Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Equal reductions in heart rate (44 beats X min-1) were obtained in cats by treatment with either the beta blocking agent timolol or alinidine, an agent claimed to cause bradycardia without interfering with beta adrenoceptor function. Infarct size was measured by staining with triphenyltetrazolium-chloride after 5 h of coronary occlusion and related to the area of hypoperfused myocardium as measured by autoradiography. Regional myocardial blood flow was measured by 15 micron radiolabelled microspheres. Compared with the control cats, in whom 87.4 (SEM 2.2)% of hypoperfused myocardium developed into necrosis, timolol reduced infarct size to 65.8 (SEM 2.6)% (p less than 0.001) and alinidine to 76.2 (SEM 3.1)% (p less than 0.01) of the hypoperfused area. Timolol reduced infarct size more than did alinidine (p less than 0.01). Necrosis was more extensive in the endocardium than in the epicardium in all groups. In the subendocardium timolol and alinidine reduced infarct size to the same extent, whereas timolol reduced infarct size more than alinidine in the subepicardium. Although heart rate proved to be the dominant haemodynamic predictor of infarct size, this study indicates that mechanisms other than reduced oxygen demand associated with bradycardia and cardiodepression are operating in the ischaemic myocardium during beta adrenergic blockade.
 ...
PMID:Is reduced cardiac performance the only mechanism for myocardial infarct size reduction during beta adrenergic blockade? 375 74

The effects of lipoxygenase enzyme inhibitor nafazatrom on infarct size, haemodynamics, and prostanoid release was studied in a canine occlusion-reperfusion model of ischaemic myocardial injury. Treatment was with 10 mg/kg nafazatrom i.d., starting before coronary occlusion, 2 h and 6 h thereafter, and was repeated in 6 h intervals. The left anterior descending (LAD) coronary artery was occluded for 6 h and reperfused for 42 h. Infarct size and anatomic area dependent on the occluded LAD were determined post mortem by the tetrazolium staining technique. Nafazatrom significantly reduced the extent of irreversible myocardial ischaemic damage whether it was expressed as g/100 g left ventricle (24 +/- 4 vs. 46 +/- 6 in controls; p less than 0.01; mean +/- SEM) or as percentage of LAD risk region for infarcting (38 +/- 8 vs. 65 +/- 7% in controls; p less than 0.05). Nafazatrom did not affect peripheral haemodynamics but during drug vehicle treatment and LAD occlusion systemic blood pressure, left ventricular pressure and dP/dtmax decreased while filling pressure, heart rate, and the S-T segments of the ECG increased. The incidence of ventricular fibrillation was 8% during drug treatment and coronary ligature vs. 25% in controls (n.s.). During reperfusion, nafazatrom reduced the incidence of ventricular premature contractions and tachycardia. Ex vivo platelet aggregation in response to collagen was not inhibited by nafazatrom. Prostanoid release (thromboxane B2 and 6-keto-prostaglandin F1 alpha as breakdown products of thromboxane A2 and prostacyclin, respectively) remained unaltered in vehicle controls but nafazatrom treatment elevated prostacyclin release significantly at 4 and 5 h during LAD occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effects of nafazatrom in an acute occlusion-reperfusion model of canine myocardial injury. 384 82

