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Biomedical subjects

R W Hobson

Publications and source records attributed to R W Hobson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Role of eicosanoids and white blood cells in the beneficial effects of limited reperfusion after ischemia-reperfusion injury in skeletal muscle.

Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation.

Animals↗
PubMed1990

Diagnosis of acute deep venous thrombosis.

This article outlines the application of continuous-wave Doppler, plethysmographic techniques, and B-mode ultrasonography to the diagnosis of suspected deep venous thrombosis in ambulatory patients. Methodology is evaluated, and the diagnostic accuracy and application of these studies are reviewed. The authors' current algorithm for the application of these noninvasive studies also is presented.

Humans↗
PubMed1990

Iloprost infusion decreases skeletal muscle ischemia-reperfusion injury.

Iloprost (a long-acting prostacyclin analog) has been demonstrated to decrease cardiac muscle infarct size after ischemia-reperfusion injury. We investigated the ability of iloprost to decrease skeletal muscle injury and platelet sequestration after ischemia-reperfusion injury in a canine bilateral isolated gracilis muscle model. Anesthesized animals (n = 13) were subjected to 6 hours of gracilis muscle ischemia and 1 hour of reperfusion. Fifteen minutes before muscle reperfusion, the animals were infused with radium 111-labeled autogenous platelets. Experimental animals (n = 7) received a continuous preischemic intravenous infusion of iloprost (0.45 microgram/kg/hr) and two 0.45 microgram/kg intravenous injections of iloprost (10 minutes before the ischemic interval and 10 minutes before reperfusion). Muscle injury was measured with triphenyltetrazolium chloride histochemical staining. Platelet sequestration within ischemic muscle specimens was determined by measuring indium 111 activity in a gamma counter. Iloprost infusion decreased muscle infarct size from 57.0% +/- 12.6% in control animals to 15.8% +/- 4.4% in experimental animals (p less than 0.05). Platelet uptake in experimental and control muscle was 1.2 +/- 0.21 x 10(7) and 2.17 +/- 0.48 x 10(7) platelets/gm ischemic muscle, respectively (p = 0.1). Although platelet sequestration was not altered significantly in this experiment, a reduction in skeletal muscle injury was confirmed. Further investigation on the mechanisms of action of iloprost in chronic and acute skeletal muscle ischemia is warranted.

Animals↗
PubMed1990

Popliteal artery agenesis: a new anatomic variant.

Agenesis of the popliteal artery has not been described as a vascular anomaly in the lower extremity. This case report describes congenital absence of the popliteal artery discovered during operative exploration after a traumatic injury to the lower extremity. The preoperative arteriogram suggested acute occlusion of the popliteal artery. Intraoperative exploration and arteriography were consistent with agenesis of the popliteal arterial segment, and postmortem examination confirmed these arteriographic and intraoperative observations. Embryologically, failure of the middle portion of the sciatic artery to persist would account for this anomaly. A review of series reporting congenital anomalies of the lower extremity vasculature failed to discover previous mention of this particular abnormality. Agenesis of the popliteal artery should be included among those vascular anomalies that may affect management of lower extremity vascular disease.

Adult↗
PubMed1990

Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion.

Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified.

Animals↗
PubMed1990

Reduced dependency on arteriography for penetrating extremity trauma: influence of wound location and noninvasive vascular studies.

Indications for arteriography in penetrating extremity trauma remain controversial. We reviewed our clinical experience in 454 patients (514 extremities) with penetrating trauma admitted during a prior 3 1/2-year period. Injuries were caused by stab wounds in 60 (11.7%) extremities and by gunshot wounds in 454 (88.3%) extremities. Thirty-three of the 60 stab wounds (55%) required urgent exploration, and 27 underwent arteriography. No arteriograms were positive for unsuspected arterial injury in this group. Forty-two of 454 gunshot wounds (9.3%) underwent mandatory exploration; arteriograms were performed on 412 extremities. Forty-four arteriograms (10.7%) demonstrated evidence of unsuspected arterial injuries. During the last year, randomly selected extremities (n = 23) have been studied with B-mode ultrasonography and segmental Doppler pressure measurements. Using the subsequent arteriography as the "gold" standard, sensitivity was 83% and specificity was 100%. Gunshot wounds were categorized according to location and positive arteriograms. Injuries to the lateral thigh and arm resulted in no positive arteriograms, while positive studies were observed in 11% of medial and posterior arm, 14% of antecubital fossa, 25% of forearm, 7.5% of medial and posterior thigh, 8% of popliteal fossa, and 26% of calf injuries. We recommend arteriography for gunshot injuries to identified high-risk areas, while clinical evaluation alone is accurate in all stab wounds to the extremities and gunshot wounds to the lateral thigh and outer arm. Preliminary data suggest expanded use of B-mode ultrasonography may further reduce our dependency on arteriography in these cases.

