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Keywords:

  • Detrusor instability;
  • pig;
  • ischaemia;
  • hypoxia;
  • radiolabelled microspheres;
  • oxygen-sensitive electrode

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors

Objective To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs.

Materials and methods Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described.

Results In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals.

Conclusion In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors

BOO is known to be associated with a variety of morphological, contractile and biochemical changes within the bladder. In addition, the development of detrusor instability may follow that of BOO and some or all of the bladder changes may be implicated in its pathogenesis. An attempt has been made to rationalize these changes into a common ‘unifying’ hypothesis [1]. Most evidence in this field is derived from a variety of animal experimental models of BOO [2], supported by a few results in humans [3,4].

Several authors have reported that ischaemia or hypoxia of the bladder produces functional changes similar to those seen in obstruction [5,6], whilst others have reported biochemical changes in obstructed bladders which are interpreted as indicating the presence of in vivo hypoxia [7,8], or the adaptation of the bladder towards an anaerobic rather than aerobic metabolism [9,10]. A common feature both in obstructed and unstable bladders is a partial loss of cholinergic motor neurones within the detrusor. This is seen in obstructed [3], neuropathic [11] and idiopathic detrusor instability [12] in human bladders, and in the established obstructed pig model of detrusor instability [2]. The aetiology of this denervation and its role in the pathophysiology of detrusor instability is yet to be established but it is thought to be implicated in the smooth muscle changes detectable in these bladders [1].

Despite speculation that in vivo ischaemia/hypoxia may be responsible for the development of bladder dysfunction in BOO [13], it is not known whether this is mediated directly through an effect on the detrusor smooth muscle [14], or as a result of neuronal loss and subsequent smooth muscle changes [15]. To date there has been only one report that obstructed human bladders may be hypoxic [16] and one report indicating that acute bladder neck obstruction may lead to impaired blood flow and oxygenation in a dog model [17].

The present study was designed to investigate changes in detrusor blood flow and oxygenation in response to chronic BOO in a group of obstructed pigs compared with control animals, using radiolabelled microsphere and oxygen-sensitive electrode techniques.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors

In five female Large White pigs of 10–15 kg body weight, a partial urethral obstruction was created by placing a 7 mm (internal diameter) silver ring around the urethra, as described previously [2]. Five animals acted as sham-operated controls, where the urethra was exposed but the ring was not implanted. The animals were then allowed to grow over 12 weeks to a weight of 35–40 kg before experimentation.

After premedication using intramuscular ketamine (6.25 mg/kg) and midazolam (0.375 mg/kg) the animals were sedated with an intravenous infusion of propofol (1.5 mg/kg/h). Cystometry was then conducted via an 8 F double-lumen urethral catheter at a filling rate of 60 mL/min until voiding occurred. General anaesthesia was then induced with an intravenous bolus of ketamine/midazolam at the above doses, and maintained by infusing ketamine (6 mg/kg/h) and midazolam (0.18 mg/kg/h). The animals were intubated and allowed to breath spontaneously, initially on room air.

