Effect of MCI-154, a cardiotonic agent, on regional contractile function and myocardial oxygen consumption in the presence and absence of coronary artery stenosis in dogs

The effects of MCI-154 (6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)- pyridazinone hydrochloride.3H2O), a cardiotonic agent with calcium sensitizing actions, on regional contractile function and myocardial oxygen consumption (MVO2) were studied in the dog hearts with and without partial occlusion of the left anterior descending coronary artery and compared with those of dobutamine. Segment shortening by sonomicrometry, regional myocardial blood flow by microspheres and the oxygen content of coronary venous blood drawn from the ischemic left anterior descending coronary artery area were simultaneously measured. The ischemic zone segment shortening and left ventricular (LV) dP/dtmax were decreased after partial occlusion. The infusion of MCI-154 starting 20 min after ischemia improved the depressed segment shortening and LV dP/dtmax without increasing the ischemic zone MVO2 and regional myocardial blood flow. In the nonischemic hearts, MCI-154 did not increase MVO2 and coronary blood flow despite the augmentation of myocardial contractility. MCI-154 decreased LV end-diastolic pressure and systemic blood pressure. On the other hand, dobutamine failed to increase the ischemic zone segment shortening, but the drug increased MVO2, coronary blood flow and LV dP/dtmax in both ischemic and nonischemic hearts. These results indicate that MCI-154 alleviates the ischemic contractile failure without increasing myocardial oxygen demand. Thus, MCI-154 may be useful in the management of heart failure with reduced coronary reserve.     

Influence of tachycardia on regional myocardial flow in chronic experimental coronary occlusion

The influences of tachycardia on regional myocardial flow was studied in normal dogs and in dogs with chronic coronary artery occlusions. Coronary vasodilation was induced by coronary occlusion and subsequent release, i.e. by reactive hyperemia. Local myocardial blood flow was determined with the tracer microspheres technique. In normal hearts atrial pacing produced a slight but significant increase in coronary resistance in the subendocardial layers of the left ventricle. The coronary resistance of the subepicardium remained unaffected. In the right ventricle atrial pacing had no influence on the resistance to flow. In hearts with multiple coronary occlusions tachycardia-induced changes of coronary resistance were more pronounced. In the collateral dependent subendocardium coronary resistance increased from 0.4-2.2 resistance units when the heart rate was raised to 200 beats/min. Perfusion of the right ventricular myocardium became also rate-dependent when the right coronary artery was chronically occluded. We conclude that regional perfusion dependes upon the relationship between the effective perfusion pressure, which is reduced in chronic coronary occlusion, and the integral of effective tissue pressure, which is increased with tachycardia. The results cannot be explained by assuming excessive O2-demand but rather by a rate-induced lowered O2-supply.     

One-year effect of myocardial revascularization on resting left ventricular function and regional thallium uptake in chronic CAD

It is still unclear whether in patients with chronic coronary artery disease (CAD) the improvements in myocardial perfusion and left ventricular (LV) function induced by revascularization persist in the long run. This study was planned to evaluate the 1-yr effects of successful revascularization on myocardial perfusion and LV function in patients with CAD and to assess the accuracy of thallium imaging in the prediction of functional recovery 1 yr after revascularization. METHODS: Thirty-eight patients with chronic CAD who were revascularized (experimental group) underwent, while off drugs, 201Tl tomography, two-dimensional echocardiography and radionuclide angiography before and after a 1-yr follow-up. Twenty-nine patients with similar characteristics who were not revascularized (control group) and completed the 1-yr follow-up were also studied. Regional thallium activity was quantitatively measured in 13 segments per patient. Systolic function was assessed by echocardiography in corresponding segments. RESULTS: In the experimental group, at baseline, on the basis of regional LV function and thallium uptake, 276 segments were normal, 169 dysfunctional-viable and 49 nonviable. After revascularization, the majority (75%) of the dysfunctional-viable segments at baseline showed functional recovery at follow-up, whereas the majority (81%) of the nonviable segments at baseline did not. Simultaneously, LV ejection fraction increased 4 wk after revascularization (from 39% +/- 9% to 42% +/- 10%, p < 0.01) and remained unchanged after 1-yr (43% +/- 8%, p < 0.01 versus baseline study). LV wall-motion score index after 1 yr was reduced (from 1.68 +/- 0.4 to 1.42 +/- 0.3, p < 0.001) as compared with baseline. On the contrary, in the control group, no change in myocardial perfusion and LV function was detected after the 1-yr follow-up. CONCLUSION: In patients with chronic CAD, successful coronary revascularization induces a stable improvement in myocardial perfusion and LV function, which is still detectable after a 1-yr follow-up. Furthermore, preserved thallium uptake in dysfunctional regions is predictive of functional recovery after revascularization.     

