Model Of Coronary Artery Occlusion Research Articles

Early Administration of Amrinone Does Not Impair Regional Metabolism of O2 or Lactate and, by Improving Myocardial Performance, Preserves Myocardial Blood Flow in the Ischemic Canine Heart

The inotropic and vasodilating effects of amrinone can upset the balance of O2 supply and demand by changing those components in opposite directions simultaneously. We used a canine model of acute coronary artery occlusion to test our hypothesis that early administration of amrinone (before failure of the heart) would have beneficial effects on hemodynamic status and regional metabolism during ischemia, even before heart failure. Twenty dogs anesthetized with thiamylal were subjected to 50%, 75%, and 100% occlusion of the left anterior descending coronary artery. Half of the dogs were given a bolus injection of amrinone (0.75 mg/kg) 1-2 min before each occlusion, immediately followed by continuous infusion (10 micrograms.kg-1 x min-1) during occlusion; the other half did not receive amrinone (control). Hemodynamic and metabolic variables were measured in the ischemic area (the left anterior descending coronary artery) and in a nonischemic area (the circumflex vein). Amrinone not only decreased heart rate, left ventricular systolic and end-diastolic pressures, and mean pulmonary arterial pressure during constrictions but also maintained contractility, stroke volume index, and stroke volume index/left ventricular end-diastolic pressure before and during constrictions. Regional myocardial blood flow in ischemic areas decreased with amrinone during constrictions but was still higher than in untreated animals. Regional ischemic and nonischemic metabolic variables (metabolism of intracoronary potassium, CO2, O2, glucose, and lactate) were similar for both groups and changed to the same extent. Amrinone appears to improve left ventricular performance and increase blood flow to ischemic myocardium while not worsening regional metabolic effects during various grades of ischemia in the dog.

Fructose-1,6-diphosphate fails to limit early myocardial infarction size in a canine model

Fructose-1,6-diphosphate (FDP) appears to improve early post-myocardial infarction hemodynamics and limit early myocardial infarct size in previous canine studies. However, these studies did not account for the effect of collateral blood flow on infarct size. Our objective was to determine the effect of FDP on early infarct size and hemodynamics while measuring regional myocardial blood flow. A prospective, blinded, placebo-controlled laboratory study using a canine open-chest left anterior descending coronary artery (LAD) occlusion model. Twenty-two mongrel dogs were assigned randomly to receive either FDP (175 mg/kg, then 2 mg/kg/min for two hours) or placebo, beginning five minutes after LAD occlusion. Regional myocardial blood flow, hemodynamics, and myocardial infarct size were determined. Infarct size was assessed using magnetic resonance imaging in a subset of animals. Three of the 22 dogs had no infarct and significantly higher collateral blood flow than the 19 animals with myocardial infarction (P < .001). Four hours after LAD occlusion, cardiac index, dP/dtmax, heart rate, and systolic and mean aortic pressures were not statistically different between groups. Infarct size expressed as area of necrosis/area at risk was similar between groups (FDP, 0.55 +/- 0.28; controls, 0.59 +/- 0.31). FDP given after occlusion of the LAD in this canine model did not limit early myocardial infarct size.

"Cardioprotection" by ACE-inhibitors in acute myocardial ischemia and infarction?

