Capillary Blood Flow Distribution Research Articles

Capillary dysfunction in healthy elderly APOE ε4 carriers with raised brain Aβ deposition.

Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals. Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers. Capillary dysfunction was elevated in both prodromal and preclinical AD individuals compared to age-matched controls. Additionally, the prodromal group exhibited higher levels of capillary dysfunction compared to the preclinical group. These findings suggest that capillary dysfunction can be detected at the preclinical stage of AD and indicates a worsening of capillary dysfunction throughout the AD continuum. Understanding the interaction between capillary dysfunction and Aβ could provide insights into the relationship between cardiovascular risk factors and the development of AD. Alzheimer's disease (AD) is associated with disturbances in microvascular circulation. Capillary dysfunction can be detected in preclinical AD. As cognitive symptoms progress in prodromal AD, capillary dysfunction worsens. Capillary dysfunction may impede the clearance of beta-amyloid (Aβ). Capillary dysfunction might contribute to the development of AD.

Deletion of aquaporin-4 improves capillary blood flow distribution in brain edema.

Brain edema is a feared complication to disorders and insults affecting the brain. It can be fatal if the increase in intracranial pressure is sufficiently large to cause brain herniation. Moreover, accruing evidence suggests that even slight elevations of intracranial pressure have adverse effects, for instance on brain perfusion. The water channel aquaporin-4 (AQP4), densely expressed in perivascular astrocytic endfeet, plays a key role in brain edema formation. Using two-photon microscopy, we have studied AQP4-mediated swelling of astrocytes affects capillary blood flow and intracranial pressure (ICP) in unanesthetized mice using a mild brain edema model. We found improved regulation of capillary blood flow in mice devoid of AQP4, independently of the severity of ICP increase. Furthermore, we found brisk AQP4-dependent astrocytic Ca2+ signals in perivascular endfeet during edema that may play a role in the perturbed capillary blood flow dynamics. The study suggests that astrocytic endfoot swelling and pathological signaling disrupts microvascular flow regulation during brain edema formation.

Visualization of the intrarenal distribution of capillary blood flow.

This study describes a modified technique to fill the renal vasculature with a silicon rubber (Microfil) compound and obtain morphologic information about the intrarenal distribution of capillary blood flow under a variety of conditions. Kidneys and cremaster muscles of rats were perfused in vivo with Microfil using a perfusion pressure equal to the animal's mean arterial pressure at body temperature. Microfil did not alter arteriolar diameter or the pattern of flow in the microcirculation of the cremaster muscle. The modified protocol reproducibly filled the renal vasculature, including; glomerular, peritubular, and vasa recta capillaries. We compared the filling of the renal circulation in control rats with that seen in animals subjected to maneuvers reported to alter the intrarenal distribution of blood flow. Infusion of angiotensin II, hypotension, volume expansion, and mannitol‐ or furosemide‐induced diuresis redistributed flow between renal cortical and medullary capillaries. The advantage of the current technique is that it provides anatomical information regarding the number, diameter, and branching patterns of capillaries in the postglomerular circulation critical in determining the intrarenal distribution of cortical and medullary blood flow.

The coronary circulation in exercise training.

Exercise training (EX) induces increases in coronary transport capacity through adaptations in the coronary microcirculation including increased arteriolar diameters and/or densities and changes in the vasomotor reactivity of coronary resistance arteries. In large animals, EX increases capillary exchange capacity through angiogenesis of new capillaries at a rate matched to EX-induced cardiac hypertrophy so that capillary density remains normal. However, after EX coronary capillary exchange area is greater (i.e., capillary permeability surface area product is greater) at any given blood flow because of altered coronary vascular resistance and matching of exchange surface area and blood flow distribution. The improved coronary capillary blood flow distribution appears to be the result of structural changes in the coronary tree and alterations in vasoreactivity of coronary resistance arteries. EX also alters vasomotor reactivity of conduit coronary arteries in that after EX, α-adrenergic receptor responsiveness is blunted. Of interest, α- and β-adrenergic tone appears to be maintained in the coronary microcirculation in the presence of lower circulating catecholamine levels because of increased receptor responsiveness to adrenergic stimulation. EX also alters other vasomotor control processes of coronary resistance vessels. For example, coronary arterioles exhibit increased myogenic tone after EX, likely because of a calcium-dependent PKC signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, EX augments endothelium-dependent vasodilation throughout the coronary arteriolar network and in the conduit arteries in coronary artery disease (CAD). The enhanced endothelium-dependent dilation appears to result from increased nitric oxide bioavailability because of changes in nitric oxide synthase expression/activity and decreased oxidant stress. EX also decreases extravascular compressive forces in the myocardium at rest and at comparable levels of exercise, mainly because of decreases in heart rate and duration of systole. EX does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. While there is evidence that EX can decrease the progression of atherosclerotic lesions or even induce the regression of atherosclerotic lesions in humans, the evidence of this is not strong due to the fact that most prospective trials conducted to date have included other lifestyle changes and treatment strategies by necessity. The literature from large animal models of CAD also presents a cloudy picture concerning whether EX can induce the regression of or slow the progression of atherosclerotic lesions. Thus, while evidence from research using humans with CAD and animal models of CAD indicates that EX increases endothelium-dependent dilation throughout the coronary vascular tree, evidence that EX reverses or slows the progression of lesion development in CAD is not conclusive at this time. This suggests that the beneficial effects of EX in CAD may not be the result of direct effects on the coronary artery wall. If this suggestion is true, it is important to determine the mechanisms involved in these beneficial effects.

