Effect of coronary reocclusion after initial reperfusion on ventricular function and infarct size

Reocclusion of a coronary artery after thrombolytic therapy occurs in approximately 12% to 33% of patients; however, there are few experimental data concerning reocclusion. Accordingly, to compare the effects of reocclusion versus sustained occlusion on the myocardium, a canine model (n = 12) of 2 h of left circumflex artery occlusion, 1 h of reperfusion and 1 h of reocclusion was studied. In a control group (n = 11), 3 h of circumflex artery occlusion was followed by 1 h of reperfusion. As a result, both groups had the same total duration of ischemia (3 h) and reperfusion (1 h). Hemodynamic measurements, radioactive microsphere injections and two-dimensional echocardiography were performed at baseline, occlusion and reperfusion for both groups and at the end of reocclusion for the experimental group. In vivo risk area was determined with Evans blue dye and infarct size with triphenyltetrazolium staining methods. Similar decreases in myocardial blood flow after coronary occlusion and similar reperfusion blood flows occurred in both groups. Despite intervening reperfusion in the reocclusion group, no significant difference was found in the infarct size/risk area ratio between the reocclusion and control groups (54.5 +/- 6.9% vs. 48.4 +/- 5.1%, respectively, p = NS). Two-dimensional echocardiography demonstrated a similar degree and extent (159 +/- 9 degrees vs. 153 +/- 12 degrees, p = NS) of left ventricular dysfunction with both the occlusion and reocclusion. In addition, there were no significant differences in global or regional left ventricular function between the two groups. However, reocclusion after reperfusion did produce a further deterioration in ischemic zone wall thickening (9.5 +/- 2.0% to 0.7 +/- 1.8%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial infarct size and ventricular function in rats.

To define the relationship between infarct size and ventricular performance, we performed hemodynamic studies in rats 21 days after left coronary artery occlusion. Ventricular performance was assessed under ether anesthesia by measurements of baseline hemodynamics and stressed performance as determined by the peak cardiac output and stroke volume obtained during intravenous volume loading and by the peak left ventricular developed pressure obtained during occlusion of the ascending aorta. Infarct size was determined by planimetry of the endocardial circumference of each of four histological slices of the left ventricle. Rats with small (4-30%) myocardial infarctions had no discernible impairment in either baseline hemodynamics or peak indices of pumping and pressure-generating ability when compared to the sham-operated, noninfarcted rats. Rats with moderate (31-46%) infarctions had normal baseline hemodynamics but reduced peak flow indices and developed pressure. Rats with infarctions greater than 46% had congestive heart failure, with elevated filling pressures, reduced cardiac output, and a minimal capacity to respond to pre- and after load stresses. The entire spectrum of postinfarction ventricular function was observed, from no detectable impairment to congestive failure. In this model of histologically healed myocardial infarction, the impairment of left ventricular function was directly related to the loss of myocardium.     

Effect of spontaneous reperfusion on myocardial infarct size

The effect of perfusion of the infarct artery on myocardial infarct size was studied in 39 patients who had not received interventive therapy. At predischarge coronary angiography, 19 patients had subtotal and 20 total occlusion of the infarct artery. The early ST-segment elevation recorded on a 12-lead electrocardiogram was used as an index of the amount of initially jeopardized myocardium. Infarct size was estimated by peak serum creatine kinase and, at discharge, by a QRS score, sigma Q and sigma R on a 12-lead electrocardiogram, and by radionuclide global and infarct segment left ventricular ejection fraction. Despite a similar degree of initial ischemia (sigma ST), infarct size was smaller in the 11 patients with anterior infarction and subtotal occlusion than in the 9 patients with anterior infarction and total occlusion when measured by peak serum creatine kinase (2114 +/- 1192 U/l vs. 3653 +/- 1059 U/l, p less than 0.02), QRS score (5.0 +/- 2.7 vs. 9.6 +/- 3.5, p less than 0.01), sigma Q (3.25 +/- 2.74 mV vs. 5.92 +/- 3.56 mV, p less than 0.10), sigma R (4.36 +/- 1.25 mV vs. 2.16 +/- 0.91 mV, p less than 0.001), global left ventricular ejection fraction (45.0 +/- 12.2% vs. 33.4 +/- 6.7%, p less than 0.05), and infarct segment ejection fraction (40.4 +/- 8.2% vs. 30.3 +/- 5.4%, p less than 0.05). In the inferior infarct patients, both the degree of initial ischemia and final infarct size were similar in the 8 patients with subtotal and in the 11 patients with total occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model

