Segmental Functional Recovery Research Articles

Regional differences in postischemic recovery in the stunned canine myocardium

To determine if differences exist in the degree of ischemic damage and in postischemic recovery when different coronary arteries are occluded and reperfused, 40 barbital-anesthetized dogs were subjected to brief 15-minute periods of coronary artery occlusion followed by 3 hours of reperfusion (“stunned” myocardium) of the left anterior descending (LAD) or the left circumflex (LCX) coronary arteries. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic reperfused areas was measured by sonomicrometry, and regional myocardial blood flow was measured by radioactive microspheres. Transmural tissue blopsles were taken at the end of reperfusion for the measurement of adenine nucleotides and total tissue water content. Arterial and local coronary venous blood samples were collected during preocclusion, during occlusion, and at 30 and 180 minutes of reperfusion for determination of blood oxygen content and oxygen consumption in the ischemic area. During occlusion, subendocardial blood flow (LAD flow = 0.11 ± 0.02; LCX flow = 0.15 ± 0.04 ml/min/gm), myocardial oxygen consumption (LAD = 2.4 ± 0.7; LCX = 2.7 ± 0.7 ml/min/100 gm), and areas of the left ventricle at risk (LAD = 27.4 ± 2.3%; LCX = 32.4 ± 2.4) were similar in both groups, thus indicating equivalent degrees of ischemia. There were no differences between groups in hemodynamics throughout the experiment or in the loss of myocardial high-energy phosphates or increase in total tissue water in the ischemic reperfused area at 3 hours of reperfusion. There was a significantly greater loss ( p < 0.05) of systolic wall function during LAD versus LCX occlusion and a greater recovery of segment function from 5 minutes throughout 1 hour of reperfusion after LCX occlusion ( p < 0.05), with no difference in %SS at 2 and 3 hours following reperfusion. Thus, although similar changes occurred in blood flow, metabollte parameters, tissue edema, wall function, and overall hemodynamics when either the LAD or LCX perfusion territories were occluded and reperfused, the loss of systolic wall function and recovery of segment shortening were more variable after regional stunning of the LCX perfusion bed. These data suggest that evaluation of pharmacologic or surgical interventions to improve postischemic functional recovery may be more reliably performed when the LAD coronary artery is the vessel occluded.

Time course of recovery of “stunned” myocardium following variable periods of ischemia in conscious and anesthetized dogs

Persistence of regional contractile dysfunction after restoration of blood flow to transiently ischemic myocardium has been well described. To date, most studies have been performed in anesthetized animals. The present investigation compared the time course of recovery iof regional segment shortening (percentage of segment shortening) in anesthetized versus consclous dogs subjected to a brief period of total occlusion of the left anterior descending coronary artery. Periods of occlusion lasting 5, 10, and 15 minutes were followed by 3 hours of reperfusion. Dogs anesthetized with sodium pentobarbital (30 mg/kg intravenously) had a significantly higher heart rate and blood pressure and lower dP dt than conscious dogs. Coronary artery occlusion resulted in similar degrees of regional dyskinesis or akinesis, indicative of severe myocardial ischemia, in all experiments. During reperfusion, a gradual return of contractile function toward baseline was observed. At the end of the first 15 minutes of reflow, dogs subjected to 5 minutes of coronary occlusion demonstrated approximately 70% of control segment shortening in the previously ischemic zone. Animals subjected to 10- and 15-minute periods of coronary artery occlusion showed approximately 60% and 40% of control segment shortening at the same time point, respectively. The remainder of the 3-hour reperfusion period was characterized by a more gradual recovery of regional segment function. No differences were observed between anesthetized and conscious animals. It is concluded that the time course of functional recovery of postischemic reperfused myocardium is directly related to the duration of coronary occlusion and is similar in conscious and anesthetized dogs.

Effect of nifedipine on the myocardial and vascular response to myocardial ischemia.

Nifedipine reduces reactive hyperemia following brief coronary artery occlusions. To determine whether this is related to improvement in collateral blood flow to ischemic myocardium or alterations in myocardial oxygen consumption, ten chloralose anesthetized dogs were instrumented with coronary sinus catheters, circumflex artery flowmeters, and ultrasonic microcrystals for measurement of myocardial segment shortening. Myocardial oxygen consumption and circumflex coronary artery flow were determined at rest and during incremental infusions of isoproterenol. Myocardial blood flow measured with microspheres and segmental function were assessed during and following 30- and 60-second coronary artery occlusions. Thirty minutes after the intravenous administration of nifedipine, 10 micrograms/kg iv, all measurements were repeated. Nifedipine did not alter myocardial oxygen consumption or the relationship between oxygen consumption and circumflex coronary artery flow either at rest or during isoproterenol infusion. Following 60-second coronary occlusions, nifedipine reduced peak circumflex coronary artery flow (176 +/- 99 vs. 128 +/- 68 cc/min) and reactive hyperemia debt repayment (221 +/- 84 vs. 158 +/- 66%; p less than 0.01). Nifedipine did not alter flow to ischemic segments during coronary artery occlusions (0.16 +/- 0.10 vs. 0.19 +/- 0.13 ml/min/g mean transmural flow). Furthermore, nifedipine did not affect the severity of ischemic segment dysfunction, nor the rate of recovery of ischemic segment function following release of coronary artery occlusion. We conclude that the reduction in reactive hyperemia induced by nifedipine was not related to alterations in the severity of hypoperfusion in ischemic areas, or alterations in myocardial oxygen consumption. Reductions in reactive hyperemia produced by nifedipine did not impair recovery of mechanical function in postischemic myocardium.

Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs.

Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.

Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine.

The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 micrograms/kg followed by 25 micrograms/kg/min, i.v.) or nifedipine (3 micrograms/kg followed by 1 microgram/kg/min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (approximately 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil, or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of left ventricular segmental function after long-term reperfusion following temporary coronary occlusion in conscious dogs. Comparison of 2- and 4-hour occlusions.

Recovery of left ventricular segmental function after long-term reperfusion following temporary coronary occlusion in conscious dogs. Comparison of 2- and 4-hour occlusions.

Long-term recovery of regional segmental function after temporary coronary occlusion

Long-term recovery of regional segmental function after temporary coronary occlusion

Early recovery of regional performance in salvaged ischemic myocardium following coronary artery occlusion in the dog.

Although numerous agents have been shown experimentally to protect ischemic myocardium, a critical unanswered question is whether function is preserved in the salvaged tissue. Accordingly, 38 openchest dogs had measurements of percent segment length shortening (%SS) and velocity of segment length shortening either in midmyocardial or subepicardial and subendocardial ischemic segments before and after 60 min of left anterior descending coronary artery occlusion during 5 h of reperfusion; 10 additional dogs were subjected to 3 h of coronary occlusion followed by 72 h of reperfusion. 15 min after coronary artery occlusion, radiolabeled microspheres were injected into the left atrium for measurement of regional myocardial blood flow, and dogs were treated with 1 mg/kg i.v. (n = 23) of an anti-inflammatory drug, flurbiprofen or an equal volume of saline (n = 25). The ischemic myocardium-at-risk for necrosis was determined by injecting methylene blue dye into the left atrium with the coronary artery reoccluded at the end of the reperfusion period, slicing the left ventricle into thin transverse sections, and measuring the areas of each slice that were not perfused (pink unstained tissue) by methylene blue. The quantity of necrotic tissue in each transverse section was measured by planimetry after incubation of the slices in triphenyltetrazolium chloride, and by direct histological examination in dogs with 72 h of reperfusion. Regional myocardial blood flow of the ischemic segments between the ultrasonic dimension crystals was similar in treated (0.34+/-0.03 ml/min per g) and control dogs (0.35+/-0.03 ml/min per g). In saline-treated control dogs subjected to a l-h coronary occlusion, 17.9+/-1.8% of the myocardium-at-risk became necrotic but in flurbiprofen-treated dogs none of the tissue became necrotic. In saline-treated dogs passive lengthening of the previously ischemic segments persisted through 5 h of reperfusion in all three regions of myocardium after a 1-h coronary occlusion. In flurbiprofen-treated dogs regional function returned to normal within 5 min of reperfusion in both the subendocardium (%SS preocclusion = 17.2+/-2.0%; 5 min reperfusion = 17.8+/-3.1%; P = NS) and in the midmyocardium (%SS preocclusion = 17.8+/-2.2%; 5 min reperfusion = 17.9+/-2.3%; P = NS) and was not significantly different after 5 h of reperfusion from what it was before coronary occlusion. In the subepicardium of treated dogs regional function began to improve within 15 min of drug administration even during coronary occlusion. Regional function was not different from preocclusion values after either 5 min or 5 h of reperfusion (%SS preocclusion = 21.0+/-2.4%; 5 min reperfusion = 20.6+/-3.8%; P = NS). In dogs subjected to 3 h of coronary occlusion and 72 h of reperfusion, the administration of flurbiprofen was also associated with significantly smaller infarcts and a significantly more rapid rate of functional recovery than in control dogs.Thus, it appears that flurbiprofen not only decreased the quantity of necrosis in tissue made ischemic after coronary occlusion and then reperfused, but also allowed more rapid recovery of segmental function in ischemic but nonnecrotic tissue and in tissue with patchy necrosis; such recovery did not occur in equally ischemic myocardium in untreated control dogs. Earlier functional recovery of reversibly injured tissue following prolonged periods of ischemia is an additional important role for agents that protect ischemic myocardium from necrosis.

The loss of radioactive microspheres from canine necrotic myocardium.

The loss of radioactive microspheres from canine necrotic myocardium.

The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation.

The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation.