Control of intraaortic balloon pumping: Theory and guidelines for clinical applications

The effectiveness of intraaortic balloon pumping was investigated by using a lumped parameter model of the cardiovascular/assist device system. The model consists of a time-varying elastance left ventricular simulation, a 2-element windkessel arterial simulation, and an RC venous return and pulmonary simulation. The four major hemodynamic variables, stroke volume (SV), aortic mean diastolic pressure (MDP), tension time index (TTI), and aortic end diastolic pressure (EDP), were divided into two categories related to system energy supply and demand: “external” and “internal” variables. The effects of balloon pumping on these variables can be described by closed-form equations that yield an optimal solution. The model prediction suggests that, in the ideal case, optimization of balloon pumping calls for instantaneous inflation of the balloon to maximum volume at end systole and instantaneous complete deflation at end diastole. For finite inflation/deflation rates, the optimal time for the start of inflation is end systole. Deflation timing, however, involves a tradeoff between maximizing the external variables and minimizing the internal variables. These predictions were tested using a nonlinear digital computer model. The results also suggest that when SV is not being monitored, optimal inflation timing can be controlled from the measurements of TTI or pulmonary venous pressure; optimal deflation timing can be controlled by a weighted combination of MDP and EDP.     

Hemodynamic and metabolic effects of para- versus intraaortic counterpulsatile circulation supports

Despite the success of intraaortic balloon counterpulsation, data on physiologic indices and optimal inflation/deflation timing control of chronic counterpulsation devices are unclear. This study explored the acute hemodynamic and metabolic efficacy of a novel 40-ml stroke volume paraaortic blood pump (PABP) versus a standard intraaortic balloon pump (IABP). Acute porcine model was used with eight pigs randomly divided into PABP (n = 4) and IABP (n = 4) groups. Hemodynamic and metabolic measurements were obtained with and without mechanical assistance. In one pig, the inflation/deflation control was adjusted to different settings, with corresponding performance indices measured. The PABP significantly improved classical counterpulsation indices (p ≤ 0.05) and achieved an average beneficial effect on these indices 1.5-3.5 times greater than that of the IABP. Classical metabolic indices (tension time index and endocardial viability ratio [EVR]), and indices new to chronic counterpulsation research (coronary perfusion, left ventricular stroke work (SW), and a newly derived EVR) were also used in assessment. Both IABP assistance and PABP assistance improved these physiologic indices, with a trend toward PABP superiority in reducing left ventricular SW (p = 0.08). An optimal PABP deflation timing occurs during systole (25 milliseconds after the R-wave) and can minimize coronary regurgitation.     

基于体外实验和数值仿真的冠脉介入手术中球囊去充盈瞬间的血流动力学研究

目的研究冠脉介入手术中血流参数在球囊去充盈瞬间发生的动态变化,探讨球囊去充盈对术后无复流发生风险的潜在影响。方法搭建体外实验装置,利用高速摄像机拍摄球囊变形过程和由染色剂标记的流场(流体介质为水),使用图像分析技术提取球囊变形参数,并估测球囊下游的流体流动速度;构建计算机仿真模型,导入实测的球囊变形数据,在多种灌注压和流体介质条件下模拟球囊去充盈过程。结果球囊在去充盈过程中呈现显著的非线性变形特征。球囊下游流速的数值计算结果与实测数据吻合良好,两者均显示流速随去充盈后的时间增长和灌注压升高而增大。数值计算进一步揭示,球囊下游流速在接近冠脉血流速度生理值时,球囊-管壁间隙流速和壁面剪应力分别达到其生理值的8~10倍和60~70倍。结论球囊去充盈引起球囊-管壁间隙流体急剧加速和壁面剪应力异常升高,从而增大斑块、血栓碎屑剥离的风险。鉴于壁面剪应力的升高程度随灌注压升高而增大,在冠脉介入手术中采取术前降压或选择舒张期去充盈等措施可能有助于降低无复流的发生风险。     

