B I Jugdutt

Myocardial infarction in the conscious dog: three-dimensional mapping of infarct, collateral flow and region at risk.

Myocardial infarcts were examined in dogs to determine the spatial distribution of infarction in the region at risk and the relation between infarction and collateral blood flow. Permanent occlusion of the left circumflex (LC) coronary artery at a constant site was made in 27 conscious dogs that were sacrificed 2 days later. The anatomic region at risk was defined by postmortem coronary arteriography as the volume of the occluded LC coronary bed. The masses of the left ventricle (LV), infarct (I) and risk region (R) were calculated from planimetered areas of weighed “bread-loaf” sections of LV. Infarct size was directly related to the mass of the risk region (I = 0.53 R - 9.87; r = 0.97;P < 0.001). There was no infarction when R was less than about 20 g or 20% of the LV. The infarcts were mainly subendocardial and tapered from base to apex of the LV; 34% of the risk region became infarcted at the base compared with 22% at the apex. In all dogs, a significant rim of noninfarcted myocardium was identified at lateral aspects of the risk region, even at the endocardial surface. Using 9-μ radioactive microspheres, initial postocclusion flow at the margin of the infarct, but well within the risk region, was higher than at the center, and outer flows were higher than inner flows. Postocclusion flow was even higher in the noninfarcted rim within the risk region, but was still significantly less than flow to normal, nonrisk areas. Collateral flows throughout the risk region increased during the first hour after occlusion, and were even higher at 2 days. Epicardially and laterally within the anatomic risk region there is a substantial amount of tissue that does not infarct despite initially reduced blood flow.

Effect of indomethacin on collateral blood flow and infarct size in the conscious dog.

We examined the hypothesis that prostaglandin inhibition by indomethacin (I) increases infarct size in a conscious dog in which the anatomic risk region, infarct size, and collateral flow can be measured. We randomized 45 instrumented dogs into three groups: 21 were pretreated with I (10 mg/kg i.v.), 10 were given only the vehicle (V) (0.1 M sodium phosphate buffer), and 14 were controls (C). Acute permanent occlusion of the left circumflex (LC) coronary artery was made in the conscious state in all dogs. After the dogs were sacrificed 2 days later, the occluded LC bed was defined by stereoscopic coronary arteriography. The mass of infarct (MI), risk region (R), and left ventricle (LV) were calculated from planimetered areas of weighed transverse sections of LV. Total MI was greater in the I dogs (23.2 ± 2.7 g (SEM), n = 15) infarct size was greater in I dogs than in C and V dogs. Morphologically, I increased infarct size in both subepicardial and lateral directions within R, and this effect was uniform from base to apex of LV. Hemodynamic changes followed similar trends in all three groups, with slightly higher postocclusion mean arterial pressure (p>0.05) and heart rate (p>0.1) in I dogs than V and C dogs. Changes in collateral flow, measured using 9-A radioactive microspheres, were not significantly different in the three groups. The mechanism by which I increases infarct size appears to be related to increased oxygen demands and possible cellular membrane effects rather than effects on collateral flow.

Salvage of ischemic myocardium by ibuprofen during infarction in the conscious dog.

Abstract Because nonsteroidal anti-inflammatory drugs differ in potency and degree of prostaglandin inhibition, they may have different effects on ischemic myocardium. The effect of ibuprofen, an agent of this type, on myocardial infarct size was measured 2 days after occlusion of the left circumflex coronary artery in conscious dogs. Treatment was randomized in dogs after occlusion: Intravenous infusions of ibuprofen (6.25 mg/kg per hour) were administered to 13 dogs and saline solution (0.9 percent) to 13 control dogs over a period of 6 hours. The boundary of the occluded coronary bed, or anatomic risk region, was defined by postmortem coronary arteriography. Masses of infarct and occluded bed were measured by planimetry of weighed transverse sections of the left ventricle. Ibuprofen decreased infarct size compared with that in control dogs, both as percent of the left ventricle (mean ± standard error of the mean 7.5 ± 1.4 versus 15.2 ± 3.1, p

Effect of intravenous nitroglycerin on collateral blood flow and infarct size in the conscious dog.

SUMMARY This study was performed to determine whether nitroglycerin (NG) can increase collateral flow to ischemic myocardium and reduce ultimate infarct size. Permanent occlusion of the mid-circumflex coronary artery was produced in 43 previously instrumented conscious dogs and within 3 minutes, 6-hour intravenous infusions were begun of saline (controls, n = 18), NG in doses to reduce mean arterial pressure by 10% but not below 90 mm Hg (n = 15), or NG followed by methoxamine (MX) to correct the NG-induced fall in blood pressure (n = 10). After sacrifice 2 days later, the occluded coronary bed was defined by postmortem coronary arteriography and masses of infarct and occluded bed were measured by planimetry of weighed rings of the left ventricle (LV). Infarct size was significantly less with NG than saline, both as a percent of LV (12.1 vs 6.4%, p < 0.05) and as a percent of occluded bed (32.0 vs 15.9%, p < 0.005). NG plus MX did not reduce infarct size more than NG alone: 6.6 vs 6.4% of LV, and 16.0 vs 15.9% of occluded bed. Masses of LV and occluded bed did not differ significantly among the three groups. Coronary blood flow (CBF), measured by 7–10-μm radioactive microspheres, increased by more than 50% throughout the occluded bed (p < 0.005) after NG, and was more than the spontaneous increase seen in controls (p < 0.05), but MX had no additional effect on CBF over NG alone. Six-hour infusions of NG therefore decreased infarct size and improved CBF, and addition of MX to reverse the systemic effects of NG did not lessen the benefit. The results suggest that under the conditions of this study, myocardial protection by NG did not depend on a decrease in myocardial oxygen demands, but rather on an increase in collateral flow resulting from a direct vasodilating action of NG on the coronary bed.

