Dataset Information

Metabolic and perfusion responses to recurrent peri-infarct depolarization during focal ischemia in the Spontaneously Hypertensive Rat: dominant contribution of sporadic CBF decrements to infarct expansion.

ABSTRACT: Peri-infarct depolarizations (PIDs) contribute to the evolution of focal ischemic lesions. Proposed mechanisms include both increased metabolic demand under conditions of attenuated perfusion and overt vasoconstrictive responses to depolarization. The present studies investigated the relative contributions of metabolic and perfusion effects to PID-associated infarct expansion during middle cerebral artery (MCA) occlusion in the Spontaneously Hypertensive Rat. The initial distribution of ischemic depolarization (ID) was established within minutes after MCA occlusion at a cerebral blood flow threshold of ?40?mL/100?g per minute, with expansion of the depolarized territory during 3?hours detected in half of the animals. Peri-infarct depolarizations were associated with transient metabolic responses, comparable to those observed after spreading depression, with no evidence of cumulative energy failure after multiple transient depolarizations during 1?hour. Speckle contrast imaging of PID-associated flow transients documented prominent distal hyperemic flow responses that became progressively attenuated in regions of already impaired perfusion, with modest propagated flow decreases more proximal to the ischemic core. However, sporadic PIDs were associated with persistent decrements in perfusion, increasing tissue volume below the threshold for energy failure, ID and infarction. These latter, comparatively rare, events can account for the pattern of stepwise infarct expansion in this model.

SUBMITTER: Takeda Y

PROVIDER: S-EPMC3185883 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Metabolic and perfusion responses to recurrent peri-infarct depolarization during focal ischemia in the Spontaneously Hypertensive Rat: dominant contribution of sporadic CBF decrements to infarct expansion.

Takeda Yoshimasa Y Zhao Liang L Jacewicz Michael M Pulsinelli William A WA Nowak Thaddeus S TS

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20110427 9

Peri-infarct depolarizations (PIDs) contribute to the evolution of focal ischemic lesions. Proposed mechanisms include both increased metabolic demand under conditions of attenuated perfusion and overt vasoconstrictive responses to depolarization. The present studies investigated the relative contributions of metabolic and perfusion effects to PID-associated infarct expansion during middle cerebral artery (MCA) occlusion in the Spontaneously Hypertensive Rat. The initial distribution of ischemic ...[more]

PMID: 21522165

Similar Datasets

Project description:CD36 fatty acid translocase plays a key role in supplying heart with its major energy substrate, long-chain fatty acids (FA). Previously, we found that the spontaneously hypertensive rat (SHR) harbors a deletion variant of Cd36 gene that results in reduced transport of long-chain FA into cardiomyocytes and predisposes the SHR to cardiac hypertrophy. In the current study, we analyzed the effects of mutant Cd36 on susceptibility to ischemic ventricular arrhythmias and myocardial infarction in adult SHR-Cd36 transgenic rats with wild-type Cd36 compared with age-matched SHR controls. Using an open-chest model of coronary artery occlusion, we found that SHR-Cd36 transgenic rats showed profound arrhythmogenesis resulting in significantly increased duration of tachyarrhythmias (207 ± 48 s vs. 55 ± 21 s, P < 0.05), total number of premature ventricular complexes (2,623 ± 517 vs. 849 ± 250, P < 0.05) and arrhythmia score (3.86 ± 0.18 vs. 3.13 ± 0.13, P < 0.001). On the other hand, transgenic SHR compared with SHR controls showed significantly reduced infarct size (52.6 ± 4.3% vs. 72.4 ± 2.9% of area at risk, P < 0.001). Similar differences were observed in isolated perfused hearts, and the increased susceptibility of transgenic SHR to arrhythmias was abolished by reserpine, suggesting the involvement of catecholamines. To further search for possible molecular mechanisms of altered ischemic tolerance, we compared gene expression profiles in left ventricles dissected from 6-wk-old transgenic SHR vs. age-matched controls using Illumina-based sequencing. Circadian rhythms and oxidative phosphorylation were identified as the top KEGG pathways, while circadian rhythms, VDR/RXR activation, IGF1 signaling, and HMGB1 signaling were the top IPA canonical pathways potentially important for Cd36-mediated effects on ischemic tolerance. It can be concluded that transgenic expression of Cd36 plays an important role in modulating the incidence and severity of ischemic and reperfusion ventricular arrhythmias and myocardial infarct size induced by coronary artery occlusion. The proarrhythmic effect of Cd36 transgene appears to be dependent on adrenergic stimulation.

