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Biomedical subjects

M Eldar

Publications and source records attributed to M Eldar.

At least 37 records · Page 2Linked to original sources
PubMed2000

Randomized comparison of J-shaped and straight atrial screw-in pacing leads.

OBJECTIVE: To study the importance of a J shape in atrial pacing leads. PATIENTS AND METHODS: We compared in a randomized controlled study acute and chronic results with 2 steroid-eluting, polyurethane, screw-in atrial lead models that differ only in shape. A total of 208 patients were randomized to have implantation of either a straight atrial lead (n = 105) or a J-shaped atrial lead (n = 103). Patients were followed up for 1 year. RESULTS: On implantation, there were no significant differences between leads in rates of failure to implant, implant measurements, number of attempts to achieve an acceptable position, and fluoroscopy times. Before discharge and at 3-month and 1-year follow-up, electrical measurements showed no statistical differences between leads. During the first year after implantation, there were 2.9% early dislodgments (< 1 week after implantation) and 2.9% late dislodgments in the straight lead group (5.9% rate of all dislodgments) vs no dislodgments in the J-shaped lead group (P = .01). There was a trend toward higher rates of exit block and lead malfunction in the J-shaped lead group. Rates of pericardial complications, subclavian/axillary thrombosis, and chronic atrial fibrillation were the same in both groups. CONCLUSIONS: Both leads appear to have an equally favorable performance profile for 1 year of follow-up. The J-shaped lead seems to be more stable and have fewer dislodgments, although it may have a somewhat higher malfunction rate.

Adult↗
PubMed2000

S-nitrosoderivative of a recombinant fragment of von Willebrand factor (S-nitroso-AR545C) inhibits thrombus formation in guinea pig carotid artery thrombosis model.

Antiplatelet drugs are the mainstays of therapy for acute and chronic cardiovascular diseases. S-nitroso-AR545C - an S-nitrosoderivative of a recombinant von Willebrand factor fragment AR545C spanning Ala 444 to Asp 730 and containing an Arg 545 Cys mutation, was previously found to inhibit ristocetin- and ADP-induced platelet aggregation and the interaction of platelets with extracellular matrix (ECM). In the current study we tested the antithrombotic properties of S-nitroso-AR545C on guinea pig platelets and in a platelet-rich thrombosis model in the guinea pig. Preincubation of guinea pig platelets with 0.1 microM of S-nitroso-AR545C decreased ristocetin-induced agglutination by 40% (p = 0.009) and completely abolished ADP-induced aggregation (p <0.0001). At concentration of 1.0 microM, S-nitroso-AR545C completely inhibited platelet adhesion (represented by surface coverage - SC) and decreased aggregate formation (represented by average aggregate size - AS) by more than 50%. Treatment of guinea pigs with 1.0 mg/kg S-nitroso-AR545C resulted in a significantly delayed time to arterial occlusion (31.7+/-6.0 min vs. 13.9+/-3.2 min, p <0.02). Similarly, total patency time was longer in the group injected with S-nitroso-AR545C compared to the control group. However, the difference was not statistically significant (33.8+/-6.3 min vs. 20.2+/-3.3 min, p = 0.07). No change in platelet count, hematocrit and bleeding time was observed 60 min after injection compared to baseline. In contrast, a significant decrease in SC (p <0.0001) and AS (p <0.01) were observed 60 min after the injection of S-nitroso-AR545C, whereas no change in these parameters was observed in the control group. These observations indicate that S-nitroso-AR545C exhibits significant antiadhesive and antiaggregating effects in-vitro and inhibits clot formation in-vivo suggesting that this compound may have potential therapeutic advantages.

Animals↗
PubMed1999

Long-term follow-up of patients with long-QT syndrome treated with beta-blockers and continuous pacing.

BACKGROUND: The long-QT syndrome is associated with sudden cardiac death. Combination of beta-blocker and pacing therapy has been proposed for treatment of drug-resistant patients. The purpose of this study was to summarize our long-term experience with combined therapy in patients with long-QT syndrome. METHODS AND RESULTS: A total of 37 patients with idiopathic long-QT syndrome were treated with combined therapy consisting of continuous cardiac pacing and maximally tolerated beta-blocker therapy and followed up for 6.3+/-4. 6 years (mean+/-SD). The group consisted of 32 female and 5 male patients with a mean age of 31.6 years. The mean paced rate was 82+/-7 bpm (range, 60 to 100 bpm). On follow-up, recurrent symptoms caused by pacemaker malfunction were documented in 3 patients. Four patients died during the follow-up period: 2 adolescents stopped beta-blocker therapy, 1 patient died suddenly while treated with combined therapy, and 1 patient died of unrelated causes. In addition, 3 patients had resuscitated cardiac arrest while on combined therapy, and 1 patient had repeated, appropriate implantable cardioverter-defibrillator discharges on follow-up. CONCLUSIONS: Because 28 of 37 patients remain without symptoms with beta-blocker therapy and continuous pacing, combined therapy appears to provide reasonable, long-term control for this high-risk group. However, the incidence of sudden death and aborted sudden death (24% in all patients and 17% in compliant patients) strongly suggests the use of a "back-up" defibrillator, particularly in noncompliant adolescent patients. Implantable cardioverter-defibrillator therapy, however, may be associated with recurrent shocks in susceptible patients.

Adolescent↗
PubMed1999

Complete atrioventricular block complicating acute myocardial infarction in the thrombolytic era. SPRINT Study Group and the Israeli Thrombolytic Survey Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial.

OBJECTIVES: We assessed the incidence, associated clinical parameters and prognostic significance of complete atrioventricular block (CAVB) complicating acute myocardial infarction (AMI) in the thrombolytic era and compared them to data from the prethrombolytic era. BACKGROUND: The introduction of new therapeutic modalities to treat AMI, aimed to enhance coronary reperfusion and to limit myocardial necrosis, was expected to decrease the incidence of CAVB and to improve prognosis. However, there are only limited data regarding the incidence and the prognosis of AMI patients with CAVB in the thrombolytic era. METHODS: Data from 3,300 patients from the Israeli Thrombolytic Surveys (prospective, nationwide surveys of consecutive patients with AMI in all 25 coronary-care units in Israel in 1992 and 1996) were analyzed and compared with data from 5,788 patients included in the SPRINT (Secondary Prevention Reinfarction Israeli Nifedipine Trial) Registry (1981 to 1983). RESULTS: During the 1990s, the incidence of CAVB was 3.7% compared with 5.3% in the 1980s, p = 0.0007. In the 1990s, mortality of patients with CAVB was significantly higher than in those without CAVB at 7 days (odds ratio [OR] = 4.05 95% CI [confidence interval] 2.34 to 6.82, 30 days OR = 3.98 [95% CI 2.44 to 6.43] and one-year hazard ratio [HR] = 2.36, [95% CI 1.68 to 3.30]) and similar in thrombolysis-treated and not-treated patients. Mortality of patients with CAVB has not changed significantly between the two periods; seven-day OR = 0.82 (95% CI 0.46 to 1.43); 30-day OR = 0.78 (95% CI 0.45 to 1.33) and one-year HR = 0.79 (95% CI 0.54 to 1.56), respectively, in the 1990s as compared to a decade earlier. CONCLUSIONS: The incidence of CAVB complicating AMI is lower in the thrombolytic era than in the prethrombolytic era. Mortality among patients with CAVB is still high and has not declined within the last decade. The AMI patients who develop CAVB in the thrombolytic era have significantly worse prognosis than do patients without CAVB.

Aged↗
PubMed1999

Unique antiplatelet effects of a novel S-nitrosoderivative of a recombinant fragment of von Willebrand factor, AR545C: in vitro and ex vivo inhibition of platelet function.

The recombinant fragment of von Willebrand factor (vWF) spanning Ala444 to Asp730 and containing an Arg545Cys mutation (denoted AR545C) has antithrombotic properties that are principally a consequence of its ability to inhibit platelet adhesion to subendothelial matrix. Endothelial-derived nitric oxide (NO) can also inhibit platelet function, both as a consequence of inhibiting adhesion as well as activation and aggregation. Nitric oxide can react with thiol functional groups in the presence of oxygen to form S-nitrosothiols, which are naturally occurring NO derivatives that prolong the biological actions of NO. Because AR545C has a single free cysteine (Cys545), we attempted to synthesize the S-nitroso-derivative of AR545C and to characterize its antiplatelet effects. We successfully synthesized S-nitroso-AR545C and found that it contained 0.96 mol S-NO per mole peptide. S-nitroso-AR545C was approximately 5-fold more potent at inhibiting platelet agglutination than was the unmodified peptide (IC(50) = 0.02 +/- 0. 006 micromol/L v 0.1 +/- 0.03 micromol/L, P =.001). In addition and by contrast, S-nitroso-AR545C was a powerful inhibitor of adenosine diphosphate-induced platelet aggregation (IC(50) = 0.018 +/- 0.002 micromol/L), while AR545C had no effect on aggregation. These effects were confirmed in studies of adhesion to and aggregation on extracellular matrix under conditions of shear stress in a cone-plate viscometer, where 1.5 micromol/L S-nitroso-AR545C inhibited platelet adhesion by 83% and essentially completely inhibited aggregate formation, while the same concentration of AR545C inhibited platelet adhesion by 74% and had significantly lesser effect on aggregate formation on matrix (P </=.004 for each parameter by ANOVA). In an ex vivo rabbit model, we also found that S-nitroso-AR545C had a more marked and more durable inhibitory effect on botrocetin-induced platelet aggregation than did AR545C, and these differences were also reflected in the extent and duration of effect on the prolongation of the bleeding time in these animals. These data show that S-nitroso-AR545C has significant and unique antiplatelet effects, inhibiting both adhesion and aggregation, by blocking platelet GPIb receptor through the AR545C moiety and elevating platelet cyclic 3',5'-guanosine monophosphate through the -SNO moiety. These observations suggest that this NO-modified fragment of vWF may have potential therapeutic benefits as a unique antithrombotic agent.

Adult↗
PubMed1999

Catheter-induced mechanical trauma to accessory pathways during radiofrequency ablation: incidence, predictors and clinical implications.

OBJECTIVES: To evaluate the incidence, predictors and clinical implications of nonintentionally catheter-induced mechanical trauma to accessory pathways during radiofrequency ablation procedures. BACKGROUND: Data on the incidence and significance of catheter-induced trauma to accessory pathways are scarce. METHODS: Consecutive patients (n = 381) undergoing radiofrequency ablation of accessory pathways at two different institutions were closely monitored for appearance of mechanical block of accessory pathways during catheter manipulation. RESULTS: Mechanical trauma to accessory pathways was observed in 37 (9.7%) patients. According to a multivariate analysis, the only independent variable associated with this phenomenon was the anatomical pathway location (p = 0.0001). The incidence of trauma of either right anteroseptal (38.5%) or right atriofascicular pathways (33.3%) was significantly greater than that of pathways (< or =10%) at all remaining locations (p < 0.0001). The duration of conduction block observed ranged from < or =1 min to >30 min in 19% and 35% of patients, respectively. "Immediate" application of radiofrequency pulses at sites of mechanical block (<1 min after occurrence) was associated with a 78% long-term success rate at follow-up. This contrasted with a 25% long-term success rate in patients in whom pulses were delivered 30 min after occurrence of block ("delayed pulses"). Finally, in 24% of patients persistent trauma-induced conduction block led to discontinuation of the ablation procedure. CONCLUSIONS: Trauma to accessory pathways is more common than previously recognized and frequently results in prolongation or discontinuation of the ablation procedure and in lower success rates. The only independent predictor of catheter-trauma to accessory pathways is the pathway location.

Adolescent↗
PubMed1999

Does the coronary care unit improve prognosis of patients with acute myocardial infarction? A thrombolytic era study.

