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Biomedical subjects

G C Friesinger

Publications and source records attributed to G C Friesinger.

At least 19 recordsLinked to original sources
PubMed1992

Studies of Left Ventricular Dysfunction (SOLVD) Registry: rationale, design, methods and description of baseline characteristics.

The Studies of Left Ventricular Dysfunction (SOLVD) comprises 2 double-blind, randomized clinical trials to test improved survival by angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction, with or without congestive heart failure. Patients entering the trials may be a highly selected subset of the population of such patients; those with the worst and best prognosis are likely to be excluded. To obtain the clinical history of a broader group, a registry of 6,273 patients included a relatively unselected cohort of patients with heart failure or left ventricular dysfunction, or both, from SOLVD hospitals. Registry data were obtained from hospital records. Because data collection from medical records may lead to incomplete data and more investigations in "sicker" patients, 898 randomly chosen subjects from different disease strata were seen in clinic where neurohumoral measures, echocardiograms, x-rays and electrocardiograms were obtained, and a 6-minute walking test was performed. The design and methodologic features, and the baseline characteristics of the participants in this 2-tiered registry are described, and its use in complementing the results and interpretation of the SOLVD trials is discussed.

Adult↗
PubMed1992

Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction.

BACKGROUND: There is a lack of consensus among cardiologists about the potential benefit of thrombolytic therapy for suspected acute myocardial infarction in older patients. To investigate this issue, we constructed a decision-analytic model for patients 75 years of age or older who present with ST-segment elevation within six hours of the onset of symptoms suggesting acute myocardial infarction. METHODS: The variables incorporated in this model were the probability that the patient has an acute myocardial infarction, the probability of in-hospital death among patients with acute myocardial infarction who do not receive thrombolytic therapy, the probability of a fatal or incapacitating complication resulting from thrombolytic therapy, and the expected relative reduction in the risk of death associated with thrombolytic therapy in patients with acute myocardial infarction. Our analyses were based primarily on the use of streptokinase as the thrombolytic agent. RESULTS: Given our base-line assumptions, the probability of dying in the hospital was 21.4 percent if thrombolytic therapy was given and 24.4 percent if it was not given. In one-way sensitivity analyses, thrombolytic therapy decreased the risk of dying if the probability that the patient had an acute myocardial infarction was assumed to be greater than 9 percent, if the probability of dying in the hospital after an acute myocardial infarction without thrombolytic therapy was assumed to be greater than 3 percent, if the rate of fatal or incapacitating complications due to thrombolytic therapy was assumed to be 4 percent or less, or if the relative reduction in the risk of death associated with thrombolytic therapy was assumed to be greater than 1 percent. On the basis of our base-line assumptions, our estimate of the cost effectiveness of streptokinase therapy (the cost per year of life saved) for an 80-year-old patient with suspected acute myocardial infarction was $21,200. For a wide range of assumptions about risks, benefits, and costs, the cost per year of life saved remained less than $55,000. CONCLUSIONS: Within the limitations imposed by the assumptions used in our analysis, thrombolytic therapy with streptokinase was found to be a beneficial and cost-effective treatment for suspected acute myocardial infarction in elderly patients in a wide variety of clinical circumstances.

Age Factors↗
PubMed1991

Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction.

Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1990

Ethics in cardiovascular medicine. Task Force IV: Scientific responsibility and integrity in medical research.

Ethical standards are a set of affirmative responsibilities to which the investigator must subscribe; behavior that is incompatible with these responsibilities should be presumed unethical, whether or not it is explicitly proscribed. This Task Force sought to present these standards as principles or guidelines. In undertaking research an investigator must accept that publicly funded or supported research is intended to yield public benefit; personal gain should be only incidental to and not at the expense of the public benefit. The responsibilities of the investigator are summarized as follows: Design of Research To develop a research design that effectively and efficiently addresses the scientific question while minimizing the likelihood of incorrect or misleading results. To protect the rights and welfare of human subjects, assure the humane use of laboratory animals and protect the safety of laboratory workers and the environment. Conduct of Research To ensure that accepted laboratory and research practices are followed and that all data are accurately collected and properly recorded; the investigator must participate in the review of original data. To carry out research in accordance with that approved by the institutional review board and ensure that fully informed consent is obtained, that the welfare of human subjects is protected and that animal welfare and laboratory safety procedures are carried out. To provide effective ongoing supervision of research trainees and technicians. In multidisciplinary collaborative research, to have at least an overview familiarity with the work outside his or her areas of expertise. In fixed protocol, multicenter collaborative research the investigator must be satisfied with the adequacy of the collaborative activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomedical Research↗
PubMed1989

Effects of methoxamine and phenylephrine on left ventricular contractility in rabbits.

The end-systolic pressure-volume relation is employed to evaluate left ventricular contractility. In clinical studies, pharmacologic vasoconstriction is used to increase left ventricular systolic pressure to assess pressure-volume relations. However, the effect of vasoconstrictors on the ventricular contractile state is not well characterized. The effects of methoxamine and phenylephrine on systemic arterial pressure and left ventricular contractility in rabbits were studied with three protocols. In protocol 1, anesthetized rabbits (n = 10) were injected with incremental doses of methoxamine and phenylephrine intravenously. Methoxamine (4 mg) increased the mean arterial pressure by 50 +/- 12% (mean +/- SE) (n = 5, p = 0.001). Phenylephrine (0.2 mg) increased mean arterial pressure by 82 +/- 14% (n = 5, p = 0.004). In protocol 2, isolated blood-perfused hearts were injected with incremental doses of these drugs in the ascending aorta in amounts approximately equal to the concentrations injected in the intact rabbits. Methoxamine (2 mg) reduced isovolumic peak systolic left ventricular pressure by 43 +/- 9% (n = 7, p = 0.003), whereas phenylephrine (0.1 mg) increased the isovolumic pressure by 24 +/- 9% (n = 7, p less than 0.05). These responses indicated an enhanced contractile state with phenylephrine and a reduced contractile state with methoxamine. Pretreatment with propranolol blunted the effect of phenylephrine on isovolumic pressure (n = 6, p less than 0.02). In protocol 3, cross-circulation experiments allowed study of the effect of these drugs on isovolumic left ventricular pressure in the isolated heart and simultaneously on the systemic arterial pressure in the intact anesthetized rabbit (support rabbit).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Intrinsic left ventricular contractility in normal subjects.

The influence of autonomic tone on left ventricular (LV) contractility, along with the range of normal values and the effects of exercise on contractile state, were studied in 12 normal volunteers. Serial reproducibility was examined in a subgroup of 6. LV contractility was estimated by the LV peak-systolic pressure to end-systolic volume relation (pressure-volume relation), and the ratio of peak-systolic pressure to end-systolic volume (pressure/volume ratio). The cuff blood pressure and radionuclide ventriculogram were recorded at rest, during exercise and during pharmacologic pressure-afterloading with phenylephrine, before and after vagal and beta-adrenergic "blockade." Both the pressure/volume ratio and ejection fraction increased during the stimulus of exercise (both p less than or equal to 0.008). After blockade, the pressure-volume relations were highly linear (r = 0.95 +/- 0.05 [standard deviation], n = 12), and there was no systematic difference in their slopes induced by blockade. The serial studies of pressure-volume relations showed no significant differences. The results demonstrated that vagal and sympathetic tone were not important in the support of LV contractility in normal subjects at rest, and that the pressure-volume relation and pressure/volume ratio are reproducible between studies. Also, the findings confirmed that both the pressure/volume ratio and the ejection fraction were sensitive to exercise-induced changes in contractility. This demonstration of intrinsic LV contractility in normal subjects, plus the reproducibility of the measurements, supports the feasibility of serial study of LV contractility.

Adult↗
PubMed1987

Right ventricular hypertrophy is an important determinant of right ventricular infarction complicating acute inferior left ventricular infarction.

To explore the role of right ventricular hypertrophy and chronic obstructive pulmonary disease in the pathogenesis of right ventricular infarction, 27 consecutive patients with a first inferior left ventricular infarction were prospectively studied. Right ventricular infarction was diagnosed using established hemodynamic criteria. Right ventricular hypertrophy was defined as right ventricular free wall thickness greater than or equal to 5 mm. Patients were classified into two groups: Group I patients with right ventricular infarction (n = 15), and Group II patients without right ventricular infarction (n = 12). The ratio of forced expiratory volume over forced vital capacity (FEV1/FVC) and forced expiratory flow between 25 and 75% expired volume (FEF) as a percent of predicted values were significantly reduced in Group I versus Group II (90 +/- 5 versus 105 +/- 6% and 63 +/- 13 versus 103 +/- 15%, respectively; p less than 0.05). This was associated with increased right ventricular wall thickness (Group I 5.5 +/- 0.3 mm versus Group II 3.9 +/- 0.2 mm, p less than 0.001). Multiple logistic regression analysis demonstrated that right ventricular wall thickness was the strongest predictor of right ventricular infarction (p less than 0.0005). No significant difference was found in the site of right coronary occlusion, collateral blood supply or extent of coronary artery disease between the two groups. These findings suggest that right ventricular hypertrophy predisposes patients with acute inferior myocardial infarction to right ventricular infarction independent of the site or extent of coronary artery disease.

Adult↗
PubMed1987

Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model.

The administration of a drug soon after reperfusion that could enhance myocardial salvage would have important clinical application. The aim of this study was to assess the long-term effect of the perfluorochemical, Fluosol DA 20%, on infarct size, infarct morphology, ventricular ectopic activity and serial regional ventricular function in a 2 week closed chest canine model. After 90 minutes of proximal left anterior descending artery occlusion, animals randomly received either oxygenated Fluosol DA (n = 9) or saline solution (n = 9) intracoronary at 15 ml/kg body weight over 20 to 30 minutes. Hemodynamic variables were similar in the two groups except for transient elevation of left ventricular filling pressure immediately after infusion in the treated group. Infarct size was markedly reduced in the perfluorochemical-treated animals when expressed as a percent of the risk region (10.8 +/- 1.8% versus 28.9 +/- 5.5%, p less than 0.02) or as a percent of the total left ventricle (3.7 +/- 1% versus 10.8 +/- 8%, p less than 0.006). This was associated with greater improvement in radial shortening in the jeopardized zone at 2 weeks after reperfusion (15.3 +/- 2.8% versus 5.2 +/- 2.1%, p less than 0.01). Histologic examination revealed adequate healing in the treated animals with an increased number of swollen mononuclear cells in the border zones. Holter electrocardiographic recordings demonstrated a low frequency of ventricular ectopic beats in both groups. This study suggests that the perfluorochemical, Fluosol DA, may be a potentially useful agent in enhancing myocardial salvage after successful reperfusion.

Animals↗
PubMed1987

Fungal endocarditis complicating treatment of prosthetic valve bacterial endocarditis: value of prophylactic oral nystatin.

We describe two patients in whom fungal endocarditis occurred during antibiotic therapy for prosthetic valve bacterial endocarditis. Successful management of both patients was eventually achieved with antifungal therapy and replacement of the prosthetic valves. These cases and review of the literature suggest that (1) high-dose antibacterial therapy predisposes to fungal endocarditis; (2) during prolonged antibiotic therapy in patients predisposed to endocarditis, clinicians should consider the use of oral nystatin as prophylaxis against fungemia and possible fungal endocarditis; and (3) early replacement of prosthetic valves infected with fungi is indicated because chemotherapy alone is predictably inadequate to effect a cure.

Adult↗
PubMed1987

Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.

To explore the role of oxygen free radicals produced by the xanthine oxidase pathway on infarct size and left ventricular function, the effect of oxypurinol, an active metabolite of allopurinol and a potent noncompetitive inhibitor of xanthine oxidase, was assessed in a 90 min, closed-chest, canine preparation of occlusion-reperfusion. Animals were randomized to receive 25 mg/kg iv oxypurinol (n = 13) or saline (n = 13) 60 min after occlusion. Regional myocardial blood flow was measured with radioactive microspheres and regional ventricular function with contrast ventriculography. Hemodynamic variables, regional myocardial blood flow, and size of the occluded bed were similar in the two groups. Oxypurinol failed to reduce infarct size 24 hr after reperfusion when expressed as a percentage of the area at risk (36.3 +/- 4.9% vs 36.0 +/- 5.6%; p = NS). Both groups exhibited comparative radial shortening at baseline and similar degrees of dyskinesia 1 hr into occlusion (-6.6 +/- 1.2% vs -4.9 +/- 1.0%). However, oxypurinol-treated animals demonstrated an improved regional ventricular function at 3 hr after reperfusion (0.7 +/- 2.6% vs -2.8 +/- 2.0%) and a significant improvement at 24 hr (5.4 +/- 2.5% vs -3.2 +/- 1.7%; p less than .05). A reduced neutrophil infiltrate was observed in the border zone in treated animals. These findings suggest that oxygen free radicals derived from the xanthine oxidase pathway contribute to stunning of reversibly damaged myocardium but do not determine the final extent of myocardial necrosis in a canine preparation of reperfusion.

Animals↗
PubMed1987

Reduction of reperfusion injury in the canine preparation by intracoronary adenosine: importance of the endothelium and the no-reflow phenomenon.

We hypothesized that the endogenous coronary vasodilator adenosine may reduce infarct size by progressively increasing reflow in a preparation of coronary occlusion-reperfusion. After 90 min of proximal left anterior descending artery occlusion, 20 dogs were randomized to blood reperfusion with (n = 10) or without (n = 10) adenosine into the proximal left anterior descending vessel at 3.75 mg/min for 60 min after reperfusion. Regional myocardial blood flow was determined serially with microspheres and regional ventricular function was assessed by a computerized radial shortening method. At 24 hr, the area at risk was defined in vivo with monastral blue dye and area of necrosis was determined after incubation of left ventricular slices in triphenyltetrazolium chloride. Hemodynamic variables were similar in the two groups during the experimental protocol. Infarct size was significantly reduced in treated animals, both when expressed as a percentage of the area at risk (9.9 +/- 2.8% vs 40.9 +/- 6.6%, p less than .001) and as a percentage of the left ventricle (4.6 +/- 1.3% vs 18.0 +/- 3.4%, p = .002). This was associated with significant improvement in radial shortening in the ischemic zone 24 hr after reperfusion (10.1 +/- 2.5 vs -2.8 +/- 2.2%, p less than .01). Regional myocardial blood flow was significantly increased in endocardial and epicardial regions from the lateral ischemic zone 1 hr after reperfusion in adenosine-treated animals. Light microscopy demonstrated decreased neutrophil infiltration in the ischemic zone and electron microscopy showed relative preservation of endothelial structure in the subendocardium with reduced neutrophil and red cell stagnation of capillaries in the treated group. These findings suggest that intracoronary administration of adenosine after reperfusion significantly reduces infarct size and improves regional ventricular function in the ischemic zone in the canine preparation.

Adenosine↗
PubMed1986

Determinants of left ventricular aneurysm formation after anterior myocardial infarction: a clinical and angiographic study.

To determine factors involved in left ventricular aneurysm formation after transmural anterior myocardial infarction, 79 patients with a first myocardial infarction who underwent cardiac catheterization within 6 months of infarction were evaluated. Patients who had received thrombolytic therapy were excluded. Patients were divided into four groups depending on the status of the left anterior descending artery and the presence or absence of a left ventricular aneurysm: Group I (n = 25): aneurysm with occluded left anterior descending artery; Group II (n = 27): no aneurysm and occluded left anterior descending artery; Group III (n = 23): no aneurysm and patent left anterior descending artery; and Group IV (n = 4): aneurysm with patent left anterior descending artery. Single vessel disease was more common in Group I (aneurysm) compared with Groups II and III (no aneurysm) (chi 2(4) = 12.8; probability value equal to 0.012). Collateral blood supply in the presence of an occluded left anterior descending artery was significantly less in Group I (aneurysm) compared with Group II (no aneurysm) (0.9 versus 2.4, p less than 0.001). The extent of coronary artery disease and collateral blood supply in Groups I and II were directly related (p = 0.012). Neither age, sex nor risk factors for coronary disease correlated with aneurysm formation. At a mean follow-up of 48 months, no differences were observed in the incidence of recurrent angina, new myocardial infarction, embolic events or sudden death. More patients in Group II underwent coronary artery bypass surgery. Total occlusion of the left anterior descending artery in association with inherent poor collateral blood supply is a significant determinant of aneurysm formation after anterior myocardial infarction. Multivessel disease with either good collateral circulation or a patent left anterior descending artery is uncommonly associated with the development of left ventricular aneurysm.

Angiography↗
PubMed1986

A new model to study quantitative effects of laser angioplasty on human atherosclerotic plaque.

A new model for analyzing the major effects of the use of any laser angioplasty system is described. Changes in any of the six major determinants of effect (energy, duration, wavelength, medium, absorption, geometry) can be evaluated. In this report a neodymium: yttrium aluminum garnet (Nd:YAG) laser was used to make 408 laser exposures in vitro on segments of human cadaveric atherosclerotic aorta. Energy, medium (air, human blood, perfluorochemical and saline), geometry and duration were varied. The depth and width of the resultant plaque craters were measured. A large amount of exposure to exposure variability was found in all groups of experiments, even when conditions were held as constant as possible in this rigidly controlled laboratory setting. This variability is attributable to differences in energy absorption by the plaque. Changes in media and fiber optic tip to plaque distance also markedly altered exposure outcome. For example, the average depth of the hole created by a 15 W, 2 second blast with the fiber tip adjacent to the plaque in blood was 1.7 +/- 0.1 mm (n = 27), but the range was between 0.5 and 2.7 mm. Under the same conditions, except with the fiber tip 1 mm away from the plaque, the average hole depth was 0.4 +/- 0.1 mm (n = 12) and the range was 0.0 to 1.7 mm. The use of this model to analyze the major determinants of lasing effects in different laser angioplasty systems should help to select the best conditions for lasing and allow assessment of the variability of outcome.

Aorta, Abdominal↗