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Microvascular injury associated with ischemia/reperfusion (I/R) is characterized by both "no reflow" and "reflow paradox." Prophylactic isovolemic hemodilution with dextran 60 to a hematocrit of 30% has been shown to prevent I/R-induced capillary no reflow in striated muscle. The objective of the present study was to analyze whether hemodilution prior to ischemia has the potential to reduce postischemic leukocyte-endothelium interaction, which is known to be one of the major components of I/R-induced reflow paradox. Syrian golden hamsters (n = 21) were fitted with a dorsal skinfold chamber, which contains striated muscle and subcutaneous tissue and allows for repetitive analyses of the microcirculation by means of intravital fluorescence microscopy. Four hr of pressure-induced ischemia and 30 min of subsequent reperfusion (controls, n = 7) resulted in a significant (P < 0.05) increase of microvascular leukocyte accumulation (40,630 +/- 12,731 mm-3) and adherence to the endothelial lining of postcapillary venules (74.2% +/- 11.5%) when compared to preischemic baseline (7,502 +/- 1,700 mm-3 and 3.4% +/- 1.0%, respectively). Recovery was not complete after an observation period of 24 hr reperfusion [13,735 +/- 2,666 mm-3 (P < 0.05) and 18.5% +/- 6.0% (P < 0.05)]. Prophylactic isovolemic hemodilution with 6% dextran 60 (Dx60) to a hematocrit of 30% (Dx60, n = 7) significantly attenuated postischemic leukocyte accumulation (23,402 +/- 13,837 mm-3; P < 0.05 vs. controls) and adherence (22.6% +/- 6.4%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The semitendinosus muscle of the rabbit is composed of a homogeneous fiber population. Fiber typing was carried out by means of light and electron microscopy according to which this muscle exhibits structural features that are either characteristic for both "red" and "white" fibers, or that do not allow for any classification according to the A-, B-, C-fiber system. Hence the long-held assumption that the semitendinosus muscle of the rabbit represents a classical paradigm of a "red" muscle should be revised in light of the present results.

Two different types of paracrystalline mitochondrial inclusions identical with or very similar to those already described in the literature for a variety of muscle diseases were found in human skeletal muscle biopsies obtained under general anesthesia before ischemia and after various periods of anoxia up to 150 min. As these crystalloids could be observed in seven of 14 healthy subjects and occurred in five of these seven cases either before or only 10 min after onset of ischemia, it is suggested that such mitochondrial inclusions develop not only under the influence of variant noxious stimuli, but may also represent a normal constituent of human skeletal muscle mitochondria.

Human skeletal muscle shows reflow impairment after prolonged tourniquet ischemia of 1-3 hours, increasing with the duration of ischemia. A sample of 275 cross-sectioned capillary profiles from muscle biopsies of human m. quadriceps femoris made totally ischemic by tourniquet for 90-180 minutes (mean 110 min.) from 5 patients during surgery, show frequent evidence of ultrastructural damage to microvascular membranes and organelles. Frequency analyses demonstrate a significant increase in damage during ischemia (p = 0.03), but not increasing further following 5 min of reperfusion. One of the signs of ischemic damage was endothelial swelling, found in some endothelial cells, lying next to ultrastructurally intact ones. The swelling found cannot be explained by a general loss of volume control of the microvascular endothelium during ischemia, since a computerized morphometry on the entire sample shows a preserved capillary wall thickness during ischemia and following reperfusion. During reperfusion the capillaries dilate with an increase in median max. diameter from 3.4 micron (4.7 micron shrinkage-corrected) to 3.9 micron (5.4 corr.) (p less than 0.001), despite reported reperfusion impairment. However, since capillaries in skeletal muscle consist of 20-40 endothelial cells, a distribution of such localized endothelial swelling or luminal membrane changes in a few percent of the microvascular endothelial population after ischemia, trapping leucocytes, would affect microvascular hydraulic conductance to reperfusion.

