Virtual histology: a window to the heart of atherosclerosis.

Intravascular ultrasound has done much to improve our understanding of atherosclerosis and the impact of percutaneous intervention on the coronary artery. However, subjectivity in interpreting the acoustic reflection of the ultrasound signal has spawned the development of other progressive technologies. Virtual histology intravascular ultrasound (VHIVUS) utilises the ultrasound backscatter signal in order to colour code plaque into four pre-specified subtypes based on their histological composition. We review the background behind traditional grey scale intravascular ultrasound (IVUS) and examine the current evidence for VHIVUS and its potential for use in clinical interventional practice.

Integrated coronary physiology in percutaneous intervention: a new paradigm in interventional cardiology.

Coronary angiography has provided an unrivalled appreciation of coronary anatomy fostering a far greater appreciation of the extent of atherosclerotic disease. However, the subjectivity of coronary angiography at determining the extent of plaque has been exposed with IVUS. Indices of coronary physiology have provided valuable adjunctive information as to the physiological importance of specific lesions. Fractional flow reserve is an established method for evaluating the significance of epicardial stenoses. Fractional flow reserve guided percutaneous coronary intervention is associated with improved outcomes when compared to a conventional angiographic guided strategy, particularly in intermediate lesions. The use of coronary physiology in the cath lab represents a new avenue to guide appropriate patient specific revascularisation strategies. This review examines the theory and evidence for fractional flow reserve and its use in percutaneous coronary intervention.

Phosphorylation of troponin I by protein kinase A accelerates relaxation and crossbridge cycle kinetics in mouse ventricular muscle.

Phosphorylation of cardiac myofibrils by cAMP-dependent protein kinase (PKA) can increase the intrinsic rate of myofibrillar relaxation, which may contribute to the shortening of the cardiac twitch during beta-adrenoceptor stimulation. However, it is not known whether the acceleration of myofibrillar relaxation is due to phosphorylation of troponin I (TnI) or of myosin binding protein-C (MyBP-C). To distinguish between these possibilities, we used transgenic mice that overexpress the nonphosphorylatable, slow skeletal isoform of TnI in the myocardium and do not express the normal, phosphorylatable cardiac TNI: The intrinsic rate of relaxation of myofibrils from wild-type and transgenic mice was measured using flash photolysis of diazo-2 to rapidly decrease the [Ca(2+)] within skinned muscles from the mouse ventricles. Incubation with PKA nearly doubled the intrinsic rate of myofibrillar relaxation in muscles from wild-type mice (relaxation half-time fell from approximately 150 to approximately 90 ms at 22 degrees C) but had no effect on the relaxation rate of muscles from the transgenic mice. In parallel studies with intact muscles, we assessed crossbridge kinetics indirectly by determining f(min) (the frequency for minimum dynamic stiffness) during tetanic contractions. Stimulation of beta-adrenoceptors with isoproterenol increased f(min) from 1.9 to 3.1 Hz in muscles from wild-type mice but had no effect on f(min) in muscles from transgenic mice. We conclude that the acceleration of myofibrillar relaxation rate by PKA is due to phosphorylation of TnI, rather than MyBP-C, and that this may be due, at least in part, to faster crossbridge cycle kinetics.

Positive force- and [Ca2+]i-frequency relationships in rat ventricular trabeculae at physiological frequencies.

The isometric force-frequency relationship of isolated rat ventricular trabeculae (diameter <250 micrometer) was examined at 24, 30, and 37 degreesC at stimulation frequencies (0.1-12 Hz) encompassing the physiological range. Some muscles were microinjected with fura PE3 to monitor the diastolic and systolic intracellular concentration of Ca2+ ([Ca2+]i). At a near-physiological external Ca2+ concentration ([Ca2+]o) of 1 mM, a positive force-frequency relationship was demonstrated at all temperatures. The force-frequency relationship became negative at high frequencies (e. g., >6 Hz at 30 degreesC) at 1 mM [Ca2+]o or at low frequencies at 8 mM [Ca2+]o. The twitch and Ca2+ transient became shorter as stimulation frequency increased; these changes were related to changes in systolic, rather than diastolic, [Ca2+]i and were not blocked by inhibitors of Ca2+/calmodulin-dependent protein kinase II. The positive force-frequency relationship of rat trabeculae was caused by a frequency-dependent loading of the sarcoplasmic reticulum (SR) with Ca2+. We suggest that at high frequencies, or under conditions of Ca2+ overload, this loading saturates. Processes that tend to decrease SR Ca2+ release will then predominate, resulting in a negative force-frequency relationship.

Effects of 1- or -adrenoceptor stimulation on work-loop and isometric contractions of isolated rat cardiac trabeculae.

1. We studied the effects of alpha1- or beta-adrenoceptor stimulation on the contractility of isolated rat ventricular trabeculae at 24 degrees C using the work-loop technique, which simulates the cyclical changes in length and force that occur during the cardiac cycle. Some muscles were injected with fura-2 to monitor the intracellular Ca2+ transient. 2. Comparison of twitch records revealed that peak force was greater and was reached earlier in work-loop contractions than in corresponding isometric contractions. This was attributed to the changes in muscle length and velocity during work-loop contractions, since the Ca2+ transients were largely unaffected by the length changes. 3. Stimulation of alpha1-adrenoceptors (with 100 microM phenylephrine) increased net work, power production, the frequency for maximum work, and the frequency for maximum power production (fopt). The increase in net work was due to the positive inotropic effect of phenylephrine, which was similar at all frequencies investigated (0. 33-4.5 Hz). The increase in fopt was attributed to an abbreviation of twitch duration induced by alpha1-stimulation at higher frequencies (> 1 Hz), even though the twitch became longer at 0.33 Hz. 4. beta-Adrenoceptor stimulation (with 5 microM isoprenaline) produced marked increases in net work, power output, the frequency for net work, and fopt. These effects were attributed both to the positive inotropic effect of beta-stimulation, which was greater at higher frequencies, and to the reduction in twitch duration. beta-stimulation also abolished the frequency-dependent acceleration of twitch duration. 5. The increase in power output and fopt with alpha1- as well as beta-adrenoceptor stimulation suggested that both receptor types may contribute to the effects of catecholamines, released during stress or exercise, although the greater effects of beta-stimulation are likely to predominate.

