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Biomedical subjects

G H Mudge

Publications and source records attributed to G H Mudge.

At least 55 records · Page 3Linked to original sources
PubMed1985

Attenuation of coronary vascular resistance by selective alpha 1-adrenergic blockade in patients with coronary artery disease.

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phentolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha 1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 +/- 5 beats/min (+/- 1 SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 +/- 4% (102 +/- 14 to 111 +/- 14 mm Hg, p less than 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 +/- 19% (1.02 +/- 0.46 to 1.15 +/- 0.57 units, p less than 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 +/- 5% (p less than 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 +/- 11%, p = NS), which was significantly less than before trimazosin (p less than 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha 1-receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1985

Comparative costs versus symptomatic and employment benefits of medical and surgical treatment of stable angina pectoris.

For patients who underwent cardiac catheterization for stable angina pectoris at the authors' hospital, initial treatment charges including the cardiac catheterization were approximately $28,000 for coronary surgery and $6,000 for medical therapy. Even after controlling for disease severity and after including medical patients who crossed over to surgery, the slightly increased 3-year follow-up costs of medical therapy offset only approximately 11% of the far higher initial costs of surgery. Surgical patients were more likely to have sustained, substantial symptomatic improvement at 3 years (68% vs. 53%, P less than 0.05) but were no more likely to have, maintain, or regain a job. Although the cost-effectiveness of coronary surgery may compare favorably with other modern therapies for other conditions, coronary surgery did not pay for itself at 3-year follow-up in our patients.

Angina Pectoris↗
PubMed1984

Effects of prostacyclin on coronary hemodynamics at rest and in response to cold pressor testing in patients with angina pectoris.

To assess the effect of prostacyclin on the diseased coronary circulation basally and, in particular, on the coronary responses to the cold pressor test, a small dose of 4 ng/kg/min and a large dose of 8 to 10 ng/kg/min was infused in 11 patients with stable angina pectoris. Coronary blood flow was measured by coronary sinus thermodilution technique. The mean blood pressure decreased from 97 +/- 5 to 89 +/- 5 mm Hg during the low-dose infusion (p less than 0.005) and to 81 +/- 5 mm Hg during the high-dose infusion (p less than 0.001); the heart rate increased from 65 +/- 4 to 69 +/- 4 beats/min during the low-dose infusion (p less than 0.05) and to 78 +/- 5 beats/min during the high-dose infusion (p less than 0.001). Systemic vascular resistance decreased by 11 +/- 4% with small doses (p less than 0.05) and by 38 +/- 4% with large doses (p less than 0.001) of prostacyclin, and coronary vascular resistance decreased by 16 +/- 7% (p less than 0.05) with the small dose and by 29 +/- 6% (p less than 0.001) with the large dose of prostacyclin. Seven of 11 patients showed a baseline vasoconstrictor response to the cold pressor test (increase in coronary vascular resistance of 11 +/- 2%). This increase in coronary vascular resistance was not altered by either the small or the large dose of prostacyclin. Thus, prostacyclin causes marked coronary and systemic vasodilation, with no evidence of selective enhancement of the sensitivity of the diseased coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Giant cell myocarditis after mitral valve replacement: case report and studies of the nature of giant cells.

A 22-year-old man with Marfan's syndrome and a history of antinuclear antibody-positive hepatitis died 25 days after undergoing cardiac valve replacement surgery for mitral valve prolapse. Giant cell myocarditis was found at autopsy. The multinucleated giant cells were shown by immunoperoxidase techniques to contain lysozyme, but not myosin or creatine phosphokinase, suggesting that they were derived from macrophage, rather than myocyte, precursors.

Adult↗
PubMed1984

The selective impact of a cardiology data bank on physicians' therapeutic recommendations.

We asked the physicians and medical students caring for 60 patients with symptomatic coronary artery disease, immediately after reviewing cardiac catheterization data, to choose medical or surgical therapy and to estimate prognosis one and three years after either therapy. The next day, each participant was given prognostic estimates generated from a large coronary artery disease data bank and again asked to estimate prognosis and choose therapy. Participants unanimously chose medicine for 20 patients (Group I) and surgery for 21 patients (Group III). For 19 patients (Group II), participants were divided on their choice of therapy. After seeing data bank estimates, participants rarely changed recommendations for Group I or Group III, but changed ten percent (9/90, p less than 0.01) of their Group II recommendations. Changes of recommendations by far (9/12, p = 0.02) favored medicine, causing the majority recommendation to change to medicine for two Group II patients. Therapeutic recommendations were guided mostly by pathoanatomy and the chance of improving medical regimens. Computer-generated prognostic data selectively influenced choices among the Group II cases where recommendations had been divided, resulting in changes toward less costly therapy.

Cardiac Catheterization↗
PubMed1983

Effect of the cold pressor test on regional myocardial blood flow in patients with coronary artery disease.

The cold pressor test is a potent alpha-adrenergic vasoconstrictor stimulus, but its effect on regional myocardial blood flow in patients with coronary artery disease is unknown. In this study, 17 patients with chest pain syndromes who were receiving beta-adrenergic-blocking drugs underwent regional myocardial blood flow determination by the xenon-133 technique before and after the cold pressor test. Nineteen of 28 regions analyzed were distal to significant coronary artery lesions (greater than 70% reduction of luminal diameter), while the remainder were in patients with normal coronary arteries. Patients with normal and stenotic coronary arteries had a similar increase in heart rate-pressure product, but in patients with normal coronary arteries, regional myocardial blood flow increased in nine of nine regions (average increase 11.6 +/- 1.3%, p less than 0.01) while either decreasing or remaining unchanged in 14 of 19 regions distal to coronary artery lesions (average decrease 13.6 +/- 1.6%, p less than 0.05). This difference between groups was significant (p less than 0.01), demonstrating an inappropriate reduction of regional myocardial blood flow and suggesting that alpha-adrenergic vasoconstriction may contribute to myocardial ischemia.

Adrenergic beta-Antagonists↗
PubMed1983

Clinical utility and management impact of M-mode echocardiography.

To determine the clinical utility and management impact of M-mode echocardiography, 182 echocardiograms were analyzed at a university teaching hospital. The physicians who ordered the echocardiograms said that 12 percent provided crucial information that was not available from other tests and that 26 percent resulted in a change in patient management. According to two independent board-certified cardiologist-reviewers, 86 percent of echocardiograms were appropriately ordered, but only 15 echocardiograms (8 percent) were actually needed for a change to a new and appropriate management. According to the reviewers, the 77 Group I M-mode echocardiograms (those ordered to evaluate left ventricular function, left atrial size, potential cardiac sources of emboli, or the possibility of bacterial endocarditis, or those ordered in patients who, according to the ordering physician, had undergone or would undergo catheterization regardless of the results of echocardiography) were less likely than the 105 Group II M-mode echocardiograms (those ordered to evaluate possible mitral valve prolapse, hypertrophic cardiomyopathy, valvular function, or the pericardium) to be ordered appropriately, to provide helpful information, or to provide crucial results. Group I echocardiograms had reviewer-assessed appropriate management impact in only one case (1 percent) compared with a 13 percent rate of management impact for Group II M-mode echocardiograms (p less than 0.01). Although echocardiography can be accurate and valuable with yields similar to those of other noninvasive procedures, 77 (42 percent) of 182 M-mode echocardiograms in this hospital could be predicted at the time of ordering to be in a low-yield group.

Echocardiography↗
PubMed1983

The changing "natural history" of symptomatic coronary artery disease: basis versus bias.

In contrast to the 20 to 30% reduction in ischemic heart disease mortality that has been demonstrated by national mortality statistics and by several randomized controlled trials, an uncritical reading of recent "natural history" studies suggests far greater improvements in the survival of symptomatic coronary patients. Although the intrinsic accuracy of such natural history studies is not questioned, attempts to compare patients from different studies and different eras may greatly overestimate the true improvement in natural history because of at least 3 biases in the selection of cases from the spectrum of diseased patients. Because of lead-time bias, patients who are diagnosed earlier live longer regardless of whether interventions are efficacious. Because of referral bias, current patients may have symptoms or anatomy that place them at a different stage of severity than patients who were chosen for earlier studies. Because of incidence-prevalence bias, prevalence studies will be over-represented with survivors of previous incidence cohorts who have slower-progressing disease. We suggest that all natural history studies be carefully scrutinized for such biases before they are compared with each other.

Analysis of Variance↗
PubMed1983

Prevention by nifedipine of cold pressor-induced decrease in left ventricular ejection fraction.

To examine the effects of nifedipine on changes in ventricular function produced by cold, the cold pressor test was administered to eight patients with angiographically documented coronary artery disease. Radionuclide ventriculograms were obtained at baseline and during the cold pressor stimulus both before and after administration of nifedipine, 10 mg buccally; thus, four serial radionuclide ventriculograms were obtained per patient. The cold pressor stimulus did not produce any significant difference in the mean (+/- standard deviation) peak rate-pressure product during the control or nifedipine test (10,900 +/- 3,390 versus 10,600 +/- 3,700). However, the increase in systolic blood pressure (p = 0.05) and the peak systolic blood pressure achieved (p less than 0.001) were greater during the control (134 +/- 19 to 160 +/- 25 mm Hg) than during the nifedipine (125 +/- 18 to 145 +/- 21 mm Hg) cold pressor test. The mean global left ventricular ejection fraction decreased during the control cold pressor test from a baseline value of 0.60 +/- 0.08 to 0.52 +/- 0.08 (p = 0.004). After nifedipine, this variable did not change during the repeat cold pressor test (0.63 +/- 0.09) compared with the repeat baseline value (0.63 +/- 0.11). Therefore, the difference in left ventricular ejection fraction response during control versus nifedipine cold pressor testing was highly significant (p less than 0.0001). In patients with obstructive coronary artery disease, nifedipine abolished the decrease in left ventricular ejection fraction observed during the control cold pressor test and may be of value to protect patients from cold-induced left ventricular dysfunction. The mechanism may be a combination of coronary artery vasodilation and systolic unloading of the left ventricle.

Adult↗
PubMed1983

Acetaminophen metabolism in subjects fed charcoal-broiled beef.

The effects of consumption of charcoal-broiled beef on the metabolism of acetaminophen by conjugation were determined in nine normal subjects. We had reported that beef prepared in this manner accelerates the oxidative metabolism of drugs, including the oxidation of phenacetin to N-acetyl-p-aminophenol (acetaminophen). In nine normal subjects, a control diet was followed by a charcoal-broiled beef diet, which was followed by the control diet. The charcoal-broiled beef had little or no effect on the plasma-level profile of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate, or on the urinary excretion of acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, 3-methoxy-acetaminophen, or the cysteine and mercapturic acid conjugates of acetaminophen. Results indicate that the enzyme systems that conjugate acetaminophen in man are subject to little or no influence by charcoal-broiled beef. Therefore dietary factors that increase drug oxidations cannot be assumed to have a similar effect on drug conjugation.

Acetaminophen↗
PubMed1983

Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease.

Although beta-adrenergic blocking agents reduce myocardial oxygen consumption and symptoms of myocardial ischemia in patients with coronary artery disease (CAD), propranolol has been reported to exacerbate coronary artery spasm in some patients with variant angina. To determine whether increased coronary vasomotor tone can be induced by beta-adrenergic blockade, we measured the changes in coronary vascular resistance (CVR) during cold pressor testing (CPT) in 15 patients, nine with severe CAD and six with normal left coronary anatomy, before and after i.v. propranolol (0.1 mg/kg). Coronary blood flow was measured by coronary sinus thermodilution. CVR was calculated as mean arterial pressure divided by coronary sinus blood flow. Heart rate was maintained constant at a paced subanginal rate of 95 +/- 5 beats/min. Before propranolol, CPT induced significant increases in coronary vascular resistance in patients with CAD (15.0 +/- 2.2%, p less than 0.02), but no increase in CVR in the normal patients. After propranolol, the CVR change during CPT was augmented for patients with CAD (29 +/- 6%, p less than 0.01) and for the normal population (9 +/- 5%, NS). The potentiated increase in CVR occurred without significant changes in resting CVR or in the magnitude of the hypertensive response to CPT. We conclude that beta-adrenergic blockade with propranolol can potentiate coronary artery vasoconstriction in some patients with CAD, possibly mediated by unopposed alpha-adrenergic vasomotor tone. These changes may be important in patients in whom intense adrenergic stimulation may increase coronary artery tone and adversely influence the balance between myocardial oxygen supply and demand.

Adrenergic beta-Antagonists↗
PubMed1983

Thrombosis associated with a porcine bioprosthesis and ascending aortic graft in a patient with the Marfan syndrome.

A fatal thrombosis originating at the junction of an aortic bioprosthetic heart valve and a Dacron aortic graft was observed in a patient with the Marfan syndrome, who had had replacement of the ascending aorta with a valved conduit 29 months previously. This unique complication raises the question of whether patients with such prostheses should be on a program of full anticoagulation.

Adult↗
PubMed1982

Metabolism of acetaminophen by the isolated perfused kidney.

Acetaminophen (APAP) produces proximal tubular necrosis in the Fisher 344 rat. This lesion may result from the covalent binding of reactive intermediates of APAP to cellular macromolecules when glutathione (GSH) is sufficiently depleted. Experiments were designed to evaluate the ability of the kidney to convert APAP to reactive electrophilic metabolites capable of depleting renal GSH by quantifying GSH concentrations in isolated perfused kidneys perfused with APAP. Perfusion without APAP reduced (3 X 10(-5) -3 X 10(-5) M) to the perfusion medium further reduced renal GSH content. Treatment of rats with polybrominated biphenyls enhanced the ability of 3 X 10(-8) M APAP to deplete GSH. In contrast, treatment with piperonyl butoxide reduced the depletion of GSH produced by 3 X 10(-5) M APAP. At 3 X 10(-5) M APAP, the glucuronic acid, sulfate and the mercapturic acid conjugates were excreted by the isolate perfused kidneys. After treatment with polybrominated biphenyls, mercapturic acid excretion increased 4-fold, whereas the glucuronic acid and sulfate conjugate excretions were unaffected. These data suggest that the kidney can produce an electrophilic metabolite of APAP which can combine with and deplete renal GSH. An electrophilic metabolite of APAP produced by the kidney may initiate APAP induced renal necrosis.

Acetaminophen↗
PubMed1982

Beneficial effects of nifedipine on regional myocardial blood flow in patients with coronary artery disease.

Nifedipine inhibits the slow-channel calcium current, which plays a major role in vascular smooth-muscle contraction. However, the effect of nifedipine on regional myocardial blood flow (RMBF) in patients with coronary artery disease (CAD) is unknown. In 18 patients with chest pain syndromes, RMBF was determined with xenon-133 before and after nifedipine. In patients with CAD. 25 regions were analyzed distal to significant coronary obstruction(greater than 70% reduction in luminal diameter) and eight regions were analyzed in patients with normal coronary arteries. In patients with CAD, RMBF increased in 21 of 25 regions (average 17.4 /+- 5.7%,p less than 0.01), but decreased in all eight regions in patients with normal coronary arteries, by an average of 14.4 /+- 2.3% (p less than 0.01). The difference between groups was significant (p less than 0.01). In our patients with CAD, improved RMBF appears to be related to a decrease in coronary vascular tone and suggests a physiologic basis for the beneficial effect of nifedipine in ischemic heart disease.

Adult↗