Micromachined Fused Silica Liquid Core Waveguide Capillary Flow Cell.

A planar, chip-based flow cell for UV-vis absorbance detection in HPLC is presented. The device features a microfabricated free-standing liquid core waveguide (LCW) capillary detection tube of long path length that is based on total internal reflection. We report on the linearity and calibration slope characteristics of lithographically produced LCWs with different interior/exterior geometries. 3D ray tracing was indispensable in modeling behavior in the more demanding geometries: multipath behavior may be intrinsic to these waveguides with consequent nonlinearity. Fortunately, nonlinearity in lithographically easy-to-produce waveguide geometries (such as with a flat, concave exterior and a round interior) is not as detrimental as might be initially expected. Experimental performance is predictably affected by the attainable surface quality of the LCW and efficient and reproducible coupling of the input light into the LCW.

Profound Vagal Tone and Bradycardia Mimicking Asystole: A Resuscitation Case Report.

A 48-year-old man presented with dizziness. When he arrived at the emergency department, he collapsed and became pulseless. Prior to his collapse, he was asymptomatic and now even participated in multiple marathon and ultra-running events per year. However, he previously experienced a vasospastic inferior STEMI eight years prior from cocaine use. As a result, he had an ischaemic cardiomyopathy with LVEF of 45%. He never took any further illicit substances after the STEMI; instead, he changed his lifestyle completely and commenced extreme endurance sports. After one hour of alternations between VF/VT rhythms and asystole, a rhythm check demonstrated a single complex with a corresponding pulse. He had received 12 mg of epinephrine up to that point as per local resuscitation guidelines. Upon diagnosing extreme bradycardia, 2 mg of total atropine administration resulted in ROSC. We theorise that this bradycardia was a result of increased vagal tone as ROSC was quickly achieved following atropine administration.

Skeletal muscle as the potential power source for a cardiovascular pump: assessment in vivo.

Skeletal muscle ventricles (SMVs) were constructed from canine latissimus dorsi and connected to a totally implantable mock circulation device. The SMVs, stimulated by an implantable pulse generator, pumped continuously for up to 8 weeks in free-running beagle dogs. Systolic pressures produced by the SMVs, initially of 139 +/- 7.2 mmHg and after 1 month of continuous pumping of 107 +/- 7 mmHg, were comparable to normal physiologic pressures in the adult beagles (114 +/- 21 mmHg). After 2 weeks of continuous pumping, the mean stroke work of the SMVs was 0.4 X 10(6) ergs, a performance that compares favorably with the animal's cardiac ventricles. This study shows that canine skeletal muscle which has not received prior training or electrical conditioning can perform sustained work at the high levels needed for an auxiliary cardiovascular pump. It might be possible eventually to use such muscle pumps in humans to assist the failing circulation and to provide support in children with certain types of congenital heart defects.

Oxidative stress and lipid retention in vascular grafts: comparison between venous and arterial conduits.

BACKGROUND: Because saphenous vein grafts (SVGs) exhibit greater cellular heterogeneity and worse clinical outcomes than arterial grafts (AGs), we examined oxidative stress and lipid retention in different vascular conduits. METHODS AND RESULTS: In a porcine model of graft interposition into carotid artery, superoxide anion (.O(2)(-)) was measured at 2 weeks after surgery. SVGs demonstrated increased.O(2)(-) production compared with AGs (SOD-inhibitable nitro blue tetrazolium reduction, P<0.01). The NAD(P)H oxidase inhibitor diphenyleneiodonium (P<0.01) abolished SVG-derived.O(2)(-), whereas the inhibitors of other pro-oxidant enzymes were ineffective. The change in oxidative stress was also reflected by lower activity of the endogenous antioxidant superoxide dismutase in SVGs than in AGs (P<0.001). SVG remodeling was associated with increased synthesis of sulfated glycosaminoglycans and augmented expression of a core protein, versican. These changes were accompanied by SVGs retaining significantly more (125)I-labeled LDL than AGs ex vivo (P<0.001). In hyperlipemic animals, lipid accumulation and oxidized epitopes were preferentially noted in the intima of SVGs at 1 month after surgery. CONCLUSIONS: This study demonstrated significant differences in the biology of SVGs and AGS: SVGs exhibited higher oxidative stress, LDL accumulation, and the presence of oxidized epitopes. These findings suggest that proatherogenic changes in SVGs may commence early after surgical revascularization.

Hydraulic pouches of canine latissimus dorsi. Potential for left ventricular assistance.

We have studied the fatigue rates of hydraulic pouches constructed in the form of a multilayered conical spiral using the latissimus dorsi muscle of 17 beagles. The roles that electrical muscle conditioning and early interruption of collateral blood supply have in the prevention of pouch fatigue were evaluated. The length of time that a pouch could generate flow in a hydraulic test system was measured; afterload was set at 80 mm Hg and preload 24 mm Hg. Pouches (N = 3) fashioned from muscles subject to neither electrical conditioning nor a vascular delay generated an initial flow of 990 +/- 346 ml/min, but could sustain flow for only 2.3, 3.8 and 3.6 minutes. Pouches (N = 5) constructed with electrically unconditioned muscles after a vascular delay (median 3 weeks) demonstrated a variable improvement in fatigue rates (initial flow 826 +/- 265 ml/min; time to no forward flow, 2.5, 7.5, 7.5, 10, and 200 minutes). Four of six pouches that received the benefit of long-term electrical muscle conditioning and a vascular delay (N = 6) were able to generate flow for a 4 hour period, at which time the experiment was terminated (initial flow 478 +/- 204 ml/min; final flow 195 +/- 157 ml/min). After the 4 hour fatigue test was completed, one electrically conditioned pouch was placed in series with the heart and served as a counterpulsator. The initial volume of blood pumped by the muscle pouch was 262 ml/min or 13.8% of cardiac output. After the pouch had contracted at a rate of approximately 45 beats/min for 1 hour, the volume of blood pumped was 178 ml/min, or 11% of cardiac output. In three other animals a pouch was fashioned and then left in situ for a 1 to 3 week period before hydraulic testing. These pouches generated significant initial flows (390 +/- 60 ml/min), which demonstrates the feasibility of further study of permanent pouches. These results suggest that permanent electrical muscle conditioning and perhaps a vascular collateral delay might permit an auxiliary skeletal muscle-powered ventricle to assume a portion of left ventricular function.

Complications from heparin-induced thrombocytopenia in patients undergoing cardiopulmonary bypass.

The purpose of this study was to evaluate retrospectively the incidence and severity of heparin-induced thrombocytopenia (HIT)-related complications in patients undergoing cardiopulmonary bypass. We reviewed the records of 1,500 consecutive patients who underwent cardiopulmonary bypass between August 1987 and December 1991 at Thomas Jefferson University Hospital. During this period of time, there were 1,155 coronary artery bypass graft operations (77 percent); 225 valve replacements and repairs, or both (15 percent); 60 combination coronary artery bypass graft or valve operations, or both (4 percent); and 60 miscellaneous procedures (4 percent). Although not all patients with postoperative complications were tested for the HIT antibody, 11 patients (0.75 percent) were diagnosed with HIT. There were 17 complications in these 5 men and 6 women including 6 cases of ischemic limbs which required amputation, 4 strokes, 2 instances of saphenous vein graft occlusion with resulting myocardial infarction, 2 cases of pulmonary emboli, 1 case of phlegmasia cerulea dolens, and 2 deaths. The complications occurred an average of 3.6 days postoperatively, with a range of occurrence of 1 to 11 days postoperatively. The mean nadir platelet count at the time of recognition was 123,000/mm3 (range 32,000 to 193,000/mm3) with 9 of 11 patients (81.8 percent) having counts greater than 100,000/mm3. There was, however, a mean percent decrease in the platelet count of 50 percent (range, 31 to 75 percent) from the time of first exposure to heparin to the time of recognition of HIT. In our patients, HIT was not related to the type, duration of treatment with or amount of heparin, or to pretreatment with aspirin.

