requiring the proper selection from the vast pharmaceutic and interventional options available.

Angina, Unstable↗
PubMed2001

Electrocardiographic diagnosis of acute myocardial infarction: Current concepts for the clinician.

BACKGROUND: Over the past 2 decades, the 12-lead electrocardiogram has attained special significance for the diagnosis and triage of patients with chest pain because timely detection of myocardial injury and a rapid assessment of myocardium at risk proved pivotal to implementing effective reperfusion therapies during acute myocardial infarction. However, this wealth of information could still be underutilized by clinicians who may restrict their diagnostic quest in patients with chest pain to the more classic electrocardiographic signs. METHODS: The medical literature on electrocardiographic manifestations of acute myocardial infarction was extensively reviewed. RESULTS: The widespread utilization of both coronary angiography and methods to determine myocardial function and metabolism in patients with acute myocardial infarction over the last 10 years has provided the means for rigorous comparisons with electrocardiographic information. We summarize these electrocardiographic signs and patterns in terms of their relevance to the clinician to help reduce the incidence of "nondiagnostic electrocardiograms" and improve timely decision-making. CONCLUSIONS: The electrocardiogram continues to be an invaluable tool in the initial evaluation of patients with chest pain. The plethora of data currently available on electrocardiographic changes correlating with myocardial injury allows clinicians to make faster and better decisions than ever before.

Bundle-Branch Block↗
PubMed2000

Validated risk stratification model accurately predicts low risk in patients with unstable angina.

BACKGROUND: In the mid 1990s, two unstable angina risk prediction models were proposed but neither has been validated on separate population or compared. OBJECTIVES: The purpose of this study was to compare patient outcome among high, medium and low risk unstable angina patients defined by the Agency for Health Care Policy and Research (AHCPR) guideline to similar risk groups defined by a validated model from our institution (RUSH). METHODS: Four hundred sixteen patients consecutively admitted to the hospital with unstable angina between January 1, 1995, and December 31, 1997, were prospectively evaluated for risk factors. The presence of major adverse events such as myocardial infarction (MI), death and heart failure was assessed for each patient by chart review. RESULTS: The composite end point of heart failure, MI or death occurred in 3% and 5% of the RUSH and AHCPR low risk categories, respectively, and in 8% and 10% of AHCPR and RUSH high risk categories, respectively. Recurrent ischemic events were best predicted by the RUSH model (high: 24% vs. medium: 12% and low: 10%, p = 0.029), but not by the AHCPR model (high: 14% vs. medium: 13% and low: 9%, p = 0.876). The RUSH model identified five times more low risk patients than the AHCPR model. CONCLUSIONS: Both models identify patients with low and high event rates of MI, death or heart failure. However, the RUSH model allowed for five times more patients to be candidates for outpatient evaluation (low risk) with a similar observed event rate to the AHCPR model; also, the RUSH model more successfully predicted ischemic complications. We conclude that the RUSH model can be used clinically to identify patients for early noninvasive evaluation, thereby improving cost effectiveness of care.

Aged↗
PubMed2000

Effect of serum albumin on vascular smooth muscle metabolism.

In studies on metabolism of vascular smooth muscle, it was observed that incubation of intact porcine carotid artery strips with 3% bovine or porcine serum albumin had profound effects on the oxidation of substrates and O2 consumption. Arteries incubated over 180 min with charcoal-treated and dialyzed albumin demonstrated time-dependent stimulation of glucose oxidation (145%; P < 0.0001, n=6) and O2 consumption (116%; P< 0.001, n=6). These results were not mimicked by incubation with 3% solutions of ovalbumin or porcine skin gelatin. However, the oxidation of the medium chain fatty acid octanoate was inhibited in the presence of albumin over a broad range of octanoate concentrations (0.5-5.0 mM). Short chain fatty acid oxidation (acetate, 5 mM), in contrast, was not inhibited by albumin. Wash-out of albumin only partially reversed the stimulation of O2 consumption and incubation of arteries with a polyanionic compound, polyethylene sulfonate (5 mg/ml), blunted the stimulatory effect of albumin on O2 consumption. Albumin also produced anaplerosis of the Krebs cycle, and an increase in the content of glutamate and alanine (P < 0.005, n=8). The metabolic effects of albumin were associated with time-dependent uptake of albumin (30.9 +/- 1.5 nmol/g per 210 min; P<0.01, n=15). ATP-dependent proteolysis of the albumin taken up was also observed. These results demonstrate novel and important intracellular effects of serum albumin on energy metabolism of vascular smooth muscle.