Catheters were placed in the left ventricle and right common femoral artery using the Seldinger technique after direct exposure of the left external carotid and right superficial femoral arteries, respectively. The abdomen was then opened by a short lower midline incision to expose the anterior wall of the bladder, which was then filled to a volume of 200 mL. A Clark-type polarographic oxygen-sensitive electrode system (Continucath 1000™, Biomedical Sensors, High Wycombe, England) was used to measure detrusor layer oxygen tension (PdetO2). The electrode was calibrated in saline bubbled with air at room temperature, subsequent measurements being corrected for ambient (the animal’s rectal) temperature. The electrode was positioned in the detrusor muscle layer using a 14 G intravenous cannula needle as a trocar. Great care was taken to avoid damage to the bladder wall vasculature. The abdomen was then closed with interrupted sutures. Systemic arterial oxygen tension (PaO2) was varied between ≈ 8 kPa and 80 kPa by altering the percentage of oxygen in an oxygen/nitrogen gas mixture delivered via a standard anaesthetic apparatus. At inspired oxygen fractions of 12.5%, 33%, 66% and 100%, PdetO2 was measured when the electrode output had stabilized, and a simultaneous arterial blood-gas specimen was taken from the left ventricular catheter. PaO2 was subsequently measured using a blood gas analyser (ABL3, Acid Base Laboratory System, Radiometer, Copenhagen, Denmark). After completing the PdetO2/PaO2 measurements, radiolabelled microspheres were injected to measure bladder blood flow, according to a standard technique [18]; 15 µm diameter 141Ce-labelled microspheres were used for the first injection. Before injection the total radioactivity in each microsphere vial was determined in a radioisotope calibrator (Amersham ARC 120, Capintec Inc., New Jersey, USA). After the injection all remaining radioactivity was measured and subtracted to obtain the injected dose. The injection was given into the left ventricle and the reference sample withdrawn from the femoral artery. The animal’s bladder was then filled to its capacity, as determined by the original cystometry, and the PdetO2 and PaO2 re-measured. A second microsphere sample was then injected as above, using 103Ru-labelled microspheres, to measure blood flow at cystometric capacity. The two isotopes used allow differential blood flow measurements to be obtained from the same tissue specimens.

The animals were then killed by injecting saturated potassium chloride solution into the left ventricle. The bladders were excised, transecting them at the level of the ureteric orifices, and weighed. A biopsy was taken from the dome of the bladder and prepared for cryostat sectioning by freezing it in isopentane cooled in liquid nitrogen. A 1 cm midline sagittal strip of bladder was taken from the posterior wall. After removing the mucosa from the strip, it was cut into 10 segments each of 0.5–1 g. The weighed biopsies, two standards each consisting of pure sample of one of each microsphere used, and the collected reference blood were counted for radioactivity in a multichannel gamma counter with automatic background subtraction. The two isotopes were discriminated by using different counting windows. All samples were counted for 5 min with correction for cross-talk between isotopes and decay during the counting procedure, using appropriate decay equations. Using the summed weights and counts from the 10 specimens, detrusor blood flow was calculated as [18]:

Regional blood flow (mL/min/100 g) = (counts/100 g tissue) × (V)/counts from reference sample

where V is the reference sample withdrawal rate(mL/min).

The frozen biopsies were sectioned on a cryostat and stained histochemically to detect neurones showing acetylcholinesterase activity [19]. Nerve densities were estimated using a point-counting technique and graticule eyepiece on randomly selected high-power microscope fields. No correction for tissue hypertrophy or fibrosis was made.

The slopes of PdetO2 as a function of PaO2 were estimated using a linear mixed-effects model [20] for each data group, which takes into account the repeated-measures structure of the experiment. The models were fitted with no intercept; these models were then used to predict the value of PdetO2 for a PaO2 of 11 kPa. Previous observation (unpublished) showed that the mean PaO2 of a fully conscious pig breathing room air to be 11 kPa. The standard errors of these predictions were obtained using a ‘bootstrap’ procedure with 1000 replicates for each model. Statistical significance was inferred where the 95% CIs did not overlap. The microsphere-derived detrusor blood flow data were normally distributed and analysed using paired and unpaired t-tests, as appropriate. The cystometric capacity, Pdet at end-filling, bladder weight and nerve density data were analysed using the exact Wilcoxon rank-sum test.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors

Three of the obstructed and none of the sham-operated animals showed evidence of detrusor instability on their initial cystometry, with phasic changes in detrusor pressure (Pdet) (Fig. 1). Under experimental conditions the animals showed a progressive rise in Pdet during filling and then emptied their bladders by simply relaxing the urethral sphincter, producing no additional detrusor contraction.

image

Figure 1. Urodynamics recording from an obstructed pig showing phasic detrusor contractions and a progressive increase in detrusor pressure. Filling rate 60 mL/min. *Start of bladder emptying. Detrusor pressure (Pdet, green), vesical pressure (Pves, red) and rectal pressure (Pabdo, light green).

