Biomechanical assessment of the aortic root using novel force transducers.

In recent years the use of valve sparing techniques has become more common in selected patients with aortic valve insufficiency. However, limited experimental research has been performed to document the biomechanical effect of these techniques. One experimental platform is to evaluate how the normal physiological aortic root forces are altered or re-established after the surgical intervention. Hence, the aim of this project was to develop new implantable force transducers for a biomechanical description of various aortic root repair techniques. Two novel force transducers were developed. Both transducers were manufactured using rapid prototyping and were instrumented with miniature strain gauges. Before implantation both transducers were calibrated using a dedicated setup, yielding very linear correlation between the applied load and transducer output. The developed force transducers were implanted and tested in an 80kg porcine model. In the post-cardioplegic heart, the peak annular forces varied in the range of 2-4N and the commissural forces varied from 0.4 to 0.8N with a left ventricular pressure of 111mmHg. In conclusion, the two new force transducers to measure forces in the aortic root have successfully been developed. With these new devices a novel versatile and direct force measurement system has been provided.

Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation.

Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P <0.01). In contrast, SERT and TPH-1 were up-regulated in AP and LV compared to MV (P <0.05). In MV, mRNA levels were increased for 5-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) in sMR vs. CON. There were no group differences in 5-HT2BR staining (IHC) but co-localisation was found with α-SMA-positive cells in 91% of all valves and with 33% of histological lesions. In LV, 5-HT1BR mRNA levels were increased in sMR vs. CON (P = 0.01). In conclusion, these data suggest that MR may affect mRNA expression of valvular 5-HT2BR and SERT, and left ventricular 5-HT1BR in some pigs.

Heart rate limitation and cardiac unloading in sevoflurane post-conditioning.

BACKGROUND: Sevoflurane post-conditioning (SePost) has been found to alleviate ischemic myocardial reperfusion injury through the activation of prosurvival kinases. Lowered myocardial oxygen demand from reduced cardiac work may also contribute to cardioprotection, and is much less well-studied. Our aim was to examine the simultaneous effects of SePost on cardiac work (here, rate-pressure product, RPP) and myocardial infarct size in a porcine model. METHODS: Anesthetized 25 kg pigs were randomly allocated to two groups and underwent 45 min regional coronary artery balloon occlusion and subsequent 2 h reperfusion. SePost (n = 10) was given as sevoflurane 1.5-3% end-tidal concentration during reperfusion while controls (n = 12) were untreated. Aortic blood pressure was measured directly, while mixed-venous oxygen saturation and cardiac output were measured in the pulmonary artery. Cardiac work was determined as RPP. Post-mortem, histologic myocardial infarct size (IS), and area at risk were determined in transverse heart slices after tetrazolium stain. RESULTS: Myocardial infarct size was reduced from (control) 55.0 (mean) ± 13.6% (standard deviation) to 32.5 ± 13.4% in group SePost (P = 0.0009). During reperfusion, SePost resulted in lower heart rate (P = 0.0003), cardiac output (P = 0.0123), mixed-venous oxygen saturation (P = 0.0103), blood pressure, and RPP (P < 0.0001). RPP was highly correlated to IS (P = 0.0055). CONCLUSION: SePost (1.5-3%) reduced infarct size after regional myocardial ischemia in vivo and reduced cardiac work was significantly correlated to myocardial salvage.

In Vitro System for Measuring Chordal Force Changes Following Mitral Valve Patch Repair.

BACKGROUND: Attention towards optimization of mitral valve repair methods is increasing. Patch augmentation is one strategy utilized to correct functional mitral regurgitation or systolic anterior motion in complex mitral valve repairs. This article describes a system for investigating the redistribution of chordae tendineae tension as a reflection of altered stress distribution of the valve leaflet following patch augmentation. METHODS AND MATERIALS: An in vitro test setup was constructed to hold native porcine mitral valves containing an annulus and papillary muscle positioning system. The alterations caused by patch augmentation should be visual from both the atrial and ventricular views. Ventricular pressure was regulated stepwise in a range of 0-150 mmHg. To test the system, the anterior mitral leaflet was extended by a pericardial patch sutured to the mid/basal part of the leaflet, and the chordae tendineae force was measured as the ventricular pressure was applied. RESULTS: The system demonstrated the capacity to hold native porcine mitral valves and introducing patch repairs according to clinical practice. The porcine mitral valve test setup indicated strong correlation between the forces in the mitral valve secondary chordae tendineae and the applied transvalvular pressure (R2 = 0.95). CONCLUSION: This test setup proved the ability to obtain normal mid-systolic mitral valve function, secondary chordae force measurements, and important preservation of the visual access: Hence, obtaining the pressure-force relationship as well as identifying any shift of the secondary chordae insertion point on the anterior leaflet relative to the coaptation zone was made possible.