An autologous biologic pump motor.

Latissimus dorsi skeletal muscle ventricles were constructed in six beagles. They first underwent a period of vascular delay and of electrical preconditioning over several weeks. The skeletal muscle ventricles were then connected to a totally implantable mock circulation that allowed for the chronic measurement of pressures and flows produced by the muscle. The skeletal muscle ventricles were actuated by stimulation of the motor nerve with an implanted generator that delivered brief pulse trains. The skeletal muscle ventricles pumped continuously against an afterload of 80 mm Hg with a preload of 40 to 50 mm Hg at a rate of 54 times per minute. At initiation of pumping, systolic pressure was 135 +/- 24 mm Hg and flow was 464 +/- 116 ml/min. After 2 weeks of continuous pumping, the systolic pressure was 104 +/- 1 mm Hg and continuous flow was 206 +/- 16 ml/min. Two of the skeletal muscle ventricles pumped continuously for 5 and 9 weeks, respectively. At the end of that time one was still capable of generating pressure up to 205 mm Hg and the other, 160 mm Hg. These results suggest that a chronic auxiliary skeletal muscle ventricle is a feasible approach to the treatment of end-stage cardiac failure.

Wound healing around and within saphenous vein bypass grafts.

BACKGROUND: Myofibroblasts are a prominent cell type in wound healing. The goal of this study was to examine the extent to which myofibroblasts contribute to structural changes in saphenous vein bypass grafts. METHODS AND RESULTS: Control veins and reversed saphenous vein bypass conduits of porcine carotid arteries were examined 2 to 4, 7 to 14, and 30 to 90 days after surgery with immunohistochemical markers of cellular proliferation (proliferating cell nuclear antigen), cytoskeletal protein production (alpha-smooth muscle actin and desmin), and histochemistry (Verhoeff's stain). Control veins demonstrated an extremely low level of cellular proliferation and no evidence of myofibroblasts in the adventitia, media, or intima. After bypass grafting, cellular proliferation was followed by myofibroblast formation, which occurred in the perivascular area and within the media. This was evidenced by a dense, but transient, expression of alpha-smooth muscle actin and a variable expression of desmin at 1 to 2 weeks, and with a significant increase in collagenous tissue by 1 to 3 months. Major cytoskeletal protein changes also occurred in the intima, with the appearance of alpha-smooth muscle actin positive cells at 7 to 14 days. alpha-Smooth muscle actin was still present in the neointima at 1 to 3 months, which is compatible with a persistent myofibroblast formation. CONCLUSION: Myofibroblast formation occurs around and within saphenous veins after bypass grafting. This phenomenon is associated with significant remodeling of the vein grafts. The histologic changes are strikingly similar to events that occur during wound healing and may have implications for the development of neointimal hyperplasia and late vein graft disease.

The effect of basic fibroblast growth factor on the blood flow and morphologic features of a latissimus dorsi cardiomyoplasty.

Previous studies designed to determine whether latissimus cardiomyoplasty could be used to revascularize ischemic myocardium showed that after operation the latissimus was ischemic and had severely deteriorated. This study was undertaken to determine whether basic fibroblast growth factor, a potent angiogenic peptide, would improve the vascularity of the latissimus and enhance collateral formation between the muscle of the cardiomyoplasty and ischemic myocardium. In goats, myocardial ischemia was induced with an ameroid constrictor and cardiomyoplasty performed. The latissimus was continuously stimulated electrically at 2 Hz for 6 weeks and given four weekly bolus injections of human recombinant basic fibroblast growth factor (80 micrograms infused into the left subclavian artery). In eight animals, rates of regional blood flow were measured and both the heart and latissimus were evaluated histochemically. The latissimus blood flow rate was 0.114 +/- 0.029 ml/gm per minute, which was three times greater than that of historical controls (chronically stimulated latissimus cardiomyoplasty without basic fibroblast growth factor treatment; 0.042 +/- 0.007 ml/gm per minute, p < 0.05). Associated with the improved blood flow, there was significantly less evidence of skeletal muscle fiber dropout and muscle fibrosis in the animals treated with basic fibroblast growth factor. Latissimus-derived collateral flow to ischemic myocardium developed in five of the eight goats and averaged 0.288 +/- 0.075 ml/gm per minute. This flow was 42.8% +/- 15.7% (n = 5) of the flow required by normal myocardium (which was 0.728 +/- 0.095 ml/gm per minute). This value for latissimus-derived collateral blood flow was almost twice that of the historical controls (24.0% +/- 3.9%), but the increase did not achieve statistical significance (p = 0.08). These results hold the promise that basic fibroblast growth factor treatment might enhance the formation of extramyocardial collaterals to the heart and improve skeletal muscle function.

