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Biomedical subjects

O Hudlicka

Publications and source records attributed to O Hudlicka.

At least 37 records · Page 2Linked to original sources
PubMed1996

Appearance of the capillary endothelial glycocalyx in chronically stimulated rat skeletal muscles in relation to angiogenesis.

The endothelial glycocalyx layer of capillaries was stained with Ruthenium Red and examined by transmission electron microscopy in rat extensor hallucis proprius muscles after 2 or 4 days of indirect electrical stimulation via implanted electrodes. The layer appeared continuous on the luminal surface of 63% capillaries in control muscles and absent 13%. This situation was reversed in muscles stimulated for 2 or 4 days, with a continuous layer in 12 and 10% of capillaries and no glycocalyx in 44 and 58%, respectively. The greater disruption of the endothelial luminal glycocalyx in capillaries from stimulated muscles suggests that flow-related shear forces on endothelial cells could be important signals for initiation of angiogenesis in actively contracting skeletal muscle.

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PubMed1995

The effect of long-term tilting on capillary supply in rat hindlimb muscles.

Rats were kept for three weeks tilted head-up at 45 degrees and their capillary supply (capillary density CD, number of capillaries/mm2, and capillary/fibre ratio C/F), fibre density FD, and muscle weights were compared with a group of animals with similarly restricted movement but at horizontal position, and with control freely moving animals. Movement restriction caused loss of muscle (but not body) weight in fast muscles in all rats, and gain of weight in slow postural soleus in the tilted group. Neither of these changes were due to changes in the content of water. Loss of weight was accompanied by increased fibre density indicative of muscle atrophy due to movement restriction. Capillary supply was not affected by movement restriction, but was significantly decreased, particularly in the oxidative part of tibialis anterior and in the soleus of tilted animals (C/F: 1.78 +/- 0.11 vs 2.11 +/- 0.05 and 2.06 +/- 0.08 vs 2.29 +/- 0.10). It is assumed that this reduction might be explained by changes in hemodynamic characteristics of the venous vascular bed due to a chronic increase in hydrostatic pressure load.

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PubMed1994

Chronic muscle stimulation improves ischaemic muscle performance in patients with peripheral vascular disease.

There is currently no established treatment for intermittent claudication with proven long term benefit. Exercise classes have been shown to improve walking distance. Chronic electromyostimulation (CEMS) a method of stimulating skeletal muscle has effects on normal muscle which may also benefit claudicants. We investigated the effects of one month of CEMS on claudicants in a single blind placebo controlled study. Patients were randomised to either CEMS (treatment) or transcutaneous nerve stimulation (TENS) placebo. The effects of the two modalities were assessed using the conventional measures of claudicating distance (CD), maximum walking distance (MWD), ankle-brachial pressure index (ABPI) and pressure recovery time (PRT). Muscle performance was assessed by the fatigue index (FI) a technique determining the decrease in ischaemic muscle response to repeated contraction. After 4 weeks treatment the CEMS group showed significant improvements in their median CD (88 to 111) and MWD (118 to 158); this was not seen in the control group. Muscle performance also increased significantly during the 4 weeks of treatment in the CEMS group but not in the control group. These changes were not maintained after CEMS was stopped. This pilot study suggests that CEMS may well have a role to play in the treatment of intermittent claudication though a number of further studies need to be undertaken.

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PubMed1994

Long term bradycardia by electrical pacing: a new method for studying heart rate reduction.

OBJECTIVE: The aim was to develop a method of inducing bradycardia on a chronic basis by electrical pacing and to study its effect upon myocardial capillarity in pigs. METHODS: Farm pigs were instrumented with Medtronic dual chamber telemetric pacemakers and two leads, either both atrial or one atrial and one ventricular. Bradycardia was achieved by linking pacing stimuli to endogenous atrial or ventricular events for the different electrode positions respectively, and monitored postoperatively for 4-5 weeks by implanted telemetric ECG devices. Myocardial capillary supply (lectin staining) and myocyte cross sectional areas were then estimated in sections of the left ventricle. RESULTS: Heart rates were reduced by 40-50 beats.min-1 at operation from a resting rate of 110(SEM 3) beats.min-1 in eight animals and bradycardia maintained upon recovery from anaesthesia for up to five weeks, with no obvious limitations for the animals. After this time, heart rates measured under anaesthesia were found to remain low for up to 2 h after pacing had been switched off. There was no evidence of myocyte hypertrophy, yet mean capillary density.mm-2 was significantly increased by pacing, from 1470(50) to 1734(82), p < 0.02. CONCLUSIONS: It is possible to produce primary heart rate reduction in the pig by a novel means of pacing on a chronic basis, leading to increased myocardial capillary supply without myocyte hypertrophy. This method can provide a basis for future investigations of the beneficial effects of heart rate reduction in the vascularly compromised heart.