AIMS: The purpose of our study was to examine and compare the prognosis of acute myocardial infarction patients hospitalized in an intensive coronary care unit and in an internal medicine ward, in the era of reperfusion therapy, and to identify factors associated with the observed outcomes. METHODS AND RESULTS: Patients hospitalized for acute myocardial infarction during the period 1994-1997 at the Sheba Medical Center, Tel Hashomer, Israel (n=2114), were grouped according to the hospital department in which they were treated: the intensive coronary care unit (n=1443, 68.3%) or an internal medicine ward (n=671, 31.7%). Baseline characteristics, comorbidity, hospital course, use of procedures and 30-day mortality were compared between the groups. Stepwise logistic regression was used to identify the factors associated with 30-day mortality. Crude 30-day mortality rates were 5.4% among all patients hospitalized in the intensive coronary care unit compared with 15.9% for all patients in an internal medicine ward (P<0.001); in a subgroup of patients aged 70 years and above these rates were 11.0% and 21.0%, respectively (P<0. 001). Among the independent predictors of the 30-day mortality identified in multivariate analysis was treatment only in an internal medicine ward (odds ratio: 1.48; 95% confidence interval: 1. 00-2.18). Reperfusion therapy was independently associated with a 53% reduction in 30-day mortality. CONCLUSIONS: Our findings emphasize the importance of the treatment of acute myocardial infarction in the setting of intensive coronary care units in the thrombolytic era, in order to ensure early access to advanced diagnostic and therapeutic options for all patients, including the elderly.

Aged↗
PubMed1999

Allicin-induced decrease in formation of fatty streaks (atherosclerosis) in mice fed a cholesterol-rich diet.

BACKGROUND: Garlic (Allium sativum) has been considered to exhibit therapeutic features for many years. The effects of garlic on levels of serum lipids and on atherosclerosis have been investigated extensively. We have previously demonstrated that allicin, an active component of garlic, exerts a beneficial effect on lipid profile in hyperlipidemic rabbits. OBJECTIVE: To investigate the effects of allicin on formation of fatty streaks (atherosclerosis) and lipid profile in mice. METHODS: Allicin was extracted from garlic and kept in a buffer citrate solution at 4 degrees C. Sixty C57BL/6 mice were fed Paigen diet (17% fat, 1.25% cholesterol) for 15 weeks. Thirty randomly selected animals were administered allicin solution (9 mg/kg) and 30 were administered placebo. Blood lipid profile was evaluated five times during the study. At the end of the 15-week period, the animals were killed and the aortic sinus was evaluated for formation of fatty streaks (atherosclerosis). RESULTS: We observed no statistically significant differences between blood lipid profiles of groups. Microscopic evaluation of aortic sinus formation of fatty streaks (atherosclerosis), however, showed that values for mice in the allicin-treated group were significantly lower: areas of formation of fatty streaks (atherosclerosis) were 13,440 +/- 3310 and 23,410 +/- 3723 micron 2, respectively, for allicin-treated and control mice (means +/- SEM; P = 0.023). CONCLUSIONS: These results indicate that allicin reduces formation of fatty streaks (atherosclerosis) in hyperlipidemic mice. These changes do not seem to occur through an alteration in blood lipid profile.

Animals↗
PubMed1999

Atypical AV nodal reentry with bystander accessory pathway: an unusual mechanism of preexcited tachycardia.

We present an unusual mechanism of preexcited tachycardia--atypical AV nodal reentry with bystander AP. It can be differentiated from other preexcited tachycardias by its variable degree of preexcitation (either spontaneous or in response to atrial pacing), higher degree of preexcitation with pacing near the origin of the AP than during tachycardia, inability to preexcite the tachycardia by either late atrial or ventricular premature beats, the presence of nonpreexcited atypical AV nodal reentry tachycardia following successful AP ablation, and by exclusion of atrial tachycardia.

Adolescent↗
PubMed1999

Effects of electrophysiologic-guided therapy with Class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome.

INTRODUCTION: Implantation of a implantable cardioverter defibrillator (ICD) is viewed universally as the "gold standard" therapy for patients with idiopathic ventricular fibrillation (VF). We sought to study the long-term value of electrophysiologic (EP)-guided therapy with Class IA antiarrhythmic drugs in patients with idiopathic VF with or without the Brugada syndrome. METHODS AND RESULTS: We performed EP studies in 34 consecutive patients who had idiopathic VF with (n = 5) or without (n = 29) the Brugada syndrome. All patients with inducible sustained polymorphic ventricular tachycardia (SPVT) or VF underwent repeated EP evaluation after oral administration of a Class IA antiarrhythmic drug (mainly quinidine). Patients rendered noninducible received this therapy on a long-term basis. SPVT/VF were induced in 27 (79.4%) patients at baseline studies. Class IA drugs effectively prevented induction of SPVT/VF in 26 (96%) patients. Of the 23 patients treated with these medications, no patient died or had a sustained ventricular arrhythmia during a mean follow-up period of 9.1 +/- 5.6 years (7 to 20 years in 15 patients). Two deaths occurred in patients without inducible SPVT/VF at baseline studies who had been treated empirically. CONCLUSION: Our results suggest that EP-guided therapy with Class IA agents is a reasonable, safe, and effective approach for the long-term management of patients with idiopathic VF. A randomized prospective study of EP-guided Class IA therapy in patients with ICDs seems warranted.

