Healing after myocardial infarction in the dog: Changes in infarct hydroxyproline and topography

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.

Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction.

“…On the other hand, this finding is consistent with prolonged scar formation in the myocardium. [6][7][8][9][10] The peak serum PIIINP values were significantly correlated to the estimated infarction sizes, based on sequential determination of serum LD and CK-MB. This correlation is in accordance with that between the rate of collagen deposition during the early stage of infarction healing (measured by tissue hydroxyproline content) and the infarction size, as demonstrated by Jugdutt et al 8 Collagen type III plays a dominant role in early granulation tissue formation (scars).…”

Delayed Enhancement and T2-Weighted Cardiovascular Magnetic Resonance Imaging Differentiate Acute From Chronic Myocardial Infarction

“…Moreover, the induction of reperfusion marks the rapid evolution of an inflammatory-like response of which interstitial edema is a substantial feature. In chronic MI, on the other hand, enlargement of the extracellular space is mostly the result of the relatively large collagen matrix 19 in the absence of myocardial edema. 20 These considerations explain our findings that DE is a feature of MI regardless of its age and that high SI in edema-sensitive T2-weighted imaging is a feature of acute but not chronic MI.…”

Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction.

“…This resulted in a low mortality rate of 12%, but the infarct scar at 6 weeks was small (9.5% of left ventricular mass), in agreement with previous reports.242527,28,1 As noted previously,31 because the infarct scar contracts and compacts over the 6 weeks, an infarct that is about 19% of left ventricular mass 1 day after coronary ligation is roughly equivalent to 14% at 1 week and 10% at 6 weeks. 25 Nevertheless, in the untreated group, morphometric analysis and infarct mapping showed that the transmural extent at 6 weeks averaged 62%, and echocardiograms revealed infarct-zone akinesis and dyskinesis, expansion, thinning, and aneurysmal bulging and noninfarct-zone hypertrophy and expansion and larger cavity size. A limitation of our canine model is that the dog heart has a rich collateral supply, the infarct-related artery remained permanently ligated, and the noninfarct-related arteries probably remained open throughout infarct healing.…”

“…Seventy-five healthy mongrel dogs (weight, 16 to 29 kg) of either sex were instrumented through a left lateral thoracotomy under general anesthesia (sodium pentobarbital, 30 mg/kg IV), as described previously. 25 (11 control, 11 nitrate). The dogs were allowed free access to fluids, and no attempt was made to treat heart failure by fluid restriction or pharmacotherapy.…”