phosphorus-radioisotopes and Myocardial-Ischemia

Coronary artery disease (CAD) is the most common cause of death in women. In general, noninvasive testing in women is less reliable compared with testing in men, and most major clinical trials in CAD have included only a minority of female subjects. The Women's Ischemia Syndrome Evaluation (WISE) Study--sponsored by the National Heart, Lung, and Blood Institute--was initiated to improve diagnostic testing in women. The study consisted of four centers that tested existing methodologies as well as innovative techniques to improve diagnostic testing in women. The WISE study also aimed to clarify physiologic determinants of myocardial ischemia and determine whether angiographically normal coronary arteries are associated with myocardial ischemia. The following discussion provides an overview of the WISE study and reviews the reported and published data from the study.

Topics: Anticholesteremic Agents; Clinical Protocols; Coronary Angiography; Diagnostic Techniques, Cardiovascular; Echocardiography, Stress; Exercise Test; Female; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Myocardial Ischemia; Phosphorus Radioisotopes; Sensitivity and Specificity; Women's Health

We investigated the effects of metformin on myocardial metabolism during ischemia by 31P-nuclear magnetic resonance (NMR) in isolated rabbit hearts. Metformin was administered 60 min prior to induction of global ischemia, or in combination with a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 min or 60 min prior to the ischemia. Normothermic global ischemia was then carried out for 45 min. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: a control (C) group; an M group receiving metformin treatment alone; an M+L (5) group receiving metformin treatment with L-NAME at 5 min before ischemia; and an M+L (60) group receiving metformin treatment with L-NAME at 60 min before ischemia. During ischemia, the decrease in adenosine triphosphate (ATP) was significantly inhibited in the M group in comparison with the C group (p < 0.01). However, this preservation of ATP in the M group was inhibited in the M+L (5) group during ischemia. In contrast, in the M+L (60) group, this preservation of ATP in the M group was not inhibited during, but not at the end of, ischemia. These results suggest that metformin has a significant beneficial effect for improving the myocardial energy metabolism during myocardial ischemia. This cardioprotection may be more dependent on nitric oxide synthase during ischemia than during pre-ischemia.

Topics: Animals; Cardiotonic Agents; Drug Interactions; Energy Metabolism; Enzyme Inhibitors; Hypoglycemic Agents; Magnetic Resonance Spectroscopy; Male; Metformin; Myocardial Ischemia; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phosphorus Radioisotopes; Rabbits; Radionuclide Imaging

We investigated if blockade of ATP-sensitive K+ channels (KATP) abolishes the protective effect of ischemic preconditioning (IP) on myocardial metabolism and ischemia-induced reactive hyperemia (RH) in pigs.. IP was elicited by a single cycle of 5 min occlusion and 5 min reperfusion of coronary artery, followed by 15 min of test ischemia and 120 min of reperfusion. Vehicle or the ATP-sensitive K+ channels (KATP) blocker, glibenclamide (3 or 6 mg/kg; G3 or G6) was administered before IP (groups; IP, G3+IP, G6+IP). As respective controls, the same treatment was performed in groups without IP (groups; C, G3, G6). Tissue levels of ATP, creatine phosphate (CP) and intracellular pH (pHi) in the area at risk were measured by 31P-nuclear magnetic resonance spectroscopy. RH after 5 min of preconditioning ischemia was assessed by regional myocardial blood flow.. ATP and pHi were preserved after 15 min of ischemia in the IP group [C/IP; ATP=57+/-4/76+/-10% of baseline, pHi=6.18+/-0.08/6.66+/-0.03, P<0.05, C vs. IP]. Both doses of glibenclamide completely abolished the ATP sparing effect of IP. The high dose completely abolished pHi preservation (G6+IP=6.33+/-0.06), while the low dose showed only a partial effect (G3+IP=6.48+/-0.03). Glibenclamide did not adversely affect myocardial metabolism in groups without IP. Glibenclamide attenuated RH after 5 min of ischemia by 30% in both subendocardium and subepicardium.. Blockade of KATP abolished the preconditioning effect on myocardial metabolism, and partially attenuated post-ischemic reactive hyperemia in pigs. These results indicate that KATP activation might be involved in the mechanisms of these phenomena, reactive hyperemia is not sufficient to induce IP protection.