Project description:OBJECTIVE: To develop a new method for the cardiac MR (CMR) quantification of peri-infarct ischaemia using fused perfusion and delayed-enhanced images and to evaluate this method using quantitative single photon emission CT (SPECT) imaging as a reference. METHODS: 40 patients presenting with peri-infarct ischaemia on a routine stress (99m)Tc-SPECT imaging were recruited. Within 8 days of the SPECT study, myocardial perfusion was evaluated using stress adenosine CMR. Using fused perfusion and delayed-enhanced images, peri-infarct ischaemia was quantified as the percentage of myocardium with stress-induced perfusion defect that was adjacent to and larger than a scar. This parameter was compared with both the percent myocardium ischaemia (SD%) and the ischaemic total perfusion deficit (TPD). The diagnostic performance of CMR in detection of significant coronary artery stenosis (of ≥70%) was also determined. RESULTS: On SPECT imaging, in addition to peri-infarct ischaemia, reversible perfusion abnormalities were detected in a remote zone in seven patients. In the 33 patients presenting with only peri-infarct ischaemia, the agreement between CMR peri-infarct ischaemia and both SD% and ischaemic TPD was excellent [intraclass coefficient of correlation (ICC) = 0.969 and ICC = 0.877, respectively]. CMR-defined peri-infarct ischaemia for the detection of a significant coronary artery stenosis showed an areas under receiver-operating characteristic curve of 0.856 (95% confidence interval, 0.680-0.939). The best cut-off value was 8.1% and allowed a 72% sensitivity, 96% specificity, 60% negative predictive value and 97% positive predictive value. CONCLUSION: This proof-of-concept study shows that CMR imaging has the potential as a test for quantification of peri-infarct ischaemia. ADVANCES IN KNOWLEDGE: This study demonstrates the proof of concept of a commonly known intuitive idea, that is, evaluating the peri-infarct ischaemic burden by subtracting delayed enhancement from first-pass perfusion imaging on CMR.

Project description:Background and purposeRapamycin is a clinically approved mammalian target of rapamycin inhibitor that has been shown to be neuroprotective in animal models of stroke. However, the mechanism of rapamycin-induced neuroprotection is still being explored. Our aims were to determine if rapamycin improved leptomeningeal collateral perfusion, to determine if this is through eNOS (endothelial nitric oxide synthase)-mediated vessel dilation and to determine if rapamycin increases immediate postreperfusion blood flow.MethodsWistar and spontaneously hypertensive rats (≈14 weeks old, n=22 and n=15, respectively) were subjected to ischemia by middle cerebral artery occlusion (90 and 120 minutes, respectively) with or without treatment with rapamycin at 30-minute poststroke. Changes in middle cerebral artery and collateral perfusion territories were measured by dual-site laser Doppler. Reactivity to rapamycin was studied using isolated and pressurized leptomeningeal anastomoses. Brain injury was measured histologically or with triphenyltetrazolium chloride staining.ResultsIn Wistar rats, rapamycin increased collateral perfusion (43±17%), increased reperfusion cerebral blood flow (16±8%) and significantly reduced infarct volume (35±6 versus 63±8 mm3, P<0.05). Rapamycin dilated leptomeningeal anastomoses by 80±9%, which was abolished by nitric oxide synthase inhibition. In spontaneously hypertensive rats, rapamycin increased collateral perfusion by 32±25%, reperfusion cerebral blood flow by 44±16%, without reducing acute infarct volume 2 hours postreperfusion. Reperfusion cerebral blood flow was a stronger predictor of brain damage than collateral perfusion in both Wistar and spontaneously hypertensive rats.ConclusionsRapamycin increased collateral perfusion and reperfusion cerebral blood flow in both Wistar and comorbid spontaneously hypertensive rats that appeared to be mediated by enhancing eNOS activation. These findings suggest that rapamycin may be an effective acute therapy for increasing collateral flow and as an adjunct therapy to thrombolysis or thrombectomy to improve reperfusion blood flow.

Dataset Information

Metabolic and perfusion responses to recurrent peri-infarct depolarization during focal ischemia in the Spontaneously Hypertensive Rat: dominant contribution of sporadic CBF decrements to infarct expansion.

Publications

Metabolic and perfusion responses to recurrent peri-infarct depolarization during focal ischemia in the Spontaneously Hypertensive Rat: dominant contribution of sporadic CBF decrements to infarct expansion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets