Intermittent Coronary Sinus Occlusion Research Articles

Improved Distribution of Cardioplegia with Pressure-Controlled Intermittent Coronary Sinus Occlusion

Coronary occlusions may alter the distribution of antegrade cardioplegia and result in ischemic damage. This study was undertaken to determine whether pressure-controlled intermittent coronary sinus occlusion (PICSO) could improve antegrade cardioplegic delivery when coronary occlusions are present. Twenty pigs were subjected to 120 minutes of ischemic arrest with antegrade, multidose, potassium crystalloid cardioplegia. During arrest, the mid-left anterior descending artery was occluded with a snare, which was released on reperfusion. In 10 pigs, a balloon-tipped catheter was placed in the coronary sinus and PICSO was performed during each cardioplegia dose. PICSO-treated hearts had faster arrests (27 ± 5 versus 102 ± 21 [SE] seconds; p < 0.02), as well as lower temperatures (18.4 ± 1.0 versus 22.0 ± 1.4°C; p < 0.05) and higher tissue pH (6.58 ± 0.09 versus 6.31 ± 0.09; p < 0.05) just before aortic unclamping. Postischemic end-diastolic volume was unchanged with PICSO, but it decreased in non-PICSO-treated hearts. PICSO-treated hearts generated a higher postischemic stroke work index (0.70 ± 0.08 versus 0.38 ± 0.08 g-m/kg; end-diastolic volume, 60 ml; p < 0.05). We conclude that PICSO improves cardioplegic distribution, thus reducing ischemic injury.

Clinical Evaluation of Pressure-Controlled Intermittent Coronary Sinus Occlusion: Randomized Trial During Coronary Artery Surgery

Pressure-controlled intermittent coronary sinus occlusion (PICSO) was evaluated in a randomized trial in 30 patients undergoing bypass surgery. PICSO was applied for one hour during early reperfusion. Myocardial function was determined from short-axis cross-sectional views of intraoperative two-dimensional echocardiography. Changes of sectional and segmental wall motion during extracorporeal circulation were analyzed. Although sectional wall motion did not change significantly, hypokinetic segments were preserved better in PICSO-treated patients than in controls (–1.3 ± 2.4 versus –9.1 ± 2.6δ% fractional area change; p < 0.04). Although not significant, the same trend was found for normal and severely hypokinetic segments. Cumulative enzyme release was related to coronary sinus occluded pressure ( r = 0.94; p < 0.006), indicating washout of metabolites during PICSO. Three months after operation, functional classification was similarly favorable in both groups. Long-term effects of PICSO cannot be predicted because PICSO was applied only during early reperfusion. We conclude that PICSO is a safe procedure and that its short-term beneficial effects on myocardial function suggest a preservation of myocardial viability.

Computation of derived diagnostic quantities during intermittent coronary sinus occlusion in dogs.

The haemodynamic responses to pressure controlled intermittent coronary sinus occlusion (PICSO) were recorded intraoperatively in dogs. After analogue-digital conversion the data for coronary sinus pressure were submitted to numerical analysis for detection of systolic and diastolic envelopes and their subsequent fitting by a non-linear model. From the model variables derived quantities, such as plateau and rise times, were constructed so as to resemble the most important features of coronary sinus pressure rise during each occlusion-release cycle. The derived quantities were then monitored during all consecutive cycles throughout the entire experiment. In each dog the measurements were taken during normal coronary artery perfusion, left anterior descending coronary artery infarction, and reperfusion. The analysis comprise time course, stability, and physiological correlates of the derived quantities, on some of which a closed loop regulation may be based. Predicted plateaus (systolic and diastolic) and mean integrals (systolic and diastolic) were found to be stable quantities which, on subaveraging of about five successive estimates, yielded a 10% accuracy on the mean. By contrast, the rise times required subaveraging of about 15 cycles to achieve the same relative stability. It is concluded that, on subaveraging, derived quantities lend themselves for closed loop regulation input. Thus this quantitative assessment of numerical coronary sinus pressure analysis, as obtained from animal data, may lay the basis for future human application.