Effect of perfusion flow rate on the tissue uptake of solutes after dermal application using the rat isolated perfused hindlimb preparation.

The rat perfused hindlimb preparation was investigated as a model to study the dermal clearance and tissue distribution of three solutes with differing physicochemical properties ([3H]water, [3H]diazepam, and [14C]lignocaine). The dermal clearance of each solute increased and the depth of tissue preparation decreased with increasing perfusion flow rate. The half-life for solute efflux from tissues into perfusate, and the peak times for amount of solute in tissue were in the order water > lignocaine > diazepam. Topical iontophoresis, which has previously been shown to achieve similar clearances from topical sites to those seen following passive dermal application, resulted in a clearance of lignocaine in the perfused hindlimb comparable with that obtained in the preparation following passive absorption through exposed dermis. The distribution of capillary blood flow in the perfused hindlimb was quantified using 51Cr-labelled 15-microns microspheres, with greater increases in flow found in deeper muscle tissues with increasing perfusion flow rate compared with superficial layers. Microsphere studies in anaesthetized rats also demonstrate slight differences in the distribution of flow within the hindlimb compared with the perfused preparation. We conclude that the rat perfused hindlimb preparation successfully combines many of the advantages of in-vitro and in-vivo methods and has potential for routine use in the study of solute dermal absorption kinetics.

Counterpoint: There is not capillary recruitment in active skeletal muscle during exercise

The notion that a substantial proportion of capillaries do not contain moving red blood cells (RBCs) in muscle at rest but are “recruited,” i.e., begin flowing with RBCs during contractions, is one basis for our present understanding of blood-muscle exchange during exercise ([20][1], [28][2]).

Intravital microscopic observations of 15-μm microspheres lodging in the pulmonary microcirculation

Vascular infusions of 15-microm-diameter microspheres are used to study pulmonary blood flow distribution. The sites of microsphere lodging and their effects on microvascular perfusion are debated but unknown. Using intravital microscopy of the subpleural surface of rat lungs, we directly observed deposition of fluorescent microspheres. In a pump-perfused lung model, approximately 0.5 million microspheres were infused over 30 s into the pulmonary artery of seven rats. Microsphere lodging was analyzed for the location in the microvasculature and the effect on local flow after lodging. On average, we observed 3.2 microspheres per 160 alveolar facets. The microspheres always entered the arterioles as singlets and lodged at the inlets to capillaries, either in alveolar corner vessels or small arterioles. In all cases, blood flow continued either around the microspheres or into the capillaries via adjacent pathways. We conclude that 15-microm-diameter microspheres, in doses in excess of those used in typical studies, have no significant impact on pulmonary capillary blood flow distribution.

Coupling of muscle metabolism and muscle blood flow in capillary units during contraction.