Dissimilar effects of prostacyclin, prostaglandin E1, and prostaglandin E2 on myocardial infarct size after coronary occlusion in conscious dogs.

We studied the effects of prortaglandin PGE1, PGE2, and prostacyclin (PGI2) on collateral blood flow (CBF) and myocardial infarct size in conscious dogs. Beginning 5 minutes after acute permanent occlusion of the mid left circumflex coronary artery, 6-hour infusions of PGE1 (0.6 μg/kg per min in 150 saline, 13 dogs), PGE2, (0.7 μg/kg per min in 150 ml saline, 11 dogs), PGI2, (0.5 μg/kg per min in 150 saline, 19 dogs) or saline alone (150 ml, 15 control dogs) were given into the left atrium. In the three treatment groups, similar reductions occurred in mean arterial pressure (PGE1, 11%, PGE2, 10%; PGI2, 5%) and mean left atrial pressure (PGE1, 44%; PGE2, 30%; PGI2, 36%), whereas heart rate was unchanged. Mean arterial pressure remained above 80 mm Hg throughout the infusions. After the dogs were killed 2 days later, the boundaries of the occluded bed were defined by coronary arteriography. The mass of infarct and occluded bed were measured by planimetry of weighed transverse sections of the left ventricle (LV). Although the mass of occluded bed and LV were similar in the four groups, infarct size was significantly less (P< 0.005) with PGIi and PGE2 compared to PGE1, or controls, both as percent LV (4.7 vs. 7.3 vs. 14.4 vs. 14.8%, respectively) and as percent of the occluded bed (12.3 vs. 16.4 vs. 38.5 vs. 37.7%, respectively). Over the 6-hour infusion period, CBF (7–10 μm radioactive microspheres) increased throughout the occluded bed in PGI2 and PGE1, but not in PGE2 and control dogs. Transmural CBF (ml/min per g) by the 8th hour, in the center of the infarct region, was greater (P < 0.05) in PGI2, (0.30 ± 0.05) and PGE1, (0.28 ± 0.04) than in PGE2, (0.09 ± 0.03) or control dogs (0.11 ± 0.01). Since peripheral hemodynamic effects with the different PGs were similar, myocardial protection with PGI2, and PGE1, appears to be attributable largely to the increase in collateral flow. However, both PGI2 and PGE1 also produced myocardial salvage in hearts with low levels of collateral flow, suggesting that cellular and metabolic effects may also have contributed to their protective action.

The loss of radioactive microspheres from canine necrotic myocardium

To verify whether there is a loss of radioactive microspheres (RM) from regions undergoing myocardial infarction, we injected 7-10 fan RM into the left atrium in 75 dogs before left circumflex (LC) coronary artery occlusion and measured the myocardial RM content when the dogs were killed 6- 96 hours later. The preocclusion RM content per gram in the occluded LC bed was not significantly different from that in the nonoccluded left anterior descending (LAD) coronary bed in dogs killed within 6 hours and in those without necrosis and killed later. In contrast, in dogs with necrosis, the relative RM content in the LC bed was significantly reduced, indicating an apparent loss of RM averaging 19% (LC/LAD at 12-24 hours - 0.84; 48 hours - 0.80; 96 hours - 0.80). The percent of apparent RM loss from transmural samples correlated closely with the percent necrosis in the samples (r = · 0.93, P < 0.001). Desiccation of samples revealed that edema in the infarct accounted for about 40% of this apparent loss. Most of the remaining 60% appeared to represent true physical loss as evidenced microscopically by decreased RM counts in infarcted tissue, especially in zones of coagulative necrosis. Furthermore, following systemic RM injections and, more importantly, selective intracoronary RM injections into the occluded coronary bed, more RM were found in the lungs and neck lymph nodes in dogs with necrosis than in dogs without necrosis. These results indicate that apparent RM loss from necrotic myocardium is related both to increased tissue water and true physical RM loss and suggest that measurements of flow in infarct regions by RM may be reduced falsely. Ore Res 45: 746- 756, 1979

Relationship between myocardial infarct size and occluded bed size in the dog: difference between left anterior descending and circumflex coronary artery occlusions.

