Changes In Myocardial Metabolism Research Articles

Alterations in Myocardial Metabolism in the Diabetic Myocardium

Free fatty acids are the preferred substrate for the myocardium. However, under conditions of ischemia, glucose becomes the primary myocardial energy source. Its metabolism avoids the toxic end-products of free fatty acids, which include oxygen free radicals. Patients with diabetes mellitus have impaired uptake of glucose. As a consequence the diabetic myocardium relies heavily on free fatty acid metabolism as its energy source. The results of these alterations in myocardial metabolism ultimately contribute to changes in endothelial function, inflammation, and oxidative stress. This review describes the defects in diabetic myocardial metabolism and how they contribute to cardiovascular dysfunction. The mechanisms by which intravenous insulin infusions can be used to modulate these changes in myocardial metabolism to improve clinical outcomes are discussed.

Isoflurane and sevoflurane during reperfusion prevent recovery from ischaemia in mitochondrial KATP channel blocker pretreated hearts

Inhalation anaesthetics given only during post-ischaemic reperfusion have some protective effect against reperfusion injury in the heart. Adenosine triphosphate-regulated mitochondrial potassium channels have been shown to be an important mediator of cardioprotection. Thus, we investigated whether 5-hydroxydecanoate, a putative mitochondrial potassium channel blocker, prevents the cardioprotective effect of volatile anaesthetics. Forty rats were randomly allocated to four groups of equal size: control group, 5-hydroxydecanoate group, 5-hydroxydecanoate + sevoflurane group and 5-hydroxydecanoate + isoflurane group. Seven minutes after the start of perfusion, normal saline (control group) or 5-hydroxydecanoate (the other groups) was administered. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min. One minute before the end of the ischaemic period, 2.7% sevoflurane or 1.4% isoflurane were administered in the 5-hydroxydecanoate + sevoflurane or 5-hydroxydecanoate + isoflurane groups respectively. The heart was reperfused for 10 min. Adenosine triphosphate content at the end of reperfusion in the 5-hydroxydecanoate + sevoflurane group was significantly lower (P < 0.05) than those in the control and the 5-hydroxydecanoate + isoflurane groups (19.9 +/- 8.7, 28.1 +/- 3.4 and 30.4 +/- 2.3 micromol g(-1), respectively). In addition, the combination of inhalation anaesthetics and 5-hydroxydecanoate decreased the ratios of recovered hearts from ischaemia (5-hydroxydecanoate + sevoflurane group: 40%, 5-hydroxydecanoate + isoflurane group 50%). 5-hydroxydecanoate alone caused no significant changes in haemodynamics and myocardial metabolism. However, the combination of 5-hydroxydecanoate and volatile anaesthetics impaired the recovery from ischaemia. Although animal data cannot be extrapolated to human beings, we suggest that more attention be paid to patients on sulphonylurea drugs, which inhibit potassium channels, when they are anaesthetized with volatile anaesthetics.

Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial

The benefit of reperfusion therapies for ST-elevation acute myocardial infarction (STEMI) is limited by post-infarction left-ventricular (LV) dysfunction. Our aim was to investigate the effect of autologous bone marrow-derived stem cell (BMSC) transfer in the infarct-related artery on LV function and structure. We did a randomised, double-blind, placebo-controlled study in 67 patients from whom we harvested bone marrow 1 day after successful percutaneous coronary intervention for STEMI. We assigned patients optimum medical treatment and infusion of placebo (n=34) or BMSC (n=33). Our primary endpoint was the increase in LV ejection fraction and our secondary endpoints were change in infarct size and regional LV function at 4 months' follow-up, all assessed by MRI. We assessed changes in myocardial perfusion and oxidative metabolism with serial 1-[11C]acetate PET. Analyses were per protocol. This study is registered with , number NCT00264316. Mean global LV ejection fraction 4 days after percutaneous coronary intervention was 46.9% (SD 8.2) in controls and 48.5% (7.2) in BMSC patients, and increased after 4 months to 49.1% (10.7) and 51.8% (8.8; OR for treatment effect 1.036, 95% CI 0.961-1.118, p=0.36). Compared with placebo infusion, BMSC transfer was associated with a significant reduction in myocardial infarct size (BMSC treatment effect 28%, p=0.036) and a better recovery of regional systolic function. Myocardial perfusion and metabolism increased similarly in both groups. We noted no complications associated with BMSC transfer and all but one patient in the BMSC group completed the 4 months' follow-up. Intracoronary transfer of autologous bone marrow cells within 24 h of optimum reperfusion therapy does not augment recovery of global LV function after myocardial infarction, but could favourably affect infarct remodelling.

Myocardial Substrate Metabolism in the Normal and Failing Heart

The alterations in myocardial energy substrate metabolism that occur in heart failure, and the causes and consequences of these abnormalities, are poorly understood. There is evidence to suggest that impaired substrate metabolism contributes to contractile dysfunction and to the progressive left ventricular remodeling that are characteristic of the heart failure state. The general concept that has recently emerged is that myocardial substrate selection is relatively normal during the early stages of heart failure; however, in the advanced stages there is a downregulation in fatty acid oxidation, increased glycolysis and glucose oxidation, reduced respiratory chain activity, and an impaired reserve for mitochondrial oxidative flux. This review discusses 1) the metabolic changes that occur in chronic heart failure, with emphasis on the mechanisms that regulate the changes in the expression of metabolic genes and the function of metabolic pathways; 2) the consequences of these metabolic changes on cardiac function; 3) the role of changes in myocardial substrate metabolism on ventricular remodeling and disease progression; and 4) the therapeutic potential of acute and long-term manipulation of cardiac substrate metabolism in heart failure.

Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats

Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM. Rats received high-fat (HFD) or low-fat (LFD) diets for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile function and insulin signalling were assessed in papillary muscles and ventricular lysates, respectively. Fasting and post-load blood glucose levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed structural changes and triglyceride accumulation. HFD-muscles developed higher baseline and maximum forces, but showed impaired recovery from higher workloads. Insulin-associated modulation of Ca2+-induced force augmentation was abolished in HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol 3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of phospholamban, a critical regulator of myocardial contractility, was decreased in HFD-hearts (p < 0.05). HFD induced a hypertrophy-like cardiac phenotype, characterised by a higher basal contractile force, an impaired recovery from increased workloads and decreased insulin-mediated protection against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin resistance and phospholamban hypophosphorylation. Our data suggest that myocardial insulin resistance, resulting from exposure to excessive alimentary fat, may contribute to the pathogenesis of diabetes-related heart disease.

Basal Metabolic State of Hearts of Patients With Congenital Heart Disease: The Effects of Cyanosis, Age, and Pathology

Background Experimental models have established numerous myocardial metabolic changes with chronic hypoxia and maturation. We conducted this study to specifically look at the effects of cyanosis, age, and pathology upon the basal metabolic state of the immature human heart. Methods One hundred and eighty-one pediatric patients (37 cyanotic, 144 acyanotic) undergoing open heart surgery were recruited. A myocardial biopsy was collected before ischemia and analyzed for adenine nucleotides, purines, and lactate. The effect of cyanosis was estimated by an analysis of age-matched pairs of children with either ventricular septal defects or tetralogy of Fallot, and by multiple regression modeling. The effects of age and pathology were estimated in acyanotic children also by multiple regression modeling (adjustments were made for baseline differences). Results The only effect of cyanosis was for lactate where the paired t test, and unadjusted and adjusted regression analyses were all consistent (ranging from 1.33 to 1.48 times higher in cyanotic than acyanotic children). The concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) declined with age, whereas the ATP/ADP ratio increased; these associations remained significant even in the adjusted regression analysis. None of the effects of acyanotic pathology were highly significant ( p < 0.01), implying that few important metabolic differences were attributable to pathology. Conclusions Cyanosis and age are important factors that determine the basal metabolic state of the pediatric heart. Cyanotic patients have higher myocardial lactate concentrations, whereas young age is associated with lower ATP/ADP ratios and higher adenine nucleotide levels.

