Myocardial Extraction Research Articles

Enhanced detection of reversible perfusion defects by Tc-99m sestamibi compared to Tc-99m tetrofosmin during vasodilator stress SPECT imaging in mild-to-moderate coronary artery disease

OBJECTIVESWe prospectively compared dipyridamole single-photon emission computed tomography (SPECT) imaging with Tc-99m sestamibi and Tc-99m tetrofosmin for the detection of reversible perfusion defects in patients with mild-to-moderate coronary artery disease.BACKGROUNDTc-99m tetrofosmin has a lower first-pass myocardial extraction fraction compared to Tc-99m sestamibi and thus could underestimate mild perfusion defects.METHODSEighty-one patients with 50% to 90% stenosis in one or two major epicardial vessels without previous myocardial infarction, and seven with <5% probability of coronary artery disease underwent dipyridamole SPECT imaging with both agents. The SPECT data were analyzed quantitatively.RESULTSTc-99m sestamibi detected reversible perfusion defects in a greater number of segments (total 363 and 285, p < 0.001, and mean ± SD, 2.2 ± 3.0 and 1.8 ± 2.5 per patient, p = 0.008, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively), demonstrated a larger extent of perfusion defect (mean ± SD, 15.8% ± 12.3% and 12.0% ± 11.4%, p < 0.03, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively) and more often correctly identified patients with disease in more than one coronary artery (p = 0.02). There was better defect contrast with Tc-99m sestamibi (defect/normal wall count ratios were 0.60 ± 0.15 vs. 0.73 ± 0.14 for Tc-99m sestamibi and Tc99m tetrofosmin, respectively, p = 0.01, for reversible defects seen in identical segments with both agents; and 0.73 ± 0.16 vs 0.79 ± 0.17, respectively, p <0.01, for reversible defects detected with either agent alone). There was no significant difference in diagnostic sensitivity or image quality.CONCLUSIONSThese differences between two commonly used tracers may have significant diagnostic and prognostic implications.

A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Reprinted from Life Sci. 28:89-94, 1981.

A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Reprinted from Life Sci. 28:89-94, 1981.

Aging Blunts the Effect of Nitric Oxide on Myocardial O2 Consumption.

penicillamine (SNAP, 10 -4 M, a nitric oxide donor) was applied to the left ventricle. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption. Wall thickening was determined ultrasonically. Cyclic GMP and guanylyl cyclase activity were determined. RESULTS. Myocardial O2 extraction, flow, O2 consumption and wall thickening were comparable in young and old hearts. The EPI and ENDO O2 consumption of the SNAP treated young hearts decreased significantly (>25%) compared to vehicle, Fig. 1 (left). However, SNAP had no significant effects on the O2 consumption of old hearts. SNAP also decreased the % wall thickening in the young (18.0±1.7 to 13.4±1.6%), but not old hearts (14.5±0.9 to 11.4%). The basal cyclic GMP levels in the old hearts were greater (~70%) than those in young hearts, Fig. 1 (right). SNAP increased cyclic GMP in EPI and ENDO of young, but not old, hearts. Guanylyl cyclase activity was assessed in both the young and old hearts at baseline and after increasing concentrations of sodium nitroprusside. Guanylyl cyclase activity was elevated in the old rabbit hearts with 0.5 mM nitroprusside (131±12 vs. 80±12 pmol/min/mg protein).

Effect of hyperinsulinemia on myocardial amino acid uptake in patients with coronary artery disease