Saphenous vein graft protection: effects of c-myc antisense.

OBJECTIVE: Saphenous vein grafting is associated with extensive medial remodeling, characterized by cellular proliferation, loss of smooth muscle cells, and an inflammatory response. In this study, we examined whether unfavorable responses to vein grafting could be modified by the intraoperative application of c-myc antisense oligomers. METHODS: The intragraft cell proliferation, macrophage infiltration, and medial preservation were examined in a porcine model in the control and antisense-treated groups (n = 36). RESULTS: Saphenous veins showed transmural distribution of oligomers within 30 minutes of the ex vivo incubation. A concentration-dependent inhibition of cell proliferation in the media of saphenous grafts was noted 3 days later (0 to 200 mumol/L, p = 0.005). The growth inhibition was sequence-specific, because control oligomers produced only insignificant effects (20 mumol/L). Vascular effects of c-myc antisense were associated with a significant attenuation of macrophage infiltration in saphenous grafts. A concentration-dependent decrease in tissue edema (p = 0.0005) and the attenuated loss of smooth muscle cells (p = 0.002) were noted in the media of the arterialized venous conduits after c-myc antisense. CONCLUSIONS: Direct application of synthetic DNA to harvested saphenous veins resulted in a rapid transmural distribution. The inhibition of the intragraft cell proliferation in vivo after c-myc antisense was sequence dependent. Decrease in vein graft injury resulted in an attenuated inflammatory response and better medial preservation. These findings provide a rationale for assessment of the long-term effects of vein graft protection with c-myc antisense.

Pneumothorax during positive-pressure mechanical ventilation.

The hemodynamic and respiratory effects of unilateral pneumothorax were studied during positive-pressure mechanical ventilation in five sheep. The sheep were anesthetized, intubated, and placed on mechanical ventilation with positive end-expiratory pressure (5 cm H2O). After baseline studies, including chest roentgenograms, were taken, increments of air were injected into the right pleural cavity. Measurements were repeated at pneumothoraces of 500, 1,000, and 1,500 ml. There was a steady fall in cardiac output (p less than 0.02) at pneumothoraces of 1,000 and 1,500 ml. The decrease in cardiac stroke volume paralleled that of cardiac output. Heart rate rose (p less than 0.05) at a pneumothorax of 1,500 ml. There appeared to be a linear relationship between the percent increase in pneumothorax as estimated by roentgenogram and the percent fall in cardiac output (r = 0.991). There was a steady rise in mean pulmonary arterial, pulmonary arterial capillary wedge, superior vena caval, and inferior vena caval pressures, although the changes in inferior vena caval pressure were not statistically different from baseline. Peak airway pressure increased from baseline at pneumothoraces of 1,000 and 1,500 ml. Both right and left end-expiratory intrapleural pressures increased and were statistically different (p less than 0.01) from baseline. However, there was a substantially greater rise in right intrapleural pressure than left. Arterial oxygen tension remained physiological throughout the study. This study indicates that cardiac output decreases as the amount of pneumothorax increases in sheep during mechanical ventilation. This study also demonstrates that, during positive-pressure mechanical ventilation, a relatively benign-appearing pneumothorax by chest roentgenogram may be associated with a significantly depressed cardiac output. In addition, arterial oxygen tension may not be useful in predicting the onset of pneumothorax during mechanical ventilation.

