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Distinct basal ganglia territories are engaged in early and advanced motor sequence learning.

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Adult↗

An anaesthetic protocol in the young domestic pig allowing neuromuscular blockade for studies of cardiac function following cardioplegic arrest and cardiopulmonary bypass.

BACKGROUND: Neuromuscular blockade should, for ethical reasons, not be allowed in animal experiments unless the use is strongly motivated. Beforehand, the anaesthetic protocol must be documented without muscle relaxation in the species studied. Documentation is difficult to obtain from the scientific literature. When focusing on cardiac function over time, in particular, the ideal anaesthetic protocol should cause no or minor alterations in cardiac variables. METHODS: We intended to document an anaesthetic protocol involving ventilation with N(2)O combined with loading doses and continuous infusions of pentobarbital, fentanyl and midazolam in seven pigs by applying potentially painful stimuli every 15 min for 7 h. Subsequently, left ventricular global and regional function was studied with conductance catheter and strain rate imaging by echocardiography in eight pigs with pancuronium included. RESULTS: Pigs without pancuronium were completely immobilized and unresponsive to potentially painful stimuli and sternotomy, with no accumulation or degradation of anaesthetic agents. With pancuronium included, left ventricular preload gradually decreased together with reduction of cardiac index from 3.52 +/- 0.14 at 2 h to 2.84 +/- 0.11 L min(-1). m(-2) (+/-SEM) after 7 h of observation. Preload recruitable stroke work decreased after 7 h, whereas peak systolic strain in the anterior left ventricular wall and load-independent indices of diastolic function were not significantly altered. CONCLUSION: In specific experimental protocols, the anaesthetic protocol described could allow the use of muscular paralysis in young domestic pigs, for instance when involving hypothermic cardiopulmonary bypass, cardioplegic arrest and reperfusion.

Adjuvants, Anesthesia↗

[Recovery from aphasia and cerebral blood flow: a comparison between cerebral hemorrhage and cerebral thrombosis].

To compare cerebral circulation in aphasic patients who had cerebral hemorrhage against those who with cerebral thrombosis, we studies 50 patients with hypertensive intracranial (putaminal) hemorrhage and 20 patients with cerebral thrombosis whose diagnoses were confirmed on repeated CT scan and cerebral angiography. The measurements of regional cerebral blood flow (rCBF) by the 133Xe intraarterial injection method was carried out in 40 patients. The evolution of the aphasic syndrome was analyzed according to Hirano's classification and the patients were divided into two groups: those having a favorable recovery from aphasia; those with a poor recovery. Twelve out of 20 patients with cerebral hemorrhage showed a favorable recovery from aphasia, whose left hemispheric mean blood flow (mCBF) was 33.1 +/- 9.7 ml/100 g/min. The mCBF was 30.8 +/- 10.3 ml/100 g/min in 8 patients with a poor recovery. There was no significant difference in mCBF values between the two groups. The favorable recovery group showed slightly higher regional values in the left frontal and temporal lobes than did the poor recovery group, but no significant difference was found between the two group. Here, rCBF values failed to correlate between the two kinds of recovery from aphasia in patients with cerebral hemorrhage. The marked variability in rCBF values in the acute stage might partly account for the poor correlation in cerebral hemorrhage. In contrast, a series of rCBF studies demonstrated that rCBF values stabilized in the acute and subacute stage in cerebral thrombosis. Nine out of 20 patients with cerebral thrombosis had a favorable recovery from aphasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aphasia↗

Noninvasive mapping of left ventricular electromechanical asynchrony by three-dimensional echocardiography and semi-automatic contour detection.

A system for analyzing left ventricular (LV) electromechanical asynchrony based on transesophageal 3-dimensional echocardiography (3-DE) and semi-automatic endocardial contour detection is described. Eighteen consecutive patients underwent 3-DE. Using TomTec 4DLV software, a 3-dimensional endocardial surface was reconstructed throughout the cardiac cycle. Matlab software generated color-coded polar maps, displaying regional LV displacement and its timing. At the segmental level, Bland-Altmann assessment showed intraobserver variability of LV displacement of 0.1 +/- 3.0 mm and timing of -5.6 +/- 160 ms (bias +/- 2 SD) for all segments and -1.6 +/- 94 ms for the nonapical segments. The combination of 3-DE and semi-automatic contour detection is feasible and provides unique information for assessing regional LV endocardial displacement and electromechanical asynchrony.

Aged↗

Pharmaco-EEG profile of maroxepine: third example to discuss the predictive value of pharmaco-electroencephalography in early human pharmacological evaluations of psychoactive drugs.

This publication forms the third part of a critical evaluation of pharmaco-EEG applications as an instrument for assessing the profile of action of psychoactive drugs based on the trial results of three new psychoactive test substances: savoxepine, levoprotiline and maroxepine. After the presentation, in Parts I (savoxepine) and II (levoprotiline), of trial substances for which compatible results were obtained in the pharmaco-EEG model and in the clinical studies, a case with discrepant and less predictive results has been presented, and on this basis the limitations of the pharmaco-EEG model in the evaluation of therapeutic efficacy are discussed. The substance examined in this report, the tetracyclic dibenzoxepine derivative, maroxepine, produced prominent central effects in pharmacological studies which pointed to a bipolar profile of action, i.e., the EEG showed similarities both to antidepressants and antipsychotics. The pharmaco-EEG effects of maroxepine were investigated in a randomised, double-blind study in 15 young healthy male subjects and compared with those of placebo and the reference substances, chlorpromazine and imipramine. The experimental design was a cross-over uncompleted block design with five consecutive trial days one week apart. The pharmaco-EEG was recorded from the occipito-temporal and frontocentral regions before, 3 and 6 h after application of 2.5 mg and 5.0 mg maroxepine, 75 mg chlorpromazine, 75 mg imipramine and placebo. The selected target variables for descriptive statistical evaluation were the Spectral Difference Index (SDI), the absolute and relative power values in seven predetermined frequency bands within the range 1.5 to 30.0 Hz, the dominant frequency (6.0 to 18.0 Hz) and the alpha slow-wave index (ASI). The results show that maroxepine has a potent central nervous action and a strong sedative potential. The EEG effects consisted of a shift to the left of the relative power spectrum of the occipital lead, accompanied by an increase in the absolute beta power in the frontocentral region. Discriminative inspection of the profiles of EEG changes, induced by maroxepine and the reference drugs, revealed closer similarity of maroxepine with chlorpromazine than with imipramine. Maroxepine showed vigilance-decreasing features like imipramine. This is one condition to be able to interfere with depressive illness. The underlying hypothesis is that depressive illness is based on affective and vigilance disturbance. Maroxepine furthermore showed the typical neuroleptic-like shift from resting alpha to resting subalpha (theta F band) which we assume related to the anti-productive properties of neuroleptics in schizophrenia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Comparison of nifedipine and metoprolol on collateral coronary blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia.

PURPOSE: This study compared the effects of nifedipine and metoprolol on collateral-dependent myocardial blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia. METHODS: Collateral coronary circulation was induced in 15 three-week-old piglets by banding of the proximal left anterior descending coronary artery (LAD). After 8-10 wk, the distal LAD was ligated and the open-chest pigs were randomized to receive infusions of either saline, nifedipine (5 micrograms.kg-1.min-1) or metoprolol (10 micrograms.kg-1.min-1) for 30 min during isoflurane anaesthesia (2%). Transient ischaemia was induced by 30 sec occlusion of the left circumflex artery. Arterial blood pressures, heart rate and regional myocardial blood flow (radiolabelled microspheres technique) were measured at the end of drug infusion (baseline) and one minute after transient ischaemia. RESULTS: No differences in the blood flow to the collateral-dependent (CD) myocardium or haemodynamic variables were observed at baseline among the three groups. Following transient ischaemia, in the nifedipine but not in the metoprolol group, blood flow to the CD myocardium was reduced by 28 +/- 24% in the epicardium (P < 0.05) and 56 +/- 20% in the endocardium (P < 0.01), resulting from intercoronary and transmural steal. This was associated with a moderate increase (10%, P < 0.05) in the heart rate in the nifedipine group. CONCLUSIONS: In a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia, the collateral coronary blood flow was maintained in the presence of metoprolol, but reduced in the presence of nifedipine following transient ischaemia due to intercoronary and transmural steal.

Adrenergic beta-Antagonists↗

A chronic focal epilepsy with mossy fiber sprouting follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infant rats.

Studies were conducted to characterize a chronic epileptic condition that follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infancy. Wistar rat pups received a single injection of tetanus toxin in the right CA3 region on postnatal day 10. Animals were monitored for epileptiform activity by video electroencephalographic or visual observation during the following three to five days. Repeat evaluation six months later demonstrated interictal discharges in 79% (11 of 14) and electrographic seizures in 42% (six of 14) of adult rats with tetanus toxin-induced seizures in infancy. Five of the animals had interictal activity which occurred focally in either the left (n = 2) or right (n = 3) hippocampus. One animal had focal interictal activity independently in these regions and in the left and right cortical regions. The remaining five animals had interictal activity in the hippocampus and synchronously in the ipsilateral cortex or the contralateral hippocampus. Electrographic seizures were focal (nine of 14) or bilateral (five of 14) in onset. The behaviors that accompanied these seizures were quite variable. Clonic face and forelimb movements were observed in some animals. However, a significant portion of rats had electrographic seizures with no associated behavioral change. Timm staining was performed on hippocampal sections from experimental and control animals. There was a significantly greater Timm score (aberrant Timm granules) in the inner molecular layer of the dentate gyrus in tetanus toxin-treated rats than in control rats. Our findings suggest that intrahippocampal tetanus toxin injection in infant rats results in a chronic focal epilepsy that persists for at least six months and is associated with aberrant mossy fiber sprouting in the dentate gyrus. The model described here contributes significantly to the evidence for chronic effects of recurrent seizures in early life, and provides a model for investigation of the molecular and cellular events that contribute to the development of chronic epilepsy.

Aging↗

[Mechanisms and consequences of changes of the vasomotor activity in cardiac insufficiency].

Changes in vasomotor tone in cardiac failure are related to the severity of the cardiac failure. The causative factors include dysfunction of the baroreceptor reflex, abnormal stimulation of the normal physiological regulators of cardio-circulatory function such as the sympathetic nervous and the renin-angiotensin-aldosterone system, and certain local factors characteristic of cardiac failure such as salt and water retention at vascular wall and interstitial level or changes in the metabolism of certain tissues. These changes are variable according to the region perfused and their interaction results in preferential redistribution of blood flow to the coronary and cerebral circulations at the expense of other regions such as the splanchnic and cutaneous vessels. In addition, they play a key role in the adaptive peripheral mechanisms to left ventricular failure and to the modulation of the vascular effects of drug therapy. An improvement in our understanding of these mechanisms and their consequences is important from the physiopathological, prognostic and therapeutic points of view.

Cardiac Output↗

The use of positron emission tomography imaging in the management of patients with ischemic cardiomyopathy.

Rational management of patients with CAD and poor left ventricular function relies on proper identification of the subgroup at high risk and those who have the highest potential of benefiting from a particular type of treatment. It is now well recognized that patients with CAD and left ventricular dysfunction have a high but variable mortality rate while receiving medical therapy. Many of these patients who have intractable heart failure are considered candidates for cardiac transplantation. Despite favorable survival after cardiac transplantation, this procedure cannot be performed in 90% of the heart failure patients who are potentially eligible because of the shortage of donor hearts. Cardiac transplantation is also an expensive procedure. Perfusion-FDG metabolism PET imaging has become the gold-standard noninvasive imaging method to identify the presence and extent of hibernating myocardium. Positron emission tomography accurately predicts recovery of regional and global left ventricular dysfunction after revascularization. In patients with poor left ventricular function, the PET pattern of perfusion metabolism mismatch is also predictive of improvement in heart failure symptoms and survival benefit after myocardial revascularization. These data suggest that a rational approach may be developed for cost-effective management of patients with CAD and poor left ventricular function.

Cell Survival↗

Quantification of left atrial appendage spontaneous echo contrast in patients with chronic nonalvular atrial fibrillation.