Topics: Adenosine Triphosphate; Animals; Blood Glucose; Coronary Vessels; Glyburide; Hemodynamics; Hydrogen-Ion Concentration; Hypoglycemic Agents; Ischemic Preconditioning, Myocardial; Magnetic Resonance Spectroscopy; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Phosphates; Phosphocreatine; Phosphorus Radioisotopes; Potassium Channel Blockers; Regional Blood Flow; Swine; Time Factors

Our objective was to test the effects of exogenous L-aspartate and L-glutamate on myocardial energy metabolism during ischemia-reperfusion.. Phosphorus 31-magnetic resonance spectroscopy was used to observe cellular energetics and intracellular pH in isolated pig hearts perfused with blood (group A, n = 8) or blood enriched with 13 mmol/L each of L-aspartate and L-glutamate (group B, n = 6). The hearts were subjected to 30 minutes of total normothermic ischemia and then reperfused for 40 minutes. Two hearts from each group were inotropically stimulated by titration with calcium after normokalemic reperfusion. Left ventricular function was measured with the use of a compliant balloon and oxygen consumption was calculated.. Magnetic resonance spectroscopy showed no decrease in the rate of energy decline during ischemia for group B versus group A. No significant differences were observed between the two groups in terms of myocardial function, oxygen consumption, or the rate or extent of high-energy phosphate recovery after normokalemic reperfusion or inotropic stimulation. Inotropic stimulation of postischemic hearts, however, led to dramatic improvement in myocardial function in both groups (p < 0.05 for all parameters) and significant improvement in oxygen consumption (p = 0.01).. In a normal, isolated, blood-perfused pig heart subjected to 30 minutes of total normothermic ischemia, (1) enrichment of the perfusate with aspartate/glutamate before and after ischemia affects neither myocardial energy metabolism during ischemia-reperfusion nor postischemic recovery of myocardial function or oxygen consumption and (2) inotropic stimulation can recruit significant postischemic function and sufficient aerobic respiration to support it, irrespective of aspartate/glutamate enrichment.

Topics: Adenosine Triphosphate; Animals; Aspartic Acid; Cardioplegic Solutions; Chromatography, High Pressure Liquid; Energy Metabolism; Glutamates; In Vitro Techniques; Magnetic Resonance Spectroscopy; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Oxygen Consumption; Phosphocreatine; Phosphorus Radioisotopes; Stimulation, Chemical; Swine

A study of the protective efficiency imparted by intermittent warm blood cardioplegia (WBCP) using perfused rat heart model.. Hemodynamic parameters were monitored simultaneously with metabolic changes in high-energy phosphates using 31P-NMR spectroscopy. Following 30 min perfusion with Krebs-Henseleit (KH) buffer, all hearts were arrested for one hour (G1 and G2) and than reperfused with KH for 30 minutes. A warm oxygenated crystalloid cardioplegia (WCCP, modified St Thomas' hospital solution) was used for the control group (G1). The second group of hearts (G2) were arrested with oxygenated WBCP (K+ = 15 mM; Hct = 15-20%) and the third group (G3), was subjected to a protocol consisting of 4 periods (10 min each) of WBCP interspersed by 10 min of global ischaemia.. The post-arrest percentage recoveries of LVDP, +dP/dt and HR were respectively: 88, 93 and 90 for G1 (n = 8); 97, 100 and 98 for G2 (n = 10); 76, 79 and 91 for G3 (n = 12). The corresponding metabolic recoveries of ATP and PCr were respectively, 85 and 90 for G1; 91 and 98 for G2 and 73 and 85 for G3. The PCr level declined during the arrest period in G1 contrasting with elevated PCr level (> 140%) during the WBCP arrest in G2. After an initial rise to approximately 140%, PCr level gradually decreased during the intermittent WBCP interval (G3).. At normothermia, with equal CF rates, continuous WBCP provides better myocardial protection, through an effective oxygen supply, compared with WCCP. During the intermittent periods of ischaemia, certain metabolic and hemodynamic dysfunction occurs.

Topics: Animals; Chemotherapy, Cancer, Regional Perfusion; Disease Models, Animal; Heart; Heart Arrest, Induced; Hemodynamics; Magnetic Resonance Spectroscopy; Myocardial Ischemia; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley