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Biomedical subjects

M S Sumeray

Publications and source records attributed to M S Sumeray.

10 recordsLinked to original sources
PubMed2000

Infarct size and nitric oxide synthase in murine myocardium.

Controversy surrounds the involvement of nitric oxide (NO) in myocardial ischaemia-reperfusion injury and the balance between deleterious and beneficial effects. NO synthase (NOS) is expressed constitutively as two isoforms: endothelial (eNOS) and neuronal (nNOS). Knockout mice lacking the gene for either eNOS (eNOS KO) or nNOS (nNOS KO), were compared with wild-types (WT) during a protocol of global ischaemia-reperfusion injury. Thirty-six mouse hearts (12 from each group) were isolated and the aorta cannulated for Langendorff perfusion with modified Krebs solution at constant pressure. An apical suture connected the left ventricle to a force transducer via a light weight coupling rod. Following stabilization hearts were subjected to 30 min of global ischaemia at 37 degrees C. During 30 min reperfusion, the recovery of baseline force-rate product (F%) was recorded. Hearts were then stained with tetrazolium, frozen, sliced, and fixed with formalin. Slices were compressed between plexiglas plates, and a magnified video image digitized to allow planimetry for infarct size (as percentage of ventricular volume I/R). Although recovery of contractile function did not differ between groups, eNOS KOs suffered significantly larger infarcts than WT or nNOS KOs (41 v 33 and 30% respectively, P<0.05 for both comparisons). A protective role for eNOS against global ischaemia-reperfusion injury has been demonstrated for the first time in murine myocardium. This may have important clinical implications for future pharmacotherapy to enhance myocardial protection.

Animals↗
PubMed1998

Ischaemic preconditioning reduces infarct size following global ischaemia in the murine myocardium.

Ischaemic preconditioning has not been demonstrated to reduce infarct size following global ischaemia in murine myocardium. Eighteen mouse hearts were isolated, perfused in the Langendorff mode, and randomised to control or preconditioning groups. Preconditioned hearts received four periods of five minutes global ischaemia with five minutes of intervening reperfusion. Control hearts were perfused normally during this period. Both groups were then subjected to 30 minutes global ischaemia followed by 30 minutes reperfusion. Infarct size, contractile recovery and LDH leakage were assessed. Mean infarct size was reduced from 57% of ventricular volume (controls) to 33% in preconditioned hearts (P = 0.003). A small improvement in contractile recovery was also observed (6.3% of baseline in controls, 15.5% in preconditioned hearts; P = 0.004). Release of LDH did not differ significantly between groups. This study confirms for the first time that ischaemic preconditioning can delay the onset of myocardial necrosis following global ischaemia in the isolated mouse heart.

Animals↗
PubMed1998

Ischaemic preconditioning: present position and future directions.

Preconditioning the myocardium using short episodes of sublethal ischaemia will delay the onset of necrosis during a subsequent lethal ischaemic insult. This powerful protective adaptation of the myocyte has also been observed in other cell types. The potential for clinical application to benefit patients with a variety of pathological conditions has led to an expansion in our knowledge concerning the pathophysiology of ischemia-reperfusion injury and the regulatory mechanisms underlying cellular metabolism. We feel it is timely to assess the current position in this field and provide a critical appraisal to facilitate future research.

Animals↗
PubMed1998

Beyond coagulation: fibrinogen as a cause of cardiovascular surgical disease.

Fibrinogen is generally considered to be an important mediator of clot formation. However, its effects on clots and perhaps other more direct effects may also make it a powerful mediator in the genesis and progression of atheromatous disease. Indeed, raised fibrinogen levels may pose as great a cardiovascular risk as classical risk factors such as elevated blood pressure or cholesterol levels. The plasma fibrinogen level of any given individual, and its associated cardiovascular risk, is dependent upon an interaction between environmental and intrinsic (genetic) factors. Most environmental factors associated with elevated fibrinogen levels are also potent cardiovascular risk factors (e.g., cigarette smoking). Less is known of the role played by genetic factors. However, as research into the genotypic influences on both basal and "stimulated" fibrinogen production continues, high-risk groups may be identified that may benefit from therapeutic intervention aimed at lowering plasma fibrinogen.

Blood Coagulation Disorders↗
PubMed1998

Ischaemic preconditioning: a clinical perspective.

Ischaemic preconditioning is an endogenous mechanism of myocardial protection which may allow us to slow the progress of myocardial necrosis, increasing the time available for effective reperfusion. Recent evidence suggests that the human myocardium can be preconditioned. This article reviews the current literature and suggests clinical situations where this potent treatment might be relevant.

Humans↗
PubMed1998

Characterisation and validation of a murine model of global ischaemia-reperfusion injury.

A specially designed Langendorff apparatus was constructed to allow perfusion of the isolated mouse heart. Hearts were randomised into groups to receive differing periods of global (zero flow) ischaemia or continuous perfusion (controls). During reperfusion, recovery of baseline force was recorded and perfusate collected for LDH assay (U/L/g wet weight). After 30 min reperfusion, hearts were stained with tetrazolium and planimetry performed to measure infarct size. Dose-response relationships were demonstrated for all 3 end-points against duration of ischaemic insult. Functional recovery and enzyme leakage correlated well with infarct size (r = 0.77, p < 0.001 and r = 0.73, p < 0.001 respectively). Transgenic mice may now be used to study the effect of specific phenotypic changes on the pathogenesis of ischaemia-reperfusion injury using a reliable and reproducible technique.

Animals↗
PubMed1997

Myocardial preconditioning. What have we learned?

It is now 10 years since the phenomenon termed 'ischaemic preconditioning' was formally recognised. The possibility that an innate mechanism of myocardial protection might be inducible in the human heart has generated considerable excitement and enthusiastic research. This has led to a more detailed understanding of the mechanisms underlying ischaemia-reperfusion injury and has provided reason to believe that the progress of myocardial necrosis might be modified by invoking a protective adaptation within the myocyte. Considerable progress has been made towards the identification of cell triggers and transduction mechanisms that may be involved in the process of preconditioning. It is likely that future studies will examine the effect of several classes of pharmacological agents that may prove capable of mimicking the protective effect of sub-lethal ischaemia.

Adaptation, Biological↗