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Biomedical subjects

C R Lambert

Publications and source records attributed to C R Lambert.

At least 37 records · Page 2Linked to original sources
PubMed1995

Influence of left ventricular mass on left ventricular diastolic filling in normotensive morbid obesity.

To identify factors influencing left ventricular (LV) diastolic filling in patients with morbid obesity, we performed transthoracic and Doppler echocardiography on 50 subjects whose actual body weight was > or = twice their ideal body weight and on 50 normal lean control subjects. The transmitral Doppler E/A ratio and E wave deceleration half-time were used to assess LV diastolic filling. Significant negative correlations were seen between the E/A ratio and the LV internal dimension in diastole (r = 0.819, p = 0.0001), systolic blood pressure (r = 0.751, p = 0.0001), LV end-systolic wall stress (r = 0.782, p = 0.0001), and LV mass/height index (r = 0.901, p = 0.0001). Significant positive correlations were seen between the E wave deceleration half-time and the LV internal dimension in diastole (r = 0.743, p = 0.0001), systolic blood pressure (r = 0.789, p = 0.0001), LV end-systolic wall stress (r = 0.828, p = 0.0001), and LV mass/height index (r = 0.831, p = 0.0001). No correlation was seen between diastolic blood pressure and either index of LV diastolic filling. Thus increasing LV mass is associated with progressive impairment of LV diastolic filling in morbidly obese individuals. The aforementioned alterations in LV loading conditions may contribute to impairment of LV diastolic filling directly or by increasing LV mass.

Adult↗
PubMed1995

Time-series analysis of long-term ambulatory myocardial ischemia: effects of beta-adrenergic and calcium channel blockade.

We have previously demonstrated the utility of time-series analysis applied to 72-hour ambulatory electrocardiographic data in patients with coronary artery disease. The present investigation applied time-series analysis to long-term (120-hour) ambulatory electrocardiographic data to determine the minimal period of monitoring needed (1) to detect periodicity of ischemia-related variables in ambulatory patients, (2) to describe auto-correlation and cross-correlation functions for heart rate and ischemia, and (3) to describe the effects of beta-adrenergic and calcium channel blockade on circadian characteristics and coupling of heart rate and ischemia. A double-blind crossover design was used to obtain 120-hour recordings during placebo, atenolol (200 mg/day), and diltiazem (360 mg/day) administration. During all three treatment periods, distinct circadian variation of heart rate was documented by autocorrelation and Fourier analysis. Ischemia did not exhibit clear periodicity as indexed by autocorrelation in any period; however, it was coupled to heart rate in all treatment periods as reflected in cross-correlation analysis. Although diltiazem did not quantitatively alter the circadian characteristics of heart rate or ischemia, atenolol produced a shift in the coupling between remaining ischemia and heart rate in time. Significant autocorrelation was detected for all treatment periods after 72 hours of monitoring, suggesting that 72 hours is the minimum amount of time needed for analysis of ambulatory electrocardiographic data in patients with coronary artery disease.

Atenolol↗
PubMed1995

A closed-chest porcine model of coronary dissection and thrombosis.

BACKGROUND: Coronary dissection and thrombosis are important as pathophysiological mechanisms in acute coronary syndromes and as consequences of various interventional procedures. The present study was designed to develop and characterize a simple percutaneous method to produce coronary dissection and thrombosis in the pig. METHODS: The porous balloon (Wolinski type) was slightly oversized (balloon-to-artery ratio, 1.21 +/- 0.08) and placed in the left anterior descending artery in 12 domestic pigs using standard percutaneous techniques. The balloon was inflated using a pressure-activated syringe at 5 atm to deliver 1 ml of either saline or a small amount of bovine thrombin (500 units) in saline. The balloon was withdrawn, serial angiograms recorded, and ECG and aortic pressure were monitored throughout. At coronary occlusion or at 30 min, the hearts were removed and fixed for histological analysis. RESULTS: Seven pigs received thrombin and five received saline. On microscopic examination the internal elastic lamina was disrupted in all arteries in both groups. Subintimal and medial dissection was noted in 80% of arterial cross sections in the saline group, and 86% in the thrombin group. Partial occlusion of the coronary artery with thrombus was seen in 20% of samples in the saline group and in 43% of the thrombin group. Thrombus with complete occlusion of the coronary artery was observed in 86% of thrombin-treated vessels but in none of the arteries that received saline. Complete occlusion was observed at 28 +/- 9 min by angiography. CONCLUSIONS: Percutaneous delivery of a small amount of thrombin through a slightly oversized porous balloon catheter produces coronary dissection and thrombosis in a more reproducible and timely fashion than previously described methods. This model may be useful for testing interventional and pharmacologic treatment strategies.