The administration of a drug soon after reperfusion that could enhance myocardial salvage would have important clinical application. The aim of this study was to assess the long-term effect of the perfluorochemical, Fluosol DA 20%, on infarct size, infarct morphology, ventricular ectopic activity and serial regional ventricular function in a 2 week closed chest canine model. After 90 minutes of proximal left anterior descending artery occlusion, animals randomly received either oxygenated Fluosol DA (n = 9) or saline solution (n = 9) intracoronary at 15 ml/kg body weight over 20 to 30 minutes. Hemodynamic variables were similar in the two groups except for transient elevation of left ventricular filling pressure immediately after infusion in the treated group. Infarct size was markedly reduced in the perfluorochemical-treated animals when expressed as a percent of the risk region (10.8 +/- 1.8% versus 28.9 +/- 5.5%, p less than 0.02) or as a percent of the total left ventricle (3.7 +/- 1% versus 10.8 +/- 8%, p less than 0.006). This was associated with greater improvement in radial shortening in the jeopardized zone at 2 weeks after reperfusion (15.3 +/- 2.8% versus 5.2 +/- 2.1%, p less than 0.01). Histologic examination revealed adequate healing in the treated animals with an increased number of swollen mononuclear cells in the border zones. Holter electrocardiographic recordings demonstrated a low frequency of ventricular ectopic beats in both groups. This study suggests that the perfluorochemical, Fluosol DA, may be a potentially useful agent in enhancing myocardial salvage after successful reperfusion.     

Nitrates in myocardial infarction: influence on infarct size, reperfusion, and ventricular remodelling.

OBJECTIVE--To assess the possible benefits of intravenous isosorbide dinitrate in acute myocardial infarction and oral isosorbide mononitrate in subacute myocardial infarction. METHODS--316 patients presenting with acute myocardial infarction were entered into double blind placebo controlled clinical trials assessing infarct size by enzyme release, ventricular size and function by echocardiography, reperfusion by continuous 12 lead ST segment monitoring and late potentials by high resolution electrocardiography. RESULTS--301 patients, of whom 292 (97%) received thrombolytic treatment, were randomised on admission to intravenous isosorbide dinitrate or placebo. Overall, there was no significant effect of treatment on infarct size, ST segment resolution, ventricular remodelling, or late potentials at day 3. A trend was observed towards a reduction in infarct size in patients with non-Q wave infarction treated with isosorbide dinitrate. Heterogeneity of nitrate effect was observed in relation to the degree of ST segment elevation on presentation with a clear benefit of isosorbide dinitrate in patients with moderate ST segment elevation (472 U/l v 704 U/l, P = 0.003) and a trend towards a deleterious effect in patients with marked ST segment elevation (1152 U/l v 1058 U/l, P = 0.2). ST segment re-elevation was more common among patients receiving nitrate treatment than in those assigned to placebo (29 v 16, P < 0.05). Some 160 patients underwent a further randomisation to sustained release isosorbide mononitrate or placebo on day 3. Echocardiographic volumes after 6 weeks of treatment were similar in the two groups. CONCLUSIONS--No benefit was observed with administration of nitrates in the treatment groups as a whole for either acute or subacute infarction. There was, however, evidence of heterogeneity of effect in the different subgroups of acute infarction, and the possibility that nitrates may have differing actions in different groups of patients should be considered.     

Left ventricular unloading during reperfusion does not limit myocardial infarct size

To determine whether venting the left ventricle during coronary reperfusion limits myocardial infarct size, we studied paced (200 beats/min) Langendorff rabbit hearts, perfused with blood from a support rabbit. A left coronary artery was occluded for 60 minutes, followed by 2 hours of reperfusion. Four experimental conditions, as follows, were used: In group 1 (control), the hearts contracted isovolumetrically on a fluid-filled balloon in the left ventricle during both occlusion and reperfusion. In group 2, the balloon was present only during occlusion, and the heart was vented during reperfusion. Hearts in group 3 were vented during occlusion and developed pressure during reperfusion. In group 4, the left ventricle was vented during occlusion and reperfusion. Perfusion pressure (91.2 +/- 0.9 mm Hg) and coronary flow (0.88 +/- 0.03 ml/min/g) were not different between groups. Left ventricular pressures (mean of all groups) were 87.3 +/- 1.5 mm Hg systolic and 6.5 +/- 0.6 mm Hg diastolic. Infarcted myocardium was assessed by triphenyl tetrazolium staining and expressed as a percentage of the area at risk, as measured by fluorescent particles. Venting during both ischemia and reperfusion (n = 10) did result in significantly smaller infarcts than in the unvented controls (n = 10), that is, 13 +/- 5% vs. 41 +/- 6%, respectively. Venting only during reperfusion (n = 10) or occlusion (n = 11) did not significantly limit infarct size (57 +/- 6% and 32 +/- 5%, respectively), as compared with controls. Thus, the clinically feasible intervention of left ventricular venting during reperfusion was not cardioprotective.     

Lack of correlation after reperfusion between ventricular function and infarct size estimated by thallium single-photon emission computed tomography

In 32 patients with acute myocardial infarction, who had undergone successful intracoronary thrombolysis, the results of regional wall motion measured from contrast cineangiograms 10 to 21 days after thrombolysis were related to the results of thallium single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Wall motion was measured by means of the centerline method, and thallium defect size was estimated by comparing the patient's circumferential profile with that of 20 normals. No correlation was found between ejection fraction or regional wall motion and thallium defect size. The time from symptom onset to thrombolysis was inversely correlated with the degree of hypokinesis (r=–0.51) but not with thallium defect size. In patients treated within 3 hours, hypokinesis was significantly less than in patients treated later (–1.1±0.6 SD vs –2.2±0.8 SD, p<0.01) whereas thallium defect size was not significantly different in both groups. It is concluded that, in patients after thrombolysis, thallium defect size determined by SPECT does not reflect the degree of left ventricular dysfunction.     

Enzymatic and scintigraphic determined infarct size: significance for left ventricular function following infarct

In a prospective study, the relationship between extent and location of myocardial infarction and the resulting left ventricular dysfunction was assessed and the question asked, how well these parameters may be assessed non-invasively a few weeks after the acute event. One hundred and fifty survivors of a first myocardial infarction were studied in the acute stage by serial ECG and CPK recordings and 5 weeks later by thallium201-(Tl)-scintigraphy and radionuclide angiocardiography. Myocardial damage was assessed enzymatically (maximal CPK; CPKmax) in the acute phase and scintigraphically in the subacute phase using a Tl-score considering extent (in percent of total myocardium in each projection) and severity (decrease in thallium-uptake) of scintigraphic infarct defects. There were significant correlations between Tl-score and max. CPK (r = .69) as well as between Tl-score and left ventricular ejection fraction (LVEF) (r = .65; p less than .001 each), but this correlation was better for subgroups with anterior vs. inferior infarctions (r = -.68 vs. r = -.59; p less than or equal to .001 for each). Furthermore, LVEF could be predicted based on the Tl-score: 88% of patients with values less than 7 had an LVEF of greater than 45%, whereas 77% of patients with a thallium-score of more than 12 had an LVEF less than 45%. Reproducibility of the Tl-score assessed in 30 patients over 3 months was excellent (r = .96) with low variability between the two analyses (+/- 1.5). Thus, after a first myocardial infarction, a direct relationship between enzymatically and scintigraphically, assessed infarct size and LVEF could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of inosine on ventricular regional perfusion and infarct size after coronary occlusion.

In 16 dogs inosine was infused at 0.5 mmol/min i.v. for 5 min beginning 15 min after coronary occlusion. Tracer microspheres were used to estimate flow in subepicardium and subendocardium of nonischemic, central ischemic, and borderline ischemic muscle. Estimates of flow before occlusion, 5 min after occlusion, during inosine infusion, 30 min after infusion and 60 min after infusion were obtained. Coronary occlusion reduced flow in the central ischemic regions by 75-95%. The reduction in flow was greatest in subendocardium. In the borderline regions subendocardial flow was reduced by 30% while subepicardial flow was unaffected. The major effects of inosine were seen in nonischemic and borderline ischemic regions. Flow in borderline subendocardium returned to its pre-occlusion value, and flow in nonischemic myocardium increased by approximately 60-80%. However, only in the ischemic regions was the increase in flow sustained for the entire 60 min. In 20 dogs infarct size was determined using nitro blue tetrazolium stain. In 10 controls infarct size was 20.1%, while in 10 inosine-treated dogs infarct size was 15.2% of left ventricular weight (p less than 0.01). Thus, following coronary occlusion inosine infusion was associated with an increase in perfusion of ischemic myocardium and a reduction in infarct size.     

