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Biomedical subjects

P H Lehan

Publications and source records attributed to P H Lehan.

At least 19 recordsLinked to original sources
PubMed2001

Effect of fructose-1, 6-diphosphate versus diphenhydramine on mortality in compound 48/80-induced shock.

Fructose-1,6-diphosphate (FDP) has a salutary effect on hemorrhagic, traumatic and endotoxic shock. The role of FDP on compound 48/80-induced shock was therefore investigated. Sprague Dawley aged male rats (448+/-7.4 gm body weight) were randomly assigned into three groups and treated intraperitoneally with diphenhydramine (DPHM) 15 mg/kg (n=11), 12.5 ml of 10% FDP (n=10) and 12.5 ml saline (n=10). The rats were injected with compound 48/80 (5 mg/kg) 30 min later, and monitored every 10 min for 60 min. Arterial pressure was higher in FDP rats than in DPHM (P<0.01) or saline (P<0.005) groups. Plasma potassium (K(+)) was lower in the FDP group (P<0.01). Arterial pO2 and pCO2 were within physiological range in all groups. A profound decrease in arterial pH and bicarbonate (HCO3(-)) was also observed in all groups. Mortality at 48 h in the saline group was 100%, in the DPHM group 91%, and in the FDP group 20% (P<0.001 and P<0.005, respectively). FDP improved survival significantly in this study.

Adenosine Triphosphate↗
PubMed2000

Metabolic responses to fructose-1,6-diphosphate in healthy subjects.

Fructose-1,6-diphosphate (FDP) is an important naturally occurring intracellular metabolite with a direct regulatory role in many metabolic pathways. The most important and widely studied of the FDP effects has been its regulation of glycolysis, particularly the enzyme that synthesizes FDP--phosphofructokinase (PFK). Since it was observed experimentally that FDP does indeed modulate carbohydrate metabolism, we investigated whether FDP would similarly enhance carbohydrate utilization in man. The study used indirect calorimetry and was open to healthy adults (N = 45) of either sex and above legal age. After a steady metabolic state was obtained, 5 g of FDP (10%) was infused into a brachial vein. In 10 subjects, glucose (5 g) or FDP (5 g) was sequentially infused. The rapid intravenous infusion of FDP produced a slight but significant decrease in heart and respiration rates (P < .05). A significant increase in the serum concentration of inorganic phosphate (P < .0001) and the intraerythrocytic concentration of adenosine triphosphate (ATP) (P < .01) was also observed. The FDP infusion produced a decrease in plasma cholesterol and triglycerides (P < .001 and P < .01, respectively). The indirect calorimetric data indicate that the infusion produced a highly significant increase in the respiratory quotient ([RQ] P < .0001) and the energy derived from carbohydrates (P < .0001) and a significant decrease in the energy derived from lipids (P < .0001). Glucose infusion did not cause changes in any of the parameters. These data indicate that carbohydrate metabolism is stimulated by FDP.

Calorimetry, Indirect↗
PubMed1999

Fructose-1,6-diphosphate in the treatment of oleander toxicity in dogs.

Oleander, a flowering plant that grows in the Mediterranean and southern US, contains the cardiac glycosides oleandrin, digitoxigenin and nerium, which inhibit Na(+)-K+ ATPase. Clinical manifestations of oleander toxicity include gastrointestinal irritation, marked hyperkalemia, A-V block, ventricular dysrhythmia, and not uncommonly death. Because fructose-1,6-diphosphate (FDP) has been shown to attenuate digoxin toxicity, we determined whether this agent would be effective in the treatment of the toxicity of these similarly-structured cardiac glycosides. Anesthetized dogs (n = 12) were infused i.v. for 5 min with 40 mg oleander extract/kg and then 6 dogs randomly selected from that group received a 50 mg/kg bolus of 10% FDP followed by a constant infusion. The other control animals received the same dosage of 10% dextrose. Within 5 min after oleander administration, all dogs developed dysrhythmias. The FDP-treated animals reverted to sinus rhythm within 1.58 +/- 0.15 h; none in the control group returned to sinus rhythm. One control dog died at 3 h from ventricular fibrillation. Marked hyperkalemia was observed in the control group; plasma K+ remained unchanged in the FDP group. Throughout the 4 h experimental period the FDP group maintained normal arterial pressures; in the control dextrose group, pressures were profoundly depressed. Cardiac output declined in both groups but remained higher in the FDP group. To determine the mechanism whereby FDP attenuates oleander toxicity, we studied the in vitro effect of FDP on oleander poisoned myocardial sarcolemmal membranes. At concentrations of 1 and 2 mg oleander inhibited Na(+)-K+ ATPase activity and addition of 500 microM FDP restored myocardial sarcolemmal Na(+)-K+ ATPase function. FDP effectively prevented hyperkalemia, reversed dysrhythmias and improved hemodynamics in vivo in this canine model of oleander toxicity and also restored sarcolemmal Na(+)-K+ ATPase activity in vitro.