Coronary artery occlusion results in the acute activation of the renin-angiotensin system and production of angiotensin II, a potent vasoconstrictor and positive inotropic agent. This has raised the possibility that angiotensin converting enzyme (ACE) inhibitors might be "cardioprotective" (that is, might attenuate myocardial injury, dysfunction and necrosis) in the setting of acute ischemia and infarction. Captopril, enalapril and ramipril have, in fact, been reported to acutely limit myocardial injury and necrosis in models of permanent coronary artery occlusion. The mechanisms responsible for this cardioprotection are complex, but include favorable alterations in myocardial oxygen supply/demand, and, in some instances, inhibition of bradykinin metabolism and/or increased prostaglandin synthesis. Other studies, however, have failed to document a reduction in infarct size with ACE inhibitor treatment. Results obtained in models of coronary occlusion/reperfusion have also been mixed. In models of brief transient ischemia not associated with necrosis, captopril and zofenopril have consistently been found to attenuate postischemic contractile dysfunction of the viable but "stunned" myocardium during the early hours following relief of ischemia. In contrast, there is no consensus on the effects of enalapril on the stunned myocardium: both positive and negative results have been obtained. Similar disparity has been reported in models of more prolonged ischemia/reperfusion resulting in subendocardial necrosis: some studies have reported myocardial salvage, while others have provided disturbing evidence of apparent exacerbation of myocardial necrosis with captopril and enalapril therapy. Thus, after a decade of investigative effort, the question of whether ACE inhibitors are "cardioprotective" in the setting of acute myocardial ischemia and infarction remains unresolved. Nonetheless, clinical protocols are in progress to assess the effects of early ACE inhibitor treatment in patients with acute myocardial infarction.

Cardioprotective effects of the vasodilator/beta-adrenoceptor blocker, carvedilol, in two models of myocardial infarction in the rat.

The purpose of this study was to evaluate the cardioprotective effects of carvedilol, a beta-adrenergic blocker and vasodilator, in two models of ischemic myocardial damage in the rat. Following coronary artery occlusion for 0.5 h and reperfusion for 24 h (MI/R group), left ventricular (LV) injury was determined by planimetric analysis of triphenyltetrazolium chloride-stained tissue, and polymorphonuclear leukocyte infiltration was assessed by measuring myeloperoxidase (MPO) activity. In the vehicle-treated MI/R group, infarct size was 14.2 +/- 1.3% of the LV (n = 16), and MPO activity was increased to 2.8 +/- 0.7 from 0.14 +/- 0.03 U/g tissue in the vehicle-treated sham-occluded group (p less than 0.01). Carvedilol (1 mg/kg i.v., 15 min prior to coronary artery occlusion and at 3.5 h following reperfusion) reduced myocardial infarct size to 7.5 +/- 1.2% of the LV (n = 14; p less than 0.01) and attenuated the increase in MPO activity to 1.4 +/- 0.4 U/g tissue (p less than 0.05). A lower dose of carvedilol (i.e. 0.3 mg/kg i.v.) did not limit myocardial infarct size or the increase in MPO activity. In a model of permanent coronary artery occlusion, 24-hour survival was reduced from 85% in sham-occluded animals (n = 38) to 44% in the vehicle-treated MI group (n = 84; p less than 0.01). In comparison to the vehicle-treated MI group, carvedilol (0.3 mg/kg i.v., 15 min prior to coronary artery occlusion and 1 mg/kg 4 h after occlusion) improved survival by 55% (n = 64; p less than 0.05, compared to the vehicle-treated MI group), whereas the same dose of propranolol (n = 42) had no significant effect on survival. These results indicate that carvedilol reduces myocardial ischemia/reperfusion injury, and significantly improves survival in a permanent coronary artery occlusion model of myocardial infarction.

Effect of brief regional ischemia followed by reperfusion with or without superoxide dismutase and catalase administration on myocardial sarcoplasmic reticulum and contractile function