QT interval dispersion changes according to the vessel involved during percutaneous coronary angioplasty

Increased QT dispersion (QTd) is a noninvasive marker of an electrophysiologic abnormality associated with high mortality in coronary artery disease. The purposes of this study were to measure changes in QTd and ST-segment changes immediately before, during and after intracoronary balloon inflation and to determine whether the coronary artery vessel involved and/or the duration of inflation affect(s) QTd. A total of 45 patients (32 men, 13 women, mean age 58 +/- 11 years) who were referred for elective percutaneous transluminal coronary angioplasty were included. The mean QT interval dispersions for all patients before the inflation, during the balloon inflation at 60 sec and after the balloon deflation at 5 min were 68 +/- 13 ms, 82 +/- 16 ms and 71 +/- 13 ms, respectively. There was no significant difference between baseline and 5 min after deflation. The increase in QTd during the balloon inflation was significant (p<0.01). There was no significant QTd change in patients with left circumflex artery (Cx) lesions during inflation and after deflation compared with baseline. The differences were statistically significant only in patients with left anterior descending (LAD) lesions and right coronary artery (RCA) lesions at 60 sec during balloon inflation (p=0.001 vs. p=0.04). Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd limited to the LAD and RCA vessels. Therefore, when using QTd as a marker of myocardial repolarization abnormality due to acute reversible ischemia, the involved coronary artery vessel must be taken into account.     

Changes in thermal homeostasis in humans due to repeated cold water immersions

The purpose of this study was to monitor changes in body and skin temperatures, heat production, subjective shivering, cold sensation and body fat content in humans after intermittent cold water immersion. Repeated exposures of young sportsmen to cold water (head out, 14 °C, 1 h, 3 times per week for 4–6 weeks) induced changes in regulation of thermal homeostasis. ‘‘Cold acclimated’’ subjects exhibited an hypothermic type of adaptation. Central and peripheral body temperatures at rest and during cold immersion were lowered. The metabolic response to cold was delayed and subjective shivering was attenuated. The observed hypothermia was due to the shift of the threshold for induction of cold thermogenesis to lower body temperatures. ‘‘Cold acclimated’’ subjects also showed a lowered cold sensation. Because of the observed physiological changes, about 20% of the total heat production was saved during one cold water immersion of ‘‘cold acclimated’’ subjects. Maximal aerobic and anaerobic performances were not altered. No change in the thermosensitivity of the body temperature controller, as assessed from the unchanged slope of the relation between the deep body temperature and total heat production, was observed. Changes in cold sensation and regulation of cold thermogenesis were noticed first after four cold water immersions and persisted for at least 2 weeks after termination of the adaptation procedure. A trend towards a small increase in the body fat content was also observed. This findll as the increased vasoconstriction, evidenced by the lowered skin temperature, indicate that slight changes in body insulation may also occur after ‘‘cold acclimation’’ in humans. Received: 30 December 1995/Received after revision and accepted: 25 March 1996     

Microprocessor control of intra-aortic balloon pumping

An automatic control scheme for the control of intra-aortic balloon pumping has been implemented on a Digital Equipment Corporation LSI-11 micro-processor system and tested in experiments conducted on a mock circulatory loop as well as in a series of acute animal experiments. The control algorithm employed by the digital controller (LSI-11) is identical in form to that employed by Clark et al. (3), and consists of [1] the beat-by-beat evaluation of a performance index that reflects the objectives of balloon pumping, and [2] the adjustment of balloon inflation and deflation times within the diastolic period so as to maximize this performance index according to a steepest ascent algorithm. In order to reduce convergence time and minimize disturbances around the optimum operating point, a scheme that reduces search step size as the search proceeds from initial values is also incorporated in the algorithm. Importantly, this system obeys a bedside measurement constraint in that it requires only readily available physiologic signals for its operation; the ECG for timing purposes, and the central aortic pressure for evaluation of the system performance index. A number of conventional safety features are also implemented in the controller to, for example, guard against untimely balloon inflation in the occurrence of aberrant heart beats. Finally, the ability of this digital controller to reach an optimum independent of the dynamics of the particular pneumatic pumping system utilized, coupled with the flexibility in design capability and relatively low cost of implementation via the microprocessor system, provide a significant advance in the area of the automatic control of intra-aortic balloon pumping.     