After acute regional coronary occlusion, myocardial tissue PCO2, as measured by mass spectrometry, rises, reaches a peak, and then gradually falls. This late fall in myocardial tissue PCO2 could be due to (1) a gradual increase in tissue blood flow (and hence improved carbon dioxide washout), (2) a gradual consumption of tissue bicarbonate, (3) a gradual reduction in the production of carbon dioxide due to progressive cellular damage, or (4) an artifact caused by the continued presence of the mass spectrometer probe in the ischemic tissue. To determine which of these four mechanisms is responsible for the late fall in myocardial tissue PCO2, we subjected 27 anesthetized open-chest dogs to 3-hour occlusion of the left anterior descending coronary artery. Both myocardial tissue PCO2 and intramyocardial hydrogen ion concentration were measured in the myocardial segment supplied by the left anterior descending coronary artery. Ten dogs (group 1) were killed after the occlusion (occlusion I), and 11 dogs (group 2) underwent reocclusion (occlusion II) at the same site after a 45-minute period of reflow. Regional myocardial blood flow was measured periodically by the intramural injection of 127Xe. Changes in myocardial tissue PCO2 and hydrogen ion concentration were related to ultrastructural changes in the tissues adjacent to the myocardial tissue PCO2 probe. Regional myocardial blood flow remained unchanged throughout the 3-hour occlusion, ruling out increased carbon dioxide washout as a cause for its late fall. Tissue hydrogen ion concentration, as measured by a new lead glass electrode, correlated well with myocardial tissue PCO2, with the reduction in regional myocardial blood flow, and with ischemic damage assessed histologically. Myocardial hydrogen ion concentration also exhibited a late fall after the occlusion, from a peak of 199.8 +/- 27.8 nmol/liter to 91.9 +/- 12.1 nmol/liter (mean +/- SEM). This ruled out consumption of tissue bicarbonate as the cause for the late fall in myocardial tissue PCO2. Peak rise in myocardial tissue PCO2 after occlusion II (71.2 +/- 7.9 mm Hg) was significantly lower than peak myocardial tissue PCO2 after occlusion I (116.7 +/- 13.9 mm Hg, P less than 0.001). The difference between these latter two values, as well as the magnitude of fall in myocardial tissue PCO2 during occlusion I, related directly to the degree of histological damage observed.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The significance of the late fall in myocardial PCO2 and its relationship to myocardial pH after regional coronary occlusion in the dog. 391 63

Thallium-201 (201Tl) uptake and redistribution kinetics were examined in an open-chest canine preparation of occlusion and reperfusion. Seven dogs (group I) underwent 3 hr of sustained occlusion and received 1.5 mCi of 201Tl after 40 min of occlusion of the left anterior descending coronary artery (LAD). Group II (n = 18) underwent 60 min of LAD occlusion followed by sudden and total release of the ligature. Group IIa (n = 8) received intravenous 201Tl during occlusion of the LAD, whereas group IIb (n = 10) received intravenous 201Tl at the time of peak reflow. Group III dogs (n = 26) also underwent 60 min of LAD occlusion that was followed by gradual reflow through a residual critical stenosis. Animals in this group also received 201Tl either before (IIIa; n = 16) or after reflow was established (IIIb; n = 10). In group I, the relative 201Tl gradient (nonischemic minus ischemic activity) decreased from 88 +/- 8% (mean +/- SEM) to 59 +/- 6% during 3 hr of coronary occlusion (p = .034). After rapid and total reperfusion (group IIa), this gradient decreased from 71 +/- 6% during occlusion to 26 +/- 5% after reflow (p less than .001). After slow reperfusion through a residual stenosis (group IIIa), the gradient decreased from 81 +/- 5% to 31 +/- 5% (p less than .001) (p = .56 compared with group IIa). In rapidly reperfused dogs receiving intravenous thallium during peak reflow (IIb), initial 201Tl activity in the ischemic zone was 155 +/- 20% of initial normal activity and fell to 93 +/- 13% of normal after 2 hr of reperfusion. Similarly, in dogs reperfused slowly through a critical stenosis (IIIb), which received 201Tl during reflow, 201Tl activity soon after reflow was 94 +/- 4% of initial normal and decreased to 80 +/- 6% at 2 hr of reperfusion (p = .10). Histochemical evidence of necrosis was present in the biopsy region in 80% of the 20 dogs subjected to triphenyl tetrazolium chloride (TTC) staining. Microsphere-determined transmural blood flow was similar in all groups during LAD occlusion and final flows after 2 hr were comparable in all subgroups undergoing reflow. Ischemic zone flow (% normal) was significantly higher at the time of 201Tl administration in groups IIb (192 +/- 25%) and IIIb (110 +/- 5%), which received 201Tl during reflow, than in groups IIa (31 +/- 9%) and IIIa (22 +/- 5%), which received 201Tl during occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Myocardial thallium-201 kinetics during coronary occlusion and reperfusion: influence of method of reflow and timing of thallium-201 administration. 394 Jun 65

Using sonar microcrystals implanted in conscious dogs, we have characterized left ventricular segmental relaxation (LVSR) by measuring the mean rate to half end-diastolic thinning (RHEDT) and the late diastolic thinning fraction (TF). In protocol 1 (five nonischemic dogs), RHEDT correlated with changes in left ventricular dP/dt (r = .87) and systemic arterial pressure (r = -.80) but not with alterations in heart rate. Only systemic arterial pressure importantly influenced TF (r = -.65). In protocol 2 (21 dogs), LVSR paralleled net systolic segmental wall thickness (NET) during both 2 and 4 hr of coronary occlusion followed by 1 month reperfusion. Both LVSR and NET remained depressed during 2 and 4 hr of coronary occlusion and through 24 hr of reperfusion, but both also gradually improved afterwards. In protocol 3, 31 dogs underwent 4 hr of coronary occlusion with 1 month of reperfusion. Among these animals, 11 dogs (group S4) received saline after 1 hr of occlusion, nine dogs (group P4) received propranolol, and 11 dogs (group D4) received diltiazem. Drug therapy was stopped at 2 hr of reperfusion. In segments with mildly and moderately depressed NET, LVSR was significantly increased in group D4 vs group S4 animals during the diltiazem infusion. Expressed as mean percentage of control value +/- SEM, RHEDT of moderately dysfunctional segments in group D4 compared with group S4 measured 53 +/- 10% vs 25 +/- 5%, respectively, at 2 hr of occlusion of the left anterior descending coronary artery (p = .03), 76 +/- 17% vs 28 +/- 8%, respectively, at 4 hr of occlusion (p = .01), and 74 +/- 11% vs 33 +/- 10%, respectively, at 1 hr of reperfusion (p less than .05). The differences in TF at these same time points were 106 +/- 10% vs 70 +/- 9% (p less than .03), 105 +/- 7% vs 65 +/- 16% (p less than .02), and 106 +/- 11% vs 74 +/- 13% (p less than .05), respectively. The improvement in LVSR occurred independently of changes in NET. The values of LVSR in the diltiazem-treated dogs fell to the levels of groups S4 and P4 within 24 hr of stopping the intervention. Propranolol did not significantly alter LVSR over the short or long term. The increase in LVSR during administration of diltiazem did not appear to be mediated by changes in contractility or regional myocardial blood flow, but were probably mediated in part by afterload reduction and possibly by a reduction in calcium entry into ischemic myocardium.
 ...
PMID:Effect of diltiazem and propranolol on left ventricular segmental relaxation during temporary coronary arterial occlusion and one month reperfusion in conscious dogs. 396 19

Eight open chest dogs underwent 25 min of coronary occlusion to determine whether brief myocardial ischemia disrupts the normal myocardial inotropic response to sympathetic nervous stimulation. If so, this could represent a mechanism contributing to postischemic myocardial dysfunction. Myocardial segment shortening was measured using ultrasonic dimension crystals before and after coronary artery occlusion and reperfusion. Left ansa subclavia stimulation and systemic norepinephrine (NE) infusion were used to test the myocardial inotropic response to neural stimulation and direct exposure to the sympathetic mediator, respectively. Before coronary artery occlusion, base-line preischemic segment shortening (12.5 +/- 1.6%) (SEM) increased during both sympathetic stimulation (20.2 +/- 1.4%) and NE infusion (19.7 +/- 1.1%). The control segment responded similarly. After ischemia and reperfusion there was no significant change in heart rate, aortic or left ventricular pressures, nor changes in control segment shortening. In contrast, shortening in the postischemic segment was markedly reduced compared to baseline (4.1 +/- 2.4%), and no longer responded to sympathetic stimulation (2.4 +/- 2.8%), while responsiveness to systemic NE was maintained (12.9 +/- 2.0%), P less than 0.001, which suggested injury to the sympathetic-neural axis during the period of ischemia. This reduced response to neural stimulation was persistent for up to 2 h after reperfusion. Left atrial or intracoronary infusion of bretylium tosylate, which releases norepinephrine from nerve terminals, resulted in an immediate inotropic response in the postischemic segment, which indicated that total depletion of NE from nerve terminals during the ischemic period had not occurred. Disruption of sympathetic neural responsiveness is likely a component of the mechanism of postischemic myocardial dysfunction whenever there is appreciable sympathetic drive to the heart.
 ...
PMID:Reduction of sympathetic inotropic response after ischemia in dogs. Contributor to stunned myocardium. 399 47