The effect of reperfusion with and without free radical scavengers on sarcoplasmic reticulum and contractile function was examined in a canine model of 15-minute coronary artery occlusion followed by reperfusion. Dogs were reperfused with (n = 13) or without (n = 16) superoxide dismutase and catalase or were killed at 15 minutes of ischemia (n = 17). Superoxide dismutase and catalase were administered as a bolus (20,000 and 12,500 U/kg, respectively) begining 1.25 minutes before reperfusion followed by infusion of 16,000 and 12,500 U/kg/hr, respectively. Sarcoplasmic reticulum function was evaluated from the rate of calcium uptake of unfractionated subepicardial, subendocardial, and transmural homogenates determined with and without ruthenium red to close the calcium release channel. Mechanical function was evaluated by means of sonomicrometry. Fifteen minutes of ischemia significantly ( p < 0.05) depressed the sarcoplasmic reticulum calcium uptake rate only in the subendocardium (from 25 ± 2 to 14 ± 1 nmol/min/mg without ruthenium red and from 60 ± 3 to 49 ± 3 nmol/min/mg with ruthenium red). Reperfusion with or without superoxide dismutase and catalase restored homogenate calcium uptake rates to normal, although severe contractile dysfunction persisted. This indicates that damage to the sarcoplasmic reticulum may not be the major cause of postreperfusion contractile dysfunction. Ischemia-reperfusion caused a decrease in systolic shortening from 19 ± 2% to 1 ± 2% with and from 18 ± 1% to 4 ± 1% without free radical scavengers ( p = NS between groups). Thus administration of superoxide dismutase and catalase beginning shortly before reperfusion had no effect on postreperfusion contractile dysfunction or sarcoplasmic reticulum function.

U74006F, a novel 21-aminosteroid, inhibits in vivo lipid peroxidation but fails to limit infarct size in a canine model of myocardial ischemia reperfusion

Peroxidation of membrane lipids has been suggested to play a role in the pathogenesis of myocardial ischemia/reperfusion injury. We therefore assessed the efficacy of U74006F, a potent in vitro vitamin E-like inhibitor of lipid peroxidation, in limiting infarct size in a canine model of transient coronary artery occlusion. Twenty dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 6 hours of reperfusion. U74006F or saline solution was administered continuously from 1 hour of occlusion to the end of the experiment. U74006F blunted any increase in production of conjugated dienes (an index of lipid peroxidation) at both 30 minutes (1.73 ± 0.16 mol/L × 10 −4 vs 2.62 ± 0.22 in control dogs, p < 0.05) and 6 hours (1.39 ± 0.22 vs 2.06 ± 0.18 in control dogs, p < 0.05) after reperfusion. Furthermore, 6 hours after reflow vitamin E levels tended to be lower than baseline values in control dogs and higher than baseline values in dogs treated with U74006F. However, analysis of infarct size indicated no statistically significant difference between the two groups when expressed either as a percentage of the left ventricle (10.4 ± 1.8% in U74006F vs 15.2 ± 2.4% in control dogs) or as a percentage of the area at risk (33.0 ± 5.5% in U74006F vs 37.8 ± 4.5% in control dogs). Although U74006F appeared to be a potent in vivo inhibitor of lipid peroxidation, it failed to limit infarct size after 2 hours of occlusion and 6 hours of reperfusion in this canine model.

Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.

1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity.

In vivo assessment of class III agents and their antiarrhythmic activity

AbstractA variety of in vivo models have been used to detect and develop novel antiarrhythmic/antifibrillatory agents. However, most of these models primarily have identified the class I agents that block sodium ion currents during the upstroke of the cardiac action potential. Since we are interested in identifying agents with a class III electrophysiologic action, i.e. delayed repolarization of the cardiac action potential, we have focused our drug discovery process on a specific, somewhat uncommon in vivo canine model. These studies have demonstrated that class I agents such as encainide, disopyramide, or U58797, a novel benzamide, are clearly identified in the ouabain‐toxic dog or the postinfarction (24–48 hr) conscious dog. In contrast, class III agents such as clofilium sotalol are identified in an acute canine model of coronary artery occlusion and reperfusion. This occlusion‐reperfusion model allows us to further identify the antiarrhythmic and antifibrillatroy actions of novel class III agents.

The Effects of L655,240, a Selective Thromboxane and Prostaglandin Endoperoxide Antagonist, on Ischemia- and Reperfusion-Induced Cardiac Arrhythmias

The purpose of this investigation was to provide a detailed analysis of the effects of the thromboxane antagonist L655,240 (0.3 mg/kg i.v.) on early ischemia- and reperfusion-induced arrhythmias in a canine model of coronary artery occlusion. In a dose that abolished the pulmonary response to U46619, L655,240 attenuated markedly the severity of those arrhythmias that resulted from reperfusion of the myocardium; survival from the combined occlusion-reperfusion insult was increased from 10% in control animals to 70% in dogs administered L655,240. Drug intervention did not significantly alter the total number of arrhythmias during the period of ischemia, but a detailed analysis of the different types of arrhythmia that occurred during this period showed that L655,240 significantly reduced those arrhythmias in phase 1a (0-10 min of occlusion) without affecting the later phase 1b arrhythmias. This was particularly shown in the marked reduction in the number of salvos (couplets and triplets) during this period. Neither those arrhythmias occurring later in the ischaemia period (phase 1b) nor the total number of single ectopics and salvos or the incidence and duration of ventricular tachycardia was modified by L655,240. These results reveal that thromboxane antagonism protects especially against reperfusion-induced ventricular fibrillation and against early (phase 1a) ischemia-induced arrhythmias, possibly implicating a role for thromboxane in the genesis of these cardiac rhythm disturbances.

Evaluation of Reperfusion Hyperemia With Myocardial Contrast Echocardiography

In this study we used myocardial contrast echocardiography to evaluate reperfusion hyperemia in an open-chest canine model of temporary coronary artery occlusion. Eight dogs had coronary occluders and electromagnetic flow probes on the left circumflex coronary artery. Aortic root injections of agitated sodium diatrizoate and saline solution were used for myocardial contrast. Data were collected at baseline (n = 16), during coronary occlusion (n = 18), immediately after coronary release (n = 18), and 5 minutes after coronary artery release (n = 12). Baseline coronary flow was 23.8 +/- 5.9 ml/min, decreasing to 0 ml/min during coronary occlusion. Immediately after coronary release flow was 96.6 +/- 41 ml/min (p less than 0.001 compared with baseline), and 5 minutes after coronary release flow was 68.2 +/- 27.9 ml/min (p less than 0.001 compared with baseline). The myocardial image intensity change after injection of contrast material was 74.25 +/- 30.6 ml/min at baseline and declined to 10.4 +/- 10.9 ml/min during coronary occlusion (p less than 0.001 compared with baseline). During reperfusion hyperemia image intensity change was 102.3 +/- 33.3 ml/min (p less than 0.001 compared with occlusion, p less than 0.02 compared with baseline, p less than 0.001 compared with remote regions). Considering all observations, myocardial image intensity change after contrast injection correlated positively with coronary flow (r = 0.67, p less than 0.001). Correlations within individual dogs ranged from r = 0.70 to 0.98. We conclude that image intensity change after aortic root injection of echocardiographic contrast correlates with coronary blood flow. Objective measurements of contrast intensity reflect increases in coronary flow associated with reactive hyperemia after coronary occlusion and release.

Effective separation of normal, acutely ischemic, and reperfused myocardium with P-31 MR spectroscopy.

The ability of phosphorus-31 magnetic resonance (MR) spectroscopy to accurately characterize myocardium as normal, ischemic, or reperfused but viable was examined in the canine model of acute coronary artery occlusion. P-31 MR measurements of in vivo myocardial pH, phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were made at baseline and for 6 hours after sustained coronary occlusion (ten animals) or coronary occlusion reperfused after 60 minutes (12 animals). Ten control animals were studied in parallel fashion, without coronary occlusion. Myocardial tissue characterization derived from the P-31 MR spectroscopy data by logistic regression analysis had an overall accuracy of 89%. Overall accuracy was unaffected by duration between coronary occlusion and P-31 MR study. Thus, metabolic data obtained with P-31 MR spectroscopy effectively separate normal, acutely ischemic, and reperfused but viable myocardium.