Abnormal electrical stimulus of an intra-aortic balloon pump with concurrent support with continuous veno-venous hemodialysis

Malfunction of electronic medical support apparatus utilized in the ICU usually causes system failure. We report several occurrences of a potentially dangerous interaction between a continuous veno-venous hemodialysis (CVVHD) system and an intra-aortic balloon pump (IABP) counterpulsation device in four patients requiring both systems. The patients had acute renal failure in the face of multi-organ failure and were dependent upon the balloon pump for pressure support. Electrical interference created by the roller pump action of the CVVHD system was identified by the balloon pump as cardiac in origin, and it responded by inflation and deflation. As the blood pump rate was reduced, the interference reduced to the point of complete cessation when the blood pump was shut down. Whereas one patient transiently had a significant drop of mean arterial pressure (from 70 +/- 4 to 40 +/- 2 mm Hg) the other observed occurrences had no clinically significant sequelae. Electrocardiogram (ECG) tracings identified the abnormal stimulus and systematic review identified as potential sources for the creation of this interference static electricity buildup, piezoelectric properties of the polyvinyl chloride tubing, and, possibly but less likely, radiofrequency interference. A newer generation ECG cable and advanced cardiac rhythm recognition software (CardioSync) have been introduced with the Datascope System 98, and the ECG interference, although still occasionally present, does not cause erratic inflation and deflation of the intra-aortic balloon pump. Interference between different electrical support systems may occur, and we suggest that the systems be tested for compatibility before combined use and that older equipment be more rigorously tested for potential clinically significant interference.     

Gait control system for functional electrical stimulation using neural networks

In functional electrical stimulation (FES) systems for restoring walking in spinal cord injured (SCI) individuals, hand switches are the preferred method for controlling stimulation timing. Through practice the user becomes an ‘expert’ in determining when stimulation should be applied. Neural networks have been used to ‘clone’ this expertise but these applications have used small numbers of sensors, and their structure has used a binary output, giving rise to possible controller oscillations. It was proposed that a threelayer structure neural network with continuous function, using a larger number of sensors, including ‘virtual’ sensors, can be used to ‘clone’ this expertise to produce good controllers. Using a sensor set of ten force sensors and another of 13 ‘virtual’ kinematic sensors, a good FES control system was constructed using a three-layer neural network with five hidden nodes. The sensor set comprising three sensors showed the best performance. The accuracy of the optimum three-sensor set for the force sensors and the virtual kinematic sensors was 90% and 93%, respectively, compared with 81% and 77% for a heel switch. With 32 synchronised sensors, binary neural networks and continuous neural networks were constructed and compared. The networks using continuous function had significantly fewer oscillations. Continuous neural networks offer the ability to generate good FES controllers.     

Angioplasty pressure-volume measurement

An instrument has been developed for controlled inflation and deflation of an angioplasty balloon. The mean difference between inflation to 800 kPa in air and a simulated coronary artery is 71.2kPa. The repeatability of four inflation/deflation cycles is 6.4 kPa with the balloon in air and 9.0 kPa in the simulated artery.     