Myocardial metabolic changes during pediatric cardiac surgery: A randomized study of 3 cardioplegic techniques

BackgroundBlood cardioplegia and terminal warm blood cardioplegic reperfusion (“hot shot”) reduce myocardial injury and improve metabolic recovery in hypoxic but not normoxic experimental models. However, there is little evidence of a benefit of either technique in pediatric clinical practice compared with crystalloid cardioplegia. MethodsPediatric patients undergoing cardiac surgery were randomized to receive intermittent antegrade cold crystalloid cardioplegia, cold blood cardioplegia, or cold blood cardioplegia with a hot shot. Right ventricular biopsy specimens were collected before ischemia, at the end of ischemia, and 20 minutes after reperfusion. Cellular metabolites were analyzed. In acyanotic patients postoperative serum troponin I levels were also measured at 1, 4, 12, 24, and 48 hours. ResultsOf 103 patients recruited, 32 (22 acyanotic and 10 cyanotic), 36 (24 acyanotic and 12 cyanotic), and 35 (25 acyanotic and 10 cyanotic), respectively, were allocated to the groups receiving cold crystalloid cardioplegia, cold blood cardioplegia, and cold blood cardioplegia with a hot shot. Cyanotic patients were younger, with longer crossclamp times. There were no significant differences in clinical outcomes between cardioplegic methods. The cardioplegic method had no overall effect in terms of adenosine triphosphate, ln(adenosine triphosphate/adenosine diphosphate), or ln(glutamate) in acyanotic patients (P = .11, P = .66, and P = .30, respectively). Also, there was no significant difference between groups in troponin I release. However, in cyanotic patients cold blood cardioplegia with a hot shot significantly reduced the decrease in adenosine triphosphate, ln(adenosine triphosphate/adenosine diphosphate), and glutamate observed at the end of ischemia and after reperfusion compared with the decrease seen in those receiving cold crystalloid cardioplegia (P = .002, P = .003, and P = .008, respectively), with cold blood cardioplegia representing an intermediate. ConclusionsFor cyanotic patients (younger, with longer crossclamp times), cold blood cardioplegia with a hot shot is the best method of myocardial protection. For acyanotic patients (older, with shorter crossclamp times), cardioplegic technique is not critical.

Myocardial redox state during coronary artery bypass grafting assessed with microdialysis.

Microdialysis allows the biochemical analysis of interstitial fluids of nearly every organ as a bedside procedure. This technique could be useful to reveal data about the myocardial metabolism during cardiopulmonary bypass in human coronary artery bypass graft (CABG) surgery. In 17 patients undergoing CABG a myocardial microdialysis catheter (CMA 70, CMA/Microdialysis AB, Sweden) was inserted in the apical region of the beating heart. Microdialysis measurements were performed at timed intervals before, during, and after cardiopulmonary bypass (CPB). The concentrations of lactate and pyruvate were analyzed semi-continuously. During CPB the myocardial lactate-pyruvate-ratio (LPR) rose from an initial 11 (8-15) to 33 (29-41) ( P<0.01). After CPB the LPR decreased to 4 (3-7) at the end of observation ( P<0.05). The pyruvate concentration showed an immediate increase from 34 (30-42) microM at the end of CPB to 181 (147-234) microM after removal of the cross-clamp with subsequent increase during reperfusion ( P<0.01). Plasma lactate and pyruvate showed no essential changes during the study. Using the microdialysis technique it was possible to analyze myocardial metabolic changes during CABG. The course of myocardial LPR as a sensitive indicator of the myocardial redox state showed profound changes during and after CPB. We propose the microdialysis technique as an additional monitoring tool in CABG.

Myocardial Hemodynamics, Physiology, and Perfusion With an Axial Flow Left Ventricular Assist Device in the Calf

The Jarvik 2000 axial flow left ventricular assist device (LVAD) is used clinically as a bridge to transplantation or as destination therapy in end-stage heart disease. The effect of the pump's continuous flow output on myocardial and end-organ blood flow has not been studied experimentally. To address this, the Jarvik 2000 pump was implanted in eight calves and then operated at speeds ranging from 8,000 to 12,000 rpm. Micromanometry, echocardiography, and blood oxygenation measurements were used to assess changes in hemodynamics, cardiac dimensions, and myocardial metabolism, respectively, at different speeds as compared with baseline (pump off, 0 rpm) in this experimental model. Microsphere studies were performed to assess the effects on heart, kidney, and brain perfusion at different speeds. The Jarvik 2000 pump unloaded the left ventricle and reduced end-diastolic pressures and left ventricular dimensions, particularly at higher pump speeds. The ratio of myocardial oxygen consumption to coronary blood flow and the ratio of subendocardial to subepicardial blood flow remained constant. Optimal adjustment of pump speed and volume status allowed opening of the aortic valve and contribution of the native left ventricle to cardiac output, even at the maximum pump speed. Neither brain nor kidney microcirculation was adversely affected at any pump speed. We conclude that the Jarvik 2000 pump adequately unloads the left ventricle without compromising myocardial metabolism or end-organ perfusion.

Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy

ObjectivesThis study noninvasively examined total creatine (CR) of the myocardium in dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) using proton magnetic resonance spectroscopy (1H-MRS). BackgroundAbnormalities in CR metabolism in failing hearts have been reported. A biochemical study suggested that myocardial metabolic changes are very similar in DCM and HCM despite the different heart failure (HF) mechanisms. MethodsUsing cardiac-gated 1H-MRS with magnetic resonance image (MRI)-guided point-resolved spectroscopy (PRESS) localization, we quantitatively measured septal CR. Patients with either DCM (n = 11) or HCM (n = 7) and age-matched normal subjects (n = 14) were examined. ResultsMyocardial CR was significantly lower in DCM patients (16.1 ± 4.5 μmol/g wet weight [range 10.2 to 22.9], p < 0.05) than that in subjects with normal hearts (27.6 ± 4.1 μmol/g [range 21.4 to 36.2]). Myocardial CR in HCM patients (22.6 ± 8.1 μmol/g [range 12.2 to 34.5]) was significantly lower than that in subjects with normal hearts (p < 0.05) but was significantly higher than that in DCM patients (p < 0.05). In 18 patients with either DCM or HCM, myocardial CR correlated positively with left ventricular ejection fraction (LVEF) (y = 0.22x + 9.8, r = 0.73, p = 0.0006) but correlated negatively with plasma B-type natriuretic peptide (BNP) levels (y = −0.012x + 22.4, r = −0.54, p = 0.022). ConclusionsThis study showed that 1H-MRS can noninvasively detect CR depletion associated with the severity of HF in cardiomyopathy.

Changes in myocardial oxidative metabolism after biventricular pacing as evaluated by [11C]acetate positron emission tomography

A 70-year-old woman with dilated cardiomyopathy and recurrent severe heart failure was admitted for biventricular pacing (BVP), which was recently reported to have clinical efficacy for severe heart failure with intraventricular conduction delay. An electrocardiogram showed complete left bundle branch block, and the QRS interval was markedly prolonged at 195 msec. Echocardiogram showed marked dilatation, diffuse hypokinesis and dyssynchrony of the left ventricle, and grade III mitral valve regurgitation. The patient underwent implantation of an atriobiventricular pacemaker and three pacing leads transvenously. The QRS interval shortened to 165 msec immediately after the BVP therapy, and improvements in echocardiographic parameters were seen at 5 months after BVP therapy. Myocardial oxidative metabolism was assessed by the monoexponential clearance rate of [11C]acetate (Kmono) as measured by positron emission tomography (PET), and myocardial efficiency was assessed by the work metabolic index (WMI) at 1 and 5 months after the BVP therapy. The PET images obtained 5 months after BVP therapy showed a decrease in the clearance of [11C]acetate compared with that obtained 1 month after BVP therapy. The Kmono of the whole left ventricle decreased from 0.051 at 1 month to 0.038 min-1 at 5 months after BVP therapy, and that of the septum, anterior wall, lateral wall and posterior wall also decreased. The WMI increased from 4.2 x 10(6) to 6.8 x 10(6) mmHg. ml/m2. These results suggest that BVP improved left ventricular function without increasing myocardial oxidative metabolism, resulting in improved myocardial efficiency, and that BVP may improve the long-term prognosis of heart failure patients with ventricular dyssynchrony. [11C]acetate PET is a useful method of evaluating global and regional myocardial oxidative metabolism in patients who have undergone BVP therapy.

Aging-related changes in myocardial purine metabolism and ischemic tolerance

Impaired tolerance to ischemia-reperfusion in older hearts may stem in part from alterations in purine catabolism, impacting on maintenance of energy state and protective signaling via extracellular adenosine. We characterized effects of aging on normoxic and post-ischemic purine metabolism in hearts from young (2–4 month), middle-aged (12 month), old (18 month), and senescent (24–28 month) C57/Bl6 mice. Normoxic function was similar in all age groups while normoxic purine efflux increased gradually with age. This was the result of enhanced efflux of hypoxanthine, xanthine and uric acid, with extracellular accumulation of adenosine and inosine remaining unchanged. While total purine washout during 60 min reperfusion following 20 min global ischemia was unaltered by aging (1057±109 nmoles/g in young vs. 1221±127 nmoles/g in senescent hearts), selective changes in purine catabolism were evident. Accumulation of adenosine and inosine were reduced by 50 and 80%, respectively, matched by 400 and 300% elevations in hypoxanthine and xanthine accumulation, respectively. Uric acid remained unchanged. Thus, while adenosine and inosine represented 15±2 and 47±3% of total purine efflux in young hearts, these values decreased to only 6±1 and 9±2% in senescent hearts. Efflux of IMP also increased 500% with aging whereas 5′-AMP was unaltered. These changes were associated with a substantial fall in ischemic tolerance, with left ventricular developed pressure recovering to 46±3% in young hearts vs. only 24±6, 16±4, and 19±4% in middle-age, old and senescent hearts, respectively. Our data collectively support a pronounced shift in purine catabolism, with reduced accumulation of salvageable and cardioprotective adenosine, and enhanced accumulation of poorly salvaged (and potentially injurious) hypoxanthine and xanthine. Mechanisms underlying this shift have yet to be determined. However, this may play a role in the marked decline in myocardial tolerance to ischemia with aging and senescence.

Validity of the microdialysis technique for experimental in vivo studies of myocardial energy metabolism.

The validity of the microdialysis technique for experimental in vivo studies of myocardial energy metabolism is not known. To address this question interstitial levels of energy-related metabolites (lactate, adenosine, inosine and hypoxanthine) obtained by the microdialysis technique were compared with corresponding metabolites from myocardial biopsies at given intervals in a porcine heart model using different protocols of ischaemia and reperfusion. In an open chest porcine heart model, interstitial levels of energy-related metabolites were monitored using the microdialysis technique. All animals (n = 23) were subjected to 120-min pretreatment followed by 40 min of regional ischaemia and 120 min of reperfusion. Tissue biopsies were obtained in the beginning, middle and at the end of the 40-min ischaemic period and at the end of the reperfusion period. Pretreatment consisted of either rest (group 1, n = 7), or rest for 90 min and one ischaemia/reperfusion (10 + 20 min) cycle (group 2, n = 9), or four ischaemia/reperfusion cycles (10 + 20 min each) (group 3, n = 7). Interstitial levels of energy-related metabolites monitored by the microdialysis technique correlated with tissue biopsy levels of lactate (r = 0.90, P < 0.001), adenosine (r = 0.89, P < 0.001), inosine (r = 0.88, P < 0.001) and hypoxanthine (r = 0.91, P < 0.001), respectively, which were obtained by tissue biopsies at given time intervals. These significant correlations were valid regardless of the functional state of the myocardium. We observed significant correlations between microdialysis probe levels and tissue biopsy levels of energy-related metabolites in both ischaemic and non-ischaemic tissue. These data assess the validity of the microdialysis technique (in the current setting) for studying dynamic changes of myocardial energy metabolism.