Adolescent↗
PubMed1990

Penetrating extremity trauma: identification of patients at high-risk requiring arteriography.

Indications for arteriography in patients with penetrating trauma to the extremities remain controversial. Some clinicians have recommended universal use of arteriography, whereas others prefer to rely on physical findings alone. To better define our indications for contrast studies, we reviewed clinical data on 306 patients (349 extremities) with penetrating trauma who were admitted during a prior 2-year period (1985 to 1987). Injuries were caused by stab wounds in 50 (14.3%) extremities and by gunshot wounds in 299 (85.7%) extremities. Twenty-seven of the 50 stab wounds (54%) required urgent exploration based on physical findings, whereas 23 underwent arteriography. None of these studies showed unsuspected arterial injury. Twenty-nine of 299 gunshot wounds (9.7%) underwent mandatory exploration, and arteriograms were performed on 270 extremities; findings in 30 studies (11.1%) were positive for unsuspected arterial injuries. Gunshot wounds were categorized according to location and number of arteriograms with positive results. Arteriograms of lateral thigh and upper arm injuries resulted in no positive outcomes. Positive study results were recorded in 22.9% of calf injuries, 20% of forearm and antecubital injuries, 9.5% of popliteal fossa injuries, 9.0% of medial and posterior thigh injuries, and 8.3% of medial and posterior upper arm injuries. We recommend arteriography for penetrating injuries to these high-risk areas. However, clinical evaluation alone is accurate for identification of arterial trauma with lateral thigh or upper arm wounds and stab wounds to the extremities.

Adolescent↗
PubMed1990

First phase report of cooperative Veterans Administration asymptomatic carotid stenosis study--operative morbidity and mortality.

Ten Veterans Administration medical centers representing all regions of the country participated in a cooperative study to evaluate the etiologic importance of asymptomatic carotid disease in the development of transient ischemic attack and stroke. The study prospectively randomized patients between carotid endarterectomy and nonoperative treatment with both groups receiving 1300 mg aspirin daily. All patients considered for the study had carotid angiography. Inclusion in the study required at least a 50% diameter reduction of the internal carotid artery. Four hundred forty-four patients were randomized between nonoperative (233 patients) and operative groups (211 patients). In the operative group 195 had unilateral carotid endarterectomies, and eight patients had staged bilateral procedures, for a total of 211 carotid operations. Thirty-day mortality was 1.9% (4/211); all resulting from cardiac causes. One patient who died also had a neurologic deficit. The incidence of stroke was 2.4% (5/211), and the combined stroke and mortality rate was 4.3%. Transient ischemic events occurred in two patients (0.9%). Coronary artery disease is the prime determinant of operative mortality and justifies rigorous preoperative cardiac evaluation to identify those patients at risk. This multicenter prospective clinical trial demonstrates that carotid endarterectomy can be safely performed and provides a valid standard with which to compare the nonoperative cohort.

Carotid Arteries↗
PubMed1989

Postischemic hypothermia diminishes skeletal muscle reperfusion edema.

The mechanisms of ischemia-reperfusion injury in skeletal muscle remain controversial. We investigated the ability of postischemic hypothermia to diminish reperfusion edema and improve skeletal muscle pH in a bilateral, in vivo isolated canine gracilis muscle model. In five anesthetized animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. After 5 hr of warm ischemia, one gracilis muscle was cooled to 21 degrees C (cold reperfusion, CR) while the contralateral gracilis muscle was maintained at ambient temperature (warm reperfusion, WR). Reperfusion muscle edema was quantitated by measurement of gracilis muscle weight gain. Interstitial muscle pH was monitored by glass microelectrodes. Vascular permeability was measured by analysis of albumin (125I-Alb) leak. Results are presented as the means +/- SEM. (table; see text) Postischemic hypothermia significantly increased the interstitial muscle pH and significantly reduced postreperfusion muscle edema, without changing the vascular permeability to albumin. These data suggest that hypothermia may provide a clinical method for salvaging ischemic skeletal muscle from the postreperfusion edema that can lead to compartment syndromes, reperfusion injury, and subsequent limb loss.

Animals↗
PubMed1989

The role of leukocytes in the pathophysiology of skeletal muscle ischemic injury.