Relation between infarct size and ventricular arrhythmia.

In order to determine whether ventricular arrhythmia is quantitatively related to infarct size estimated enzymatically we studied 31 patients with acute myocardial infarction without cargiogenic shock. Infarct size index was estimated from hourly serum creatine kinase (CK) changes during periods of 48 to 72 hours. Ventricular arrhythmia was quantified by automated analysis of continuous electrocardiographic recordings over a period of 20 hours with the use of the Argus/H computer system. Patients were classified into three groups according to infarct size index. Patients in all groups had similar average heart rate, blood pressure, serum potassium, and arterial pH and PCO2 values during the first 10 hours after admission. The total number of ventricular ectopic beats (VEB), frequency of couplets, and ventricular tachycardia, and peak rate of ventricular ectopic beats during the first 10 hours after admission were all related to infarct size index. For example, patients with small, medium, and large estimated infarct size averaged 26, 104, and 405 ventricular ectopic beats, respectively. These results suggest that the severity of ventricular arrhythmia early after myocardial infarction is related to the extent of myocardial injury as estimated enzymatically. Thus the apparent efficacy and therefore the evaluation of antiarrhythmic agents early after myocardial infarction may be influenced by the magnitude of injury sustained by the heart.     

Myocardial infarct size and left ventricular function in diabetic patients]

We determined the relationship between myocardial infarct size (MIS) estimated by electrocardiographic measurements of infarct size (QRS score) and left ventricular function estimated by angiographically left ventricular ejection fraction (EF). MIS estimated by QRS score were the same in both DM and NDM (5.2 +/- 0.5 vs 4.3 +/- 0.4: p greater than 0.05), but EF in DM was significantly lower than in NDM (43.1 +/- 1.4 vs 51. +/- 1.1%: p less than 0.05). There was clear linear correlation between MIS and EF in NDM (r = -0.71) but not in DM. EF was much lower in DM than in NDM even at the same QRS score level. There were no differences in blood pressure, serum lipid levels, age, and the site of the myocardial infarction. The most likely explanation for this appears to be due to a previous left ventricular disease in DM.     

Use of computerized tomography to assess myocardial infarct size and ventricular function in dogs during acute coronary occlusion and reperfusion

Prospectively ECG-gated and nongated computed tomography (CT) can be used to assess global and regional left ventricular (LV) function and to measure myocardial infarct (MI) size. In the current study, CT was used to assess the effects of coronary occlusion and reperfusion in 16 dogs. Ten dogs were subjected to permanent occlusion of the proximal left anterior descending coronary artery and 6 dogs were reperfused after a 2-hour period of total coronary occlusion. Gated scans were used to quantitate the extent of wall thickening in the ischemic zone and to assess changes in mid-LV cross-sectional chamber area at end-diastole and end-systole. Nongated scans were used to estimate the size of the initial perfusion defect during contrast injection shortly after coronary occlusion and the size of the MI as indicated by delayed enhancement of the infarct 10 to 30 minutes after cessation of contrast administration. Neither group showed significant changes in end-diastolic chamber area during acute occlusion or 3 days later. Both groups showed a significant deterioration in percent change in chamber area both early after coronary occlusion and 3 days later; however, in the permanent occlusion group, percent wall thickening in the ischemic zone decreased from 46.2 +/- 16.5% (mean +/- standard deviation) to 1.6 +/- 9.0% during acute occlusion (p less than 0.01) and thickening remained depressed 3 days later (2.4 +/- 10.1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pacing-induced dyssynchrony during early reperfusion reduces infarct size.

