Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg^–1 in two animalsand 0.6 µg. kg^–1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin the control group (0.58± 0.38 vs 3.42 ± 0.84),in contrast to nearly baseline values in the experimental group(0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.     

Low molecular weight heparin (Fragmin(R)) prevents early reocclusion following femoral artery thrombolysis with rt-PA in rabbits

The purpose of this study was to evaluate the effect of lowmolecular weight heparin Fragmin on thrombolysis with tissue-typeplasminogen activator (rt-PA) and to compare its effect to thatof standard heparin. A rabbit thrombosis model was used, consistingof a blood clot produced in an isolated femoral artery segmentwith superimposed endothelial damage and distal stenosis. Thirtyrabbits were randomized to three treatment groups with rt-PA(30 µ.g. kg^–1. min^–1 for 60 min and no additionaltherapy), rt-PA with Lv. standard heparin (200 IV. Kg^–1bolus and then 70 IU. Kg^–1 hourly) and rt-PA with s.c.Fragmin (a single dose of 500 IU. Kg^–1) prior to rt-PAadministration. In six of 10 rabbits given rt-PA only, recanalizationwas observed, which was persistent in three. In eight of 10rabbits given rt-PA with intravenous heparin, reflow was achieved,which was persistent in three. Fragmin resulted in recanalizationin eight of 10 rabbits, with persistent patency in each recanalizedrabbit. Reflow time was not shortened with either standard heparinor Fragmin compared with rt-PA alone (64±41, 56 ±18, 50 ±23 min respectively), (P=0·7). Persistentreocclusion after reflow was not observed with Fragmin (0/8)but was present with both standard heparin (518, P=0·03vs Fragmin) and rt-PA alone (316, P=0·05 vs Fragmin). Thus, in the femoral artery of the rabbit, Fragmin, unlike standardheparin, was found to prevent reocclusion following rt-PA thrombolysis.     

Range of normal values for left and right ventricular ejection fraction at rest and during exercise assessed by radionuclide angiocardiography

In order to reach a world-wide consensus on the normal rangeof left (LV) and right ventricular (RV) ejection fraction (EF)at rest and during exercise, pooled data of 1200 normal subjectsfrom 28 leading centres in the field of nuclear cardiology (68%of those contacted) was analysed. Weighted mean normal valuesfor LVEF at rest were 62.3±6.1% (1SD) with a lower limitof normal of 50% and for RVEF 52.3±6.2% (N=365) witha lower limit of normal of 40%. During exercise, LVEF increasedin 475 subjects by +8.0 EF% (range 3–15%), a normal increasebeing accepted to be 5% over a normal resting value for bothLVEF and RVEF. Subgroup analysis of results at rest revealedno significant differences regarding selection of normal subjects(based on normal catheterization findings vs. normal volunteerswith low probability of disease), age or sex. During exercise,however, significantly larger increases in LVEF measurementswere noted for men versus women (P<0.01), for normal volunteersversus subjects selected as ‘normals’ based on anormal coronary angiogram (P<0.001) and for younger versusolder subjects (P<0.001). Data on reproducibility and variabilityshowed that radionuclide angiocardiography can be consideredto be a reliable method today. No consensus was found for measurementsof regional LV function or wall motion mainly because of differencesin methodology used. These normal values may serve as generalguidelines for future applications of these techniques but factorswhich may influence the normal range as defined and discussedin this study should be recognized.     

A Closed-Chest Pig Model of Sustained Ventricular Tachycardia

The goal of this study was to develop and explore a closed-chest animal model of sustained VT. Seven of 11 domestic pigs had successful induction of myocardiai infarction by injection of agarose gel microbeads into the left anterior descending coronary artery tbrougb an inflated balloon angioplasty catheter. Four of the first five pigs died and seem to represent a "learning experience." During a 3- to 50-day follow-up period, each pig underwent 1 -3 electropbysiological studies. Sustained, monomorpbic VT was induced 1–4 times in 5 of the 7 pigs (a total of 19 episodes), was reproducible during the same study in all pigs, and could be repetitively induced during successive studies in some. Ventricular fibrillation was induced less frequently (nine episodes) and was successfully terminated by DC shock in eight episodes. We conclude tbat a closed-cbest pig model of VT is feasible and is associated witb a relatively bigb induction rate of sustained, monomorpbic, and reproducible VT and a relatively low mortality rate.     

