Occlusion Reperfusion Research Articles

Effects of AH-1058, a new antiarrhythmic drug, on experimental arrhythmias and cardiac membrane currents.

AH-1058 is a newly synthesized antiarrhythmic agent. We investigated the antiarrhythmic and electrophysiological effects of AH-1058 in experimental arrhythmia models and isolated cardiomyocytes. In the ouabain-induced arrhythmia model of the guinea pig, pretreatment with AH-1058 (0.1-0.3 mg/kg, i.v.) delayed the appearance of premature ventricular complex (PVC) and ventricular fibrillation (VF) induced by intravenous infusion of ouabain. However, disopyramide (10 mg/kg, i.v.) delayed only that of PVC, and verapamil (1 mg/kg, i.v.) failed to affect the ouabain-induced ventricular arrhythmias. In the reperfusion-induced arrhythmia model of the rat, in which 5-min coronary occlusion and 10-min reperfusion were produced, AH-1058 (0.1-0.3 mg/kg, i.v.) inhibited the incidence of both ventricular tachycardia (VT) and VF, whereas disopyramide (5 mg/kg, i.v.) inhibited only reperfusion-induced VF. On the other hand, a higher dose of AH-1058 (1 mg/kg, i.v.) did not affect the aconitine-induced arrhythmias in rats, which were inhibited by disopyramide (5 mg/kg, i.v.). We also confirmed oral activity of AH-1058 in the reperfusion-induced arrhythmia model of the rat. AH-1058, at doses of 2-4 mg/kg, dose-dependently inhibited VT and VF. Electrophysiological experiments with patch-clamp techniques revealed that AH-1058 potently suppressed the L-type Ca2+ currents in isolated cardiomyocytes of the guinea pig. These results suggest that AH-1058 is a potent antiarrhythmic drug having a Ca2+ channel-blocking action. The antiarrhythmic profile of AH-1058 is different from that of disopyramide and verapamil.

Myocardial Perfusion Abnormalities by Intravenous Administration of the Contrast Agent NC100100 in an Experimental Model of Coronary Artery Thrombosis and Reperfusion.

The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the study of myocardial perfusion. In eight anesthetized open-chest dogs, this agent was injected intravenously under baseline conditions, during acute coronary thrombosis, and after reperfusion, using both fundamental (FI) and harmonic (HI) imaging, both continuous and intermittent imaging, and both ultrasound (US) and integrated backscatter (IBS) imaging. Contrast injections did not modify the hemodynamic parameters. With all imaging modalities, myocardial contrast enhancement (MCE) was higher with intermittent than with continuous imaging (134 vs 82 gray level/pixel using FI, P = 0.02; 62 vs 32 acoustic units using US HI, P = 0.02; and 52 vs 12 dB using IBS, P = 0.05). MCE equally increased using either US or IBS imaging. The accuracy of MCE in detecting perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis was very good (sensitivity and specificity = 93% and 95% and 89% and 93%, respectively). The extent of myocardial perfusion defects by echo contrast showed a closer correlation with microspheres using HI (r = 0.82) than FI (r = 0.53). Thus, the intravenous administration of NC100100 during intermittent HI allows myocardial perfusion abnormalities to be accurately detected during acute myocardial infarction.

PentaLyte decreases lung injury after aortic occlusion-reperfusion.

Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO, an oxidant-generating enzyme), released from reperfusing liver and intestines, mediating a significant component of this injury. Since pentastarch administration decreases intestinal reperfusion injury, we determined whether resuscitation with PentaLyte (a pentastarch-containing solution) would decrease hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung injury after aortic occlusion- reperfusion. Aortic occlusion was established in rabbits for 40 min, and was followed by 3 h of reperfusion, during which either PentaLyte or lactated Ringer's solution-based resuscitation was administered. Sham-operated animals served as controls. Hepatoenteric reperfusion injury, as manifested by release of the enzyme aspartate aminotransferase and decreased gastric intramucosal pH, was significantly (p < 0.0167) attenuated by PentaLyte administration after aortic occlusion-reperfusion, as compared with its occurrence in animals given lactated Ringer's solution. The release of XO after aortic occlusion-reperfusion was 4-fold smaller after PentaLyte administration than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte administration following aortic occlusion-reperfusion than after administration of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary injury is significantly decreased by concomitant PentaLyte-mediated reduction of hepatoenteric reperfusion injury and XO release.

Differences in Heart Rate Variability in the Acute Phase of First and Second Attacks of Myocardial Infarction

The purpose of the study was to examine the differences between first and second myocardial infarctions with respect to improvement in measures of heart rate variability (HRV). The study population comprised 48 non-diabetic patients with acute myocardial infarction (AMI), and with angiographically documented coronary artery occlusion and successful reperfusion. The subjects were grouped as 35 cases with a first AMI attack and 13 with their second AMI. Two weeks after the onset of infarction, indices of HRV were higher in first infarction cases than in second infarction cases. In the latter, there were no significant increases in HRV indices from day of onset to 2 weeks later, nor were there any significant changes in left ventricular ejection fraction (LVEF) from onset to 3 weeks later. All patients studied had a patent infarct-related artery 3 weeks later. We found sustained low values of HRV after a second AMI. Different risk stratification may be needed between uncomplicated first AMI and second AMI cases.

Antiarrhythmic Effect of Repeated Coronary Occlusion During Balloon Angioplasty

Objectives. The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty protect against ischemia-induced ventricular ectopy.Background. Most sudden cardiac deaths are caused by fatal ventricular arrhythmias precipitated by early myocardial ischemia of acute coronary occlusion. In animals, a preceding 3- to 5-min coronary occlusion protects against malignant ventricular arrhythmias during a subsequent prolonged coronary occlusion. Whether such an antiarrhythmic effect caused by ischemic preconditioning occurs in humans is not known.Methods. To assess the effects of a preceding, brief vessel occlusion–reperfusion cycle on the occurrence of ventricular ectopy, continuous electrocardiographic, heart rate and blood pressure recordings were performed in 156 patients before and during two identical balloon occlusions of a coronary artery (mean 111 s) separated by a 5-min equilibration period.Results. The occluded vessel was the left anterior descending coronary artery in 94 patients, the left circumflex branch in 29 patients and the right coronary artery in 33 patients. Balloon occlusion of a coronary artery caused ventricular ectopy in 24 patients. The incidence of ventricular ectopy was higher during the first occlusion than during the second occlusion (21 patients [13.5%] vs. 11 patients [7%], p = 0.02). In 13 patients, ventricular ectopy was observed only during the first occlusion; in 8 patients during both occlusions; and in 3 patients only during the second occlusion. Bigeminal or repetitive ectopic beats were observed in eight patients during the first coronary occlusion and in four patients during the second occlusion. Atrial premature beats occurred during the first occlusion in three patients, but in none of the patients during the second occlusion. The 24 patients with ventricular ectopy during coronary occlusion had milder stenosis than the rest of the patients (mean [±SD] 74 ± 12% vs. 81 ± 12%, p = 0.01). The 13 patients with ventricular ectopy only during the first occlusion did not, however, differ significantly with respect to any clinical or angiographic features from the rest of the patients with ventricular ectopy. There were no significant differences in the signs of myocardial ischemia or hemodynamic variables between the sequential occlusions.Conclusions. A preceding, short vessel occlusion–reperfusion cycle seems to increase the electrical stability of ischemic myocardium.(J Am Coll Cardiol 1997;29:1035–8)© 1997 by the American College of Cardiology

Prolonged coronary artery occlusion—reperfusion sequences reduce myocardial free radical production: An electron paramagnetic resonance study

Our purpose was to determine whether prolonged myocardial ischemia attenuates free radical production after early reperfusion. Twenty-two mongrel dogs underwent left anterior descending coronary artery occlusion for 20, 40, or 60 minutes followed by 30 minutes of reperfusion. Electron paramagnetic resonance spectroscopy was used to measure ascorbate free radical in the coronary vein effluent. Ascorbate free radical production during reperfusion was significantly ( p < 0.05) reduced in the dogs undergoing 60 minutes of coronary artery occlusion compared with the dogs undergoing 40 and 20 minutes of occlusion. We conclude that prolonged myocardial ischemia results in less free radical production on reperfusion than do shorter periods of ischemia followed by reperfusion.

Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 +/- 3.38% to 138.1 +/- 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 +/- 1.8% to 55.7 +/- 1.4%) reaching a peak (64.5 +/- 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 +/- 3.4% to 61.0 +/- 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 +/- 2.2% to 46.7 +/- 1.0%), followed by an increase during late reperfusion (59.2 +/- 1.5%). Contrarily, protein C increased during occlusion and early reperfusion (from 44.7 +/- 2.6% to 79.4 +/- 2.4%), but declined to 49.6 +/- 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.

Preconditioning is not abolished by the delayed rectifier K+ blocker dofetilide.

ATP-sensitive potassium channels are thought to play an important role in preconditioning. possibly due to shortening of the action potential duration (APD). The purpose of this study was to determine the effect of the class III antiarrhythmic agent dofetilide on preconditioning at a dose that abolishes APD shortening during ischemia A pilot study was performed to find a dose of dofetilide that would abolish the APD shortening effect of preconditioning Anesthetized dogs were subjected to 5-min coronary occlusion (or sham) and 10-min reperfusion followed by 60-min coronary occlusion. Monophasic action potentials were recorded periodically throughout the experiment. Significant APD shortening was observed during the 5- and 60-min ischemic periods, although preconditioning did not further enhance APD shortening during the prolonged ischemia. Dofetilide (1 mg/kg + 0.01 mg.kg-1.h-1 iv) abolished the APD shortening effect of ischemia. The effect of this dose of dofetilide on the protective action of preconditioning was then determined. Preconditioning significantly reduced infarct size expressed as a percentage of the area at risk compared with nonpreconditioned hearts. Dofetilide had no effect on infarct size when given to nonpreconditioned hearts. In addition, dofetilide did not alter the protective effect of preconditioning. No differences in collateral blood flow during ischemia were observed for any group. This study shows that the class III antiarrhythmic agent dofetilide does not abolish preconditioning and that the cardioprotective effect of preconditioning is independent of APD shortening below baseline values.

MR Imaging of Gadolinium-DTPA-BMA-Enhanced Reperfused and Nonreperfused Porcine Myocardial Infarction

To investigate whether Gd-DTPA-BMA-enhanced MR imaging permits differentiation between reperfused and nonreperfused myocardial infarction, myocardial infarction was induced in 12 domestic pigs. In 6 pigs, Gd-DTPA-BMA, 0.3 mmol/kg b.w. was administered i.v. 60 min after the occlusion. In 6 other pigs, the infarctions were reperfused 80 min after the occlusion, followed by injection of Gd-DTPA-BMA after 20 min of reperfusion. Radiolabeled microspheres were used to confirm zero-flow during the occlusion period and reperfusion in the infarcted myocardium. All pigs were killed 20 min after injection of contrast medium, and the hearts were excised and imaged with MR. The Gd concentration was measured in infarcted and nonischemic myocardium by ICP-AES. In the reperfused hearts, the infarctions were strongly highlighted, corresponding to a 5-fold higher Gd concentration in infarcted vis-à-vis nonischemic myocardium. In the hearts subjected to occlusion without reperfusion, there was only a rim of enhancement in the peripheral part of the infarctions.

938-56 Myocardial Contrast Echocardiography: What is the Meaning of Regional Perfusion Abnormalities After Release of Temporary Coronary Occlusions?

Myocardial contrast echocardiography (MCE) has been used to demonstrate regional perfusion abnormalities (RPA) in the presence of coronary occlusions, severe coronary stenosis, and myocardial infarctions (MI). We have observed such abnormalities following the release of a temporary occlusion in the absence of MI. To further define this, we studied 54 open-chest dogs. Temporary coronary occlusions were performed (Group A = 15 minutes; Group B = 30 to 360 minutes), followed by release of the occlusions and by the administration of dobutamine IV (10 μg/kg/min). Myocardial contrast echocardiography was performed with aortic root injections of sonicated albumin (Albunex ® ) during occlusion and following reperfusion with and without dobutamine. Postmortem TTC staining (+ stain = viable myocardiuml was used to determine the presence/absence of MI All Group A dogs (n = 14) showed no evidence of MI. In Group B (n = 40), 14 dogs showed no evidence of MI, whereas the other 26 did (12 papillary muscle, 7 subendocardial, and 7 transmural). The presence of RPA in all groups is shown below: Occlusion Reperfusion Reperfusion+ Dobutamine Group A 13/14 2/14 2/14 Group B 35/40 17/39 20/39 • No MI 11/14 7/13 8/13 • Papillary MI 10/12 3/12 5/12 • Subendocardial MI 7/7 3/7 3/7 • Transmural MI 7/7 4/7 4/7 In conclusion, the presence of a RPA following the release of coronary occlusions most likely indicates abnormal coronary reserve rather than the presence of myocardial necrosis.