Adolescent↗
PubMed1999

Insights into the mechanism of sustained ventricular tachycardia after myocardial infarction in a closed chest porcine model using a multielectrode "basket" catheter.

INTRODUCTION: Accurate analysis of the arrhythmia substrate is important for successful radiofrequency ablation of sustained ventricular tachycardia (VT) after myocardial infarction (MI). METHODS AND RESULTS: A multielectrode "basket" catheter capable of endocardial recording and pacing was inserted percutaneously into the left ventricle of post-MI swine for analysis of the mechanism of sustained VT. Sustained VT was induced in 42 of 61 pigs that survived an acute MI produced by percutaneous transluminal coronary angioplasty balloon occlusion of the left anterior descending coronary artery and injection of agarose gel beads. A multielectrode "basket" catheter (Constellation) with 64 electrodes was inserted in 35 of these animals for analysis of the VT. Induced VT had a cycle length of 179 +/- 25 msec at control and 230 +/- 43 msec after administration of intravenous procainamide. Presystolic electrical activity was recorded from at least 1 of 32 bipolar pairs of electrodes at a mean 40.7 +/- 23.6 msec prior to QRS onset. Isolated mid-diastolic potentials were recorded in 26 of 35 animals. In 22 animals, there were multiple isolated potentials recorded from adjacent electrode pairs. Isochronal maps demonstrated that these potentials returned to the systolic site of origin. Resetting of sustained VT by single premature ventricular stimuli was observed in 6 of 12 animals. Entrainment with overdrive pacing was seen in 19 of 26 animals with induced VT. Concealed entrainment was observed in ten animals. The mean stimulus to QRS interval was 45 +/- 28 msec. Concealed entrainment was observed from adjacent electrode pairs with different stimulus to QRS intervals. CONCLUSION: These data suggest that sustained VT in this model is due to reentry with an excitable gap. A multielectrode "basket" catheter is useful for analyzing the zone of slow conduction participating in the tachycardia circuit. Such analysis may provide useful information to guide successful catheter ablation of sustained VT after MI.

Animals↗
PubMed1998

Noninvasive diagnosis of dual AV node physiology in patients with AV nodal reentrant tachycardia by administration of adenosine-5'-triphosphate during sinus rhythm.

BACKGROUND: Atrioventricular nodal reentry tachycardia (AVNRT) represents the most commonly encountered type of regular paroxysmal supraventricular tachycardia. This study determined whether administration of adenosine-5'-triphosphate (ATP) during sinus rhythm may be useful in the noninvasive diagnosis of dual AV nodal pathways. METHODS AND RESULTS: During electrophysiological study, we intravenously administered incremental doses of ATP (from 10 to 50 mg) during sinus rhythm to patients with spontaneous and inducible sustained AVNRT (study group, n=42) and to patients with no evidence of dual AV nodal physiology or inducible AVNRT (control group, n=21). Signs suggestive of dual AV node physiology after ATP administration during sinus rhythm ("jump" of AH > or =50 ms between 2 consecutive beats, > or =1 AV nodal echo beat, or initiation of AVNRT) were observed in 32 (76%) of 42 study patients but in only 1 (5%) of the 21 control patients (P<0.001). Similar results were observed when only surface lead recordings (without intracardiac recordings) were evaluated. Signs suggestive of dual AV node physiology by the ATP test were observed in 29 (80.5%) of 36 patients who had electrophysiological demonstration of dual AV node physiology and in 3 (50%) of 6 patients without AV nodal duality (P=NS). Signs suggestive of dual physiology according to the ATP test disappeared in 11 (92%) of the 12 patients who underwent successful slow AV nodal ablation but persisted in 8 (62%) of 13 patients who underwent AV nodal modification. CONCLUSIONS: Administration of ATP during sinus rhythm may be a useful bedside test for identifying patients with dual AV nodal pathways who are prone to AVNRT. This simple test should be considered as a screening test for patients with symptoms suggestive of paroxysmal supraventricular tachycardia but no documented arrhythmias or for patients with documented narrow complex tachycardia of unclear mechanism.