RASONs: a novel antisense oligonucleotide therapeutic approach for asthma.

Inhalation based approaches enable the local delivery of antisense oligonucleotides (ASONs) to the respiratory tract and thus facilitate the ability of ASONs to target and modulate the activity of discordantly expressed respiratory disease genes. Studies involving EPI-2010, a respirable antisense oligonucleotide (RASON), targeting the adenosine A(1) receptor, a G-protein-coupled-receptor (GPCR) that plays an important role in the aetiology of asthma, demonstrate that ASON therapeutics can be delivered directly to the lung as an aerosol. EPI-2010 has been shown to inhibit adenosine A(1) receptor expression and significantly improve allergen-induced airway obstruction and bronchial hyper-responsiveness in animal models of human asthma. Absorption, tissue distribution, metabolism and excretion (ADME) and safety studies of aerosolised EPI-2010 suggest that phosphorothioate RASONs can be delivered to target respiratory tissues in low, safe, efficacious and long-acting doses. This supports the concept that RASONs offer the potential to address a variety of respiratory targets including those for which approaches employing systemic distribution and systemic bioavailability of the therapeutic agent may be undesirable. In addition, our studies with EPI-2010 indicate that the RASON approach may represent a technology that is uniquely positioned to address the challenges of the post-genome era in respiratory drug discovery, since it enables simultaneous in vivo target validation and antisense therapeutic discovery in an accelerated timeframe.

Risks of subsequent pregnancies on mother and newborn in female heart transplant recipients.

BACKGROUND: Female heart transplant recipients are able to carry pregnancies successfully. This study evaluates the effect of subsequent pregnancies on newborn and maternal outcomes and graft survival. METHODS: Subjects were identified through a previously reported multicenter study, case reports from literature review, and recipients entered in the National Transplantation Pregnancy Registry. A retrospective analysis was completed of 35 heart transplant recipients with first pregnancies (FP) and 12 who had one or two additional pregnancies (P>1). Newborns were assessed for gestational age, neonatal birth weight, and complications. Maternal data included pregnancy outcome, peripartum complications, including infection and rejection, current graft function, and recipient survival. RESULTS: Forty-seven pregnancies (35 FP and 12 P>1) from 35 heart transplant recipients were studied. FP outcomes included 26 live births (one set of twins), four miscarriages, and six therapeutic abortions, whereas P>1 outcomes included 11 live births (one set of twins), and two miscarriages. There was no significant difference between mean birth weights (2353+/-986 gm vs 2588+/-521 g, P>1 vs FP; mean+/-SD; p=NS) or prematurity incidence (<37 weeks; 50% vs 40%; p=NS) for the live-born infants. Compared with the FP group, there was a trend toward increased neonatal complications in P>1 (40% vs 12%; p=NS). Complications were significantly more common in premature newborns compared with full-term newborns (33% vs 5%; p < 0.05). No structural malformations were identified in the live-born infants. Maternal complication rates were the same in both groups (40%). Of 28 recipients available for follow-up, the maternal survival rate was 75% for the FP group and 89% for the P> group. Mean rejection rate per year was slightly increased after pregnancy in the P>1 group. Surviving recipients had similar graft function by echocardiographic left ventricular ejection fraction. CONCLUSIONS: Post-heart transplantation pregnancies often have successful outcomes, but there is a high incidence of prematurity and low birth weight. Subsequent pregnancies do not seem to significantly increase the incidence of complications in either the newborn or mother or increase graft rejection or failure. Larger studies of posttransplantation pregnancies may provide more definitive information.

Canine diaphragm muscle after 1 yr of continuous electrical stimulation: its potential as a myocardial substitute.

Skeletal muscle has been rendered fatigue resistant by chronic stimulation and therefore has potential as an active substitute for damaged myocardium. It is therefore important to know whether stimulation produces any deleterious effects in the long term. Hemidiaphragm muscles of four dogs were examined after chronic stimulation for 1 yr at either 2 or 4 Hz. The stimulated hemidiaphragms appeared normal on gross inspection and were still contracting vigorously. By histochemical and immunohistochemical criteria, they had acquired a uniformly type I character, in contrast to the mixed fiber type composition of the unstimulated hemidiaphragms. This transformation was also reflected in their complement of myosin isozymes. There was some enzymatic evidence of an associated shift towards aerobic pathways of energy generation. Histological examination revealed no evidence of degenerative changes. Trends, observed in the shorter term (6-8 wk), toward a decrease in fiber area and an increase in connective tissue showed no further progression at 1 yr. Thus hemidiaphragm muscle stimulated at frequencies at or above the normal heart rate does not appear to undergo adverse long-term changes that would constrain its use in a myocardial assist role.

Contractile smooth muscle cell apoptosis early after saphenous vein grafting.

BACKGROUND: The media of saphenous veins is composed of two cell populations: smooth muscle (SMC) and non-smooth muscle (NSMC) cells. Previous studies demonstrate a loss of SMCs by 3 days after grafting, despite an increase in cell proliferation. The purpose of this study is to determine the rates of apoptotic cell death versus cell proliferation for the two major cell populations of the media. METHODS: Veins (six/time point) were examined at 0.5, 1, 2, 4, 8, 24, and 48 hours after grafting in crossbred pigs. Terminal transferase-mediated dUTP nick end labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) stains were used to assess apoptosis and proliferation. Apoptosis was also corroborated with confocal and electron microscopy. RESULTS: Apoptosis was high in both cell populations: at 8 hours, SMC and NSMC apoptosis peaked at 14.5% +/- 3.5% and 49.9% +/- 7.8%, respectively. In contrast, cell proliferation was different between the two populations. SMC proliferation was low at all time points, whereas NSMC proliferation rose to 22% +/- 5.4% by 48 hours. CONCLUSIONS: Medial SMCs are removed through apoptosis and appear to be replaced by fibrous tissue (NSMCs) early after vein grafting. This reciprocal change between the medial SMC and NSMC populations may contribute to late vein graft degeneration.

Early injury to the media after saphenous vein grafting.

BACKGROUND: Injury to the smooth muscle cells of the media affects the remodeling process of vein grafts. The purpose of this study was to determine whether different techniques of surgical preparation influence the degree of medial smooth muscle injury. METHODS: Carotid-saphenous vein interposition grafting was performed in crossbred pigs (n = 32), using distended (n = 16) or nondistended (n = 16) conduits. After 3 to 90 days, the media was evaluated for the presence of smooth muscle cells (desmin stains), myofibroblast formation (transient alpha-SM actin expression), and apoptosis (TdT-mediated dUTP nick end-labeling [TUNEL]). RESULTS: Smooth muscle loss was uniformly severe; only 5% +/- 5% (p < 0.01) and 14% +/- 9% (p < 0.01) of the medial area of distended and nondistended veins were desmin positive in comparison with 80% +/- 9% of controls. Apoptosis appeared to contribute to medial smooth muscle loss (5.7% +/- 4.3% in vein grafts versus 0.0% +/- 0.0% of TUNEL-positive cells in controls; p = 0.05). There was a time dependent increase in medial myofibroblast formation (p < 0.05). CONCLUSIONS: Severe medial smooth muscle loss occurs in vein grafts, even when prepared without distension. Apoptosis contributes to the early disappearance of smooth muscle cells. Adjunctive measures, in addition to ideal surgical techniques, should be developed to prevent medial muscle loss.

Sustained reduction of neointima with c-myc antisense oligonucleotides in saphenous vein grafts.

