Alterations of myocardial capillary permeability by albumin in the isolated, perfused rabbit heart.

Mann, Giovanni E.

doi:10.1113/jphysiol.1981.sp013910

Cited by 61 publications

(35 citation statements)

References 30 publications

(33 reference statements)

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“…Using Crone's method for estimating the product of capillary permeability and surface area (PS), Alvarez and Yudilevich (3) observed that the ratios of solute permeability to free diffusion coefficient (P/D) were very nearly the same for urea, glycerol, glucose, sucrose, and inulin. This fact was confirmed by other researchers using the same technique (10,45), and refinements of the methods for tracer analysis have not changed the observation (9). This result implies that permeation of these solutes is dependent only on the solute diffusion coefficient and not on any steric hin-drance due to glycocalyx or cell walls; the cleft widths between adjacent endothelial cells must be at least 10-20 nm for this to be true.…”

supporting

confidence: 73%

An integrative model of coupled water and solute exchange in the heart

Kellen

Bassingthwaighte

2003

American Journal of Physiology-Heart and Circulatory Physiology

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.-Physiologists have devised many models for interpreting water and solute exchange data in whole organs, but the models have typically neglected key aspects of the underlying physiology to present the simplest possible model for a given experimental situation. We have developed a physiologically realistic model of microcirculatory water and solute exchange and applied it to diverse observations of water and solute exchange in the heart. Model simulations are consistent with the results of osmotic weight transient, tracer indicator dilution, and steady-state lymph sampling experiments. The key model features that permit this unification are the use of an axially distributed blood-tissue exchange region, inclusion of a lymphatic drain in the interstitium, and the independent computation of transcapillary solute and solvent fluxes through three different pathways. microcirculation; capillary permeability; osmotic transient; lymph; multiple-indicator dilution PHYSIOLOGISTS ARE INTERESTED in the exchange of material between capillaries and their surrounding tissues because this process is fundamental to the viability of multicellular life. The kinetics of coupled solute-solvent exchange across capillary walls can be described phenomenologically by three parameters: the hydraulic conductivity (L p ), the permeability (P), and the reflection coefficient () (37). The values of these parameters can be determined by several experimental methods, including measurement of the outflow concentration time courses of solutes after a bolus injection of tracers (the multiple-tracer indicator dilution technique), gravimetric or isogravimetric measurements of the response to perturbations of osmotic or hydrostatic pressures (the osmotic transient method), and simultaneous measurements of solute concentrations in lymph and plasma (lymph sampling techniques). Reasonable fits to data from these sources have been obtained with relatively simple analytical methods, like the Crone-Renkin (18, 52) estimate of capillary permeability, the Vargas and Johnson (65) estimate of reflection coefficient, and the "pore-stripping" analysis of Renkin et al. (52a). These analysis methods have enjoyed widespread use in determining transport parameter values from indicator dilution, osmotic transient, and lymph data, respectively.Although mathematically independent, all three phenomenological transport parameters must ultimately arise from the physical and chemical properties of the exchanging solution and the anatomic structures that create the pathways for its exchange across capillary walls. Consequently, hydrodynamic models of solute and fluid movements through the endothelial cell junction, represented as idealized pores in the capillary wall, have been developed to relate the transport parameters to mechanistic quantities such as solute size and diffusion coefficient and pore radius and relative area (12,19,44,48,49). Even though there is no strict correspondence between the idealized pores and actual capillary morphology, pore models have proven...

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supporting

confidence: 73%

An integrative model of coupled water and solute exchange in the heart

Kellen

Bassingthwaighte

2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Adult New Zealand rabbits of either sex and 2-4 kg in weight were sacrificed by a rapid blow to the head. The hearts were excised and immediately perfused through a cannula in the aorta at a constant flow rate of approximately I ml min-' g-' (Mann, 1981). The coronary sinus effluent drained from the ventral surface of the horizontally mounted heart.…”

Section: Methodsmentioning

confidence: 99%

“…In these experiments hearts were perfused at flow rates between 0-9 and 2-2 ml min-g'l. Following a bolus injection (100 #1 in 1-2 s) of an isotope mixture containing 1251-labelled albumin (intravascular reference tracer), D-[3H]mannitol (extracellular tracer) and L-[8-'4C]noradrenaline into the perfusate tubing close to the aorta, the coronary sinus effluent was immediately collected at regular intervals (Mann, 1981). These venous samples were directly counted in a Packard y spectrometer set for the spectrum of 121I.…”

Section: Noradrenaline Influx Kinetics In the Heartmentioning

confidence: 99%

“…The fractional capillary extraction (E) of a test solute relative to '281-labelled albumin was calculated from: E = 1-C/Cr, where Ct and Cr are the initial venous concentrations of the test and intravascular reference tracers, respectively (for details see Mann, 1981). The capillary permeability-surface area product (PS) was calculated from the measured extraction (E) and coronary perfusion flow (F) using the expression defined by Renkin (1959) and Crone (1963): PS = -Fln (1-E).…”

Section: Noradrenaline Influx Kinetics In the Heartmentioning

confidence: 99%

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Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart.

