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J P Blackburn

Publications and source records attributed to J P Blackburn.

At least 19 recordsLinked to original sources
PubMed1997

Connexin43 gap junction levels during development of the thoracic aorta are temporally correlated with elastic laminae deposition and increased blood pressure.

A characteristic property of the vascular smooth muscle cell is its ability to modulate between a contractile phenotype, responsible for control of vascular tone, through to a synthetic phenotype, capable of migration and synthesis of extracellular matrix molecules. Smooth muscle cells are coupled by gap junctions, the membrane structures which permit direct intercelluar passage of ions and small molecules, and which play a role both in electrical coupling and intercellular communication during patterning and development. We have previously found that connexin43 type gap junction expression is upregulated in the synthetic phenotype smooth muscle cell in vitro and during atherosclerotic plaque formation in human coronary arteries. On the basis of immunohistochemical labelling, confocal laser scanning microscopy and digital image analysis, we now report that relatively high levels of connexin43 are expressed during development of the rat thoracic aorta, temporally correlating with reported periods of smooth muscle cell proliferation and secretion of elastic laminae. A major peak in expression occurs at seven days post-natal, with a second less pronounced peak at 72 days post-natal. The principal peak in gap junction levels appears to coincide with increased post-natal blood pressure and aorta media thickening. The amount of gap junction labelling falls off to normal adult levels as the smooth muscle cells modulate towards the contractile phenotype and growth is completed. The results indicate an association between direct cell-to-cell communication and synthetic phenotype smooth muscle cell activity during aortic growth and patterning.

Animals↗
PubMed1995

Upregulation of connexin43 gap junctions during early stages of human coronary atherosclerosis.

Interactions between cells form the framework for understanding the pathogenesis of atherosclerosis, but little information is available on the role of direct intercellular communication via gap junctions in this process. To investigate gap junction expression in the pathogenesis of human atherosclerosis, lesions representing different stages of the disease were obtained from coronary arteries of hearts removed from patients undergoing cardiac transplantation. Twelve hearts, each providing 1 to 3 segments of artery, were used in the study. Sections were examined by confocal laser scanning microscopy after immunofluorescent labeling with a specific antibody against connexin43, the major gap-junctional protein of smooth muscle cells, to permit high-definition visualization of immunolabeled gap junctions through the depth of the specimen. Double labeling using anti-connexin43 and cell type-specific antibodies demonstrated colocalization of gap junctions with smooth muscle cells but not with macrophages, a relationship confirmed by electron microscopy. Regions of intimal thickening and early atheromatous lesions showed markedly increased expression of connexin43 gap junctions between intimal smooth muscle cells compared with the undiseased vessels. This increase in gap junctions was most marked in regions of intimal thickening, semiquantitative analysis of the confocal digital images revealing a > 10-fold increase compared with the undiseased vessel. The quantity of labeled gap junctions in early atheromatous lesions, although higher than that of the undiseased vessel, was lower than that of intimal thickenings, and this trend toward reduced levels of gap junction immunolabeling with lesion progression continued, the value observed in the most advanced atheromatous lesions being lower than that of the undiseased vessel. As the quantity of gap junctions declined, their distribution became more patchy and the sizes of individual junctions larger. The results suggest that enhanced expression of gap junctions between smooth muscle cells may play a role in maintaining the synthetic phenotype during early growth of the atherosclerotic plaque.

Aged↗
PubMed1982

Propranolol uptake by dog lung: effect of pulmonary artery occlusion and shock lung.

First-pass lung uptake of propranolol in catheterized ambulant dogs was measured by comparison the difference between the ratios of [14C]propranolol to indocyanine green (ICG) before and after a single passage through the pulmonary circulation. Uptake was 56 +/- 5, 53 +/- 8, and 61 +/- 10% (mean +/- SD) when 0.02, 0.2, and 2.0 mg of propranolol were injected, respectively. There was a negative though unimportant correlation between percent uptake and cardiac output. Analysis of paired propranolol and ICG outflow curves confirmed the lack of saturation with increasing dose and suggested the involvement of simple diffusion. In four dogs uptake fell from 4.76 +/- 6.8 to 40.4 +/- 8.2% (0.05 greater than P greater than 0.025) during partial occlusion of the pulmonary circulation by a Swan-Ganz catheter balloon and rose again to 51.2 +/- 6.4% after relief of the occlusion. Propranolol uptake, measured serially in five dogs with indwelling catheters, was initially 55% but fell linearly to 30% over 2 wk (r = -0.59, P less than 0.001), and necropsy showed pathological features of shock lung. A similar study performed on three dogs within 4 days of catheterization showed no change in uptake of the drug. Propranolol uptake appears to reflect both quantitative and qualitative changes in the pulmonary endothelium. This method may therefore be valuable in studying the pulmonary endothelium in health and disease.

Animals↗
PubMed1981

First-pass lung uptake of propranolol enhanced in anaesthetized dogs.

Uptake of 14C-propranolol after a single passage through the pulmonary circulation was studied in three groups of Labrador dogs using a double indicator dilution method. Uptake in conscious, ambulant animals was 53%. This increased to 81% in dogs anaesthetized with thiopentone, nitrous oxide and halothane and to 64% in dogs anaesthetized with thiopentone, nitrous oxide and fentanyl. Interaction between lipid-soluble anaesthetic agents and pulmonary endothelial cell membranes may be an important factor in increasing lung uptake of lipophilic propranolol, although alteration in pulmonary perfusion associated with a reduction in cardiac output during general anaesthesia may play a part. The pharmacological effects of propranolol administered i.v. during general anaesthesia may be unpredictable.

Anesthesia, General↗
PubMed1980

Evaluation of the Datex CD-101 and Godart Capnograph Mark II infra-red carbon dioxide analysers.

Performance of the Datex CD-101 and Godart Capnograph Mark II infra-red carbon dioxide analysers was investigated. The Datex machine uses a solid-state infra-red detector, while the Godart instrument uses a Luft detector. Both instruments were easy to use and the small size and light weight of the Datex was an added convenience. Linearity, stability, response time and the effect of nitrous oxide were within specification in both machines except when 10% carbon dioxide was used with the Datex analyser. Linearity of the Godart instrument was considerably better than 1% full scale deflection (fsd) quoted in the specification, while the Datex analyser was within 2% fsd (4% fsd with 10% carbon dioxide).

Anesthesia, Inhalation↗
PubMed1979

Evaluation of tests for predicting the viability of axial pattern skin flaps in the pig.

The viability of axial pattern skin flaps in pigs was assessed by the use of intravenous fluorescein, intradermal injection of 133Xe in saline, intravenous 51Cr tagged red cells, and angiography. The results were correlated with flap survival at 4 days postoperatively. Intravenous fluorescein provided the most accurate method for prediction of viable tissue at the time of operation. There was no evidence of vascular perfusion in the distal portions of these flaps. These axial pattern flaps differed in their viability from similar flaps in humans, and anastomoses between discrete vascular territories were infrequent in pigskin.

Animals↗
PubMed1979

First pass uptake of 14C-propranolol by the lung.

Uptake of 14C-propranolol by the lungs during a single passage through the pulmonary circulation was measured in ten patients at cardiac catheterisation. Mean lung uptake of propranolol was 75% in seven patients who were not previously taking the drug and 33% in three patients who were taking it as regular oral treatment. Lung uptake of propranolol in man is therefore considerable and is partly saturable by normal oral doses. This may alter the dose response relation for propranolol and a wide range of other drugs when given intravenously. The method used to study lung uptake is simple and might be suitable for studies of endothelial cell function in disease.

Administration, Oral↗
PubMed1979

Effects of pulmonary circulation on blood levels of insulin and glucagon in ambulant dogs.

The effect of the lung on insulin and glucagon were studied by comparing aortic and mixed venous levels in ambulant dogs with indwelling catheters. In the resting state ther was no difference for either hormone. After injection of insulin aortic levels exceeded mixed venous for 10 min; mixed venous levels exceeded aortic for the next 36 min. After injection of glucagon mixed venous levels consistently exceeded aortic. Single-pass studied showed an apparent gain in immunoreactive insulin as compared with [14C]inulin and 125I-albumin during passage through the lung; but no effect on glucagon could be demonstrated. A loss of immunoreactive hormone across the lung might be explained by degradation within the capillary lumen be endothelial cell surface peptidases or uptake onto specific receptors. The apparent gain of immunoreactive insulin across the lung might be due to displacement of immunoreactive exogenous hormone competing for receptor sites or modification of exogenous hormone by the lungs with increase in immunoreactivity.

Animals↗
PubMed1978

A simple ventilator suitable for respiratory gas studies.

A simple ventilator is described where a spring-loaded bellows is filled from a compressed gas supply. The outflow from the bellows to the subjects is controlled by solenoid valves. The device is a minute volume divider and the durations of inspiration and expiration are set by timers that operate the solenoid valves. The valves are positioned near the subject to minimize dead space and gas compression effects. Precise valve timing ensures separation of inspirate and expirate. The ventilator is suitable for respiratory gas studies on animals and may be modified for human use if required.

Animals↗
PubMed1975

A simple method for computing acid-base state.

Simple methods are described for computing the variables derived from the Siggaard-Andersen nomogram, where the in vitro buffer line is either established by direct measurement or calculated from measurements of pH, Pco2 and haemoglobin. Calculations are performed using the equation of the pH-log Pco2 buffer line, the Henderson-Hasselbalch equation, and the polynomials: BE=-38.402+1.8970 (SB)-0.013342 (SB)-2 m-equiv/litre; SL=-69.046+17.377 (pH40)-1.1121 (pH40)-2; SH=-123.30+31.357 (pH40)-2.0143 (pH40)-2. Then haemoglobin=7.5 (1+(S-SL)/(SH-SL)) G/100 ml, where S is the slope of the buffer line. Results are sufficiently accurate for clinical purposes.

Acid-Base Equilibrium↗