PubMed Health⌕ Search

Biomedical subjects

Hazel Sutherland

Publications and source records attributed to Hazel Sutherland.

6 recordsLinked to original sources

Counterpulsation from the skeletal muscle ventricle and the intraaortic balloon pump in the normal and failing circulations.

BACKGROUND: The intra-aortic balloon pump (IABP) is the device that is in most common use to provide cardiovascular support. A skeletal muscle ventricle (SMV) was configured to produce counterpulsation in the thoracic aorta similar to that obtained with an IABP. The hemodynamic effects of an IABP and a SMV in the same animal and in both normal and failing circulations were assessed. METHODS AND RESULTS: SMVs were connected to and IABPs were placed in the thoracic aorta of 12 anesthetized pigs. Hemodynamic parameters during the IABP- or the SMV-assisted beat were compared with those during the preassist beat. Acute heart failure was induced in 6 of the pigs by snaring the left anterior descending coronary artery (LAD). The hemodynamic effects of the IABP and the SMV were then reassessed. In the assisted cycles, SMV activation increased the mean aortic diastolic pressure (MADP) by 26.5+/-3.5%, the mean diastolic LAD flow by 48.4+/-7.2%, and endocardial viability ratio (EVR) by 31.6+/-3.8% (P<0.0001). In the same animals, IABP assist increased MADP by 19.8+/-2.3%, mean diastolic LAD flow by 37.2+/-3.9%, and EVR by 21.4+/-3.0% (P<0.0001). Under acute heart failure conditions, both SMV and IABP assist significantly increased MADP, mean diastolic LAD flow, and EVR. CONCLUSIONS: In both the normal and failing circulations, the SMV was an effective counterpulsator, providing cardiac assist that was at least equal to that available from an IABP. The SMV may therefore provide the proven benefits of an IABP in ambulant patients.

Animals↗

Adaptive conditioning of skeletal muscle in a large animal model (Sus domesticus).

Recognition of the adaptive capacity of mammalian skeletal muscle has opened the way to a number of clinical applications. For most of these, the fast, fatigue-susceptible fibres need to be transformed stably to fast, fatigue-resistant fibres that express the 2A myosin heavy chain isoform. The thresholds for activity-induced change are size-dependent, so although the requisite patterns of electrical stimulation are known for the rabbit, in humans these same patterns would produce type 1 fibre characteristics, with an undesirable loss of contractile speed and power. We have used histochemistry, immunohistochemistry and electrophoretic separations to evaluate a possible conditioning regime in a large animal model. Stimulation of the porcine latissimus dorsi muscle with a phasic 30-Hz pattern for up to 41 days converted all type 2X and 2A/2X fibres to 2A with only a small increase in the type 1 population, from 17% to 22%. Stimulation for longer periods increased the proportion of type 1 fibres to 52%. Based on this model, stimulation regimes designed to achieve a stable 2A phenotype in humans should deliver fewer stimulating impulses, possibly by a factor of 2, than the pattern assessed here. Any such pattern needs to be tested for at least 8 weeks.

Adaptation, Physiological↗

Determination of the chronaxie and rheobase of denervated limb muscles in conscious rabbits.

Measurements of the rheobase and chronaxie can be used to define the excitability of nerves and muscles. The aim of this study was to obtain a record over many weeks of changes in the rheobase and chronaxie of denervated rabbit tibialis anterior muscle (TA). A custom-built electronic stimulator was implanted into the peritoneal cavity of New Zealand White rabbits. Large stainless steel electrodes were placed on the denervated TA muscle. Rheobase and chronaxie were measured noninvasively at weekly intervals by means of a laptop PC, which communicated with the stimulator via a radio-frequency link. At each setting the denervated TA was palpated manually to detect the response of the muscle. During the first few days after denervation the rheobase increased transiently to 0.8 +/- 0.13 mA, approximately twice the value for normal innervated muscle, then decreased to normal for the remainder of the experimental period. Chronaxie underwent a significant 3-fold increase from 4.5 +/- 1.1 ms to 14.1 +/- 1.1 ms during the first two weeks of denervation and remained elevated throughout. The custom-built implantable electronic stimulator allowed changes in muscle excitability to be studied over a long period of denervation within individual animals, providing an accurate assessment of the time course of denervation-induced changes in muscle excitability.

Analysis of Variance↗

A nonradioactive assay for nitric oxide synthase activity in tissue extracts.

We describe a fluorescence assay for nitric oxide synthase activity based on a new indicator, 4,5-diaminofluorescein (DAF-2). The method offers the advantage of being safer and more convenient than the citrulline radioassay in common use. The rapid and irreversible binding of DAF-2 to oxidized nitric oxide (NO) enables NO production to be measured in real time. The protocol is applied to the measurement of nitric oxide synthase in crude extracts of skeletal muscle.

Animals↗

The hemodynamic function of intrathoracic skeletal muscle ventricles after recovery from surgery in pigs.

The shortage of donor organs for heart transplantation highlights the need for new approaches to end-stage heart failure. A promising experimental technique is the use of pumping chambers formed from the latissimus dorsi muscle. We formed such skeletal muscle ventricles (SMVs) and connected them to the descending thoracic aorta in a single surgical procedure in pigs. Activation of conditioned SMVs from the end of systole for 80% of diastole increased mean aortic diastolic blood pressure by 11.2 +/- 1.6% in 1 animal and by 15.8 +/- 0.3% in another. The left-ventricular stroke work in the postassisted beat was decreased by 8.7 +/- 5.8% and 10.1 +/- 2.2% and the overall stroke work by 7.4 +/- 1.2% and 9.4 +/- 0.8%. The key to forming and connecting the SMV in a single procedure was the use of a composite homograft lining. In future clinical practice, this component could be replaced by a synthetic composite or by a tissue lining produced in vitro.

Animals↗