Micromechanical studies of mitotic chromosomes

Mitotic chromosomes respond elastically to forces in the nanonewton range, a property important to transduction of stresses used as mechanical regulatory signals during cell division. In addition to being important biologically, chromosome elasticity can be used as a tool for investigating the folding of chromatin. This paper reviews experiments studying stretching and bending stiffness of mitotic chromosomes, plus experiments where changes in chromosome elasticity resulting from chemical and enzyme treatments were used to analyse connectivity of chromatin inside chromosomes. Experiments with nucleases indicate that non-DNA elements constraining mitotic chromatin must be isolated from one another, leading to the conclusion that mitotic chromosomes have a chromatin ‘network’ or ‘gel’ organization, with stretches of chromatin strung between ‘crosslinking’ points. The as-yet unresolved questions of the identities of the putative chromatin crosslinkers and their organization inside mitotic chromosomes are discussed.     

Stem cell clinical trials for spinal cord injury: readiness, reluctance, redefinition

A wealth of scientific and clinical research has focused on the use of stem cells as a potential therapy for spinal cord injury (SCI), culminating most recently in the initiation of clinical trials. However, with the urgency that scientists and clinicians have undertaken to move forward with novel therapies for this devastating injury, the perspectives of stakeholders who live with a SCI have been left behind. Translational research in this rapidly growing field therefore overlooks a critically important viewpoint. We address this concern with a qualitative study of the perspectives on experimental stem cell treatments from individuals who have actually suffered a spinal cord injury. Using focus groups and interviews, we engaged individuals with thoracic and cervical SCIs at sub-acute and chronic stages post-injury. We found four major themes that inform the progression of stem cell research to clinical trials: ‘readiness’, ‘the here and now’, ‘wait and see’, and ‘informed hope’. Taken together, the data suggest a profound difference related to target timing of stem cell clinical trials and the perspectives about timing from those who are the end-beneficiaries of therapy. To bridge this gap, we conclude with a number of considerations for the timing disparity of trials and recommendations for improving informed consent.     

Haemostatic investigations: The impact of new technologies

Blood loss following trauma is controlled by a complex series of interactions involving the vascular surface, blood platelets and ‘activated’ coagulation factors. Activation of the coagulation cascade involves a series of zymogen to enzyme transformations with each enzyme associating with a co-factor on a ‘surface’ such as negatively charged platelet membrane phospholipid to form reaction complexes. In physiological terms it is possible that this system is continuously switched on producing low levels of activated serine proteases which are continuously being neutralised by protease inhibitors and co-factor neutralising reactions which down-regulate blood clotting processes, thus maintaining patency of the vascular tree. It is in this context that the concept of identifying molecular markers of haemostatic activation is well recognised. The haemostatic investigations now include biochemical and immunological investigations in order to detect small concentrations of products from intravascular thrombin generation, platelet-specific proteins released as a consequence of platelet release reaction, circulating activated clotting factors, activation peptides and ‘activated clotting factor-inhibitor’ complexes. This review will concentrate on new markers of haemostasis which are currently being used in the investigation of thrombosis.     

Retrospective evaluation of a decision support system for controlled mechanical ventilation

Management of mechanical ventilation in intensive care patients is complicated by conflicting clinical goals. Decision support systems (DSS) may support clinicians in finding the correct balance. The objective of this study was to evaluate a computerized model-based DSS for its advice on inspired oxygen fraction, tidal volume and respiratory frequency. The DSS was retrospectively evaluated in 16 intensive care patient cases, with physiological models fitted to the retrospective data and then used to simulate patient response to changes in therapy. Sensitivity of the DSS’s advice to variations in cardiac output (CO) was evaluated. Compared to the baseline ventilator settings set as part of routine clinical care, the system suggested lower tidal volumes and inspired oxygen fraction, but higher frequency, with all suggestions and the model simulated outcome comparing well with the respiratory goals of the Acute Respiratory Distress Syndrome Network from 2000. Changes in advice with CO variation of about 20% were negligible except in cases of high oxygen consumption. Results suggest that the DSS provides clinically relevant and rational advice on therapy in agreement with current ‘best practice’, and that the advice is robust to variation in CO.     

