Myocardial thallium-201 kinetics and regional flow alterations with 3 hours of coronary occlusion and either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis

Myocardial thallium-201 kinetics and regional blood flow alterations were examined in a canine model using 3 hours of coronary occlusion and different methods of reperfusion. Group I comprised 10 dogs undergoing a 3 hour left anterior descending artery occlusion and no reperfusion. Group II comprised seven dogs undergoing 3 hours of left anterior descending artery occlusion and rapid reperfusion through a totally patent vessel. Group III comprised 10 dogs undergoing 3 hours of left anterior descending artery occlusion and slow reperfusion through a residual stenosis. All dogs received 1.5 mCi of thallium-201 after 40 minutes of coronary occlusion. During occlusion and 2 hours of reperfusion, serial hemodynamic, blood flow and myocardial thallium-201 activity measurements were made. The relative thallium-201 gradient (normal zone minus ischemic zone activity when initial normal activity is expressed as 100%) during left anterior descending coronary occlusion was similar in all groups. Group I, 87 +/- 3%; Group II, 78 +/- 6%; Group III, 83 +/- 6% (p = NS). After 2 hours of either method of reperfusion, the final relative gradient had decreased to a similar level (Group II, 51 +/- 9%; Group III, 42 +/- 6%). These values were not significantly different from the final relative thallium-201 gradient seen in dogs undergoing a sustained 3 hour occlusion (Group I, 55 +/- 5%). After 2 hours of reperfusion, both methods of reflow were associated with similar degrees of "no reflow." Transmural flows in the central ischemic zone were 89 +/- 10% of normal in Group II and 71 +/- 6% of normal in Group III after reperfusion, with both flows substantially higher than the relative thallium-201 activities in these dogs. Infarct size (percent of left ventricle) determined with triphenyltetrazolium chloride was similar in all groups (Group I, 24 +/- 4%; Group II, 29 +/- 4%; Group III, 25 +/- 4%). Thus, in this experimental canine model, 3 hours of coronary occlusion followed by either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis resulted in little delayed thallium-201 redistribution or myocardial salvage as assessed histologically, despite significant recovery of regional flow.     

Anterior transmural myocardial infarction: effects of surgical coronary reperfusion on global and regional left ventricular function

Global and regional left ventricular function were assessed before and after surgical coronary reperfusion in 54 patients surviving anterior transmural myocardial infarction. Two groups were identified. Group I (n = 34) was treated within 4.8 +/- 0.7 (mean +/- standard deviation) hours of onset of symptoms of anterior transmural myocardial infarction, and Group II (n = 20) was treated 9.2 +/- 4.8 hours from the onset of symptoms (p less than 0.01). On study entry, the two groups were similar in all characteristics except global left ventricular ejection fraction (48 +/- 9 versus 42 +/- 13%, p less than 0.05). Regional ejection fraction was obtained by computer-assisted planimetry from ventriculographic tracings at end-systole and end-diastole. The anterior wall was divided into four equal segments from the apex (area 1) to base (area 4). Areas 2 and 3 defined the midportion of the anterior wall of the left ventricle. This yielded four fractional changes expressed as ejection fraction in percent. Global and regional ejection fractions (from apex to base) of the anterior wall significantly improved in Group I (from 48 +/- 9 to 55 +/- 11%; 7 +/- 17 to 18 +/- 20%; 12 +/- 14 to 25 +/- 18%; 25 +/- 15 to 38 +/- 17%; and 39 +/- 13 to 41 +/- 12%) (p less than 0.05, except for the basal area), but only to a minor degree in Group II (from 42 +/- 13 to 45 +/- 16%; 9 +/- 10 to 13 +/- 15%; 10 +/- 10 to 17 +/- 10%; 27 +/- 16 to 32 +/- 14%; and 37 +/- 10 to 36 +/- 13%) (all p values were not significant [NS] except for region 2). These data suggest significant enhancement of global function and regional wall motion in selected patients if surgical reperfusion is performed within 6 hours from the onset of symptoms of anterior infarction. Little improvement can be expected when the procedure is instituted later than 6 hours from peak symptoms, although improvement in some patients occurs if adequate collateral perfusion or nontotal left anterior descending coronary occlusion is present. In spite of functional improvements, some contractile deficit persisted throughout the period studied even when successful reperfusion was achieved early during evolving anterior transmural myocardial infarction.     