Muscle blood flow is tightly coupled to the level of skeletal muscle activity: Indices of skeletal muscle metabolic rate, for example oxygen consumption or muscle work, are directly related to the magnitude of the change in muscle blood flow. Despite the large amount that is known about individual aspects of local metabolic vasodilation, the mechanisms underlying integrated aspects of the response remain largely unknown. Arteriolar dilation serves both to increase blood flow through the muscle and also to recruit capillaries and control capillary blood flow distribution. Conceptually, these two apparently separate functions of larger vs. more terminal arterioles (where larger vessels subserve conductance changes while the smaller more distal vessels have a primary role in capillary blood flow control) can be met, at least in part, by differential sensitivity of large vs. small arterioles to metabolites and agonists relevant to the metabolic response. However, longitudinal differences in sensitivity through the arteriolar network will not by themselves account for observed heterogeneities in capillary perfusion or for the close matching between blood flow and metabolism that occurs even in mixed muscles. In mixed skeletal muscles, fibres of widely different metabolic profile are dispersed throughout the muscle and even fibres of a single motor unit are not perfused by common arterioles but are matched with arterioles arising from widely disparate regions within the microvascular network. In this review we present findings that support the notion that capillaries are an integral part of the mechanism underlying this close matching between blood flow and metabolism. We review studies that indicate that capillaries are capable of responding to stimuli in their immediate environment and, importantly, are able to communicate with arterioles located remotely upstream in the arteriolar tree. Not only can skeletal muscle capillary endothelial cells induce remote arteriolar vasodilatory and vasoconstrictor responses to pharmacological stimuli such as acetylcholine or noradrenaline, but they can also initiate these remote arteriolar responses in response to skeletal muscle contraction. Capillary endothelial cells respond to skeletal muscle contraction by transmitting a dilatory signal to at least three branch orders of arterioles proximal to the capillary; these upstream dilations present a mechanism whereby capillaries can initiate their own recruitment, and whereby increased blood flow can be directed only to those exchange vessels associated with the contracting muscle fibres and where, presumably, the initiating signal is sensed. This signal involves KATP channels, although their location (on endothelial, vascular smooth muscle or skeletal muscle cells) is not yet known and has a nitric oxide-dependent component. The studies reviewed here thus indicate that capillaries have the capacity to play an active role in co-ordination of muscle blood flow responses to changed muscle metabolism. Much more remains to be learned, however, about the mechanisms underlying the signals generated by the contracting muscle and the mechanisms of transmission of the signals upstream.

Severe microcirculatory abnormalities elicited by E. coli hemolysin in the rabbit ileum mucosa.

Decreased capillary flow and heterogeneity of microvascular perfusion are hallmarks of septic circulatory disturbances, and the gastrointestinal mucosa is considered to be particularly prone to such abnormalities. We investigated the impact of Escherichia coli hemolysin (HlyA), a medically relevant pore-forming bacterial toxin, on the mucosal microvasculature in a constant-flow blood-perfused rabbit ileum model. Microsensor techniques were employed to assess spatial distribution of mucosal hemoglobin oxygenation and relative mucosal hemoglobin content, as well as mucosal-arterial PCO(2) gap. Administration of low doses of HlyA (0.005 to 0.1 hemolytic units [HU]/ml) into the mesenteric artery provoked a transient vasoconstrictor response. Whereas physiological mucosal oxygenation is homogeneous, severe heterogeneity in capillary blood flow distribution appeared, paralleled by a marked increase in the mucosal-arterial PCO(2) gap. In addition, HlyA provoked a dose-dependent increase in relative hemoglobin concentration (rel Hb(conc)) values and edema formation, suggesting postcapillary vasoconstriction and capillary leakage. The observed changes occurred while fully maintaining mesenteric oxygen delivery. We conclude that low doses of HlyA may elicit severe mucosal microcirculatory disturbances in the rabbit ileum under maintenance of global hemodynamics, reminiscent of septic perfusion abnormalities. Pore-forming bacterial toxins may thus be considered as contributors to splanchnic mucosal damage under conditions of severe infection and sepsis.

Specific blood flow reducing effects of hyperoxaemia on high flow capillaries in the pig brain.

