Effects of verapamil on intracellular lipid accumulation in cat hearts with 3 h of regional-ischaemia

In the regionally ischaemic heart lipid droplet accumulation is found in the ischaemic area and is most pronounced in the periphery. The purpose of the present study is to explore the potential effects of the calcium-channel-blocker verapamil on this accumulation. The drug is known to reduce the intensity of myocardial ischaemic injury. The myocardial ultrastructure was studied in anaesthetized open chest cats with 3 h of coronary artery occlusion. Biopsies were taken from the ischaemic, border and normally perfused myocardium defined in vivo injections of fluorescein and verified by blood flow measurements using radiolabelled microspheres. Arterial concentration of non esterified fatty acids (NEFA) was measured during the ischaemic period. A higher accumulation of lipid droplets was found in the central ischaemic myocardium of verapamil-treated cats than in control animals (p less than 0.05). The normally perfused and borderline areas were unaffected by verapamil as far as lipid accumulation was concerned and showed the same pattern as in the untreated group. The increased accumulation of lipid droplets in the ischaemic myocardium, after treatment with verapamil, may reflect a preserved metabolic activity in the ischaemic tissue or result from a higher supply of fatty acids due to increased perfusion of the central ischaemic tissue.     

Local myocardial function following coronary occlusion in cats,Effect on non-ischaemic regions

Summary. The mechanical function and perfusion in ischaemic and non-ischaemic myocardium after coronary occlusion was studied in 10 cats using pressure-length loop analysis and radiolabeled microspheres. Measurements in three regions—ischaemic, adjacent normal and remote normal myocardium—all showed different responses to coronary occlusion. In the ischaemic region loop area, segment shortening and tissue flow were markedly reduced. In the adjacent normal region, both loop area and segment shortening as well as flow increased. In the remote normal region, neither loop area, segment shortening nor flow showed consistent changes. End-diastolic segment length increased in all regions, most in the ischaemic region and least in the remote region. The increased end-diastolic segment length in all regions after coronary occlusion indicates activation of the Frank-Starling mechanism as an attempt to maintain stroke volume. However, the end-diasolic segment length did not increase uniformly for all normal myocardium: it depended on the proximity to the ischaemic region. Increased contractile function in the adjacent normal myocardium due to non-uniform distribution of the Frank-Starling effect is the most likely mechanism behind the left ventricle's ability to partially compensate for loss of contractile mass during acute regional ischaemia in anaesthetized cats.     

Moderate normovolaemic haemodilution increases regional myocardial blood flow but has no effect on experimental infarct size

Regional myocardial blood flow was measured with radioactive microspheres before and 1, 3, 6, and 12 h after occlusion of the left anterior descending coronary artery (LAD) in anaesthetized cats. In one group of cats, 1 h after LAD occlusion, moderate normovolaemic haemodilution was started with a dextran 40 solution, which reduced the haematocrit by 20-25% throughout the rest of the experiment. In the other group, the haematocrit was kept at the original level. Infarct size was measured planimetrically 12 h after the coronary ligation, using the tetrazolium staining technique for disclosing the ischaemic myocardium. Haemodilution increased blood flow in the non-ischaemic myocardium and in the so-called 'border zone' comprising both normal, and ischaemic tissue. However, in the severely ischaemic myocardium dependent on collateral blood flow, where there was no admixture of non-ischaemic myocardium, the blood perfusion was not significantly affected by the haemodilution. After 12 h of ischaemia the infarct size in the control group was fully comparable with that in the haemodiluted group: 28 +/- 3 and 27 +/- 4 (percentage of the left ventricle, mean +/- SEM), respectively.     

Does α1-adrenergic blockade influence regional blood flow regulation in hearts with coronary artery occlusion?

Summary. The effects of selective α₁-adrenergic blockade with doxazosin on regional myocardial tissue blood flow was studied in anaesthetized cats with acute coronary artery occlusion. Reflex tachycardia was prevented by selective β₁-adrenergic blockade with atenolol and coronary perfusion pressure was kept constant by partial stenosis of the descending aorta. Administration of atenolol reduced cardiac mechanical work-load by its negative inotropic and chronotropic effects, and reduced myocardial tissue blood flow in normally perfused myocardium. This reduction was most pronounced in the endocardial half-layer of the myocardium adjacent to the ischaemic region. Administration of doxazosin in this situation clearly reduced peak systolic and coronary perfusion pressure. But when coronary perfusion pressure was raised to pre-administration values, measurements of regional blood flow revealed no changes either in ischaemic or non-ischaemic myocardium. Also, there was no sign of redistribution of blood flow between endocardial and epicardial tissue in any area. This study, therefore, indicates that α₁-adrenoceptors play a minor role in the regulation of coronary blood flow in normal myocardium as well as ischaemic myocardium.     

Relationship between myocardial adenine nucleotide catabolism and tissue blood flow rate in experimental ischaemia

A method was developed for tissue preservation and evaluation of the adenine nucleotide metabolism in small samples of myocardium after 45 min of ischaemia. Ischaemia was produced by coronary artery occlusion in anaesthetized cats. Adenine nucleotides and their metabolites were measured by isocratic liquid chromatographic systems which allow quantitative analysis of the nucleotides and their metabolites inosine, hypoxanthine and xanthine in biopsies of 5-20 mg tissue. Regional myocardial blood flow was measured in the tissue surrounding the biopsies by the distribution of 15 micron radiolabelled microspheres. In central ischaemic regions the ATP level was approximately 1 mumol/g wet weight, whereas in normally perfused myocardium the ATP level was approximately 5 mumol/g tissue. In tissue with intermediate flow values, intermediate ATP levels were found. Energy charge, which summarizes all adenine nucleotide concentrations, was reduced from 0.88 to 0.50, and the molar concentrations of inosine, hypoxanthine and xanthine increased in ischaemic tissue. We conclude that this method provides reliable characterization of the local cellular energy status in cat hearts with ischaemic regions.     

Dobutamine induces ineffective work in regional ischaemic myocardium: an experimental strain rate imaging study

In the present study, we sought to investigate the effects of differing inotropic conditions on regional myocardial function in ischaemic segments. In an experimental pig model ( n =11), the regional deformation parameters peak systolic strain rate [SR(SYS) (peak velocity of thickening)], systolic strain [epsilon(SYS) (systolic wall thickening)] and post-systolic strain [epsilon(PST) (ongoing wall thickening after end of systole)] were measured during normal perfusion and regional ischaemia of the posterior wall. These parameters were compared with global contractility [E(ES) (end-systolic elastance)] measured by a conductance catheter. Ischaemia was induced by an active coronary hypoperfusion in the circumflex coronary artery. Measurements were done at baseline, during dobutamine and during esmolol infusion. In normal perfused hearts, SR(SYS) (4.8+/-0.2 s(-1) at baseline) increased during dobutamine infusion, decreased during esmolol infusion and correlated significantly with global E(ES). In addition, epsilon(SYS) averaged 93+/-3% at baseline and there was almost no epsilon(PST) (4+/-1%) in normal myocardium. In ischaemic myocardium, SR(SYS) and epsilon(SYS) were significantly reduced compared with normal myocardium at baseline (SR(SYS)=2.8+/-0.3 s(-1), and epsilon(SYS)=43+/-6%; P <0.001 compared with normal perfused hearts), whereas global E(ES) was unchanged. In contrast, epsilon(PST) was significantly increased in regional ischaemic segments compared with the non-ischaemic myocardium (15+/-2%; P <0.001). During the dobutamine infusion, SR(SYS) remained unchanged. In contrast, epsilon(SYS) decreased (25+/-5%; P <0.001) and epsilon(PST) increased (25+/-4%; P <0.05) significantly during dobutamine infusion in ischaemic myocardium. In ischaemic segments, an inotropic stimulation with dobutamine resulted in a shift of strain from systole (epsilon(SYS)) to post-systole (epsilon(PST)). Thus dobutamine induced ineffective myocardial work in ischaemic segments.     

Regional myocardial tissue blood flow during β-adrenergic blockade in cat hearts with acute ischaemia

Summary. Selective β₁ or β₂-adrenergic blockade was achieved by practolol or IPS 339, respectively, in cats with acute ligation of a coronary artery. During blockade, heart rate was kept constant by atrial pacing and blood pressure reduction was prevented by aortic clamping. Regional myocardial blood flow was measured by the distribution of 15 μm labelled microspheres. Practolol slightly reduced epicardial blood flow in ischaemic myocardium, while blood flow in border and normally perfused myocardium remained unchanged. Following IPS 339, myocardial tissue flow increased in normally perfused myocardium, on average by 37% in the endocardium and 30% in the epicardium. No changes occurred in the other regions. The flow changes brought about by IPS 339 were unrelated to haemodynamic changes, and the coronary vascular resistance was reduced. These results are indicative of coronary vasodilation related to β₂-adrenergic receptor blockade and was confined to well-oxygenated areas surrounding the acutely ischaemic zone.     

Myocardial blood flow conditions at re-perfusion following acute ischaemia

The purpose of this study was to investigate the effect of re-perfusion upon distribution of radioactive microspheres in ischaemic myocardium. Ten anaesthetized cats were given 15-micron microspheres prior to left anterior coronary artery occlusion, at 1 h of occlusion, and after 1 h of subsequent re-perfusion. Pre-occlusion blood flow estimates were lower in tissue which had been ischaemic compared with nonischaemic regions in the same heart (1.44 versus 1.87 ml X min-1 X g-1, p less than 0.001), corresponding to 23% apparent loss. Loss also occurred in ischaemic right ventricular tissue (32%). In left ventricular ischaemic endocardium, apparent loss was due to development of oedema. Oedema was also significant in epicardial ischaemic tissue. Correction for oedema eliminated two-fifths of the loss, while three-fifths was due to physical loss. Oedema increased linearly with the level of re-perfusion. During re-perfusion, myocardial blood flow in previously ischaemic tissue was inhomogeneously distributed and, on average, 28% lower than in non-ischaemic myocardium. The 15-micron spheres appeared to pass through capillaries in the ischaemic subepicardium, but this process was not enhanced by reperfusion.     

Effect of practolol on blood flow distribution in the myocardium during acute regional ischaemia in cats

The β-adrenergic blocking agent practolol was given to 11 cats with acute coronary artery ligation, and regional myocardial tissue blood flow was measured by the distribution of 15 μm labelled microspheres. Practolol reduced heart rate and cardiac contractility, but left ventricular end-diastolic pressure rose in eight animals. In three animals, however, the haemodynamics were essentially unchanged and these are referred to as non-responders. No changes in regional myocardial blood flow were observed after practolol administration, either in ischaemic, border or normal areas of the left ventricle. This indicates less serious imbalance between oxygen demand and delivery in ischaemic tissue. There was no endocardial/epicardial redistribution of tissue flow. Practolol did not appear to improve coronary perfusion, and beneficial clinical effects of practolol are therefore probably related to reduction of myocardial oxygen demands.     

Effect of hyaluronidase on substrate exchange and blood flow in the ischaemic myocardium of the dog

Summary. The mechanism for reduced myocardial ischaemic injury by hyaluronidase was studied in open chest anaesthetized dogs. Repeated coronary artery occlusions were performed and the effect of hyaluronidase (225 NF units per kg) was studied during infusion of noradrenaline 0·125 mg/kg · min. Ischaemic injury was measured as the sum of ST-segment elevations (S?ST) at 10–15 sites. Regional myocardial blood flow was determined by tracer microspheres. Blood for metabolic studies was sampled from a local coronary vein draining ischaemic tissue and from the coronary sinus draining predominantly non-ischaemic tissue. Hyaluronidase reduced S?ST and increased subepicardial and transmural blood flow in ischaemic myocardium, but flow was not significantly changed in the ischaemic subendocardium or in non-ischaemic myocardium. Hyaluronidase had no significant effect on arterio-local venous differences of oxygen, glucose, lactate or free fatty acids across the ischaemic myocardium. In conclusion, reduction of myocardial ischaemic injury by hyaluronidase can be explained by increased collateral blood flow and not by an effect on fluxes of substrates across the ischaemic myocardium.     

Relative rates of oxidation of glucose and free fatty acids by ischaemic and non-ischaemic myocardium after coronary artery ligation in the dog

Abstract. 1. Small regional ischaemic lesions, involving about 7 % of the volume of the whole heart, were produced in the greyhound dog by ligation of a branch of the anterior descending coronary artery. Arteriovenous differences across ischaemic tissue were studied by cannulation of a local vein visibly draining the ischaemic area, whereas arteriovenous differences across the non-ischaemic tissue were obtained by coronary sinus samples. This system permitted study of those ischaemic cells draining into the local vein and perfused by residual collateral circulation. Flow factors were common to all metabolites measured in local venous blood, thereby allowing detection of changes in substrate metabolism relative to each other. As the contribution of local venous blood to coronary sinus blood was negligible, it was possible to use coronary sinus values as non-ischaemic control data for each local venous sample.—2. The contributions of glucose, free fatty acids (FFA) and other substrates (lactate, pyruvate, ketones, triglycerides) to the residual oxidative metabolism of the ischaemic, infarcting dog myocardium were indirectly assessed by calculations of the oxygen extraction ratio (OER), and directly by the rate of ¹⁴CO₂ formation from ¹⁴C-labelled glucose or palmitic acid.—3. Within two hours of arterial ligation, the arteriovenous difference of glucose across the ischaemic tissue was increased relative to that of IT A. Whether calculated from OER or from ¹⁴CO₂ data, there was an increase in the oxidation rate of glucose relative to that of FFA. In absolute terms the oxygen uptake of ischaemic tissue fell almost as much as the flow rate, and the glucose uptake probably fell too. Nevertheless, glucose competed more favourably than did FFA for the residual oxidative metabolism of the ischaemic tissue.—4. In coronary sinus blood, draining predominantly non-ischaemic tissue, formation of ¹⁴CO₂ accounted for about half the uptake of ¹⁴C-glucose and formation of ¹⁴C-lactate was very low. In local venous blood draining predominantly ischaemic tissue, ¹⁴CO₂ formation accounted for about 30–40% and ¹⁴C-lactate for about 10% of the arteriovenous difference of ¹⁴C-glucose. The chemical oxygen extraction ratio of glucose and FFA could account for 90–100% of the residual oxygen uptake of the ischaemic myocardium 60–100 min. post-ligation, with glucose accounting for nearly twice as much oxygen as FFA. Thus an unexpected finding was that a major part of the glucose extracted by the ischaemic myocardium was oxidized, possibly because local venous blood drained the less severely ischaemic areas.—5. The major fate of labelled FFA extracted by the non-ischaemic myocardium also appeared to be oxidation. After arterial ligation, rates of FFA oxidation fell as assessed by both OER calculation and by rates of ¹⁴CO₂ formation. More ¹⁴C-label was recovered in the “mitochondrial” and less in the “microsomal” lipid fractions of the ischaemic tissue.—6. Lactate uptake by the normal myocardium was changed to lactate discharge by the ischaemic myocardium. Initially, tissue glycogen was the major source of the lactate formed, but 60–120 min. after arterial ligation there was less discharge of lactate and circulating ¹⁴C-gIucose became a major source of venous lactate.—7. It was concluded that not only was anaerobic metabolism of glucose accelerated by coronary artery ligation, but the aerobic metabolism of glucose increased relative to that of FFA.     

Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.

The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels.     

Regional perfusion in hearts with acute coronary artery occlusion and subsequent β2- and α1-adrenergic blockade

Summary. Blockade of cardiac adrenoceptor subtypes, coronary or myocardial, might elicit compensatory interaction from remaining unblocked subtypes. An attempt to explore this interplay was made by studying regional myocardial blood flow alterations associated with β₂-adrenergic blockade followed by β₁-adrenergic blockade in anaesthetized cats with acute coronary occlusion. In order to maintain constant needs for perfusion, atrial pacing was established and the aortic blood pressure was kept constant. In myocardium remote from the ischaemic region, β₂-adrenergic blockade produced higher endocardial blood flow whereas no flow changes were observed close to the ischaemic region. With subsequent β₁-adrenergic blockade, blood flow increased endocardially in non-ischaemic regions, but remained unchanged in epicardial tissue. Control experiments without coronary ligation revealed no increase in left ventricular oxygen consumption during the experiments and support the theory that the observed blood flow increase in the coronary ligation group, following drug interventions, was not caused by increased cardiac work. This study indicates that combined β₂- and α₁-adrenergic blockade alters the balance between receptor subtypes. Unopposed β₁-mediated vasodilation is the most likely candidate to explain why endocardial flow was increased.     