Branched-chain amino acids (BCAAs) are oxidative energy substrates for the heart and may exert anabolic effects on myocardial protein. The factors regulating their myocardial uptake in patients with ischemic heart disease are therefore of interest. To examine whether myocardial BCAA utilization is influenced by the circulating insulin concentration, in 10 patients with chronic ischemic heart disease, we measured transmyocardial amino acid balance during fasting and again during a 90-minute euglycemic insulin infusion (plasma insulin, 218 ± 25 μU · mL −1) with plasma BCAA concentrations held constant by coinfusion. In the fasting state, the myocardial fractional extraction of leucine (8%), isoleucine (9%), and valine (5%) from arterial plasma was slightly greater than that of glucose (3%), while net myocardial BCAA uptake (leucine, 409 ± 207 nmol · min −1; isoleucine, 220 ± 144 nmo · min −1; valine, 407 ± 326 nmol · min −1; and total BCAA uptake, 1.0 ± 0.3 μmol · min −1) was about 13% that of glucose (8 ± 2 μmol · min −1). During euglycemic hyperinsulinemia, myocardial glucose uptake increased 3-fold, but there was no change in the arterial-coronary sinus balance or net myocardial uptake of any BCAA under conditions where their plasma concentrations were held constant. Instead, the myocardial uptake of each BCAA correlated positively with its concentration in arterial plasma. These results demonstrate that in patients with cardiovascular disease, myocardial utilization of BCAAs is insensitive to the circulating insulin level and is regulated instead by their availability in arterial plasma. Hyperinsulinemia reduced the magnitude of both net glutamate uptake and alanine release, suggesting a possible salutary effect on myocardial oxidative efficiency.

Myocardial outflow of prostacyclin in relation to metabolic stress during off-pump coronary artery bypass grafting

Background. The metabolic changes, possible myocardial damage, and influence on the vascular endothelium during off-pump coronary artery bypass grafting have been investigated. Methods. Coronary sinus and arterial blood samples were obtained before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 patients who had an anastomosis performed to the left anterior descending coronary artery off-pump bypass Results. The mean ischemic time was 14 ± 1 minutes. The arteriovenous difference in lactate decreased during ischemia to reach a minimum at 1 minute of reperfusion (−0.15 ± 0.06 μmol/L compared to 0.21 ± 10 μmol/L before ischemia; p < 0.01). Myocardial lactate extraction decreased from 14.2 ± 6.8 μmol/min before ischemia to −10.9 ± 6.5 μmol/min after 1 minute of reperfusion ( p < 0.01). Simultaneously, the arteriovenous difference in 6-keto-PGF 1α, the stable metabolite of prostacyclin, decreased from −30 ± 26 pg/mL to −258 ± 80 pg/mL at 1 minute of reperfusion ( p < 0.05), and the 6-keto-PGF 1α extraction over the heart decreased −556 ± 466 pg/min to −18,560 ± 5,683 pg/min ( p < 0.01). Conclusions. The localized myocardial ischemia associated with these procedures causes changes in the myocardium and endothelial influence. Coronary bypass surgery performed on the beating heart may not be superior in preventing cardiac ischemia and endothelial disturbance, compared with conventional bypass surgery.

Increased 8-Hydroxyguanine Formation and Endonuclease Activity for Its Repair in Ischemic-Reperfused Hearts of Rats

H.-j. You, G.-t. Kim, Y.-h. Kim, Y.-s. Chun, J.-w. Park, M.-H. Chung and M.-s. Kim. Increased 8-Hydroxyguanine Formation and Endonuclease Activity for Its Repair in Ischemic-Reperfused Hearts of Rats. Journal of Molecular and Cellular Cardiology (2000) 32, 1053–1059. A type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua) formation, and the activity for its subsequent repair, 8-OH-Gua endonuclease activity, were examined in an ischemia-reperfusion model of isolated rat hearts. The level of 8-OH-Gua in myocardial DNA was measured by a high performance liquid chromatography (HPLC) equipped with an electrochemical detector, and the 8-OH-Gua endonuclease activity was analysed by the endonuclease nicking assay using a synthetic double-stranded oligonucleotide containing an 8-OH-Gua residue as a substrate. The Langendorff-perfused rat hearts were subjected to 30 or 60 min of global ischemia, followed by reperfusion with an oxygenated or a nitrogenated Krebs-Henseleit solution. The 8-OH-Gua content in the DNA of the ischemic hearts reperfused with an oxygenated solution was three to four times higher than that of the control hearts. The levels of 8-OH-Gua did not increase either in the ischemic hearts reperfused with a nitrogenated solution or in the ischemic-reperfused hearts treated with SOD, mannitol or allopurinol. When the myocardial extract was incubated with the 8-OH-Gua-containing oligonucleotide substrate, a specific cleavage at the site of an 8-OH-Gua residue was detected. The endonuclease activity responsible for this cleavage increased two-fold in the ischemic-reperfused hearts, compared to the control. This study demonstrates that the formation of 8-OH-Gua in DNA as well as the level of its repair process, 8-OH-Gua endonuclease activity, increase in the ischemic-reperfused rat hearts in response to oxidative stress due to higher levels of oxygen free radicals.

