Ineffective Perfusion-Contraction Matching in Conscious, Chronically Instrumented Pigs With an Extended Period of Coronary Stenosis

Abstract

Abstract-Several models purported to represent hibernating myocardium involve a coronary stenosis (CS) to reduce blood flow (BF) and function without eliciting necrosis in anesthetized pigs. The goal of the present study was to determine whether sustained moderate reduction in coronary BF in conscious pigs induced hibernating myocardium, ie, perfusion-contraction matching with no necrosis. These experiments were conducted in conscious pigs chronically instrumented with a coronary artery BF probe and hydraulic occluder, left ventricular (LV) pressure gauge, and wall thickening (WT) crystals in the potentially ischemic and nonischemic zones. The hydraulic occluder was inflated to induce a stable 41Ϯ4% reduction in BF for 24 hours. Ischemic zone systolic WT fell initially with CS and then continued to decline during the period of CS even though blood flow did not change further, suggesting the induction of myocardial stunning. At 2 days after release of CS, WT was still depressed by 48Ϯ15%. Assessment of necrosis by histology or triphenyltetrazolium chloride showed 40Ϯ5% multifocal patchy necrosis interspersed with normal tissue involving the inner one third to one half of the ventricular wall. Regional myocardial BF (radioactive microsphere technique) was assessed by dividing the entire LV into an average of 488Ϯ59 pieces and examining the spatial distribution of BF within the area at risk (AAR). BF in the samples in the area of patchy necrosis was reduced (Ϫ66Ϯ4% from a baseline of 1.55Ϯ0.27 mL ⅐ min Ϫ1 ⅐ g Ϫ1 ), whereas BF was maintained in samples in the AAR without necrosis (Ϫ2Ϯ7% from a baseline of 1.25Ϯ0.22 mL ⅐ min Ϫ1 ⅐ g Ϫ1 ). These findings indicate that when hypoperfusion induced by CS in conscious pigs is sustained, the result is necrosis rather than hibernating myocardium. The remainder of the AAR, which lacked necrosis, might have been mistaken for hibernating myocardium had only histology been evaluated and BF not been measured and found to be at normal levels. (Circ Res. 1998;82:1199-1205.) Key Words: hibernating myocardium Ⅲ coronary blood flow Ⅲ coronary artery disease Ⅲ myocardial ischemia Ⅲ myocardial stunning

Dissociation of Regional Adaptations to Ischemia and Global Myolysis in an Accelerated Swine Model of Chronic Hibernating Myocardium

“…Hemodynamics were similar to those of conscious swine, 17 and heart rates were similar to average values recorded by Holter monitoring of unrestrained swine (authors' unpublished data, 2002). Although speculative, spontaneous increases in myocardial oxygen demand likely led to episodic ischemia when the animals were unmonitored.…”

“…Importantly, we avoided any circumstance in which the stenosis might cause prolonged acute ischemia, as reported in previous models of "short-term hibernation." [13][14][15][16][17][18] The results demonstrate that the physiological and molecular changes typical of hibernating myocardium can be induced within days after an acute critical stenosis. Although the myolytic phenotype also develops rapidly, the morphological changes occur globally and are dissociated from the regional adaptive responses in hibernating myocardium.…”

Gene program for cardiac cell survival induced by transient ischemia in conscious pigs

“…The coronary stenosis was maintained for 90 min, followed by complete deflation of the occluder and reperfusion. Measurement of regional blood flow by microspheres was performed as described previously (8). All hemodynamics were recorded in the conscious state.…”

Mitochondrial Preference for Short Chain Fatty Acid Oxidation During Coronary Artery Constriction

“…The open-chest animals were instrumented and hemodynamics recorded as previously described. 11 The left main coronary artery was dissected proximal to its bifurcation, and a catheter was placed as previously described. 12 A Silastic catheter was placed retrograde into the coronary vein for myocardial venous sampling.…”

“…14 Myocardial oxygen consumption was determined with a blood gas machine (ABL 725, Radiometer Copenhagen) and calculated as oxygen uptake (volume percent from A-V difference) multiplied by mean coronary blood flow (mL/min). Regional myocardial blood flow measurement with radioactive microspheres 11 was administered at baseline, twice during LAD constriction before substrate infusion (30 minutes and just before substrate infusion), and again during constriction with substrate infusion (20-minute infusion).…”