Effect of verapamil on infarct size in dogs subjected to coronary artery occlusion with transient reperfusion

Reocclusion after successful coronary reperfusion occurs in 15 to 35% of patients receiving thrombolytic therapy for acute myocardial infarction. The present study was designed to simulate the clinical situation of reocclusion and determine whether verapamil might be effective in reducing myocardial necrosis and preserving high energy phosphates in this setting. Pentobarbital-anesthetized, open chest dogs underwent occlusion of the left anterior descending coronary artery for 2 hours followed by 1 hour of reperfusion and a further 4 hours of coronary artery occlusion. Treatment with verapamil (intravenous bolus dose of 0.2 mg/kg body weight followed by infusion of 0.56 +/- 0.14 mg/kg per h) was begun 1 hour after occlusion and infusion was continued for the remainder of the experiment. The dose of verapamil was adjusted to lower mean arterial pressure to approximately 90 mm Hg. The area at risk was determined by intraatrial injection of monastral blue dye and the area of necrosis was assessed by triphenyltetrazolium chloride staining. In vivo myocardial needle biopsy for determination of adenosine triphosphate and creatine phosphate was performed at the end of the experiment. The area of the left ventricle at risk was similar in both groups (control [n = 8], 20.2 +/- 1.6% versus verapamil-treated [n = 9], 23.1 +/- 2.9%; p = NS). The area of necrosis expressed as a percent of the area at risk was reduced in the verapamil-treated group compared with the control group (43.3 +/- 5.0% versus 63.1 +/- 6.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of infarct size induced by pressure-controlled intermittent coronary sinus occlusion

The effect of pressure-controlled intermittent coronary sinus (CS) occlusion on myocardial infarction (MI) size was evaluated. A device for this purpose was developed that consisted of a balloon catheter and pump system that produced controlled, intermittent occlusion of the CS and used CS pressure as a feedback to determine the duration of occlusion. It was hypothesized that proper selection of occlusion and nonocclusion times would both facilitate improved retrograde flow to ischemic areas and allow for more complete venous washout of metabolites. In 13 treated dogs and 12 control dogs before treatment, myocardium at risk of MI was estimated by injection of technetium-labeled microspheres. Intermittent CS occlusion was then begun, 15 minutes after coronary artery occlusion, and continued until termination of the experiment 6 hours later. Postmortem determination of infarct size was performed using the triphenyltetrazolium chloride staining technique. Intermittent CS occlusion begun 15 minutes after coronary artery occlusion and continued for 6 hours resulted in a 45% average reduction in MI size (p <0.001). During CS occlusion, the sinus systolic mean pressure increased from 10 to 44 mm Hg, while the distal coronary artery mean pressure increased by an average of 36% (from 22 to 30 mm Hg, p <0.05). These results suggest intermittent occlusion may be an effective treatment for evolving MI. This therapy, used alone or combined with other therapies (e.g., administration of pharmacologic agents), appears to have great clinical potential.     

Reduction of infarct size by oxygen inhalation following acute coronary occlusion.

This study was carried out in order to determine the effects of the inspiration of O2-enriched air on the size of myocardial infarction. In 15 anesthetized dogs, epicardial electrograms were recorded from 10 to 14 sites on the anterior surface of the left ventricle before and after intermittent occlusion of the left anterior descending coronary artery or one of its major branches. In each dog, one occlusion was carried out while the fraction of inspired oxygen (FIO2) was 0.20 and the other while the FIO2 was 0.40. With an FIO2 of 0.20 the average ST-segment elevation (ST) was 4.0 +/- 0.6 mV (SEM) and the number of sites exhibiting ST-segment elevations exceeding 2 mV (NST) 15 minutes following occlusion was 6.2 +/- 0.7 sites; comparable values following occlusion with an FIO2 of 0.40 were 1.8 +/- 0.4 mV (P less than 0.01) and 2.7 +/- 0.7 sites (P less than 0;01), reflecting reduction in acute myocardial ischemic injury; An FIO2 of 1.0 did not decrease myocardial injury further. In 24 other dogs, occlusion was maintained for 24 hours. In nine dogs in which FIO2 was increased from 0.20 to 0.40 30 minutes after occlusion, myocardial creatine phosphokinase activity (CPK) was less depressed in sites having comparable levels of ST-segment elevation at 15 minutes than in dogs that respired an FIO2 of 0.20 during the entire 24 hours. All (54) sites with ST-segment elevations greater than 3 mV in the 0.20 FIO2 group showed early signs of myocardial infarction, while only 49% of such specimens showed infarction in the 0.40 FIO2 group. Thus it is concluded that 0.40 FIO2 following an experimental coronary artery occusion decreases acute ischemic injury and reduces the eventual development of necrosis, as evaluated by enzymatic and histological techniques.     