Recent studies have demonstrated a depressant effect of increased delivery of FFA to the hypoxic heart. Because catecholamines are released in acute myocardial infarction, it is likely that lipolytic activity is increased. The purpose of this study was to determine whether inhibition of hormone-sensitive lipases influence the extent and severity of myocardial ischemic injury produced by coronary occlusion. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery in open-chest dogs. 15 min later a surface map of S-T segments was obtained with the use of 10-14 epicardial leads in the distribution area of the occluded artery. Average S-T segment elevation of all sites was used as an index of myocardial ischemic injury. Before coronary occlusion, the average S-T segment elevation was 0.3+/-0.2, which increased to 4.1+/-0.7 mV (SEM, 12 dogs) after occlusion. Inhibition of lipolytic activity by beta-pyridyl-carbinol before repeated coronary occlusion reduced the occlusion-induced S-T segment elevation to 2.1+/-0.6 mV (P < 0.001). When arterial concentrations of FFA were raised by i.v. infusion of a triglyceride emulsion and heparin, average S-T segment elevation after coronary occlusion increased from 1.2+/-0.7 to 2.2+/-0.8 mV (P < 0.05) in animals treated with beta-pyridyl-carbinol, which suggests an unfavorable effect of circulating FFA in this setting. Isoproterenol given before a repeated occlusion increased the severity and extent of the ischemic injury. The effect of isoproterenol on the occlusion-induced S-T segment elevation was reduced, however, when the lipolytic effect of the drug was inhibited by beta-pyridyl-carbinol. Our study suggests that beta-pyridyl-carbinol during acute coronary artery occlusion may be of importance in reducing the extent and severity of myocardial ischemic injury.
 ...
PMID:Effect of inhibition of lipolysis on infarct size after experimental coronary artery occlusion. 471 63

While the reflex influence of selective coronary arterial occlusion on the resistance vasculature has been well delineated, the reflex influence of coronary occlusion on the total capacitance vasculature has not been examined. Thus, selective coronary occlusions were performed in 65 anesthetized dogs. Blood was drained from the vena cavae and returned to the right atrium at a constant rate so that changes in total intravascular volume could be recorded as reciprocal changes in extracorporeal reservoir volume. In 10 animals, 2.5 min of left anterior descending occlusion was associated with only an insignificant total volume increase of 6 +/- 4 ml (SEM), whereas 2.5 min of left circumflex occlusion was associated with a 27 +/- 4 ml (P less than 0.001) increase in volume, which was significantly attenuated (P less than 0.001) to only a 7 +/- 3 ml increase after cervical vagectomy. Epicardial lidocaine in four animals reduced the volume increment associated with circumflex occlusion from 30 +/- 3 to 11 +/- 4 ml (P less than 0.025). The volume increase was attenuated from 45 +/- 6 to 24 +/- 5 ml with propranolol administration (P less than 0.001) (seven animals) and from 26 +/- 5 to 17 +/- 6 ml with atropine (P less than 0.025) (eight animals), but was not attenuated with phenoxybenzamine (28 +/- 7 ml before and 25 +/- 2 ml after phenoxybenzamine) (five animals). Double blockade with propranolol and atropine reduced the volume increase to 3 +/- 2 ml (NS) in four of these animals. In order to compare the influences of selective beta-1 adrenergic blockade and combined beta-1 and beta-2 blockade, volume responses were assessed before and after administration of metoprolol or propranolol in doses that produced the same amount of beta-1 blockade (15 animals). The volume increase associated with circumflex occlusion was not attenuated after beta-1 blockade (20 +/- 4 ml before and 18 +/- 5 ml after metoprolol) (eight animals) but was attenuated from 30 +/- 5 to 14 +/- 5 ml after propranolol (P less than 0.05) (seven animals). To examine further the efferent limb of the observed reflex, circumflex occlusions were performed before and after either vagectomy at the level of the diaphragm or section of the sympathetic splanchnic nerves in 12 animals. The volume increment was significantly attenuated after either procedure. In four animals undergoing prior arterial baroreceptor denervation, volume still increased 30 +/- 6 ml (P less than 0.001) with circumflex occlusion. Thus, inferior myocardial ischemia is associated with an autonomic reflex that acts to increase total intravascular volume. The afferent limb is mediated through the vagi, and the efferent limb, throug
 ...
PMID:Reflex influence of selective coronary artery occlusion on the total capacitance vasculature in the dog. 614 Feb 72