Exercise Training Enhances Glycolytic and Oxidative Enzymes in Canine Ventricular Myocardium

S. R. Stuewe, P. A. Gwirtz, N. Agarwal and R. T. Mallet. Exercise Training Enhances Glycolytic and Oxidative Enzymes in Canine Ventricular Myocardium. Journal of Molecular and Cellular Cardiology (2000) 32, 903–913. Aerobic exercise training evokes adaptations in the myocardial contractile machinery that enhance cardiac functional capacity; in comparison, the effects of training on the myocardium's energy generating pathways are less well characterized. This study tested the hypothesis that aerobic exercise training can increase the capacities of the major pathways of intermediary metabolism in canine myocardium. Mongrel dogs were conditioned by a 9-week treadmill running program or cage rested for 4 weeks. Exercise conditioning was evidenced by 26% and 22% decreases (P<0.05) in respective heart rates at rest and during submaximal exercise and by a 40% increase (P<0.05) in citrate synthase (CS) activity of thevastus lateralis . Glycolytic, TCA cycle, and β -oxidative enzymes were assayed in myocardial extracts at 37°C. Relative to sedentary controls, training increased glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity by 49% in left and 33% in right ventricle, and pyruvate kinase, CS, and 3-hydroxyacyl CoA dehydrogenase (HADH) activities by 74%, 91%, and 77%, respectively, in left ventricle (P<0.05). Immunoblotting further confirmed that training increased left ventricular contents of CS and GAPDH. Other measured enzymes (hexokinase, phosphofructokinase, lactate dehydrogenase, α -ketoglutarate dehydrogenase, malate dehydrogenase) were not altered by training in either ventricle. Kinetic analyses revealed increased maximum rates but unaltered substrate affinities of GAPDH, CS and HADH following training. Thus, aerobic exercise training augments the intermediary metabolic capacity of canine myocardium by selectively increasing the concentrations of regulatory enzymes of glycolysis and oxidative metabolism.

Static Versus Dynamic Teboroxime Myocardial Perfusion SPECT in Canines.

Tc-99m-teboroxime is a perfusion tracer with high myocardial extraction, fast washin and washout kinetics, and excellent imaging properties. The fast kinetics pose some problems for static imaging, but they also allow for back-to-back stress / rest studies to be performed very quickly. Furthermore, such fast kinetics are ideally suited for dynamic imaging. We have compared static versus dynamic myocardial perfusion SPECT with teboroxime in canines using microsphere-derived flow values as the gold standard. Dynamic data were successfully acquired at rest and under adenosine stress in seven dogs using a fast serial scanning protocol. The data were analyzed in two ways: summing timeframes to create a single, static dataset with consistent projections; and 4D reconstruction and kinetic parameter estimation for a two compartment model. In both cases imaging data (voxel intensity or washin rate parameter) were correlated with flow values measured by microspheres. The static summing procedure that produced the best correlation with flow consisted of summing the projection data acquired from 60 to 180 seconds post-injection. The washin rate parameter was found to provide better correlation with flow than static image intensity in six of seven animals. When the data were pooled over all studies, washin provided significantly better correlation with flow than static imaging (p<0.01). We conclude that dynamic imaging of teboroxime with compartmental modeling provides a better measure of flow than can be obtained from static imaging techniques.