OBJECTIVES: The left atrial (LA) appendage is the most common site of thrombus formation in patients with atrial fibrillation, and integrated backscatter allows the quantiative assessment of LA spontaneous echo contrast (SEC). Integrated backscatter was used to examine the significance of measuring appendage SEC, specifically in relation to echocardiographic variables implying thromboembolism, in patients with chronic nonvalvular atrial fibrillation. METHODS: Fifty-two patients with chronic nonvalvular atrial fibrillation and no prior anticoagulant therapy (35 men, 17 women, mean age 66 +/- 7 years) underwent transesophageal echocardiography with integrated backscatter analysis. The LA and LA appendage integrated backscatter intensity were measured with the regions of interest placed in the LA cavity and the appendage, respectively. The integrated backscatter intensity values for these two chambers (corrected "LA" and "LA appendage" integrated backscatter intensity, respectively) were corrected using values from the left ventricular cavity. RESULTS: The LA appendage integrated backscatter intensity values were available in 44 patients (85%). Overall, the corrected LA appendage integrated backscatter intensity was significantly increased compared with the corrected LA integrated backscatter intensity (2.8 +/- 2.2 vs 2.0 +/- 1.8 dB, p < 0.001). The corrected LA appendage integrated backscatter intensity was inversely correlated with the LA appendage velocity (r = -0.37, p < 0.05), but not with the LA dimension, appendage size, or left ventricular function. The corrected appendage integrated backscatter intensity (4.5 +/- 2.3 vs 2.4 +/- 1.9 dB, p < 0.01) and LA integrated backscatter intensity (3.2 +/- 2.1 vs 1.7 +/- 1.7 dB, p < 0.05) were higher in patients who had LA appendage thrombus (n = 8) than those who did not. With the corrected appendage integrated backscatter intensity set at > or = 2.5 dB, the sensitivity for the presence of appendage thrombus was 88% and the specificity was 64%. CONCLUSIONS: Patients with chronic nonvalvular atrial fibrillation had a denser SEC in the LA appendage compared with SEC in the main LA cavity. The severity of the appendage SEC was influenced by the LA appendage function rather than its size. Quantification of SEC in the appendage, rather than main LA cavity, was more valuable for assessing embolic potential.

Aged↗

Widespread Molecular Imprints in the Serum Proteome of COVID-19 Convalescents Uncovering Immune System Sequelae.

Post-COVID-19 sequelae have become an emerging global health issue, but the mechanisms for the sustained susceptibility of convalescents to the sequelae remain poorly understood. Here we report the use of a restricted open-search approach to explore the molecular imprints of SARS-CoV-2 infection left on the proteome of 412 COVID-19 patients and convalescences. A total of 827 non-standard amino acid variations, chemically modified residues as well as post-translational modifications, termed non-coded amino acids (ncAAs), are found spreading over 29,814 sites in patient's serum proteins. Markedly, widespread ncAAs are induced and sustainedly imprinted on the serum proteome predominately perturbing the immunoglobulin-mediated immune response, complement activation and coagulation regulation even 12 months after recovery. Sustained amino acid variations and chemical modifications are found in the complementary&#x2011;determining regions (CDRs) of the variable region of immunoglobulin contributing to the interactions between the emerging antibody and antigens; durable chemical amino acid modifications found in the hyper ncAA-modified regions of the constant region of immunoglobulin important for the interaction with the complement and regulatory receptors. In the complement system, inducible ncAAs are memorized in the components essential for the complement activation, amplification cascades and membrane attack processes. Thus, the workflow described in this study can be used to identify the molecular imprints of viral infection at the proteomic scale, particularly the specific antibodies and the immune targets left in COVID-19 patients and convalescents.

Humans↗

Neurosarcoma of the face: MRI.

Neurosarcoma is a rare tumour originating from the sheath of peripheral nerves. Facial lesions have been reported in about 20 patients. We describe the MRI appearances of neurosarcoma with histological correlation in three patients. The lesions lay in the submandibular region, the left parapharyngeal space and the right orbit. MRI showed a well-defined mass with mixed components. The lesions were moderately heterogeneous on T1-weighted images in two cases and on T2-weighted images in all cases. Gadolinium enhancement occurred in all cases to variable degrees. In two cases, small high signal foci were seen on T2-weighted sequences. MRI appearances of neurosarcoma are not specific.