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Table 1 summarizes the effects of BOO on the animal’s cystometric capacity, Pdet at end-filling, bladder weight and acetylcholinesterase-positive nerve density. Bladder weight increased significantly, whilst cystometric capacity and Pdet at the end of filling were not significantly changed. Overall, the estimated nerve density was significantly lower in the obstructed animals. The three obstructed bladders, which showed evidence of detrusor instability, had a distinctive pattern of loss of acetylcholinesterase-positive nerve fibres. In these specimens some of the smooth muscle bundles showed normal staining whilst others showed very little or no staining (Fig. 2); the proportion of denervated bundles was 20–50%. None of the control or either of the obstructed animals with stable bladders showed a similar pattern of denervation. There was no apparent association between the presence of this patchy denervation and the degree of bladder hypertrophy.

Table 1.  The bladder characteristics of the control and obstructed pigs
Mean (sd) Control Obstructed
  • *

    P < 0.05 obstructed vs. control, Wilcoxon rank-sum test.

Cystometric capacity (mL)890 (194)1256 (247)
Pdet at end filling (cmH2O)37.4 (12.8)40.0 (19.3)
Bladder weight (g)36.7 (9.55)49.9 (6.32)*
Nerve density (mm2)252 (10.1)199 (46.7)*
image

Figure 2. Photomicrograph of detrusor muscle stained histochemically to detect acetylcholinesterase-containing nerve fibres. † indicates a muscle bundle with normal acetylcholinesterase staining, and * indicates a muscle bundle with no staining. Scale bar = 100 µm.

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Figure 3 shows the individual plots of PaO2 vs PdetO2, together with the fitted linear mixed-effects model regression line and slope (with the sem) for each series. Table 2 compares the effects of bladder filling on detrusor blood flow and PdetO2 at a PaO2 of 11 kPa in the two groups. The obstructed bladders had a detrusor blood flow that was 54.9% of the control bladders at low volume and 47.5% of the controls at capacity. The values for PdetO2 are 74.3% and 42.5%, respectively. Detrusor blood flow decreased by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decline in the controls, but decreased by 42.7% in the obstructed bladders. The data from the obstructed animals showed no correlation between the apparent ‘degree’ of obstruction, as assessed by the changes in the physical characteristics of the bladders, and the changes in PdetO2 and blood flow. Nor was there any relationship between the presence of detrusor instability/patchy denervation in the obstructed animals and the magnitude of the changes in detrusor blood flow and PdetO2.

image

Figure 3. The effect of BOO and bladder filling on the relationship between PaO2 and PdetO2, showing the regression lines derived from the mixed-effects analysis. The vertical line indicates the mean PaO2 in a conscious pig breathing room air. The mean (sem) slopes are: red, control animals, 200 mL in the bladder, 0.29 (0.013); green, control animals, at capacity, 0.26 (0.013); black, obstructed animals, 200 mL in the bladder, 0.21 (0.009); light green, obstructed animals, at capacity, 0.12 (0.009).

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Table 2.  The effect of filling on blood flow and oxygen tension (PaO2 = 11 kPa) in control and obstructed bladders
  Control Obstructed
Mean ( s e m ) at 200 mL at capacity at 200 mL at capacity
  • * 

    P < 0.05 capacity vs 200 mL,

  • † 

    obstructed vs control, t-test; statistical significance inferred, mixed-effects analysis,

  • ¶ 

    capacity vs 200 mL,

  • ‡ 

    ‡ obstructed vs control.

Detrusor blood flow (ml/min/100g)75.8 (5.2)54.7 (6.2)*41.6 (5.8)26.0 (3.1)*
PdetO2 (kPa)3.12 (0.13)3.13 (0.11)2.32 (0.07)1.33 (0.09)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors

The bladders from the obstructed animals showed a significant increase in weight, which was interpreted as being consistent with the development of BOO. Histochemically there was evidence of detrusor denervation, which in three of the animals occurred in a patchy distribution, as noted previously in other animal studies (unpublished observation), and in humans with idiopathic detrusor instability [12]. The mechanism causing this pattern of denervation is not understood, but it may be related to the distribution of the cell bodies of the cholinergic motor neurones. In the pig, as in the human, some of the parasympathetic ganglia are in the wall of the bladder, whilst others lie in the pelvic plexus. If the insult responsible for the loss of the neurones is confined to the bladder then postganglionic neurones originating in the pelvic plexus will be preserved. Previous studies which have reported that BOO causes a partial denervation [2,3] have been criticised, as it is very difficult to compensate for the effects of muscle cell hypertrophy and connective tissue deposition occurring as a result of BOO. However, the present patchy distribution of denervation cannot be explained by this effect as the hypertrophy and connective tissue deposition occurs evenly throughout the tissue.

The use of radiolabelled microspheres to measure local organ blood flow is a well established technique and has been used by others to measure bladder blood flow, with values of 20–50 mL/min/100 g reported [21,22]; the present values are of a similar magnitude. The measurement of issue oxygen tension with an implanted electrode is less well established but has been validated for the electrode system used here [23,24]. A potential error with any polarographic oxygen measurement system is that the electrode consumes oxygen at a rate directly related to the current generated. This potential error may be especially significant at low tissue PO2 but may be minimized by using electrodes that generate relatively low currents. The oxygen consumption of the Continucath 1000 electrode at a PO2 of 2.03 kPa is estimated to be 2.36 × 10−13 mol/s [25]. This compares to an estimated oxygen delivery of 5.01 × 10−11 mol/s at a blood flow of 26 mL/min/100 g. The PO2 and blood flow levels used in these calculations correspond to the lowest levels observed experimentally. As a result, oxygen consumption by the electrode would not appear to be significant at these PO2 and blood flow levels.

Tissue oxygen levels in smooth muscle have not been widely reported but are 2–5 kPa [26], in agreement with the levels recorded in the present animals. In their study on anaesthetized dogs with acute BOO, Azadzoi et al.[17] reported bladder wall PO2 levels which are ≈ 1 kPa higher than those in the present study. This difference may be partly explained because Azadzoi et al. made no correction for potential alteration in tissue PO2 as a result of changes in PaO2 under anaesthesia.

The present results show that both bladder filling and outlet obstruction result in significant decreases in detrusor blood flow, whilst PdetO2 in the obstructed bladders declined as a result of filling and was lower than that of the control bladders. The obstructed bladders showed greater changes in blood flow and PdetO2 as a result of bladder filling. Whilst the magnitude of the changes in the obstructed bladders might be expected to correlate with the degree to which they were obstructed, no such relationship was detected. Unfortunately, the experimental conditions did not permit an accurate assessment of the degree of obstruction, e.g. by pressure-flow analysis. In addition, the relatively few animals used precludes a significant result unless the relationship was close.

We have previously reported that in conscious normal pigs bladder filling does not alter blood flow unless Pdet increases [27]. Others have also reported that bladder filling causes a decrease in blood flow in association with a rise in Pdet [22]. The present findings support the view that the increase in Pdet observed in these animals during filling may account for the fall in detrusor blood flow, which in turn may be responsible for the changes in PdetO2, as observed in other tissues [28]. Nielsen [29], using 133Xe-washout measurements in pigs, reported that partial BOO did not alter bladder blood flow, but resulted in a decrease in blood flow in response to bladder filling which did not occur in the animals before the establishment of BOO. Nielsen’s study differs in the choice of measurement technique and in that it was a longitudinal study, with measurements taken in the same animals at different ages and weights, differences which may, at least partly, account for some of the discrepancies with the present results. The present differences in detrusor blood flow and PdetO2 at low bladder volume cannot be explained by differences in Pdet and must therefore reflect a difference in blood flow and oxygen availability in the obstructed bladders, as suggested by the shallower slopes of the PdetO2/PaO2 relationships for the obstructed bladders. The potential mechanisms underlying this are unknown, but may be related to the muscle hypertrophy and collagen deposition which is known to occur in obstructed bladders [3], with subsequent impairment of oxygen diffusion to the tissues. In pigs, as in humans, obstructed bladders appear ‘hypervascular’. BOO in rats has been shown to produce a rapid microvascular growth [30], but in pigs the vascular length densities were unaltered by BOO [29]. How this relates to the degree of hypoxia in the present animals is unknown. In the heart, rapid hypertrophy may outstrip vascular growth, leading to myocardial hypoxia [31]; the same phenomenon may be occurring in the pig bladder in response to BOO. Neurones are known to be very sensitive to hypoxic damage, with grey matter more easily damaged than white [32]. Unfortunately, very little is known about the sensitivity of postganglionic parasympathetic neurone cell bodies and axons to hypoxia. Whether the present degree of hypoxia is sufficient to account for the denervation found in obstructed bladders is therefore unknown. This impaired blood flow and hypoxia, perhaps compounded by the greatly increased metabolic demands of producing high-pressure voiding contractions, may result in the development of some of the widespread functional and structural changes seen in obstructed bladders.