Adenosine A 1 Receptor Induced Delayed Preconditioning in Rabbits

Transient adenosine A(1) receptor (A(1)R) activation in rabbits induces delayed preconditioning against myocardial infarction 24 to 72 hours later. The cellular mechanisms downstream of A(1)R mediating this delayed cardioprotection have not been elucidated. This study examined the role of protein kinase C (PKC) and tyrosine kinases (TKs) in the signaling cascade mediating A(1)R-induced late preconditioning in rabbits. The small heat shock protein Hsp27 has been shown to confer cytoskeletal protection when in the phosphorylated state. We therefore also evaluated the potential role of the p38 mitogen-activated protein kinase (p38 MAPK) and Hsp27 as distal mediators of A(1)R-induced delayed preconditioning. Pharmacological preconditioning of rabbits with the selective A(1) agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA; 100 microgram/kg) significantly reduced myocardial infarct size compared with control animals, after 30-minute regional ischemia/2-hour reperfusion in vivo 24 hours later (23.7+/-3.1 versus 43.0+/-4.1%; P<0.05). This delayed protection was abrogated by prior inhibition of either PKC with chelerythrine chloride (5 mg/kg) or of TKs with lavendustin A (1.3 mg/kg), suggesting that both PKC and TK are crucial for the development of delayed preconditioning after A(1) receptor activation in the rabbit. Myocardial tissue extracts obtained 24 hours after CCPA treatment were analyzed for p38 MAPK catalytic activity using an in vitro kinase assay. This showed an almost 7-fold increase in p38 MAPK activity in myocardial samples pretreated with CCPA compared with control hearts. Two-dimensional gel electrophoresis revealed an increase in the phosphorylated isoforms of Hsp27 in hearts pretreated with CCPA compared with control hearts. Prior inhibition of either PKC or TK prevented the CCPA-induced increase in p38 MAPK activity and phosphorylation of Hsp27. This study identifies new components of the signaling mechanism of A(1)R-induced delayed preconditioning. Our results suggest an important role for both PKC and TK as mediators of late preconditioning against infarction after A(1)R activation and, although correlative, point to the p38 MAPK/Hsp27 pathway as a potential distal effector of this protection.

Contributions of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease.

In the past decade, significant advances have been made in the ability to image the heart with radionuclide tracers under stress and resting conditions in patients with suspected or known coronary artery disease (CAD) for the detection of ischemia, determination of prognosis, assessment of myocardial viability, preoperative risk assessment for patients undergoing noncardiac surgery, and evaluation of the efficacy of revascularization in patients undergoing coronary artery bypass surgery or an interventional procedure.1 For many years, planar imaging and SPECT with 201Tl constituted the only scintigraphic techniques available for detecting CAD and assessing prognosis in patients undergoing stress perfusion imaging. The major limitation of 201Tl scintigraphy is the high false-positive rate observed in many laboratories, which is attributed predominantly to image attenuation artifacts and variants of normal that are interpreted as defects consequent to a significant coronary artery stenosis. Although quantification of 201Tl images improves specificity, the false-positive rate remains problematic, particularly in women and in obese patients. Breast attenuation artifacts in women are sometimes difficult to distinguish from perfusion abnormalities secondary to inducible ischemia or myocardial scar. In recent years, new 99mTc-labeled perfusion agents have been introduced into clinical practice to enhance the specificity of SPECT and to provide additional information regarding regional and global left ventricular systolic function via ECG gating of images. It was immediately apparent that the quality of images obtained with these new 99mTc-labeled radionuclides was superior to that of images obtained with 201Tl because of the more favorable physical characteristics of 99mTc imaging with a gamma camera. With 99mTc, doses of ≈10 to 20 times higher than those that are feasible with 201Tl can be administered, yielding images with higher count density. 99mTc demonstrates less scatter and attenuation than 201Tl, which is associated …

Effects of modest anemia on systemic and coronary circulation of septic sheep.