Intermittent coronary sinus occlusion in humans: pressure dynamics and calculation of diagnostic quantities.

Pressure controlled intermittent coronary sinus occlusion (PISCO) was applied in 30 patients undergoing coronary artery bypass surgery. The occlusion and release times were manually adjusted according to visual control of the intraoperatively monitored coronary sinus pressure. In six patients the coronary sinus measurements were additionally digitised with a personal computer before postoperative mathematical analysis, which comprised automatic detection of systolic peaks, diastolic troughs, and the calculation of derived quantities. The purpose of the analysis was (a) to assess quantitatively human coronary sinus pressure dynamics, (b) to determine whether visual control and interpretation of coronary sinus pressure rise could be replaced by a mathematical model, and (c) to ascertain whether the occlusion and release cycle lengths were adequate. Numerical estimates for intraindividual and interindividual spread of calculated quantities were produced, the mathematically obtained results were related to a possible physiological interpretation, and the most efficient method of statistical analysis was ascertained. These results form the numerical basis for a closed loop adjustment of pressure controlled intermittent coronary sinus occlusion cycling.

Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion

Recent experimental studies have shown that pressure-controlled intermittent coronary sinus occlusion effectively reduces both infarct size and myocardium at risk after coronary artery occlusion. This study was undertaken to determine whether this modality was equally effective in altering reperfusion damage after a period of ischemic arrest. Fourteen pigs were placed on cardiopulmonary bypass and subjected to 2 hours of ischemic arrest with multidose potassium crystalloid cardioplegia supplemented with topical and systemic hypothermia (28 degrees C). During arrest, the mid-left anterior descending artery was occluded with a snare, which was released immediately after aortic unclamping. In seven pigs, a 7F balloon-tipped catheter was positioned in the coronary sinus and pressure-controlled intermittent coronary sinus occlusion was performed for 60 minutes after aortic unclamping. Seven other pigs served as controls. Parameters measured included stroke work index, ejection fraction, and myocardial pH in the distribution of the distal left anterior descending artery. Pigs treated with pressure-controlled intermittent coronary sinus occlusion had a significantly higher myocardial pH (6.99 +/- 0.06 versus 6.67 +/- 0.05, p less than 0.01), ejection fraction (50% +/- 2% versus 33% +/- 6%, p less than 0.01), and stroke work index (0.87 +/- 0.07 versus 0.61 +/- 0.05 gm-m/kg, p less than 0.01) after 60 minutes of reperfusion compared with those of the group not treated in this way. We conclude that pressure-controlled intermittent coronary sinus occlusion effectively reverses reperfusion damage after periods of ischemic arrest.

Coronary sinus interventions: from concept to clinics.

For almost 100 years the coronary venous system has attracted researchers as an access route to deprived myocardium. Different concepts have been tried and numerous experimental studies have been performed to evaluate whether coronary sinus occlusion, retroinfusion, and retroperfusion of arterial blood via the coronary sinus represent an effective treatment of myocardial ischemia. The early successful studies of Drs. Gregg, Eckstein, Beck and others led to the application of the Beck II procedure, a permanent retroperfusion technique used in the early 1950s to revascularize patients with diffuse atherosclerosis. The coronary sinus route was also used to retroperfuse blood intraoperatively during opening of the heart to keep the heart beating. Excessive mortality and severe side effects, such as myocardial edema and hemorrhage, and an insufficiently advanced technology resulted in the temporary demise of the coronary sinus approaches. Recently, however, the need to improve myocardial protection, despite enormous advances in coronary bypass surgery and interventional cardiology, has resulted in renewed interest in the coronary sinus as an access route to deprived myocardium. Advances in technology such as percutaneous catheter techniques have improved access to the coronary venous system and allowed for a physiological adaptation of coronary sinus retroperfusion techniques. Today the three major coronary sinus techniques, i.e., sychronized retroperfusion (SRP), retroinfusion of cardioplegia during cardiac arrest and retroinfusion of pharmaceutical agents in the normal working heart, and pressure-controlled intermittent coronary sinus occlusion (PICSO) have been documented as providing superior protection of jeopardized myocardium in selected subsets of patients. All of these techniques currently are under clinical consideration; the retroinfusion of cardioplegia has already found wide clinical acceptance, SRP and PICSO have only recently been tested in first clinical trials. Due to a vast resurgence in interest, it is desirable to survey the results obtained with each of these techniques, to discuss the pathophysiology and mode of action of coronary sinus interventions, and to assign them a place in the perspective of conventional therapies. Furthermore, an attempt will be made to weigh individual coronary sinus techniques against each other, discuss in which clinical settings each of them may be most effective, and define issues facing current development.

Intermittent coronary sinus occlusion in dogs: Reduction of infarct size 10 days after reperfusion

Intermittent balloon occlusion of the coronary sinus was applied to 11 open chest dogs subjected to 3 hours of ligation of the left anterior descending coronary artery followed by 8 to 12 days of reperfusion. Anticoagulants were not given during the reperfusion period. Risk region was assessed by planimetry of autoradiographs made from ventricular slices. Infarct size was equivalent when assessed by planimetry of ventricular slices before and after staining with triphenyltetrazolium chloride. In the seven survivors, 30 +/- 8% of the risk region was infarcted. Seven of 11 control dogs survived (p = NS); 75 +/- 4% of the risk region was infarcted in the control animals (p less than 0.01 versus treated survivors). Light microscopic inspection of specimens stained with hematoxylin-eosin confirmed the border between necrotic and preserved myocardium. Thrombus was observed in the coronary sinus in all survivors in the treatment group. These findings confirm earlier short-term studies that demonstrated a potent anti-ischemic effect of intermittent coronary sinus occlusion. At the same time, coronary sinus thrombosis warrants caution in the application of this technique to myocardial ischemia in humans.

Model of the haemodynamic reactions to intermittent coronary sinus occlusion

Coronary sinus pressure data have been obtained from anaesthetized dogs during pressure controlled intermittent coronary sinus occlusion. It is the main aim of this paper to provide a mathematical procedure for modelling the typical time course of sinus pressure after temporary obstruction of the sinus. The model is produced by fitting a parameterized function to the systolic and diastolic pressures in order to represent mathematically the shape of the curves. The parameters characterize the rise in coronary sinus pressure following occlusion, and are used to calculate ‘derived quantities’ which mimic the physician's visual assessment of trace recordings and their clinical implications in certain forms of coronary sinus pressure reaction. This procedure should be thought of as a kind of pattern recognition which reflects the changing state of the myocardium. The mathematical results are shown to bear a close resemblance to the clinical effects of coronary sinus occlusion.

Analysis of coronary-sinus-occlusion pressure by iterating the convolution integral

Intermittent coronary sinus occlusion (ICSO) has been shown to reduce infarct size and to improve regional myocardial function. Since the efficiency of the procedure is closely related to proper intervals of occlusion and release of the coronary sinus, the reactions of coronary haemodynamics to this intervention have to be investigated. Coronary sinus pressure measurements obtained from anaesthetized dogs are analysed for three different conditions: normal coronary perfusion, experimentally induced infarction of the LAD performed according to a specific time pattern. The mathematical modelling of the coronary sinus pressure (CSP) reaction upon ICSO is accomplished by a convolution integral, incorporating a memory functoin g(x). With the aid of a numerical technique this function is evaluated to reproduce the measured data as closely as possible. Since g(x) describes the CSP response in a universal manner it can serve subsequently to predict reactions to different occlusion and release patterns not actually measured. This use of a mathematical model may provide economical paths for future investigations by avoiding prohibitively large numbers of animal studies. For different physiological states; normal perfusion, infarction and reperfusion; we obtained different memory functions. These differences in g(x) are then shown to be precisley related to known characteristics of the normal and diseased state of the myocardium. Understanding the link between cardiovascular physiology and its mathematical representation is seen as an important aid in the selection of therapeutic interventions.

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)

Reduction of infarct size induced by pressure-controlled intermittent coronary sinus occlusion

The effect of pressure-controlled intermittent coronary sinus (CS) occlusion on myocardial infarction (MI) size was evaluated. A device for this purpose was developed that consisted of a balloon catheter and pump system that produced controlled, intermittent occlusion of the CS and used CS pressure as a feedback to determine the duration of occlusion. It was hypothesized that proper selection of occlusion and nonocclusion times would both facilitate improved retrograde flow to ischemic areas and allow for more complete venous washout of metabolites. In 13 treated dogs and 12 control dogs before treatment, myocardium at risk of MI was estimated by injection of technetium-labeled microspheres. Intermittent CS occlusion was then begun, 15 minutes after coronary artery occlusion, and continued until termination of the experiment 6 hours later. Postmortem determination of infarct size was performed using the triphenyltetrazolium chloride staining technique. Intermittent CS occlusion begun 15 minutes after coronary artery occlusion and continued for 6 hours resulted in a 45% average reduction in MI size (p <0.001). During CS occlusion, the sinus systolic mean pressure increased from 10 to 44 mm Hg, while the distal coronary artery mean pressure increased by an average of 36% (from 22 to 30 mm Hg, p <0.05). These results suggest intermittent occlusion may be an effective treatment for evolving MI. This therapy, used alone or combined with other therapies (e.g., administration of pharmacologic agents), appears to have great clinical potential.

Coronary flow as an independent determinant of myocardial contractile force.

ARTICLESCoronary flow as an independent determinant of myocardial contractile forceVJ Fisher, RA Martino, RS Harris, and F KavalerVJ Fisher, RA Martino, RS Harris, and F KavalerPublished Online:01 Oct 1969https://doi.org/10.1152/ajplegacy.1969.217.4.1127MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByRole of Nitric Oxide Synthase, Cytochrome P-450, and Cyclooxygenase in the Inotropic and Lusitropic Cardiac Response to Increased Coronary PerfusionJournal of Cardiovascular Pharmacology, Vol. 40, No. 1Effect of graded reductions of coronary pressure and flow on myocardial metabolism and performance: A model of “hibernating” myocardiumJournal of the American College of Cardiology, Vol. 17, No. 7No effect of coronary perfusion on regional myocardial function within the autoregulatory range in pigs. Evidence against the Gregg phenomenon.Circulation, Vol. 83, No. 4Mathematical evidence for flow-induced changes in myocardial oxygen consumptionAnnals of Biomedical Engineering, Vol. 16, No. 4Effects of pressure-controlled intermittent coronary sinus occlusion on regional ischemic myocardial functionJournal of the American College of Cardiology, Vol. 5, No. 4Early changes in contractility and coronary blood flow in the normal areas of the ischemic porcine heartAmerican Heart Journal, Vol. 93, No. 3Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts.Circulation Research, Vol. 37, No. 6The effects of three vaporizable fire extinguishing agents on myocardial metabolism and cardiovascular dynamics in the anesthetized dogToxicology and Applied Pharmacology, Vol. 34, No. 1Cardiovascular effects of diazepam and chlordiazepoxideEuropean Journal of Pharmacology, Vol. 32, No. 1Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat HeartsCirculation Research, Vol. 32, No. 6Coronary Flow Supplementation in Experimental Myocardial Infarction with ShockChest, Vol. 61, No. 4Excitation contraction correlates in true ischemiaJournal of Electrocardiology, Vol. 5, No. 3Effects of Coronary Blood Flow and Perfusion Pressure on Left Ventricular Contractility in DogsCirculation Research, Vol. 27, No. 6�ber die Beteiligung des basalen Sauerstoffverbrauches, der Aktivierung des Myokards sowie h�modynamischer Parameter am Gesamtsauerstoffverbrauch des HerzensKlinische Wochenschrift, Vol. 48, No. 13Coronary vasodilatation following diazepam (Valium)19 July 2012 | British Journal of Pharmacology, Vol. 38, No. 3 More from this issue > Volume 217Issue 4October 1969Pages 1127-1133 Copyright & PermissionsCopyright © 1969 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1969.217.4.1127PubMed5824315History Published online 1 October 1969 Published in print 1 October 1969 Metrics