Contractile performance, mitochondrial function and blood flow distribution in porcine heart with induced coronary collateral circulation.

Progressive stenosis of the proximal left anterior descending coronary artery in young pigs was surgically induced over eight weeks and was accompanied by the development of a coronary collateral circulation originating from the right coronary artery. The antero-apical left ventricular myocardium dependent on this induced collateral blood supply became hypokinetic compared with the other regions of the left ventricle in the same hearts, and compared with the same region in different hearts, where the native circulation exists. Regional myocardial mechanics determined as fractional systolic shortening was 12.5 +/- 1.5% in normal regions, 0.7 +/- 2.4% in collateral-dependent myocardium, and in acutely ischemic myocardium was -2.0 +/- 1.3%, indicative of systolic lengthening. The rate of state 3 respiration of isolated mitochondria was depressed by 20% in collateral regions and by 64% in acutely ischemic regions relative to values obtained in mitochondria from respective normal myocardium (300 natoms of oxygen/min/mg mitochondria protein). Regional myocardial blood flow determined by 15 mu radionuclide labelled spheres revealed subendocardial hypoperfusion of 0.34 +/- 0.11 ml/min/g tissue in the collateral-dependent regions compared to 1.06 +/- 0.26 ml/min/g tissue in the normal regions. Transmural ischemia was observed (less than 0.10 ml/min/g tissue) in regions subjected to acute coronary artery ligation. Light microscopy revealed patchy fibrotic lesions predominately associated with the subendocardial half of the collateral dependent myocardial wall. Accordingly, the hypokinesia of collateral-dependent myocardium is more likely the result of blood flow abnormalities and loss of contractile elements than from mitochondrial dysfunction.