Age Differences in Genetic and Environmental Variations in Stress-Coping During Adulthood: A Study of Female Twins

The way people cope with stressors of day to day living has an important influence on health. The aim of the present study was to explore whether genetic and environmental variations in stress-coping differ over time during adulthood. The brief COPE was mailed to a large sample of the UK female twins (N = 4,736) having a wide range of age (20–87 years). Factor analyses of the items of the brief COPE yielded three coping scales: ‘Problem-Solving’, ‘Support Seeking’, and ‘Avoidance’. Monozygotic and dizygotic twin correlations tended to become lower with age for all three scales, suggesting that unique environmental factors may become more important with age during adulthood. Model-fitting results showed that relative influences of unique environmental factors increased from 60 % at age 20 years to 74% at age 87 years for ‘Problem-Solving’ and 56 % at age 20 years to 76% at age 87 years for ‘Avoidance’. During the same age period, genetic factors decreased from 40 to 26 % for ‘Problem-Solving’ and from 44 to 24 % for ‘Avoidance’. For ‘Seeking Support’, the magnitude of genetic and unique environmental factors was not significantly different across the adulthood. For all three scales, shared environmental effects were negligible. Overall, our findings implicate that the effects of environment that stem from idiosyncratic experience of stressful life events accumulate and become increasingly important in adulthood.     

Left ventricular afterload and systemic hydraulic power during in-series cardiac assistance: Studies using intraaortic balloon pumping in dogs

The effects of in-series mechanical assistance on left ventricular (LV) afterload and aortic power dissipation were studied in four groups of open chest mongrel dogs: control, acute myocardial ischemia, cholinergic and beta-adrenergic blockade, and combined ischemia and blockade. Aortic root pressure, flow, power, and impedance and LV pressure and power were obtained. Assistance was provided by intraaortic balloon pumping. Times of inflation and deflation of the balloon were controlled to maintain a phase difference of 180° between the fundamental components of aortic root pressure and flow. Differences in hemodynamic parameters before and after 2–5 min of cardiac assistance were calculated. The results confirm other observations regarding effects of in-series assistance on LV and aortic pressure, cardiac output, and peripheral resistance. No consistent changes were obtained in the pulsatile components of aortic input impedance. A significant decrease (14–20%) was observed in the dc component of the impedance in all animals. The results reported here contradict previous reports regarding decreased LV power generation. It was found that LV power generation and aortic power dissipation increased significantly during assistance (LV, 3–17%; aortic, 4–19%). The results of this investigation also appear to conflict with previous reports regarding the role of cardiovascular control in “counteracting” the effects of assistance in the normal experimental preparation. They suggest that the short term effects are attributable directly to the device and are not mediated by the autonomic nervous system. This work was supported in part by SUPHS Grant HL-13737 to Sinai Hospital and by NSF Grant ENG 74-21085 to the University of Rhode Island. Portions of this investigation were performed while D. Jaron was Director of the Surgical Research Laboratory at Sinai Hospital of Detroit.     

Effect of cold water immersion on 100-m sprint performance in well-trained swimmers

The aim of the present study was to examine the effect of cold water immersion (CWI) on sprint swimming performance in simulated competition conditions. Ten well-trained swimmers (5 males, 5 females; 19.0 ± 3.9 years) performed two 100-m swimming sprints (S1 and S2) interspersed with a 30-min passive recovery period, during which athletes were randomly assigned to 5 min of CWI (14°C) or an out-of-water control condition (CON 28°C). During tests, sprint times, heart rate (HR), pre- and post-race parasympathetic activity via HR variability (natural logarithm of the square root of the mean of the sum of the squares of differences between adjacent normal R–R intervals; Ln rMSSD) and blood lactate accumulation ([La]_ac) and clearance ([La]_cle) were recorded. Rates of perceived recovery (RPR) and exertion (RPE) were evaluated before and after each sprint. CWI was associated with a ‘likely’ decrease in swimming performance [1.8% (90% CI 0.2, 3.5)], as well as ‘likely’ lower peak HR [−1.9% (−3.6, −0.2)]. CWI was also associated with a ‘likely’ smaller decrease in Ln rMSSD after the first sprint [−16.7% (−30.9, −4.1)]. RPR was ‘likely’ better [+27.2% (−3.7, 68.0)] following CWI. ‘unclear’ effects were observed for [La]_ac [+24.7% (−13.4, 79.5)], [La]_cle [−7.6% (−24.2, 12.7)] or RPE [+2.0% (−12.3, 18.5)]. Following CWI, changes in sprint times were ‘largely’ correlated with changes in peak HR (r = 0.80). Despite a subjective perception of improved recovery following CWI, this recovery intervention resulted in slower swimming times in well-trained athletes swimming in simulated competition conditions.     

