Prostaglandin E1 was administered by means of coronary venous synchronized retroperfusion and the effectiveness of the combined (prostaglandin-retroperfusion) system was examined during acute myocardial ischemia in 10 closed chest anesthetized dogs. Such treatment was administered between 30 minutes and 3 hours after occlusion of the proximal left anterior descending coronary artery. An equivalent series of 10 dogs with arterial blood retroperfusion alone and 9 untreated dogs served as control subjects. Standardized two-dimensional echocardiographic measurements of global and regional left ventricular function were performed in five short-axis cross sections. The global low left ventricular section and its profoundly ischemic anterolateral region exhibited distinctly improved systolic fractional area changes as a result of the prostaglandin E1 retroperfusion treatment between 30 minutes and 3 hours after occlusion (22.9 +/- 1.5 to 41.2 +/- 4.0% and 1.8 +/- 3.6 to 29.4 +/- 5.6%, respectively). In contrast, further deterioration in function was noted during an untreated equivalent coronary occlusion period (16.3 +/- 2.7 to 10.0 +/- 3.3% and 12.6 +/- 6.1 to 4.1 +/- 6.9%). Although arterial blood retroperfusion alone provided distinct benefits in the ischemic region of a midpapillary echo section (from 13.4 +/- 3.9 to 32.1 +/- 10.4%, p less than 0.05), no improvements were observed in profoundly jeopardized segments at the low left ventricular level (5.6 +/- 6.0 to 0.9 +/- 5.7%). Triphenyltetrazolium chloride delineation of infarction revealed significant myocardial salvage with prostaglandin E1 retroperfusion as compared with findings in untreated control dogs (3.7% +/- 1.3% of the left ventricle versus 9.3 +/- 1.9%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The rate and form of creatine kinase-MB (CK-MB) enzyme release following reflow to ischemic myocardium has not been specifically examined in man. In this investigation, we examined the combined CK-MB time-activity curves during acute transmural myocardial infarction (AMI) in a group of patients receiving conventional therapy (CAMI) (n = 109), and in a group of nine patients with successful reperfusion by fibrinolytic therapy (RAMI). The average time of reflow in the latter group was 4.2 ± 1.7 hours (mean ± SD) following the onset of symptoms. The average time-to-peak CK-MB for the CAMI group was 18.3 ± 5.5 hours and for RAMI it was 9.9 ± 1.1 p < 0.001). At hour 4 (about the time of reflow), the two groups had similar CK-MB elevations (CAMI = 11 ± 7, RAMI = 13 ± 11 LU/L). By hour 6 (reflow + 2 hours), the RAMI CK-MB values were significantly higher (55 ± 33 vs 20 ± 15 IU/L, p < 0.02) than the CAMI group, demonstrating an increase in the release rate of CK-MB associated with reperfusion. We conclude that in man, reflow to the ischemic myocardium significantly augments the release rate of CK-MB.

Elevation of levels of the myocardial-specific isoenzyme of creatine kinase (CK-MB) in the immediate postoperative period in patients undergoing coronary artery bypass grafting is usually associated with myocardial necrosis. However, mean isoenzyme elevations of 18 +/- 2 IU/L (standard error of the mean) were recently observed in 6 patients in the absence of electrocardiographic or scintigraphic (technetium 99m stannous pyrophosphate) evidence of perioperative myocardial infarction. To test the hypothesis that surgical trauma of the atrium and aorta during cannulation for cardiopulmonary bypass might contribute to elevated CK-MB levels, biopsy of the right atrial appendage and aorta of 7 patients was done at operation, the tissue samples were assayed for total creatine kinase (CK) activity using the Rosalki technique, and for CK-MB using column chromatography. The results indicate that the human atrium is a rich source of CK, with the proportion of CK-MB similar to that present in the ventricle (20%). In addition, technical considerations inherent in the performance of coronary bypass surgery may result in release of CK-MB, causing elevated serum enzyme levels in the post-coronary artery bypass patient in the absence of myocardial infarction.

Although digoxin is used frequently in patients in the prophylaxis of postoperative supraventricular tachyarrhythmias, the effects of the drug on myocardial oxygen supply and demand after coronary bypass have not been described. Seven adult patients with good ventricular function who underwent myocardial revascularization were studied before and three hours after digoxin (0.5 mg, iv). There were no significant changes observed in any measured systemic hemodynamic variable. Evaluation of global myocardial metabolism showed an increase in myocardial oxygen consumption (P less than 0.05) which was compensated satisfactorily, as no significant alteration was noted in the coronary sinus oxygen content, or in the lactate gradient across the myocardium. Since the authors studied the effects of only one dose of digoxin, the effects of full digitalization in these patients remains to be defined.

