[Cholesterol lowering therapy after myocardial infarction. Consequences of the CARE study]. / Kolesterolsenkende behandling etter hjerteinfarkt. Konsekvenser av CARE-studien.

In the recently published CARE-study, 4,159 patients aged 21-75 years were included and randomised to treatment with pravastatin 40 mg once daily or placebo 3-20 months following a myocardial infarction. Inclusion criteria were a total cholesterol < 6.2 mmol/l and LDL-cholesterol 3.0-4.5 mmol/l. Mean follow-up time was five years. Average reduction of total cholesterol was 20% and of LDL-cholesterol 28% in the treatment group. The incidence of coronary death or non-fatal myocardial infarction was reduced by 24% (p = 0.003). The cholesterol levels in the CARE-study were similar to those in most western populations and lower than in the 4S study. This must be considered when evaluating the different results of the treatment in the two studies. It seems fair not only to offer statin treatment to patients complying with the 4S inclusion criteria, but also to patients with values as in the CARE population.

Carvedilol improves function and reduces infarct size in the feline myocardium by protecting against lethal reperfusion injury.

This study examined the effect of carvedilol, a vasodilating beta-adrenoceptor antagonist and antioxidant, on lethal reperfusion injury in feline hearts subjected to 40 min of regional ischemia and 180 min of reperfusion. 30 open chest anaesthetized cats were randomized into three groups. A control (n = 10) was compared with a group given carvedilol before coronary artery occlusions (n = 10) and a group given carvedilol immediately before and during early reperfusion (n = 10). Regional myocardial function was measured by sonomicrometry. Infarct size was determined by staining the left ventricle with triphenyl tetrazolium chloride. Myocardial blood flow was measured by radiolabeled microspheres. Tissue levels of glutathione were measured after reperfusion. Infarct size was significantly reduced compared to control both when carvedilol was given before ischemia (0.2 +/- 0.1 vs. 17.6 +/- 3.6%, P < 0.05). and when given immediately before reperfusion (3.7 +/- 1.3 vs. 17.6 +/- 3.6%, P < 0.05). Regional shortening improved significantly and the incidence of ventricular fibrillation during early reperfusion was reduced in both groups treated with carvedilol compared to control. Oxidized glutathione did not differ between groups in the post-ischaemic myocardium. This study supports that lethal reperfusion injury is a significant phenomenon. Furthermore, carvedilol reduces infarct size and reperfusion arrhythmias, and improves post-ischaemic regional myocardial function by protecting against both ischaemic and lethal reperfusion injury. The present study does not answer whether it is the non-selective beta- or alpha 1-receptor antagonism, the antiarrhythmic or the antioxidant actions of carvedilol that is responsible for the protective effect.

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium.

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3-8 micrograms kg-1 min-1 in group I (n = 8); left ventricular peak systolic pressure (LVSP) 84 +/- 4 mmHg (mean +/- SEM) during coronary artery occlusion. In group II (n = 7) LVSP was increased to 188 +/- 10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8 +/- 2.0% vs. 11.0 +/- 1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30 +/- 0.18 vs. 1.34 +/- 0.08 mL min-1 g-1 and 2.58 +/- 0.23 vs. 1.49 +/- 0.07 mL min-1 g-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.

Peroxisomal fatty acid oxidation capacity is more resistant to ischaemic and reperfusion injury than mitochondrial fatty acid oxidation capacity in feline hearts.

We investigated ischaemic and postischaemic mitochondrial and peroxisomal fatty acid oxidation capacity, ATP levels and regional function in 40 anaesthetized open chest cats subjected to 10 or 40 min of regional myocardial ischaemia with or without 3 h of reperfusion (n = 10 in each situation). Following 10 min of ischaemia, the mitochondrial fatty acid oxidation capacity measured in tissue extracts from ischaemic tissue (nmol min-1 mg protein-1) was reduced in both subepi- and subendocardium, but was normalized in reperfused tissue extracts from both wall layers (0.29 +/- 0.03 and 0.30 +/- 0.04 vs. 0.57 +/- 0.05 and 0.59 +/- 0.05. P < 0.05). Peroxisomal fatty acid oxidation capacity in tissue extracts was unaffected by ischaemia and reperfusion. ATP levels and regional function measured in the LAD region was partly restored transmurally. After 40 min of LAD occlusion, mitochondrial fatty acid oxidation capacity was reduced, with higher activity in subepi- than in subendocardium (0.27 +/- 0.05 vs. 0.19 +/- 0.04. P < 0.05). Reperfusion did not restore mitochondrial fatty acid oxidation capacity. Peroxisomal fatty acid oxidation capacity was increased in the ischaemic subendocardium compared with levels in non-ischaemic subendocardium (0.53 +/- 0.02 vs. 0.45 +/- 0.03, P < 0.05), with normalization at the end of reperfusion. ATP levels were non-uniformly reduced during ischaemia and not repleted during reperfusion. Regional function recovered in circumferential segments but not in longitudinal segments following 40 min of ischaemia. In conclusion fatty acid oxidation enzymes seem to be more resistant to ischaemia in peroxisomes than in mitochondria. Mitochondrial fatty acid oxidation is fully reversible following shortlasting ischaemia, but remains depressed following prolonged ischaemia and reperfusion.

Myocardial perfusion and function in dogs with moderate coronary stenosis.

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl = 1.077 +/- 0.15 versus ANT:POS StD = 0.477 +/- 0.11, P < 0.03) and was confirmed with radiolabeled microspheres measurements (ANT:POS Cntl = 1.18 +/- 0.2 ml/min/g versus ANT:POS StD = 0.44 +/- 0.1 ml/min/g; P < 0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P < 0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P = NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl = 0.964 +/- 0.02 versus StD = 0.884 +/- 0.03; P < 0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.

Midazolam in combination with fentanyl/fluanisone and nitrous oxide as anaesthesia in rabbits--cardiovascular parameters.

When establishing a rabbit model for cardiovascular research in our laboratory we have used midazolam in combination with fentanyl/fluanisone (MFF) and nitrous oxide as anaesthesia. In this study we focused on the effect of the anaesthetic regimen on cardiovascular parameters during open-chest surgery in 12 rabbits. Rabbits were tranquillized by intramuscular injection of fentanyl/fluanisone (0.2 ml/kg of the drug that contained 10 mg/ml fentanyl and 0.2 mg/ml fluanisone). After an intraperitoneal injection of midazolam (4 mg/kg) and additional i.m. injection of fentanyl/fluanisone (0.1 ml/kg) the rabbits were tracheotomized and ventilated on a respirator delivering a gas mixture of 50% N2O, 47.5% O2, and 2.5% CO2. The femoral vein and artery were cannulated and then rabbits received a supply of MFF intravenously. The chest was opened by midline sternotomy and the left ventricle was instrumented with piezo-electric crystals for measurement of regional left ventricular function and with a pressure catheter to measure left ventricular pressure. Radiolabelled microspheres were used to assess cardiac output and left ventricular tissue blood flow. Blood gas analysis showed no difference in the values of pH, pCO2 and pO2 between the open-chest and the closed-chest states. Mean aortic pressure was 74 +/- 4 mmHg in the closed-chest state and 65 +/- 4 mmHg in the open-chest state. Tissue blood flow showed that the left ventricle was well perfused, and mean tissue blood flow values varied between 1.80 and 2.36 ml/min.g. We conclude that the anaesthetic regimen used is easy to control. It is well tolerated in rabbits and is suitable for studies on myocardial contraction in rabbits.

Effects of endurance training on left ventricular performance: a study in anaesthetized rabbits.