Exercise-induced reduction in myocardial infarct size after coronary artery occlusion in the rat

Chronic exercise (E) has been thought to be beneficial to the cardiovascular system by increasing energy production and utilization, improving myocardial contractility and increasing myocardial vascularity; whether or not any of these effects are beneficial to ischemic myocardium is uncertain. In this study, rats were forced to swim one hr/day, 5 days/wk for 5 weeks. They were sacrificed and the myocardial capillary bed was perfused with carbon black. Using a calibrated eyepiece grid, histologic sections of heart were examined to determine capillary/fiber ratios (C/F) and myocardial fiber diameter. C/F was increased by 30% in E rats [0.87 +/- 0.06 (mean +/- SE) (N = 4 rats)] when compared with sedentary controls (C) [0.67 +/- 0.04 (N = 4 rats), P is less than 0.05]. This training effect occurred in the absence of hypertrophy since there were no differences in ventricular weight (1.21 +/- 0.04 mg in E rats vs 1.16 +/- 0.03 mg in C rats) or in fiber diameter (13.0 +/- 0.2 mu in E rats vs 13.1 +/- 0.2 mu in C rats) in the two groups. An additional 27 E rats and 25 C rats underwent left coronary artery occlusion and were sacrificed 48 hr later. Myocardial infarct size was measured by planimetry of histologic sections of serial slices of left ventricle (LV). In the 27 E rats, 21.5 +/- 1.9% of the LV was infarcted compared with 31.3 +/- 2.6% in the 25 C rats (P is less than 0.005). Thus, infarct size was reduced by 30% in E rats. In the rat, exercise results in a reduction of myocardial infarct size after coronary artery occlusion which, at least in part, may be related to increased myocardial vascularity.     

The influence of reperfusion on infarct size after experimental coronary artery occlusion

Summary Reperfusion following various intervals of coronary occlusion has produced conflicting results: increase in infarct size, especially with hemorrhage into the tissue, was reported as well as salvage of ischemic myocardium. To examine the problem and for the validation of our own method for infarct size measurement, which depends to a certain degree on reperfusion, we occluded two coronary arteries of the same heart in each of 12 open-chest dogs. One artery was reperfused, the other not. Comparable conditions for both occlusions were warranted by selection of small-to-medium sized arteries of equal size and by maintaining of constant MVO₂.Reperfused and non-reperfused myocardium did not differ with regard to infarct size, neither after a three-hour nor after a six-hour occlusion. Reperfusion always led to hemorrhagic infarction when performed after six-hour occlusion, while nonreperfused infarctions showed no hemorrhage. Hemorrhagic infarcts were not larger as compared to the non-hemorrhagic infarct in the same heart.

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Der Einfluß der Reperfusion auf die Infarktgröße nach experimentellem Koronarverschluß

Zusammenfassung Über die Wirkung einer Reperfusion nach unterschiedlich langem Koronargefäßverschluß liegen einander widersprechende Ergebnisse vor: Rettung ischämischen Myokards einerseits und Vergrößerung des Infarkts andererseits, besonders im Zusammenhang mit hämorrhagischer Infarzierung. Zur Abklärung dieser Frage und zur Bewertung unserer eigenen Methode der Infarktgrößenbestimmung, die z. T. auf einer Reperfusion beruht, wurden an 12 Hunden 2 Koronargefäße des jeweils selben Herzens okkludiert. Ein Gefäßgebiet wurde reperfundiert, das andere nicht. Durch die Auswahl zweier klein- bis mittelgroßer Arterien mit vergleichbarem Perfusionsgebiet und durch Aufrechterhaltung eines konstanten MVO₂ waren die Bedingungen beider Okklusionsperioden vergleichbar.Die Infarktgröße von reperfundiertem und nichtreperfundiertem Myokard war identisch-sowohl nach drei wie nach sechs Stunden Okklusionsdauer. Reperfusion nach sechsstündiger Okklusion war immer mit hämorrhagischer Infarzierung verknüpft, während nichtreperfundierte Infarkte hämorrhagiefrei blieben. Jedoch unterschieden sich hämorrhagische und nichthämorrhagische Infarkte aus einem Herzen nicht in ihrer Ausdehnung.

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With 3 figures and 1 table     

Effect of myocardial oxygen consumption on infarct size in experimental coronary artery occlusion

Summary The influence of myocardial oxygen consumption (MVO₂) at the moment of coronary occlusion on the size of the ensuing necrosis was investigated in 12 anaesthetised dogs. A two-infarction model was used with a sequential occlusion of two distant coronary branches in the same heart, however under different levels of MVO₂. One group of occlusions was produced at a high MVO₂ of 21.6±3.0 ml O₂... min^–1. 100 g^–1. This group was compared with a second in which necrosis proceeded at a low MVO₂ estimated to be 5.9±1.5 ml O₂·min^–1. 100 g^–1 averaged over a 90-min occlusion period. Infarct size expressed as percentage of perfusion area was 43±28% in group 1 and 11±11% in group 2 (p<0.005). The mass of the perfusion area was equal in both groups (17±4 g, 19±6 g). The amount of myocardial necrosis, which after a 90-min occlusion depends on the acute collateral blood flow, was in every case greater under high MVO₂. Thus a low MVO₂ at the moment of occlusion can postpone myocardial necrosis.

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Zusammenfassung Der Einfluß des kardialen Sauerstoffverbrauchs (MVO₂) auf die Infarktgröße wurde bei 12 narkotisierten Hunden untersucht. Zwei voneinander völlig getrennte Seitenäste der linken Koronararterie wurde nacheinander am selben Herzen verschlossen. Das erste Gefäßkollektiv wurde bei einem MVO₂ von 21,6±3,0 ml ·min^–1. 100 g^–1 okkuldiert, das zweite bei einem MVO₂ von 5,9±1,5ml·min^–1 ·100g^–1. Die Infarktgröße, ausgedrückt als Fraktion des Perfusionsgebietes, war 43±28% in Gruppe 1 und 11±11% in Gruppe 2 (p<0,005). Die Perfusionsgebiete, die okkludiert wurden, waren in beiden Gruppen gleich (17±4g, 19±6 g). Die Infarktgröße, die nach einer 90-min-Okklusion vom akuten Kollateralfluß abhängt, war in jedem Fall größer bei einem höheren MVO₂. Somit kann ein, niedrigerer MVO₂ zum Zeitpunkt des Verschlusses die Entwicklung der Nekrose zumindest hinauszögern.

     

Reduction in myocardial infarct size by basic fibroblast growth factor following coronary occlusion in a canine model