The effect of batroxobin on coronary segmental resistance and coronary blood flow in acute myocardial ischemic dogs

To study the effects of batroxobin on coronary circulation and cardiac performance in acute myocardial ischemia, Batroxobin was given intravenously to dogs with experimental coronary stenosis. A dose-dependent increase of coronary blood flow (CBF) was observed. Forty minutes after batroxobin (2 BU.kg-1 at infusion rate 0.1 BU.kg-1.min-1) administration, CBF increased by 12% (P < 0.05), small coronary resistance(RS) decreased from 4.1 +/- 0.5 to 3.2 +/- 0.5 mmHg.min.ml-1 (P < 0.01), while large coronary resistance(RL) changed insignificantly from 3.9 +/- 0.8 to 3.8 +/- 0.7 mmHg.min.ml-1 (P > 0.05). Two hours following drug administration, the changes in CBF, RS and RL still remained and RT decreased by 13% (P < 0.05). The + LV(dp/dt)max and -LV(dp/dt)max increased by 14% and 16% (P < 0.05) respectively compared with those in control group. It is concluded that batroxobin improves the ischemic canine coronary circulation and cardiac performance by way of lowering the small coronary resistance and thus increasing CBF. The data also suggest the benificial effect of batroxobin in acute myocardial ischemia.     

Effects of halothane on global and regional biventricular performances and on coronary hemodynamics before and during right coronary artery stenosis in the dog

BACKGROUND: Previously, it was suggested that right ventricular (RV) free wall dysfunction does not necessarily elicit global hemodynamic alterations. This was investigated in a canine model of halothane-induced right coronary artery (RCA) insufficiency. METHODS: Two concentrations (0.8% and 1.6% end tidal) of halothane on global and regional RV and left ventricular (LV) performance and on coronary, pulmonary, and systemic hemodynamics were studied in 10 open-chest dogs first before and, subsequently, during critical RCA stenosis. RESULTS: In the absence of stenosis, halothane caused progressive and comparable depression of regional and global RV and LV function and reduction of RCA flow. Halothane administered during RCA stenosis caused disproportionate decreases in RCA flow and segment shortening and increases in systolic segment lengths in the area supplied by the stenosed RCA that were approximately twice as great as before stenosis. Such severe regional RV dysfunction was not accompanied by greater depression of global RV and LV pump function (systolic pressures and stroke volume). CONCLUSIONS: In the canine heart with its dominant left coronary system, RCA insufficiency (on the basis of halothane-induced hypotension) caused regional RV dysfunction suggesting ischemia that was not accompanied by global hemodynamic alteration.     

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.     

Preservation of regional myocardial function and myocardial oxygen tension during acute ischemia in pigs: comparison of selective synchronized suction and retroinfusion of coronary veins to synchronized coronary venous retroperfusion

OBJECTIVES: The efficacy of selective synchronized suction and retroinfusion of coronary veins was compared with synchronized coronary venous retroperfusion in preventing ischemic reduction of regional myocardial function and myocardial oxygen tension. BACKGROUND: Because incomplete protection by synchronized coronary venous retroperfusion during ischemia might result from nonselective retroinfusion and only passive drainage of the veins, a suction device was added to a retroinfusion system. METHODS: Regional myocardial function (ultrasonic crystals) and myocardial oxygen tension (polarographic electrodes) were studied in 30 pigs during 10-min occlusion of the left anterior descending coronary artery (ischemia), followed by reperfusion. During ischemia, group A (n = 10) was supported by selective synchronized suction and retroinfusion; group B (n = 10) was supported by synchronized coronary venous retroperfusion, and group C (n = 10) was not supported by retroinfusion. RESULTS: In group A, subendocardial segment shortening decreased from 21 +/- 4% (mean +/- SD) before ischemia to 11 +/- 5% during ischemia. In contrast, systolic dyskinesia was observed in group B (-2 +/- 4%, p < 0.001) and group C (-2 +/- 5%, p < 0.001). During ischemia, the decrease in intramyocardial oxygen tension was less pronounced in group A (41 +/- 15 vs. 27 +/- 12 mm Hg) than in group B (40 +/- 10 vs. 19 +/- 10 mm Hg, p = 0.1) or group C (33 +/- 11 vs. 12 +/- 8 mm Hg, p = 0.002). During ischemia, myocardial surface oxygen tension was preserved > 0 mm Hg only in group A. CONCLUSIONS: Preservation of regional myocardial function and myocardial oxygen tension was substantially higher by selective synchronized suction and retroinfusion of coronary veins than by synchronized coronary venous retroperfusion in pigs.     