Technetium-99m-labelled HL91 and technetium-99m-labelled MIBI SPECT imaging for the detection of ischaemic viable myocardium: a preliminary study

Purpose: The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work‐up of patients with coronary artery disease. Technetium‐99m labelled sestamibi (^99mTc‐MIBI) myocardial perfusion imaging may underestimate the viability of ischaemic myocardium. Technetium‐99m labelled 4,9‐diaza‐3,3,10,10‐tetramethyldodecan‐2,11‐dione dioxime (^99mTc‐HL91) is a hypoxia‐avid agent which can identify acutely ischaemic viable myocardium in a canine model using a standard gamma camera. The aim of this study was to evaluate uptake character of ischaemic viable myocardium and diagnostic performance of single‐photon emission computed tomography (SPECT) imaging by ^99mTc‐HL91 and ^99mTc‐MIBI in detecting ischaemic viable myocardium in coronary heart disease. Methods: A total of 41 patients with coronary artery disease were recruited from March 2008 to May 2009. For detecting ischaemic viable myocardium, SPECT imaging by ^99mTc‐HL91 and ^99mTc‐MIBI were performed in all patients before coronary revascularization. Six patients with single ischaemic myocardial segment received a 2‐day SEPCT/CT imaging protocol and the uptake of ^99mTc‐HL91 in ischaemic myocardium was quantitatively analysed. The remaining 35 patients received a 1‐day ^99mTc‐HL91 and ^99mTc‐MIBI SPECT imaging protocol. Resting ^99mTc‐MIBI myocardial perfusion imaging in 3–18 months after revascularization was used as the standard methodology to evaluate the myocardial viability. Results: In 41 patients, 66 ischaemic myocardial segments were proven to be viable and 12 to be necrotic by resting ^99mTc‐MIBI myocardial perfusion imaging after coronary revascularization. Furthermore, 60 viable segments with negative uptake of ^99mTc‐MIBI showed positive uptake of ^99mTc‐HL91. The remaining six viable segments and 12 necrotic segments showed both negative uptake of ^99mTc‐HL91 and ^99mTc‐MIBI. The sensitivity, specificity, accuracy, Younden Index, positive predictive value and negative predictive value for evaluating ischaemic viable myocardium were 90·9%, 100%, 92·3%, 90·9%, 100% and 66·7%, respectively. Ischaemic viable myocardium had the negative ^99mTc‐MIBI uptake and positive ^99mTc‐HL91 uptake, which demonstrated a mismatched uptake character. Quantitative analysis indicated the uptake of ^99mTc‐HL91 in viable myocardium was increasing in the first 1–3 h and remained stable at the 3–4 h after injection. Conclusion: Functional SPECT imaging with ^99mTc‐HL91 and ^99mTc‐MIBI can be used to detect the seriously ischaemic but viable myocardium with a mismatched uptake character. The uptake of ^99mTc‐HL91 in the viable myocardium reached a stable level at 3–4 h after injection.     

Myocardial ischaemic preconditioning in the pig has no effect on the ventricular fibrillation and defibrillation thresholds

INTRODUCTION: The effects of myocardial ischaemia preconditioning in pigs on the vulnerability to ventricular fibrillation during subsequent ischaemic events are controversial. This study examined the time course of changes in ventricular fibrillation (VFT) and defibrillation (DFT) thresholds during transient myocardial ischaemia after a 45 min preconditioning period. METHODS AND RESULTS: In five open-chest pigs, VFT was measured after 3 min of regional myocardial ischaemia, at time 0, 2, 15, 30, 60 and 90 min (Control group). In seven other pigs (Test group), VFT was measured before (time 0) and 2, 15, 30, 60 and 90 min after ischaemic preconditioning by three consecutive 5 min periods of regional coronary occlusion, followed by 10 min of reperfusion. DFT was measured by increasing the stored energy systematically until successful defibrillation. Ischaemic preconditioning caused no significant change in the effective refractory period (ERP), VFT or DFT over the 90 min of the experiments. In the Control group, ERP remained stable for 30 min, though was significantly lower at 90 min (178 +/- 28 ms) than at baseline (204 +/- 32 ms, P = 0.007). VFT and DFT remained unchanged throughout the experiments, and no difference was observed in ERP, VFT and DFT between the two groups at any time during the experiment. CONCLUSION: No changes were observed in the refractory duration, ventricular vulnerability or defibrillation energy requirements up to 90 min after ventricular ischaemic preconditioning in the pig.     