Effect of verapamil on postischemic “stunned” myocardium: Importance of the timing of treatment

Timely administration of verapamil has been shown to reduce indexes of ischemic injury in experimental models of prolonged coronary artery occlusion, yet its effect on contractile function of reversibly injured (that is, “stunned”) myocardium remains unknown. The objective of the present study was to determine whether verapamil—administered either 30 min before coronary artery occlusion, at the time of reperfusion or 30 min after reperfusion—could attenuate the regional contractile dysfunction and alterations in high energy phosphate metabolism produced by 15 min of transient coronary artery occlusion in anesthetized, open chest dogs.All treatment groups exhibited passive systolic bulging during occlusion. In the control dogs receiving saline solution, segment shortening in the previously ischemic tissue averaged only 31 ± 8% of normal baseline values after 3 h of reperfusion. In addition, endocardial adenosine triphosphate (ATP) stores were depleted by −8.7 ± 0.8 nmol/mg cardiac protein to 26.5 ± 1.1 nmol/mg protein, and endocardial creatine phosphate content increased by 9.6 ± 4.3 nmol/mg cardiac protein over normal values. Pretreatment with verapamil essentially ablated the phenomenon of postischemie stunning: segment shortening was restored to 115 ± 8% of normal after 3 h of reflow (p < 0.01 versus control), endocardial ATP stores were partially preserved (30.6 ± 1.2 nmol/mg protein; p < 0.05 versus control) and creatine phosphate overshoot was blunted (endocardial creatine phosphate content decreased by −5.6 ± 2.9 nmol/mg protein; p < 0.05 versus control).Verapamil administered at or after reperfusion also attenuated postischemic contractile dysfunction: segment shortening for both groups recovered to 65 ± 9% of baseline at 3 h after reperfusion (p < 0. 05 versus control). Verapamil given at or after repcrfusion had no beneficial effect, however, on high energy phosphate stores. Thus, even when treatment was “delayed,” that is, initiated at or after reperfusion, administration of verapamil significantly increased contractile function of the postischemic stunned myocardium.

The effect of digitalis on experimental myocardial infarct size and hemodynamics

Early studies suggested that digitalis exacerbated ischemia (ST segment data); however, there are no studies assessing the effect of this agent on anatomic infarct size with the use of a risk zone technique. Therefore, the aim of this study was to assess quantitatively whether digitalis extends necrosis in a model of coronary artery occlusion. Anesthetized dogs were subjected to 6-hour occlusion and, 30 minutes after occlusion, were randomized to digoxin (250 μg bolus/5 min intravenously, n = 9) or saline (n = 9) groups. At 6 hours, in vivo area at risk was determined by monastral blue dye injection and area of necrosis was assessed by tetrazolium staining. Heart rate and blood pressure were not different between groups before treatment or at 6 hours after occlusion. Left ventricular dPdt was similar in both groups before occlusion (2350 ± 293 mm Hg/sec digoxin vs 1839 ± 122 mm Hg/sec saline, p = NS), but after 6 hours of coronary occlusion, had increased in the digoxin group to 2583 ± 340 mm Hg/sec while it decreased in the saline group to 1517 ± 128 mm Hg/sec (p < 0.05 between groups at 6 hours), suggesting that digoxin increased contractility. Area at risk was 17.7 ± 1.3% of the left ventricle in the digoxin group and 20.9 ± 2.0% of the left ventricle in the saline group (p = NS). Area of necrosis, expressed as a percentage of area at risk, was 90.0 ± 3.5% in the digoxon group vs 88.6 ± 2.1% in the saline group (p = NS). Therefore, during acute myocardial infarction, digitalis confers a moderate increase in contractility without extending necrotic damage.

Temporary physiologic pacing in inferior wall acute myocardial infarction with right ventricular damage

Atrioventricular (AV) sequential pacing for chronic complete heart block is clearly superior in both the laboratory animal and in humans. 1–3 The importance of AV synchrony in patients with acute myocardial infarction (AMI) is not well appreciated. Some investigators suggest that AV synchrony is extremely important in patients with inferior AMI, right ventricular (RV) dysfunction and nonsinus bradyarrhythmias. 4–6 The predominantly used pacing mode in such patients is ventricular demand pacing with aggressive fluid loading. 7 A canine model of right coronary artery occlusion, septal damage and complete heart block conclusively showed that addition of AV synchrony improves mean arterial pressure 29% and cardiac output 34% . 8 This study compares the hemodynamics of ventricular demand and atrial or AV sequential pacing in 5 patients with inferior AMI, RV dysfunction and non-sinus bradyarrhythmias.

Effects of calcium antagonists on infarcting myocardium

Numerous studies have been conducted over the past 10 years on the effects of calcium antagonists on regional myocardial ischemia and infarct size. Verapamil, for example, reduced the degree of adenosine triphosphate degradation during 15 minutes of coronary occlusion followed by reperfusion in an anesthetized canine preparation. It also preserved the ultrastructural appearance of mitochondria in myocardium subjected to 1 hour of ischemia. Using an 8-hour permanent coronary artery occlusion model in which risk zone was assessed with radioactive microspheres and infarct size determined by tetrazolium staining, verapamil, administered 1 hour after occlusion, resulted in a modest decrease in infarct size. In a reperfusion model in which anesthetized dogs were subjected to 3 hours of coronary artery occlusion followed by 3 hours of reperfusion, verapamil decreased infarct size when it was administered during the period of ischemia, but failed to decrease infarct size when administered only during the reperfusion phase, i.e., after 3 hours of ischemia. Although verapamil is known to have negative inotropic effects, the newer calcium antagonist agent nisoldipine is less negatively inotropic, and might therefore be preferable in the situation of compromised hemodynamics. In a 6-hour permanent coronary artery occlusion model, nisoldipine decreased infarct size without decreasing left ventricular contractility. Most published reports support the concept that calcium antagonists decrease infarct size in models of experimental infarction. Of 4 major clinical studies, only 1 has shown that calcium antagonists are capable of reducing infarct size in man. However, in most of these studies, drug therapy commenced relatively late—4 or more hours after symptoms. In order for these drugs to demonstrate beneficial effects, the risk zone may have to be small and the degree of collateral flow adequate, the drug may have to be given very early or even before coronary occlusion (in a prophylactic fashion) and administration of the drug may have to be coupled to early coronary reperfusion.

A comparison of two methods for estimating the area at risk in experimental myocardial infarction

In a canine model of coronary artery occlusion and reperfusion, we assessed the amount of myocardium at risk for necrosis using both post-mortem perfusion staining with triphenyltetrazolium-chloride (TTC) and autoradiography following in vivo injection of 141Ce microspheres. Twenty-four transverse slices of 5 dog hearts were analyzed. In the same heart slice planimetry was performed both on the calibrated colour picture taken after TTC staining (A) and on the autoradiogram (B). The values for the area at risk, as determined by both methods, were very closely correlated and almost identical: A = 0.977 B + 31.4 mm2, r = 0.99, p less than 0.001. This is in contrast to an earlier report where a different autoradiographic technique was used. In short-term experimental models of coronary artery occlusion, autoradiography delineates an area at risk, matching very closely the area at risk obtained after TTC staining.

The effects of metoprolol and dazmegrel, alone and in combination, on arrhythmias induced by coronary artery occlusion in conscious rats.

The effects of metoprolol and the thromboxane synthetase inhibitor dazmegrel, alone and in combination, were examined in a model of coronary artery occlusion in conscious rats. In a dose (2 mg kg-1), intravenously, that resulted in a marked bradycardia (of 50-80 beats min -1) metoprolol did not influence the incidence or severity of the ventricular arrhythmias that occur in the first 20 min following occlusion, nor did it improve survival (assessed at both 20 min and 16 h). In a dose (5 mg kg-1), intravenously, that in another conscious rat model involving tissue hypoperfusion inhibited thromboxane production, dazmegrel also did not modify ischaemic arrhythmias or survival. In contrast, metoprolol and dazmegrel (2 mg kg-1 and 5 mg kg-1 i.v.) when given together prior to coronary artery occlusion, produced a significant reduction in mortality both at 20 min and 16 h (e.g. from 60-75% in the control, metoprolol alone and dazmegrel alone groups and only 25% in the combined-treatment group). This was due to a decrease in the incidence of terminal ventricular fibrillation. The results suggest that a combination of beta-adrenoceptor blocking drug with a drug that inhibits thromboxane synthesis may offer more protection against ischaemia-induced ventricular fibrillation than either drug used alone. They suggest a role for both catecholamines and thromboxane in the genesis of ischaemia-induced ventricular fibrillation.

