Pressure-controlled Intermittent Coronary Sinus Occlusion Research Articles

Myocardial Protection Via the Coronary Sinus Long-Term Effects of Intermittent Coronary Sinus Occlusion as an Adjunct to Reperfusion in Acute Myocardial Infarction

Recent reports on facilitated reperfusion therapy re-address interests in coronary sinus interventions (CSI). Patients in whom short time results have been reported earlier were re-evaluated, with the aim of gathering the long-term results of pressure-controlled intermittent coronary sinus occlusion (PICSO) generated in patients with acute myocardial infarction (MI) and revascularization. Thirty-four patients with ST elevated MI, in whom complete revascularization was achieved, underwent primary thrombolysis with or without PICSO. Follow-up data from these patients were collected for at least 48 months. Immediate perioperative differences were observed for time to peak creatine kinase (CK), as well as cumulative CK. In addition, the time until reperfusion was considerably less than for the control group (p=0.014). Long-term data showed significant differences in reinfarction (p=0.015), as well as in major adverse cardiovascular events, between the 2 groups (p<0.0001). These data, because of the wide interval between collection and current analysis, could have inherited historical bias. Nonetheless, they are also uniquely indicating the potential of CSI to induce not only immediate, but also clinically significant long-term, effects as an adjunct to reperfusion therapy. Therefore, CSI should be, once again, on the study agenda and be placed under contemporary and best-available scientific scrutiny.

Intermittent pressure elevation of the coronary venous system as a method to protect ischemic myocardium

Beating heart surgery leaves myocardial areas underperfused and rendered ischemic during brief coronary artery occlusions. In a recent meta-analysis in experimental myocardial infarction, intermittent coronary sinus occlusion (ICSO) proved valid to salvage ischemic myocardium by 30%. Moreover, benefit of this effect can be optimised using coronary venous pressure data. The aim of this study was to evaluate optimisation criteria investigating coronary venous flow data during pressure controlled intermittent coronary sinus occlusion (PICSO). PICSO was performed in 12 adult anaesthetised sheep during occlusion of the left anterior descending (LAD). Additional to coronary sinus pressure (CSP) recordings, venous flow was measured in the great cardiac vein (GCV) via continuous wave Doppler sonography. Experimental studies provide evidence of retrograde flow toward ischemic zone originating from PICSO. Mean antegrade flow, during specific cycle, is significantly higher than the mean retrograde flow (P<0.007). Additionally, differences between various cycles can be considered significant, too (P<0.05). These experimental data support the notion that transient pressure elevation in the coronary venous system recruits collateral flow towards ischemic myocardium. Optimal timing significantly improves the effectiveness of the method. Ease of this intervention makes PICSO capable of protecting myocardial performance during beating heart surgery even without active retroperfusion.

The Effect of Pressure-Controlled Intermittent Coronary Sinus Occlusion on the Reduction of the Myocardial Infarction Size

The Effect of Pressure-Controlled Intermittent Coronary Sinus Occlusion on the Reduction of the Myocardial Infarction Size

Combining percutaneous bypass with coronary retroperfusion limits myocardial necrosis

After an acute coronary occlusion that results in hemodynamic instability, the institution of percutaneous bypass (PB) can effectively support the failing myocardium. However, PB cannot augment coronary blood flow, and substantial regional myocardial necrosis can still occur. This experimental study was undertaken to determine whether combining PB with coronary venous retroperfusion using pressure-controlled intermittent coronary sinus occlusion (PICSO) would limit myocardial necrosis after an acute coronary occlusion. In 30 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, 10 pigs were placed on PB, 10 pigs received PB+PICSO, and 10 pigs received no support (unmodified). Hearts treated with the combination of PB+PICSO had the highest wall motion scores (unmodified, 1.4 +/- 0.3; PB, 1.4 +/- 0.3; PB+PICSO, 2.8 +/- 0.3 [p < 0.05 versus unmodified and PB]) and the lowest area of necrosis in the area at risk (unmodified, 73% +/- 3%; PB, 43% +/- 2%; PB+PICSO, 14% +/- 2% [p < 0.05, PB and PB+PICSO versus unmodified; p < 0.05, PB+PICSO versus PB]). We conclude that combining PB with coronary venous retroperfusion significantly limits myocardial necrosis.

Simultaneous arterial and coronary sinus cardioplegic perfusion: an experimental and clinical study.

The existence of inhomogeneous distribution of coronary flow with antegrade or retrograde perfusion alone has led to alternating between these delivery routes to maximize their individual benefits. Concern over myocardial damage prevented the simultaneous application of antegrade and retrograde cardioplegic blood delivery. Based upon the predominance of retrograde drainage via Thebesian veins, and evidence that pressure-controlled intermittent coronary sinus occlusion during antegrade cardioplegic delivery enhances its distribution and protective properties, this study tests (a) the hypothesis that simultaneous aortic and coronary sinus perfusion is safe during aortic clamping, and (b) reports initial clinical application of this combined strategy in 174 patients. Five minipigs (25-30 kg) underwent 1 hr of aortic clamping with simultaneous aortic (antegrade) and coronary sinus (retrograde) perfusion at 200 ml/min with normal blood (37 degrees C) before and after 30 minutes of perfusion with either warm (37 degrees C) or cold (4 degrees C) blood cardioplegia (BCP). Furthermore, the combined strategy was used in 174 high-risk patients (NYHA class III-IV) at 3 university hospitals to perform myocardial protection during CABG or valve replacement, or a combination of both. Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. In both the clinical and the experimental studies the coronary sinus pressure was always < 40 mmHg in beating or arrested hearts. Compared to control values (81.4 +/- 0.4% tissue water content), no right-ventricular (80.8 +/- 0.8%) or left-ventricular (79.5 +/- 0.3%) edema developed, no lactate was produced (control: -1.0 +/- 0.5 mg/100 g/min, empty beating: -0.64 +/- 5, and BCP arrest: -8.6 +/- 6.6).(ABSTRACT TRUNCATED AT 250 WORDS)

The Relevance of Coronary Sinus Interventions in Cardiac Surgery

The concept of arterialization of the coronary venous system was first discussed almost 100 years ago. Subsequently, those attracted by this approach have chosen the coronary veins as an alternative route for interventional and surgical therapy. Modern techniques of coronary sinus interventions (CSI) have been suggested mainly for temporary support and protection of ischemic myocardium. Based on the dense meshwork structure of the venous vasculature, CSI may be effective even in the presence of serious coronary artery disease. Three major techniques have been suggested for different indications in cardiology and cardiac surgery: 1) ECG-synchronized retroperfusion of arterial blood, which is supposed to positively affect ischemic myocardium by phasic supply of oxygen to deprived areas mainly in cardiac emergencies, 2) retroinfusion of cardioplegia in the arrested heart, which is now a well-established clinical technique, and 3) intermittent coronary sinus occlusion during antegrade cardioplegic delivery in the arrested heart and in the early reperfusion period after surgical revascularization, or in cardiac emergencies. The beneficial effect of pressure-controlled intermittent coronary sinus occlusion is assumed to result from cyclic occlusion and release of the coronary sinus shifting venous blood to underperfused regions, thereby facilitating substrate delivery and subsequent washout of metabolites. Experimental studies and first clinical trials suggest that all methods of CSI are safe and feasible, and the ultimate goals of reduction of infarct size and preservation of jeopardized ischemic myocardium will be achieved.

Coronary sinus occlusion: Effect on ischemic left ventricular dysfunction and reactive hyperemia

Pressure-controlled intermittent coronary sinus occlusion (PICSO) has been shown to reduce experimental infarct size. To examine the role of PICSO in limiting the consequences of brief ischemia on left ventricular function, we studied the effect of PICSO in nine open-chest anesthetized dogs. PICSO was performed using a pump-inflated, balloon-tipped catheter in the coronary sinus until coronary sinus occlusion pressure reached a plateau (10 ± 3 seconds). The balloon was then rapidly deflated (2 seconds) and the cycle was repeated. Regional left ventricular function in the ischemic zone was assessed by sonomicrometry. Coronary blood flow was measured with a flow probe around the left anterior descending artery (LAD) proximal to an occluding suture. Measurements were obtained at baseline, during a 3-minute LAD occlusion, and for 10 minutes of reperfusion. In an additional five dogs, this sequence was repeated during an infusion of adenosine at a dose that abolished reactive hyperemia following LAD occlusion. The addition of PICSO beginning 15 minutes prior to ischemia and continuing throughout LAD occlusion and reperfusion did not prevent, reduce, or shorten ischemic left ventricular dysfunction. PICSO uniformly blunted reactive hyperemia during reperfusion. However, PICSO also reduced coronary blood flow during maximal vasodilatation achieved by adenosine infusion prior to LAD occlusion. Therefore, it is likely that PICSO decreases reactive hyperemia due to mechanical factors arising from venous engorgement rather than by reducing the ischemic stimulus causing vasodilation.

Computation of diagnostic data from coronary sinus pressure: a comparison between two possible models

We have evaluated two mathematical models to describe the increase in coronary sinus pressure (CSP) following pressure controlled intermittent coronary sinus occlusion (PICSO). The models are evaluated and compared on the basis of human and canine data. Both models were fitted by non-linear least squares algorithms. Next, derived quantities, such as plateau, rise-time and mean integral of the coronary sinus pressure were calculated from the model parameters. Corresponding quantities for the two models were compared with regard to mean values, rate of successful calculation and specific features characterizing the human or canine case. One model was found to be superior for investigational purposes. The other model was found to be more stable in critical situations and is therefore suggested for usage in closed loop regulation of PICSO. Physiologically, the differences in mean values of the derived quantities between the two models were found to be negligible. The formal statistical significance of the differences is but a consequence of the large number of PICSO cycles analysed.

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.

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.

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.

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.

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.

Coronary sinus occlusion pressure and its relation to intracardiac pressure

The hemodynamic components of coronary sinus (CS) occlusion pressure in humans have not been well described. If no other outflow for venous blood were present, then after acute occlusion of the coronary sinus the pressure would increase and equal aortic pressure. However, if thebesian vein drainage between the left ventricle and the coronary veins has an important role in humans, then CS occlusion pressure might reflect left ventricular (LV) pressure through transmitted LV pressure or intramyocardial pressure. To study this relation, 27 patients who underwent routine diagnostic cardiac catheterization were evaluated. Occlusion was accomplished by sudden inflation of a No. 7Fr balloon-tipped catheter placed into the CS. LV end-diastolic pressure and end-diastolic CS occlusion pressure were simultaneously recorded at rest. LV end-diastolic pressure (16.7 ± 5.6 mm Hg) was not significantly different from end-diastolic CS occlusion pressure (15.9 ± 5.4 mm Hg). LV end-diastolic and end-diastolic CS occlusion pressures were positively correlated (p < 0.001) over the entire range of pressures (9 to 27 mm Hg). In contrast, systolic CS occlusion pressure was significantly lower than LV systolic pressure and unrelated to right-sided heart pressures. It is concluded that in humans, end-diastolic CS occlusion pressure closely parallels LV end-diastolic pressure, and measurement of CS occlusion pressure to assess LV end-diastolic pressure may have clinical use. These findings also suggest the existence of hemodynamically important thebesian vessel connections that may have implications for retroperfusion or pressure-controlled intermittent CS occlusion in humans.

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