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size limitation in conscious dogs

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size was studied in four groups of conscious dogs undergoing acute left anterior descending coronary artery occlusion. Group I received placebo for 48 hours before and for 24 hours after occlusion; group II received placebo before and nisoldipine (0.3 mg/kg orally every 6 hours) after occlusion; group III received nisoldipine before and placebo after occlusion; and group IV received nisoldipine before and after occlusion. Infarct size was quantified with the tetrazolium red staining technique. Infarcted ventricular mass was 24.5 +/- 6.6% (mean +/- SD) for group I (control), 21.4 +/- 4.4% for group II (p = NS against control), 13.9 +/- 4.5% for group III (p less than 0.05), and 14.1 +/- 4.0% for group IV (p less than 0.05). Post occlusion sudden death was 30% in non-pretreated dogs and 0% in pretreated dogs (p less than 0.001). We conclude that prophylactic oral treatment with nisoldipine decreases infarct size and lowers the incidence of sudden death in conscious dogs undergoing acute coronary occlusion.     

Experimental study on myocardial salvage by coronary thrombolysis and mechanical recanalization

Salvage of the ischemic myocardium by coronary thrombolysis and mechanical recanalization (simulated angioplasty) was studied in a canine experimental model of acute myocardial infarction induced by coronary occlusive thrombus at the left anterior descending coronary artery. Forty-four open-chest dogs divided into three groups were studied. Group I (n = 15, control group) was observed for 6 hours following the onset of infarct. In group II (n = 14, thrombolysis group), thrombolysis was obtained by intravenous administration of urokinase 2 hours after the onset of infarct. In group III (n = 15, mechanical recanalization group), simulated angioplasty was performed 2 hours after infarct. Coronary reperfusion was continued for 4 hours in groups II and III. The areas of left ventricular risk and infarct were measured by double staining methods with Evans blue dye and triphenyl tetrazolium hydrochloride. There were no significant differences in control blood flow and risk area in the three groups. Myocardial infarct area/risk area was 65 +/- 3% in group I, 45 +/- 1% in group II, and 35 +/- 2% in group III (group I vs II, p less than 0.001; group II vs III, p less than 0.001). Restored coronary blood flow in the left anterior descending artery was 8 +/- 1 ml/min in group II and 14 +/- 1 ml/min in group III (p less than 0.001). The data suggest that coronary mechanical recanalization is more effective than thrombolysis in salvaging the ischemic myocardium in the early phase of myocardial infarction, most probably because coronary blood flow is better restored by mechanical recanalization.     

Value of percutaneous transluminal coronary angioplasty after unsuccessful intravenous streptokinase therapy in acute myocardial infarction

The effect of sequential high-dose intravenous streptokinase (SK) (1.5 million units) followed by emergency percutaneous transluminal coronary angioplasty (PTCA) on preserving left ventricular function was assessed prospectively in 34 patients with acute myocardial infarction (AMI). Intravenous SK therapy was initiated 2.6 +/- 1.3 hours (mean +/- standard deviation) after the onset of chest pain. Urgent coronary angiography showed persistent total occlusion in 13 patients, significant diameter stenosis (70 to 99%) in 18 patients and a widely patent artery (less than 50% stenosis) in 3 patients. Emergency PTCA was performed in 29 patients 5.0 +/- 2.1 hours after symptom onset. Successful recanalization was achieved in 33 of the 34 patients (97%) treated with sequential therapy. Repeat contrast ventriculograms recorded 7 to 10 days after intervention in 23 patients showed that the left ventricular ejection fraction increased from 53 +/- 12% to 59 +/- 13% (area-length method, p less than 0.002). Regional wall motion of the infarcted segments improved from -2.7 +/- 1.1 to -1.5 +/- 1.7 SD/chord (centerline method, p less than 0.003). In the subgroup of patients with an occluded artery on initial angiography (group A, n = 10), both global left ventricular ejection fraction (49 +/- 12% vs 59 +/- 12%, p less than 0.002) and regional wall motion (-3.2 +/- 1.0 vs -1.9 +/- 1.7 SD/chord, p less than 0.002) improved significantly. In contrast, no significant improvement was seen in patients with a patent artery on initial angiography (n = 13). Thus, sequential intravenous SK and emergency PTCA is efficacious in achieving coronary reperfusion and in improving both global and regional left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatty acid analogue accumulation: a marker of myocyte viability in ischemic-reperfused myocardium

A 3-methyl substituted radioiodinated long chain fatty acid analogue was evaluated as an agent for the noninvasive detection of altered fatty acid uptake in reperfused, postischemic myocardium. This iodinated fatty acid analogue, 15-(para-iodophenyl)-3-methyl pentadecanoic acid, was given intravenously at 3 hours of reperfusion following 15 minutes (Group 1, n = 5 dogs) or 60 minutes (Group 2, n = 5 dogs) of left anterior descending coronary artery occlusion. Myocardial blood flow (MBF) was measured during occlusion and reperfusion with radiolabeled microspheres administered via the left atrium. Paired ultrasonic subendocardial crystals were placed in the ischemic perfusion bed to assess regional left ventricular systolic function at baseline, during ischemia and reperfusion. Electron microscopic analysis and staining with triphenyltetrazolium chloride (TTC) was performed. Groups 1 and 2 dogs had similar (p = NS) myocardial blood flows during occlusion. TTC positive 1 g endocardial segments from Group 1 (n = 98) and Group 2 (n = 71) had 37% greater fatty acid analogue activity (0.26 +/- 0.04 vs. 0.19 +/- 0.09 percent injected dose per gram; p less than 0.05) compared with TTC negative segments from Group 2 dogs (n = 37). When fatty acid analogue activity was related to near simultaneous reperfusion blood flow, this ratio was 27% greater (p less than 0.05) in TTC positive segments (0.38 +/- 0.1) compared with TTC negative (0.30 +/- 0.16) segments, and 9% greater than normal (0.35 +/- 0.09; p less than 0.05). While ischemic regions from both Groups 1 and 2 dogs became similarly dyskinetic during occlusion (systolic shortening, -11 +/- 6 vs. -11 +/- 2%; p = NS), TTC negative segments remained akinetic (= 1 +/- 7%) at 3 hours of reperfusion while TTC positive zones had recovered partial systolic function (8 +/- 22%). Electron microscopy confirmed the presence of reversible ultrastructural changes in TTC positive regions. A 60-minute occlusion, 3-hour reperfusion model adapted for in vivo single photon emission computed tomography showed a similar excess of 123I fatty acid activity over flow when compared to perfusion (as measured with 201Tl) in the ischemic border zone of 4/4 canine myocardial infarcts. We conclude that the accumulation of this non-beta-oxidized fatty acid analogue noninvasively identifies zones of discordance between fatty acid and flow distribution that are characteristic of ischemically "stunned" but viable myocardium.     

Recombinant tissue-type plasminogen activator ameliorates ischemic derangements induced by thrombotic occlusion in closed chest anesthetized dogs.

Effects of thrombotic coronary occlusion followed by thrombolytic reperfusion with recombinant tissue-type plasminogen activator (rt-PA) on infarct size and left ventricular function were studied in anesthetized closed chest dogs. After thrombotic occlusion of the left anterior descending coronary artery was produced by a copper coil technique, 74 dogs were randomly alloted to three groups; dogs treated with rt-PA at 90 min (n = 23) (group I) and at 180 min (n = 25) (group II) of the thrombotic occlusion, and 26 dogs treated with saline solution (permanent thrombotic occlusion, group III). The loading dose of intravenous rt-PA was 8,160 IU/kg body weight per min at the initial 60 min and the maintenance dose was 2,450 IU/kg per min continuously infused for 24 h. Thrombolytic recanalization was achieved at 15 +/- 4 and 18 +/- 6 min after rt-PA infusion in groups I and II, respectively. Infarct size and area at risk were determined by triphenyltetrazolium chloride staining and postmortem angiography; infarct size/area at risk ratio was 10 +/- 3% (n = 10), 33 +/- 7% (n = 9) and 63 +/- 3% (n = 10) in groups I, II and III, respectively (difference significant among groups). To examine whether infarct size and left ventricular function after thrombolytic reperfusion differ from those after mechanical reperfusion, 39 other dogs (group IV) underwent mechanical coronary occlusion for 106 +/- 1 min (occlusion period comparable with that of group I) and reperfusion using a balloon catheter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart

The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Iloprost (0.1-100 microM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Iloprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5a in each of the groups was control 13.3 +/- 1.8 units/g tissue (n = 12) and iloprost 6.5 +/- 0.9 units/g (n = 12), p less than 0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 +/- 3.1% of the area at risk (n = 15) compared with 42.4 +/- 3.3% of control (n = 13), p less than 0.01. Iloprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the interface between infarcted and noninfarcted tissue: control (n = 9) 9.0 +/- 1.8 units/g tissue, iloprost (n = 6) 2.0 +/- 0.4 units/g, p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnesium-enriched coronary sinus retroperfusion during acute coronary artery occlusion

BACKGROUND: The protective effect of coronary sinus retroperfusion in cases of ischaemic myocardium is clearly known. It restores the blood flow to the ischaemic tissue, reduces the infarct size, and improves the left ventricular pump function. METHODS: In this study, we investigated the effects of coronary sinus retroperfusion with the addition of magnesium sulphate on myocardial haemodynamics. A total of sixteen animals were entered into the study and divided equally into four groups: group I, control group, left anterior descending (LAD) coronary artery occlusion only; group II, LAD artery occlusion and Mg SO infusion; group III, LAD occlusion and retrograde coronary sinus perfusion; and group IV, LAD occlusion, retrograde coronary sinus perfusion and Mg SO infusion.(4) (4) RESULTS: Haemodynamic measurements were obtained throughout the study, at baseline, during the first and third hour of occlusion, and in the second, fourth and sixth hour of reperfusion. Although, the cardiac index was decreased in all groups, in the second hour of reperfusion it was significantly higher in groups III and IV compared to the control group. In the second hour of reperfusion cardiac index values were 56 +/- 5 and 63 +/- 6 ml/kg per min in groups III and IV respectively (P < 0.05) and as time passed this incremental change in groups III and IV became more apparent. In the fourth hour of reperfusion, group II showed significantly higher values than the control group. Group IV had higher values compared to group III at the fourth and sixth hours post-reperfusion. In general there were significant differences between groups II, III and IV at four and six hours post-reperfusion. The first derivative of pressure measured over time-the dP/dt value-was higher in groups III and IV compared to the control group in the first hour of occlusion (being 1650 +/- 55 and 1700 +/- 35 in groups III and IV respectively, and 1420 +/- 45 in the control group) and these differences continued throughout the occlusion and the reperfusion periods (P < 0.05). Group IV had the highest left ventricular stroke work index (LVSWI) values compared to the other groups in various pulmonary capillary wedge pressure (PCWP) measurements (P < 0.05). It was 0.78 g.m/kg at the 20 mmHg PCWP. CONCLUSIONS: Magnesium, if administered in an antegrade direction had only a limited effect, whereas magnesium-enriched retrograde coronary sinus perfusions appeared to significantly protect the ischaemic myocardium against the hazardous effects of ischaemic reperfusion injury.     

Anterior lead ST-segment depression in inferior wall infarction. Early angiographic study. Effect on the results of intracoronary thrombolysis

Of 32 patients with inferior myocardial infarction undergoing coronary angiography in the first 6 hours for intracoronary streptokinase thrombolysis, 19 (Group I) had ST depression of more than 1 mm in the anterior chest wall leads (VI-V4) whilst 13 (Group II) had no ST changes in these leads. Quantitative analysis of left ventricular angiograph showed a significantly lower ejection fraction in Group I (52 +/- 8.5%) compared to Group II (59 +/- 8%, p less than 0.05) and that this difference was due to a greater zone of inferior wall hypokinesia, irrespective of whether this was assessed by measuring its surface area (HKS cm2: Gr I: 11 +/- 6, Gr II: 4 +/- 3, p less than 0.01) or percentage ventricular perimeter (HK%: Group I 45 +/- 15, Group II 26 +/- 12, p less than 0.001). On the other hand, anterior wall motion was normal in both groups. Coronary angiography showed proximal obstruction of the right coronary artery in 84% of patients in Group I. In Group II, the coronary obstruction tended to be distal or incomplete. The prevalence and average severity of associated stenosis of the left anterior descending artery were the same in both populations. The success rate of thrombolysis was not significantly different between the two groups. In successful procedures with a patent artery on the 14th day, improved regional contractility was only observed in Group I (HKS cm2: 11.5 +/- 6 vs 8 less than 4.4, p less than 0.05; HK%: 47 +/- 14 vs 38 +/- 9, p less than 0.05): the hypokinetic zone was unchanged in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of pressure-controlled intermittent coronary sinus occlusion on regional ischemic myocardial function

Pressure-controlled intermittent coronary sinus occlusion has been reported to reduce infarct size in dogs with coronary artery occlusion, possibly because of increased ischemic zone perfusion and washout of toxic metabolites. The influence of this intervention on regional myocardial function was investigated in open and closed chest dogs. In six open chest dogs with severe stenosis of the left anterior descending coronary artery and subsequent total occlusion, a 10 minute application of intermittent coronary sinus occlusion increased ischemic myocardial segment shortening from 5.5 +/- 1.2 to 8.2 +/- 2.6% (NS) and from -0.1 +/- 2.1 to 2.3 +/- 1.2% (NS), respectively. In eight closed chest anesthetized dogs, intermittent coronary sinus occlusion was applied for 2.5 hours between 30 minutes and 3 hours of intravascular balloon occlusion of the proximal left anterior descending coronary artery. Standardized two-dimensional echocardiographic measurements of left ventricular function were performed to derive systolic sectional and segmental fractional area changes in five short-axis cross sections of the left ventricle. Fractional area change in all the severely ischemic segments (less than 5% systolic wall thickening) was -4.0 +/- 4.7% at 30 minutes after occlusion, and increased with subsequent 60 and 150 minutes of treatment to 13.1 +/- 3.3 and 7.0 +/- 3.3%, respectively (p less than 0.05). At the most extensively involved low papillary muscle level of the ventricle, regional ischemic fractional area change was increased by intermittent coronary sinus occlusion between 30 and 180 minutes of coronary occlusion from -0.4 +/- 0.1 to 14.4 +/- 4% (p less than 0.05), whereas a further deterioration was noted in untreated dogs with coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental and clinical investigations for the time interval from onset of symptoms to the coronary reperfusion

To clarify the relationship between time interval from the onset of coronary occlusion to the reperfusion and reperfusion rates or left ventricular function, an experiment with 113 mongrel dogs was carried out. Coronary thrombi experimentally induced within 4 hours in 63 dogs were rapidly lysed by intracoronary thrombolytic agent (Experiment 1). Infarct size was investigated in 17 dogs. The infarct size (% of left ventricle) in 9 dogs with 4-hour reperfusion following 2-hour coronary occlusion was significantly smaller than that in 8 dogs with 6-hour occlusion (12.0 +/- 7.9 vs 19.1 +/- 8.7% respectively p less than 0.05) (Experiment 2). The infarct size in 8 dogs with 7-day reperfusion following 2-hour occlusion was also significantly reduced compared to that in 7 dogs with 7-day occlusion (16.3 +/- 7.4 vs 28.5 +/- 8.9%, respectively p less than 0.02) (Experiment 3). The infarct size in 11 dogs with 4-hour reperfusion with verapamil administration following 2-hour occlusion was significantly reduced compared to that in 7 dogs with 6-hour occlusion without verapamil (5.5 +/- 1.9 vs 20.3 +/- 3.3%, respectively p less than 0.01) (Experiment 4). In experiment 3, anterior wall motion also was assessed by contrast ventriculography and infarct related areas in reperfused group was found to be improved compared to non-reperfused group at 7 days after infarction. In clinical studies, 121 patients who were admitted within 12 hour of onset of symptoms, were investigated to evaluate reperfusion rates and left ventricular function. The reperfusion rate of young age thrombus within 3 hours was 89% of 18 patients with completely occluded coronary artery. It was 77% of the 52 patients with 3 to 6 hour occlusion and 72% of the 18 patients with over 6 hour occlusion. There was a tendency towards high reperfusion rates in younger thrombus. In patients who were recanalized within 3 hours from the onset of symptoms ejection fraction of left ventricle at the chronic stage had a significantly higher percentage when compared to the unsuccessful group. Wall motion of infarct-related areas in patients who were thrombolysed within 6 hours was improved compared to the unsuccessful group. Administration of verapamil during reperfusion in patients with acute myocardial infarction suppressed rapid CK release and sigma CK. Thus, young age thrombus can be lysed easily, earlier recanalization after coronary occlusion can reduce infarct size and improve left ventricular function. Reinforced administration of verapamil during reperfusion can also reduce infarct size.     

Short-term treatment with synchronized coronary venous retroperfusion before full reperfusion significantly reduces myocardial infarct size.

The efficacy of short-term synchronized coronary venous retroperfusion (SRP) before full arterial reperfusion was studied in a canine model. A control group (n = 6) was subjected to 90 minutes of occlusion of the left anterior descending coronary artery, which was followed by 6 hours of reperfusion. In another group (n = 6) the left anterior descending coronary artery was occluded for 2 hours followed by 5.5 hours of reperfusion. In this group SRP was applied for 30 minutes before full reperfusion. Myocardial regional blood flow was measured with the use of colored microspheres. During occlusion of the left anterior descending coronary artery, there was severe myocardial ischemia in both groups. Blood flow in the subendocardial area was, however, significantly better in the SRP group (0.51 +/- 0.17 ml/min/gm after 3.5 hours of reperfusion) than in the control group (0.29 +/- 0.16 ml/min/gm) after 4 hours of reperfusion (p less than 0.05). Left ventricular function was assessed as global ejection fraction from a left ventriculogram. Ejection fraction was reduced during ischemia in both groups (control = 38% +/- 3%, SRP = 32% +/- 8%). This dysfunction remained after 4 hours of reperfusion. Infarct size was assessed by means of triphenyltetrazolium chloride staining. The myocardial area at risk was similar in the two groups (control = 33.1% +/- 5.3%, SRP = 30.6% +/- 6.5%). Infarct size, which was expressed as the percent of the area at risk, was significantly smaller in the SRP group (17.2% +/- 14.6%) than in the control group (36.0% +/- 8.1%; p = 0.0197).(ABSTRACT TRUNCATED AT 250 WORDS)     

N-2-mercaptopropionylglycine improves recovery of myocardial function after reversible regional ischemia

Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties, to attenuate postischemic dysfunction in open chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. Treated animals received an infusion of N-2-mercaptopropionylglycine (50 mg/kg per h) for 4 hours starting 15 minutes before coronary occlusion. Collateral flow, as determined with radioactive microspheres after 10 minutes of ischemia, was 0.07 +/- 0.01 ml/min per g (mean +/- SE) in both control (n = 20) and treated (n = 13) groups. The occluded vascular bed, as determined by postmortem perfusion, averaged 26.1 +/- 1.2% of the weight of the left ventricle in control and 29.6 +/- 1.3% in treated animals. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs at 1 hour (44.6 versus 12.8%, p = 0.05), 2 hours (64.0 versus 31.6%, p less than 0.02), 3 hours (77.1 versus 36.7%, p less than 0.01) and 4 hours of reperfusion (75.0 versus 40.0%, p less than 0.05). Thus, N-2-mercaptopropionylglycine produced a significant and sustained improvement in recovery of contractile function after a brief episode of regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early reperfusion therapy improves left ventricular function after acute inferior myocardial infarction associated with right coronary artery disease

