Dual-head lithotripsy in synchronous mode: acute effect on renal function and morphology in the pig

Abstract

Objective: To assess the effect of dual-head lithotripsy on renal function and morphology in a pig model of shockwave (SW) injury, as lithotripters with two shock heads are now available for treating patients, but little information is available with which to judge the safety of treatment with dual pulses.

Materials and methods: A dual-head electrohydraulic lithotripter (Duet, Direx Corp., Natick, MA, USA) was used to treat the lower renal pole of anaesthetized pigs with a clinical dose of SWs (2400 dual SWs; 10 kidneys) delivered in synchronous mode, i.e. both heads fired simultaneously. For comparison, pigs were treated with either 2400 SWs (12 kidneys) or 4800 SWs (eight) with a conventional electrohydraulic lithotripter (HM3, Dornier, Wessling, Germany).

Results: Dual-pulse SW treatment with the Duet lithotripter caused a decline in the mean (sd) glomerular filtration rate (GFR) of 4.1 (1.9) mL/min, with a trend for the effective renal plasma flow (RPF), at 31 (19) mL/min, to also decrease. These changes in renal haemodynamics were similar to the decreases in GFR and RPF in response to treatment with the HM3 lithotripter with 2400 SWs, at 4.8 (0.8) and 32 (10) mL/min, respectively, or 4800 SWs, at 5.4 (1.0) and 68 (14) mL/min, respectively. Linear association analysis showed that the functional response to dual-pulse SWs was more variable than with conventional SWs. Morphological quantification of kidney damage (expressed as a percentage of functional renal volume, FRV) showed that tissue injury with 2400 paired SWs with the Duet, at 0.96 (0.39)% FRV, was similar to injury produced by either 2400 single SWs, at 1.08 (0.38)% FRV, or 4800 single SWs, at 2.71 (1.02)% FRV, with the HM3. However, morphological damage was less consistent with the Duet (measurable in only five of eight kidneys) than that with the HM3 (measurable in all 12 kidneys). Acoustic output and the timing of dual SWs in synchronous mode increased in variability as the electrodes aged, affecting the amplitude and targeting of focal pressures.

Conclusion: With the caveat that variability in the timing of dual SWs will unpredictably alter the distribution of SW energy within the kidney, this study shows that a clinical dose of dual-head SWs delivered in synchronous mode elicits a renal response similar to, but more variable than, that with a clinical dose of SWs from a conventional electrohydraulic lithotripter.

Figure 1

Renal filtration and perfusion responses in the SWL-treated kidney. Individual responses are shown with black lines, and the mean and Standard Error of the Mean (SEM) value of the group response are shown in red. GFR = glomerular filtration rate, RPF = effective renal plasma flow, Basal = baseline value, pSWL = 1 h post-treatment (sham or SWL) value, * = P<0.05 from baseline value.

Figure 2

Gross morphology of kidneys at the time of autopsy. No sites of subcapsular hemorrhage were seen on any of the sham-treated kidneys (panel a). Two of the ten Duet treated kidneys showed sites of subcapsular bleeding with one kidney having a well defined subcapsular hematoma in the targeted pole (arrow, panel b), while nine of the twelve HM3 2400 SW treated kidneys (arrow, panel c) and five of the seven HM3 4800 SW treated kidneys (arrow, panel d) showed well defined subcapsular hematomas that were always large in size. Magnification, ×1.2 (a–d).

Figure 3

Digitized and colorized cross-sections of Duet-treated and HM3-treated kidneys. The degree of intraparenchymal hemorrhage induced by the Duet lithotripter varied from no detectable lesion in one animal (panel a) to a lesion size of 3.16% of FRV (panel b). The sites of intraparenchymal hemorrhage were noted in the papilla (double arrows) and adjacent cortical tissue (arrow) within the focal zone. All kidneys that received 2400 SWs (panel c) or 4800 SWs (panel d) from the HM3 lithotripter had lesions similar to that seen in the Duet-treated kidneys. Sites of intraparenchymal hemorrhage were seen in the medulla (double arrow) and cortex (arrows). Magnification, ×1.2 (a–d).

Figure 4

Histopathologic examination of sites of cortical and medullary damage induced by the Duet and HM3 lithotripters. Cortical damage was primarily localized to the walls of veins and arteries within the area targeted by the focal zone, and varied from dissection of the tunica media with blood cells and damaged smooth muscle cells (arrows, panels a and b) to rupturing of the vessel wall permitting the release of blood into the interstitial space. Histopathologic examination of damaged papilla from both the Duet- and HM3-treated kidneys show cellular distruption of vasa recta resulting in intraparenchymal hemorrhage (arrows panel c) and injury to nearby tubules that included cellular necrosis and tearing of the tubular basement membrane (arrows, panel d). The pattern of cortical and medullary injury was similar between the two lithotripters. Magnification, x1,200 (a); ×1,000 (b–d).

Figure 5

The effect of inter-pulse time delay on waveforms from the Duet lithotripter fired at 17kV. (A) When the two electrodes fired in precise synchrony (with no inter-pulse delay), acoustic pressures at the focal point of the lithotripter were about twice that produced by a single electrode. (B) A slight delay in timing (<1μs) resulted in two peaks, the second of which was typically higher in amplitude. (C) A longer delay (6μs) between the firing of the electrodes separated the peaks, which were correspondingly lower in amplitude, and similar to SWs fired from a single source.

Figure 6

Acoustic output for a single shock source of the Duet lithotripter fired at 17 kV, 1Hz. Shown here are waveforms for two shock pulses selected to demonstrate the variability in output from a single shock source (bottom head) in the Duet. SW 210 had low amplitude (~20 MPa peak P⁺) and relatively long pulse duration (~2μs), while SW 200 was high amplitude (~70 MPa peak P⁺) and shorter duration (~1μs). Also shown is the trace generated from the average of values over the recommended lifetime (2400 SWs) of the electrode (30 MPa P⁺, duration 1.5μs, ~5MPa P⁻).

Figure 7

Photodiode measures of inter-pulse delay for a set of Duet electrodes fired in synchronous mode. Early in the life of the electrodes, firing was nearly simultaneous and the majority of paired pulses were separated by a delay of ≤2 μs (dashed line). As the electrodes aged, the inter-pulse delay increased, such that during the last 1400 paired pulses only ~27% were simultaneous (≤2 μs). Solid line tracks mean values for inter-pulse delay at 100 shot intervals.