BACKGROUND: Treatment of saphenous veins with c-myc antisense oligomers during preparation for grafting reduces medial cellular proliferation and macrophage infiltration, and preserves medial smooth muscle content at 3 days. Accordingly, the purpose of this study was to examine whether c-myc antisense oligomers have an impact on late vein graft remodeling. METHODS: Sixty-two pigs underwent unilateral saphenous vein-carotid artery interposition grafting. Harvested veins were incubated either in saline (control group) or 20-micromol/L or 200-micromol/L concentrations of c-myc antisense oligomers (treated groups) for 30 minutes intraoperatively. Three months after surgery, vein graft histology was assessed. RESULTS: Forty-five of 62 randomized animals survived the experiment; no differences in animal survival or graft patency among the groups were observed (p = NS, chi2). C-myc antisense oligomers significantly decreased neointimal and wall thickness, as well as increased lumenal index, in treated groups (p<0.04, p<0.03, and p<0.001, respectively, analysis of variance). In contrast, there was no difference in medial thickness or perivascular wound healing. CONCLUSION: Intraoperative treatment of saphenous veins with c-myc antisense oligomers decreased neointimal formation at 3 months after grafting. In conjunction with our previous reports, these findings suggest that early inhibition of cellular proliferation and inflammatory infiltration results in a sustained reduction in neointimal formation and favorable graft remodeling.

Basic fibroblast growth factor identified in chronically stimulated cardiomyoplasties.

In the presence of myocardial ischemia, chronic electrical stimulation of a latissimus dorsi (LD) cardiomyoplasty enhances extramyocardial collateral blood flow. We postulated that basic fibroblast growth factor (bFGF) may mediate extramyocardial collateral formation. To test this hypothesis, LDs from goats with cardiomyoplasties were probed for the presence of bFGF by Western blot analysis and immunohistochemistry. Three groups were studied: static LD cardiomyoplasty (group 1); LD cardiomyoplasty stimulated at a 2-Hz frequency for 6 weeks (group 2); and LD cardiomyoplasty electrically stimulated and given human recombinant bFGF (group 3). There was no evidence of bFGF in the left LDs of group 1 by Western blot. Basic fibroblast growth factor-like immunoreactive evidence was found in the left LDs of group 2 goats by both Western blot and immunohistochemistry. In the right LDs of group 2, bFGF-like material was found by immunohistochemistry but not by Western blot, which suggests that the tissue concentrations were low (near the limits of detection). The left LDs of group 3 were positive for bFGF by Western blot and immunohistochemistry. Group 3 right LDs were positive for bFGF by immunohistochemistry. Immunohistochemical findings in group 2 indicate that bFGF is present in goat skeletal muscle. Western blot data from groups 1 and 2 suggest that bFGF may be increased in chronically stimulated cardiomyoplasties. From findings in group 3, we conclude that exogenous bFGF does not downregulate, and may upregulate, endogenous production. These results support the possibility that skeletal muscle bFGF is an important factor in extramyocardial collateral formation.

Heparin-induced thrombocytopenia: bovine versus porcine heparin in cardiopulmonary bypass surgery.

BACKGROUND: Studies have demonstrated a high incidence of antibodies to heparin/platelet factor 4 complexes, the antigen in heparin-induced thrombocytopenia, in patients after cardiopulmonary bypass surgery. In many hospitals, beef lung heparin has been used historically for cardiopulmonary bypass, and there has been reluctance to change to porcine heparin despite concerns of an increased incidence of heparin-induced thrombocytopenia in patients receiving bovine heparin. METHODS: A prospective randomized trial comparing bovine and porcine heparin in cardiopulmonary bypass surgery was conducted. Presurgery and postsurgery heparin antibody formation was studied using the serotonin release assay and a heparin/platelet factor 4 enzyme-linked immunosorbent assay. RESULTS: Data available on 98 patients, randomized to receive either bovine or porcine heparin, revealed no significant difference in patient positivity by serotonin release assay (12% in both groups) or by the heparin/platelet factor 4 enzyme-linked immunosorbent assay (29% with porcine and 35% with bovine heparin) postoperatively. There were no significant differences between preoperative and postoperative platelet counts or thromboembolic complications. CONCLUSIONS: Our study does not support the belief that bovine heparin is more likely than porcine heparin to induce the development of antibodies to heparin/platelet factor 4.