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Biomedical subjects

R W Hobson

Publications and source records attributed to R W Hobson.

At least 127 records · Page 7Linked to original sources

Regional hypothermia protects against ischemia-reperfusion injury in isolated canine gracilis muscle.

Regional hypothermia is known to protect many tissues from ischemic injury. We investigated the relationship between regional hypothermia and skeletal muscle ischemia-reperfusion injury in a bilateral in vivo isolated canine gracilis muscle model. In five anesthetized dogs, one gracilis muscle was subjected to 6 hours of ischemia followed by 1 hour of reperfusion while the contralateral muscle served as a nonischemic control. Localization and quantitation of skeletal muscle injury was determined by histochemical staining with triphenyl tetrazolium chloride (TTC) followed by computerized planimetry of the infarct size. Muscle pH and temperature were monitored continuously in the proximal, middle, and distal segments by using pH electrodes and needle thermistors. Muscle pH was calculated by use of the Nernst equation with temperature correction, and hydrogen ion washout rates (H+) were derived from the observed change in muscle pH during reperfusion. A significant (p less than 0.05) regional hypothermia was observed in the distal third of the muscle. The preischemic temperature in the distal muscle was 27 +/- 2 degrees (SEM) C, compared to 34 +/- 1 degree and 32 +/- 2 degrees C in the proximal and middle segments of muscle, respectively. This temperature gradient was sustained throughout the experiment. The distal third of the ischemic muscle demonstrated significantly less (p less than 0.05) injury than the proximal and middle thirds as measured by TTC infarct size (31 +/- 10%, compared to 71 +/- 3% and 78 +/- 6%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heparinization reduces endothelial permeability and hydrogen ion accumulation in a canine skeletal muscle ischemia-reperfusion model.

Skeletal muscle injury after revascularization (ischemia-reperfusion) continues to be a major clinical problem. Although heparinization has been recommended, its action in an experimental model of I-R has not been evaluated. We investigated the ability of heparinization to decrease I-R injury in 10 anesthetized dogs (nonheparinized, n = 5; heparinized, n = 5), subjecting one gracilis muscle to 6 hours of ischemia followed by 1 hour of reperfusion while the identically prepared contralateral muscle served as a nonischemic control. Skeletal muscle infarction was determined by Tc-PYP uptake. Endothelial permeability was quantified by measurement of skeletal muscle 125I-Alb activity after intravenous injection. Interstitial hydrogen ion (H+) accumulation was determined by a miniature pH electrode inserted into the gracilis muscle. Isotopic activities from the ischemic muscle were calculated as a percentage of the contralateral nonischemic muscle (mean +/- SEM). Nonheparinized ischemic muscles had an increase in the activities of Tc-PYP and 125I-Alb of 684% +/- 149% and 742% +/- 130%, which were reduced to 218% +/- 54% and 378% +/- 85% by heparinization, respectively (p less than 0.05). During ischemia, the nonheparinized muscles accumulated 1223 +/- 121 nmol of H+ compared with 785 +/- 95 nmol in the heparinized animals (p less than 0.01). This significant reduction in I-R injury may be causally related to diminished endothelial permeability and H+ accumulation.

Animals↗

Poststenotic flow velocity changes as a function of stenosis geometry.

We used an in vitro pulsatile flow model to examine the velocity profile distal to a variable nonaxisymmetric stenosis. Using a continuous-wave Doppler velocimeter, the peak systolic frequency was determined distal to the stenosis and in planes parallel and perpendicular to the long axis of the stenosis. In both planes, an exponential regression best describes the relationship between peak systolic frequency and reduction in cross-sectional area. Regressions at each point of insonation diverged as a direct function of reduction in cross-sectional area and as an indirect function of distance from the stenosis. At each point of insonation, regressions representing the relationship in the mutually perpendicular planes diverged in direct proportion to reduction in cross-sectional area. Slopes were greater in parallel planes of insonation. These data demonstrate that two variables, distance and geometry, may influence the results of spectral analytic studies.

Arterial Occlusive Diseases↗

Microvascular transport and endothelial cell alterations preceding skeletal muscle damage in ischemia and reperfusion injury.

We determined the leakage of macromolecules using FITC-dextran-150 as a tracer and measured the extent of no-reflow phenomenon by video field analysis. The cremaster muscle of anesthetized rats was fashioned as a single layer, splayed on a lucite chamber and suffused with bicarbonate solution at 35 degrees C. After a 1 hour period of baseline data collection, ischemia was produced by cross-clamping the cremasteric vascular pedicle for periods of 30 minutes and 2 hours in separate experiments. Macromolecular leakage was visualized after reinstitution of perfusion. Leakage occurred at postcapillary venules 15 to 50 micron in diameter and quickly spread to the interstitium. The magnitude of leakage decreased as a function of time with continuous buffer suffusion, but remained higher than in the control period. No reflow occurred in approximately 30 percent of the muscle microvasculature upon reperfusion. The no-reflow values at 30 minute and 2 hour periods of ischemia were significantly different from the control values but were not from each other. Electron micrographs demonstrated endothelial cell swelling and migration of leukocytes and normal myocytes after 1 hour of reperfusion following 2 hours of ischemia. Our results demonstrate that permeability changes, occurrence of no reflow, and leukocyte migration precede the onset of damage to skeletal muscle in ischemia and reperfusion injury.

Animals↗

Assessment of ischemia reperfusion injury in skeletal muscle by macromolecular clearance.

Qualitative changes in skeletal muscle injury after ischemia are well known; however, quantitative assessments have not been well documented. We have determined microvascular permeability changes by measuring the clearance of fluorescein-labeled dextran of MW 150,000 (FITC-Dextran-150). The cremaster muscle of anesthetized rats was fashioned as a single layer, splayed on a lucite chamber and suffused with bicarbonate buffer solution at 35 degrees C. Clearance is the product of suffusion rate times the ratio of suffusate to plasma concentrations of FITC-Dx 150. After a 1-hr period of baseline data collection, ischemia was produced by cross-clamping the cremasteric vascular pedicle for periods of 30 min and 2 hr in separate experiments. Clearance of FITC-Dx 150 increased from a control value (mean +/- SE) of 8.3 +/- 2.7 to 29.9 +/- 8.1 microliters/min/g after reperfusion following a 30-min period of ischemia, and from a control value of 36.2 +/- 13.6 to 274 +/- 94.5 after 2 hr of ischemia. The differences were statistically significant (P less than 0.05). Our results show a significant increase in microvascular permeability occurring after only 30 min of ischemia. They also demonstrate a direct relationship between the extent of the permeability change and the duration of the ischemic period.

Animals↗

Quantitative histochemical evaluation of skeletal muscle ischemia and reperfusion injury.

Acute arterial obstruction to the extremities is associated with significant morbidity and mortality. The evaluation of accompanying skeletal muscle injury has thus far been indirect and imprecise. Triphenyltetrazolium chloride (TTC) is an oxidation-reduction indicator which allows for the histochemical quantitation of skeletal muscle injury. In 21 anesthetized nonheparinized adult mongrel dogs, the isolated in vivo gracilis muscle underwent 4, 6, or 8 hr of ischemia with and without reperfusion. The muscles were excised and cut into 1-cm segments, representative muscle biopsies for electron microscopy were taken, each segment was stained in 1% TTC, and the total area of staining was measured with computerized planimetry. All control muscles stained completely with a dark red color. After 4, 6, or 8 hr of ischemia, quantitative measurements of muscle staining indicative of normal tissue were present in 98 +/- 1%, 59 +/- 5%, and 23 +/- 9% of the total muscle areas, respectively. Six hours of ischemia followed by reperfusion was associated with only 36 +/- 9% of the muscle being stained. Segmental TTC staining demonstrated that reperfusion was associated with greater injury, and less TTC staining, in the proximal portion of the gracilis muscle at the site of entry of the major arterial pedicle. The distal muscle did not demonstrate increased damage with reperfusion. It is hypothesized that protection of the distal muscle from reperfusion injury may be due to an absence of reflow farther away from the artery.

Animals↗

Vascular complications related to drug abuse.