Myocardial tactile stiffness: a variable of regional myocardial function

OBJECTIVES: We developed a new sensor system for in situ measurement of myocardial tactile stiffness-stiffness in a direction perpendicular to the wall-and validated its use for providing a reasonable estimation of regional myocardial function. BACKGROUND: Numerous attempts have been made to directly assess regional myocardial function. The complexity and highly invasive nature of the measuring devices have hampered their in situ application. METHODS: In open chest mongrel dogs, myocardial tactile stiffness, ventricular pressure and ventricular volume were monitored. Under the preload reduction, these variables were measured to determine the relation between the end-systolic pressure-volume relation (ESPVR) and the end-systolic tactile stiffness-volume relation (ESSVR). The changes in myocardial tactile stiffness were monitored in the regional ischemic myocardial model and infarcted model to evaluate their usefulness as indexes of regional myocardial function. RESULTS: Myocardial tactile stiffness changed cyclically and followed a time course similar to left ventricular pressure. When preload was altered, the ESSVR was as linear as the ESPVR. The slope of the ESSVR and that of the ESPVR showed a strong correlation over a wide range of contractility. These results suggest that myocardial tactile stiffness can be a good index of regional wall stress or fiber stress. End-systolic myocardial tactile stiffness of ischemic and infarcted regions decreased significantly, with a concomitant increase in end-diastolic stiffness compared with that of intact myocardium. CONCLUSIONS: Using our tactile sensor system, regional myocardial tactile stiffness of a beating heart was measured with reasonable temporal resolution. We consider myocardial tactile stiffness to be a useful index of regional myocardial function.     

Effects of hyperthermic stress on myocardial function during experimental coronary ischemia

We evaluated hyperthermic influences on ischemic hearts by comparing two groups of intact working swine hearts (n = 20) made globally ischemic. Heart muscle temperature was selectively increased from 37.5 +/- 0.3 degrees C to 39.7 +/- 0.3 degrees C in one group (n = 11) by warming the coronary perfusate. Ischemia in normothermic hearts significantly (P less than 0.05) decreased mechanical function (as reflected by increases in left ventricular end-diastolic pressure [LVEDP]), myocardial oxygen consumption (MVO2), glucose uptake, glycolytic flux, free fatty acid (FFA) uptake and oxidation, and tissue stores of high energy phosphates. Hearing in ischemic hearts further depressed mechanical function at similar reductions in coronary flow and MVO2. Glucose uptake was terminally increased over normothermic values (329 vs. 221 mumol/hr per g) as was glycolytic metabolism, FFA uptake (26 vs. 17 mumol/hr per g), and FFA oxidation (21 vs. 11 mumol/hr per g). However, these changes were not translated into increased energy stores of tissue creatine phosphate and ATP. Thus, in ischemic hearts, hyperthermia neither prevented the development of mechanical deterioration nor improved oxidative phosphorylation despite increases in metabolic substrate utilization. These data suggest that in experimental global ischemia heat is an added energy drain in already burdened myocardium.     

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.     