Quantitative global and regional ventriculographic analysis was performed acutely and 1 week later in 46 patients undergoing reperfusion procedures within 6 hours of acute inferior myocardial infarction due to right coronary artery disease. While serial improvement in global left ventricular ejection fraction was not demonstrated for the group, infarct zone regional wall motion did improve (-2.7 +/- 0.9 vs -2.3 +/- 1.4 SD/chord, p less than 0.007). Serial improvement in global ejection fraction was demonstrated in the subgroup of patients treated within 2 hours of symptom onset (55 +/- 10 vs 62 +/- 10%; n = 5; p less than 0.03). Infarct zone regional wall motion improved serially only in the subgroup of patients treated within 3 hours of symptom onset (-2.4 +/- 1.1 vs -1.3 +/- 1.7 SD/chord; n = 11; p less than 0.007). Patients with initially patent arteries had a higher ejection fraction on follow-up catheterization than did those with initially occluded vessels (61 +/- 11 vs 55 +/- 7%; p less than 0.02), and patients with patent arteries at follow-up had a higher ejection fraction than did those whose arteries were occluded (60 +/- 9 vs 48 +/- 4%; p less than 0.0001). We conclude that significant improvement in global and regional left ventricular function in patients with inferior myocardial infarction is possible when reperfusion therapy is begun early or when arterial patency is achieved.     

Response of reperfusion-salvaged, stunned myocardium to inotropic stimulation

The purpose of this study was to determine whether myocardium salvaged by reperfusion following coronary occlusion could respond to inotropic stimulation by dopamine. Mongrel dogs underwent a 2-hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for 5 or 28 hours. Dopamine (5 to 10 micrograms/kg/min) or dextrose was administered 1 hour or 24 hours after the onset of reperfusion. Serial, computer-assisted, two-dimensional echocardiographic determination of percentage of systolic wall thickening (%SWT) and cross-sectional ejection fraction (% delta area) were used to evaluate the response to treatment. Myocardium in the region of central ischemia contracted poorly after 1 hour of reperfusion (mean %SWT = 1.3 +/- 13.3% [mean +/- SD] compared to preocclusion value of 43.6 +/- 18.5%, p less than 0.001) and tended to thin at 24 hours of reperfusion (mean %SWT = -6.0 +/- 12.3%, p less than 0.001). After 1 hour of reperfusion, dopamine produced a greater than fourfold improvement in %SWT within the reperfused zone (to 15.3 +/- 7.3%, p less than 0.05). After 24 hours of reperfusion, dopamine again produced an improvement in %SWT (to 5.8 +/- 12.5%, p less than 0.05). There were no significant changes in %SWT with dextrose infusion. Thus, dopamine stimulates the reperfusion-salvaged but noncontracting (stunned) myocardium to contract as early as 1 hour after reperfusion.     

Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase

Therapy directed against the toxic effects of reactive oxygen species may reduce the final extent of ischemic injury in otherwise viable tissue irreversibly injured by the abrupt reoxygenation of reperfusion. In four groups of dogs, superoxide dismutase plus catalase (groups I-III) or saline (controls) (group IV) was infused into the left atrium. Group I received the infusion for 2 hours, beginning 15 minutes before occlusion of the left circumflex coronary artery (90 minutes) and ending 15 minutes after reperfusion. Group II received the infusion for 1 hour starting 15 minutes before reperfusion. Group III received the infusion for 1 hour beginning 40 minutes after reperfusion. Dogs were killed the next day, and infarct size was determined by dissection and weighing, and confirmed histologically. Infarct size expressed as percent of the anatomic area at risk was: group I, 19.4 +/- 5.0; group II, 21.8 +/- 3.3; group III, 47.6 +/- 10.3; group IV, 43.6 +/- 3.5 (mean +/- SEM). Analysis of variance followed by Duncan's multiple range test showed that ultimate infarct size as assessed in groups I and II differed significantly (P less than 0.05) from that observed in the control animals in group IV, whereas infarct size between groups III and IV did not differ significantly (P greater than 0.05). The percent of left ventricle at risk did not differ between the four groups. The beneficial effects of superoxide dismutase plus catalase could not be explained by hemodynamic differences. Similar protection of jeopardized myocardium in groups I and II suggest that potentially viable tissue is salvaged by scavenging free radicals during early reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Right ventricular hypertrophy is an important determinant of right ventricular infarction complicating acute inferior left ventricular infarction