The mechanisms behind oxygen mediated changes in tissue blood flow remain unsettled. Today these are thought to (from experiments on separate vessels and other tissues than the brain) operate through the vessels themselves, probably by involvement of the endothelium in the distal parts of the vascular tree. The aim of this study was to investigate how hyperoxaemia affects the cerebrocortical capillary blood flow distribution in order to gain further knowledge of oxygen mediated blood flow regulating mechanisms. The experiments were performed on seven ventilated anaesthetized pigs. A multiwire Clark-type microelectrode, placed on the brain surface (motor cortex), was used for capillary blood flow (hydrogen clearance) and oxygen pressure measurements, both of which were made at normoxaemia (arterial PO2 14.4 kPa) and hyperoxaemia (arterial PO2 50.4 kPa)(the animals serving as their own control). Blood pressure, arterial PCO2 and pH remained unchanged throughout the experiments. During hyperoxaemia a 11% reduction in the cerebrocortical capillary blood flow was found (P < 0.001). This flow reduction was seen mainly in two capillary blood flow classes (6/7 animals). In parallel a heterogeneous increase in the cerebrocortical oxygen pressures from 4.5 to 10.1 kPa (mean) (P < 0.001) was found. These results show that hyperoxaemia causes a selective reduction in capillary blood flow affecting capillaries at specific flow levels. A finding that suggests, for the brain, that both the oxygen sensor and effect mechanism is situated distally, in the vascular tree.

Adverse effects of hyperoxemia during cardiopulmonary bypass

Objective: Aiming at elucidating the effects on capillary blood flow and tissue oxygenation of hyperoxemia during cardiopulmonary bypass, we studied skeletal muscle surface oxygen tensions in 10 patients undergoing elective cardiac operations. Methods: In a prospective investigation each patient was exposed to normoxemia (arterial oxygen tension 75 to 115 mm Hg) and hyperoxemia (arterial oxygen tension > 185 mm Hg, inspired oxygen fraction = 1.00) during normal anesthetized conditions before and after cardiopulmonary bypass, as well as during normothermic and hypothermic continuous-flow bypass. In each state hemodynamic variables and arterial and mixed venous blood gas and acid base values were measured. From these data oxygen transport variables were calculated. Tissue oxygenation was studied with the use of a multiple-point polarographic oxygen microelectrode, known to provide measures of oxygen tensions at the capillary level. The oxygen distribution profile of such a sample is also indicative of capillary blood flow distribution changes. Results: In all patients and at each occasion of the investigation markedly low mean surface oxygen tensions in skeletal muscle were registered. When hyperoxemia was instituted, a significant decrease in these surface oxygen tensions together with an increase in distribution heterogeneity was seen during all stages. Contrary to prebypass, postbypass, and hypothermic bypass, where vascular resistance, oxygen delivery, and oxygen consumption remained similar during hyperoxemia and normoxemia, a significant ( p < 0.05) increase in vascular resistance together with a decline in oxygen consumption was seen during hyperoxemic normothermic (35° to 36°C) cardiopulmonary bypass. Conclusion: These findings show that the microcirculatory response to hyperoxemia, seen under other circumstances, persists during continuous-flow cardiopulmonary bypass, normothermic as well as hypothermic. If these adverse effects on tissue oxygenation by hyperoxemia can be further verified and shown to be valid for other organs than skeletal muscle, we would suggest that hyperoxemia should be avoided, especially during normothermic cardiopulmonary bypass. (J T HORAC C ARDIOVASC S URG 1996;112:812-9)

Increasing nitric oxide production improves survival in experimental hemorrhagic shock

The purpose of this study was to evaluate the importance of nitric oxide (NO) upon outcome following hemorrhagic shock. l-Arginine, an NO precursor, and l-NMMA, an inhibitor of NO synthesis, were added to resuscitation in a prospective, randomized, and double-blinded experimental model, and the effects upon blood pressure and survival were measured. Methods: 60 Sprague-Dawley rats were anesthetized and subjected to phlebotomy to induce hemorrhagic shock. After a 45 min shock period, animals were resuscitated with either lactated Ringer's alone (control), l-NMMA in lactated Ringer's, or l-arginine in lactated Ringer's. Blood pressure was monitored, and animals were observed for survival. As an additional control experiment, 15 additional animals underwent the same protocol, but underwent sham shock, i.e. were not haemorrhaged. Results: l-NMMA increased blood pressure transiently following sham shock, but increased blood pressure to a greater extent and for a longer duration following hemorrhage. However, l-NMMA had no effect upon survival. l-Arginine had no measurable effect upon blood pressure, but significantly increased survival. Conclusion: NO may play an important role following hemorrhage. The effectiveness of l-NMMA as a pressor suggests that NO contributes to hypotension following hemorrhage. However, reversing hypotension with l-NMMA did not improve survival in this model. In contrast, l-arginine did not further lower blood pressure, but had significant survival benefit. This suggests a possible protective effect of NO after hemorrhage, perhaps by improving the distribution of capillary blood flow and/or by decreasing platelet aggregation and leukocyte adhesion within the microcirculation.