In a canine model of permanent coronary occlusion it has been shown that basic fibroblast growth factor (bFGF) reduced infarct size and this was associated with an increase in myocardial capillary density a week after infarction. In a preliminary work from our own laboratory using a model of occlusion followed by prolonged reperfusion we observed a similar reduction in infarct size without evidence of myocardial neovascularization. The aim of the present investigation was to evaluate the effects of bFGF on infarct size and blood flow to the infarct zone in an acute experiment in which myocardial neovascularization would be excluded as a mechanism by the short duration of the study. Seventeen mongrel dogs were anesthetized and the heart was exposed through a left thoratocomy. The left anterior descending (LAD) coronary artery was isolated and occluded for 3 h. Fifteen min after LAD occlusion dogs received bFGF 20 μg of bFGF (n=6) or placebo (n=11) by intracoronary injection infused over 5 min. We measured heart rate, aortic pressure, regional coronary blood flow (CBF), regional shortening fraction (SF) at 1, 30 and 180 min of occlusion, then the LAD was reperfused for 5 min then the dogs were euthanized and infarct size was measured. Regional CBF was similar between the two groups of dogs throughout all the study. The SF was similar between the two groups prior the onset of ischemia and at the beginning of the ischemic period. After 180 min of ischemia SF was 2.7±4.1% for bFGF and −3.1±4.7 for placebo (P=0.049), and during reperfusion SF was 3.4±4.6% for bFGF and 0.4±1.0% for placebo treated dogs (P=0.023). The infarct size, normalized for the area at risk was 14.2±5.2% in bFGF group vs 25.8±8.2% in placebo group (P=0.015). In summary we have demonstrated that bFGF significantly limits myocardial necrosis after acute coronary occlusion, and that this occurred without an increase in regional myocardial perfusion and within a period of time too brief for angiogenesis to have occurred. By exclusion, it appears that the salutary effect of bFGF is likely to be mediated by a cellular mechanism. The mechanism or mechanisms responsible for myocardial salvage by bFGF may have significant potential to be exploited in the clinical arena as the basis for therapies to protect the acutely ischemic myocardium.     

Increased myocardial infarct size by thiopental after coronary occlusion in the dog

The effect of a single dose (10 mg/kg) of intravenous thiopental (TP), during acute myocardial infarction, on infarct size was studied in conscious dogs randomized 10 minutes after left circumflex coronary artery occlusion to either the TP group (n = 10) or a control group given 0.9% saline solution (n = 10). During the first hour following therapy, myocardial blood flow (microspheres), arterial pressure, left atrial pressure, and arterial blood gases were similar in the two groups, but the heart rate (140 +/- 3 vs 110 +/- 3 bpm; p less than 0.001) and rate-pressure product (15,090 vs 12,210 bpm X mm Hg; p less than 0.025) were greater in the TP group. Infarct size (planimetry) and occluded bed size (postmortem coronary arteriography) measured 2 days later revealed that: the slope of the relation between infarct and occluded bed mass, as a percentage of the left ventricle (% LV) was greater with TP than with saline solution (1.10 vs 0.61; p less than 0.001); excluding hearts (four TP and three saline solution) with small occluded beds (less than 22% LV), infarcts were also larger with TP (n = 6) than with saline solution (n = 7), both as a percentage of the left ventricle (26.4 vs 12.2%; p less than 0.02) or occluded bed (61.5 vs 28.9%; p less than 0.005); and transmural and endocardial extents of the infarcts on topographic maps were greater with TP than with saline solution. In 12 other conscious dogs, increasing the heart rate between 10 and 70 minutes after left circumflex coronary artery occlusion to the average rate of the TP group (140 bpm) by atrial pacing resulted in infarcts larger than those in control dogs but similar to those in the TP group. Thus, TP therapy after left circumflex occlusion increased infarct size in dogs. This effect appeared to be due mainly to the increased heart rate, probably via increased myocardial oxygen demands.     

Intermittent coronary sinus occlusion in dogs: reduction of infarct size 10 days after reperfusion

Intermittent balloon occlusion of the coronary sinus was applied to 11 open chest dogs subjected to 3 hours of ligation of the left anterior descending coronary artery followed by 8 to 12 days of reperfusion. Anticoagulants were not given during the reperfusion period. Risk region was assessed by planimetry of autoradiographs made from ventricular slices. Infarct size was equivalent when assessed by planimetry of ventricular slices before and after staining with triphenyltetrazolium chloride. In the seven survivors, 30 +/- 8% of the risk region was infarcted. Seven of 11 control dogs survived (p = NS); 75 +/- 4% of the risk region was infarcted in the control animals (p less than 0.01 versus treated survivors). Light microscopic inspection of specimens stained with hematoxylin-eosin confirmed the border between necrotic and preserved myocardium. Thrombus was observed in the coronary sinus in all survivors in the treatment group. These findings confirm earlier short-term studies that demonstrated a potent anti-ischemic effect of intermittent coronary sinus occlusion. At the same time, coronary sinus thrombosis warrants caution in the application of this technique to myocardial ischemia in humans.     

Reduction in infarct size by the prostacyclin analogue iloprost (ZK 36374) after experimental coronary artery occlusion-reperfusion

In this study we attempted to determine whether administration of iloprost (ZK 36374), a chemically stable prostacyclin analogue, would reduce infarct size after experimental coronary artery occlusion and reperfusion. One hour of coronary artery occlusion was performed in 28 open-chest, anesthetized rabbits++, followed by 5 hours of reperfusion. Two minutes after occlusion, 99mTc-labeled albumin microspheres were injected into the left atrium for later assessment of the area at risk of infarction. Fifteen minutes after occlusion animals were randomly assigned to either the treatment group (iloprost, 1.2 micrograms/kg/min intravenously for 6 hours; n = 14) or the control group (n = 14). In vitro platelet aggregation was inhibited in rabbits receiving iloprost. In 10 rabbits (five treated and five control) regional myocardial blood flow was also measured by means of differentially labeled radioactive microspheres. Infarct size was significantly smaller in treated rabbits (53.6 +/- 4.1% of the risk zone vs 89.4 +/- 3.8% in control rabbits; p less than 0.001). Flow to the nonischemic myocardium was higher in treated animals, that is, 1.87 +/- 0.20 ml/min/gm of tissue 50 minutes after occlusion and 1.90 +/- 0.20 ml/min/gm of tissue 4 hours after reperfusion, compared with 1.54 +/- 0.20 and 1.64 +/- 0.30 ml/min/gm of tissue, respectively, in control rabbits (p less than 0.01). Collateral flow to the ischemic region was not affected by the drug. Mean arterial blood pressure, heart rate, and pressure-rate product in treated rabbits were not significantly different from values in control rabbits. In conclusion, administration of iloprost reduced myocardial infarct size in this model of myocardial ischemia and reperfusion in absence of major hemodynamic effects.     

Effects of ortho-iodo sodium benzoate on acute myocardial ischemia, hemodynamic function, and infarct size after coronary artery occlusion in dogs

Ortho-iodo sodium benzoate (OISB) decreases the affinity of blood for oxygen, thus enhancing potential tissue oxygen delivery. To test the hypothesis that a change in oxygen affinity would ameliorate regional myocardial ischemic injury resulting from occlusion of the left anterior descending (LAD) coronary artery, experiments were carried out in 55 anesthetized dogs which received an intravenous infusion of OISB. In Protocol I studies (n = 9), preocclusion intravenous infusion of OISB (500 mg/kg) reduced epicardial S-T segment elevation 15 minutes after coronary occlusion, while a similar volume of normal saline solution did not affect this index of ischemic damage. In Protocol II experiments, 34 dogs were randomized to either an OISB or saline group, after which the LAD was ligated, the chest closed, and the animal allowed to recover from anesthesia. Myocardial infarction (MI) size was assessed after the animal died or was killed 8 to 24 hours later, and was found to be 29% smaller in dogs receiving OISB. In 6 dogs, blood P50 (the partial oxygen pressure at which hemoglobin is 50% saturated with oxygen) was increased by OISB infusion, confirming that its administration effected a rightward shift in the oxyhemoglobin dissociation curve. Protocol III studies assessed the effects of OISB on cardiac hemodynamic function and acute myocardial ischemic damage when infusion was begun 15 minutes after LAD occlusion: average epicardial S-T segment elevation was not altered by saline solution, but decreased when OISB was infused during the last 15 minutes of myocardial ischemia. Reductions in heart rate, left ventricular dP/dt, and cardiac output were observed in 7 dogs during OISB infusion, but there were no changes in these measurements during coronary occlusion in 5 dogs receiving a constant infusion of saline solution. There were no changes in regional myocardial blood flow (microsphere technique) to either ischemic or nonischemic zones in either the saline control or OISB treatment groups. Thus, both acute myocardial ischemic injury (assessed by epicardial electrocardiographic mapping) and ultimate MI size are reduced when OISB is infused before experimental coronary artery occlusion. OISB also reduces myocardial ischemic injury when its administration is begun 15 minutes after coronary occlusion, while effecting decreases in heart rate, left ventricular contractility, and cardiac output.     

Reduction of infarct size following acute coronary occlusion by augmenting collateral blood supply induced by infusion of tricyclic antidepressants

Summary Previously, it has been shown that following occlusion of the left anterior descending artery (LAD) in cats, i.v. administration of tricyclic antidepressants (TCAD) significantly decreases the incidence of ventricular fibrillation (VF), which terminates spontaneously upon appearance. Furthermore, this treatment significantly decreases the size of the unperfused ventricular muscle (ischemic myocardium) from 44%–84% (mean 61%) to 17%–56% (mean 34%). This latter effect was demonstrated by using color demarcation of the perfused myocardium with the injection of a dye into the left atrium after 2 h of LAD occlusion in both control and treated cats. It was assumed that reduction of the unperfused area was due to an increase of collateral blood supply to the ischemic area.Although the beneficial effect of TCAD on the collateral blood supply has been clearly demonstrated in cats randomly assigned to two groups, the present study was designed to investigate the changes in the size of the ischemic area in the same animal by using two different dyes. Both dyes were injected into the left auricle after the LAD occlusion: The first was injected before the TCAD treatment and the second after the treatment.Two days after fixation in 4% formaldehyde, the hearts were sliced into three or four transverse sections. Examination of the sections indicated that there were three types of myocardial markings: (a) totally unperfused myocardium; (b) an area perfused by both colors; (c) an area perfused only by the second dye, indicating an increased collateral blood supply, the effectiveness of which was increased by the TCAD treatment.To date, there has been no report on any antiarrhythmic drug possessing the combined effects of enabling spontaneous defibrillation and increasing the collateral blood supply to the ischemic area.The contribution by Neuman is part of an M.Sc. Thesis submitted to the Tel Aviv University Medical School     

The relationship between the perfusion deficit,infarct size and time after experimental coronary artery occlusion

It is well known that coronary occlusions of short duration do not produce infarcts in the dog heart, but permanent occlusions always do. The aim of this paper was to investigate with quantitative direct measurements the determinants of infarct size within these two extremes. We measured left ventricular MV2, coronary and collateral blood flow and infarct size after occlusion times varying between 45 minutes and 24 hours. MVO2 was kept low in one group by establishing low heart rates with a synthetic opiate. In another group, MV2 was kept elevated by giving synthetic catecholamines (dobutamine) that stimulated contractility and heart rate. Under the described experimental conditions LV-coronary blood flow reflected the true demand for blood and oxygen. The ratio of collateral blood flow over coronary blood flow (both measured with tracer microspheres) was therefore a good approximation of the supply-demand ratio (SD). Since collateral flow was inhomogeneously distributed across the left ventricular wall, the SD-ratio showed similar variations. As the collateral blood flow increased with elapsed time after coronary occlusion, the SD-ratio improved. Since high LV-O2-demand increased coronary flow but exerted practically no influence on collateral flow, this situation influenced the SD-ratio in a negative way. Decreased O2-demand had the opposite effect. The SD-ratio is thus a valid expression of the relative and absolute blood flow deficit as influenced by the local and general O2-demand. We found significant and characteristic correlations between the SD-ratio and infarct which was only influenced by time. A blood flow deficit of 90% (i.e., collateral flow = 10% of required flow) produced a 50%-infarct (relative to the risk-region) with a 45-min occlusion but a 90%-infarct with occlusion times of 3 hrs and longer. If the perfusion deficit is only 0.5 (collateral flow = 50% of required flow), no infarct is detectable at occlusion times shorter than 3 hrs. Small perfusion deficits of only 20% below required flow caused infarctions at 24 hrs and longer. In the group where the SD-ratio was closer to unity because of a low overall LV-O2-consumption (bradycardia), infarcts at t = 24 hrs were significantly smaller than in the group with a high LV-MVO2.     