The effects of prostacyclin (PGI2) on ventricular arrhythmias following 20 min of coronary occlusion and release were studied in 34 conscious dogs. We administered PGI2 at 100 ng/kg/min and did not observe significant changes in heart rate, blood pressure, or systemic vascular resistance. During the control period, heart rate was 97 +/- 30 (mean +/- SEM) vs. 99 +/- 28 in the PGI2-treated group. Mean arterial pressure was 115 +/- 26 mm Hg and 109 +/- 10 mm Hg in the control and PGI2 groups, respectively. Systemic vascular resistance declined minimally from 2,985 +/- 221 dyn . s . cm-5 to 2,484 +/- 135 dyn . s . cm-5 during the PGI2 infusion (p = NS). Following coronary occlusion, the frequency of ventricular fibrillation was reduced from 53% (9/17) in the control group to 6% (1/17) in the PGI2 group (p less than 0.01). Overall 80-min postinfarction survival was 64% in the group receiving PGI2 infusion compared to 24% in the control group (p less than 0.05). The effects of PGI2 in preventing ventricular fibrillation following acute coronary occlusion can be ascribed to a direct action of this prostaglandin on the myocardium, rather than to an indirect effect due to a reduction in systemic vascular resistance.
 ...
PMID:Administration of prostacyclin prevents ventricular fibrillation following coronary occlusion in conscious dogs. 618 7

The effects of heart rate, autonomic stimulation, and arterial blood pressure upon the multiple repetitive extrasystole threshold (MRET) were studied after coronary occlusion in anesthetized dogs. The MRET was unaffected by changes in heart rate. Sympathetic stimulation alone reduced the MRET from 52.4 +/- 3.7 (mean +/- SEM) to 41.3 +/- 2.7 mA. Vagal stimulation alone was without effect. During simultaneous sympathetic and vagal stimulation the threshold was 48.7 +/- 3.0 mA. This supports the contention that vagal activity serves mainly to oppose the tendency for sympathetic activity to lower the MRET. Reduction of blood pressure significantly decreased the average MRET from 38.6 +/- 2.5 to 34.4 +/- 1.8 mA. The presence of a post junctional site for the observed sympathetic-vagal interaction was investigated using isoproterenol infusion and vagal stimulation. Infusion of isoproterenol lowered the MRET. Vagal stimulation in this situation raised the MRET; the effect varied directly with the rate of isoproterenol infusion. This suggests that part of the vagal effect is exerted postjunctionally; that is, directly upon the myocardial cell and not merely by inhibition of adrenergic transmitter release at sympathetic nerve endings.
 ...
PMID:Interactions among heart rate, autonomic activity, and arterial pressure upon the multiple repetitive extrasystole threshold in the dog. 619 7


<< Previous 1 2 3 4 5 6 7 8 Next >>