Although a lower transfusion trigger is generally recommended, little evidence is available about the physiological mechanisms of mild anemia in diseases with an imbalance between O2 supply and O2 demand such as sepsis. This study was undertaken to describe the systemic and coronary metabolic O2 reserve in an awake sheep model of hyperdynamic sepsis comparing two different hemoglobin levels. Twenty-four hours after sheep were rendered septic by cecal ligation and perforation (CLP), blood transfusion (n = 7, hemoglobin = 120 g/l) and isovolemic hemodilution (n = 8, hemoglobin = 70 g/l), respectively, were performed. Another 24 h later, we measured hemodynamics, organ blood flows, and systemic and myocardial O2 metabolism variables at baseline and through four stages of progressive hypoxia. Maximum coronary blood flow was 766.3 +/- 87.4 ml. min(-1). 100 g(-1) in hemodiluted sheep group versus 422.7 +/- 53.7 ml. min(-1). 100 g(-1) in the transfused sheep (P < 0.01). Myocardial O2 extraction was higher in the transfusion group (P = 0.03) throughout the whole hypoxia trial. In the hemodilution group, coronary blood flow increased more per increase in myocardial O(2) uptake than in transfused sheep (P < 0.01). This was accompanied by a lower left ventricular epicardial-to-endocardial flow ratio in hemodiluted sheep (1.13 +/- 0.07) than in transfused sheep (1.34 +/- 0.02, P < 0.05). We conclude that the lower coronary blood flow and greater myocardial O2 extraction in transfused septic sheep preserves transmyocardial O2 metabolism better in comparison to hemodiluted sheep.

The effect of ischemic injury on the cardiac transport of Tc-99m N-NOET in the isolated rabbit heart

Background. Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (TcN-NOET) is a neutral lipophilic myocardial perfusion agent. The effect of ischemic injury on the cardiac transport of TcN-NOET and thallium-201 was determined in isolated rabbit hearts. Methods and Results. The multiple indicator dilution method was used to determine the maximum (E max) and net extraction (E net, at 5 minutes) of TcN-NOET and Tl-201 at control and after 10 minutes (n = 4) or 45 minutes (n = 4) of no-flow ischemia. After 10 minutes of ischemia the mean E max for Tl-201 was unchanged, 0.86 ± 0.03 vs 0.85 ± 0.02, whereas Tl-201 E net showed a small decrease from 0.46 ± 0.03 to 0.40 ± 0.03, P < .001. Forty-five minutes of ischemia mildly reduced E max for Tl-201 (0.87 ± 0.04 to 0.74 ± 0.04, P < .001) and severely reduced E net (0.46 ± 0.03 vs 0.16 ± 0.04, P < .001). Neither E max nor E net for TcN-NOET was significantly affected by 10 minutes of ischemia (0.54 ± 0.04 vs 0.58 ± 0.03 and 0.24 ± 0.04 vs 0.26 ± 0.04, respectively). However, severe ischemic injury caused significant reductions versus control in both E max (0.59 ± 0.06 vs 0.42 ± 0.05, P < .001) and E net (0.27 ± 0.03 vs 0.18 ± 0.05, P < .01). Conclusions. TcN-NOET is a new myocardial perfusion agent with moderate myocardial extraction. Although less sensitive than Tl-201 to mild ischemic injury, TcN-NOET extraction and retention are decreased by severe ischemic injury, making uptake of TcN-NOET a possible marker of myocardial viability.

Effects of defibrillator implantation testing on myocardial metabolism.