Adenosine Triphosphate↗
PubMed1998

Significance of paroxysmal atrial fibrillation complicating acute myocardial infarction in the thrombolytic era. SPRINT and Thrombolytic Survey Groups.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is considered a frequent complication of acute myocardial infarction (AMI), associated with increased in-hospital and long-term mortality rates. This notion is based on data collected before thrombolysis and additional modern methods of treatment became widely available, and no information is available on the significance of PAF in the general population with AMI in the thrombolytic era. The aim of the present study was to define the incidence, associated clinical parameters, and short- and long-term prognostic significance of PAF in patients with AMI in the thrombolytic era. METHODS AND RESULTS: A prospective, nationwide survey was conducted of 2866 consecutive patients admitted with AMI in all 25 coronary care units in Israel during January/February 1992, 1994, and 1996 (thrombolytic era [TE]). The data were compared with a previous Israeli study of 5803 patients with AMI hospitalized in 1981 through 1983 (prethrombolytic era [PTE]). Patients in the TE with PAF were older and had a worse risk profile than those without PAF. PAF in the TE was independently associated with increased 30-day (odds ratio, 1.32; 95% confidence interval, 0.92 to 1.87) and 1-year (relative risk, 1.33; 95% confidence interval, 1.05 to 1.68) mortality rates. The incidence of PAF (8.9% and 9.9%) and the 30-day (25.1% and 27.6%) and 1-year (38.4% and 42.5%) mortality rates of patients with PAF were similar in the TE and PTE, although PAF in the TE occurred in older and sicker patients than those in the PTE. After adjustment for conventional risk factors, PAF was associated with significantly lower 30-day (odds ratio, 0.64; 95% confidence interval, 0.44 to 0.94) and 1-year (relative risk, 0.69; 95% confidence interval, 0.54 to 0.88) mortality rates compared with the PTE. CONCLUSIONS: Patients with AMI who develop PAF in the TE have significantly worse short- and long-term prognoses than patients without PAF, mostly due to their worse risk profile. After adjustment for confounding factors, patients with PAF in the TE have a better overall outcome than counterparts in the PTE, probably reflecting the better management of patients with AMI in the TE.

Acute Disease↗
PubMed1998

Continuous administration of insulin-like growth factor-I and basic fibroblast growth factor does not affect left ventricular geometry after acute myocardial infarction in rats.

We examined the long-term effect of exogenous administration of bFGF and IGF-I on myocardial geometry in 72 Sprague-Dawley male rats subjected to AMI. A preloaded miniature osmotic pump subsequently implanted in the peritoneum for continuous infusion (1 week) of IGF-I, bFGF, IGF-I+bFGF or rat albumin. Six weeks following AMI the rats were killed and cross-section slices were analyzed for left ventricular geometry. No differences were observed between IGF-I-treated, bFGF-treated, IGF-I+bFGF-treated and control groups in all parameters of the left ventricle.

Animals↗
PubMed1998

Pneumothorax: an unusual cause of ICD defibrillation failure.

We describe two patients with defibrillation failure of implantable cardioverter defibrillators (ICDs) resulting from large left pneumothoraxes following subclavian vein puncture during the implantation. Following pneumothorax drainage, low defibrillation thresholds (DFTs) were attained without further manipulations. The absence of other signs and symptoms of pneumothorax and the presence of satisfactory pacing function during the procedure, resulted in a significant delay in diagnosis. Pneumothorax should be included in the differential diagnosis when unexpected high DFTs are found during ICD implantation or predischarge testing. This complication is avoidable by a different surgical approach, cephalic vein cutdown.

Aged↗
PubMed1998

Basic fibroblast growth factor induces myocardial hypertrophy following acute infarction in rats.

