Stearidonic and γ-linolenic acids in echium oil improves glucose disposal in insulin resistant monkeys.

Echium oil (EO) contains stearidonic acid (18:4), a n-3 polyunsaturated fatty acids (PUFAs), and gamma-linolenic acids (18:3), a n-6 PUFA that can be converted to long chain (LC)-PUFAs. We aimed to compare a safflower oil (SO)-enriched diet to EO- and fish oil (FO)-enriched diets on circulating and tissue PUFAs levels and glycemic, inflammatory, and cardiovascular health biomarkers in insulin resistant African green monkeys. In a Latin-square cross-over study, eight monkeys consumed matched diets for 6 weeks with 3-week washout periods. Monkeys consuming FO had significantly higher levels of n-3 LC-PUFAs and EO supplementation resulted in higher levels of circulating n-3 LC-PUFAs and a significant increase in dihomo-gamma linolenic acid (DGLA) in red blood cells and muscle. Glucose disposal was improved after EO consumption. These data suggest that PUFAs in EO supplementation have the capacity to alter circulating, RBC and muscle LC-PUFA levels and improve glucose tolerance in insulin-resistant monkeys.

Cycled enteral antibiotics reduce sepsis rates in paediatric patients on long-term parenteral nutrition for intestinal failure.

BACKGROUND: Long-term parenteral nutrition has transformed the prognosis for children suffering from intestinal failure. However, parenteral nutrition itself is associated with considerable morbidity and mortality including that caused by sepsis. AIM: To examine a strategy of cycled enteral antibiotics in reducing the incidence of sepsis in paediatric intestinal failure patients. METHODS: Retrospective analysis of the incidence of sepsis rates of patients on long-term parenteral nutrition, at a tertiary paediatric hospital. Patients were separated into those who received cycled enteral antibiotics and a control group. Sepsis rates before and during cycled enteral antibiotics were compared with comparable timeframes between the cycled enteral antibiotics and control groups. Central venous catheter removal rates were also compared. RESULTS: Fifteen patients (eight cycled enteral antibiotics, & seven controls) received 9512 parenteral nutrition days, with a total of 132 sepsis episodes. All eight patients of the treatment group demonstrated a decrease in the frequency of episodes of sepsis following the introduction of cycled enteral antibiotics. The cycled enteral antibiotics group had a significant reduction in infection rate during the treatment period (from 2.14 to 1.06 per 100 parenteral nutrition days, P = 0.014: median effect size -1.04 CI 95%-1.93, -0.22), whereas the controls had no significant change (1.91 - 2.36 per 100 parenteral nutrition days P = 0.402: median effect size 0.92 CI 95%-1.96, 4.17). The central venous catheter survival rates increased in the cycled enteral antibiotics group from 0.44 central venous catheter removals per 100 parenteral nutrition days to 0.27 central venous catheter removals per 100 parenteral nutrition days, although this was not statistically significant. CONCLUSIONS: Cycled enteral antibiotics significantly reduced the rate of sepsis in a small group of paediatric intestinal failure patients. Larger well-designed prospective studies are warranted to further explore this finding.

Progress in treatment and outcome for children with neonatal haemochromatosis.

AIM: To evaluate the role of antioxidant treatment and liver transplantation in the management of neonatal haemochromatosis. METHODS: A retrospective review was performed of eight infants with acute liver failure and raised ferritin levels between 1990 and 1998. From 1994, treatment with an antioxidant cocktail (vitamin E, N-acetylcysteine, selenium, prostaglandin E1, and desferrioxamine) was begun once the diagnosis was suspected. Pathological and other findings were reviewed, and outcome before and after antioxidant treatment was evaluated. RESULTS: Median age at presentation was 4 days with median ferritin levels of 4180 micro g/l (range 1650-40 000 micro g/l; normal range 110-503 micro g/l). Three infants presented before 1994. One infant died before liver transplantation from acute liver failure and one from neurological damage after transplantation. The third patient underwent successful transplantation at day 13 and remains well on follow up 8 years later. From 1994, five patients received antioxidant treatment, of whom two responded: both responders started antioxidants earlier (by day 5) than non-responders and had lower peak ferritin levels (< 4200 micro g/l) and a milder phenotype. Treatment was continued until ferritin levels were < 500 micro g/l. Both children remain well with mean follow up of 42 months, with no recurrence of iron overload. One child showed a partial response to treatment and survived long enough for a liver transplant, but died from graft failure after the transplant. Two children did not respond to antioxidant treatment; both had multiorgan failure and were not listed for transplantation. Only three of the eight patients survived (37.5%) over this time period. CONCLUSION: Neonatal haemochromatosis can be a fatal disease with > 60% mortality. Early treatment with antioxidant cocktail is beneficial and may be curative in those who present with milder phenotype. Liver transplantation should always be considered at an early stage in non-responders and in children with more severe acute liver failure.

