Identification of occult shock is a major clinical problem compounded by inadequate criteria for assessing the efficacy of fluid resuscitation. We suggest that these problems may be resolved in part by understanding both the physiological mechanisms underlying oxygen debt accumulation and, more importantly, the debt repayment schedule during resuscitation. We present a simplified tutorial that incorporates the concept of the oxygen supply-delivery relationship with that of oxygen debt and show how this is relevant to the understanding of shock and resuscitation. Use of oxygen debt metrics as end points for shock have been controversial; however, much of the controversy may have been due to incomplete understanding of basic physiology of shock and semantic confusion between the various metrics proposed as end points. Here, we provide working definitions for the frequently misunderstood concepts of oxygen deficit and oxygen debt and discuss the relatively novel concept of oxygen debt repayment schedule. We introduce predictions made on the basis of data derived from animal models of hemorrhagic shock. Our calculations suggest that the amount of debt repaid in the first 2 h of resuscitation, rather than the restoration of volume per se, influences the likelihood of organ damage. Because of difficulties inherent in measuring oxygen debt in the prehospital and emergency settings, various metabolic end points such as lactate and base deficit have been proposed as surrogates. We demonstrate the heuristic value of this model in providing a predictive framework for both the optimum therapeutic time window and optimum fluid loadings before critical transitions to an irreversible shock state can occur. The model also provides an unambiguous and objective standard for quantifying the behavior of various postulated shock "markers".

Although the mouse is the most commonly used transgenic species, little is known regarding cardiovascular and fluid homeostasis in this animal. Therefore, the reference microsphere and dilution techniques were adapted for the measurement of cardiac output (CO), regional blood flows, and intravascular fluid volumes in the conscious mouse. Previously acclimatized C3H mice were studied 4-5 h after surgery and recovery from anesthesia. Approximately 40,000 85Sr-labeled microspheres were injected into the left ventricle while a reference sample was withdrawn at one of two rates from the femoral artery. 51Cr and 125I were used for the determination of blood volume (BV), plasma volume (PV), and Fcells ratio (whole body hematocrit/large vessel hematocrit). CO and BV in the conscious mouse were 16 +/- 1.4 ml/min and 2.3 +/- 0.1 ml, respectively. Anesthesia lowered heart rate, blood pressure, PV, and altered the distribution of CO. Two successive injections of 15,000-20,000 microspheres were tolerated in the mouse without an increase in total peripheral resistance. The results indicate that the microsphere and indicator dilution techniques can be applied to study cardiovascular and fluid homeostasis in the mouse.

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AIMS The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0–100% scale) and standardized verbal sensory thresholds using a novel, touch-screen “sensation meter.” 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity–sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way.

AIMS Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics. METHODS Patients reporting urgency most or all of the time based on ICIq-OAB survey scores were prospectively enrolled in an extended repeat fill-and-empty urodynamics study designed to identify a correlate of adjustable preload tension which we now call “dynamic elasticity.” Cystometric capacity was determined during initial fill. Repeat fills to defined percentages of capacity with passive emptying (via syringe aspiration) were performed to strain soften the bladder. A complete fill with active voiding was included to determine whether human bladder exhibits reversible strain softening. RESULTS Five patients completed the extended urodynamics study. Intravesical pressure (pves) decreased with subsequent fills and was significantly lower during Fill 3 compared to Fill 1 (P =0.008), demonstrating strain softening. Active voiding after Fill 3 caused strain softening reversal, with pves in Fill 4 returning to the baseline measured during Fill 1 (P = 0.29). Dynamic elasticity, the urodynamic correlate of adjustable preload tension, was calculated as the amount of strain softening (or its reversal) per % capacity (Δaverage pves between fills/Δ%capacity). Dynamic elasticity was lost via repeat passive filling and emptying (strain softening) and regained after active voiding regulated the process (strain softening reversal). CONCLUSIONS Improved understanding of dynamic elasticity in the human bladder could lead to both improved sub-typing and novel treatments of overactive bladder.