Attenuation corrected myocardial PET after application of 18FDG: effect on the determination of regional myocardial uptake values

AIM: Post injection transmission measurement (PIT) can be performed using rotating 68Ge/68Ga linesources. This study estimates attenuation coefficients, count densities and relative regional uptake values of PIT corrected cardiac PET (E-PIT) compared to routinely pre-injection transmission measurement (RT). METHODS: A thorax-phantom with homogeneously filled myocardium or with simulated defects and six patients with advanced coronary artery disease were studied using ECAT Exact tomograph (Siemens CTI) equipped with three rotating linesources. Transmission was performed twice (PIT, RT), attenuation coefficients and emission data were analysed, the latter without attenuation correction (E-UK), corrected with PIT (E-PIT) and with RT (E-RT) (count density, standard and relative uptake values). RESULTS: Both in phantom and patient studies attenuation coefficients differed significantly between PIT and RT. Comparing E-PIT and E-RT, regional uptake values were different only in phantom simulation with myocardial radioactivity concentrations higher than 10 kBq x ml-1. The image contrast between defects and remaining myocardium in the phantom studies or the standard and relative uptake values in patient studies did not vary significantly. CONCLUSION: Under clinical conditions a post injection transmission measurement does not influence the accuracy of regional myocardial uptake values relevantly.     

Effects of alpha-adrenergic blockade on regional myocardial function in canine ischemic myocardium during beta-adrenergic blockade

OBJECTIVE: The contribution of alpha-adrenergic receptor subtypes in mediation of coronary vasoconstriction during ischemia remains controversial. This study investigated the effects of alpha-adrenergic subtypes blockade on regional myocardial function in a canine ischemic model. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental animal laboratory in a university medical center. PARTICIPANTS: Thirty-two adult dogs, weighing 13 to 22 kg. INTERVENTIONS: The animals were prepared with pentobarbital, oxygen, enflurane and pancuronium. Two selective alpha 1-adrenergic antagonists (bunazosin, 50 micrograms/kg/min, n = 8, and prazosin, 25 micrograms/kg/min, n = 8) and the alpha 2-adrenergic antagonist (yohimbine, 15 micrograms/kg/min, n = 8) were administered after the partial occlusion of the left circumflex coronary artery (LCX) during beta-adrenergic blockade (propranolol, 1 mg/kg). MEASUREMENTS AND MAIN RESULTS: Myocardial systolic segment shortening (%SS) and a myocardial lactate extraction ratio (LER) were used as indices of regional myocardial and metabolic function. Compared with poststenotic condition, coronary blood flow of the LCX was increased by 123% with bunazosin and 138% with prazosin (p < 0.05, respectively). Both %SS and LER in the ischemic myocardium were significantly improved after treatment with both alpha 1-adrenergic antagonists (in the bunazosin group, %SS, 8.3 +/- 1.9 to 10.4 +/- 2.2%, p < 0.05; LER, -12.8 +/- 12.3 to 6.2 +/- 15.9%, p < 0.01; in the prazosin group, %SS, 8.5 +/- 1.6 to 10.3 +/- 1.9%, p < 0.05; LER, -10.2 +/- 5.7 to 3.6 +/- 10.2%, p < 0.05). In contrast, coronary blood flow of the LCX, %SS and LER were not different from poststenotic condition during alpha 2-adrenergic receptor blockade with yohimbine. The salutary effect of bunazosin was also observed after mechanically controlling for the afterload reduction produced by alpha 1-adrenergic blockade (n = 8). Prazosin and yohimbine were found to produce a significant increase in plasma norepinephrine levels in contrast to bunazosin, which had no significant effect. CONCLUSIONS: These data indicate that alpha 1-adrenergic blockade increases coronary blood flow and improves regional myocardial function during myocardial ischemia.     

The effects of Escherichia coli sepsis and short-term ischemia on coronary vascular reactivity and myocardial function

A moderately stable protein with typical folding kinetics unfolds and refolds many times during its cellular lifetime. In monomeric lambda repressor this process is extremely rapid, with an average folded state lifetime of only 30 milliseconds. A thermostable variant of this protein (G46A/G48A) unfolds with the wild-type rate, but it folds in approximately 20 microseconds making it the fastest-folding protein yet observed. The effects of alanine to glycine substitutions on the folding and unfolding rate constants of the G46A/G48A variant, measured by dynamic NMR spectroscopy, indicate that the transition state is an ensemble comprised of a disperse range of conformations. This structural diversity in the transition state is consistent with the idea that folding chains are directed towards the native state by a smooth funnel-like conformational energy landscape. The kinetic data for the folding of monomeric lambda repressor can be understood by merging the new energy landscape view of folding with traditional models. This hybrid model incorporates the conformational diversity of denatured and transition state ensembles, a transition state activation energy, and the importance of intrinsic helical stabilities.     

