Electrophysiologic effects of quinaprilat in dogs during acute myocardial ischemia and following reperfusion

BACKGROUND: There have been few studies concerning the electrophysiologic changes associated with the use of angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction. We examined the electrophysiologic effects of quinaprilat in dogs during acute myocardial ischemia and following reperfusion. METHODS: The left anterior descending coronary artery was occluded for 10 min and reperfused for 10 min. Animals received intravenous quinaprilat (3 micrograms/kg per min, quinaprilat group) or saline (control group). We measured the ventricular effective refractory period and intra-myocardial conduction time within the left anterior descending coronary artery region (ischemic region) during myocardial ischemia and following reperfusion, and determined the frequency of ventricular fibrillation. RESULTS: The effective refractory period in the ischemic region decreased during myocardial ischemia and decreased further immediately after reperfusion in the control group. The intra-myocardial conduction time in the ischemic region increased during myocardial ischemia but rapidly shortened after reperfusion in the control group. In the quinaprilat group, however, no significant differences were evident between the ischemic and non-ischemic regions in either the effective refractory period or the intra-myocardial conduction time during myocardial ischemia or following reperfusion. The percentage shortening of the effective refractory period and the percentage prolongation of the intra-myocardial conduction time in the ischemic region were significantly lower in the quinaprilat group than in the control group during myocardial ischemia and following reperfusion. The frequency of ventricular fibrillation during myocardial ischemia and following reperfusion was significantly lower in the quinaprilat group (21%) than in the control group (74%; P < 0.01). CONCLUSIONS: Quinaprilat protects against electrophysiologic abnormalities, and may decrease arrhythmias during acute myocardial ischemia and following reperfusion.     

A comparison of the cerebral protective effects of etomidate, thiopental, and isoflurane in a model of forebrain ischemia in the rat

We evaluated the effect of etomidate, thiopental, and isoflurane on ischemic neuronal injury in rats. Control group animals received 1.2% isoflurane. The animals in the etomidate and thiopental groups received an infusion of either etomidate or thiopental until electroencephalographic (EEG) burst-suppression was attained. In the fourth group, the isoflurane concentration was increased to 3% (sufficient to produce EEG burst-suppression). Forebrain ischemia was induced by bilateral carotid artery occlusion with simultaneous hypotension for 10 min. Three days after ischemia, two blinded observers evaluated neuronal injury in coronal brain sections stained with hematoxylin and eosin. Injury to the ventral CA1 of the hippocampus was less in the etomidate group than in the control group. Injury to the entorhinal cortex was less in the thiopental group than in the control group. Histopathologic outcome in animals anesthetized with 1.2% isoflurane and 3% isoflurane was not different. Although these data indicate that etomidate and thiopental might reduce ischemic injury in some structures, the magnitude of the protective effects observed was small.     

Brainstem auditory evoked potentials during brainstem ischemia and reperfusion in gerbils

To evaluate the reversibility of neural function in the brainstem following ischemia, we investigated the effect of transient brainstem ischemia on the brainstem auditory evoked potential in gerbils. Brainstem ischemia was produced by bilateral extracranial occlusion of vertebral arteries. Local cerebral blood flow was measured by quantitative autoradiography after 5 min of ischemia and was reduced to less than 3 ml/100 g per min in the pons and lower midbrain, indicating severe and reproducible brainstem ischemia. During brainstem ischemia, brainstem auditory evoked potential waveforms disappeared completely. After a brief ischemic insult (5 min), all four brainstem auditory evoked potential components recovered to normal. After longer ischemic insults (10-30 min), brainstem auditory evoked potential components never recovered to normal. Microtubule-associated protein 2 immunoreactivity revealed differential vulnerability of the acoustic relay nuclei in the brainstem. Neurons in the lateral lemniscus were most vulnerable, followed in order by neurons in the trapezoid body, the superior olive and the cochlear nucleus. We also demonstrated a close relationship between the reversibility of ischemia-induced changes on brainstem auditory evoked potential and ischemic lesions of these relay nuclei. These data may be useful for evaluating the therapeutic window of thrombolytic therapy during acute vertebrobasilar occlusion.     