Mann¹,

Yudilevich²

1984

The Journal of Physiology

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SUMMARY1. Capillary permeability and cellular uptake of noradrenaline by the isolated artificially perfused rabbit heart was measured using rapid (< 30 s) single-circulation tracer-dilution techniques.2. In a single coronary circulation capillary extractions of L-[14C]noradrenaline and D-[3H]mannitol (extracellular reference) relative to an intravascular marker, 1251_ labelled albumin, were similar and above 60 %.3. The 'apparent' volume of distribution for tracer noradrenaline was 2-5-fold larger than that measured for D-mannitol (0-32 ml g-1) suggesting cellular uptake of the amine.4. Unidirectional noradrenaline uptake was estimated by directly comparing coronary sinus dilution profiles ofL-[3H]noradrenaline and D-[14C]mannitol. MichaelisMenten saturation kinetics based on a single-entry system were determined (Km = 2-8 + 1 5 /M, Vmax = 2-1 + 0-5 nmol min' g-1, n = 4) by perfusing hearts with varying concentrations of L-noradrenaline (1-10 ,M).5. Various known inhibitors ofnoradrenaline uptake were investigated to determine whether uptake was mediated by neuronal (uptake,) and/or extraneuronal (uptake2) mechanisms. Desipramine (5 zM), imipramine (5/M) and metaraminol (2 /M) resulted in a 66-940 inhibition of noradrenaline influx. In comparison, the steroids, 17 ,Joestradiol (1 uM) and corticosterone (10 /M), and the noradrenaline metabolite normetanephrine (5/tM) caused virtually no inhibitory effects. The 6-adrenergic antagonist propranolol (5/M) was also relatively ineffective.6. These results together with the kinetic constants estimated suggest that the rapid noradrenaline uptake reflects transport into adrenergic neurones lying in the coronary interstitium. The high resolution of this paired-tracer dilution technique has permitted a 'non-invasive' study of neuronal uptake mechanisms and its application may be of clinical value.

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“…1) or 18 weeks (data not shown). The continuous increase in flow was probably due to washout of albumin, as discussed previously (19) . Transcapillary insulin transfer in hearts from animals aged 7 and 18 weeks.…”

Section: Resultsmentioning

confidence: 67%

Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.

et al. 2000

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Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat, which exhibits the metabolic syndrome of obesity, insulin resistance, hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these alterations served as controls. Animals of both groups were normotensive (mean arterial pressure 136 ± 2 mmHg). Hearts from obese and lean rats aged 7 (n = 6) or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51 min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a validated method, and interstitial insulin was determined with a radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both experimental groups (half-times of transfer: 11 ± 0.2 min in obese and 18 ± 4 min in lean rats; NS), but at 0.5 U/l, the respective half-times were 7 ± 1 min in lean and 13 ± 2 min in obese rats (P < 0.05). The steady-state level of insulin in the interstitium was 34 ± 1% of the vascular level at 0.1 U/l and reached the vascular level (102 ± 2%) at 0.5 U/l in both lean and obese rats. In rats aged 18 weeks, the half-times of insulin transfer were 31 ± 2 and 14 ± 1 min in obese rats and 10 ± 0.3 and 7 ± 0.3 min in lean rats (P < 0.05). Again, interstitial steady-state levels were similar in both groups. Finally, postprandial insulin dynamics were simulated over a period of 120 min with a peak concentration of 0.8 U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38 ± 0.02 U/l in lean rats and 0.24 ± 0.02 U/l in obese rats (P < 0.05), and a similar difference was noted throughout insulin infusion (areas under the transudate concentration-time curves: 17 and 11 U/min per l, respectively). These data show, for the first time in a genetic animal model of insulin resistance, that transfer of insulin across the endothelium is substantially delayed in obese insulin-resistant rats and that it likely contributes to the postprandial alterations of glucose metabolism observed in the metabolic syndrome. Diabetes 49:803-809, 2000

show abstract

Alterations of myocardial capillary permeability by albumin in the isolated, perfused rabbit heart.

Cited by 61 publications

References 30 publications

An integrative model of coupled water and solute exchange in the heart

An integrative model of coupled water and solute exchange in the heart

Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart.

Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.

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