Neutrophilic leukocytes have been implicated as important mediators of ischemic myocardial injury. We investigated the role of neutrophils in skeletal muscle ischemia/reperfusion injury by using the rat hindlimb ischemia model. We rendered Wistar rats neutropenic by administering 750 rad of whole-body radiation (mean white blood cell count, 300 +/- 50/mm3; 3 days after radiation). In anesthetized rats (10 neutropenic and 10 control), 3 hours of ischemia were induced in one hindlimb by application of a tourniquet to the proximal thigh; the contralateral limb served as an internal, nonischemic control. After 1 hour of reperfusion the gastrocnemius and soleus muscles were excised bilaterally and evaluated for ischemic injury by means of a quantitative spectrophotometric assay of triphenyltetrazolium chloride (TTC) reduction. In control rats the reduction of TTC by ischemic muscle averaged 27.0% +/- 7.3% of that by nonischemic muscle; whereas in neutropenic rats the value for ischemic muscle was 65.4 +/- 11.6% (p less than 0.05). To determine if the contribution of the neutrophils to ischemic injury is due to oxygen-derived free radical formation, an additional 10 animals were infused with 5000 units of super-oxide dismutase and 10,000 units of catalase at the time reperfusion was restored. After treatment with free radical scavengers, TTC reduction by ischemic limbs was 25.5% +/- 7.0% of that by nonischemic limbs and did not differ from that in control animals (p greater than 0.05). The results show a protective effect of neutropenia and suggest a significant role of the white cell in the pathophysiology of ischemic skeletal muscle injury.

Animals↗
PubMed1989

Intraarterial urokinase increases skeletal muscle viability after acute ischemia.

Administration of intraarterial fibrinolytic agents has been recommended after balloon catheter thrombectomy to reduce retained thrombus and to improve the patency of collateral vasculature. However, the potential for improvement in the viability of skeletal muscle after ischemia as a result of this therapy has not been evaluated. We investigated the effect of intraarterial urokinase (UK) on the salvage of ischemic skeletal muscle in a bilateral, in vivo, isolated gracilis muscle model. In six anesthetized dogs each gracilis muscle was subjected to 5 hours of ischemia by temporary occlusion of the gracilis artery. Before reperfusion, the experimental muscle received an intraarterial infusion of UK (30,000 units) whereas the control muscle received saline solution. Each muscle was then reperfused for 90 minutes. Triphenyltetrazolium chloride staining demonstrated infarction of 20.2% +/- 8.1% in control muscles compared with 8.6% +/- 6.2% in UK-infused muscles (p less than 0.01). Control muscles gained significantly more weight from edema (33.6 +/- 5.9 gm) than UK-infused muscles (18.2 +/- 4.1 gm; p less than 0.05). Coagulation studies confirmed that an isolated fibrinolytic effect occurred on the experimental side. These studies suggest that intraarterial UK may be a useful adjunctive therapy after revascularization of the acutely ischemic limb and that further clinical trials are recommended.

Acute Disease↗
PubMed1988

Heparin decreases ischemia-reperfusion injury in isolated canine gracilis model.

The mechanisms of ischemia-reperfusion injury in skeletal muscle remain controversial. Some investigators have demonstrated that heparin can ameliorate ischemic injury to heart, brain, and renal tissue. We investigated the ability of heparin sodium to decrease ischemia-reperfusion injury in an isolated gracilis muscle model in ten anesthetized mongrel dogs. One gracilis muscle was perfused normally while the contralateral muscle was subjected to six hours of ischemia followed by one hour of reperfusion. Five dogs were given a preischemic bolus of heparin sodium (200 U/kg, intravenously followed by a continuous infusion (15 U/kg/h, intravenously), and five control dogs received no heparin. Quantitation of skeletal muscle ischemia-reperfusion injury was determined by histochemical staining with triphenyl tetrazolium-chloride and computerized planimetry of the infarct size. Results from the ischemic muscle demonstrate a significant beneficial effect of heparinization. The nonheparinized dogs had a 72% +/- 5% infarct size, which was significantly reduced to 24% +/- 8% in the heparinized dogs. The mechanism of this protective effect may be due to heparin's anticoagulant, antiplatelet, or anti-inflammatory action.

Acute Disease↗
PubMed1988

Doppler ultrasound, laser Doppler, and perfusion fluorometry in bowel ischemia.

Improved accuracy and objectivity in the evaluation of intestinal viability has been reported by some investigators using Doppler ultrasound, and more recently laser Doppler velocimetry and perfusion fluorometry. To compare the sensitivity and clinical applicability of these techniques, intestinal viability was evaluated by each method in nine 15- to 50-cm loops of small bowel prepared by division of the mesenteric vasculature in five anesthetized dogs. The sensitivity of Doppler ultrasound was 86%, of laser Doppler flow velocity 85%, of laser Doppler index 94%, and of perfusion fluorometry 95%. Though the sensitivity of Doppler ultrasound is significantly less than that of laser Doppler and perfusion fluorometry, this is not unexpected since the latter two techniques are more quantitative than Doppler ultrasound. Clinically, Doppler ultrasound compares favorably with laser Doppler and perfusion fluorometry, and its low cost and simplicity suggest its adjunctive use in the operative setting.

Animals↗
PubMed1988

Rate of reperfusion blood flow modulates reperfusion injury in skeletal muscle.

The mechanisms of ischemia-reperfusion (I-R) injury in skeletal muscle remain controversial. We investigated the effect of the rate of reperfusion blood flow on I-R injury in an isolated in vivo canine gracilis muscle model in six anesthetized dogs. In all animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. During reperfusion, one gracilis artery was partially occluded to limit the rate of reperfusion blood flow to its preischemic rate (limited reperfusion, LR), while the contralateral artery was allowed to perfuse freely at a normal rate (normal reperfusion, NR). Muscle injury was quantified by histochemical staining (triphenyltetrazolium chloride, TTC) with computerized planimetry of the infarct size, and by spectrophotometric determination of technetium-99m pyrophosphate uptake. Endothelial permeability was quantified by measurement of gracilis muscle weight gain and 125I-albumin radioactivity after intravenous injection. Results are presented as the means +/- SEM, and differences are considered to be statistically significant if P less than 0.05 by Student's t test for paired data. LR resulted in significantly less blood flow (9.7 +/- 1.7 cc/min/100 g) when compared to NR (55.7 +/- 11.6 cc/min/100 g). I-R injury was significantly reduced by LR as evidenced by a decrease in TTC infarct size from 41 +/- 7% to 11 +/- 5%, and a decrease in technetium-99m pyrophosphate uptake from 512 +/- 20 to 163 +/- 44 X 10(3) counts/min/g. LR also significantly decreased the postreperfusion edema formation as evidenced by a reduction in the muscle weight gain from 27 +/- 6 to 9 +/- 1 g, and a reduction in the 125I-albumin radioactivity from 45 +/- 14 to 32 +/- 8 counts/min/g. These data suggest that the hyperemic rate of reperfusion blood flow is a significant factor in the pathophysiology of postreperfusion edema and that clinical control of reperfusion injury in skeletal muscle may be achieved by limiting the rate of reperfusion blood flow.

Animals↗
PubMed1988

A new quantitative spectrophotometric assay of ischemia-reperfusion injury in skeletal muscle.

Characterization of ischemia-reperfusion injury of skeletal muscle remains poorly defined. A new quantitative assay to measure ischemic skeletal muscle injury is described and validated in a rat hindlimb model. This biochemical spectrophotometric technique measures triphenyltetrazolium chloride reduction in ischemic muscle. The reduction assay demonstrated significant injury after 3 hours of ischemia (25.4 +/- 9.7 percent of control activity; p less than 0.05). More severe injury occurred after 4 or more hours (less than 3 percent of control activity; p less than 0.05). This assay is an objective and quantitative method for characterizing ischemia-reperfusion injury.

Animals↗
PubMed1988

Technetium 99m pyrophosphate quantitation of skeletal muscle ischemia and reperfusion injury.

The study of ischemia and reperfusion injury in the extremity has been hampered by lack of an accurate method of measuring skeletal muscle injury. We used a bilateral isolated in vivo canine gracilis muscle model in 15 anesthetized dogs. The experimental muscles had 4, 6, or 8 hours of ischemia and 1 hour of reperfusion. The contralateral gracilis muscle served as a control. Technetium 99m pyrophosphate (99mTc-PYP), an agent which localizes in injured muscle cells, was used to quantitate canine skeletal muscle damage. After 6 hours of ischemia and 1 hour of reperfusion, there was a significant increase of 215% of 99mTc-PYP uptake in the experimental vs the control muscle. Experimental muscle uptake was 8% greater than control after 4 hours and 405% more after 8 hours of ischemia and reperfusion. Segmental distribution of 99mTc-PYP uptake showed localization to be greatest in the middle of the muscle at the entry site of the gracilis artery. Electron microscopic evaluation also documented this area to have undergone the most severe injury. Distal portions of the muscle did not show increased damage. Our results show that 99mTc-PYP effectively quantitates skeletal muscle ischemia and reperfusion injury. The pattern of 99mTc-PYP uptake suggests that considerable injury is caused during reperfusion.

Animals↗