Effects of BMY21190, an Inhibitor of cAMP Phosphodiesterase, on Infarct Size and Myeloperoxidase Activity in the Ischemic Myocardium of a Canine Occlusion-Reperf usion Model

This study was performed to assess the effect of BMY21190, an inhibitor of cAMP phosphodiesterase, on infarct size using a canine ischemic model that underwent a 90-min occlusion and a 6-hour reperfusion of the left coronary artery. The infarct zone/area at risk of the BMY21190 group was significantly smaller than that of the vehicle group (36.1 +/- 7.8%; 62.4 +/- 4.3%, respectively; p < 0.05). Myeloperoxidase activity, an indicator of neutrophil infiltration, was significantly correlated to infarct size (r = 0.6893, p < 0.02). Myeloperoxidase activity (0.14 +/- 0.07 U/100 mg tissues) measured in the area at risk from hearts of the BMY21190-treated group was significantly lower than that of the vehicle-treated tissue (0.40 +/- 0.08 U/100 mg tissue, p < 0.05). It is suggested that BMY21190 reduces infarct size through the inhibition of neutrophil infiltration in the canine model.

Nucleoside transport inhibitors enhance the infarct size-limiting effect of ischemic preconditioning.

We recently observed that dipyridamole pretreatment significantly enhanced the infarct size (IS)-limiting effect of preconditioning (PC), which was attenuated by adenosine receptor antagonist. This potentiation of PC was interpreted to result from inhibition of nucleoside transport by dipyridamole, but contribution of other pharmacologic actions of dipyridamole could not be excluded. To confirm that inhibition of nucleoside transport leads to PC enhancement, we assessed alteration of mild PC by two different nucleoside transport inhibitors, dilazep and R75231, which, unlike dipyridamole, lack action on phosphodiesterase (PDE) and prostacyclin. Myocardial infarction was induced in rabbits by 30-min coronary occlusion and 72-h reperfusion. IS and area at risk (AAR) were determined by histology and fluorescent particles, respectively. Rabbits either were untreated or received dilazep (0.34 mg/kg intravenously, i.v.) or R75231 (0.05 mg/kg i.v.) before coronary occlusion. In other groups of rabbits, PC was conducted with 2-min ischemia and 5-min reperfusion with or without injection of the nucleoside transport inhibitor (0.34 or 0.10 mg/kg dilazep or 0.05 mg/kg of R75231) before PC. IS expressed as percentage of AAR (%IS/AAR) was 43.9 +/- 2.3% (SE) in untreated controls; dilazep (0.34 mg/kg) and R75231 alone did not modify IS (%IS/AAR = 50.6 +/- 4.7 and 42.7 +/- 11.9%, respectively). PC tended to reduce IS (%IS/AAR = 33.3 +/- 3.5%), but the combination of dilazep or R75231 with PC significantly limited %IS/AAR (%IS/AAR = 22.5 +/- 5.0% after low-dose dilazep plus PC, 27.6 +/- 4.9% after high-dose dilazep plus PC, and 19.9 +/- 3.6%, after R75231 plus PC).(ABSTRACT TRUNCATED AT 250 WORDS)

Dispersion of ventricular refractoriness in experimental myocardial infarction: effect of sotalol.

Dispersion of refractoriness may contribute to the propensity for reentrant arrhythmias. This study was performed to assess the effect of sotalol on the dispersion of refractoriness in experimental myocardial infarction. In 9 mongrel dogs, 14 days after induction of myocardial infarction by an occlusion reperfusion technique, programmed ventricular stimulation and epicardial mapping were performed before and during (3 mg/kg + 0.5 mg/kg per hour) sotalol administration. To assess the spatial distribution of refractoriness, ventricular fibrillation (VF) intervals were analyzed. The rationale for this method is that, during VF, when multiple reentrant wavelets are present, cells are excited as soon as they recover from previous activation. The coefficient of variation (standard deviation x 100) served as an index of spatial distribution of refractoriness. VF was induced before sotalol in 7 dogs and in 5 of 7 during sotalol administration. The mean value of the index VF intervals decreased from 19.8 +/- 2.3 at baseline to 15.8 +/- 2.6 during sotalol (P = 0.011), indicating a more homogeneous distribution of refractoriness. Thus, the antiarrhythmic effects of sotalol may be mediated by its action on the dispersion of refractoriness.

Effect of E-4031, a class III antiarrhythmic agent, on experimental infarct size in a canine model of myocardial ischemia-reperfusion injury.

Class III antiarrhythmic agents such as E-4031 have demonstrated efficacy in preventing and/or terminating malignant ventricular arrhythmias in experimental models. It has recently been suggested that Class III agents might possess additional antiischemic properties that may translate into a reduction in the frequency or severity of arrhythmia. The potential for the Class III antiarrhythmic agent E-4031 to limit the extent of developing myocardial infarction was assessed in a barbiturate-anesthetized canine model of ischemic-reperfusion injury. Untreated control (n = 13) and E-4031-treated animals (n = 8, 300 micrograms/kg, i.v., immediately preceding myocardial ischemia) were subjected to a 90-min period of left circumflex coronary artery occlusion followed by a 5-h period of reperfusion. The predominant hemodynamic effect displayed by E-4031 was a reduction in heart rate throughout the period of coronary artery occlusion and early reperfusion. Areas at risk of infarction, expressed as percentages of left ventricle, were equivalent in the control and E-4031 treatment groups (38.5 +/- 1.0 and 34.6 +/- 1.9%, respectively). Posterolateral myocardial infarct sizes, expressed either as percentages of risk area or of total left ventricle, were reduced slightly but not significantly in the E-4031 treatment group compared to the control group (35.2 +/- 5.6 and 45.4 +/- 3.0% of risk area, respectively; 12.7 +/- 2.4 and 17.6 +/- 1.4% of left ventricle, respectively). Regional myocardial blood flows in nonischemic and central ischemic zones of myocardium did not differ significantly between the control and E-4031 treatment groups before and during the period of coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of α-Tocopherol (Vitamin E) in a Porcine Model of Stunned Myocardium

Oxygen free radicals have been suggested to cause the myocardial damage resulting in the prolonged contractile depression following brief periods of regional ischemia. In pigs, we infused the natural antioxidant alpha-tocopherol as its water-soluble acetate [0.3 g/kg intravenously (i.v.), n = 6] three times during 1 week, prior to thoracotomy, 8-min distal left anterior coronary artery (LAD) occlusion and 90-min reperfusion. Plasma levels of alpha-tocopherol [high-performance liquid chromatography (HPLC)] on the experimental day were 148.91 +/- 21.47 micrograms/ml as compared to preinfusion control of 0.51 +/- 0.14 micrograms/ml. Myocardial levels of alpha-tocopherol were elevated to 93.15 +/- 14.78 micrograms/g as compared to 4.08 +/- 0.60 microgram/g in the control group (n = 6). Malondialdehyde levels in ischemic-reperfused myocardium of the treatment group were insignificantly lower (441.96 +/- 59.55 nmol/g) as compared to the control group (500.9 +/- 72.72 nmol/g). Heart rate was significantly higher in the treatment group by the end of the experiments (135 +/- 10 vs. 105 +/- 4 beats/min, p less than 0.01). Regional segment shortening (SS, sonomicrometry) became normal within 1 min of reperfusion in both the treatment and the control group. During the following 10 min, SS decreased to 52 +/- 6% of preischemic control in the alpha-tocopherol group and to 54 +/- 7% in the control group (NS). SS remained at these depressed values throughout the reperfusion period. Pretreatment with the antioxidant alpha-tocopherol resulted in a tendency to lower lipid peroxidation products but did not prevent development of contractile depression in reversibly ischemic reperfused myocardium.

A simple technique for occlusion and reperfusion of coronary artery in conscious rats.

A simple technique to occlude and reperfuse the coronary artery of conscious rats, which can freely move about, has been developed. After rats had been anesthetized and thoracotomized, the left coronary artery (LCA) was tied loosely (an occluder), and two other sutures (releasers) were tied to the knot so that it could be loosened to allow for reperfusion. Acute LCA occlusion (0.5 h) with reperfusion (3.5 h) or permanent LCA occlusion (4 h) was done to different groups of rats. Almost the same infarct size had formed in rats of either group (approximately 60% of the left ventricular weight); however, when arterial blood flow was restored (occlusion with reperfusion group), scattered bleeding and cell damage occurred. Plasma concentration of creatine phosphokinase (CPK) (4-h permanent occlusion group) increased by approximately 400%, which depended on infarct size (r = 0.89, P less than 0.001); whereas CPK concentrations in the occlusion with reperfusion group were significantly low. After permanent LCA occlusion or reperfusion occlusion, approximately 40% of the rats died of ventricular fibrillation within 4 h, and most of them died within the first 30 min. In the occlusion with reperfusion group, an additional number died as a result of reperfusion. Electromyocardiograms clearly reflected the regional ischemia as evidenced by an increase of 2-2.5 mV in the S-T segment; the phenomenon disappeared after reperfusion. In conclusion, our simple technique could be used to study the biochemistry, electrophysiology, and morphology of a conscious animal that has undergone occlusion with reperfusion of the LCA.