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs

The neurotoxicity of dibucaine was compared with that of commercially available local anesthetics in studies using rabbit desheathed cervical vagus nerve preparation. Dibucaine dose-dependently suppressed the evoked action potential of myelinated A beta nerve component and nonmyelinated C nerve component. The potential of A beta nerve component was more strongly suppressed, compared with that of C nerve component. At low concentrations of 0.0001-0.001%, the suppression was reversible and recovery with C nerve component was faster and more complete. At higher concentrations, the suppression was irreversible. The minimum concentrations of irreversible blockade were 0.003% for A beta nerve component and 0.03% for C nerve component. Electron microscopically, marked damages in the myelin layer and intraaxonal structure were observed in nerves treated with 0.03% dibucaine. When the neurotoxic effect of dibucaine was compared, in terms of safety margins (minimum concentration of irreversible blockade/clinically used concentrations), with those of commercially available local anesthetics, the rank order was dibucaine, tetracaine and bupivacaine; dibucaine showing the lowest safety margin.     

Technetium-99m teboroxime regional myocardial washout in subjects with and without coronary artery disease

The aim of this study was to test the hypothesis that regional myocardial washout of technetium-99m teboroxime is slowed in the presence of coronary stenosis. Washout was assessed in 33 catheterized patients and in 13 with a low likelihood of coronary artery disease, using a triple detector camera and dynamic single-photon emission computed tomography, with serial 1-minute acquisitions after injection of 20 to 25 mCi of teboroxime at the third minute of adenosine-induced hyperemia. Washout was measured as the percent change in counts between the first, second and third minutes after injection, as measured in 6 short-axis myocardial regions of interest. Myocardial regions were classified as ischemic (> or = 50% diameter stenosis and no prior myocardial infarct), infarcted, normal (no significant coronary stenosis) or "low likelihood" (from the 13 patients with a low likelihood of coronary artery disease). Teboroxime washout was significantly (p < 0.001) slowed in the ischemic myocardium (12.7 +/- 8.3%) compared with the normal (18.5 +/- 5.7%), low-likelihood (17.8 +/- 6.1%) and infarcted (17.8 +/- 4.4%) zones. There was regional variability in washout rates (% washout/min), with the anterior wall having the lowest (13.8 +/- 3.4%/min) and the inferior wall the highest (20.7 +/- 7.9%/min) values. In regard to individual coronary territories, 21 of 41 ischemic, noninfarcted territories (51%) had abnormal washout compared with 3 of 43 normal territories (7%) (p = 0.001). In conclusion, regional washout of teboroxime is detectably slowed in ischemic, noninfarcted myocardium. The clinical value of washout analysis in teboroxime single-photon emission computed tomography warrants further investigation.     

The effect of hemodilution with stroma-free hemoglobin and dextran on collateral perfusion of ischemic myocardium in the dog

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.     

Exercise-induced T-wave normalization predicts recovery of regional contractile function after anterior myocardial infarction

AIMS: We investigated the ability of T-wave pseudonormalization and ST-segment elevation, which are demonstrated in infarct-related leads during submaximal exercise testing, to predict late recovery of contractile function. METHODS: We studied 88 consecutive patients (73 males, mean age 59 +/- 8 years) with anterior infarction, persistent T-wave inversion and a documented lesion of the proximal segment of the left anterior descending coronary artery. They all underwent 2D-echocardiography on admission, 4 weeks as well as 6 months after myocardial infarction to evaluate the dysfunction score and the ejection fraction. Submaximal (75% of maximal predicted heart rate) exercise testing was performed in 80 patients 2 weeks after myocardial infarction following discontinuation of treatment. RESULTS: During exercise testing, 59 of the 88 patients showing negative T-waves on the resting electrocardiogram exhibited pseudonormalization (group A) in at least three adjacent precordial leads, whilst 29 (group B) did not. Patients of group A more frequently exhibited an early creatine kinase peak (41% vs 24%, P < 0.05) and residual angiographic perfusion (97% vs 69%, P < 0.05). The dysfunction score did not change in group B (from 19 +/- 7 to 22 +/- 4), but decreased in group A (from 18 +/- 4 to 11 +/- 6 P < 0.05). The ejection fraction was similar in the two groups on admission (group A: 48 +/- 7%, group B: 45 +/- 10%), but was significantly different at 4-week (52 +/- 99 vs 42 +/- 11%, P < 0.05) and 6-month follow-up (58 +/- 9 vs 44 +/- 10%, P < 0.01). The concomitant presence of ST-segment elevation and T-wave normalization showed the highest positive predictive value for left ventricular function recovery (100%). CONCLUSIONS: T-wave normalization induced by submaximal exercise test is frequently associated with residual perfusion to the infarct area and predicts progressive improvement in regional wall motion, especially if associated with ST-segment elevation. Therefore, these electrocardiographic findings may be used as easily obtainable markers of residual viability that predict late recovery in contractile function.     

