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Biomedical subjects

G H Mudge

Publications and source records attributed to G H Mudge.

At least 73 records · Page 4Linked to original sources
PubMed1981

Coronary vasoconstrictor effect of indomethacin in patients with coronary-artery disease.

Prostaglandins may be important regulators of coronary blood flow. To investigate this possibility, we studied the effect of blockade of prostaglandin synthesis by indomethacin in nine patients with coronary-artery disease. Coronary-sinus blood flow (determined with the thermodilution technique) was recorded, together with mean arterial blood pressure and the myocardial arteriovenous oxygen difference from simultaneously obtained arterial and coronary-sinus blood samples, before and 20 minutes after an intravenous dose of indomethacin (0.5 mg per kilogram of body weight). There were significant increases (P less than 0.05) in mean arterial pressure (from 99 +/- 4 to 118 +/- 5 mm Hg [+/- S.E.M.]), coronary vascular resistance (+73 per cent), and myocardial arteriovenous oxygen difference (from 107 +/- 5 to 138 +/- 4 ml per liter) after indomethacin, but coronary blood flow fell significantly, from 181 +/- 29 to 111 +/- 14 ml per minute (P less than 0.05). Thus, despite an increase in myocardial oxygen demand, coronary blood flow fell and coronary vascular resistance increased. This coronary vasoconstrictor effect may have been due to blockade of vasodilatory prostaglandin synthesis or to a direct drug effect. Whatever the mechanism, indomethacin should be used with caution in patients with severe coronary-artery disease.

Blood Pressure↗
PubMed1981

Decreased lymphocyte beta-adrenergic-receptor density in patients with heart failure and tolerance to the beta-adrenergic agonist pirbuterol.

We compared the initial and long-term effects of the beta-adrenergic agonist pirbuterol in 12 patients with chronic congestive heart failure. The drug's initial effect was a 35 per cent increase in cardiac index, but there was no significant change in heart rate or mean arterial pressure. After one month of therapy, the mean cardiac index and ejection fraction had returned to base-line values, and no clinical effect was evident in most patients. This apparent tolerance was not accompanied by changes in heart rate, blood pressure, or body weight, and it occurred in the presence of therapeutic drug levels during long-term therapy. The density of beta-adrenergic receptors on lymphocytes from patients treated with pirbuterol was significantly depressed as compared with that of patients with heart failure of comparable severity but not treated with pirbuterol. We conclude that tolerance to the hemodynamic and clinical effects of pirbuterol develops during long-term administration; this tolerance may be related to a decrease in myocardial or vascular beta-adrenergic receptors or both.

Adrenergic beta-Agonists↗
PubMed1981

Five to eight-year follow-up of patients undergoing porcine heart-valve replacement.

To evaluate the clinical course after porcine heart-valve replacement, we followed 128 patients for five to eight years after surgery. Aortic-valve replacement was performed in 47 patients, mitral-valve replacement in 62, and combined aortic-valve and mitral-valve replacement in 19. Four patients died within 30 days of surgery (operative mortality, 3 per cent), and 20 died later (16 per cent); the actuarial probability of survival at eight years for all patients was 80 +/- 4 per cent (mean +/- S.E.M.). Thromboemboli were found in two of 43 patients after aortic-valve replacement, in nine of 62 after mitral-valve replacement, and in four of 18 after combined aortic-valve and mitral-valve replacement. Valve dysfunction resulted from bacterial endocarditis in five patients (4 per cent) and from primary valve dysfunction in another five.

Actuarial Analysis↗
PubMed1981

Therapy of coronary vasoconstriction in patients with coronary artery disease.

Patients with obstructive coronary artery disease and stable, exertional angina respond to the alpha adrenergic stimulus of the cold pressor test with an inappropriate increase in coronary vascular resistance. The clinical significance of this abnormal response and its possible role in the pathogenesis of ischemic heart disease are discussed. Comparison of the anti-anginal agents currently in use of undergoing investigation suggests that the calcium antagonists may be the most effective therapy for coronary vasoconstriction. Nifedipine, 10 mg buccally, successfully prevented the increase in coronary vascular resistance during the cold pressor test in 10 of 10 patients, whereas the response in placebo-treated patients was unaltered. This dose of nifedipine was without effect on systemic hemodynamics or myocardial oxygen consumption, suggesting a selective antivasoconstrictor effect on the coronary vasculature.

Angina Pectoris↗
PubMed1981

Prevention of nifedipine of abnormal coronary vasoconstriction in patients with coronary artery disease.