Unrestrained Acoustic Plethysmograph for Measuring Tidal Volume in Mice

The traditional method for measurement of tidal volume in unrestrained mice relies on pressure changes induced by a freely respiring animal in a whole body plethysmograph. These changes have been assumed to be the result of thermo-hygrometric differences between respired air and gas within the chamber. It is known, however, that gas compression in the lung can also contribute significantly to changes in plethysmograph pressure. This study describes an acoustic plethysmograph for mice that is capable of measuring the tidal volume time series without the errors associated with the traditional method.The plethysmograph was designed as a resonating cavity at a fixed frequency. It had a sharp resonant peak and was tuned so that changes in body volume produced nearly linear changes in sound amplitude. The plethysmograph was tested with a water filled balloon connected to a syringe pump. The volume of the balloon was varied as a triangle wave with an amplitude of 250 μL. The RMS error between measured and delivered volume was 4.43 μL. A volume step test, performed to assess the response time of the system, showed that the plethysmograph responded in less than one millisecond.     

Bioenergetics and biomechanics of cycling: the role of ‘internal work’

The ‘dissection’ of energy expenditure of cycling into the metabolic equivalent of the different forms of mechanical work done, inaugurated 30 years ago by di Prampero and collaborators, has been much debated in the last few decades. The mechanical internal work, particularly, which is currently associated to the movement of the lower limbs, has been approached, estimated and discussed in several different ways and there is no agreed consensus on its role in cycling. This paper, through re-processing previously published data of oxygen consumption during pedalling at different frequency, external load and limb mass, proposes a model equation and a multiple non-linear regression as the method to assess the internal work of cycling. With that tool a very consistent metabolic equivalent of the internal work is obtained. However, a software simulation of pedalling limbs showed, as suggested in the literature, that the link with the chain ring allows the system to passively revolve forever, after an initial push. This result challenges the very existence of the ‘kinematic internal work’ of cycling. We conclude and suggest that the ‘viscous internal work’, an often neglected and almost unmeasurable portion of the internal work that could be proportional to the ‘kinematic’ form, is responsible for the extra metabolic expenditure as measured when the pedalling frequency of cycling increases.     

Auditory temporal modulation of the visual Ternus effect: the influence of time interval

Research on multisensory interactions has shown that the perceived timing of a visual event can be captured by a temporally proximal sound. This effect has been termed ‘temporal ventriloquism effect.’ Using the Ternus display, we systematically investigated how auditory configurations modulate the visual apparent-motion percepts. The Ternus display involves a multielement stimulus that can induce either of two different percepts of apparent motion: ‘element motion’ or ‘group motion’. We found that two sounds presented in temporal proximity to, or synchronously with, the two visual frames, respectively, can shift the transitional threshold for visual apparent motion (Experiments 1 and 3). However, such effects were not evident with single-sound configurations (Experiment 2). A further experiment (Experiment 4) provided evidence that time interval information is an important factor for crossmodal interaction of audiovisual Ternus effect. The auditory interval was perceived as longer than the same physical visual interval in the sub-second range. Furthermore, the perceived audiovisual interval could be predicted by optimal integration of the visual and auditory intervals.