The effects of fibrillation/defibrillation episodes (FDEs) during defibrillator implantation on myocardial metabolism were investigated at various defibrillation energies in patients with different cardiac pathologies. Myocardial lactate extraction (MLE) was examined during defibrillation threshold (DFT) testing in patients with either coronary artery disease (CAD, n = 20) or non-ischemic cardiomyopathy (CM, n = 10). Defibrillation pulses were released 15 seconds after induced fibrillation. A test cycle of four FDEs separated by 2-minute intervals was applied in each case. Mean MLE decreased significantly from 28 +/- 4% before FDEs to 8 +/- 5% immediately after all episodes in CAD patients, but recovered to 27 +/- 7% within 2 minutes even in patients with reduced left-ventricular function. In patients with CM mean MLE decreased markedly from 29 +/- 3% to -11 +/- 3% immediately after each FDE but increased to baseline (33 +/- 8%) within the recovery period. MLE changes were independent of defibrillation energy in all cases. Myocardial lactate production, suggesting cardiac ischemia, was observed in patients with CM, but not in patients with CAD. But recovery of myocardial lactate extraction was not faster in CAD patients, indicating that the fixed FDE cycle used was well tolerated by all patients.

Sublingual nifedipine in elderly patients: even a low dose induces myocardial ischaemia.

1. Low doses of sublingual nifedipine are still used for the treatment of hypertensive crises, although recent studies have raised concerns that sublingual nifedipine may cause serious dose-dependent adverse effects. The present study was performed to test the safety of low-dose sublingual nifedipine administered to elderly hypertensive patients. 2. Systemic blood pressure measurements and electrocardiographic (ECG) examinations were performed before and 45-60 min after a 5 mg dose of sublingual nifedipine in 93 consecutive hypertensive patients, 65 years of age or older, who were without coronary artery disease. In 33 patients, the effects of nifedipine on myocardial lactate metabolism were studied during cardiac catheterization. 3. In all patients, following nifedipine administration, blood pressure (BP) decreased significantly, while heart rate (HR) increased, and symptoms associated with elevated BP disappeared. However, changes consistent with myocardial ischaemia appeared on the ECG in six of 55 patients with left ventricular hypertrophy (LVH) and in one of 38 patients without LVH, although only two of these seven patients experienced angina-like precordial tightness. Sublingual nifedipine decreased myocardial lactate extraction from 52 +/- 13 to 38 +/- 19% in 20 patients with LVH (P = 0.02), but myocardial lactate extraction remained stable in 13 patients without LVH (49 +/- 7 to 50 +/- 5%; NS). The change in lactate extraction was significantly correlated with the percentage change in diastolic arterial pressure (r = 0.77, P < 0.001). 4. These results suggest that sublingual nifedipine, even at the low dose of 5 mg, may cause myocardial ischaemia in some elderly patients with LVH that is associated with a marked reduction in coronary perfusion pressure.

Myocardial outflow of calcitonin gene-related peptide in relation to metabolic stress during coronary artery bypass grafting without cardiopulmonary bypass

Objective: Because of adverse effects of cardiopulmonary bypass and the prospect of shortening intensive care and hospital stay, coronary artery bypass grafting without cardiopulmonary bypass is gaining increased attention. The impact of the localized myocardial ischemia that is inherent in these procedures has not been thoroughly investigated in human beings. We have investigated metabolic changes, possible myocardial damage, and myocardial outflow of the vasodilator calcitonin gene-related peptide during coronary artery bypass grafting without cardiopulmonary bypass. Methods: Coronary sinus and arterial blood was sampled before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 consecutive patients (mean age 70 ± 5 years) who had an anastomosis performed to the left anterior descending artery without cardiopulmonary bypass. Results: No perioperative myocardial infarctions occurred. The arteriovenous difference in lactate decreased during ischemia, to reach a minimum after 1 minute of reperfusion (–0.17 ± 0.25 vs 0.15 ± 0.25 mmol/L before ischemia; P = .008). Myocardial lactate extraction decreased (from 11.2 ± 13.6 μmol/min before ischemia to –3.0 ± 7.0 μmol/min after 1 minute of reperfusion; P = .012), that is, a net production of lactate. The arteriovenous difference in calcitonin gene-related peptide decreased from –0.1 ± 2.6 pmol/L before ischemia to –30.5 ± 26.5 pmol/L ( P = .008) after 1 minute of reperfusion. Conclusions: The localized myocardial ischemia associated with these procedures causes metabolic changes in the myocardium, but no myocardial damage. The ischemia-related outflow of calcitonin gene-related peptide indicates that the vasodilating and cardioprotective properties of this peptide that are known from animal studies may be of importance in myocardial ischemia in human beings. (J Thorac Cardiovasc Surg 1999;117:447-53)

BMIPP-design and development.

In the early 1980s a major obstacle for myocardial SPECT using iodine-123-labeled fatty acids and imaging technology available at that time was the rapid metabolism and myocardial washout of activity. Development of the 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) fatty acid analogue was based on the established effects of methyl-branching in delineating the enzymatic aberration in Refum's disease and our early studies with the tellurium (Te)-substituted fatty acid analogues. Extensive animal studies with the Te-fatty acids demonstrated that this major structural alteration did not affect initial myocardial extraction, but could successfully inhibit subsequent metabolism and significantly delay washout. Tracer kinetic evaluation and metabolic studies on experimental animals and Langendorff-perfused rat hearts clearly demonstrated that introduction of methyl-branching is an effective approach which alters tracer kinetics by delaying myocardial washout of radioiodinated fatty acids by increasing myocardial retention. Although irreversible retention of iodine-123 BMIPP is not observed, subsequent extensive human studies have clearly substantiated the delayed myocardial washout of BMIPP in comparison with the p-IPPA straight chain analogue. Although contemporary SPECT capabilities allow much more rapid acquisition periods, the delayed washout is still a practical benefit in relation to the use of BMIPP. Most important, the unexpected mis-match which has been widely observed between perfusion tracer distribution and the regional BMIPP distribution (i.e. BMIPP < flow tracer) has been linked to the identification of jeopardized, but viable myocardial regions. In this paper the development of BMIPP is discussed and the results of recent studies focusing on evaluating the effects of the absolute configuration of the branched methyl group using the 3(R)-BMIPP and 3(S)-BMIPP are described.

Acupuncture for Relief of Angina

To the Editor: I read with interest the ESBY study (Electrical Stimulation versus coronary artery BYpass surgery in severe angina pectoris) by Mannheimer et al.1 They found that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe angina pectoris and concluded that CABG and SCS are equivalent methods in terms of symptom relief. In a previous report,2 these authors showed that myocardial extraction of β-endorphin during control atrial pacing changed to release at the maximum pacing rate during SCS. Furthermore, their results indicate local myocardial turnover of β-endorphin, leuenkephalin, and calcitonin-gene–related …

Additive effects of hyperinsulinemia and ischemia on myocardial GLUT1 and GLUT4 translocation in vivo.

Myocardial ischemia increases glucose uptake through the translocation of GLUT1 and GLUT4 from an intracellular compartment to the sarcolemma. The present study was performed to determine whether hyperinsulinemia causes translocation of myocardial GLUT1 as well as GLUT4 in vivo and whether there are additive effects of insulin and ischemia on GLUT1 and GLUT4 translocation. METHODS ADN RESULTS: Myocardial glucose uptake and transporter distribution were assessed by arteriovenous measurements, cell fractionation, and immunofluorescence. In fasted anesthetized dogs, hyperinsulinemia increased myocardial glucose extraction 3-fold (P<0.01) and the sarcolemmal content of GLUT4 by 90% and GLUT1 by 50% (P<0.05 for both) compared with saline infusion. In subsequent experiments, glucose uptake and transporter distribution were determined in ischemic and nonischemic regions of hearts from hyperinsulinemic animals during regional myocardial ischemia. Glucose uptake was 50% greater in the ischemic region (P<0.05). This was associated with a 20% increase in sarcolemmal GLUT1 and a 60% increase in sarcolemmal GLUT4 contents in the ischemic region (P<0.05 for both). Insulin stimulates myocardial glucose utilization through translocation of GLUT1 as well as GLUT4. Insulin and ischemia have additive effects to increase in vivo glucose utilization and augment glucose transporter translocation. We conclude that recruitment of both GLUT1 and GLUT4 contributes to increased myocardial glucose uptake during moderate reductions in coronary blood flow under insulin-stimulated conditions.

Preservation of myocardial metabolism in acute coronary artery occlusions with retrograde coronary sinus perfusion and iloprost

A total of 12 healthy mongrel dogs were subjected to the study. The left anterior descending artery was occluded. The occlusion was done for 15 min. At the end of this period, without removing the occlusion, the heart was retroperfused for 3 h. Then, occlusion was removed and reperfusion was supplied. Animals were divided into two equal groups. Six animals received iloprost and the other six control did not receive any additional treatment. In the iloprost group, the drug was administered into the coronary sinus. After 15 min following occlusion, iloprost was infused at a rate of 50 μg/min continuously. Cardiac output (CO), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), heart rate (HR), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), myocardial oxygen extraction (MOE) and myocardial lactate extraction (MLE) parameters were examined in the two groups, before and during retroperfusion and during the reperfusion (1–4 h). Iloprost retroperfusion (50 μg/min) was started at the fifteenth minute of occlusion and continued till the end of the observation period (3 h). The measured hemodynamic data showed that the hearts treated with iloprost had satisfactory preservation of cardiac function. At the end of the reperfusion period cardiac output was 1.5 ± 0.06 L/min in the control and 1.7 ± 0.04 L/min in the iloprost group ( P < 0.05). At the end of the reperfusion period, tumor necrosis factor level was raised significantly in the control group ( P < 0.05). Myocardial lactate release was also high in the control group ( P < 0.05). CPK-MB release was low in the iloprost group ( P < 0.05). We conclude that retrogradely administered iloprost reduced the risk of myocardial injury and it is probable that this drug effectively distributes to the area of myocardium at risk.

Intermittent warm blood cardioplegia--an experimental study

The influence of intermittent warm blood cardioplegia (WBCP) on myocardial function and metabolism was studied. Fourty-two adult mongrel dogs were used. The isolated heart of one dog was perfused by the cross circulation method with another support dog. The dogs then were divided into three groups. In group I (n = 6), the empty beating heart was perfused with warm blood (WB) kept at 36 degrees C for 100 minutes. In group II (n = 7), the arrested heart was perfused with continuous WBCP using modified Fremes solution for 100 minutes. In group III (n = 8), the arrested heart was perfused with WBCP for 10 minutes following a 15-minute non-perfusion period. This perfusion method was repeated four times. The E max, LV developed pressure, +/- LV dp/dt and LVEDP were all measured to evaluated the myocardial function. In addition, the coronary venous blood pH, myocardial oxygen consumption, myocardial lactate extraction, coronary blood flow, myocardial high energy phosphate content and myocardial water content were also studied in order to elucidate the myocardial metabolism. Regarding the myocardial function, no significant difference was observed between the three groups. The results of chemical studies on the myocardial metabolism were as follows: (1) the coronary venous blood pH in group III decreased at the end of the no perfusion period of WBCP. But it thereafter gradually returned to the normal physiological range; (2) the myocardial oxygen consumption in group III increased just after each interruption, but then gradually decreased toward following intermittent WBCP; (3) the myocardial lactate extraction decreased at the end of the non-perfusion period. However, it gradually returned to the control value by the end of each period of WBCP perfusion; (4) after 60 minutes of reperfusion, the coronary venous blood pH, myocardial oxygen consumption and myocardial lactate extraction showed no significant differences between the groups; (5) the coronary blood flow in group III increased significantly after 1 minute of reperfusion; (6) the ATP value in group III decreased significantly after 60 minutes of reperfusion. The ADP and AMP values demonstrated no significant difference between the groups during the same period; and (7) no significant difference was seen in the myocardial water content between the groups after 60 minutes of reperfusion. It is thus concluded that 10 minutes of intermittent WBCP followed by a 15-minute interruption appeared to have no deleterious effect on the myocardial function and metabolism.