Adolescent↗

Individual variability in cortical organization: its relationship to brain laterality and implications to function.

The human brain and the brains of most mammals studied for this purpose demonstrate hemispheric asymmetry of gross anatomical landmarks and/or architectonic cortical subdivisions. The magnitude as well as the direction of these cortical asymmetries vary among individuals, and in some species there exist significant population directional biases. The magnitude, if not the direction, of cortical asymmetry is found to predict for relative numbers of neurons comprising a given pair of hemispheric architectonic homologues such that the more asymmetric the region is, the smaller the number of neurons. Similarly, the more asymmetric a region is, the smaller the density of interhemispheric connections and (probably) the greater the density of intrahemispheric connections. Developmentally, the decrease in the number of neurons characterizing the more asymmetrical regions appears to reflect mainly increased unilateral ontogenetic cell loss, and diminished callosal connectivity might signify increased developmental axonal pruning. These relationships between cell numbers, callosal connections, and presumed intrahemispheric relationships can be entertained to explain variability in anatomo-clinical correlations for language function and aphasia between left- and right-handers and men and women.

Animals↗

Assessment of coronary stenoses of graded severity by myocardial contrast echocardiography.

BACKGROUND: Myocardial contrast echocardiography (MCE) has potential value in the assessment and quantitation of myocardial perfusion defects. However, the severity of stenosis detectable by MCE and its diagnostic accuracy remain undefined. Thus, we produced coronary stenoses of variable severity and quantified their effect on MCE. METHODS AND RESULTS: Three grades of left anterior descending (LAD) obstructions were produced in 7 open-chest swine. The stenoses were nonflow-limiting at rest, but decreased coronary hyperemia by 31.3% +/- 4.7%, 69.9% +/- 5.3% and 98.9% +/- 1.1%, respectively. Regional myocardial blood flow (RBF) was measured with fluorescent microspheres and was expressed as the ratio of LAD and control (LCx) beds. MCE was performed with 0.3 mg/kg intravenous AF0150 during ECG-gated harmonic imaging in short-axis view. Background-subtracted peak intensity (PI) was expressed as the ratio of LAD/LCx beds. Both RBF and PI ratios progressively decreased with increasing grades of stenosis. MCE showed a significant correlation with RBF (r = 0.74; P <.0001). Ratios of both PI and RBF differed significantly from baseline when coronary hyperemia was reduced more than 50%. An LAD/LCx ratio less than 0.6 by MCE yielded 61% and 83% sensitivity and 85% and 76% specificity with stenosis that reduced coronary hyperemia more than 50% and more than 75%, respectively. CONCLUSION: MCE with intravenous AF0150 during vasodilation correctly depicted the progressive reduction of flow ratios produced by graded coronary stenoses. A significant reduction of PI ratio was observed with stenosis causing more than 50% reduction of coronary hyperemia. An MCE ratio in stenosed/control beds could be selected, which exhibited good sensitivity and specificity in the identification of coronary stenosis.

Animals↗

Beneficial effects of fenoldopam on systemic and regional hemodynamics in rabbits with congestive heart failure.

Fenoldopam (SKF 82526 J) is a selective DA-1 receptor agonist and thus of a potential benefit for promoting afterload reduction, renal vasodilatation, and diuresis in congestive heart failure. To examine the acute effects of fenoldopam in heart failure, studies were performed in control rabbits (n = 6) and in rabbits with chronic congestive heart failure (CHF, n = 6) induced by adriamycin treatment. Cardiovascular variables and regional blood flows were determined before and after an infusion of fenoldopam (150 micrograms/kg total dose). Resting hemodynamics differed in CHF and control groups. In the CHF group, mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were reduced and right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), and total peripheral resistance (TPR) were increased. Renal blood flow was much reduced in the CHF as compared with the control group (5.1 +/- 0.8 vs. 9.1 +/- 0.6 ml/min.g, p less than 0.05). Similar falls in MAP were noted after fenoldopam in CHF (-13 +/- 2%) and control rabbits (-12 +/- 3%) due to falls in TPR. An increase in CO was observed in both groups, the rise being more pronounced in the CHF group (22 vs. 12%). Heart rate was unchanged by fenoldopam in CHF rabbits but increased in controls. After fenoldopam, CHF rabbits exhibited significantly greater increases in blood flow to each of the three vascular beds studied: renal (113 +/- 27% vs. 7 +/- 13%), mesenteric (249 +/- 60% vs. 15 +/- 19%) and cerebral (145 +/- 13% vs. 12 +/- 12%). Plasma renin and norepinephrine (NE) levels increased after fenoldopam in both control and CHF rabbits. These results show that acute administration of fenoldopam produces favourable systemic and regional hemodynamic responses in rabbits with low output heart failure. However, long-term benefit remains to be demonstrated, particularly considering the hormonal responses.