Aortic Dissection↗
PubMed1995

Interrelationship of left ventricular mass, systolic function and diastolic filling in normotensive morbidly obese patients.

OBJECTIVE: To determine the interrelationship of left ventricular (LV) mass, systolic function and diastolic relaxation in morbidly obese subjects. METHOD: We obtained echocardiograms (M-mode, two dimension) and cardiac Doppler studies (pulse wave, continuous wave colour flow) on 50 subjects whose actual body weight was > or = twice ideal body weight. LV mass/height index was calculated from echocardiographic data (Penn Convention). LV systolic function was assessed by calculating LV fractional shortening. LV diastolic filling was assessed by measuring the transmitral Doppler E/A ratio and the transmitral E wave deceleration time. RESULTS: There were significant positive correlations between LV mass/height index and the LV internal dimensions in diastole, systolic blood pressure, LV end-systolic wall wall stress and the transmitral E wave deceleration time. There were significant negative correlations between LV mass/height index and both LV fractional shortening and the transmitral Doppler E/A ratio. There were significant negative correlations between LV fractional shortening and the LV internal dimension in diastole, systolic blood pressure LV end-systolic wall stress and the transmitral E wave deceleration time. There was a significant positive correlation between LV fractional shortening and the transmitral Doppler E/A ratio. There were significant positive correlations between the transmitral E wave deceleration time and LV internal dimension in diastole, systolic blood pressure and LV end-systolic wall stress. There were significant negative correlations between the transmitral Doppler E/A ratio and the aforementioned variables. CONCLUSIONS: Unfavourable alterations in LV loading conditions contribute to the development of LV hypertrophy and impairment systolic dysfunction in morbidly obese subjects. Increasing LV mass and altered loading conditions may synergistically contribute to impairment of LV diastolic filling in such individuals.

Adult↗
PubMed1994

In vivo metabolic studies of the trans-(R,R) isomer of radioiodinated IQNP: a new ligand with high affinity for the M1 muscarinic-cholinergic receptor.

E-(R,R)-IQNP is a new ligand analogue of IQNB, which has high affinity for the cholinergic-muscarinic receptor. Earlier studies have demonstrated high cerebral uptake of activity with selective localization in M1 receptor subtype areas of the brain. In this paper we describe the results of metabolic studies of E-(R,R)-IQNP directed at determining the metabolic fate of this ligand and the identification of the radioactive species observed in the brain and heart tissue. Tissue Folch extracts demonstrated that the lipid-soluble extracts from brain contained 87.0% +/- 1.65% of the activity up to 24 h. In the heart, 61.9% +/- 7.50% of the activity was extracted in the lipid-soluble extract after 30 min, decreasing to 51.4% +/- 0.65% by 4 h. In contrast, data from other tissues studied demonstrated large amounts of either aqueous soluble activity or activity which was not extracted from the tissue pellet material; analysis of lipid organic extracts revealed the following results: liver (4 h), 7.43% +/- 0.96%; serum (4 h), 3.73% +/- 0.87%; urine (24 h), 9.4%; feces (24 h), 16.5%. Thin-layer chromatographic (TLC) and high-performance liquid chromatographic (HPLC) analyses of lipid-soluble brain extracts indicated that only unmetabolized E-(R,R)-IQNP was detected (99.4% +/- 1.25%). Activity which was extracted into the organic phase from heart tissue was also determined by TLC and HPLC analysis to contain large amounts of unmetabolized ligand after 4 h (88.5% +/- 0.57%). In addition, however, low levels of two additional radioactive components were detected which increased with time. TLC analysis of the plasma lipid extracts indicated only a small amount of unmetabolized E-(R,R)-IQNP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pressure and volume control for local drug-delivery catheters: development of a new microprocessor-controlled system.

BACKGROUND: Local drug delivery is a potential solution to postintervention restenosis. Most catheters developed for local delivery depend upon control of pressure and of delivered volume for optimal performance. The present study was designed to assess the accuracy of current methods for inflation of local delivery catheters compared with a new microprocessor-controlled system specifically designed for this application. METHODS: An in vitro gravimetric testing system was constructed to record developed pressure and delivered volume using a variety of inflation devices and a microporous infusion catheter. Experienced catheterization laboratory personnel were given commercial angioplasty indeflators and a pressure-driven syringe and asked to quickly apply 5 atm and deliver 2.0 ml. A new microprocessor-controlled system was then tested using the same protocol. RESULTS: The time required to reach a plateau pressure was lowest with the pressure-driven syringe (0.164 +/- 0.017 s) and much higher with standard indeflators (2.94 +/- 2.54, 4.64 +/- 2.98, 7.69 +/- 4.89, 8.28 +/- 6.31 s). The corresponding microprocessor-controlled value was much lower than that of the manual systems (0.84 +/- 0.37 s). The variability of plateau pressure, as measured by the standard deviation, was lowest with the pressure-driven syringe (0.029 +/- 0.014 atm) and highest with the manual systems (0.37 +/- 0.26, 0.40 +/- 0.18, 0.44 +/- 0.31, 0.32 +/- 0.10 atm). The microprocessor-controlled system also produced very little variability in pressure (0.08 +/- 0.004 atm). The volume delivered varied significantly with all manual devices (1.77 +/- 0.64, 1.74 +/- 0.66, 1.36 +/- 0.45, 1.80 +/- 0.33 ml) as well as with the pressure-driven syringe (1.86 +/- 0.32 ml), but the volume delivered by the microprocessor-controlled system was highly accurate (1.99 +/- 0.06 ml). CONCLUSIONS: Manual inflation devices do not allow precise control of pressure or volume when used with local delivery catheters. Use of a pressure-driven syringe minimizes pressure error, but does not deliver an accurate volume. The microprocessor-controlled system minimizes pressure and volume error and should maximize transfer efficiency for local delivery catheter systems.

Angioplasty, Balloon, Coronary↗
PubMed1994

Affinity thin-layer chromatography test of the immunoreactive fraction of radiolabeled antibodies.

A simple, rapid and self-contained system for assaying the immunoreactive fraction of radiolabeled antibodies was developed using affinity thin-layer chromatography (ATLC). ATLC combines use of solid-phase-bound antigen and conventional TLC. The technique is an improvement over existing means of measuring immunoreactive fraction (bead-type or cell-type assays) in that it has neither wash steps nor centrifugation steps, yet provides results essentially identical to those obtained with the more time-consuming assays. ATLC is accomplished using chromatography strips that are coated with antigen material in a discrete region near the origin. The antigen-coated strips are then blocked in serum, air-dried and stored. For use, radiolabeled antibody is spotted at the origin, and the strip is developed using a buffered solvent. Immunoreactive antibody binds to the antigen at or near the origin, while radioactivity not associated with immunoreactive antibody migrates with the solvent front. Antigen-negative strips (serum-blocked only) are used to measure "nonspecific" binding. The ATLC development time is about 16 min, and the results can be obtained in about 30 min. The assay described in this report uses antigens from colon tumor and is suitable for use with B72.3 and other colon cancer-reactive antibodies.

Animals↗
PubMed1993

Factors influencing left ventricular systolic function in nonhypertensive morbidly obese patients, and effect of weight loss induced by gastroplasty.

Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions.

Adult↗
PubMed1993

Hemodynamic and angiographic comparison of intravenous nitroglycerin and nicardipine mainly in subjects without coronary artery disease.

Twenty patients were studied during cardiac catheterization to compare hemodynamic and quantitative angiographic effects of intravenous nicardipine and nitroglycerin. After baseline measurements, nicardipine or nitroglycerin was administered by randomized continuous infusion beginning at 10 micrograms/min titrated to achieve a 10 to 12% reduction in systemic arterial pressure. Hemodynamic measurements and angiography were then repeated. Nicardipine did not change heart rate, and a small decrease (82 +/- 4 vs 75 +/- 4 beats/min) was observed with nitroglycerin, whereas mean arterial pressure decreased similarly (-11%) in both groups. Nicardipine increased (+13%) and nitroglycerin decreased (-21%) cardiac output. Although both drugs were associated with significant reductions in pulmonary artery wedge and pulmonary artery pressures, changes were greater with nitroglycerin for pulmonary artery wedge (-49% vs -26%) and pulmonary artery (-39% vs -13%) pressures, whereas only nitroglycerin reduced right atrial pressure significantly. Neither drug altered left ventricular ejection fraction or pulmonary vascular resistance, and only nicardipine decreased systemic vascular resistance significantly. Quantitative coronary angiography (videodensitometry) showed dilation of the left main, proximal, mid and distal anterior descending and circumflex segments by both nitroglycerin and nicardipine. Nicardipine dilated small (< 2 mm2) and large (> 2) arterial segments equally, whereas nitroglycerin showed a proportionately greater effect on small vessels.

Adult↗
PubMed1993

Plasma concentrations and hemodynamic effects of intravenous, sublingual, and aerosolized nitroglycerin in patients undergoing cardiac catheterization.

Intravenous, sublingual, or aerosolized nitroglycerin was administered to 19 patients with coronary artery disease during clinically indicated cardiac catheterization. Eight blood samples were collected over 15 min from each patient, and analyzed for content of nitroglycerin, 1,2-glycerol dinitrate, and 1,3-glycerol dinitrate. Simultaneously, heart rate (HR), systolic blood pressure (SBP), and left ventricular end-diastolic pressure (LVEDP) were recorded. Plasma concentrations of nitroglycerin were highest after intravenous injection and lowest after sublingual tablets. Metabolite concentrations were highest after intravenous injection at early time-points; at later time-points, no between-group differences could be detected. SBP was minimally affected by intravenous nitroglycerin but was significantly reduced by sublingual and aerosolized formulations. Minor fluctuations in HR were observed in association with all three formulations. LVEDP was reduced by all three formulations of nitroglycerin but most rapidly by the intravenous form. Overall, no differences were detected in hemodynamic responses caused by sublingual and aerosolized nitroglycerin. Efficacy of sublingual and aerosolized nitroglycerin in patients undergoing cardiac catheterization is equivalent.

Administration, Inhalation↗
PubMed1993

Local drug delivery catheters: functional comparison of porous and microporous designs.

BACKGROUND: The porous (Wolinski) balloon was designed to allow local delivery of compounds targeted to inhibit postintervention restenosis; however, successful use of the device has been hampered by arterial trauma caused by the balloon itself. This study utilized several experimental systems to assess the functional characteristics of the porous balloon catheter. This information was utilized to design and test a new microporous infusion catheter for local intra-arterial drug delivery. METHODS: Flow characteristics in fluid and semisolid media as well as arterial trauma by light and electron microscopy were documented for the porous and microporous balloons. In addition, the efficacy of methylene blue delivery in situ and in vitro was documented and quantified for the microporous design. RESULTS: The porous balloon exhibits flow characteristics consistent with orifice-related streaming that produces arterial trauma. By maximizing external balloon-pore density and minimizing pore size, the microporous design minimizes streaming in test systems. This is manifested by minimal arterial trauma when applied to intact arteries. The microporous catheter is effective for dye delivery both in situ and in vivo. CONCLUSIONS: The microporous catheter design offers improved functional characteristics when compared with the porous balloon for local intra-arterial drug delivery.

Animals↗
PubMed1993

Site-specific/stable radioiodination of 1,2-Pal-3-IPPA: an agent for the potential clinical evaluation of pancreatic insufficiency by urine analysis.