Animals↗
PubMed1997

Hemodynamic effects of fructose 1,6-diphosphate in patients with normal and impaired left ventricular function.

We compared the short-term hemodynamic effects of intravenous fructose 1,6-diphosphate (FDP) administration in patients with coronary artery disease. Hemodynamic measurements were performed before and after administration of FDP in two groups of patients: those with impaired left ventricular (LV) function, elevated LV end-diastolic pressures (LVEDP > or =12 mm Hg, n = 30), and those with normal LV function (LVEDP <12 mm Hg, n = 17). In those with impaired LV function, FDP induced a decrease in LVEDP from 22 +/- 1.31 to 16.73 +/- 1.46 mm Hg (p< 0.0001). The cardiac index increased (2.50 +/- 0.11 to 2.81 +/- 0.13 L/m2 [p < 0.0001]), as did the LV stroke work index (31.7 +/- 2.04 to 40.3 +/- 2.67 gm x m x m2 [p < 0.0001]). FDP induced no significant change in heart rate and mean aortic pressure. Pulmonary pressure and resistance declined (p<0.002 and p< 0.0001, respectively). Systemic vascular resistance decreased because of increased cardiac output and unchanged arterial pressure (p < 0.001). In those patients with normal baseline LVEDP (5.06 +/- 0.27 mm Hg), FDP decreased heart rate (p< 0.0001) and systemic and pulmonary resistance (p < 0.03 and p < 0.004, respectively), whereas LVEDP and mean aortic and pulmonary pressures remained unchanged. FDP moderately increased cardiac output (p < 0.05), stroke volume index, and LV stroke work index (p< 0.002 and p< 0.003, respectively). The observed improvement in LV function in those patients with elevated LV filling pressures is thought to be a result of an increased energy production by the Embden-Meyerhoff pathway and to act as a positive inotrope.

Cardiac Catheterization↗
PubMed1994

Plasma oxidase assay for screening of myocardial infarction.

The availability of techniques such as surgical reperfusion, angioplasty, and thrombolysis for the treatment of acute myocardial infarction (AMI) has revived interest in seeking an early detectable biochemical marker diagnostic for AMI. Therefore, we investigated whether an unidentified oxidase that is released by activated neutrophils at the onset of AMI could be used as an early diagnostic assay. The conversion by plasma oxidase of 1 microM of adrenaline to 1 microM of adrenochrome represents the plasma oxidase activity (POA) of 1 U/L. Fifty patients suspected of having AMI, 40% of whose electrocardiograms were nondiagnostic for AMI, were admitted to the coronary care unit, and venous blood samples were obtained for determination of the POA and creatine phosphokinase-MB levels. Healthy volunteers (n = 12) served as control subjects, and 8 patients with pneumonia whose leukocyte counts were greater than 15,000 microL were included in the study. In those with AMI (n = 22), as determined by serial creatine phosphokinase-MB, the mean POA (+/- standard error of the mean) was 233 +/- 13 U/L, and in those with angina and no AMI (n = 28) was 127 +/- 5 U/L (P < 0.0001). In the control group, mean POA (+/- standard error of the mean) was 84 +/- 5 U/L (control versus angina; P < 0.01) and for those with infection was 214 +/- 10 U/L. At admission, the creatine phosphokinase-MB was diagnostic for only 12 of the 22 patients with AMI (sensitivity rate of 54%), whereas in 21 of those patients, the POA values were diagnostic for AMI (sensitivity rate of 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenochrome↗
PubMed1991

Pregnancy after Fontan repair of tricuspid atresia.