Disparate effects of adhesion and degranulation of platelets on myocardial and coronary function in postischaemic hearts

Pre-mRNA splicing is an important regulatory step in the expression of most eukaryotic genes. In vitro studies have shown splicing to occur within 50-60 S multi-component ribonucleoprotein (RNP) complexes termed spliceosomes. Studies of mammalian cell nuclei have revealed larger complexes that sediment at 200 S in sucrose gradients, termed large nuclear RNP (lnRNP) particles. These particles contain all factors required for pre-mRNA splicing, including the spliceosomal U snRNPs and protein splicing factors. Electron microscopy has shown them to consist of four apparently similar substructures. In this study, mass measurements by scanning transmission electron microscopy of freeze-dried mammalian lnRNP preparations, both confirm the similarity between the lnRNP particles and reveal the mass uniformity of their subunits. Thus, the tetrameric lnRNP particle has a mass of 21.1(+/-1.6) MDa, while each repeating subunit has a mass of 4.8(+/-0.5) MDa, which is close to the estimated mass of the fully assembled 60 S spliceosome. The 1.9 MDa discrepancy between the lnRNP particle's mass and the cumulative masses of its four subunits may be attributed to an additional domain frequently observed in the micrographs. Notably, strands and loops of RNA were often seen emanating from lnRNP particles positively stained with uranyl formate. Our results support the idea that the nuclear splicing machine is a supraspliceosome complex. For clarity, we define spliceosomes devoid of pre-mRNA as spliceosome cores, and propose that the supraspliceosome is constructed from one pre-mRNA, four spliceosome cores, each composed mainly of U snRNPs, and additional proteins. In this way a frame is provided to juxtapose exons about to be spliced.     

Effects of dobutamine on myocardial blood flow, contractile function, and bioenergetic responses distal to coronary stenosis: implications with regard to dobutamine stress testing

To determine the effects of dobutamine stimulation on myocardium distal to a coronary stenosis, transmural spatially localized phosphorus 31 nuclear magnetic resonance measurements of myocardial high-energy phosphate compounds (adenosine triphosphate and phosphocreatine), inorganic phosphate, and blood flow and systolic wall thickening were made in 8 open-chested dogs. Data were collected under (1) control conditions, (2) after the application of a moderate coronary stenosis, (3) during infusion of dobutamine with continuing stenosis, and (4) after the release of the stenosis with continuing dobutamine. Stenosis was associated with concordant reductions of subendocardial blood flow, wall thickening, and high-energy phosphate, and mild elevation of inorganic phosphate; subepicardial measurements were essentially unchanged. During dobutamine infusion, blood flow increased in all myocardial layers. Wall thickening returned to control values in the subendocardium and increased nonsignificantly in the subepicardium. Additional loss of high-energy phosphate occurred only in the subepicardium. The data suggest that improved contractile function associated with dobutamine infusion resulted from the inotropic effects of dobutamine and was made possible by the improved blood flow it produced. The data indicate that measurements of blood flow and contractile function do not reliably predict the transmural myocardial metabolic responses to inotropic perturbations in the hypoperfused heart. Taken together, the present findings yield insights with regard to the interpretation of diagnostic dobutamine stimulation testing with single photon emission tomography, radionuclide angiography, and echocardiography.