Eine ausgedehnte Myokardschädigung bleibt nach wie vor die hauptsächliche Todesursache bei Patienten, die mit akutem Myokardinfarkt in ein Krankenhaus eingeliefert werden. Massive Läsionen führen zu Herzinsuffizienz, kardiogenem Schock und letalen ventrikulären Arrhythmien [6]. Es wurde daher nach einer Möglichkeit gesucht, die Ausdehnung und den Schweregrad der ischämischen Läsionen durch Erhöhung der Koronardurchblutung und/oder Reduzierung des myokardialen Sauerstoffbedarfs einzugrenzen. Die Mehrzahl der untersuchten Maßnahmen waren zwar beim Versuchstier wirksam, brachten jedoch in der Klinik bisher keinerlei zufriedenstellende Ergebnisse. Deshalb wird neuerdings der Möglichkeit einer maximalen Revaskularisation durch Wiederherstellung der antegraden Durchblutung der verschlossenen Koronararterien erhöhtes Interesse zugewandt, eine Methode, die eine radikale Änderung der Prognose von Patienten mit frischem Myokardinfarkt verspricht.

We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary No. 2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into the great cardiac vein, which peaked immediately after reperfusion, reflecting CK washout. Thus, brief periods of ischemia, which when single do not cause necrosis, have a cumulative effect and may cause myocardial necrosis. This mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes. Since many dogs of this study did not have any myocardial necrosis, the findings also suggest that intermittent reperfusion has a beneficial effect and may prevent necrosis, even when total occlusion time exceeds 200 minutes.

After experimental studies in dogs confirmed the feasibility and safety of rapid intracoronary thrombolysis by local infusion of Thrombolysin (streptokinase and plasmin), intracoronary thrombolysis was attempted in 20 patients with evolving myocardial infarction who were hospitalized within 3 hours from the onset of symptoms during the day and within 2 hours at night. Thrombolysin was infused in the immediate vicinity of the site of coronary occlusion using a 0.85 mm outer diameter catheter advanced through the lumen of the Judkins catheter. Reperfusion was achieved in four patients after an average of 43 minutes of Thrombolysin infusion at a rate of 2000 IU/min and in 15 patients after an average of 21 minutes of Thrombolysin infusion at a rate of 4000 IU/min. The failure to open the artery in one patient may have been caused by our inability to advance the infusion catheter close to the site of occlusion. Rethrombosis occurred in one patient 8 days after reperfusion and 2 days after discontinuation of anticoagulants because of a history of chronic alcoholism. Wall motion and perfusion studies showed improvement following reperfjsion. Patency of the artery was achieved an average of 4 hours after the onset of symptoms. The need for earlier reperfusion is emphasized.

Occlusive intracoronary (IC) thrombosis was produced experimentally in dogs by placement of a copper coil. The thrombus was consistently lysed by application of Thrombolysin (streptokinase and plasminogen) at the site of occlusion, 1 to 6 hours after thrombosis. Thrombolysin has no toxic effect on the coronary artery wall or the myocardium. Reperfusion after 30 to 60 minutes of occlusion frequently resulted in ventricular fibrillation, but gradual reperfusion reduced the probability of ventricular fibrillation. Intramyocardial bleeding was noted after reperfusion in areas of advanced necrosis and was shown to be the consequence, rather than the cause, of necrosis. The reperfused myocardium remained hypocontractile, but in contrast to the occlusion period, its mechanical function could be enhanced by inotropic stimulation. After experimental studies confirmed the feasibility and safety of IC thrombolysis, the technique was applied within 3 hours of onset of pain in 29 patients with evolving acute myocardial infarction (AMI) and showing ST elevations without pathologic Q waves. Nitroglycerin (NTG), 0.1 mg, was injected into the occluded coronary artery to rule out spasm; NTG failed to open the occluded artery. A special, very flexible, radiopaque No. 2 French catheter was advanced through the angiography catheter to the site of occlusion. Thrombolysin was infused at a rate of 4000 to 6000 IU/min until patency was achieved, followed by 2000 IU/min for 60 minutes. Lysis of clot was achieved in 27 of 29 patients. The single death (unrelated to the procedure) occurred subsequently in a patient in whom the artery was not reopened. After successful thrombolysis, 12 patients underwent elective coronary bypass surgery because of multiple stenoses. The need for early reperfusion is emphasized for effective IC thrombolysis therapy in evolving AMI.

The left ventricular filling pressure (LVFP) was measured within 12 hours of onset of acute myocardial infarction (AMI) in 99 patients, including 21 nonsurvivors. Initial LVFP for survivors was 18 +/- 6 mm Hg (mean +/- SD) and for nonsurvivors was 24 +/- 8 mm Hg (p less than 0.005). Of the total population, 87% had initial LVFP of 12 mm Hg or greater and all nonsurvivors were in this group. Life table analysis was employed to determine LVFP related mortality rates. If initial LVFP was less than or equal to 18 mm Hg, 72-hour mortality rate was 4% and 30-day mortality rate was 10%. For initial LVFP greater than 18 mm Hg, 72-hour mortality rate was 21% and 30-day mortality rate was 33% (p less than 0.005 for both 72 hours and 30 days). When final LVFP was analyzed 30-day mortality rate for final LVFP less than or equal to 18 mm Hg was 5%. Mortality rate of 60% was observed for final LVFP greater than 18 mm Hg. We compared sequential measurements of LVFP in a subset of survivors and nonsurvivors and observed that long-term average trend was for survivors to decrease their LVFP. We conclude that AMI mortality rate is related to LVFP and that LVFP greater than 18 mm Hg is associated with very high mortality rate when compared to LVFP less than or equal to 18 mm Hg. Thus reduction of LVFP either spontaneously or as result of therapy may lower AMI mortality rate.