The hemodynamic and myocardial metabolic responses to the cold pressor test were studied in 15 patients with coronary artery disease and stable exertional angina. Every patient had abnormal coronary vasoconstriction during a control cold pressor test, even though 14 were receiving propranolol and 12 were receiving long acting nitrates. Mean coronary vascular resistance for the group increased 18 +/- 6% (SD) (from 0.80 +/- 0.12 to 0.94 +/- 0.20 mm Hg/ml/min, p less than 0.05); coronary sinus blood was unchanged, and the arterial-coronary sinus oxygen difference widened significantly (from 11.5 +/- 1.2 to 12.3 +/- 1.2 ml/100 ml, p less than 0.05). Four patients developed angina, accompanied in each instance by a negative arterial-coronary sinus lactate difference. After the administration of nifedipine (10 mg buccally) in 10 patients, the coronary vascular responses to a repeat cold pressor test were normal in each patient. Mean coronary sinus blood flow increased 27 +/- 12% (from 122 +/- 32 to 153 +/- 35 ml/min, p less than 0.05), coronary vascular resistance decreased 10 +/- 6% (from 0.85 +/- 0.16 to 0.76 +/- 0.16 mm Hg/ml/min, p less than 0.05), and the arterial-coronary sinus oxygen difference was unchanged. No patient experienced angina. The hemodynamic and coronary vascular responses to a repeat cold pressor test in five patients given placebo were unaltered from control responses. The protective effects of nifedipine were unaccompanied by any change in mean arterial pressure, left ventricular filling pressure or myocardial oxygen consumption either at rest or in response to the cold pressor test. Nifedipine appears to exert a selective antivasoconstrictor effect on the coronary vasculature.

Adult↗
PubMed1981

Acute effects of oral pirbuterol on myocardial oxygen metabolism and systemic hemodynamics in chronic congestive heart failure.

Pirbuterol hydrochloride, an orally effective beta-adrenergic agonist, improves hemodynamic abnormalities in patients with congestive heart failure, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow have not been characterized. We studied the effects of 20-30 mg of oral pirbuterol on myocardial metabolic and hemodynamic parameters in 12 patients (six with coronary artery disease) with chronic CHF refractory to standard medical therapy. Pirbuterol induced an increase in cardiac index (1.7 +/- 0.1 to 2.3 +/- 0.2 l/min/m2, p less than 0.05) and a fall in systemic vascular resistance (1884 +/- 118 to 1391 +/- 69 dyn-sec-cm-5, p less than 0.01) 2 hours after administration. Pulmonary capillary wedge pressure fell from arterial and right atrial pressures did not change. Heart rate remained constant. Arterial-coronary sinus oxygen content difference narrowed (from 12.9 +/- 0.4 to 11.1 +/- 0.3 vol%, p less than 0.05), while no significant change occurred in MVO2. Myocardial oxygen extraction ratio and myocardial lactate extraction ratio did not change, and no patient developed angina or electrocardiographic evidence of myocardial ischemia. Patients with coronary artery disease had hemodynamic and myocardial metabolic responses similar to those without coronary artery disease. Pirbuterol effects substantial acute hemodynamic improvement in patients with chronic congestive heart failure without increasing requirements for coronary blood flow or myocardial oxygen delivery and without provoking myocardial ischemia.

Adult↗
PubMed1981

Acetaminophen nephrotoxicity: studies on renal acetylation and deacetylation.

Acetaminophen (N-acetyl-p-aminophenol; APAP) inhibits both the acetylation and uptake of p-aminohippurate (PAH) by slices of mouse kidney cortex; p-aminophenol (PAP) is more potent than APAP in inhibiting the acetylation of PAH, but has no effect on uptake of PAH. Since PAP itself is acetylated by the kidney, the action of PAP on the acetylation of PAH might be competitive. However, from kinetic analysis the inhibition is principally noncompetitive in nature. In studies on deacetylation, PAP was generated from APAP both in slices and homogenates of kidneys; acetylated PAH was relatively stable. PAP is a known nephrotoxin but has not been identified previously as a metabolite of APAP. The data indicate that the kidney has the capacity to generate a potent nephrotoxin, PAP, from a relatively benign precursor, APAP. This potentiality should be considered in further studies on the pathogenesis of analgesic nephropathy.

Acetaminophen↗
PubMed1980

Mechanism of decomposition of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen.

The decomposition of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 2), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 1) in aqueous solution is quantitatively accounted for by the appearance of equimolar amounts of p-nitrosophenol and acetaminophen. The rate of decomposition depends on initial concentration and varies with pH. Antioxidants decrease the rate of decomposition and change the products. In the presence of cysteine, N-acetyl-3-(S-cysteine)-p-aminophenol, an in vivo metabolite of acetaminophen, is a product of decomposition.

Acetaminophen↗
PubMed1980

Uptake and acetylation of p-aminohippurate by slices of mouse kidney cortex.

In slices of mouse kidney cortex, p-aminohippurate (PAH) is taken up by the organic anion transport system and then rapidly acetylated to p-acetylaminohippurate acid (PAAH), so that there is little net accumulation of PAH itself. The basic characteristics of this system have been described. Uptake may be measured as the total of PAH and PAAH combined. Both uptake and acetylation are dependent on aerobic metabolism. Succinate strongly inhibits net accumulation but has only a slight effect on the amount acetylated. This is attributed to the stimulation of efflux by succinate. In the mouse, the degree of acetylation as well as uptake varies with sex and strain, as well as with the drug used as substrate. When organic anion transport is employed as a test system for the assay of nephrotoxicity, it is proposed that slices from the mouse possess advantages over some other species in that acetylation and uptake provide dual endpoints.

Acetylation↗
PubMed1979

Inappropriate coronary vasoconstriction in patients with coronary artery disease: a role for nifedipine?

Coronary arterial vasoconstriction, well recognized in Prinzmetal's variant angina, may participate in the pathogenesis of classic angina as well. Several recent studies in patients with obstructive coronary artery disease suggest that apparently spontaneous reductions in coronary blood flow can result in myocardial ischemia and even infarction. Evidence supporting the alpha adrenergic nervous system as a cause of such coronary vasoconstriction is reviewed, particularly the results of provocative testing with the cold pressor stimulus. Upon exposure of the skin to cold, patients with coronary artery disease demonstrate an inappropriate coronary vasoconstrictor response, often sufficient to produce angina. Normal patients, by contrast, show no change in coronary vascular resistance. In patients with a diseases coronary circulation, inappropriate vasoconstriction further restricts myocardial perfusion and appears to be little affected by beta adrenergic blocking agents or nitrates in the usual dosages. Nifedipine has proved effective in preventing coronary arterial spasm in patients with Prinzmetal's angina. Studies currently in progress suggest that it is also effective in blocking inappropriate coronary vasoconstriction in patients with typical angina. Nifedipine may thus be a useful addition to the treatment of ischemic heart disease.

Angina Pectoris, Variant↗
PubMed1979

Left heart catheterization and angiography via the percutaneous femoral approach using an arterial sheath.

An arterial sheath with a proximal hemostasis valve and a side-arm extension tube was used in 562 consecutive patients undergoing cardiac catheterization and angiography via the femoral approach. Serious complications were rare. There was one death, one peripheral embolism, and one episode of delayed groin hemorrhage. The incidence of minor complications, including hematoma formation, in this series compares favorably with our own and the reported experience of others using the conventional percutaneous femoral approach. The sheath technique facilitated catheter exchanges and reduced patient discomfort. In addition, femoral artery pressure could be monitored via the side arm of the sheath during the catheterization. This proved helpful during retrograde catheterization of patients with aortic stenosis, as well as in detection of damping of coronary artery catheter tip pressure during coronary arteriography and hypotension following left ventriculography. Based upon this experience, use of an arterial sheath has become our standard practice when left heart catheterization is performed via the femoral approach, and the use of several different catheters is anticipated.

Aged↗
PubMed1979

Factors contributing to altered left ventricular diastolic properties during angina pectoris.

Mechanisms involved in the altered left ventricular (LV) diastolic properties during angina were studied in 26 patients with coronary artery disease. Angina was induced by rapid atrial pacing and measurements were made at rest and during angina in the immediate post-pacing period. No changes occurred in heart rate (71 +/- 3 to 73 +/- 3 beats/min, NS) or right ventricular (RV) end-diastolic pressure (10 +/- 1 to 11 +/- 1 mm Hg, NS), while significant increases occurred in LV end-diastolic pressure (17 +/- 1 to 30 +/- 1 mm Hg, p less than 0.01), aortic diastolic pressure (74 +/- 3 to 80 +/- 3 mm Hg, p less than 0.01), coronary sinus blood flow (133 +/- 15 to 212 +/- 32 ml/min, p less than 0.01), and the time constant (T) of LV pressure fall in early diastole (43 +/- 2 to 58 +/- 4 msec, p less than 0.01). Despite the rise in arterial pressure, a significant fall was observed in peak negative dP/dt (1961 +/- 106 to 1751 +/- 80 mm Hg/sec, p less than 0.01). Changes in RV end-diastolic pressure do not explain the increased LV end-diastolic pressure during angina. Increased aortic pressure and coronary blood flow may contribute, but the simultaneous fall in peak negative dP/dt and rise in T suggest that impaired ventricular relaxation is an important factor contributing to the previously demonstrated alteration in LV diastolic properties during angina pectoris.

Angina Pectoris↗
PubMed1979

Acute hypokalemia as a possible cause of death in a patient with advanced muscular dystrophy.

A patient with advanced muscular dystrophy of the Duchenne type developed severe hypokalemia thought to be secondary to moderate gastro-intestinal losses in association with reduced intracellular potassium stores. With correction of the hypokalemia, the cardiac rhythm became more normal. In patients with advanced dystrophy, hypokalemia may be functionally significant.

Acute Disease↗