Effects of nebivolol on ischemia-induced metabolic changes in dog hearts.

dl-Nebivolol has a beta(1)-adrenergic blocking property and l-nebivolol has an endothelial-dependent vasodilating property, sp that a racemic mixture, deltal-nebivolol, shows both properties. This study examined the effect of dl-nebivolol on ischemic myocardium in anesthetized open chest dogs. Ischemia was induced for 3 min by ligating the left anterior descending coronary artery 10 min after IV injection of vehicle, dl-nebivolol (0.03, 0.1, and 0.3 mg/kg), or d- or l-nebivolol (0.15 mg/kg). Ischemia significantly decreased the levels of ATP, creatine phosphate, and fructose-1,6-diphosphate and increased those of ADP, AMP, hexose monophosphates, and ratio of [lactate]/[pyruvate]. dl-Nebivolol at higher doses significantly attenuated some metabolic changes caused by ischemia. Although neither enantiomers significantly affected these ischemia-induced metabolic changes, d-nebivolol appeared to attenuate adenine nucleotide reduction due to ischemia. Pretreatment with Nw-nitro-l-arginine methyl ester did not abolish the restoration of ischemia-induced myocardial metabolic changes by dl-nebivolol. In conclusion, dl-nebivolol lessens ischemic derangement of myocardial metabolism, and the effects may be due mainly to its beta-adrenergic blocking property but not to endothelium-dependent vasorelaxing property.

The left ventricular myocardium in children at early stages of diabetes mellitus: Functional and morphometric parameters

Its morphometric parameters (myocardial mass according to the procedure described by R. Devereuxe, end-diastolic volume and their ratio). Sixteen healthy children of the same age formed the control group. A gradual redistribution of transmitral flow to­wards the atrial systolic phase was found in children with a more than 5-year history of diabetes, which seems to be associated im­paired L V myocardial relaxation due to myocardial metabolic changes and to the occurrence of specific microangiopathies. The found changes progressed with time and correlated with the ap­pearance ofperipheral distal neuropathy. Within the first year of diabetes, there was a transient reduction in LV contractility, which appears to be associated with myocardial metabolic im­balance during the decompensation of the disease. There is a trend to LV myocardial hypertrophy 10years after the onset of the disease.

Alterations in the myocardial creatine kinase system precede the development of contractile dysfunction in β 1-adrenergic receptor transgenic mice

The β-adrenergic receptor system not only plays a central role in modulating heart rate and left-ventricular (LV) contractility, but is also involved in the development of heart failure. We have, recently, shown that heart-specific overexpression of the β 1-adrenergic receptor in transgenic mice (TG) initially leads to increased contractility, followed by LV hypertrophy and heart failure. Since one feature for all forms of heart failure are characteristic changes in myocardial energy metabolism, we asked whether alterations in energetics are detectable in these mice before signs of LV impairment are present. Myocardial energetics ( 31P NMR spectroscopy) and LV performance were measured simultaneously in isolated perfused hearts at different workloads. LV performance as well as contractile reserve was identical for hearts of 4-month-old TG and wild-type mice. The ratio of phosphocreatine to ATP (1.16 ± 0.05 vs. 1.46 ± 0.10) and total creatine content (17.6 ± 1.2 vs. 22.6 ± 0.9 mmol/l) were significantly reduced in TG. Furthermore, there was a significant decrease in creatine transporter content (–43%), mitochondrial (–44%) and total creatine kinase (CK) activity (–21%) as well as citrate synthase activity (–25%), indicating impaired oxidative energy generation in TG. In conclusion, these findings of alterations in the CK system, creatine metabolism and mitochondrial proteins in TG hearts prior to the development of LV dysfunction provide further evidence that changes in myocardial energetics play a central role in the deterioration of cardiac function after chronic β-adrenergic stimulation.

Effect of biventricular pacing on metabolism and perfusion in patients affected by dilated cardiomyopathy and left bundle branch block: evaluation by positron emission tomography.

Evaluate the possible changes in myocardial metabolism and perfusion induced by biventricular pacing (BIVP) in patients affected by dilated cardiomyopathy (DC) and left bundle branch block (LBBB). Eight male patients (aged 60-79 years, mean 69) affected by DC (NYHA functional class III and ejection fraction <40%) were submitted to cardiac PET in basal condition and 3 weeks after the implantation of a biventricular device. Metabolism was evaluated using F18-fluorodeoxyglucose (FDG), by the glucose load-insulin technique, and perfusion by N13-ammonia (NH3), injected at rest. Visual and a semi quantitative analyses were performed, calculating by ROIs the septum to lateral uptake ratio (SLR). The myocardial blood flow (MBF) was also calculated in ml/min/g using a dynamic acquisition and a modified Patlak method. In all 8 patients a selective defect in FDG uptake in the septum was present in basal condition (mean SLR 0.59+/-0.17) with a 'reverse mismatch' effect with respect to NH3 (mean SLR 1.07+/-0.18). During BIVP the distribution of FDG in the septal area significatively improved (mean SLR 0.86+/-0.15 P=0.011 with respect to basal); on the contrary, no significant changes were found in NH3 uptake (mean SLR 1.02+/-0.23, P=ns). On quantitative analysis the mean MBF in the septum was 1.05+/-0.37 in basal condition and did not significantly change during BIVP (0.95+/-0.34, P=0.06). Our results suggest that, in patients affected by DC and LBBB, BIVP improves the septal glucose metabolism without significant changes in myocardial perfusion.

Clinical motivation for31P MRS studies on the myocardial energy metabolism of brain dead cats

Hemodynamic instability of the brain dead potential heart donor is an exclusion criterion for heart donation for transplantation. Based on the results of myocardial biopsies it has been reported that brain death-related catecholamine induced damage of the heart causes depletion of high-energy phosphates which could explain contractile dysfunction. Our group has shown in a series of31P MRS experiments in cats that neither the onset of brain death, nor the hemodynamic deterioration which follows, nor its treatment with high dosages of dopamine affect the heart energetically as expressed by PCr/ATP ratios. However, after cardioplegic arrest and explantation, an initial and prolonged lower ATP content and an anomalous higher PCr/ATP ratio in the brain death group was found when compared with controls during long-term unperfused cold storage of the hearts. During subsequent reperfusion of the hearts, ATP and PCr levels in the brain death group were lower than in controls but equal partial recovery of PCr/ATP ratios was observed in both groups. It was concluded that PCr/ATP ratios need to be interpreted with great caution. Secondly, brain death-related hemodynamic instability is not related to significant changes of myocardial energy metabolism. Thirdly, brain death does affect the myocardial energy metabolism but the impact became apparent only during hypothermic storage and subsequent reperfusion of the donor heart.

Changes in myocardial metabolism and ultrastructure of myocardial microvessels during pharmacological and cold cardioplegia under hypothermic conditions without perfusion.

A combination of pharmacological and cold cardioplegia in with hypothermia without perfusion in open-heart surgery guarantee the reversible character of shifts in energy and free radical balance in the myocardium. However, this procedure can impair coronary micricirculation due to structural and functional changes in microvessel endothelium. Our results demonstrate that new cytoprotective approaches are extremely needed for cardiac protection during surgery.

Intraoperative metabolic monitoring of the heart: I. Clinical assessment of coronary sinus metabolites

Numerous clinical studies have corroborated the ability of intraoperative sampling of coronary sinus blood to measure changes in myocardial metabolism induced by ischemia and reperfusion. Among other changes, cardiac arrest induces a period of obligate myocardial lactate production that persists for an indeterminate amount of time after reperfusion. Coronary sinus lactate assays have been established as a standard method to compare various myocardial protection strategies. Current methodology requires detailed sample processing, precluding real-time feedback in the operating room. Newer devices hold promise in allowing the online assessment of myocardial metabolism; however, these methods await precise validation.