Effects of the serotonin-antagonist ketanserin on the function of ischaemic and normally perfused myocardium and modification by β-1-blockade in anaesthetized normotensive dogs

The 5-HT-2 antagonist ketanserin (KAS) has been successfully used to treat acute hypertension in coronary bypass surgery. The present study was performed to investigate the effect of KAS on ischaemic myocardium. In 11 anaesthetized (piritramide) dogs, systolic contraction (sdL) and end-diastolic length (edL) of myocardium supplied by the left descending coronary artery (LAD) and the left circumflex coronary artery (LCX) were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular dP/dtmax and end-diastolic pressure (LVedP), heart rate (HR), stroke volume, and LAD flow (QLAD). Regional ischaemia to decrease sdLLAD (−48%) was achieved by LAD stenosis (QLAD −47%). Concomitantly, edLLAD increased by 8%. However, the other variables did not change. Then KAS was given i.v. (0.15+ 0.15+0.30+0.6mg/kg) at 15-min intervals. Following KAS, prestenotic sdLLAD recovered in a dose-dependent manner. LVedP and edLLAD decreased, sdLLCX increased, and the other variables were not affected. This functional recovery of ischaemic myocardium was attenuated by pretreatment with metoprolol (MET, 1 mg/kg) prior to LAD stenosis. The ischaemic area was not irreversibly damaged, however, as proven by the recovery of prestenotic sdLLAD values after release of the stenosis. The improved systolic shortening of ischaemic myocardium following KAS did not result from restored QLAD due to post-stenotic vasodilation or break up of platelet aggregates (QLAD did not increase) or from reduced afterload (AoP did not decrease). Obviously, it was mediated by β-1-receptors, as shown by the attenuation of the beneficial effect of KAS by pretreatment with MET.     

Discrepant outcome between myocardial energy-related metabolites and infarct size limitation during retroperfusion of the coronary sinus.

The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30 degrees C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38 degrees C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival.     

Does infarct size influence loss of embolised 15-micrometer microspheres from ischaemic myocardium?

The relationship between myocardial infarct size and loss of 15-micron microspheres from ischaemic tissue was investigated in anaesthetized cats. Radioactive microspheres were injected in the left atrium before and 5 h after left anterior descending coronary artery occlusion. Left ventricular hypoperfused zone (HZ) averaged 36.6% and infarct size (IS) 31.6%. Thus, 86% of HZ evolved into necrosis. Preocclusion blood flow was lower in ischaemic (1.62 ml/min per g) compared with non-ischaemic myocardium (2.09, p = 0.002), indicating 22% microsphere loss. In ischaemic subendocardium, oedema (3.7%) could account for the apparent loss. In ischaemic subepicardium, oedema was less pronounced and 18% physical sphere loss occurred. Subepicardial loss increased in proportion to IS and IS/HZ ratio (r2 = 0.71; p less than 0.005). Non-entrapment of 15-micron spheres in coronary circulation averaged 0.6%, and preocclusion spheres appeared in coronary sinus blood throughout the ischaemic period. In systemic circulation, non-entrapment during injection of preocclusion spheres was 7.8%, but only 1.8% 5 h later. Release of postocclusion spheres took place during KCl injection. Thus, myocardial ischaemia is associated with alterations in microvascular function allowing release of entrapped 15-micron spheres. Also, the magnitude of microsphere loss per gram tissue is related to infarct size.     

Discrepant outcome between myocardial energy-related metabolites and infarct size limitation during retroperfusion of the coronary sinus

The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30°C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38°C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival.     

Distribution of coronary blood flow during acute coronary occlusion in dogs. Effect of nicotinic acid and sodium salicylate

The effects of the antilipolytic agents nicotinic acid (NA) and sodium salicylate (SS) on the distribution of coronary blood flow during acute myocardial ischaemia were studied in open chest dogs. Fifteen min following experimental coronary artery occlusion, blood flow in the ischaemic myocardium was on average 28% of flow in the non-ischaemic myocardium. The reduction in blood flow in the ischaemic mycardium was more pronounced in the endocardial than in epicardial halves of the myocardium. No significant change in blood flow was observed after administration of NA or SS in either the ischemic or nonischemic part of the myocardium. Both drugs reduced the extent of myocardial ischaemic injury as shown by reduced epicardial ST-segment elevations. Arterial concentrations of fatty acids were lowered by NA or SS, whereas the mechanical activity of the heart remained unchanged. It is concluded that the reduction of acute myocardial ischaemic injury effected by NA or SS is not due to changes in myocardial blood flow, but more likely to lower myocardial oxygen demand related to reduced fatty acid utilization.