Classification and genetic features of neonatal haemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism.

Neonatal haemochromatosis (NH) is a severe and newly recognised syndrome of uncertain aetiology, characterised by congenital cirrhosis or fulminant hepatitis and widespread tissue iron deposition. NH occurs in the context of maternal disease including viral infection, as a complication of metabolic disease in the fetus, and sporadically or recurrently, without overt cause, in sibs. Although an underlying genetic basis for NH has been suspected, no test is available for predictive analysis in at risk pregnancies. As a first step towards an understanding of the putative genetic basis for neonatal haemochromatosis, we have conducted a systematic study of the mode of transmission of this disorder in a total of 40 infants born to 27 families. We have moreover carried out a molecular analysis of candidate genes (beta(2)-microglobulin, HFE, and haem oxygenases 1 and 2) implicated in iron metabolism. No pathogenic mutations in these genes were identified that segregate consistently with the disease phenotype in multiplex pedigrees. However, excluding four pedigrees with clear evidence of maternal infection associated with NH, a pedigree showing transmission of maternal antinuclear factor and ribonucleoprotein antibodies to the affected infants, and two families with possible matrilineal inheritance of disease in maternal half sibs, a large subgroup of the affected pedigrees point to the inheritance of an autosomal recessive trait. This included 14 pedigrees with affected and unaffected infants and a single pedigree where all four affected infants were the sole offspring of consanguineous but otherwise healthy parents. We thus report three distinct patterns of disease transmission in neonatal haemochromatosis. In the differentiation of a large subgroup showing transmission of disease in a manner suggesting autosomal recessive inheritance, we also provide the basis for further genome wide studies to define chromosomal determinants of iron storage disease in the newborn.

A novel sodium-hydrogen exchanger isoform-1 inhibitor, zoniporide, reduces ischemic myocardial injury in vitro and in vivo.

The cardioprotective efficacy of zoniporide (CP-597,396), a novel, potent, and selective inhibitor of the sodium-hydrogen exchanger isoform 1 (NHE-1), was evaluated both in vitro and in vivo using rabbit models of myocardial ischemia-reperfusion injury. In these models, myocardial injury was elicited with 30 min of regional ischemia and 120 min of reperfusion. Zoniporide elicited a concentration-dependent reduction in infarct size (EC(50) of 0.25 nM) in the isolated heart (Langendorff) and reduced infarct size by 83% (50 nM). This compound was 2.5- to 20-fold more potent than either eniporide or cariporide (EC(50) of 0.69 and 5.11 nM, respectively), and reduced infarct size to a greater extent than eniporide (58% reduction in infarct size). In open-chest, anesthetized rabbits, zoniporide also elicited a dose-dependent reduction in infarct size (ED(50) of 0.45 mg/kg/h) and inhibited NHE-1-mediated platelet swelling (maximum inhibition 93%). Furthermore, zoniporide did not cause any in vivo hemodynamic (mean arterial pressure, heart rate, rate pressure product) changes. Zoniporide represents a novel class of potent NHE-1 inhibitors with potential utility for providing clinical cardioprotection.

Tachycardia-induced primate model of heart failure in cardiovascular drug discovery.