Ineffectiveness of methylprednisolone to reduce infarct size in experimental coronary occlusion

Summary Two medium-sized branches of the left coronary artery were prepared in each of 10 anesthetized open chest dogs for later occlusion. The first artery was occluded during 90 minutes and reperfused thereafter. This occlusion produced the control infarct. Methylprednisolone (50 mg/kg i.v.) was injected, and the second artery was occluded also for 90 minutes and reperfused thereafter. Both infarcts were made visible by staining left ventricular rings with p-nitrobluetetrazolium. Infarct size was compared with the size of the perfusion area, which we obtained from the postmortem angiogram. Both infarcts were equal in size and comprised 50% of the area of perfusion of the occluded artery. Methylprednisolone in a single high dose given prophylactically did not influence infarct size nor any of the measured parameters.

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Zusammenfassung An 10 Hunden wurde die Wirkung von Methylprednisolon auf die Myokarddurchblutung und die resultierende Infarktgröße nach experimentellem Koronarverschluß untersucht. An jedem Herzen wurden hintereinander zwei mittelgroße Äste der linken Koronararterie für 90 min okkludiert und anschließend reperfundiert. Der Verschluß der 1. Arterie erfolgte unter Kontrollbedingungen, es resultierte der Kontrollinfarkt. Vor dem Verschluß der 2. Arterie wurde Methylprednisolon (50 mg/kg Körpergewicht i.v.) injiziert, es resultierte der Testinfarkt. Die hämodynamischen Parameter (LVP, LV-dp/dt, AOP, HR) wurden kontinuierlich registriert, der myokardiale Sauerstoffverbrauch wurde vom Computer mit Hilfe der Bretschneider-Formel kalkuliert. Die myokardiale Durchblutung wurde mit Hilfe der Tracer microsphere-Technik bestimmt. Das Gebiet der myokardialen Nekrose wurde mit Hilfe der p-NBT-Färbung definiert, das Perfusionsgebiet wurde mit Hilfe der Post-mortem-Angiographie bestimmt Die Infarktgröße wurde als Quotient aus Nekrose- und Perfusionsgebiet in Prozent ausgedrückt. Die hämodynamischen Bedingungen waren in beiden Verschlußperioden vergleichbar, der Kollateralfluß betrug im Gebiet der Kontrollarterie 13,9±6,2% und im Gebiet der Testarterie 14,5±7,8% der Normaldurchblutung. Die resultierenden Infarktgrößen waren ohne Unterschied, der Kontrollinfarkt betrug 51±22%, der Testinfarkt 48±25%. Durch Methylprednisolon konnte weder der Kollateralfluß noch die resultierende Infarktgröße nach Koronarligatur beeinflußt werden.

     

Histologic,ultrastructural, and enzymatic measurements of infarct size following coronary artery stenosis and occlusion

Coronary artery narrowing (CAN), which reduced resting coronary blood flow (BF) by 50%, was induced in 10 conscious dogs and was maintained for 4 hours. Five additional dogs (group 1) with complete coronary artery occlusion were compared to the dogs with CAN. serum isoenzymes of creatine phosphokinase (CK) and latate dehydrogenase (LD) were monitored hourly in all groups. After 36 hours, samples were obtained for regional myocardial BF, quantitative histology, and quantitative ultrastructural (EM) morphology. Six dogs with CAN had small infarcts (MI) of less than 1 gm and persistent myocardial cell injury (group 2). The other four dogs with CAN had only persistent myocardial cell injury by ultrastructural criteria (group 3). Peak serum CK activities in groups 2 and 3 were similar, as were MI sizes calculated from serum CK and myocardial depletion. MB CK was of diagnostic value in group 1 but not in groups 2 and 3. The ratio of $\text{LD}\text{1}\text{LD 2}$ had diagnostic value in all three groups. MI size by enzyme estimates was consistently higher than planimetered MI size at autopsy in both groups 1 and 2. All three groups had significant amounts of ultrastructural damage outside of histologically demonstrated MI. These findings suggest that (1) gross and histologic MI size determination of 36 hours after ischemia underestimate extent of damage, and (2) ultrastructural cell changes cause significant release of CK and LD in coronary disease (CAD).