Acetates↗
PubMed2000

Increased microvascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase.

Persistent vasodilation characteristic of septic shock may result from overproduction of nitric oxide and can lead to pressor-refractory hypotension and death. To evaluate the significance of cytokine-inducible nitric oxide synthase (iNOS) in the pathogenesis of sepsis, we used a clinically relevant mouse model of sepsis and compared mortality and microvascular reactivity in wild-type (WT) mice and transgenic mice deficient in iNOS. WT C57BL/6 and iNOS-deficient mice were made septic by cecal ligation and puncture. Treated mice were given fluids and antibiotics every 6 hours. Microvascular vasoconstriction in response to topical norepinephrine was measured in cremasteric arterioles (15 to 30 microm) by videomicroscopy. Mortality at 48 hours was significantly lower in treated septic iNOS-deficient mice (45%) than in treated septic WT mice (76%), untreated septic iNOS-deficient mice (87%), or untreated WT mice (100%) (P<0.01). Norepinephrine-induced vasoconstriction was decreased in WT septic mice (EC(50) 200+/-56 nmol/L) compared with WT and iNOS-deficient shams (16+/-4 and 13+/-6 nmol/L), and vasoconstriction was significantly improved in septic iNOS-deficient mice (35+/-13 nmol/L, P<0.01). Microvascular catecholamine responsiveness and survival were improved in iNOS-deficient mice in a clinically relevant model of sepsis, suggesting that iNOS plays an important, but not exclusive, role in refractory vasodilation in patients with septic shock.

Animals↗
PubMed2000

Utilization of coronary angiography and revascularization after acute myocardial infarction in men and women risk stratified by the American College of Cardiology/American Heart Association guidelines.

OBJECTIVES: We sought to determine whether men and women are equally likely to receive coronary angiography and revascularization after acute myocardial infarction (AMI) when they are risk stratified according to American College of Cardiology/American Heart Association (ACC/AHA) practice guidelines for post-MI care. BACKGROUND: Several previous studies have suggested that women may undergo angiography and revascularization procedures less frequently than men. METHODS: In 439 consecutive patients admitted to a public hospital with AMI, rates of coronary angiography and revascularization were compared in men and women categorized, according to ACC/AHA practice guidelines, as having strong (class I or IIa) or weaker (class IIb) indications for angiography. RESULTS: Women were older and more likely to be diabetic or hypertensive, but men and women were equally likely to meet class I/IIa criteria for post-MI angiography (both 51%). Angiography rates were nearly identical in men and women overall (63% vs. 64%), as well as in patients in class I/IIa (80% vs. 82%) and class IIb (46% vs. 46%) (all p > 0.80, with >80% power to detect important differences); the only multivariate predictors of post-MI angiography were age and ACC/AHA class. Significant coronary artery disease was equally prevalent in men and women undergoing angiography, and men and women were equally likely to undergo revascularization, whether they were in class I/IIa (both 55%, p = 0.90) or class IIb (59% vs. 58%, p = 0.88). No significant differences in mortality were noted between men and women. CONCLUSIONS: Despite being older and having more risk factors than men, women were equally likely to undergo coronary angiography and revascularization procedures after AMI, and they had in-hospital clinical outcomes that were at least as favorable.

Adult↗