Congestive heart failure (CHF) is a complex, multifactoral disease involving genetic and environmental factors that represents a large unmet medical need. There are currently many animal models of CHF that have provided some insight into the etiology of this disease. However, due to the complex interactions of environmental and genetic components of this disease most animal models are somewhat limited. Nonhuman primates offer a unique opportunity to investigate the genetic aspects of this complex disease due to their close genetic and phenotypic similarity to humans. Here we describe a novel tachycardia-induced primate model of CHF characterized by depressed global function that progresses to a symptomatic stage consistent with clinical data. No animal model, including this one, can exactly mimic the clinical pathophysiology of CHF. However, this tachycardia-induced primate model of CHF has similarities to the dynamic state of CHF in humans and affords the opportunity to evaluate changes in gene expression using genomic and proteomic technologies throughout the progression of the disease.

NO modulates myocardial O2 consumption in the nonhuman primate: an additional mechanism of action of amlodipine.

Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo and in vitro oxygen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen consumption in the nonhuman primate heart in vitro and to evaluate whether the seemingly cardioprotective actions of amlodipine may involve an NO-mediated mechanism. Using a Clark-type O2 electrode, we measured oxygen consumption in cynomologous monkey heart at baseline and after increasing doses of S-nitroso-N-acetylpenicillamine (SNAP; 10(-7)-10(-4) M), bradykinin (10(-7)-10(-4) M), ramiprilat (10(-7)-10(-4) M), and amlodipine (10(-7)-10(-5) M). SNAP (-38 +/- 5.8%), bradykinin (-19 +/- 3.9%), ramiprilat (-28 +/- 2.3%), and amlodipine (-23 +/- 4.5%) each caused significant (P < 0.05) reductions in myocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-L-arginine methyl ester (10(-4) M) blunted the effects of bradykinin (-5.4 +/- 3.2%), ramiprilat (-4.8 +/- 5.0%), and amlodipine (-5.3 +/- 5.0%) but had no effect on the tissue response to SNAP (-38 +/- 5.8%). Our results indicate that NO can reduce oxygen consumption in the primate myocardium in vitro, and they support a role for the calcium-channel blocker amlodipine as a modulator of myocardial oxygen consumption via a kinin-NO mediated mechanism.

Telephone triage as a strategy to ensure 24-hour access to medical care after the closure of supporting medical activity.

OBJECTIVE: The provision of telephone access to a medical officer during nonduty hours was implemented by one Army health clinic to ensure continuous access to cost-efficient care after the closure of its supporting medical activity. METHODS: After-hours phone calls were tracked for 6 months. Callers were surveyed to determine if use of the system resulted in avoidance of self-referral to civilian medical facilities. RESULTS: A mean of 70 calls per month (186 calls per 1,000 population per year) were placed to the on-call medical officer. Eight types of complaints accounted for more than three-quarters of calls. Fifty percent of callers were seen by the medical officer for an after-hours clinic visit, 38% were given advice for care at home, and 10% were referred to a civilian medical facility. Telephone triage yielded an estimated $8,447 in cost avoidance during a 6-week survey period. CONCLUSION: Telephone triage can facilitate continuous access to cost-efficient care.

Lymph isolated from a regional scald injury produces a negative inotropic effect in dogs.

Large surface-area burns in patients have been associated with a severe impairment in cardiac performance, as evidenced by a decline in cardiac output. The mechanisms responsible for this profound myocardial dysfunction are largely unknown. We investigated the effects of lymph isolated from the scalded hind limb of dogs on regional myocardial blood flow, coronary vascular reactivity, and contractile performance. Dogs were instrumented with ultrasonic dimension crystals in the myocardium supplied by the left anterior descending (LAD) and by the left circumflex (LCx) coronary arteries. After cannulating a hind limb lymphatic, lymph was infused directly into the LAD before and after a 10-second 100 degrees C hind limb scald. Scalding alone did not alter myocardial contractile performance in the LAD or LCx regions, coronary artery blood flow, or systemic hemodynamics. Interestingly, postburn lymph infused into the LAD resulted in a 38% decline in LAD zone segment shortening (p < 0.01 vs baseline) that lasted throughout the 5-hour observation period. In contrast, segment shortening in the (control) LCx region was unaffected by postburn lymph injections into the LAD. Regional myocardial blood flow (radiolabeled microspheres) in the LAD and LCx regions was unchanged after scald injury or intracoronary injection of postburn lymph. In addition, LAD coronary artery vascular reactivity to acetylcholine and nitroglycerin was also unaffected by the regional thermal injury or by injection of lymph into the LAD. These data suggest that a regional scald injury results in the production and release of a potent myocardial depressant factor(s) that produces a direct negative inotropic effect on the canine myocardium.

A finite element based method to determine the properties of planar soft tissue.

A finite element based method to determine the incremental elastic material properties of planar membranes was developed and evaluated. The method is applicable to tissues that exhibit inhomogeneity, geometric and material nonlinearity, and anisotropy. Markers are placed on the tissue to form a four-node quadrilateral element. The specimen is loaded to an initial reference state, then three incremental loading sets are applied and the nodal displacements recorded. One of these loadings must include shear. These data are used to solve an over-determined system of equations for the tangent stiffness matrix. The method was first verified using analytical data. Next, data obtained from a latex rubber sheet were used to evaluate experimental procedures. Finally, experiments conducted on preconditioned rat skin revealed nonlinear orthotropic behavior. The vector norm comparing the applied and calculated nodal force vectors was used to evaluate the accuracy of the solutions.

Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion.

Neutrophil-endothelial cell interactions are mediated by a number of cell adhesion proteins. We investigated the effects of inhibition of P-selectin and intercellular adhesion molecule-1 (ICAM-1), individually or in combination, in the ischemic-reperfused canine myocardium. Monoclonal antibodies PB1.3 (anti-P-selectin) and CL 18/6 (anti-ICAM-1) were administered to dogs subjected to coronary artery occlusion and reperfusion. After reperfusion, untreated dogs experienced a 61% decline (P < 0.01 vs. baseline) in myocardial blood flow and a ninefold increase in ischemic zone neutrophil accumulation (4.7 +/- 0.9 U/100 mg tissue myeloperoxidase activity). In contrast, PB1.3 and CL 18/6 administered individually preserved myocardial blood flow (11 and 24% decrease from baseline, respectively, both P < 0.01 vs. saline), and significantly attenuated myeloperoxidase activity (1.4 +/- 0.3 and 1.5 +/- 0.26 U/100 mg tissue, respectively, both P < 0.01 vs. saline). PB1.3 and CL 18/6 in combination resulted in significant coronary vascular and myocardial protection that was not superior to treatment with either antibody alone. Thus the coadministration of anti-P-selectin and anti-ICAM-1 monoclonal antibodies does not enhance the degree of myocardial protection in this model of reperfusion injury.

A sialyl Lewis(x)-containing carbohydrate reduces infarct size: role of selectins in myocardial reperfusion injury.

Previous studies have implicated the selectins (P- and L-selectin) in the acute phase of myocardial reperfusion injury. However, it is unclear whether these adhesion molecules are involved in the pathogenesis of myocardial reperfusion associated with longer periods of reperfusion. Dogs (n = 8/group) were subjected to 90 min of coronary ischemia and 48 h of reperfusion. Animals were initially treated with a 35 mg/kg intravenous bolus of a sialyl Lewis(x) oligosaccharide (SLe(x)-OS) 10 min before reperfusion, followed by a 1.75 mg.kg-1.h-1 infusion for the first 24 h of reperfusion. A control group of dogs received a normal saline bolus followed by saline infusion for the first 24 h of reperfusion. In a subsequent group of dogs treatment consisted of only the 35 mg/kg bolus of SLe(x)-OS to help elucidate the time course of selectin involvement. The saline control group exhibited marked decreases in blood flow in the ischemic-reperfused myocardium, sustained depression of left ventricular function, an average infarct size of 29 +/- 5% of the myocardial area at risk, and excessive polymorphonuclear leukocyte accumulation in the infarcted myocardium after 48 h of reperfusion. Dogs that received a bolus followed by an infusion of SLe(x)-OS exhibited significant preservation of myocardial blood flow and left ventricular function at 4.5 and 48 h of reperfusion, dramatic attenuation (56%) of infarct size (P < 0.05), and a 55% reduction (P < 0.05) in polymorphonuclear leukocyte accumulation compared with the saline group. Interestingly, SLe(x)-OS bolus treatment alone exerted early (i.e., at 4.5 h) cardioprotective effects that waned by 48 h of reperfusion. These results demonstrate that the selectin family of adhesion molecules plays an extended role in myocardial reperfusion injury and is not only involved in the acute phase of this disease process.

Effects of a monoclonal antibody directed against P-selectin after myocardial ischemia and reperfusion.

Neutrophils (polymorphonuclear leukocytes, PMNs) play a role in tissue injury after ischemia and reperfusion. We investigated the effects of a monoclonal antibody (MAb), PB1.3, directed against P-selectin in an acute model of myocardial ischemia-reperfusion injury. Dogs were subjected to 120 min of coronary arterial occlusion and 240 min of reperfusion. MAb PB1.3 (1 mg/kg), the nonblocking P-selectin antibody, MAb PNB1.6 (1 mg/kg), or saline was administered 5 min before reperfusion. Dogs treated with saline (n = 7), MAb PB1.3 (n = 7), and MAb PNB1.6 (n = 5) all experienced similar myocardial blood flows during ischemia, and treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow. Measurement of myocardial contractility failed to demonstrate any beneficial effects of MAb PB1.3 on postischemic myocardial contractility. However, myocardial necrosis (% of area at risk) was significantly reduced (P < 0.01) in dogs receiving MAb PB1.3 (20.8 +/- 4.8%) compared with dogs receiving either normal saline (41.7 +/- 4.5%) or MAb PNB1.6 (46.7 +/- 7.6%). Myocardial myeloperoxidase activity in the ischemic zone was 4.8 +/- 0.6 in the vehicle group and 3.7 +/- 0.5 in the MAb PNB1.6 group compared with 2.0 +/- 0.5 in MAb PB1.3-treated dogs (P < 0.01 vs. saline; P < 0.05 vs. PNB1.6). In summary, treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow or myocardial contractility. In contrast, P-selectin immunoneutralization reduced PMN accumulation and myocardial tissue injury in a canine model of coronary occlusion and reperfusion.

Nitric oxide attenuates neutrophil-mediated myocardial contractile dysfunction after ischemia and reperfusion.

With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)-medicated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n = 10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n = 9), resulted in 80.2 +/- 6.7% recovery of LVDP and 77.0 +/- 8.6% recovery of PRP. Treatment with L-arginine (2.5 mmol/L, n = 10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, NG-nitro-L-arginine methyl ester (L-NAME) treatment (250 mumol/L, n = 10) resulted in an exacerbation of contractile dysfunction, as evidence by a 93% reduction in LVDP at 45 minutes of reperfusion and a 91% reduction in PRP. The deleterious effects of L-NAME were prevented by L-arginine coperfusion. We failed to observe any cardioprotective effects when NO or L-arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusion in the absence of PMNs. In conclusion, PMN-mediated myocardial contractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.

Intracoronary nitric oxide improves postischemic coronary blood flow and myocardial contractile function.

In the present study a novel nitric oxide (NO) donor, CAS-1609, was utilized as a means of coronary NO replenishment in a canine model of myocardial ischemia-reperfusion. Administration of CAS-1609 (1.25 mg iv) 10 min before reperfusion, followed by a 1 mg/h intracoronary infusion throughout the 4.5-h reperfusion period, resulted in significant improvement in postischemic transmural myocardial blood flow (0.66 +/- 0.09 vs. 0.37 +/- 0.08 ml.min-1.g-1 for saline vehicle, P < 0.05). Dogs receiving NO supplementation also exhibited a significant recovery of myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Moreover, myocardial necrosis as a percentage of the area at risk was reduced from 28.9 +/- 4.3% in the saline group to 8.5 +/- 2.6% in the CAS-1609 group (P < 0.01), while ischemic zone myeloperoxidase activity, indicative of neutrophil infiltration, was also attenuated by 70% with NO therapy. Injection of acetylcholine and nitroglycerin into the left circumflex coronary artery revealed a significant impairment of vasodilator responses in the saline vehicle dogs at 2 h of reperfusion. However, dogs treated with the NO donor demonstrated postischemic vasodilator responses which were similar to baseline (P = not significant vs. baseline). These studies demonstrate that intracoronary administration of NO significantly augments postischemic coronary blood flow and contractile function following ischemia and reperfusion. In addition, NO therapy reduces coronary vascular injury, attenuates myocardial necrosis, and reduces neutrophil infiltration. The cardioprotective actions of intracoronary NO administration may be related to the potent antineutrophil actions of NO.

Pacemaker and defibrillator lead entrapment: case studies.

Cadavers and cineradiographic analysis have been used to document the effects of the medial subclavicular musculotendinous complex (MSMC) upon lead function. Four cadavers with pacemakers were dissected and photographed to demonstrate the course a lead takes as it passes through the costoclavicular region. One lead had been placed into the cephalic vein. In the other three cadavers, leads placed by currently accepted techniques of subclavian venipuncture were all found to pass through the soft tissues of the subclavicular region before entering the venous system. Cineradiographic results from a patient with a defibrillator, taken before and after replacement of a broken lead, show the effect of clavicular motion on a lead that passes through the MSMC. Furthermore, cineradiography makes it possible to identify the point where the lead entered the vein, and whether or not it escaped being caught up in the soft tissues of the MSMC.

A novel sialyl LewisX analog attenuates neutrophil accumulation and myocardial necrosis after ischemia and reperfusion.

BACKGROUND: Polymorphonuclear leukocytes (PMNs) have been shown to mediate coronary vascular and myocardial tissue injury after coronary artery ischemia and reperfusion. Previous studies using specific monoclonal antibodies directed against P-selectin and L-selectin have demonstrated the involvement of the selectin family of glycoproteins in the early phase of PMN-induced myocardial ischemia-reperfusion injury. We examined the effects of a novel oligosaccharide analog of sialyl LewisX (SLeX), which blocks both P-selectin and E-selectin in an acute canine model of myocardial ischemia and reperfusion. METHODS AND RESULTS: Anesthetized, open-chest dogs were subjected to 1.5 hours of left circumflex coronary artery (LCx) occlusion followed by 4.5 hours of reperfusion and randomly received the SLeX analog CY-1503 (5 mg/kg IV), the nonfucosylated analog of CY-1503, SLN (5 mg/kg IV), or saline 5 minutes before reperfusion. The investigators were blinded to the treatment until all the data analysis was completed. All three groups of dogs exhibited similar and severe reductions in transmural myocardial blood flow in the LCx region as well as pronounced myocardial contractile dysfunction during occlusion, suggesting comparable degrees of myocardial ischemia. After reperfusion, dogs receiving saline (n = 6) displayed an enhanced degree of myocardial injury that was evidenced by a dramatic elevation in plasma creatine kinase (CK) activity, PMN accumulation, and myocardial necrosis. Plasma CK activity increased from 1.9 +/- 0.5 IU/microgram protein at baseline to 73.0 +/- 11.0 IU/micrograms protein (P < .001) at 4.5 hours of reperfusion and myocardial PMN accumulation, as measured by cardiac myeloperoxidase (MPO) activity, and was significantly enhanced (P < .01) within the necrotic zone compared with the nonischemic zone (4.3 +/- 0.6 versus 0.7 +/- 0.1 U/100 mg tissue). After 4.5 hours of reperfusion, 36% of the myocardium within the ischemic zone and 17% of the left ventricle became necrotic in the dogs receiving saline. Treatment with CY-1503 (n = 6) significantly (P < .05) blunted plasma CK activity by more than 50% throughout the reperfusion period, reduced necrotic zone PMN accumulation by 63% (P < .05), and reduced myocardial necrosis in the area at risk by 65% (P < .01) and by 72% within the left ventricle (P < .01). In contrast, administration of the nonfucosylated analog of CY-1503, SLN (n = 6), failed to exert any detectable cardioprotective effects after myocardial ischemia and reperfusion. CONCLUSIONS: Our results provide strong evidence that treatment with a unique carbohydrate analog of SLeX, CY-1503, significantly reduces the degree of myocardial injury associated with coronary artery ischemia and reperfusion. The profound cardioprotection appears to be related to a reduction in PMN accumulation within the ischemic-reperfused myocardium. Additional studies investigating more-prolonged periods of reperfusion are required to determine whether CY-1503 treatment merely delays the onset or actually reduces the full extent of myocardial necrosis after ischemia and reperfusion.