To measure pancreatic lipase activity, we synthesized a triglyceride containing a radioiodinated fatty acid. The urinary excretion of radioactivity was measured in five rats following administration of the agent by feeding tube. We attached 15-phenylpentadecanoic acid (PPA) to position-3 of 1,2-dipalmitoyl-rac-glycerol (1,2-Pal) to form 1,2-Pal-3-PPA. The 1,2-Pal-3-IPPA (expected lipase substrate) was prepared by the thallation-iodide displacement method. In a dual-label study, the 125I-1,2-Pal-3-IPPA triglyceride was administered with the 131I-IPPA free acid to rats (n = 5) by oral gavage. Urine and feces were collected daily and the tissue distribution of both tracers was evaluated over a five-day period. A significant portion of the administered activity was excreted in 24 hr in the urine (125I, 30.31% + 4.32%; 131I, 35.0% + 7.29%), which cochromatographed with hippuric acid by thin layer chromatography. Release of the acidic components from the conjugated excretory products by acid hydrolysis of the urine provided the radioactive acidic metabolites. Analysis of the Folch extracts of fat samples demonstrated that the radioactive components cochromatographed in the triglyceride region. This agent appears useful for the evaluation of various gastrointestinal diseases.

Animals↗
PubMed1992

Combination therapy with nicardipine and beta-adrenergic blockade for angina pectoris.

Nicardipine a second-generation dihidropyridine calcium antagonist, has been approved in oral formulation for use in the United States, and is under review for parenteral use. Nicardipine is the most vascular-selective agent of this class currently approved and should, on theoretical grounds, be ideal for combination therapy with beta-adrenergic blocking agents. Studies have shown that the combination of nicardipine and beta-blocking agents offers additional efficacy over monotherapy with either agent alone. The hemodynamic profile of combination therapy appears to be especially favorable in patients with diminished left ventricular function needing therapy with agents of both classes. Adverse effects are few and may be improved compared with other agents of the dihidropyridine class.

Adrenergic beta-Antagonists↗
PubMed1992

Acute myocardial infarction associated with intravenous injection of pentazocine and tripelennamine.

This case report describes the evolution of an acute anteroseptal myocardial infarction in a 27-year-old man following intravenous injection of pentazocine and tripelennamine. Subsequent coronary angiography showed normal coronary arteries. Based on the known mechanism of action of these drugs, it is postulated that myocardial infarction resulted from coronary artery spasm secondary to excessive catecholamine stimulation.

Adult↗
PubMed1992

Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease.

To assess the pulmonary and systemic hemodynamic effects of oral captopril in patients with connective tissue disease and pulmonary hypertension, we performed right heart catheterization in eight patients with diffuse systemic sclerosis, the CREST syndrome, or mixed connective tissue diseases prior to and immediately following administration of captopril (dose range 12.5 to 50.0 mg, short-term study). Four of these patients underwent repeat right heart catheterization after three to six months of oral captopril therapy (long-term study). In the short-term study, oral captopril produced a significant decrease in mean pulmonary vascular resistance from 6.2 +/- 3.6 to 4.6 +/- 3.8 units (p < 0.01). This was accompanied by a significant decrease in mean pulmonary artery pressure, mean blood pressure, mean systemic vascular resistance and a significant increase in cardiac output. Similar changes in pulmonary hemodynamics were noted in the long-term study. Thus, oral captopril is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with the aforementioned connective tissue diseases.

Adult↗
PubMed1991

Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.

Ten patients with pulmonary hypertension associated with diffuse systemic sclerosis (1 patient), the CREST syndrome (calcinosis cutis, Reynaud's phenomenon, esophageal dysmotility, sclerodactyl, telangiectasia) (6 patients) and mixed connective tissue disease (3 patients) were studied to assess the effect of oral nifedipine on pulmonary and systemic hemodynamics. Each patient underwent right-sided cardiac catheterization just before nifedipine administration. Thereafter, oral nifedipine was administered in 10 mg increments every 90 minutes until pulmonary vascular resistance normalized or a total dose of 30 mg was achieved. Hemodynamic measurements were obtained at 30-minute intervals for 3 hours, then hourly for 9 hours (acute study). Hemodynamic studies were repeated 3 to 6 months after the initial catheterization with the minimum dose of oral nifedipine (administered every 8 hours) required to achieve maximal reduction of pulmonary vascular resistance in the acute study (long-term study). In the acute study, oral nifedipine produced a significant decrease in mean pulmonary vascular resistance from 6.3 +/- 3.8 to 4.3 +/- 3.6 U (p less than 0.001). Similar changes in pulmonary vascular resistance were noted in the long-term study (n = 6). The results indicate that oral nifedipine is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.

Adult↗