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Biomedical subjects

M F Haney

Publications and source records attributed to M F Haney.

7 recordsLinked to original sources

Streptozotocin induced diabetes in minipig: a case report of a possible model for type 1 diabetes?

Studies on the pathogenic process in type 1 diabetes are often performed in animal models. Low-dose administration of streptozotocin has been used to induce diabetes with pathological alterations similar to human type 1 diabetes in the animals. Rodent models are frequently used but there is a need of developing new models including larger animals. In this study we wanted to investigate to what extent a minipig was sensitive to low-dose streptozotocin for induction of diabetes with features of human Type I diabetes. A female Göttingen minipig received two low-doses (40 mg/kg) of streptozotocin with an 11-day interval. Serum was analysed for the presence of the enzyme glutamic acid decarboxylase, isoform 65, (GAD65) and autoantibodies against glutamic acid decarboxylase, isoform 65 (GAD65A), isoform 67 (GAD67A), insulinoma antigen 2 (IA-2) and insulin (IAA). Pancreas tissue was fixated in formaldehyde and was sent for pathoanatomical examination. The minipig became hyperglycaemic after the second injection of streptozotocin. The pathoanatomical examination showed atrophy of the beta-cell population, depletion of insulin with preserved glucagon content. There was no sign of insulitis. Both GAD65 and GAD65A were detected while GAD67A and IAA were absent. It is concluded that chronic diabetes developed after low-dose streptozotocin injection in a female minipig with the characteristics of the end stage of type 1 diabetes. This pilot study suggests that minipigs show promise as a model to induce diabetes by injections of low-dose streptozotocin.

Animals↗

Heart-lung interactions during positive pressure ventilation: left ventricular pressure-volume momentary response to airway pressure elevation.

BACKGROUND: Left ventricular (LV) pressure and volume changes are known to occur in response to positive airway pressure (PAP). We aimed to further describe the immediate LV response to increased PAP as demonstrated in successive heart cycles with LV pressure and volume alterations. We postulated that these acute systematic LV events during institution of PAP can follow a distinct pattern that would allow calculation of parameters of systolic function, including end-systolic elastance (Ees) and preload recruitable stroke work (PRSW). We also aimed to examine the relationship of PAP-derived Ees and PRSW to the same parameters derived from vascular occlusion. METHODS: Eight anesthetized adult pigs were studied with invasive circulatory measurements including LV pressure and volume (conductance). The PAP intervention was an airway pressure plateau of 15 cm H2O for 6 s (APP). Venous occlusion was performed by transient balloon inflation in the inferior vena cava (IVCO). Ees and PRSW were derived for each APP and IVCO intervention. RESULTS: Central circulatory variables during APP and IVCO are reported. LV systolic function parameters could be derived from each of the heart-lung interactions during APP sequences. Ees and PRSW derived from APP showed a significant positive bias in relation to those derived from the IVCO sequence. CONCLUSIONS: We conclude that the heart-lung interactions during APP of the magnitude and duration shown here can allow derivation of Ees and PRSW. These parameters are not interchangeable with Ees and PRSW derived from IVCO.

Air Pressure↗

Analysis of left ventricular systolic function during elevated external cardiac pressures: an examination of measured transmural left ventricular pressure during pressure-volume analysis.

BACKGROUND: Variations or disturbances in intrathoracic and extracardiac pressures (ECP) occur in critically ill and anaesthetised patients. There are uncertainties concerning the analysis of left ventricular pressure-volume relationship (LVPVR) and the calculation of systolic function parameters when conducted without reference to transmural left ventricular pressure (LVPtm) in the setting of elevated ECP. METHODS: In 7 anaesthetised adult pigs, we measured LVPVR using conductance volumetry and tip manometry along with measurement of pericardial and other intrathoracic pressures. Experimental pericardial infusion and pleural insufflation were performed. Transient controlled preload reductions were accomplished using balloon occlusion of the inferior vena cava. Preload recruitable stroke work (PRSW) was calculated using both intracavitary left ventricular pressure (LVPic) and LVPtm, and differences were tested for using a paired t-test. RESULTS: The pericardial and pleural interventions produced significant elevations in ECP. No difference in PRSW calculated using LVPic and LVPtm was detected. CONCLUSION: These results suggest that LVPtm need not be measured and included in LVPVR analysis of systolic function when there is significant external cardiac pressure. To be able to employ LVPVR analysis of systolic function without reference to LVPtm is important for simplified application in the clinical setting, particularly when elevated extracardiac pressures are suspected, or have been therapeutically induced, as with continuous positive pressure ventilation.

Anesthesia↗

Improvement in mitral regurgitation after aortic valve replacement.

This study sought to determine whether there is a quantitative improvement in mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis (AS) and, if so, the mechanisms for this change. MR frequently accompanies AS. The addition of mitral valve replacement to AVR significantly increases the risk of surgery. Although previous studies have suggested a qualitative improvement in MR severity after AVR, semiquantitative analysis of this improvement has not been documented nor have the underlying mechanisms been examined. We evaluated 28 patients who had undergone 2-dimensional echo and color flow Doppler imaging an average of 1.5 +/- 2.5 months before and 2.5 +/- 4.2 months after AVR. Maximum MR area, MR percentage (MR area/left atrial area), mitral annular area, left atrial area, aortic gradient, and parameters of left ventricular geometry were measured to evaluate MR severity and to assess functional mechanisms for improvement in MR. There was a significant decrease in MR area (5.5 +/- 2.8 cm2 vs 2.5 +/- 1.9 cm2, p < or =0.0001) and MR percentage (25 +/- 11% vs 12 +/- 10% after operation, p < or =0.0001) between preoperative and postoperative studies. There was a significant reduction in aortic gradient, mitral annular area, left atrial area, and left ventricular length postoperatively. In univariate analysis, MR improvement was related to the lower preoperative left ventricular fractional area change (p = 0.027) and to the changes in fractional area change (p = 0.001) and left ventricular systolic area (p = 0.001). Thus, improvement in MR after AVR is related to changes in left ventricular function postoperatively. These data suggest that reduction in MR is due not only to decreased intraventricular pressure, but also to changes in ventricular morphology.

Aged↗

Systemic embolization complicating right ventricular myocardial infarction.

We describe a patient in whom multiple episodes of pulmonary and systemic embolization occurred in the setting of right ventricular infarction. The mechanism of paradoxical embolization was determined based on transesophageal echocardiographic findings that included right atrial spontaneous contrast, appendage thrombosis, patent foramen ovale with right-to-left atrial shunting, and absence of left ventricular thrombosis. Recurrent thromboembolization was prevented by percutaneous placement of a "clam-shell" occluder across the patent foramen. This clinical scenario may be more common than previously believed and is best detected with transesophageal echocardiography. Early identification of this condition can lead to prompt treatment and prevention of subsequent thromboembolic morbidity.

Aged↗