Basic fibroblast growth factor (bFGF) is a potent mitogen which induces growth of collateral vessels in ischaemic and infarcted myocardium. The effect of systemically administered bFGF on left ventricular (LV) function, myocardial hypertrophy and LV remodelling following acute myocardial infarction (MI) have not yet been fully investigated. Thirty Sprague-Dawley male rats were randomized to receive bFGF (0.5 mg) or rat albumin intraperitoneally for 1 week, beginning immediately after the induction of MI. Five animals served as controls and did not undergo any operation. Animals were killed 6 weeks after surgery and the hearts were perfused and fixed at physiological pressure. Transverse cross-sections from infarcted areas were stained with antibodies against proliferating cell nuclear antigen (PCNA) and Masson-trichrome and analysed with a coloured-image analyser for LV area (mm2), LV cavity diameter (mm), infarcted area (%), and wall thickness (mm) in infarcted and non-infarcted regions. LV area was similar in MI rats and in controls (41.7 +/- 6.9 and 43.0 +/- 1.5 mm2, respectively) and was significantly larger in MI bFGF-treated (MI/bFGF) animals (47.6 +/- 7.1 mm2) (P = 0.023). LV cavity diameter was significantly larger in the MI group than in MI/bFGF and control animals (6.0 +/- 0.8, 4.9 +/- 1.4, and 4.4 +/- 0.8 mm, respectively, P = 0.018). Wall thickness in the non-infarcted region was significantly smaller in MI animals (1.4 +/- 0.3 mm) than in MI/bFGF animals (1.6 +/- 0.4 mm) and the control group (1.6 +/- 0.1 mm) (P = 0.015). The ratio between LV cavity diameter/non-MI wall thickness was higher in MI than in control and MI/bFGF groups (4.8 +/- 1.6, 2.7 +/- 0.6 and 3.3 +/- 1.8, respectively, P = 0.03). Proliferating endothelial cells were significantly more abundant in infarcted than in normal areas in both MI and MI/bFGF groups, but with no significant differences between the groups. Intraperitoneal administration of bFGF did not cause any untoward extracardiac effects. Thus, systemic bFGF administration following acute MI in rats prevents dilatation of the LV, induces hypertrophy of the non-infarcted myocardium and exerts no untoward effects on extracardiac organs.

Animals↗
PubMed1998

Recombinant von Willebrand factor fragment AR545C inhibits platelet aggregation and enhances thrombolysis with rtPA in a rabbit thrombosis model.

Platelet adhesion to exposed subendothelium is mediated by platelet receptor glycoprotein Ib and polymeric von Willebrand factor (vWF). To improve the results of coronary arterial thrombolysis, fragments of vWF with enhanced glycoprotein Ib binding competitive with native vWF have been proposed as adjuvants to recombinant tissue-type plasminogen activator (rtPA). We designed a recombinant vWF fragment spanning Ala444 to Asp730 that contains the Arg545Cys mutation (named AR545C) and analyzed its antiplatelet properties in vitro and in vivo. AR545C-platelet interaction was assessed by ristocetin or botrocetin-induced platelet agglutination, or interaction with extracellular matrix under arterial flow conditions. AR545C showed enhanced reactivity with platelet glycoprotein Ib at low concentrations of ristocetin, and 60% bound spontaneously to platelets. AR545C inhibited ristocetin-induced platelet agglutination in a dose-dependent manner, with a concentration necessary to inhibit 50% of agglutination of 0.16+/-0.04 micromol/L. The inhibitory effect of AR545C on rabbit botrocetin-induced platelet agglutination was also dose dependent, with a concentration necessary to inhibit 50% of agglutination of 0.3 to 0.5 micromol/L. AR545C also completely inhibited aggregate formation and decreased the adhesion of platelets to extracellular matrix by 62.5%. The effect of AR545C on thrombolysis with rtPA was evaluated using a modified rabbit femoral thrombosis model. Local injection of AR545C into the thrombosed segment of rabbit femoral artery significantly shortened the time to reperfusion with rtPA (60+/-17.3 versus 103+/-15.2 minutes, P=.05) and significantly prolonged the total patency time (175 versus 21 minutes, P=.04). No significant difference was found in the reperfusion rate or time to reocclusion. AR545C is a potential antithrombotic agent that enhances the thrombolytic effect of rtPA in the rabbit model.

Animals↗