In conclusion, in pigs with BOO, blood flow and oxygen tension in the detrusor layer appear to be less than that in controls. In addition, increasing detrusor pressure during filling brought about significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors
  • 1
    Brading AF & Turner WH. The unstable bladder: towards a common mechanism. Br J Urol 1994; 73: 38
  • 2
    Speakman MJ, Brading AF, Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA. Bladder outflow obstruction — a cause of denervation supersensitivity. J Urol 1987; 138: 14616
  • 3
    Gosling JA, Gilpin SA, Dixon JS, Gilpin CJ. Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J Urol 1986; 136: 5014
  • 4
    Cumming JA & Chisholm GD. Changes in detrusor innervation with relief of outflow tract obstruction. Br J Urol 1992; 69: 711
  • 5
    Lin AT, Wein AJ, Gill HS, Levin RM. Functional effect of chronic ischaemia on the rabbit urinary bladder. Neurourol Urodyn 1988; 7: 112
  • 6
    Gill HS, Monson FC, Wein AJ, Ruggieri MR, Levin RM. The effects of short-term in-vivo ischemia on the contractile function of the rabbit urinary bladder. J Urol 1988; 139: 13504
  • 7
    Arner A, Malmqvist U, Uvelius B. Metabolism and force in hypertrophic smooth muscle from rat urinary bladder. Am J Physiol 1990; 258: C92332
  • 8
    Polyanska M, Arner A, Malmquist U, Uvelius B. Lactate dehydrogenase activity and isoform distribution in the rat urinary bladder: effects of outlet obstruction and its removal. J Urol 1993; 150: 5435
  • 9
    Kato K, Monson FC, Longhurst PA, Wein AJ, Haugaard N, Levin RM. The functional effects of long-term outlet obstruction on the rabbit urinary bladder. J Urol 1990; 143: 6006
  • 10
    Haugard N, Potter L, Wein AJ, Levin RM. Effect of partial obstruction of the rabbit urinary bladder on maleate dehydrogenase and citrate synthase activity. J Urol 1992; 147: 13913
  • 11
    German K, Bedwani J, Davies J, Brading A, Stephenson TP. What is the pathophysiology of detrusor hyperreflexia. Neurourol Urodyn 1993; 12: 3356
  • 12
    Mills IW, Greenland JE, McMurray G, Ho KMT, Noble JG, Brading AF. The in vitro and histological properties of bladders from patients with idiopathic detrusor instability indicate that there is partial denervation of the detrusor. Br J Urol 1997; 79 (Suppl 4): 48
  • 13
    Elbadawi A, Meyer S, Regnier CH. Role of ischaemia in structural changes in the rabbit detrusor following partial bladder outlet obstruction: a working hypothesis and a biomechanical/structural model proposal. Neurourol Urodyn 1989; 8: 15162
  • 14
    Zhao Y, Levin SS, Wein AJ, Levin RM. Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder. Urology 1997; 49: 293300
  • 15
    Yokoyama O, Kawaguchi K, Hisazumi H. [Denervation supersensitivity of the detrusor muscle due to bladder overdistension, with special reference to the relationship between supersensitivity, and changes in the connective tissue]. Hinyokika Kiyo 1985; 31: 212734
  • 16
    Loran OB, Vishnevskii EL, Vishnevskii AE. [The role of detrusor hypoxia in the pathogenesis of urination disorders in patients with benign prostatic hyperplasia]. Urol Nefrol Mosk 1996; 6: 337
  • 17
    Azadzoi KM, Pontari M, Vlachiotis J, Siroky MB. Canine bladder blood flow and oxygenation: changes induced by filling, contraction and outlet obstruction. J Urol 1996; 155: 145965
  • 18
    Hales JRS. Radioactive microsphere techniques for the studies of the circulation. Clin Exper Pharm Physiol 1974; (Suppl. 1): 3146
  • 19
    Tago H, Kimura H, Maeda T. Visualisation of detailed acetylcholinesterase fibre and neuron staining in rat brain by a sensitive histochemical procedure. J Histochem Cytochem 1986; 34: 14318
  • 20
    Vonesh EF & Chinchilli VM. Linear and Nonlinear Models for the Analysis of Repeated Measurements. New York: Marcel Dekker Inc, 1997
  • 21
    Kroyer K, Bulow J, Nielsen SL, Kromann AB. Urinary bladder blood flow. I. Comparison of clearance of locally injected 99m technetium pertechnate and radioactive microsphere technique in dogs. Urol Res 1990; 18: 2236
  • 22
    Nielsen KK, Nielsen SL, Nordling J, Kromann AB. Rate of urinary bladder blood flow evaluated by 133Xe washout and radioactive microspheres in pigs. Urol Res 1991; 19: 38791
  • 23
    Hjortdal VE, Timmenga EJ, Klolseth D et al. Continuous direct tissue oxygen tension measurement. A new application for an intravascular oxygen sensor. Ann Chir Gynaecol 1991; 80: 813
  • 24
    Hofer SO, van der Kleij AJ, Bos KE. Tissue oxygenation measurement: a directly applied Clark-type electrode in muscle tissue. Adv Exp Med Biol 1992; 317: 77984
  • 25
    Lessler MA. Oxygen electrode measurements in biochemical analysis. Meth Biochem Anal 1969; 17: 129
  • 26
    Sheridan WG, Lowndes RH, Young HL. Intraoperative tissue oximetry in the human gastrointestinal tract. Am J Surg 1990; 159: 3149
  • 27
    Greenland JE & Brading AF. Urinary bladder blood flow changes during the micturition cycle in a conscious pig model. J Urol 1996; 156: 185861
  • 28
    Hofer SO, van der Kleij AJ, Grundeman PF, Scholten EW, Klopper PJ. Critical tissue oxygen tension defines tissue oxygen debt in the isolated hindlimb of the pig during progressive ischemia. Crit Care Med 1995; 23: 9318
  • 29
    Nielsen KK. Blood flow rate and total blood flow related to length density and total length of blood vessels in mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction. Neurourol Urodyn 1995; 14: 17786
  • 30
    Gabella G. Hypertrophy of visceral smooth muscle. Anat Embryol Berl 1990; 182: 40924
  • 31
    Hudlicka O & Brown MD. Postnatal growth of the heart and its blood vessels. J Vasc Res 1996; 33: 26687
  • 32
    Haddad GG & Jiang C. O2 deprivation in the central nervous system: on mechanisms of neuronal response, differential sensitivity and injury. Prog Neurobiol 1993; 40: 277318

Authors

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. References
  8. Authors

J.E. Greenland, MB, ChB, FRCS, Specialist Registrar.

J.J. Hvistendahl, MD, Research Fellow.

H. Andersen, MD, Research Fellow.

T.M. Jörgensen, MD, PhD, Consultant.

G. McMurray, BSc, PhD, Post Doctoral Research Fellow.

M. Cortina-Borja, PhD, Lecturer.

A.F. Brading, MA, PhD, Professor of Pharmacology.

J. Frøkiær, MD, Associate Professor.