The effects of FR167653 in extended liver resection with ischemia in dogs

PURPOSE: We assess the neovascularity of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody CD34 in an attempt to identify associations between angiogenesis and disease progression following radical prostatectomy. MATERIALS AND METHODS: Microvascularity was evaluated using the CD34 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 149 patients followed from 3 to 10 years (mean 6.6). Vessels were quantified by counting a minimum of 2 selected microscopic fields (200x, 0.754 mm.2) from each tumor, area of prostatic intraepithelial neoplasia and prostatic hyperplasia, and given a numerical value representing the microvessel density count. RESULTS: Mean microvessel density count did not vary significantly with age or race. There was a significant association between the count and nuclear grade, Gleason sum and pathological stage. Cox survival analysis shows that microvessel density is significantly related to time to recurrence when considered as a continuous variable (p=0.03) as well as dichotomous variable (p=0.007) (microvessel density count less than 90 and 90 or greater). The 5-year recurrence-free survival was significantly higher for patients with a count less than 90 (71%) than for those with a count 90 or greater (51%) (p=0.006). The 5-year recurrence-free survival was also significantly different when microvessel density was used as a continuous variable (p=0.02). Controlling for stage, Gleason sum, race and nuclear grade, microvessel density remained significant in predicting recurrence (p=0.03) but when pretreatment prostate specific antigen was included in the model the count was no longer significant. The microvessel density count in the tumor area significantly increased with increasing Gleason sum and nuclear grade but it did not increase significantly in the adjacent benign prostate or areas of prostatic intraepithelial neoplasia in the same specimen. CONCLUSIONS: Microvascularity or neovascularity as measured by the CD34 antigen may be a prognostic marker of recurrence for prostate cancer patients after radical prostatectomy but more study in prostate specific antigen era patients with sufficient followup is needed.     

The protective effects of dichloroacetate on cerebral ischemia after reperfusion of fed rats

OBJECTIVE: To study the brain protective mechanisms of dichloroacetate (DCA) by observing the influence of DCA on the biochemical and pathological changes in ischemic brain tissues in different periods of reperfusion. METHODS: The FED-RAT cerebral ischemic model induced by 4-vessel occlusion was applied. 55 mature male Sprague-Dawley rats were divided into the control group, normal saline and DCA-treated groups before ischemia, normal saline and DCA-treated groups after ischemia equally and randomly. RESULTS: DCA could significantly lower the brain lactic acid, water content, and the diameter of cortical neurons, and protect the pathological damage of the membranaceous structure, before or after ischemia at a dose of 25 mg/kg, compared with the normal saline treated groups. CONCLUSION: Lowering brain lactate, resisting brain edema and protecting the membranaceous structures are the main brain protective mechanisms of DCA in biochemistry and ultrastructure.     

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs

PURPOSE: To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. METHODS: Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. RESULTS: Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. CONCLUSIONS: The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.     

Comparative effects of volume loading on pulmonary venous flow in dogs with normal heart and with myocardial ischemia

