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Biomedical subjects

Joseph E Parrillo

Publications and source records attributed to Joseph E Parrillo.

45 records · Page 3Linked to original sources
PubMed2002

Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis.

OBJECTIVE: To determine whether activation of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS) contributes to mortality rate, myocardial dysfunction, and cardiovascular collapse in a porcine model of sepsis induced by implantation of an infected clot. DESIGN: Prospective, random animal study. SETTING: Research laboratory at Rush Presbyterian St. Luke's Medical Center. SUBJECTS: Twenty pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure, sonomicrometer crystals in the left ventricle to measure short axis diameter, an ultrasonic flow meter to measure cardiac output, and catheters in the pulmonary artery and aorta to measure blood pressures and collect samples. INTERVENTIONS: By using a randomized study design, we administered either the novel potent PARS inhibitor PJ34 (10 mg/kg for 1 hr, 2 mg x kg(-1) x hr(-1) for 96 hrs) or vehicle to pigs immediately before intraperitoneal implantation of Escherichia coli 0111.B4 (2.3 +/- 0.1 x 10(10) colony-forming units/kg)-laden fibrin clots to produce peritonitis and bacteremia. MEASUREMENTS AND MAIN RESULTS: In vehicle-treated pigs, 12% survival was recorded at 24 hrs, whereas 83% and 66% survival was recorded in the PJ34-treated animals at 24 and 96 hrs, respectively (p <.05). PJ34 treatment attenuated bacteremia-induced increases in systemic and pulmonary vascular resistances. In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha. PJ34 treatment significantly attenuated this cytokine response. The formation of peroxynitrite and the activation of PARS were confirmed in hearts and lungs of the septic pigs by the immunohistochemical detection of nitrotyrosine and poly(ADP-ribose), respectively. Inhibition of PARS with PJ34 abolished poly(ADP-ribose) formation in septic animals. CONCLUSIONS: Treatment with a potent PARS inhibitor improved survival and cardiovascular status and attenuated an important mediator component of the inflammatory response in a lethal porcine model of sepsis.

Animals↗
PubMed2002

Myocardial dysfunction in the patient with sepsis.

The nature of myocardial dysfunction during sepsis and septic shock has been investigated for more than half a century. This review traces the evolution of scientific thought regarding this phenomenon during this period with particular emphasis on the current understanding of both the clinical manifestations and the molecular/cellular basis of septic myocardial dysfunction in critically ill patients. Current data suggest, contrary to older literature, that patients with septic shock develop a hyperdynamic circulatory state after fluid resuscitation and maintain this hyperdynamic circulatory state until death or recovery. Overt myocardial depression, as manifested by decreased cardiac output, is decidedly uncommon, even in the preterminal phase. Nonetheless, myocardial depression, as evidenced by biventricular dilation and depression of the ejection fraction, can be demonstrated in most patients with septic shock by using either radionuclide cineangiography or echocardiography. Depression is reversible over the course of 7 to 10 days in survivors. Available evidence suggests that myocardial hypoperfusion is not responsible for septic myocardial depression, because examination of humans with septic shock demonstrates increased myocardial perfusion, and animal models of septic shock appear to maintain myocardial high-energy phosphates. A circulating factor or factors, including the cytokines tumor necrosis factor alpha and interleukin-1beta, appear to have a significant role in the phenomenon. In addition, septic myocardial depression appears to be mediated in part through combinations of nitric oxide-dependent and -independent alterations of basal and catecholamine-stimulated cardiac myocyte contractility.

Animals↗
PubMed2002

Coronary angiographic morphology in unstable angina: comparative observations of culprit lesions in saphenous vein grafts versus native coronary arteries.

GOAL: To compare angiographic characteristics of culprit lesions in saphenous vein grafts (SVG) with those in native coronary arteries (NCA) in patients presenting with unstable angina (UA). METHODS: Over 4 years, a total of 445 consecutive patients undergoing coronary angiography and percutaneous coronary intervention during hospitalization for UA were identified using a prospectively collected database. Patients with enzyme or electrocardiographic (ECG) evidence for acute myocardial infarction were excluded. Single culprit lesions in SVGs were identified by angiographic and ECG criteria in 214 patients and in NCAs in 231 patients. Culprit lesions were clearly identifiable by clinical and angiographic correlation in all cases. Morphologic analysis of the culprit lesions was performed using the Ambrose classification. RESULTS: The SVG group had male predominance (86.4% vs. 66.7%; p = 0001) and was older (67.3 +/- 9.9 years vs. 64.0 +/- 12.2 years; p = 0.0017) compared to the NCA group. Left ventricular ejection fraction was lower in the SVG group (53.8 +/- 15.5% vs. 57.5 +/- 15.2%; p = 0.063). There was a higher incidence of thrombotic-appearing lesions in SVG culprit lesions than in NCAs (31.3% vs. 6.5%; p = 0.001). There was also a higher incidence of ulcerated plaque in SVGs (36.9% vs. 22.1%; p = 0.001). Total occlusions were more common in NCAs (13.0% vs. 7.9%; p = 0.084). The composite incidence of thrombus, ulcerated plaque and total occlusion was more frequent in SVG lesions (59.4% vs. 39.8%; p = 0.001). CONCLUSIONS: In UA, culprit lesions of SVGs assessed angiographically demonstrate morphology consistent with ulcerated plaque and thrombus more frequently than lesions in NCAs, but total occlusions are more common in NCAs. Angiographically-evident active thrombotic and ulcerated lesions underlie acute ischemic syndromes more frequently in SVGs than in native vessels.

Age Factors↗
PubMedDate not supplied

The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium: a pilot study.

BACKGROUND: Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. METHODS: A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. RESULTS: A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed. Hibernating myocardium was demonstrated 4 weeks after ameroid placement by DSE. Coronary angiography demonstrated a discrete 90%stenosis in the proximal LAD at the site of ameroid constrictor placement without evidence of collaterals. Using PMR, 17 bursts were successfully delivered to the anterior wall distal to the ameroid constrictor. Four weeks after PMR, there was improvement in wall motion function in the region distal to the ameroid placement by echocardiography. Histopathologic analysis demonstrated the absence of myocardial infarction in the anterior wall distal to the ameroid constrictor. CONCLUSIONS: The performance of PMR in a porcine model of hibernating myocardium is feasible and is associated with an improvement regional wall motion function after 4 weeks.

Animals↗
PubMedDate not supplied

Risk stratification post-myocardial infarction: is early coronary angiography the more effective strategy?

The primary management strategy for the post-myocardial infarction patient continues to be controversial despite published guidelines. In part, this is the consequence of study designs that are not directly applicable to individual patients, but also to the rapidly changing pharmacological and mechanical device armamentarium that rapidly renders clinical trial results obsolete within a few years. This review attempts to highlight those areas where there is consensus as well as to explicate those situations where common clinical practice appears to be in conflict with accepted guidelines.

Acute Disease↗