We have described a patient who had a cyanotic congenital heart disease (type Ib tricuspid atresia), with initial palliation accomplished in childhood via a Glenn procedure. In 1985, she had a Fontan repair with the Bjork modification; 3 years later she achieved her first pregnancy at age 27. Maternal Doppler echocardiography in early pregnancy showed good flow through the constructed conduit, with normal left ventricular size and function. Fetal echocardiography at 22 weeks' gestation via two-dimensional, M-mode, pulsed Doppler, and color flow mapping revealed no evidence of fetal cardiac disease. At 25 weeks' gestation recalcitrant preterm labor developed, and the infant was delivered spontaneously. Labor, delivery, and puerperium were uncomplicated, and the newborn (though too premature to survive) was of appropriate weight for gestational age, without evidence of congenital heart disease or other anomalies. We believe this is the first report of pregnancy and spontaneous delivery in a patient who has had Fontan repair of a congenital heart defect.

Adult↗
PubMed1980

Hemodynamic, electrocardiographic, and metabolic effects of fructose diphosphate on acute myocardial ischemia.

The hemodynamic, electrocardiographic, and metabolic responses of dogs with acute myocardial ischemia to intravenous administration of fructose-1,6-diphosphate (FDP) were assessed. Analysis of the results (compared to dextrose control) revealed evidence of major improvement of LVEDP and cardiac output, significant decrease of the ST segment, and large increases of ATP and CP in the ischemic district and to a lesser degree in the normally perfused myocardium. These results indicate that FDP intervenes in the Embden-Meyerhof pathway not only as a high energy substrate but also as a metabolic regulator influencing the activity of phosphofructokinase and that of pyruvate kinase. FDP also stimulates glycolysis in dog erythrocytes and increases their ATP and 2-3 DPG content by a factor of 2. The most significant finding in these studies is that this biochemical intervention appears to restore the depressed activity of glycolysis in ischemic myocardium.

Adenosine Triphosphate↗
PubMed1977

Coronary revascularization in patients maintained on chronic hemodialysis.

Thirty-two thousand patients are presently maintained in chronic dialysis programs. Cardiovascular complications have been shown to be responsible for 50 to 65% of the deaths in such patients. Despite this and the increasingly frequent use of coronary bypsss surgery in the general population, only two patients have previously been reported to have successfully undergone coronary bypass surgery while maintained on chronic hemodialysis. This reports two additional such patients who successfully underwent coronary revascularization without difficulty. Pertinent details of preoperative, intraoperative, and postoperative management are outlined for these patients and the other 13 chronic dialysis patients who have had cardiopulmonary bypass for other reasons. With careful planning, coronary revascularization can be successfully carried out in this group of patients with minimally increased operative risk.

Coronary Artery Bypass↗
PubMed1976

Reversal of acute myocardial ischemia in closed chest animals by retrograde perfusion of the coronary sinus with arterial blood.

The fundamental objective of this study was to develop a technique for salvaging aco the ischemic muscle segment is the coronary venous system. We have been able to ration) in closed chest dogs by placing a double lumen balloon catheter in the coronary sinus, and perfusing it with blood derived from a peripheral artery. We have been able to partially reverse these same manifestations in similar dogs with an ischemic period of 30-60 minutes.

Animals↗
PubMed1975

Atraumatic evaluation of myocardial revascularization procedures with 43K1.

Least-squares regression analysis was computerized to provide functional color images of myocardial perfusion patterns. In 8 of the 9 patients studied, changes in pattern indicated that the revascularization procedure speeded the appearance time and/or net rate of 43K uptake. The functional images correlated well with coronary arteriograms made before and after surgery. This noninvasive isotope technique may prove to be clinically useful in (a) evaluating coronary artery disease, (b) defining the remaining viable myocardium when an aneurysm is present, and (c) determining the effectiveness of the revascularization procedure.

Adult↗
PubMed1975

Aortometric estimation of stroke volume in the presence of aortic insufficiency.

A formula has been derived for estimating the left ventricular stroke volume (SV) from measurements of the difference between maximum and minimum cross-sectional area of the ascending aorta (am), ascending aorta pulse wave velocity (c) and systolic period (TS): SV=0.54 Ts c am. In open chest dogs, this 'aortometric' formula for estimating SV compared favorably with measurements by the electromagnetic flowmeter method both with and without aortic regurgitation. This suggests that in the presence of aortic regurgitation, the aortic backflow may be estimated from the difference between the aortometric SV measurement and the systemic blood flow estimated by an independent technique.

Animals↗