1. Stroke-prone spontaneously hypertensive rats (SHRsp) have been used widely to test agents putatively capable of vascular protection. These animals present an accelerated time course of hypertension and a reduced life-span. When fed a high-sodium diet from the eighth week of life, a further acceleration in blood pressure increase is obtained, and rats start to die after 5 weeks of diet as a consequence of cerebral haemorrhage. In this model, angiotensin-converting enzyme (ACE) inhibitors were repeatedly proved to prevent vascular lesions and death. Notably, this effect was independent of any hypotensive effect. On the contrary, diuretics were shown not to be equally effective. A combination of ACE inhibitors and diuretics, although known to have synergistic effects in the therapy of hypertension, has never previously been tested. 2. Our aim was to study the effects of long-term treatment with the ACE inhibitor delapril (12 mg day-1 kg-1), the thiazide-like diuretic indapamide (1 mg day-1 kg-1), and their combination (12 and 1 mg day-1 kg-1 respectively), on the survival of SHRsp rats fed a high-sodium diet from the eighth week of life onwards. The effects of the treatments on blood pressure, body weight, food and fluid intake, diuresis, proteinuria and the appearance of lesion signs and death were assessed weekly. When control rats reached 50% mortality, they were killed, together with some drug-treated rats, to compare lesions in brain and kidney. The other drug-treated rats continued treatments until 50% mortality was reached in two treatment groups. 3. All drug treatments were able to delay death significantly when compared with control rats, which reached 50% mortality after 6 weeks of salt loading. This event was preceded by a highly significant increase in proteinuria, diuresis and fluid intake that took place 3 weeks after the increase in blood pressure over the initial range. In delapril- or indapamide-treated SHRsp these changes were never seen, even when animals started to die. In the combination-treated group, a significant increase (P < 0.01) in fluid intake and diuresis, but not proteinuria, was observed from the third week of treatment onwards. 4. Treatment with delapril or indapamide did not block the progressive increase in blood pressure as observed in control animals. However, the increase in blood pressure was markedly retarded with respect to control rats. At variance with this, in combination-treated animals blood pressure levels were maintained until the end of the experiment within the 99% confidence interval initially observed in control animals. 5. Infarctual and haemorrhagic cerebral lesions were observed in 38% of control rats; no lesions were noted in brains of age-matched rats receiving a drug treatment. Kidneys from control animals presented major degenerative lesions of glomeruli and arteries, characterized by fibrinoid necrosis. This condition was absent in drug-treated animals, which presented minor signs of ischaemic lesion. Heart hypertrophy, when heart weight was expressed as a percentage of body weight, was similar in saline-, delapril- or indapamide-treated rats. At variance with this, in combination-treated animals the heart weight to body weight ratio was significantly (P < 0.01) lower than in the other groups. 6. In conclusion, the diuretic indapamide showed similar protective effects as the ACE inhibitor delapril on acute vascular lesions and survival of SHRsp. Moreover, their combination synergized in preventing heart hypertrophy consequent to longterm hypertension. This results is probably related to the enhanced diuresis and the better control of blood pressure levels selectively found in combination-treated animals.     

Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs

BACKGROUND: Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia. METHODS: Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, cardiac output, LAD coronary blood flow velocity, and LAD and left circumflex coronary artery subendocardial segment length. Regional myocardial contractility was evaluated with the slope of the preload recruitable stroke work relationship determined from a series of left ventricular pressure-segment length diagrams in the LAD and left circumflex coronary artery zones. Diastolic function was assessed with a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity in LAD and left circumflex coronary artery regions, and regional chamber stiffness constants derived using monoexponential and three-element exponential curve fitting in each zone. On separate experimental days, hemodynamics and indices of regional functional were obtained in the conscious state and during 1.1 and 1.6 minimum alveolar concentration end-tidal desflurane or isoflurane before and during LAD occlusion. RESULTS: In conscious dogs, LAD occlusion abolished regional stroke work, increased chamber stiffness (monoexponential: 0.39 +/- 0.04 during control to 1.34 +/- 0.39 mm-1 during LAD occlusion), and decreased the rate of early ventricular filling in the ischemic zone. These changes were accompanied by increased contractility (slope: 103 +/- 8 during control to 112 +/- 7 mmHg during LAD occlusion), rapid filling rate (maximum segment lengthening velocity: 46 +/- 5 during control to 55 +/- 7 mm.s-1 during LAD occlusion), and chamber stiffness (monoexponential: 0.43 +/- 0.05 during control to 1.14 +/- 0.25 mm-1 during LAD occlusion) in the normal region. Increases in tau were also observed in the conscious state during the period of myocardial ischemia. Desflurane and isoflurane increased tau and decreased the slope and maximum segment lengthening velocity in a dose-related manner. Monoexponential and three-element element exponential curve fitting were unchanged by the volatile anesthetics in the absence of ischemia. Myocardial contractility and rapid filling rate were enhanced in the nonischemic region during LAD occlusion in the presence of desflurane and isoflurane. In contrast to the findings in the conscious state, ischemia-induced increases in tau and chamber stiffness in the ischemic and normal zones were attenuated during anesthesia induced by desflurane and isoflurane. CONCLUSIONS: The results indicate that increases in contractility of remote myocardium during brief regional ischemia were preserved in the presence of desflurane and isoflurane anesthesia. In addition, desflurane and isoflurane blunted ischemia-induced increases in tau and regional chamber stiffness in both the ischemic and nonischemic zones. These results demonstrate that the volatile anesthetics may exert important beneficial actions on left ventricular mechanics in the presence of severe abnormalities in systolic and diastolic function during ischemia.     

Cellular uncoupling during ischemia in hypertrophied and failing rabbit ventricular myocardium: effects of preconditioning

BACKGROUND: Patients with heart failure show a very high incidence of arrhythmias and sudden death that is often preceded by ischemia; however, data on electrophysiological changes during ischemia in failing myocardium are sparse. We studied electrical uncoupling during ischemia in normal and failing myocardium. METHODS AND RESULTS: Tissue resistance, intracellular Ca2+ concentration (Indo-1 fluorescence ratio), and mechanical activity were simultaneously determined in arterially perfused right ventricular papillary muscles from 11 normal and 15 failing rabbits. Heart failure was induced by combined volume and pressure overload. Before sustained ischemia, muscles were subjected to control perfusion (non-PC) or ischemic preconditioning (PC). The onset of uncoupling during ischemia was equal in non-PC normal (13.6+/-0.9 minutes of ischemia) and non-PC failing hearts (13.3+/-0.7 minutes of ischemia). PC postponed uncoupling in normal hearts by 10 minutes. In failing hearts, however, PC caused a large variability in the onset of uncoupling during ischemia (mean, 12.2+/-2.1; range, 5 to 22 minutes of ischemia). The duration of uncoupling process was prolonged in failing hearts (12.9+/-0.9 minutes) compared with normal hearts (7.8+/-0.4 minutes). The degree of heart failure and relative heart weight of the failing hearts significantly correlated with the earlier uncoupling after PC and the duration of uncoupling. In every experiment, the start of Ca2+ rise and contracture preceded uncoupling during ischemia. CONCLUSIONS: The duration of the process of ischemia-induced electrical uncoupling in failing hearts is prolonged compared with that in normal hearts. Ischemic PC has detrimental effects in severely failing papillary muscles because it advances the moment of irreversible ischemic damage.     

Cardiovascular effects of amitriptyline in anaesthetized dogs

1. The effect of amitriptyline on cardiovascular variables has been studied in anaesthetized dogs. 2. In small doses (0.25 mg/dg) amitryptyline caused small increases in heart rates, contractility, blood pressure, coronary blood flow and aortic flow. 3. Large doses produced initial depressant effects on myocardial reflex rises in these and rate and blood pressure, which were followed by secondary reflex rises in these measurements. 4. The depressant effects were dose-related and were accompanied by marked increases in coronary flow and smaller increases in ortic flow. 5. The secondary reflex rises in cardiac parameters were abolished by propranolol and that of the blood pressure was much reduced.     

Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning"

OBJECTIVES: This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect. BACKGROUND: Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemia and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC. METHODS: Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy. RESULTS: RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8+/-3.5%, 18.2+/-1.8%*, 19.6+/-1.3%*, 44.9+/-5.0%, 35.6+/-2.7% and 34.8+/-3.6% of the area at risk (*p < 0.05 vs. CNT), respectively. CONCLUSIONS: PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.     