We compared myocardial infarct size produced by permanent occlusion of the middle left anterior descending (LAD) or circumflex (LCx) coronary artery in the anesthetized dog. The dogs were killed 3–10 days later, and the occluded coronary bed was visualized by postmortem arteriography. The outlines of the infarct and occluded bed were marked on tracings of weighed left ventricular (LV) rings and the size of the infarct and occluded bed was calculated by planimetry. For both arteries, infarct size and occluded bed size were linearly related to each other, but LAD infarcts were larger relative to occluded bed size (52.0% vs 32.3%, p < 0.05). A smaller occluded bed was necessary for the appearance of an infarct after LAD occlusion than after LCx occlusion (8.3% vs 18.5% of the left ventricle, p < 0.005). Reconstructed LV ring maps indicated a significantly wider margin of noninfarcted myocardium at the lateral edge of the occluded bed for LCx infarcts than for LAD infarcts. For dogs with similar occluded bed sizes in the range of 20–35% of the left ventricle, infarct size was considerably larger for LAD occlusion (15.9% vs 6.1% of the left ventricle, p < 0.001). In this subgroup, blood pressure and heart rate 10–20 minutes after occlusion were not significantly different for the two arteries, but collateral flow, measured with 9-, u radioactive microspheres, was approximately 50% lower after LAD occlusion. The relationship between the amount of myocardium with reduced blood flow and developed infarct size was similar for the two arteries. We conclude that occlusions of the middle LAD and LCx are not equivalent. For a given occluded bed size, LAD occlusions produce larger areas of infarction, apparently related to lower levels of collateral flow delivered to the occluded region.

Ischemic ventricular fibrillation: The importance of being spontaneous

Although the energy level required to defibrillate normal myocardium is low and constant, as determined from studies of induced ventricular fibrillation, little is known of the specific energy requirements in regionally ischemic hearts for spontaneous or induced ventricular fibrillation. In this study the lowest energy threshold for defibrillation was determined in 10 open chest dogs with reversible 10 minute coronary occlusions at various sites for each of 44 events of ventricular fibrillation, using apical and superior vena caval electrodes with a generator providing variable output of 1 to 30 watt seconds. The ischemic mass, quantitated from postmortem angiographic and planimetric data, was 52 +/- 9 percent (mean +/- standard deviation) of the left ventricle in dogs with induced ventricular fibrillation (Group I), 52 +/- 12 percent in dogs with spontaneous ventricular fibrillation after occlusion (Group II) and 54 +/- 9 percent in dogs with spontaneous ventricular fibrillation after reperfusion (Group III). Defibrillation thresholds in watt seconds were 9 +/- 7 in Group I (n = 12), 19 +/- 10 in Group II (n = 13) and 18 +/- 10 in Group II (n = 19). (Group I versus Groups II and III, probability [p] less than 0.025). In nonischemic hearts, the defibrillation threshold was 3 +/- 2 (n = 32) (p less than 0.001 compared with values in Group I, II or III). Thus, despite similar masses of ischemia, twice as much energy was required for defibrillation of spontaneous ventricular fibrillation (whether after occlusion or reperfusion) as for induced ventricular fibrillation, suggesting that these conditions are caused by different metabolic or pathologic derangements. Such differences should be considered in assessing interventions such as drug therapy designed to inhibit the repetitive ventricular response and in design of implantable defibrillators.

Salvage of ischemic myocardium by dipyridamole in the conscious dog.

We investigated the effect of i.v. dipyridamole, a potent small-vessel coronary vasodilator, on myocardial infarct size in conscious dogs. Dipyridamole, 7-9.7, ug/kg; 15 dogs) or saline (15 dogs) was infused for 6 hours beginning 10 minutes after acute permanent occlusion of the mid-circumflex coronary artery. After sacrifice, 48 hours after occlusion, stereoscopic postmortem angiography was used to define the mass of the occluded coronary bed. Infarct size was determined by planimetry of weighed, unstained left ventricular slices. Dipyridamole produced a striking reduction in mean infarct mass compared with control (3.1 g vs 13.2 g, p < 0.001), while mean occluded bed mass was similar (30.3 g vs 32.7 g, NS). As a percentage of the occluded bed, mean infarct size was reduced from 36.8% to 8.6% (p < 0.001). Mean arterial blood pressure declined approximately 10% after dipyridamole. Heart rate and left atrial pressure did not change significantly. Collateral blood flow, measured with 8-M radioactive microspheres, increased in all regions during dipyridamole infusion. The infarct center and border regions had sustained increases over 6 hours of 23-80%, while nonischemic regions demonstrated a diminishing response over time, with a large (98-125%) increase 10 minutes after infusion and a smaller (22-25%) increase 6 hours later. Although antiplatelet or local metabolic effects cannot be excluded, the myocardial salvage produced by dipyridamole was most likely due to the increase in collateral blood flow.

Intravenous Therapy with Propranolol in Acute Myocardial Infarction: Effects on Changes in the S-T Segment and Hemodynamics

The effects of intravenous therapy with propranolol (0.15 mg/kg of body weight) on changes in hemodynamics and the sum of precordial elevations of the S-T segment (∑ST) were studied 8.5 hours after the onset of pain in 14 patients with acute anterior transmural myocardial infarction and without complication. Therapy with propranolol (7.5 to 15 mg) produced a significant and sustained decrease from control in ∑ST, amounting to 46 percent (from 41 to 22 mm; P