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PubMed1994

Effect of torbafylline on muscle blood flow, performance, and capillary supply in ischemic muscles subjected to varying levels of activity.

Torbafylline, a novel xanthine derivative, was given to rats by gavage (2 x 25 mg.kg-1.day-1, morning and evening) to study its effect upon fast muscles (tibialis anterior and extensor digitorum longus) made ischemic by unilateral ligation of the common iliac artery and subjected to two types of activity imposed by chronic electrical stimulation at 10 Hz: (i) strenuous, 6 h.day-1 as 3 x 2 h with 90- to 120-min intervals or (ii) mild, 105 min.day-1 as 7 x 10-15 min with 90- or 85-min intervals for 12-14 days. Some of the deleterious effects on ischemic muscles of strenuous activity (reduced blood flow during contractions, less resistance to fatigue) were remedied by torbafylline treatment, and values normalized. Most notably, torbafylline significantly reduced the degree of capillary endothelial cell swelling. In addition, the degree of atrophy was reduced and fatigue resistance improved in muscles contralateral to ischemic, which had been impaired with the strenuous regime. Torbafylline treatment had little further effect on ischemic muscles subjected to mild stimulation, which on its own improved functional hyperemia, resistance to fatigue, and the capillaries per fibre ratio in tibialis anterior, although it did significantly increase the capillary per fibre ratio in extensor digitorum longus. These data indicate a possible role for torbafylline as an adjunct to exercise therapy for chronic muscle ischemia.

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PubMed1994

Effect of long-term electrical stimulation on vascular supply and fatigue in chronically ischemic muscles.

Fast skeletal muscles of Sprague-Dawley rats [tibialis anterior (TA) and extensor digitorum longus (EDL)] were subjected to ischemia by unilateral ligation of the common iliac artery. In some animals, ischemia was combined with indirect electrical stimulation at 10 Hz either for 3 x 2 h (strenuous activity) or for 7 x 10-min bouts/day (mild activity). After 2 wk, muscle blood flow and fatigue were measured during 5-min isometric supramaximal twitch contractions at 4 Hz. Terminal arteriole diameters were assessed in TA by intravital microscopy at rest and during contractions. Vascular perfusion pressure in the muscles was estimated from measurements in the carotid and saphenous arteries below the site of ligation. Capillary supply was expressed in TA and EDL as capillary-to-fiber ratio on the basis of histochemical staining for capillaries. Strenuous stimulation of ischemic muscles increased their atrophy, failed to restore blood flow, and actually worsened fatigue. In contrast, mild stimulation improved perfusion pressure, increased capillary-to-fiber ratio in the glycolytic part of TA, restored dilatation of terminal arterioles during muscle contractions, and improved blood flow and muscle fatigue so that they were no longer significantly different from control muscles. Thus, an attenuated intermittent protocol may be indicated in the treatment of muscle ischemia.

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PubMed1994

The effect of long-term bradycardia on heart microvascular supply and performance.

Bradycardia has been shown to be beneficial for the normal and ischaemic heart because it improves diastolic perfusion and oxygen supply demand balance. Experimentally, a chronically induced decrease in heart rate, either by electrical pacing or pharmacological means, was found previously to increase myocardial capillary supply in normal rabbit and rat hearts. These studies have been extended to a larger mammal, the pig, in which a direct bradycardia (approximately 30% decrease in heart rate) was induced by electrical pacing for 4-5 weeks. There was no evidence of heart hypertrophy and capillary density was found to be significantly increased in the left, but not right, ventricle. Cardiac function during dobutamine inotropic challenge was better in pig hearts which had been paced bradycardially. They performed greater stroke work-higher stroke flow output at lower heart rate--for similar coronary blood flow, thus demonstrating an improved economy of flow utilisation. Heart rate reduction may facilitate capillary growth in the absence of cardiac hypertrophy by prolonging diastolic perfusion, and/or mechanical stretch of vessels due to increased stroke volume capacity. In either case, capillaries would be exposed to increased wall tension which could trigger angiogenesis.

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PubMed1994

Mechanical factors involved in the growth of the heart and its blood vessels.