Quantitation of perfused myocardial mass using Tl-201 and emission computed tomography.

We determined the accuracy with which perfused myocardial mass can be measured using thallium-201 and emission computed tomography in a canine model of acute coronary artery occlusion. Eight dogs underwent permanent coronary artery ligation. Transaxial emission tomography was performed using the Harvard multidetector scanning single photon emission computed tomography system beginning 10 minutes after the intravenous injection of 2 mCi of thallium-201 and 20 minutes after occlusion. After imaging, the animals were killed and the heart sectioned into 1–2-gram specimens for in vitro counting to determine the quantity of myocardium perfused greater than 75% of the maximum concentration in the left ventricle or septum. Perfusion defects were detected in five of the seven animals with perfusion defects ranging in size from 3.7 to 20.3 grams. One dog with a 1.2-g defect at the apex and another with a 6.5-g defect at the base of the left ventricle were not detected. In one of the operated dogs, no perfusion defect was detected by in vitro measurement or by imaging. Correlation between the measurement of perfused myocardial mass by emission tomography and by in vitro measurement was excellent when a variable threshold was used for defining the borders of the myocardium (for myocardium perfused ≥ 75% of maximum, r = 0.83, weight in vitro= 22.6 + 0.69 weight ECT; Sy.x = 7.3). The calculated weight of perfused myocardium was heavily dependent on the threshold when fixed values were used for defining the myocardial borders. Changes in threshold of 5% resulted in a decrease in apparent infarct size by more than 20% for thresholds ranging from 50% to 65%. Emission computed transaxial tomography with thallium-201 can be used to accurately determine the quantity of perfused myocardial mass; the accuracy of the technique is heavily dependent upon the definition of the myocardial border.

Effects of flurbiprofen in altering the size of myocardial infarcts in dogs: Reduction or delay?

Anti-inflammatory agents such as flurbiprofen have been claimed to reduce infarct size in a number of models of coronary artery occlusion. However, several of the studies are controversial and also do not allow the critical distinction between reducing and delaying injury. In the present study, a closed chest method of coronary occlusion was used to generate small areas of regional myocardial ischemia in dogs. The method involved cannulation of the coronary ostium by way of the carotid artery and coronary embolization with 2.5 mm diameter beads. Flurbiprofen (1 mg/kg) was given immediately after occlusion and thereafter every 6 hours. Groups of dogs were subjected to either 6 or 24 hours of elapsed ischemia, after which time the hearts were removed and sectioned. Frozen-tissue slices were stained with triphenyl tetrazolium in order to delineate infarct size. After staining the tissue slices were subjected to autoradiography in which microspheres given immediately after occlusion were visualized to delineate the perfusion bed served by the occluded coronary artery (zone at risk). Risk zone to infarct size ratios for drug treated and control animals revealed that flurbiprofen treatment had no effect upon infarct size as determined 24 hours after occlusion. Despite significant residual coronary flow in the ischemic area, virtually all of the risk zone deteriorated to necrotic tissue. By contrast, after 6 hours of elapsed ischemia, infarct size was considerably reduced in the flurbiprofen-treated group. With the proviso that the drug might have affected only the sensitivity to tetrazolium staining, these results indicate that in severe ischemia, flurbiprofen can greatly delay but not prevent tissue necrosis.