Differential effects of peripheral manipulations on vibrissae-related patterns in the trigeminal brainstem

The derivation of the conclusion "Anna is bigger than Mary" from the premises "Anna is bigger than Paul" and "Mary is smaller than Paul" is considered an instance of transitive deduction. For a non-verbal presentation, the premise statements were here transformed into a multiple operant discrimination task. Adult subjects were trained with overlapping pairs of a six-member stimulus series A+B-, A+C-, C+D-, D+E-, E+F-; +: choice rewarded, -: choice penalized). A computer game-type presentation that hid the actual problem structure from the subjects was employed. The effects of varying the presentation style of the task on the objective performance and the structure awareness of subjects were investigated. A first experiment used random polygons as stimuli and the relations between them were only signalled by the above reinforcement allocations. In a second experiment the stimuli were cartoon figures additionally involved in a dominance hierarchy that was suggested graphically. A third experiment used named items that were related through visible size differences in addition to the reinforcement allocations but was otherwise like an experiment using an abstract format reported by Werner et al. (1992). In all experiments a similar proportion of subjects responded transitively when subsequently tested with the pairs BD, BE and CE by preferentially choosing stimulus B or C. Each subject subsequently filled in a questionnaire, completed a stimulus ordering exercise, and was interviewed to find out whether they were explicitly aware of the stimulus hierarchy underlying each of the tasks. Although the proportion of subjects revealing an explicit transitive responding increased together with the concreteness of the stimuli and their relations across the experiments, the objective performance in terms of choice accuracy did not vary. The accuracy performance on tests could be accurately simulated with a modification of a simple conditioning model. It is concluded that an implicit mode of processing may underlie many instances of transitive responding in humans even when explicit task understanding is reported.     

Detection and effects of helicobacters in healthy dogs and dogs with signs of gastritis

OBJECTIVES: To determine prevalence, colonization density, and distribution of helicobacters and gastric histologic findings in healthy dogs and dogs with signs of gastritis; to evaluate association of colonization density and gastric inflammation; and to compare the number of Helicobacter spp with degree of inflammation. DESIGN: Cross-sectional prevalence survey. ANIMALS: 25 healthy dogs and 21 dogs with signs of gastritis. PROCEDURE: During endoscopy, gastric mucosal biopsy specimens were obtained from healthy and affected client-owned dogs. Histologic and cytologic evaluation and results of a urease test were used for detecting helicobacters, which were identified definitively by use of transmission electron microscopy and bacterial culture. RESULTS: Helicobacters were detected in all 25 healthy and 20 of 21 affected dogs. Cytologic examination was a more sensitive method than histologic examination or the urease test. Helicobacters were found least frequently and in fewest number in the antrum in both groups of dogs. Gastric inflammation was evident in both groups of dogs and did not differ significantly between groups. A significant association was not detected between colonization density or the number of Helicobacter spp and degree of gastric inflammation. In both groups, H bizzozeronii, H felis, and H salomonis were cultured. CLINICAL IMPLICATIONS: Histologically verified chronic gastritis is common in dogs with signs of gastritis as well as in healthy dogs. Colonization density of helicobacters was not associated with degree of gastric inflammation in the dogs of our study. It remains to be determined whether certain strains of Helicobacter spp can induce gastritis in dogs.     

Stereoselective effects of etomidate optical isomers on gamma-aminobutyric acid type A receptors and animals

BACKGROUND: The intravenous anesthetic etomidate is optically active and exists in two mirror-image enantiomeric forms. However, although the R(+) isomer is used as a clinical anesthetic, quantitative information on the relative potencies of the R(+) and S(-) isomers is lacking. These data could be used to test the relevance of putative molecular targets. METHODS: The anesthetic concentrations for a half-maximal effect (EC50) needed to induce a loss of righting reflex in tadpoles (Rana temporaria) were determined for both etomidate enantiomers. The effects of the isomers on gamma-aminobutyric acid (GABA)-induced currents in stably transfected mouse fibroblast cells was also investigated using the patch-clamp technique. In addition, the effects of the isomers on a lipid chain-melting phase transition were determined. RESULTS: The EC50 concentrations for general anesthesia for the R(+) and S(-) isomers were 3.4 +/- 0.1 microM and 57 +/- 1 microM, with slopes of n = 1.9 +/- 0.1 and n = 2.9 +/- 0.2, respectively. The R(+) isomer was also much more effective than the S(-) isomer at potentiating GABA-induced currents, although the degree of stereoselectivity varied with anesthetic concentration. R(+) etomidate potentiated the GABA-induced currents by increasing the apparent affinity of GABA for its receptor. Both isomers were equally effective at disrupting lipid bilayers. CONCLUSIONS: These data are consistent with the idea that the GABA(A) receptor plays a central role in the actions of etomidate. Etomidate exerts its effects on the receptor by binding directly to a specific site or sites on the protein and allosterically enhancing the apparent affinity of GABA for its receptor.     

Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia

The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p < 0.01]; and for the delayed occlusion, 18.8 +/- 3.4% versus 35.1 +/- 4.6%, respectively [p < 0.05]); however, when the infarction was induced 3 hours (31.2 +/- 3.7% versus 37.5 +/- 4.2%, respectively) or 12 hours (25.4 +/- 4.8% versus 35.0 +/- 5.3%, respectively) after repetitive ischemia, the infarct size did not differ. No differences were seen in regional myocardial blood flow or rate-pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning.     

Salutary effects of myocardial ischemia in coronary artery disease

A novel fine wire bone transport system for use with Ilizarov frames has been used in Bristol. It uses parallel wires instead of crossed wires. Its stiffness has been tested and compared with a crossed wire construct. In its basic form it is not as stiff to bending and shear loading, however, by modification it can be made at least as stiff. A parallel wire construct does not transfix as much soft tissue as a crossed wire construct when used in the leg. This is advantageous, because soft tissue transfixion causes pain and limb swelling, which impair patient mobilization.     

Protein kinase C expression and activity after global incomplete cerebral ischemia in dogs

BACKGROUND AND PURPOSE: Studies suggest that protein kinase C (PKC) activation during ischemia plays an important role in glutamate neurotoxicity and that PKC inhibition may be neuroprotective. We tested the hypothesis that elevations in the biochemical activity and protein expression of Ca2+-dependent PKC isoforms occur in hippocampus and cerebellum during the period of delayed neurodegeneration after mild brain ischemia. METHODS: We used a dog model of 20 minutes of global incomplete ischemia followed by either 6 hours, 1 day, or 7 days of recovery. Changes in PKC expression (Western blotting and immunocytochemistry) and biochemical activity were compared with neuropathology (percent ischemically damaged neurons) by means of hematoxylin and eosin staining. RESULTS: The percentage of ischemically damaged neurons increased from 13+/-4% to 52+/-10% in CA1 and 24+/-11% to 69+/-6% in cerebellar Purkinje cells from 1 to 7 days, respectively. The occurrence of neuronal injury was accompanied by sustained increases in PKC activity (240% and 211% of control in hippocampus and cerebellum, respectively) and increased protein phosphorylation as detected by proteins containing phosphoserine residues. By Western blotting, the membrane-enriched fraction showed postischemic changes in protein expression with increases of 146+/-64% of control in hippocampal PKCalpha and increases of 138+/-38% of control in cerebellar PKCalpha, but no changes in PKCbeta and PKCgamma were observed. By immunocytochemistry, the neuropil of CA1 and CA4 in hippocampus and the radial glia in the molecular layer of cerebellum showed increased PKCalpha expression after ischemia. CONCLUSIONS: This study shows that during the period of progressive ischemic neurodegeneration there are regionally specific increases in PKC activity, isoform-specific increases in membrane-associated PKC, and elevated protein phosphorylation at serine sites.