Various proteins of cardiac myocytes are preprogrammed at a very early stage of heart development, but functional load (stretch, pressure) plays an important role in their expression under both physiological and pathological circumstances. Mechanical factors are also important in growth of vessels, particularly with respect to hypertrophy or hyperplasia of vascular smooth muscle. Their effect on growth of endothelial cells is less clear. Although they have been studied in cell culture, little is known about their involvement in capillary growth in vivo. Their possible role is considered in capillary growth in the normal adult heart where it was elicited by long-term administration of various vasodilators, by long-term bradycardia, or by increased inotropic action. Here the mechanical stimuli may act either by increased shear stress (resulting from increased velocity of flow in long-term dilatation) or by increasing vessel wall tension (in conjunction with increased diameters and/or stretch produced by increased inotropism). While the role of growth factors in the development of myocytes has been established, it is still questionable in capillary growth. It is also possible that various growth factors exert their effect on vessel growth by their vasoactive activity.

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PubMed1993

Intermittent claudication incites systemic neutrophil activation and increased vascular permeability.

Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte-endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations.

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PubMed1993

Can changes in microcirculation explain capillary growth in skeletal muscle?

Capillary growth (increase in capillary/fibre (C/F) ratio by 20%) was elicited in skeletal muscles either by long-term increase in blood flow (5 weeks administration of prazosin in drinking water, 50 mg/l) or 7 days electrical stimulation (8 h/day at 10 Hz). Mechanisms that could explain it ((a) increased interaction of blood components with endothelial cells (due to increased haematocrit or decreased intermittency of flow); (b) increased velocity of flow and thus shear stress; (c) increased capillary diameters and thus wall tension) were studied in vivo. Red blood cell velocity (Vrbc), vessel diameters and intermittency of capillary flow were measured in superficially located capillaries in rat tibialis anterior muscles about 18 hours after the last treatment, in prazosin treated and chronically stimulated animals, and also in animals where red blood cell interaction with capillary endothelium was increased by elevating haematocrit from 43.2 +/- 1.7% to 60.9 +/- 0.72% by 11 weeks administration of CoCl2. Animals of comparable size and sex were used as controls. Capillaries in chronically stimulated muscles had increased Vrbc at rest (0.42 +/- 0.06 mm/s vs 0.27 +/- 0.04 in control muscles) and somewhat wider diameters, although the intermittency of flow was not different from control muscles. Capillaries in prazosin treated rats had a lower intermittency of flow, similar diameters and considerably higher Vrbc (0.53 +/- 0.06 mm/s) than control animals. CoCl2 treatment resulted in a similar intermittency of flow, did not alter capillary diameters or Vrbc and did not result in an increase in C/F ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1993

Fine structure of capillaries in ischaemic and non ischaemic rat striated muscle. Effect of torbafylline.

Capillary ultrastructure was studied in ischaemic and contralateral extensor digitorum longus (EDL) muscle, in the diaphragm and left ventricular papillary muscle of rats with unilateral ligation of the common iliac artery (L), in ischaemic stimulated muscles (SL), and in ischaemic stimulated muscles of animals treated with a new xanthine derivative, torbafylline (SL&T). Muscles were stimulated at 10Hz via implanted electrodes 7 times/day for 2 weeks. Torbafylline or water was given by gavage morning and evening. Nominal evaluation of capillary ultrastructure revealed endothelial swelling in 52.7 +/- 8.7% (mean +/- SEM) capillaries in ischaemic muscles, 35.2 +/- 5.6% in contralateral muscles and about 30% in the diaphragm and papillary muscle. Stimulation of ischaemic muscles increased this proportion to 62.6 +/- 6.2% (not significant vs. L), 57.8 +/- 9.5% (p < 0.05 vs. L), 62.6 +/- 6.3 (p < 0.05 vs. L) and 43.7 +/- 4.2% (p < 0.05 vs. L) in ischaemic and contralateral EDL, diaphragm and papillary muscle, respectively. Administration of torbafylline reduced the proportion of swollen capillaries to 37.8 +/- 6.1.45% (p < 0.02 vs. SL) in ischaemic muscles, and to 26.2 +/- 2.1% (p < 0.001) in papillary muscle, with a smaller effect in the contralateral EDL and the diaphragm. Stereological analysis showed that stimulation led to a marked increase in capillary size vs. contralateral muscles. A similar lumen volume density across all groups (Vv = 0.36-0.39), vs. control Vv = 0.47, reflected structural heterogeneity within the capillary population of EDL. For most components this intra- animal variation obscured drug treatment effects, the exception being Vv(nucleus) which was least in SL&T. Activity in ischaemic muscles can thus result in widespread capillary endothelial damage in muscles, and attenuation of this swelling by torbafylline may explain the beneficial effect of this drug on capillary perfusion and performance.

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PubMed1992

Capillary growth in the heart.

Experiments were performed to test the hypothesis that increased stretch and/or tension of myocytes in the absence of changes in blood flow could induce capillary growth in the heart. Chronic treatment with either dobutamine (rabbits) or alinidine (rats) which increased force of contraction and/or stroke volume respectively without increases in coronary blood flow led to enlargement of the anatomical size of the capillary bed, with no change in cardiac weight, thus supporting the role of external mechanical factors in angiogenesis.

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PubMed1992

Regional capillary perfusion in muscles with limited blood supply: effects of torbafylline.

Severe limitation of blood supply mainly affects the oxidative regions of skeletal muscles. In mammals, they are located medially and are thus not accessible to direct observation. We therefore investigated capillary perfusion in rat tibialis anterior, which has a predominantly glycolytic cortex and oxidative core, using timed intraarterial injection of the fluorochrome thioflavine S conjugated with serum albumin. Muscles with intact blood supply were compared with those in which the blood supply had been limited for 5 weeks by unilateral ligation of the common iliac artery. The effect of a new xanthine derivative, torbafylline (1% solution, 12.5 mg/kg, in two daily doses by gavage, 7 days/week), was also studied. The capillary/fibre ratio was estimated for perfused capillaries (those filled with fluorochrome within 7.5 s after injection; Cp) and all capillaries (those subsequently stained for alkaline phosphatase; Ct), from micrographs of cryostat sections. Regional differentiation in relative capillary perfusion was evident in all muscles samples. Cp:Ct was 0.406 +/- 0.086 (mean +/- 95% CI) in the glycolytic cortex of the contralateral normal muscle, and 0.255 +/- 0.071 in the oxidative core. Muscles with limited blood supply had a significantly lower proportion of perfused capillaries, 0.119 +/- 0.056 in glycolytic and 0.034 +/- 0.038 in oxidative regions. Torbafylline treatment nearly doubled perfusion in the glycolytic regions (Cp:Ct = 0.216 +/- 0.137) and nearly quadrupled it in oxidative (Cp:Ct = 0.121 +/- 0.151) regions of ischaemic muscles. It also improved perfusion in the contralateral muscles (Cp:Ct = 0.705 +/- 0.085 in the glycolytic cortex and 0.583 +/- 0.230 in the oxidative core).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1992

Claudication induces systemic capillary endothelial swelling.

An in vivo model of intermittent claudication has been developed to investigate systemic reperfusion injury associated with transient muscle ischaemia. Rats were subjected to unilateral common iliac artery ligation and two weeks of intermittent hind limb muscle stimulation. Electron microscopy demonstrated a significantly increased percentage of swollen capillary endothelial cells both locally and systemically in these "claudicant" rats, compared with controls or those undergoing muscle stimulation or artery ligation alone. These results support human data suggesting that claudication induces an inflammatory response which results in systemic vascular injury.

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PubMed1991

Capillary supply and cardiac performance in the rabbit after chronic dobutamine treatment.

STUDY OBJECTIVE: Growth of capillaries in the adult heart can occur after long term vasodilator treatment. This study investigated the effects of increased stroke volume and/or force of contraction in addition to coronary blood flow on myocardial capillary growth. DESIGN: Coronary blood flow, cardiac function, and capillary supply were evaluated after chronic treatment with the inotrope dobutamine, at a dose shown to increase contraction force (dP/dt) acutely by 20% (p less than 0.05) and coronary blood flow by 60% (NS). EXPERIMENTAL MATERIAL: New Zealand Red rabbits received dobutamine (20 micrograms.kg-1.min-1 by intravenous infusion) for 2 weeks prior to measurements, under pentobarbitone anaesthesia, of coronary blood flow by radiolabelled microspheres, left ventricular dP/dtmax and maximum noradrenaline induced cardiac work, computed from cardiac output (thermodilution) and blood pressure. Capillary density.mm-2 was estimated in frozen 12 microns sections of left ventricular myocardium stained for alkaline phosphatase. MEASUREMENTS AND MAIN RESULTS: Capillary density was 29% greater after 2 weeks dobutamine infusion than in saline infused controls, which exceeds increases observed after longer infusions of vasodilators alone. Cardiac function was improved; maximum stroke work was significantly higher, stroke volume capacity larger, and dP/dt increased more during noradrenaline challenge. Coronary blood flow was unchanged in dobutamine treated hearts, hence efficiency of utilisation of coronary flow in terms of work was enhanced. Heart to body weight ratio was also greater after dobutamine, at 0.238(SEM 0.008) v 0.206(0.120), p less than 0.05. CONCLUSIONS: Greater capillary growth can be elicited in the heart by increased stretch and/or force of contraction of myocytes in addition to moderate changes in blood flow than by increased blood flow alone. Chronic dobutamine treatment induced adaptive enhancement of maximal cardiac work capacity.

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