Endurance training is known to increase ventricular performance during exercise and to decrease resting heart rate. The aim of this study was to evaluate a model for endurance training in rabbits and to study the effects of endurance training on local myocardial performance in the left ventricle during resting conditions. One group of rabbits underwent a 10-week exercise training programme. The rabbits trained 5 days a week on a treadmill. Training periods increased gradually from 15 min to 1 h with increments in speed from 0.5 to 1.2 km h-1. After the training programme the rabbits were anaesthetized and studied as acute open-chest preparations. A micro-tip pressure transducer was introduced via apex to the left ventricle and two pairs of ultrasonic crystals were implanted in the left anterior wall to measure segment lengths. One pair measured shortening in the circumferential direction whereas the other pair measured shortening in the longitudinal direction. Heart rate was lower in the trained group (n = 5), 172 +/- 9 beats min-1 (mean +/- SEM), compared with 235 +/- 19 beats min-1 in the control group (n = 8) (P < 0.02). Stroke volume, measured by radio-nuclidelabelled microspheres, was greater in the trained rabbits compared with controls (P < 0.03). Shortening in both segments was of similar magnitude for the trained and control groups. End-systolic pressure-length relations (ESPLR) obtained by occlusion of the descending aorta (balloon catheter) showed reduced slopes for longitudinal segments in the trained group compared with the control group (P < 0.05). We conclude that this endurance training programme in rabbits can be used to study myocardial effects of endurance training. Furthermore, the less steep slope of ESPLRs for the longitudinal segment in the trained animals might indicate a structural myocardial remodelling and increased contractile reserve that might be recruited during adrenergic stimulation in the trained group.

Non-uniform recovery of segment shortening during reperfusion following regional myocardial ischaemia despite uniform recovery of ATP.

OBJECTIVE: This study focused on transmural postischaemic recovery of ATP and regional contractile function related to reversible and irreversible tissue injury. METHODS: Fifty anaesthetised open-chest cats were randomised into two groups. Groups I: 10 min of LAD occlusion (n = 10) and 10 min of LAD occlusion followed by 180 min of reperfusion (n = 15). Group II: 40 min of LAD occlusion (n = 10) and 40 min of LAD occlusion followed by 180 min of reperfusion (n = 15). Histochemical staining (TTC) was performed in hearts from 5 additional cats subjected to 40 min of LAD occlusion and 180 min of reperfusion. Regional function was measured by sonomicrometry in the circumferential (CIRC) and longitudinal (LONG) axis of the anterior left ventricular midwall. Myocardial blood flow was measured with radiolabelled microspheres. Adenine nucleotides in the subepi- and subendocardium were measured with high-pressure liquid chromatography after LAD occlusion and after reperfusion. RESULTS: Ten minutes of ischaemia induced a transmurally uniform ATP depletion. Repletion of ATP following reperfusion was transmurally uniform. Recovery of regional shortening was non-uniform with better recovery in CIRC (76 +/- 8% vs. LONG; 46 +/- 10%, P < 0.05). Forty minutes of ischaemia induced a more severe ATP depletion in the subendocardium compared to the subepicardium. A slight recovery of ATP following reperfusion was transmurally uniform. Recovery of function was present only in CIRC (48 +/- 6%). Tissue blood flow showed a transmurally homogenous flow restriction during ischaemia and uniform recovery following reperfusion. TTC staining demonstrated predominantly subendocardial infarctions following 40 min of regional ischaemia. CONCLUSIONS: Postischaemic recovery of regional function is non-uniform and independent of ATP repletion and collateral blood flow during ischaemia. Absence of functional recovery in LONG is associated with development of infarction.

Endogenous adenosine attenuates myocardial stunning by antiadrenergic effects exerted during ischemia and not during reperfusion.

The effect of adenosine receptor blockade and adrenergic blockade on myocardial stunning [left anterior descending coronary artery (LAD) occluded for 10 min and reperfused for 180 min] was studied in 38 open-chest cats. A control group (Control) was compared with two other groups in which adenosine receptors were blocked by 8-phenyltheophylline (7.5 mg/kg) before reperfusion (8-PT-R) or before ischemia (8-PT-I). Group A, in which adrenergic receptors were blocked (doxazosin 200 micrograms/kg + propranolol 1 mg/kg), was compared with group A + 8-PT-I, in which both adenosine and adrenergic receptors were blocked before coronary artery occlusion. Regional systolic function assessed by sonomicrometry in the LAD perfused area recovered less in 8-PT-I (55 +/- 5% recovery) as compared with Control (87 +/- 9%) and 8-PT-R (89 +/- 8%), which indicates that adenosine receptor blockade during ischemia increases stunning. Functional recovery was similar in Control, group A (96 +/- 5%), and group A + 8-PT-I (87 +/- 5%), which demonstrates that if adrenergic receptors are blocked, adenosine receptor blockade during ischemia does not increase stunning. These results may indicate that the cardioprotective effects of endogenous adenosine are mediated through antiadrenergic effects exerted during coronary artery occlusion.

Intravenous lipid infusion results in myocardial lipid droplet accumulation combined with reduced myocardial performance in heparinized rabbits.

The question addressed in this study was whether a relation between myocardial lipid droplet accumulation and depressed myocardial function existed following intralipid infusion for 45 min in open chest, anaesthetized rabbits. One group of rabbits (n = 8) received intralipid infusion whereas a control group (n = 8) received sodium chloride. Local myocardial performance was obtained by sonomicrometry and the fractional volume of myocardial lipid droplets was measured by morphometric methods. The fractional volume of lipid droplets was 0.667 +/- 0.116% in the intralipid group compared with 0.318 +/- 0.080% in the control group (P < 0.03). Cardiac output and stroke volume fell 26% (P < 0.0001) and 34% (P < 0.0001), respectively, as a result of intralipid infusion. However, myocardial blood flow obtained by radiolabelled microspheres remained unchanged. Local myocardial function was reduced for both segments after intralipid infusion; maximal systolic shortening was reduced from 15.63 +/- 1.45 to 12.07 +/- 1.55% (P < 0.002) in the circumferential segment and from 9.46 +/- 1.17 to 7.40 +/- 0.53% (P < 0.05) in the longitudinal segment. The end-diastolic length of the circumferential segment was reduced by 3% (P < 0.05) after intralipid infusion. The reduced end-diastolic length of circumferential segments together with unchanged left ventricular end-diastolic pressure might indicate reduced left ventricular end-diastolic compliance. We conclude that acute intralipid infusion in rabbits results in myocardial lipid droplet accumulation and depressed local myocardial function.

Blockade of adenosine receptors during ischaemia increases systolic dysfunction but does not affect diastolic creep in stunned myocardium.

The impact of adenosine receptor blockade on left ventricular systolic function and diastolic creep in stunned myocardium was studied in 20 sodium pentobarbital anaesthetized cats. A control group (n = 10) was compared with a group (n = 10) where adenosine receptors were blocked by 8-phenyltheophylline (7.5 mg.kg-1 i.v.) prior to a 10 min occlusion of the left anterior descending coronary artery. Regional function was assessed by sonomicrometry of the left ventricular anterior wall. Tissue blood flow and haemodynamic measurements were obtained at pre-occlusion, during occlusion, and after 30 and 60 min of reperfusion. Tissue blood flow in the LAD region was low and homogeneous during coronary occlusion in both groups. Systolic function assessed by regional shortening and inotropic parameters was significantly more reduced in the 8-PT treated group (P < 0.05). Diastolic creep and compliance assessed by the end-diastolic pressure-length relationship did not differ between groups. Thus, endogenous adenosine protects against systolic dysfunction, but appears to have no impact on diastolic creep in stunned myocardium. Furthermore, our results show that the protective effect of endogenous adenosine is not caused by increased collateral blood flow into the ischaemic area during coronary artery occlusion or by increased blood flow in the reperfusion period.

Is postsystolic shortening area always a marker of myocardial ischaemia?

UNLABELLED: Postsystolic shortening area has been shown to be a sensitive marker of myocardial ischaemia in a one-vessel model. We tested whether postsystolic shortening provoked by interaction between ischaemic and nonischaemic regions is reduced in a two-vessel model, one vessel occluded and one subjected to coronary artery stenosis. Regional function in the left ventricular anterior wall was studied by orthogonal sonomicrometry during left coronary underperfusion in 14 pentobarbital-anaesthetized cats with an acute circumflex coronary artery occlusion. Left coronary underperfusion in two discrete steps decreased subendocardial blood flow in the left ventricular anterior wall to on average 60% (P < 0.001) and 20% (P < 0.001) of control value, while subepicardial flow did not change. End-diastolic lengths of longitudinal segments increased markedly even during mild subendocardial underperfusion, whereas end-diastolic lengths of circumferential segments only increased during severe subendocardial underperfusion with concomitant increase of left ventricular end-diastolic pressure. Systolic shortening, pressure-length loop area and shortening velocity of circumferential segments did not change. In contrast, systolic shortening and total pressure-length loop area of longitudinal segments decreased progressively approaching zero values during severe coronary underperfusion. Shortening velocity of longitudinal segments also decreased progressively during experimental protocol whereas postsystolic shortening area did not change. CONCLUSIONS: postsystolic shortening area is not a marker of subendocardial ischaemia in a two-vessel model which indicates that postsystolic shortening is primarily a phenomenon related to model of ischaemia. End-diastolic lengthening is predominant in the longitudinal axis of the heart during subendocardial ischaemia.

Myocardial contractility evaluated from cross-oriented segments during beta-adrenergic blockade or sympathetic nerve stimulation.

In patient and experimental models of regions of the left ventricle subjected to ischaemia and thus made dysfunctional it is important to characterize the inotropic state of the remaining myocardium. Eighteen pentobarbitone-anaesthetized open-chest cats with an acute circumflex coronary artery occlusion were therefore studied during either sympathetic nerve stimulation (n = 9), or after beta-adrenergic blockade (n = 9). Myocardial contractility was evaluated from cross-oriented segments in the left ventricular anterior wall during stable haemodynamics and during 5 s inferior caval occlusion. The end-systolic pressure-length relationship of longitudinal segments was rather insensitive to beta-adrenergic blockade and sympathetic nerve stimulation. The end-systolic pressure-length relationship of circumferential segments was suitable as a marker of contractility in the low contractility range, whereas the peak systolic shortening velocity parameter was more suitable in the upper contractility range. The pressure-length loop area versus end-diastolic length relationship of both circumferential and longitudinal segments reflected both increased and decreased left ventricular inotropic state. We therefore conclude that the pressure-length loop area versus end-diastolic length relationship is the best index of regional myocardial contractility in regional ischaemic hearts.

Changes in myocardial contraction pattern during initial reperfusion.

The characteristics of hypercontraction during initial reperfusion were studied in 10 pentobarbitone-anesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 1 h of reperfusion, and regional function was assessed by two cross-oriented pairs of sonomicrometers placed in the left ventricular anterior wall. At 1 min of reperfusion (hyperfunctional phase) there was an uniform contraction pattern with 90% recovery of ejection shortening in both circumferential and longitudinal segments. During initial hypercontraction, end-diastolic segment lengths remained unchanged, whereas end-systolic segment lengths decreased transiently. Inotropic stimulation during reperfusion in four additional animals also affected end-systolic lengths more than end-diastolic lengths. This suggests that the initial hyperfunctional phase is due to an inotropic stimulation of the stunned myocardium, most probably caused by intracellular Ca2+ overload. At 5 min of reperfusion a nonuniform contraction pattern had developed with 68% recovery of shortening in circumferential segments vs. 25% in longitudinal segments. The decreased performance in longitudinal segments was paralleled by a delayed start of contraction as well as a decreased velocity of contraction. Because longitudinal segment shortening is a sensitive parameter of subendocardial performance, our results indicate a brief transmural hypercontraction followed by increasing dysfunction (stunning) in the subendocardial layer.

A study on lipid metabolism in heart and liver of cholesterol- and pectin-fed rats.