OBJECTIVES: Considering the recent discovery of postconditioning, we investigated whether intermittent dyssynchrony immediately upon reperfusion induces cardioprotection as well. BACKGROUND: Intermittent dyssynchrony, induced by ventricular pacing, preconditions myocardium. METHODS: Isolated ejecting rabbit hearts were subjected to 30-min coronary occlusion and 2-h reperfusion. Control, left ventricular (LV) pacing preconditioning (LVPpreC) (3 x 5-min LV pacing), and LV pacing postconditioning (LVPpostC) (10 x 30-s LV pacing during early reperfusion) groups were studied. Mechanical effects of LV pacing were determined using local pressure-length loops (sonomicrometry), whereas effects on myocardial lactate release and coronary flow were assessed from coronary effluent and fluorescent microspheres, respectively. Anesthetized pigs underwent 60-min coronary occlusion and 3-h reperfusion in control and right ventricular (RV) pacing postconditioning groups (RVPpostC) (10 x 30-s RV pacing during early reperfusion). In all hearts, area at risk and infarct size were determined with blue dye and triphenyltetrazolium chloride staining, respectively. RESULTS: Infarct size, normalized to area at risk, was 47.0 +/- 12.3% in control rabbit hearts, but significantly smaller in LVPpreC (17.8 +/- 6.4%) and LVPpostC hearts (17.9 +/- 4.4%). Left ventricular pacing significantly altered regional mechanical work, but did not affect coronary flow or lactate release. In pigs, infarct size was significantly smaller in RVPpostC (9.8 +/- 3.0%) than in control (20.6 +/- 2.2%) animals. CONCLUSIONS: Intermittent dyssynchrony during early reperfusion reduces infarct size in 2 different animal models. Dyssynchrony-induced postconditioning cannot be attributed to graded reperfusion but may be induced by modulation of local myocardial workload. Dyssynchrony-induced postconditioning opens new possibilities for cardioprotection in the clinical setting.     

Effect of frequent ventricular ectopy on myocardial infarct size in dogs

Tachycardia is known to increase the size of an evolving myocardial infarction, but the effect of frequent ventricular extrasystoles on infarct size is unknown. To determine the effect dogs were allocated to a control group (n = 15) or to groups of dogs with electrically induced ventricular bigeminy. Ventricular extrasystoles with short coupling intervals (mean 251 ms) were used to simulate interpolated premature complexes in 10 dogs, and extrasystoles with long coupling intervals (mean 606 ms) resulting in compensatory pauses were applied in 10 additional dogs. All dogs underwent single stage left anterior descending coronary artery ligation followed by a 6 h monitoring period. Premature stimulation was begun at the time of coronary artery occlusion and continued throughout the observation period. The ratio of myocardial infarct size to the region at risk of infarction was substantially larger in dogs with electrically induced, closely coupled extrasystoles (0.58(0.07); p less than 0.01) than in control dogs (0.24(0.06)) or dogs with widely coupled induced extrasystoles (0.32(0.07)). It is concluded that frequent closely coupled ventricular extrasystoles can increase the size of an evolving acute myocardial infarction.     

Mechanical left ventricular unloading prior to reperfusion reduces infarct size in a canine infarction model.

We tested the hypothesis that unloading the left ventricle just prior to reperfusion provides infarct size reduction compared with left ventricular (LV) unloading postreperfusion and reperfusion alone. Twenty-four mongrel dogs were subjected to 2 hr of left anterior descending artery occlusion and 4 hr of reperfusion. A transvalvular (TV) left ventricular assist device (LVAD) was inserted just prior to reperfusion and maintained during the rest of the experiment (LV Assist Pre group). In the LV Assist Post group, the TV LVAD was inserted and activated just after reperfusion. A control group was subjected to reperfusion alone with a sham-TV LVAD. At baseline, the hemodynamic data were similar in the three groups. Myocardial infarct size expressed as percentage of area at risk was significantly reduced in the LV Assist Pre group compared to the control group (P = 0.011) and to the LV Assist Post group (P < 0.05). At 4 hr of reperfusion, transmural myocardial blood flow in the ischemic zone was slightly higher in the animals unloaded prior to reperfusion compared to controls and significantly higher than in the LV Assist Post group (P = 0.04). Postreperfusion end-diastolic wall thickness returned to baseline level in the TV LV Assist Pre group compared to both controls and TV LV Assist Post group. In these latter two groups, a significant increase in postreperfusion end-diastolic wall thickness and contraction band necrosis in the central ischemic zone correlated well with the degree of reperfusion injury. LV unloading prior to, but not after, reperfusion reduces the extent of myocardial necrosis in canine hearts subjected to 2 hr of left anterior descending artery occlusion and 4 hr of reperfusion compared to either reperfusion alone or LV unloading after reperfusion.     

Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury

Reperfusion of ischemic myocardium may accelerate necrosis of injured myocytes. To determine the role of neutrophil leukocytes in this process, we examined whether neutrophil depletion during reperfusion could modify infarct size in anesthetized dogs. The proximal circumflex coronary artery was occluded for 90 minutes and then reperfused for 2 hours via an extracorporeal circuit with either whole blood (n = 11) or with blood depleted of neutrophils by leukocyte filters (n = 11). The leukocyte filters caused near-total neutropenia in blood reperfusing the ischemic myocardium (7 +/- 7 neutrophils/microliters compared with 2,551 +/- 317/microliters in controls, mean +/- SEM; p less than 0.001. Infarct size was measured by planimetry of myocardial slices stained with triphenyltetrazolium chloride (TTC), and the accuracy of TTC for identifying necrotic myocardium was verified by electron microscopy. The size of the ischemic risk region was the same in the control (41.6 +/- 1.0%) and neutropenic (41.8 +/- 2.1%) groups. Collateral blood flow to the risk region was the same in control (0.15 +/- 0.03 ml/min/g) and neutropenic (0.13 +/- 0.03 ml/min/g) groups. Among dogs with collateral flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic group (27.7 +/- 6.7% of risk region, n = 8), compared with control dogs (52.5 +/- 5.7%; n = 7; p = 0.02). Multiple linear regression described the relation between infarct size, risk region size, and collateral flow in the control group, and the same regression relation was used to predict infarct size for the neutropenic group. Mean predicted infarct size in the neutropenic group (n = 11) was 16.8 +/- 3.4% of left ventricle, whereas mean observed infarct size was 9.6 +/- 3.1% (p less than 0.01). The extent of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less in the neutropenic than the control group (2.2 +/- 0.8% vs. 8.1 +/- 2.7% of the risk region, p less than 0.05). Neutropenia limited to the reperfusion period is associated with significant reductions in the extent of the infarct and no-reflow zones after 90 minutes of ischemia. These findings support the hypothesis that reperfusion necrosis occurs after prolonged myocardial ischemia and indicate that neutrophil leukocytes are important mediators of such reperfusion injury.     

Relationship between angiographic infarct size and left ventricular filling.

Infarct size may influence left ventricular filling after acute myocardial infarction. Pulsed Doppler transmitral flow velocities were compared in 47 patients at 7 +/- 6 days following acute myocardial infarction and 47 age-matched controls. Patients were stratified by angiographic infarct size into Groups I, II, III (corresponding angiographic hypokinetic scores less than 2; 2-2.99; greater than or equal to 3 SD/cord). Early diastolic transmitral Doppler flow velocities did not differ between infarct groups but atrial transmitral Doppler flow measurements did: peak A velocity (p = 0.001), A velocity time integral (p less than 0.001), and total velocity time integral (p = 0.001). Compared to controls atrial transmitral Doppler flow was augmented in Group I, whilst atrial and total transmitral Doppler flow were depressed in Group III. Peak A velocity and A velocity time integral were inversely related to infarct size (R = -0.44 to -0.54) and directly to left ventricular ejection fraction (R = 0.59 to 0.65). Large infarct size following myocardial infarction is associated with lower atrial and total transmitral Doppler flow velocities.     

Acute effects of parenteral beta-blockade on regional ventricular function of infarct and noninfarct zones after reperfusion therapy in humans.

Although the mechanism is unknown, clinical trials have suggested that intravenous beta-adrenergic blockade may prevent early cardiac rupture after myocardial infarction. Previous studies have examined effects of beta-blockers on global left ventricular function after myocardial infarction; however, few data exist regarding their immediate effects on regional function or in patients after successful reperfusion. Therefore, 65 patients in whom thrombolysis with or without coronary angioplasty achieved reperfusion at 4.6 +/- 1.7 h from symptom onset were studied. Low osmolarity contrast ventriculograms were obtained immediately before and after administration of 15 mg of intravenous metoprolol (n = 54) or placebo (n = 11). Intravenous metoprolol immediately decreased heart rate (from 92 to 76 beats/min, p less than 0.0001), increased left ventricular diastolic volume (from 150 to 163 ml, p less than 0.001) and systolic volume (from 72 to 77 ml, p less than 0.0005) but did not change systolic and diastolic pressures. Although there was no difference in ejection fraction after metoprolol, centerline chord analysis revealed reduced noninfarct zone motion (from 0.41 to 0.12 SD/chord, p less than 0.05), improved infarct zone motion (from -3.1 to -2.9 SD/chord, p less than 0.01) and smaller circumferential extent of hypokinesia (from 30 to 27 chords, p less than 0.05). Patients with dyskinesia of the infarct zone had the most striking improvement in infarct zone wall motion. Because these changes occurred immediately after beta-blockade, they could not be attributed to myocardial salvage. No significant changes in heart rate, left ventricular volumes or regional wall motion were apparent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)