Animals↗

Variable ECG signs of ischemia during controlled occlusion of the left and right coronary artery in humans.

Infarct size (IS) increases with vascular occlusion time, area at risk for infarction, lack of collateral supply, absence of preconditioning, and myocardial demand for O2 supply. ECG S-T segment elevation is used as a measure of severity of ischemia and a surrogate for IS. This study in 50 patients with coronary artery disease undergoing a first 120-s balloon occlusion of a stenosis sought to determine whether S-T segment elevation, corrected for the above-mentioned variables, in the left coronary artery (LCA group, n = 36) is different from that in the right coronary artery (RCA group, n = 14) territory. After consideration of all known determinants of IS, particularly mass at risk and collateral supply, the LCA territory is more sensitive than the RCA region to a 2-min period of myocardial ischemia.

Coronary Artery Disease↗

Sequence of events in angina at rest: primary reduction in coronary flow.

To investigate the events that lead to acute myocardial ischemia we monitored continuously the ECG, the left ventricular (four patients) or aortic (two patients) pressure and the great cardiac vein oxygen saturation (CSO2S) by a fiberoptic catheter in six patients with frequent anginal attacks at rest. We recorded 137 transient ischemic episodes (10 with chest pain) characterized by ST-segment elevation in 28 episodes, depression in three episodes and by pseudonormalization of previously inverted or flat T waves in 106 episodes. The onset of electrocardiographic and hemodynamic changes was preceded by a large drop in CSO2S in all 135 episodes with ST-T changes in the anterior leads but not in two episodes with ST elevation on inferior leads. The fall in CSO2S, consistently followed by signs of left ventricular function impairment and never preceded by any detectable increase in the hemodynamic determinants of myocardial oxygen consumption, probably reflects a reduction in regional perfusion. Thus, a reduction in coronary flow may cause transient ischemia in patients with angina at rest. These episodes may be associated with variable, often minor electrocardiographic changes and occasionally with anginal pain.

Adult↗

Role of thromboxane A2 in the control of myocardial O2 supply/consumption balance and severity of ischemia during pacing-induced ischemia.

The role of thromboxane A2 (TXA2) in the control of O2 supply/consumption variables during pacing-induced ischemia was examined using the TXA2 receptor antagonist SQ 29,548. Anesthetized, open-chest dogs were subjected to left anterior descending coronary artery (LAD) stenosis that produced significant epicardial S-T segment elevation (12 mV) only when superimposed on atrial pacing. Regional myocardial blood flow was determined using radioactive microspheres, and O2 consumption was determined by measuring O2 saturation of venous blood draining the ischemic region. The dogs were treated with saline or 0.2 mg/kg + 0.2 mg/kg/hr SQ 29,548, and the effect on ischemia was determined during 5-minute pacing-induced ischemic episodes at 10, 40, and 70 minutes postdrug or saline treatment. SQ 29,548 significantly reduced S-T elevation at 40 and 70 minutes postdrug compared with saline values and at all times measured compared with its paired predrug pace+stenosis values. SQ 29,548 reduced S-T elevation approximately 45% compared with its paired predrug values at 70 minutes. SQ 29,548 resulted in a significantly higher subendocardial-to-subepicardial flow ratio (0.70 +/- 0.10, p less than 0.05) compared with saline-treated animals (0.42 +/- 0.06), with an overall increase of flow to the ischemic region of approximately 40%. This increased flow was matched by a proportional increase in O2 consumption without a change in O2 extraction. The O2 supply/consumption balance was also unchanged by SQ 29,548 implying that despite the increase in blood flow, the ischemic region was still flow-limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