Pectin is known as a cholesterol-reducing dietary fibre, and in the present study we addressed the question whether pectin affected the quantity of lipid in droplets in the myocardial cells and of lipid in the liver cells. Male Wistar rats received either a diet containing cholesterol or a standard diet without cholesterol with 0, 50 or 100 g pectin/kg incorporated for 10 d. The fractional volume of lipid droplets in the myocardial cells decreased as a function of pectin dose in both the standard-fed and the cholesterol-fed rats. Serum cholesterol was significantly reduced in both groups after addition of 100 g pectin/kg diet. The cholesterol diet increased the liver cholesterol level, and 100 g pectin/kg diet resulted in a lower concentration of liver cholesterol in the cholesterol-fed animals, but the influence on standard-fed rats was modest. Hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88; HMG-CoA reductase) activity increased when pectin was given in the standard diet. Liver triacylglycerol level increased after cholesterol and pectin feeding. Mitochondrial fatty acid oxidation and phosphatidate phosphohydrolase (EC 3.1.3.4) activity tended to decrease, whereas the peroxisomal fatty acid oxidation and acyl-CoA oxidase activity were unchanged. Increased hepatic triacylglycerol content by cholesterol and pectin treatment may be due to inhibited mitochondrial fatty acid oxidation along with increased availability of fatty acid for esterification and triacylglycerol synthesis. The presence of pectin in the diets of cholesterol-fed rats resulted in increased hepatic concentration of triacylglycerols and increased mitochondrial fatty acid oxidation. In this case the hepatic accumulation of triacylglycerol may be mediated by a reduced efflux of triacylglycerols from the liver.

Negative inotropic effect of propranolol is attenuated in underperfused feline heart with an acute ischemic region.

beta-Adrenergic blockade alleviates myocardial ischemia, probably largely through heart rate (HR) reduction. We hypothesized that the negative inotropic effect of beta-blockade, which is believed to be potentially dangerous, is attenuated in underperfused hearts with an acute coronary artery occlusion. We studied the effect of intravenous propranolol (1 mg/kg i.v.) in feline hearts with acute circumflex coronary artery (LCX) occlusion by cross-oriented segments in normally perfused and mildly underperfused left ventricular (LV) anterior wall. A control group (n = 10) was compared with a stenosis group (n = 9) in which the mean coronary perfusion pressure was reduced (91 +/- 4 g vs. 136 +/- 5 mm Hg, p < 0.01). End-systolic pressure-length (ESP-ESL) relations during dynamic afterload increase and preload reduction were calculated to evaluate regional inotropy. HR and LV peak systolic blood pressure (LVSP) decreased in both groups after beta-blockade (p < 0.05). Subendocardial and mid-myocardial blood flow measured by radiolabeled microspheres decreased in the control group (p < 0.05) but was unchanged in the stenosis group. Systolic shortening of circumferential segments also decreased in the control group (p < 0.05) but was unchanged in the stenosis group. ESP-ESL relations of circumferential segments shifted markedly rightward in the control group, whereas a modest rightward shift was noted in the stenosis group. This study in feline heart with acute LCX occlusion showed an attenuated negative inotropic effect of beta-blockade in underperfused LV anterior wall.

Non-uniform recovery of performance in stunned myocardium evaluated by two-dimensional sonomicrometry.

The objective of the present study was to assess the uniformity of contraction in reperfused myocardium. Regional function was measured by two pairs of piezo-electric crystals oriented in the circumferential and longitudinal axis of the left ventricular anterior midwall in 10 open-chest pentobarbitone-anaesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 60 min of reperfusion. Myocardial blood flow was measured four times by radioactive labelled microspheres: at pre-occlusion, occlusion and after 30 and 60 min of reperfusion. There was a severe and transmural homogenous ischaemia during coronary occlusion. The recovery of ejection shortening was on average 76% at 30 min and 77% at 60 min of reperfusion in circumferential segments versus 25 and 44% in longitudinal segments (P < 0.05). Diastolic function was deranged in longitudinal segments; at 60 min of reperfusion the end diastolic pressure-length relation was still shifted rightwards in longitudinal segments, whereas it was normalized in circumferential segments. In conclusion, systolic and diastolic dysfunction in stunned myocardium were more severe in the longitudinal axis than in the circumferential axis of the feline heart. This indicates that stunning was more pronounced in longitudinally oriented sub-endocardial fibres which were reflected by the longitudinal segment, despite transmural homogenous ischaemia during coronary artery occlusion.