To explore the role of right ventricular hypertrophy and chronic obstructive pulmonary disease in the pathogenesis of right ventricular infarction, 27 consecutive patients with a first inferior left ventricular infarction were prospectively studied. Right ventricular infarction was diagnosed using established hemodynamic criteria. Right ventricular hypertrophy was defined as right ventricular free wall thickness greater than or equal to 5 mm. Patients were classified into two groups: Group I patients with right ventricular infarction (n = 15), and Group II patients without right ventricular infarction (n = 12). The ratio of forced expiratory volume over forced vital capacity (FEV1/FVC) and forced expiratory flow between 25 and 75% expired volume (FEF) as a percent of predicted values were significantly reduced in Group I versus Group II (90 +/- 5 versus 105 +/- 6% and 63 +/- 13 versus 103 +/- 15%, respectively; p less than 0.05). This was associated with increased right ventricular wall thickness (Group I 5.5 +/- 0.3 mm versus Group II 3.9 +/- 0.2 mm, p less than 0.001). Multiple logistic regression analysis demonstrated that right ventricular wall thickness was the strongest predictor of right ventricular infarction (p less than 0.0005). No significant difference was found in the site of right coronary occlusion, collateral blood supply or extent of coronary artery disease between the two groups. These findings suggest that right ventricular hypertrophy predisposes patients with acute inferior myocardial infarction to right ventricular infarction independent of the site or extent of coronary artery disease.     

Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction.

To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 +/- 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p less than 0.05). An increase in ejection fraction in group II compared with group I was marginally significant (4.5 +/- 12.2% vs 9.2 +/- 13.0%, p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function.     

Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs

The effects of coronary artery occlusion and reperfusion at 1 hour (1-hr group), 2 hours (2-hr group), and 3 hours (3-hr group) were compared with a permanently occluded group (P group) on measurements of overall left ventricular and regional endocardial function over a 4-week period. The studies were conducted in conscious dogs 1-2 weeks after recovery from instrumentation with solid state left ventricular pressure gauges, aortic, and left atrial catheters, hydraulic occluders, and Doppler flow transducers on the left anterior descending or left circumflex coronary arteries, and multiple pairs of ultrasonic transducers implanted in the endocardial third of the left ventricular free wall to measure endocardial segment shortening. During coronary artery occlusion, similar effects were observed in the four groups. At 1 hour after coronary artery occlusion, three classes of ischemia-induced dysfunction were observed; dyskinetic (systolic shortening completely lost and replaced by paradoxical bulging), severely hypokinetic (systolic shortening depressed by 65-95%), and moderately hypokinetic (systolic shortening depressed by 40-65%). Compared with the P group, significant (P less than 0.05) return of systolic shortening and velocity of shortening gradually occurred over the 4-week period following reperfusion in all classes of segments in the 1-hour group. In the 2-hour group, systolic shortening returned in the moderately and severely hypokinetic segments, but was slight and not significant in the dyskinetic segments. In the 3-hour group, significant systolic shortening returned only in the moderately hypokinetic segments. The effects of isoproterenol, 0.04 micrograms/kg per min, and exercise were compared on "salvaged" dyskinetic segments prior to and at 1, 2, 3, and 4 weeks after coronary artery occlusion and reperfusion. The responses to isoproterenol were significantly depressed at 1 week after reperfusion and gradually recovered over the 4-week period. At 3-4 weeks after reperfusion, severe exercise also increased shortening and velocity of shortening in "salvaged" segments. Thus, in the conscious dog, coronary artery reperfusion at 1 hour after coronary artery occlusion results in substantial return of endocardial function even in the most severely ischemic myocardium. The "salvaged" myocardium responds adequately to myocardial stress with increases in the extent and velocity of systolic shortening, as long as 3-4 weeks after reperfusion are allowed for recovery. However, after 3 hours of coronary artery occlusion, little salvage of regional myocardial function can be induced by acute reperfusion in this model.