The effect of muscle contraction on lymphatic and plasma [K+], [Na+], [Ca2+], [Mg2+], [Cl-], [Pi], [lactate] ([Lac-]); [creatine] ([Cr]), ideal osmolality (OSM), and [protein] was evaluated in femoral venous blood and lymph specimens sampled from the calf muscles of rabbits before, in the course of, and after contractions. In addition, total [K+], [Na+], [Ca2+], [Mg2+], [Cl-], and [H2O] were analyzed in the muscle tissue. To facilitate lymph sampling both hind limbs were passively flexed and extended, in imitation of natural running movements, by an electrically driven crank. The muscles of one side also performed superimposed rhythmic isotonic contractions. Before contractions, lymphatic [K+], [Na+], [Ca2+], [Mg2+], [Lac-], [Cr], and OSM did not significantly differ from corresponding femoral venous concentrations, [Cl-], and [Pi] were significantly higher, [protein] significantly lower in the lymph than in the plasma. During contractions lymphatic [K+], OSM, [Lac-], and [Pi] were raised significantly more in the lymph compared with the plasma concentrations. [Na+], [Cl-], [Ca2+], and [Mg2+] showed only small changes in the course of contractions and thereafter, and they were altered in a similar way in the lymph and plasma. It was suggested that lymphatic and interstitial concentrations were in equilibrium. Comparing inactive with active muscles, the latter lost K+ but gained Na+, Cl-, and H2O, whereas minimal changes occurred in the [Ca2+] and [Mg2+]. The changes were discussed in connection with the hypothesis that electrolyte shifts might be involved in the activation of the muscular non-proprioceptive interstitial nerve endings which appear to play a role in reflexogenic cardiovascular and respiratory control.

Capillary dimensions in muscle biopsies from human musculus quadriceps femoris, sectioned at right angle to the muscle fibers, were analysed with a computerized planimetric technique giving distributions of dimensional parameters with statistics. Without corrections for estimated preparative shrinkage mean maximal diameter of lumen was 3.82 +/- 0.82 microns (5.31 +/- 1.14 micron shrinkage corrected), mean second maximal diameter, at right angle to maximal, 2.61 +/- 0.72 microns (3.62 +/- 1.00 microns corr.) and mean endothelial thickness in nuclear free sections 0.35 micron (0.49 micron corr.) micron. Using a capillarity of 360/mm2 for the human m. quadriceps femoris, the total surface area of skeletal muscle capillaries was calculated to be 5.50 X 10(3) cm2/100g and the total volume of the capillary network in the muscle to be 0.48 cm3/100g.

Prolonged ischemia is known to cause severe damage in skeletal muscle and skin as a result of reperfusion failure. Isovolemic hemodilution has been suggested as a modality to reverse microcirculatory disorders by improving flow properties and flow conditions of the blood. The aim of the present study was to investigate whether prophylactic isovolemic hemodilution could improve tissue oxygenation after 4h of pressure induced ischemia in skeletal muscle. In 17 Syrian golden hamsters a dorsal skin fold chamber and two permanent arterial and venous catheters were implanted. Following a recovery period of 48h ischemia was induced for 4h by means of a transparent stamp compressing the tissue within the chamber. In 9 animals (control, hct 43%) measurements of tissue PO2 (platinum multiwire electrode) were performed prior to and 15 min, 2h and 24h after release of ischemia. In 8 animals isovolemic hemodilution with Dextran 60 (hct 29%) was carried out prior to ischemia and measurements of local tissue PO2 were performed as reported for the control group with an additional measurement 30 min after hemodilution. In control animals tissue PO2 decreased significantly (p less than 0.01) from 20.7 +/- 2.4 mmHg prior to ischemia to 8.8 +/- 3.1 mmHg after 15 min of reperfusion; after 24h tissue PO2 was 15.6 +/- 6.1 mmHg. In hemodiluted animals tissue PO2 increased due to hemodilution from 20.9 +/- 1.6 mmHg to 23.5 +/- 2.5 mmHg (p less than 0.05); after 15 min of reperfusion tissue PO2 was 19.8 +/- 6.8 mmHg and remained unchanged for 24h (20.0 +/- 2.5 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study changes in functional capillary density and tissue PO2 in chronically ischemic skeletal muscle, a new model, using the Syrian golden hamster was developed. In the hamster dorsal skin fold, which receives its vascular supply from two cranial and two caudal feeding arteries, a double frame chamber was implanted and ischemia was induced in the cranial part by heat coagulation of the cranial arteries outside of the chamber. This technique allows for analysis of microvascular hemodynamics and local tissue PO2 prior to and during a prolonged period of ischemia in skin muscle. As result of ischemia the diameters of the arterioles increased (p less than 0.001) over the whole 11 day observation period. Functional capillary density decreased significantly (p less than 0.01) during the first 7 days, while capillary RBC-velocity was reduced throughout the 11 days of observation. RBC-velocity in collecting venules was diminished significantly throughout the postischemic observation period. The diameters of the collecting venules first increased upon ischemia (p less than 0.001) but were found decreased at 4, 7 and 11 days. Measurements of tissue PO2 demonstrated a marked decrease from a mean PO2 of 20.5 mmHg prior, to 9.5 mmHg following induction of ischemia. The model allows for induction of chronic ischemia and is suitable to study the effect of therapeutic measures on the microcirculation in chronically ischemic skeletal muscle in vivo.