Jules Osher

Consequences of reperfusion after coronary occlusion: Effects on hemodynamic and regional myocardial metabolic function

Abstract Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion. These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.

Revascularization after 3 hours of coronary arterial occlusion: Effects on regional cardiac metabolic function and infarct size

Two experimental series of closed chest dogs were compared: Group A (five dogs with 7 days of continuous occlusion of the proximal left anterior descending coronary artery); and Group B (six dogs with 7 days of reperfusion after 3 hours of acute occlusion of the same artery). Hemodynamic measurements, ventricular wall motion, coronary sinus blood flow and regional metabolism in both coronary occluded and nonoccluded segments of the left ventricle were measured sequentially. The infarct size was characterized by detailed histopathologic analysis. In the control dogs (Group A), mechanical and metabolic function remained severely depressed after 7 days of occlusion, and mean infarct size was 31.6 percent. In Group B, significant mechanical and metabolic dysfunction developed during 3 hours of occlusion and did not improve during the 1st hour of reperfusion. However, after 7 days of reperfusion, function returned to near preocclusion level. Mean infarct size was 14.2 percent, but in two of the six dogs infarct size was 43 percent and 23 percent, respectively. The study confirmed the unstable character of the early phase of reperfusion, attributed to cell swelling, edema and hemorrhages that resulted in inadequate coronary reflow, arrhythmias and functional derangements. Prolonged reperfusion for 7 days reduced mean infarct size and improved cardiac function.

Diastolic retroperfusion of acutely ischemic myocardium

The effectiveness of coronary venous retroperfusion treatment of an ischemic myocardial segment was assessed by measurements of regional and global myocardial function in 16 dogs. The left anterior descending coronary artery was acutely occluded for 75 minutes. After the first 30 minutes of occlusion, diastolic retroperfusion was instituted for 45 minutes by synchronized pumping of arterial blood from the brachial artery into the anterior interventricular coronary vein. Data collected in the preocclusion control period, during occlusion and the subsequent retroperfusion period included simultaneous measurement os ischemic and border zone myocardial forces, epicardial electrocardiographic S-T segments, intracoronary pressure, coronary blood flow and oxygen pressure (PO2) sampled distal to the site of occlusion. Retroperfusion resulted in significant improvement from the level of regional dysfunction observed after 30 minutes of occlusion: Ischemic zone myocardial force increased 106%, epicardial S-T elevation decreased 46%, normalized peripheral left anterior descending coronary arterial flow increased 50% and distal left anterior descending PO2 decreased 44%. These regional improvements were significant when compared with findings in an untreated series of 12 dogs with 75 minutes occlusion of the left anterior descending coronary artery. Diastolic-augmented coronary venous retroperfusion with arterial blood provided significant but not complete restoration of function in the ischemic segment. Therefore, in the earliest phase of acute myocardial infarction, retroperfusion might represent a useful temporary support to an otherwise inaccessible jeopardized zone of the heart. Regional retroperfusion may constitute an effective emergency procedure, particularly when the occlusive lesions are diffuse and other medical or surgical emergency procedures are inadvisable, unavailable or ineffective.

Significance of S-T segment elevations in acute myocardial ischemia: Evaluation with intracoronary electrode technique

A method is described for measuring intracoronary S-T segment elevations in the closed chest, a technique that appears to provide more reliable measurements of myocardial ischemia. Electrodes were inserted through intracoronary balloon catheters that were placed within a coronary artery and its adjoining vein both proximal and at several points distal to a coronary occlusion. Intracoronary arterial and adjacent venous electrocardiograms produced equivalent tracings. The intracoronary S-T segment elevations after coronary occlusion resembled those recorded from the epicardial surface but were free of artifacts noted in open chest studies. Study of progressive alterations of the intracoronary S-T segment after proximal occlusion of the left anterior descending coronary artery in 18 closed chest dogs revealed a peak segment elevation of 3.2 +/- 0.6 mv within 5 minutes, followed within 2 to 3 hours by spontaneous reduction by more than 40% of the S-T elevation over the occluded zone. In 44% of these animals, the S-T elevation decreased spontaneously to less than 1 mv, and in 22% it decreased to the preocclusion control level within 2 hours of occlusion. This spontaneous decrease in S-T elevation was frequently followed by a secondary increase and then S-T segment fluctuations. Reperfusion of the left anterior descending coronary artery after 30 to 60 minutes of occlusion generally led to a prompt reduction in S-T elevation. In some cases S-T elevations persisted up to 14 hours of occlusion, were reduced after reperfusion and exhibited a renewed pronounced increase after subsequent reocclusion of the left anterior descending coronary artery. During the 1st hour after occlusion, the early S-T segment elevation followed by spontaneous reduction reduction generally corresponded temporally with the derangements in myocardial lactate extraction and potassium loss. However, after 1 hour of occlusion no clear-cut correlation could be established between S-T fluctuations and changes in hemodynamic or myocardial metabolic measurements. We conclude that the new closed chest intracoronary electrocardiographic S-T technique might be of use for monitoring the early ischemic myocardial derangements and to assess benefits or drawbacks of treatment in both the experimental animal and man. Correspondence of S-T segment elevation with lactate and potassium alterations in the coronary-occluded region in the 1st hour after occlusion indicates that S-T segment elevation might represent an index of early myocardial ischemia. The spontaneous S-T changes that follow coronary occlusion must be taken into consideration when investigators utilize S-T segment modification as a sign of effectiveness of treatment.

Methylprednisolone treatment in acute myocardial infarction: Effect on regional and global myocardial function

The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment.

Regional and global myocardial effects of intravenous and sublingual nitroglycerin treatment after experimental acute coronary occlusion

The consequences of sublingual and intravenous nitroglycerin treatment after acute coronary occlusion were studied in 18 closed chest dogs. Intravenous (0.1 mg/min) or sublingual (0.4 mg/15 min) nitroglycerin therapy was instituted 1 hour after occlusion and the effects were observed over a period of 2 hours. Hemodynamics and global and regional cardiac function were measured in both the coronary occluded and nonoccluded segments of the left ventricle before and during coronary occlusion, and after administration of nitroglycerin. A similar nine dog control series was used to establish the significance of the measured effects of nitroglycerin. Intravenous nitroglycerin therapy after 1 hour of occlusion resulted in a marked increase in heart rate (37 +/- 12 [mean +/- standard error of the mean] percent), reduction of systolic blood pressure (9 +/- 3%), decrease in left ventricular end-diastolic and end-systolic volumes (32 +/- 5% and 34 +/- 5%), increase in coronary sinus flow (64 +/- 24%) and decrease in left ventricular stroke work (29 +/- 8%). Sublingually administered nitroglycerin produced similar trends but much less pronounced effects. However, intravenous or sublingual administration of nitroglycerin provided no improvement or caused further deterioration in ischemic region lactate extraction and potassium loss. The left ventricular ejection fraction, which was severly depressed after 1 hour of occlusion, changed minimally after administration of nitroglycerin, and there was no evidence of any correction of regional left ventricular akinesia or dyskinesia. Whereas mean systemic vascular resistance changed minimally as a result of nitroglycerin therapy, it increased 19 +/- 8% during a corresponding period of an untreated coronary occlusion series suggesting that nitroglycerin prevented an anticipated increase. Postocclusion S-T segment elevation in the electrocardiogram persisted after treatment. Our data corroborated that nitroglycerin reduced left ventricular volumes and increased coronary sinus flow; however, these improvements were accompanied by persisting metabolic and mechanical derangements in the ischemic region.

Derangements of myocardial metabolism preceding onset of ventricular fibrillation after coronary occlusion

To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.