No abstract

Temporal changes in infarct collagen and left ventricular topography during healing after myocardial infarction were studied in 132 dogs with coronary artery ligation: 8 sham dogs and 13 with no infarction (controls) and 111 with infarction (3 at 1 day, 54 at 2 days, 25 at 7 days, 3 at 2 weeks, 9 at 4 weeks and 17 at 6 weeks). Myocardial hydroxyproline (a marker of collagen) was measured by spectrophotometry and pathologic infarct size, arteriographic occluded bed size and topography by computerized planimetry of weighed left ventricular rings. Over 6 weeks, hydroxyproline was unchanged in normal regions (average 4.20 mg/g dry weight) but increased progressively between 7 days and 6 weeks (9.94 versus 55.55 mg/g, p less than 0.001) in infarct zones. Progressive infarct contraction occurred over 6 weeks, with infarct size at 6 weeks being 40% less than at 2 days (9.7 versus 16.3% of the left ventricle, p less than 0.001), although total infarct hydroxyproline was directly related to infarct size at each time period (r = 0.73 to 0.81, p less than or equal to 0.05). Significant (p less than or equal to 0.05) left ventricular topographic changes in infarct hearts compared with control hearts included: 1) increase in cavity area (5.0 versus 3.9 cm2), endocardial circumference (8.8 versus 7.4 cm) and expansion index (infarct/normal endocardial segment length, 1.21 versus 1.02) by 7 days; and 2) decrease in thinning ratio (infarct/normal wall thickness, 0.71 versus 0.98) by 6 weeks. Also, compared with 2 day infarcts, by 6 weeks infarct area was decreased (1.8 versus 3.4 cm2) and the noninfarcted segment length increased (6.9 versus 5.4 cm). Changes in hydroxyproline and topography were similar for anterior (n = 54) and posterior (n = 57) infarcts. Thus, healing in canine infarcts is associated with cavity dilation and infarct expansion within 7 days followed by infarct contraction and thinning by 6 weeks, whereas collagen increases between 7 days and 6 weeks. Collagen deposition in expanded and thinned infarct segments explains the permanent regional shape distortion associated with ventricular aneurysms.

Atherosclerosis-prone, insulin-resistant JCR:LA-cp male rats were treated from 6 weeks to 39 weeks of age with beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16). Body weights were reduced (13%, P < .001) at 36 weeks without any accompanying decrease in food consumption. The treatment did not cause any significant change in plasma glucose or fasting insulin concentrations. There was a significant decrease in the extreme hyperplasia of the islets of Langerhans (38%, P < .05). The marked VLDL hypertriglyceridemia was decreased by 70% (P < .001), with an accompanying significant reduction in cholesterol concentrations. The severity of raised atherosclerotic lesions on the aortic arch was very markedly reduced (P < .01) in treated rats. This was accompanied by a reduction (P < .01) in the incidence of ischemic myocardial lesions. We conclude that long-term (33 weeks) MEDICA 16 treatment of an animal model for the obesity/insulin-resistant/hyperlipidemic syndrome not only markedly improved lipid metabolism, but also inhibited the development of advanced cardiovascular disease.