Disturbances in renal microcirculation induced by myoglobin and hemorrhagic hypotension in anesthetized rat.

The question was studied of whether myoglobin (Mb), when released into the general circulation during hemorrhagic hypotension (HH), causes disturbances of renal blood flow. In anesthetized rats 250 mg/kg Mb was intravenously infused within 1 h; HH at 50 mmHg with subsequent retransfusion was induced for 30 min. By allowing two dyes to circulate for 1 and 3 min, respectively, and detecting their localization histologically after rapid freezing of the organ, intrarenal distribution of capillary blood flow was studied. In contrast to the results obtained with Mb or HH alone, when Mb was infused during HH, the development of large areas within cortex and medulla lacking any capillary perfusion was observed. In > 70% of the tissue, a distance > 60 microns to the next dye-labeled capillary was found (in controls 0%). At this time total renal flow had decreased from 5.3 to 0.20 ml/min (HH without Mb: 5.1 to 1.1 ml/min). It is concluded that the observed changes in renal blood flow contribute to the known direct nephrotoxic potential of Mb.

In Vivo Fluorescence Microscopy of Microcirculation in the Renal Cortex of Mice

An experimental model using in vivo fluorescence microscopy for studies of renal cortical blood flow was tested in 40 mice. The model was suitable for testing a wide variety of hypotheses concerning alterations in renal cortical blood flow, including the possibility of inhomogeneous capillary blood flow distribution in response to i.v. infusions. The experimental model was tested for the effects of i.v. infusion of mannitol (0.3 mol/l). Effects of anesthesia and mechanical kidney fixation on renal cortical blood flow were studied. Neuroleptic analgesia was less hazardous to the animals than pentobarbital. Due to artifacts from respiratory and peristaltic motion, it was not possible to use neuroleptic analgesia without mechanical kidney fixation. A rating scale was designed for evaluating the capillary blood flow. The correlation between repeated ratings by the same observer was 0.806 and between 2 different observers 0.59.

Arteriovenous Shunting and Regional Blood Flow in Myocutaneous Island Flaps

In eight pigs, total blood flow, regional capillary blood flow distribution, and arteriovenous (AV) shunting were studied during the first 4 postoperative hours after elevation of a myocutaneous rectus abdominis island flap. Capillary blood flow and AV shunting were measured using radioactive microspheres before flap creation and 1 and 4 hours after surgery. Total blood flow, measured continuously as venous outflow, increased in the first postoperative hour (p less than 0.05). Elevation of the flap caused a slight decrease in skin capillary blood flow (p less than 0.05), whereas muscular capillary blood flow increased (p less than 0.01). AV shunting accounted for 50 percent of the total flap blood flow, whereas it was negligible in the abdominal wall prior to flap elevation. Thus stalk blood flow, skin appearance, and skin temperature may be poor indicators of nutritional capillary perfusion. However, the clinical and nutritional consequences of these findings remain to be established.

Studies of retrograde cardioplegia: I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries

This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequate cardioplegic protection. Open-chest anesthetized dogs were studied by mixing radioactive microspheres (15 +/- 5 microns) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery open or occluded (30% +/- 2% area at risk). Nutritive flow (i.e., percentage of delivered 15 microns microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87% with antegrade cardioplegia (p less than 0.05). Retrograde and antegrade cardioplegic nutritive flow to all left ventricular regions was comparable with the left anterior descending coronary artery open (65 versus 82 ml/100 gm/min, p greater than 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 ml/100 gm/min, p less than 0.05). Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 ml/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia (less than 2 ml/100 gm/min, endocardial/epicardial, 0.29, p less than 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 ml/100 gm/min), but septal cooling was superior to antegrade cardioplegia (15 degrees +/- 1 degree C versus 20% +/- 3%, p less than 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 ml/100 gm/min during retrograde coronary sinus perfusion and was maintained normally with antegrade cardioplegia.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of capillary blood flow in rat kidney during postischemic renal failure.

Changes in distribution of intrarenal blood flow were studied in anesthetized rats during the acute phase of postischemic renal failure (1 h renal artery occlusion, 1 h reflow). Distribution of capillary plasma flow was determined by injecting fluorescein-isothiocyanate-globulin and lissamine-rhodamine-B200-globulin 1, 3, or 10 min prior to rapid freezing of the kidney. In histological sections it was possible to differentiate among the vessels perfused during the time of labeling because of their respective fluorescence. In these experiments all glomeruli became labeled within 1 min, although in contrast to the controls, the glomerular capillary network itself was not filled completely in the postocclusion organs. Incomplete labeling was far more pronounced, however, in the postglomerular network of the occlusion experiments. Due to this effect in the cortex and in the medulla, 11 and 58% of tissue, respectively, were found lying at a distance of more than 60 microns from the next vessel labeled after 1 min of dye circulation. In the control experiments there was no tissue within this distance. Prolonging the time of labeling up to 10 min caused little change in this pattern of distribution. In the occlusion experiments, the globulins were observed in nearly all Bowman spaces, but in less than half of the tubular lumina. The results strengthen the view that the ischemic insult leads primarily to disturbance of the postglomerular perfusion, which then results in trophic damage of the tubular system mainly within the renal medulla.

Evidence that capillary perfusion heterogeneity is not controlled in striated muscle

We tested the hypothesis that the heterogeneity of capillary blood flow distribution in striated muscle is inversely proportional to tissue blood flow by examining the patterns of red blood cell flow in the capillaries of hamster tibialis anterior muscles. Capillary red blood cell velocities and capillary red blood cell fluxes were measured as indexes of blood flow and red blood cell distribution in vasoconstricted and vasodilated vascular beds of resting and working striated muscle. Standard statistical parameters describing dispersion of data (standard deviation and coefficient of variation) in addition to measured and normalized histograms were compared across treatments. With vasodilation the standard deviations of both variables increased linearly with the means, and measured distributions became broader. The coefficients of variation and normalized distributions of both variables did not differ across treatments. These observations do not support the idea that the heterogeneity of capillary perfusion is controlled. Rather they suggest that fractional flow dispersion among capillaries is constant and independent of muscle blood flow and/or O2 demand.

Pharmacologic action of isoxsuprine in cutaneous and myocutaneous flaps.

The therapeutic effects of isoxsuprine on skin capillary blood flow and viability were studied in arterial buttock flaps, latissimus dorsi myocutaneous flaps, and random skin flaps in pigs. It was observed that parenteral isoxsuprine increased capillary blood flow to the skin of arterial buttock flaps and the skin and muscle of latissimus dorsi myocutaneous flaps in a dose-response manner, with a maximum vascular effect observed at 1.0 mg/kg. However, this maximum effective dose of isoxsuprine did not have any significant effect on skin viability in the cutaneous and myocutaneous flaps compared with the control. Examination of the distribution of capillary blood flow within the flaps at varying distances from the pedicle revealed that isoxsuprine did not increase capillary blood flow or perfusion distance in the distal portion of the skin of arterial buttock flaps, latissimus dorsi myocutaneous flaps, and random skin flaps. The increased capillary blood flow as a result of isoxsuprine treatment was limited only to the arterial portion of the arterial buttock flaps and latissimus dorsi flaps. Therefore, it is concluded that isoxsuprine alone is not effective in augmentation of skin viability in cutaneous and myocutaneous flaps. The pharmacologic action of isoxsuprine on the vasculature in the skin and muscle of flaps was also discussed.

Diffusion-perfusion relationships in skeletal muscle: models and experimental evidence from inert gas washout.

In order to study the dependence of blood-tissue gas exchange upon diffusion, the simultaneous washout of two inert gases of differing diffusivity was investigated in isolated-perfused dog gastrocnemius preparations. The muscles were equilibrated with CH4 and SF6 via arterial blood. The washout kinetics were determined from venous blood samples analyzed by gas chromatography. The results revealed the following features: The washout of the test gases was pronouncedly multi-exponential, and could be described by three exponential components when analyzed to 5% of the initial value. The non-exponential washout was attributed to unequal distribution of capillary blood flow to tissue volume. The mean ratio of washout rate constants CH4/SF6 was within 1.10-1.25 and was even smaller than the ratio expected for pure perfusion limitation (1.46). Therefore, no evidence for effective tissue-blood diffusion limitation was obtained. The observed washout rate constant ratio could be explained by a model with veno-arterial back diffusion which more strongly retards washout kinetics of the better diffusible gas (CH4) as compared to the less diffusible gas (SF6).