Effect of left ventricular assist device (LVAD) on myocardial pH change after regional coronary occlusion.

To evaluate the effect of an assist pump on the metabolic viability of the ischemic myocardium, myocardial pH was continuously monitored using an ion-sensitive field-effect transistor (ISFET) pH sensor in 14 dogs after coronary occlusion. In seven dogs (control group), coronary occlusion (10-20 min) and successive reperfusion (30-60 min) were performed several times. In seven dogs [left ventricular assist device (LVAD) group], the LVAD was implanted between the left atrium and the aorta. Occlusion and reperfusion were performed first with the pump on and then with the pump off. In both groups, myocardial pH fell after occlusion, and increased after reperfusion. In the control group, the fall rate of pH in the later coronary occlusion decreased to 66 +/- 7% (mean +/- SEM) of that in the previous occlusion. Contrarily, in the LVAD group, the fall rate under LVAD-off increased to 174 +/- 32% of that under the preceding LVAD-on. This indicates that progressive cellular damage occurred in the control group, while the myocardium was preserved by the assist pump in the LVAD group. LVAD is effective for preserving the metabolic viability of the ischemic myocardium.

Salvage of ischemic rabbit ear by BW-755C and steroids, but not by indomethacin

The effects of anti-inflammatory steroids and BW-755C (both of which inhibit the formation of prostaglandins and leukotrienes were studied in ischemia-induced edema and necrosis of the rabbit ear utilizing an occlusion reperfusion model. The results were compared with cyclooxygenase inhibitors which selectively block the synthesis of prostaglandins without affecting leukotriene production. Significant inhibition of the progression of necrosis was observed with both methyl prednisolone and BW-755C. The cyclooxygenase inhibitors, naproxen and low-dose indomethacin had no effect on the progression of ear necrosis. By contrast, high-dose indomethacin significantly inhibited edema but accelerated the progression of necrosis.

Importance of retrograde coronary flow in the prediction of experimental myocardial infarct size.

The relationship between myocardial infarct size (measured by a histochemical stain) and coronary collateral blood flow (measured via retrograde flow and by use of radioactive microspheres) was studied in anesthetized dogs with high, moderate and low retrograde flows undergoing a 2-hour occlusion and 30-min reperfusion of the left anterior descending coronary artery. The results demonstrate that experimental myocardial infarct size is closely related to native coronary collateral blood flow, and the large variability in collateral perfusion amongst dogs is a source of variability in the mass of myocardium undergoing irreversible damage following acute coronary occlusion. Results also demonstrate that the variability in experimental infarct size can be reduced and ultimate infarct size predicted prior to irreversible tissue injury by initial measurement of retrograde coronary blood flow.

Platelet Depletion and Infarct Size in an Occlusion Reperfusion Model of Myocardial Ischemia in Anesthetized Dogs

The formation of platelet aggregates and release of platelet-derived vasoactive mediators have been suggested to aggravate ischemic myocardium. The contribution of platelets to myocardial damage induced by 90-min occlusion and 5-h reperfusion in chloralose-anesthetized dogs was assessed after depletion of platelets with specific antidog platelet antiserum. Dogs treated with antiplatelet antiserum showed greater than 90% reduction in circulating platelets and serum TxB2 levels, but showed no reduction in infarct size (58 +/- 3 vs. 51 +/- 3% of risk area for control and thrombocytopenic dogs, respectively). Platelet depletion had no hemodynamic effect during the occlusion or reperfusion phases, nor reduced the incidence of arrhythmias. These results indicate that platelet aggregates or platelet-derived mediators do not contribute directly to the extent of damage in this occlusion-reperfusion model of myocardial ischemia.