Beneficial effect of nitroglycerin on arterial rethrombosis after thrombolysis: Results from a rabbit thrombosis model

Background: Although nitroglycerin (NTG) is commonly administeredto patients with acute myocardial infarction, its effect onconcomitant thrombolytic therapy has not been fully elucidated.We examined whether NTG administration further optimizes thrombolysiswith rt-PA, combined with aspirin and heparin. Methods and Results: Blood clots were produced in a rabbit femoralartery with endothelial damage and distal stenosis. rt-PA wasadministered in repeated bolus i. v. injections of 0.3 mg. kg^–1every 10 min for 50 min. Femoral artery flow was measured continuouslyfor 2 h. Fourteen rabbits were randomized into two groups (group A andB), both receiving aspirin (i.v. 17 mg. kg^–1) and heparin(i. v. 200 units. kg^–1) prior to the first rt-PA bolusinjection. NTG was administered in group B only, 10 min priorto the first rt-PA bolus, at 10 µg. kg^–1. min^–1for 130 min. Reperfusion at the end of the 120 min observationperiod occurred in 5/7 group A and 6/7 group B rabbits (P–ns).In 3/7 group A rabbits, re-flow was achieved but persistentre-occlusion subsequently developed in 1/3 and oscillatory re-flowand re-occlusion cycles (cyclic re-flow) with subsequent patencydeveloped in the remaining two rabbits. These flow patternswere not observed in any of group B rabbits. Overall patency duration was significantly prolonged with NTG(group B; 578/840 min) compared to controls (group A; 258/840min) (P<0.001). The mean recanalization time (group A; 30.8± 9.3 vs group B; 22.5 ± 4.7 min, P–0.16)as well as mean rt-PA boluses needed to achieve complete recanalization(group A; 4.3 ±0.7 vs group B; 3.3 ± 0.6 boluses/rabbit,P–0.3) did not differ between groups. However, NTG infusionwas associated with increased restored femoral flow followingrecanalization (expressed as % of stenotic flow value over observationtime) compared to control group (P–0.025 by repeated measuresANOVA). Conclusion: Adding NTG to a thrombolytic regimen with rt-PA,aspirin and heparin increases the magnitude of restored flowand total patency duration following recanalization in a rabbitmodel of arterial thrombosis.     

CO2 Laser Catheter Angioplasty in Human Atherosclerotic Xenograft Arteries

Human atherosclerotic xenograft arteries implanted in five mongrel dogs were subjected to in-traluminal angioplasty using CO₂ laser radiation. CO₂ laser energy was delivered through a silver halide fiber, 0.9 mm in diameter and 100 cm long, inserted into a 6 Fr angiographic catheter. Results indicated that the technique is feasible, relatively simple and may have a low potential for perforation. (J Interven Cardiol 1989:2:1)     

Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0·12 µg. kg^–1 in twoanimals and 0·6 µg. kg^–1 in four) was incorporatedinto the beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0·008) reducedin the control group (0·58± 0·38 vs 3·42± 0·84), in contrast to nearly baseline valuesin the experimental group (0·58 ± 0·33vs 1·17 ± 0·42, P=0·41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0·04). Tissue samplesfrom both groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0·04) higher inthe peri-infarct region of the experimental group, as comparedwith controls (106·5 ± 2·8 vs 92 ±4·4 gray level units). Microvessels stained for von-Willebrandfactor were similar in nwnber in both groups (P=0·8),as were mesenchymal cells stained for vimentin (P=0·7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.