The effects of adrenaline on the work- and power-generating capacity of rat papillary muscle in vitro.

The work loop technique was used to examine the effects of adrenaline on the mechanics of cardiac muscle contraction in vitro. The length for maximum active force (Lmax) and net work production (Lopt) for rat papillary muscles was determined under control conditions (without adrenaline). The concentration of adrenaline producing the maximum inotropic effect was determined. This concentration was used in the remainder of the experiments. Sinusoidal strain cycles about Lopt were performed over a physiologically relevant range of cycle frequencies (4-11 Hz). Maximum work and the frequency for maximum work increased from 1.91 J kg-1 at 3 Hz in controls to 2.97 J kg-1 at 6 Hz with adrenaline. Similarly, maximum power output and the frequency for maximum power output (fopt) increased from 8.62 W kg-1 at 6 Hz in controls to 19.95 W kg-1 at 8 Hz with adrenaline. We suggest that the power-frequency relationship, derived using the work loop technique, represents a useful index with which to assess the effects of pharmacological interventions on cardiac muscle contractility.

The length dependence of work production in rat papillary muscles in vitro.

The influence of length on work production was investigated for rat papillary muscles using the work loop technique. Active and passive length-force relationships were first determined under isometric conditions and the length for maximum force production (Lmax) was derived. Starting from different lengths within the physiological range, a series of work loops was generated using the stimulation phase shift, strain amplitude and cycle frequency previously found to be optimal for power output at 37 degrees C. The relationship between muscle length and net work was used to determine the length at which work output was maximal (Lopt). In order to examine the dynamic passive properties of the muscles, unstimulated muscles were subjected to the same regime of sinusoidal oscillation as used for the active loops. From the hysteresis loops, lengthening work (work done to extend the passive muscle), passive shortening work (work returned during shortening) and net energy loss (hysteresis) could be measured. The decline in net work production at lengths greater than 95% Lmax could largely be attributed to the rapid and non-linear increase in muscle stiffness and the increase in net energy loss over this range of lengths. The physiological significance of the length-work relationship is considered and the mechanical properties of active and passive papillary muscles are discussed with reference to sarcomere length and cardiac muscle ultrastructure.

The effect of cycle frequency on the power output of rat papillary muscles in vitro.

Papillary muscles were isolated from the right ventricles of rats and the length for maximum active force generation (Lmax) was determined isometrically. The work loop technique was used to derive the length for maximum work production (Lopt) at the cycle frequency, strain amplitude and stimulation phase shift found to be optimal for power output. Lopt was typically 7% shorter than Lmax and within the physiological length range (87.5% Lmax to Lmax). Net work and power output were measured during sinusoidal strain cycles around Lopt, over the cycle frequency range 1-9 Hz, strain amplitude and phase shift being optimised for work and power at each frequency. Experiments were performed at 37 degrees C. Distinct optima were found in both the work-frequency and the power-frequency relationships. The optimum cycle frequency for net work production was lower than the frequency for maximum power output. The mean maximum power output at 37 degrees C was 8.62 +/- 0.50 W kg-1 (mean +/- S.E.M., N = 9) and was achieved at a cycle frequency of approximately 6 Hz, close to the estimated resting heart rate of 5.8 Hz for the rats used (mean mass 223 +/- 25 g). The cycle frequency, strain amplitude and stimulation phase shift found to be optimal for power output produced an in vitro contraction closely simulating the basal in vivo contraction.

Prevalence of stress hyperglycemia among patients attending a pediatric emergency department.

OBJECTIVE: To determine the prevalence and clinical characteristics associated with stress hyperglycemia among children and adolescents attending a pediatric emergency department. DESIGN: Patients who required a venipuncture for evaluation of an acute illness or injury from October 1992 to March 1993 in an urban pediatric emergency department were enrolled and screened prospectively for hyperglycemia (glucose level > or = 8.3 mmol/L; > or = 150 mg/dl). Data were collected regarding demographic characteristics, history, clinical findings, and admission status. RESULTS: A total of 926 patients ranging in age from 3 days to 21 years were enrolled. Blood glucose values ranged from 1.94 mmol/L (35 mg/L) to 14.65 mmol/L (264 mg/dl); 35 patients (3.8%) had hyperglycemia. The prevalence of stress hyperglycemia was significantly increased among patients if they (1) had temperatures greater than 39.5 degrees C (9.3%) versus normal temperatures (2.8%) (p < 0.001), (2) had been admitted to a critical care unit of the hospital (24.1%) or to any hospital unit (4.4%) versus not having been admitted (2.6%) (p < 0.001), and (3) had received fluids intravenously (6.0%) versus having received no fluids intravenously (2.7%) (p = 0.014). CONCLUSIONS: Stress hyperglycemia is a frequent clinical occurrence in a pediatric emergency department. It does not appear to be associated with a particular diagnostic category but is significantly associated with severity of illness as measured by elevated temperature, hospital admission, and hydration status.