Comparison of battery-powered and wireless-powered pacemakers.

<p>Comparison of battery-powered and wireless-powered pacemakers.</p

Bench top and <i>in vivo</i> testing of battery powered pacemaker.

<p>(a) Current (blue) and voltage (gray) traces from the pacing catheter. (b) Frequency Response Analysis of distal and proximal pacing catheter electrodes (c) Lead II ECG recording in a mouse heart during sinus rhythm and right ventricular pacing by the battery-powered pacemaker over 5 days.</p

Assembly process of wireless powered pacemaker.

<p>(a) Platinum wire is attached to the circuit board, wound together, and coiled with a 0.5 cc syringe. (b) A bead of Silastic is placed on a piece of parafilm(1). The device is placed on the bead(2), coated with an additional layer of Silastic(3), and topped with a piece of gas permeable film(4). (c) Final product. (d) Artistic rendering of external transmitter interacting with abdominally implanted receiver in mouse.</p

<i>In vivo</i> testing of wireless pacemaker.

<p>(a) Lead II ECG during normal sinus rhythm (top) and during LV apical pacing (bottom). (b) Pacing pulse width threshold of wireless device over 30 days for all mice with stable capture. Solid red line shows linear regression on mean pulse width thresholds. Dashed black lines show 95% confidence interval bounds for the regression.</p

Layout of the wireless-powered pacemaker.

<p>(a) Circuit layout of transmitter (top) and receiver (bottom). (b) Pulsed input into transmitter from pulse generator. (c) Output from transmitter. (d) Uncapped output from receiver. (e) Capped output from receiver. (f) Receiver output decreases minimally up to 5 cm from the transmitter coil. See text for further details.</p

Parts list for wireless transmitter and receiver circuits.

<p>Parts list for wireless transmitter and receiver circuits.</p

Ventricular myocytes from double transgenic mice have impaired relaxation and enhanced contraction.

<p>(A) Representative signal averaged sarcomere length measurements during contraction recorded from acutely-induced DTG (solid line) and control cardiomyocytes (dashed line). (B) DTG myocytes had significantly shorter sarcomere lengths at both systole and diastole, (C) with an overall increase in fractional shortening (n=4 mice, 17 myocytes total for both control and DTG). (D) Addition of BDM caused significant relaxation of both DTG and control myocytes, and (E) resulted in a greater change in sarcomere length in DTG myocytes (n=3 mice each, 19 control myocytes, 23 DTG myocytes). Error bars = standard deviation. **p<0.01, +p<0.001 DTG vs. controls; # p<0.05 vs. respective baseline measurements.</p

In vivo induction of caFGFR1 in adult cardiomyocytes leads to a hypercontractile phenotype with the development of a dynamic obstruction in the proximal left ventricle.

<p>(A) Representative pressure-volume (PV) loops at baseline (1) and following increased afterload (2) in DTG mice and littermate controls induced with DOX chow for 24 hours. The slope of the end systolic pressure-volume relationship (ESPVR, dotted line) is significantly elevated in DTG mice (n=3 for DTG and control). (B) Representative pressure (top) and dP/dt (bottom) tracings suggesting the presence of a dynamic obstruction in DTG mice induced for 42 days (n_DTG=3, n_control=2). (C) Representative color Doppler images (blue = blood outflow, red = blood inflow) and (D) spectral Doppler tracings illustrating flow convergence (yellow arrow) and a high velocity late-peaking jet originating from the point of dynamic mid-cavity obstruction in DTG mice. (E) Quantitation of LV peak outflow velocity (LV POV) at the point of flow convergence. Error bars = standard deviation. *p<0.05, **p<0.01, +p<0.001.</p

Transgene induction for 42 days, followed by DOX removal for 42 days leads to partial phenotype reversal.

<p>(A,B) LV internal diastolic diameter (LVIDd, A) and LV mass index (LVMI, B) returned to near control levels after removal of DOX for 42 days (42 off). (C) LV diastolic posterior wall thickness (LVPWd) was significantly reduced in DTG mice (n=6) following DOX removal (42 off), but remained significantly elevated compared to controls (n=4). (D) Despite decreasing significantly following removal of DOX, peak outflow velocity (LV POV) from the proximal ventricle was still significantly elevated compared to controls. (E) Cardiomyocyte cross-sectional area (CM CSA) was smaller than that seen following six weeks of caFGFR1 induction (42 on), but cells were still significantly larger than controls following DOX removal (42 off). (F) Western blot analysis showing a significant decrease but persistent expression of caFGFR1 following removal of DOX (DTG 42d ON 42d OFF), compared to transgene expression after three weeks of induction (DTG 21d; protein samples from six weeks of induction were unavailable). (G-I) QRT-PCR analysis demonstrating continued overexpression of Fgfr1 in DTG hearts following 42 days off DOX (gray bar), despite a large reduction from the level of expression observed following 42 days on DOX (black bar, G). Expression of downstream mediators of FGF signaling (H) and markers of pathological LV remodeling (I) are decreased to control levels 42 days following DOX removal. Error bars = standard deviation. *p<0.05, **p<0.01, +p<0.001 compared to controls. #p<0.05 compared to DTG mice 42 days on DOX.</p

Induction of caFGFR1 in adult cardiomyocytes results in the development of concentric hypertrophy with preservation of systolic function over time.

<p>(A) LV diastolic posterior wall thickness (LVPWd, A) was significantly elevated by one day of induction, while LV mass index (LVMI) was significantly elevated (B) and LV internal diastolic diameter (LVIDd) was significantly decreased (C) within seven days of DOX induction. (D) Systolic function was maintained throughout 6 months of transgene induction. Error bars = standard deviation. *p<0.05, **p<0.01, +p<0.001. 0d: n_DTG=47, n_control=23; 1d: n_DTG=8, n_control=4; 7d: n_DTG=17, n_control=7; 42d: n_DTG=14, n_control=12; 84d: n_DTG=4, n_control=4; 126d: n_DTG=4, n_control=4; 168d: n_DTG=4, n_control=4. (E) Representative short axis echocardiographic images depicting the progression of hypertrophy in DTG animals from baseline to 168 days of induction. </p