Vascular complications resulting from drug abuse constitute a widespread and common clinical problem. A 3-year experience with 32 vascular complications (13 arterial, 19 venous) related to intravenous drug abuse is reported. Fourteen (48%) of the 29 patients in this series presented with septic vascular complications. These infections were a major cause of morbidity and mortality, resulting in two hospital deaths and a disrupted arterial repair. In addition, intra-arterial drug injection caused digital gangrene in two patients. Early recognition, diagnostic arteriography and venography, and planned therapeutic interventions are possible if a high level of suspicion is maintained.

Adult↗

Retrograde internal mammary artery flow and resistant angina pectoris: clues to the coronary-subclavian steal syndrome.

A 68-year-old woman with persistent angina immediately following coronary bypass surgery using a left internal mammary artery graft was diagnosed as having "coronary-subclavian steal syndrome" 13 years after operation. We outline clinical and angiographic clues that will aid in the identification and diagnosis of this syndrome, which may become more common with the increased use of the mammary artery as a coronary bypass conduit.

Angina Pectoris↗

Microprocessor-controlled pulsatile flow loop for hemodynamic studies.

Validation of spectral analytic techniques in the clinical assessment and quantitation of vascular stenoses has been aided by use of in vitro flow loops. We have used a recently developed microprocessor-controlled pulsatile flow model to examine the influence of varying stenoses on Doppler-shifted peak systolic frequencies. A nonaxisymmetric, vertically oriented stenosis was produced by extrinsic compression of latex rubber tubing 12 mm in diameter, reducing the cross-sectional area (CSA) by 25, 40, 50, 60, 70, 85, and 97%. A rolling diaphragm pump, driven through a slider-crank mechanism by a microprocessor-controlled stepper motor, generated characteristic arterial pulse waves at a rate of 75 cycles per minute. Using an 8 MHz, continuous-wave, directional Doppler velocimeter, the Doppler-shifted frequencies were recorded at the stenosis. Four sets of observations were made at each of the stenoses, and the peak systolic frequency (PSF) was determined using a spectrum analyzer. The PSF in the absence of an obstructing stenosis was 2.56 +/- 0.03 (KHz +/- SEM). This increased significantly (P less than 0.05) to 4.80 +/- 0.09 when the CSA was reduced by 50%, to 5.90 +/- 0.37 when the CSA was reduced by 60% (P less than 0.05), to 8.40 +/- 0.10 when the CSA was reduced by 70% (P less than 0.05), and to 17.84 +/- 0.89 when the CSA was reduced by 85% (P less than 0.05). These data establish the utility of this pulsatile flow model, confirming the direct relationship between the Doppler-shifted PSF and the percentage reduction in CSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

Effects of prostacyclin injections and infusions on canine femoral hemodynamics.

The use of prostacyclin (PGI2) infusions has been recommended in the management of patients with severe distal arteriopathy, who are not candidates for conventional bypass procedures. Further clarification regarding the route of administration and the optimal dose of this potent vasodilator, however, is needed before controlled clinical trials are initiated. We measured bilateral femoral arterial blood flow electromagnetically in seven anesthetized adult mongrel dogs. Systemic arterial pressure and cardiac output were also measured. Central venous and femoral arterial injections of PGI2 were administered in five doses ranging from 10(-4) to 10(0) micrograms X kg-1 to study the dose response. PGI2 was also infused intravenously and intra-arterially for 20 minutes at a dose of 10(-1) micrograms X kg-1 X min-1. Femoral arterial injections of PGI2 in doses from 10(-4) through 10(0) micrograms X kg-1 caused significant (p less than 0.05) and dose-dependent increases in ipsilateral femoral arterial blood flow. Intravenous injections of PGI2 caused no significant changes in the dose range from 10(-4) to 10(-2) micrograms X kg-1 but resulted in a significant (p less than 0.05) reduction in femoral arterial flow and systemic arterial pressure at doses of 10(-1) and 10(0) micrograms X kg-1. The femoral arterial infusion of PGI2 produced a significant and sustained increase in femoral arterial flow that was not observed during the intravenous infusion. Arterial pressure was unchanged with intra-arterial PGI2 but was significantly reduced during the intravenous infusion. The beneficial hemodynamic effects of intra-arterial PGI2 suggest that further clinical trials should employ this route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of isobutyl 2-cyanoacrylate glue, fibrin adhesive, and oxidized regenerated cellulose for control of needle hole bleeding from polytetrafluoroethylene vascular prostheses.

Prolonged anastomotic and needle hole bleeding from synthetic vascular prostheses is a common surgical problem in heparinized patients and in the patient with a coagulopathy. The relative effectiveness of various hemostatic agents has not previously been determined by controlled comparisons. In this study 6 mm polytetrafluoroethylene (PTFE) vascular prostheses were used to perform carotid-carotid and femorofemoral bypasses in eight heparinized dogs. The relative effectiveness of isobutyl 2-cyanoacrylate, fibrin adhesive, and oxidized regenerated cellulose was determined by application of these hemostatic agents to three sources of bleeding: arterial-PTFE anastomoses, PTFE-PTFE anastomoses, and 18-gauge needle holes in PTFE vascular prostheses. The mean time to hemostasis (MTH) was determined for each hemostatic agent. Although application of isobutyl 2-cyanoacrylate resulted in the shortest MTH in each experimental group, the reported inflammatory response that it induces and its possible carcinogenicity limits its availability for clinical use. Application of fibrin adhesive prepared from single-donor hepatitis-screened plasma resulted in a significantly shorter MTH in each experimental group when compared with oxidized regenerated cellulose. We recommend clinical use of fibrin adhesive to control needle hole and anastomotic bleeding from PTFE vascular prostheses.

Animals↗

The value of laser Doppler velocimetry and transcutaneous oxygen tension determination in predicting healing of ischemic forefoot ulcerations and amputations in diabetic and nondiabetic patients.

The ability to predict successful healing of ulcerations and amputations of the ischemic forefoot continues to be a major clinical challenge, particularly in diabetic patients whose systolic Doppler ankle pressures are often artifactually elevated. We have used the techniques of laser Doppler velocimetry (LD) and transcutaneous oxygen tension monitoring (tcPO2) to quantitatively measure skin blood flow in the distal foot. Fifty-nine limbs were studied (48 patients), of which 37 (63%) were in diabetic and 22 (37%) in nondiabetic patients. All patients were admitted with ischemic ulcerations or gangrenous changes of the forefoot or digit. Twenty transmetatarsal or digital amputations were performed; the remainder of the lesions were débrided and allowed to heal by secondary intention or were covered by a skin graft. Before operation, the systolic pressure (expressed in millimeters of mercury, mean +/- SEM) was measured by Doppler technique at the ankle, and the ankle/arm index calculated (n = 59 limbs). The tcPO2 (also expressed in millimeters of mercury, mean +/- SEM) was measured from the dorsal foot (n = 56). The baseline skin blood flow velocity (SBFV) and pulse wave amplitude (PWA) were measured with the LD (expressed in millivolts, mean +/- SEM) on the plantar aspect of the foot (n = 53 limbs). Criteria for successful healing included a tcPO2 of more than 10 mm Hg, the combination of an LD-SBFV of more than 40 mV and an LD-PWA of more than 4 mV, and an ankle systolic pressure of more than 30 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Amputation Stumps↗

Doppler-derived percentage systolic window and the quantitation of arterial stenosis.

Peak systolic frequency (PSF) and percentage systolic window (%SW) are spectral parameters used to characterize poststenotic flow velocity patterns. The PSF, obtained using a continuous-wave (CW) Doppler velocimeter, has been used more frequently, however, in the quantitation of carotid occlusive disease. The authors have employed a microprocessor-driven pulsatile flow model to evaluate more completely the relationship between stenosis and the %SW. Using an 8 MHz CW Doppler probe, the Doppler-shifted frequencies were recorded at 1, 2, 3, 4, and 5 diameters distal to a variable, nonaxisymmetric stenosis, which reduced the cross-sectional area (CSA) 25, 40, 50, 60, 70, 85, and 97 per cent. Four sets of observations were made and the %SW derived using a spectrum analyzer. At one diameter from the stenosis, the relationship between the %SW (Y) and the reduction in CSA (X) is best described by two first-order regressions (Y = MX + B). The slope of the relationship from 0 to 60 per cent reduction in CSA is nearly flat, -0.052, while there is a significant (P less than 0.05) decrease in the slope, -1.538, when the CSA is further reduced from 60 to 97 per cent. Beyond 1 diameter, the relationship is best described by a single linear regression, the gradual slope of which does not permit clinically useful comparisons. These data explain the lack of strong correlation between CSA and %SW when the data are evaluated over the entire range of stenoses. However, they do indicate that the %SW may be a useful correlate if it is obtained within one diameter of the stenosis.

Arterial Occlusive Diseases↗

Results of revascularization and amputation in severe lower extremity ischemia: a five-year clinical experience.

Aggressive revascularization of the ischemic lower extremity in atherosclerotic occlusive disease by femoropopliteal (FP) and femorotibial (FT) bypass or profundaplasty (P), as indicated, has been advocated by some authors for all patients. Others have recommended primary amputation, particularly for tibial occlusive disease. To clarify this clinical dilemma, we reviewed the results of 547 procedures performed during the last 5 years: revascularization in 375 (69%) instances and below-knee amputation (BKA) in 172 (31%) cases. Bypass procedures were used in 246 cases: FP in 155 (64%) and FT in 91 (37%). Reversed autogenous saphenous vein (ASV) was used preferentially in 125 (51%) cases, whereas polytetrafluoroethylene (PTFE) was used in 121 (49%) cases. P was performed in 129 instances accompanied by inflow procedures in 92 (71%) of these cases. Cumulative limb salvage (LS) exceeded bypass patency in all categories and resulted in 2- and 5-year LS rates of 83% and 81% for FP with the use of ASV and 52% and 35% for PTFE. The LS rate for FT was 53% and 47%, respectively, for ASV and 20% and 15% for PTFE. Rest pain was successfully relieved by P in 99 cases (77%), whereas healing occurred in only 51% of cases with tissue loss. The perioperative mortality rate for revascularization was 3%; 42% of the group died during follow-up, death usually resulting from complications of atherosclerosis. Of the 172 BKAs, primary healing occurred in 80%, but the perioperative mortality rate was 13%. FP and FT bypasses are preferred procedures if ASV is available, whereas use of PTFE should be limited to FP bypasses only. Rest pain is relieved by P but tissue loss should prompt consideration for bypass. BKA should be considered in cases of severe tibial disease only in the absence of a suitable ASV, as the perioperative mortality rate is high and ultimate rehabilitation (64%) is limited.

Amputation, Surgical↗

Asymptomatic carotid disease.

The advent of noninvasive screening tests has allowed the identification of an increasing number of patients with asymptomatic carotid stenoses. The management of these patients must be individualized, as the preferred method of therapy has not been established. Such a solution ultimately requires a prospective randomized trial to define the natural history of these lesions and to clearly establish if surgical therapy has a role. Currently, there is a Veterans Administration Cooperative Study underway which will attempt to fill the existing information gap. Specifically being examined is the relationship between subsequent cerebrovascular symptoms and the degree of stenosis, progression of stenosis, contralateral disease and non-carotid operation. This study will not be completed for five years, so that other, current guidelines must be sought. It is essential that any surgeon considering prophylactic carotid endarterectomy demonstrate combined morbidity and mortality figures of less than 3 per cent. The patients being considered must also be an acceptable cardiac risk, as myocardial infarction represents the most common postoperative complication. Until prospective data is available, with a detailed analysis of the degree of stenosis, presence of ulceration and ultimate clinical course, the surgeon undertaking prophylactic endarterectomy must carefully screen his patients and concentrate on groups at high risk. This is especially important as more data on the significant incidence (10 to 15 per cent) of carotid restenosis becomes available. The results of three studies (34, 36, 69) suggest that those patients with hemodynamically significant stenoses, identified noninvasively by OPG techniques, are at a greater risk for cerebral ischemic events than those patients without significant stenoses. In addition, an observed incidence of stroke of 17.5 per cent and an indicence of TIAs of 33 per cent in patients with disease progression demonstrated by OPG-K/CPA. The work of another researcher (71) suggests that patients with carotid stenoses can be observed until symptoms develop or until the stenosis progresses to greater than 80 per cent.(ABSTRACT TRUNCATED AT 400 WORDS)

Arterial Occlusive Diseases↗

The role of contrast arteriography in suspected arterial injuries of the extremities.

The records of 215 patients presenting with 218 penetrating or blunt injuries to the extremities from 1977 through 1983 have been reviewed. All patients presenting with pulsatile hemorrhage, expanding hematoma, or absent distal pulses were explored immediately. Patients with injuries in close proximity to a major artery but without classical signs of arterial injury were explored routinely from 1977 through 1980. Thereafter, similar patients were evaluated initially with contrast arteriography and explored only if arteriographic abnormalities suggested arterial injury. Routine exploration of proximity injuries has been compared with selective exploration based on contrast arteriography. Sixty-one patients (group 1) underwent routine exploration for proximity injuries. Vascular injuries were detected in ten (16%) patients, while 51 (84%) of the explorations were negative. Eighty-four patients (group 2) with proximity injuries were studied arteriographically. Ten patients (11.9%) were explored on the basis of abnormal arteriograms, and eight arterial injuries were confirmed. Two (2.4%) of the 84 patients in this group had negative explorations. The use of contrast arteriography enabled the authors to reduce their negative exploration rate from 84 to 2.4 per cent in the management of proximity injuries.

Adolescent↗

Simultaneous determination of brachial and femoral arterial pressures during reactive hyperemia and papaverine vasodilation.

Accurate assessment of aortoiliac occlusive disease often requires direct intraarterial pressure determination. Since these measurements may alter systemic pressure, brachial arterial pressure (BAP) and femoral arterial pressure (FAP) were obtained simultaneously to quantitate these changes. BAP and FAP were measured at rest, and then during vasodilation produced by postischemic reactive hyperemia and intra-arterial injection of papaverine. The gradient between FAP and BAP was used to assess the significance of an aortoiliac stenosis. Sixty-eight observations were performed in 19 limbs. During reactive hyperemia (n = 28), BAP was 142 +/- 7 mm Hg, which was not significantly different from the baseline BAP of 142 +/- 5 mm Hg. However, during thigh tourniquet inflation, BAP increased significantly to 158 +/- 7 mm Hg. Following papaverine injection (N = 21) BAP was 144 +/- 8 mm Hg, which was significantly different from both the baseline BAP (150 +/- 6 mm Hg) and the preinjection BAP (156 +/- 6 mm Hg). Postischemic reactive hyperemia and papaverine vasodilation produced comparable brachial to femoral pressure gradients. Use of baseline BAP is recommended for calculating gradients during reactive hyperemia, since the BAP is significantly elevated during tourniquet occlusion. Simultaneous recording of brachial and femoral pressures is recommended with intra-arterial papaverine injections, since the BAP varies significantly throughout the examination.

Aortic Diseases↗

Interpretation of Doppler segmental pressures in peripheral vascular occlusive disease.

Measurement of Doppler segmental arterial pressures in the lower extremity using narrow pneumatic cuffs has become a standard noninvasive diagnostic technique. Correlation between arteriographic and noninvasive studies was available for 345 aortoiliac segments and 326 femoropopliteal segments. If stenoses of 50% or greater and occlusions were considered hemodynamically significant, the sensitivity to aortoiliac disease was 97%, but only 67% to femoropopliteal disease. The specificity for hemodynamically insignificant disease was 50% and 68%, respectively. Accuracy was influenced by the presence of associated aortoiliac or femoropopliteal disease. The sensitivity to hemodynamically significant femoropopliteal disease was 55% if there was associated aortoiliac disease, and 89% in its absence. In the presence of significant femoropopliteal disease, specificity for the absence of aortoiliac disease decreased from 70% to 41%.

Angiography↗