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Ventricular arrhythmias associated with mitral valve prolapse (MVP) and the capacity to cause sudden cardiac death (SCD), referred to as 'malignant MVP', are an increasingly recognised, albeit rare, phenomenon. SCD can occur without significant mitral regurgitation, implying an interaction between mechanical derangements affecting the mitral valve apparatus and left ventricle. Risk stratification of these arrhythmias is an important clinical and public health issue to provide precise and targeted management. Evaluation requires patient and family history, physical examination and electrophysiological and imaging-based modalities. We provide a review of arrhythmogenic MVP, exploring its epidemiology, demographics, clinical presentation, mechanisms linking MVP to SCD, markers of disease severity, testing modalities and management, and discuss the importance of risk stratification. Even with recently improved understanding, it remains challenging how best to weight the prognostic importance of clinical, imaging and electrophysiological data to determine a clear high-risk arrhythmogenic profile in which an ICD should be used for the primary prevention of SCD., Competing Interests: Disclosure: SHBK has received travel expenses from Abbott and Medtronic. PS has received funding from Boston Scientific, Medtronic, Abbott Medical and Becton Dickenson, speaker fees from Pfizer, and a fellowship from the National Health and Medical Research Council of Australia; and has served on the advisory boards of Medtronic, Abbott Medical, Boston Scientific, CathRx and Pacemate. HSL has received funding from the Australian Government’s Medical Research Future Fund; travel expenses from the Asia Pacific Heart Rhythm Society Conference; and research support from Abbott and Medtronic; and is the Australian Representative for the AsiaPacific Heart Rhythm Society. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

Per-chromosome targeted recombination, with one to two recombinations at specific marker intervals on each chromosome, doubles the predicted genetic gains in biparental populations. We developed an integer programing model to identify where a fixed number of targeted recombinations should occur across the whole genome, without restrictions on the number of targeted recombinations on each chromosome. We compared whole-genome and per-chromosome targeted recombination in 392 biparental maize (Zea mays L.) populations and in simulation experiments. For yield, moisture, test weight, and a simulated trait controlled by 2000 quantitative trait loci (QTL), predicted gains were 8%-9% larger with 10 targeted recombinations across the entire genome than with one targeted recombination on each of the 10 chromosomes. With whole-genome targeted recombination, the number of recombinations on a given chromosome was correlated (r = 0.76-0.91) with the chromosome size (in cM). Simulation results suggested that previous results on gains from targeted recombination relative to nontargeted recombination were too optimistic by around 20%. Because the underlying QTL are unknown, studies on targeted recombination have relied on genomewide marker effects as proxies for QTL information. The simulation results indicated a 25% (for 10 recombinations) to 33% (for 20 recombinations) reduction in response due to the use of genomewide marker effects as proxies for QTL information. Overall, the results indicated that the integer programming model we developed is useful for increasing both the predicted and true gains from targeted recombination, but the predicted gains are likely to overestimate the true gains., (© 2023 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Aims: Hyperaemic and non-hyperaemic pressure ratios (NHPR) are routinely used to identify significant coronary lesions. Machine learning (ML) techniques may help better understand these indices and guide future practice. This study assessed the ability of a purpose-built ML algorithm to classify coronary ischaemia during non-hyperaemia compared with the existing gold-standard technique (fractional flow reserve, FFR). Further, it investigated whether ML could identify components of coronary and aortic pressure cycles indicative of ischaemia., Methods and Results: Seventy-seven coronary vessel lesions (39 FFR defined ischaemia, 53 patients) with proximal and distal non-hyperaemic pressure waveforms and FFR values were assessed using supervised and unsupervised learning techniques in combination with principal component analysis (PCA). Fractional flow reserve measurements were obtained from the right coronary artery (13), left anterior descending (46), left circumflex (11), left main (1), obtuse marginal (2), and diagonal (4). The most accurate supervised learning classification utilized whole-cycle aortic with diastolic distal blood pressure waveforms, yielding a classification accuracy of 86.9% (sensitivity 86.8%, specificity 87.2%, positive predictive value 86.8%, negative predictive value 87.2%). Principal component analysis showed subtle variations in coronary pressures at the start of diastole have significant relation to ischaemia, and whole-cycle aortic pressure data are important for determining ischaemia., Conclusions: Our ML algorithm classifies significant coronary lesions with accuracy similar to previous studies comparing time-domain NHPRs with FFR. Further, it has identified characteristics of pressure waveforms that relate to function. These results provide an application of ML to ischaemia requiring only standard data from non-hyperaemic pressure measurements., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Trait introgression is a complex process that plant breeders use to introduce desirable alleles from one variety or species to another. Two of the major types of decisions that must be made during this sophisticated and uncertain workflow are: parental selection and resource allocation. We formulated the trait introgression problem as an engineering process and proposed a Markov Decision Processes (MDP) model to optimize the resource allocation procedure. The efficiency of the MDP model was compared with static resource allocation strategies and their trade-offs among budget, deadline, and probability of success are demonstrated. Simulation results suggest that dynamic resource allocation strategies from the MDP model significantly improve the efficiency of the trait introgression by allocating the right amount of resources according to the genetic outcome of previous generations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Han, Cameron, Wang, Pham and Beavis.)

Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were increases in systolic, diastolic, mean, and pulse aortic pressures (all P <0.05). Post-TAVR reservoir pressure was unchanged (54.5±12.4 versus 56.6±14.0 mm Hg, P =0.30) whereas excess pressure increased 47% (29.0±10.9 versus 42.6±15.5 mm Hg, P <0.001). Wave intensity analysis (arbitrary units, au) demonstrated increased forward compression wave (64.9±35.5 versus 124.4±58.9, ×10 3 au, P <0.001), backward compression wave (11.6±5.5 versus 14.4±6.9, ×10 3 au, P =0.01) and forward expansion wave energies (43.2±27.3 versus 82.8±53.1, ×10 3 au, P <0.001). Subendocardial viability ratio improved with aortic function effectively unchanged post-TAVR. Increased central aortic pressure following TAVR relates to increased transmitted power and energy to the proximal aorta with increased excess pressure but unchanged reservoir pressure. These changes provide a potential mechanism for the improved prognosis associated with relative hypertension post-TAVR.

The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The aim was to assess whether periprocedural myocardial injury (PPMI) predicts outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). PPMI is a strong predictor of outcomes following coronary intervention, but its impact in the context of TAVR remains unclear. We performed a systematic review and meta-analysis to ascertain the association between PPMI and short- or long-term outcomes., Methods and Results: Electronic searches identified studies reporting PPMI following TAVR. Primary end point was 30-day all-cause mortality, with secondary end points, including 1-year all-cause mortality, neurological events, post-TAVR pacemaker implantation, and aortic regurgitation. Analyses were performed using random effects modeling and reported as summary odds ratio (OR) with 95% CI. Nine studies comprising 3442 patients (mean age 81.0±6.6 years, 51.2% female) were included. PPMI occurred in 25.5% of patients following TAVR. The pooled all-cause mortality at 30-days and 1-year was 5.2% and 18.6%, respectively. The occurrence of PPMI following TAVR was associated with significantly increased risk of both 30-day (OR, 4.23; CI, 1.95-9.19; P<0.001) and 1-year all-cause mortality (OR, 1.77; CI, 1.05-2.99; P<0.001). Similarly, PPMI was associated with post-TAVR neurological events (OR, 2.72; CI, 1.69-4.37; P<0.001) and post-TAVR permanent pacing (OR, 1.43; CI, 1.02-2.00; P=0.04) but not with a statistically significant increase in aortic regurgitation post-TAVR (OR, 1.39; CI, 0.93-2.08; P=0.11)., Conclusions: PPMI is common following TAVR and is strongly associated with 30-day and 1-year mortality. Detection of PPMI has potential to identify TAVR patients at highest risk of subsequent adverse events.

Key Message: Using an Operations Research approach, we demonstrate design of optimal trait introgression projects with respect to competing objectives. We demonstrate an innovative approach for designing Trait Introgression (TI) projects based on optimization principles from Operations Research. If the designs of TI projects are based on clear and measurable objectives, they can be translated into mathematical models with decision variables and constraints that can be translated into Pareto optimality plots associated with any arbitrary selection strategy. The Pareto plots can be used to make rational decisions concerning the trade-offs between maximizing the probability of success while minimizing costs and time. The systematic rigor associated with a cost, time and probability of success (CTP) framework is well suited to designing TI projects that require dynamic decision making. The CTP framework also revealed that previously identified 'best' strategies can be improved to be at least twice as effective without increasing time or expenses.

We consider the plant genetic improvement challenge of introgressing multiple alleles from a homozygous donor to a recipient. First, we frame the project as an algorithmic process that can be mathematically formulated. We then introduce a novel metric for selecting breeding parents that we refer to as the predicted cross value (PCV). Unlike estimated breeding values, which represent predictions of general combining ability, the PCV predicts specific combining ability. The PCV takes estimates of recombination frequencies as an input vector and calculates the probability that a pair of parents will produce a gamete with desirable alleles at all specified loci. We compared the PCV approach with existing estimated-breeding-value approaches in two simulation experiments, in which 7 and 20 desirable alleles were to be introgressed from a donor line into a recipient line. Results suggest that the PCV is more efficient and effective for multi-allelic trait introgression. We also discuss how operations research can be used for other crop genetic improvement projects and suggest several future research directions., (Copyright © 2017 by the Genetics Society of America.)

Dengue viruses (DENVs) are the leading cause of mosquito-borne viral disease of humans. They exist in both endemic and sylvatic ecotypes. In 2014, a viremic patient who had recently visited the rainforests of Brunei returned to Australia displaying symptoms consistent with DENV infection. A unique DENV strain was subsequently isolated from the patient, which we propose belongs to a new genotype within DENV serotype 1 (DENV-1). Bayesian evolutionary phylogenetic analysis suggests that the putative sylvatic DENV-1 Brunei 2014 (Brun2014) is the most divergent DENV-1 yet recorded and increases the time to the most recent common ancestor (MRCA) for DENV-1 from ≈120 years to ≈315 years. DENV-1 classification of the Brun2014 strain was further supported by monoclonal antibody serotyping data. Phenotypic characterization demonstrated that Brun2014 replication rates in mosquito cells and infection rates in Aedes aegypti mosquitoes were not significantly different from an epidemic DENV-1 strain. Given its ability to cause human illness and infect Ae. aegypti, potential urban spillover and clinical disease from further Brun2014 transmission cannot be discounted.

A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM antibody seroconversions were detected between paired acute and convalescent phase sera using recombinant Zika virus serology assays. This is the first known imported case of Zika virus infection into northern Queensland where the potential mosquito vector Aedes aegypti is present and only the second such reported case diagnosed within Australia.

During seedling establishment, blue and red light suppress hypocotyl growth through the cryptochrome 1 (cry1) and phytochrome B (phyB) photosensory pathways, respectively. How these photosensory pathways integrate with growth control mechanisms to achieve the appropriate degree of stem elongation was investigated by combining cry1 and phyB photoreceptor mutations with genetic manipulations of a multidrug resistance-like membrane protein known as ABCB19 that influenced auxin distribution within the plant, as evidenced by a combination of reporter gene assays and direct auxin measurements. Auxin signaling and ABCB19 protein levels, hypocotyl growth rates, and apical hook opening were measured in mutant and wild-type seedlings exposed to a range of red and blue light conditions. Ectopic/overexpression of ABCB19 (B19OE) greatly increased auxin in the hypocotyl, which reduced the sensitivity of hypocotyl growth specifically to blue light in long-term assays and red light in high-resolution, short-term assays. Loss of ABCB19 partially suppressed the cry1 hypocotyl growth phenotype in blue light. Hypocotyl growth of B19OE seedlings in red light was very similar to phyB mutants. Altered auxin distribution in B19OE seedlings also affected the opening of the apical hook. The cry1 and phyB photoreceptor mutations both increased ABCB19 protein levels at the plasma membrane, as measured by confocal microscopy. The B19OE plant proved to be a useful tool for determining aspects of the mechanism by which light, acting through cry1 or phyB, influences the auxin transport process to control hypocotyl growth during de-etiolation.

The regulation of calcium in most crustaceans is especially challenging owing to the highly mineralized cuticle that must be recalcified after each moult, a process that often occurs in environments with low concentrations of calcium. The gill and carapace epithelia separate the major calcium-containing compartments of the body and therefore see large changes in the rate of calcium flux through the moult cycle. Large changes in the ultrastructure of these cells do not, however, correlate well with the periods of calcium movement and probably reflect other physiological events. Despite the challenges to regulating calcium levels at various acclimation salinities and moult stages, the calcium concentration in the blood is maintained relatively constant. There is a rapid increase to a high rate of calcium flux across both the gill and carapace epithelium shortly after the moult; on an area-specific basis these fluxes are among the highest reported for calcium-transporting epithelia. When in water with a very low concentration of calcium, the electrochemical gradient for calcium is directed outwards and net influx must occur by active transport. Evidence suggests that changes in the electrochemical gradient, permeability and active transport are all important in the ability of crustaceans to take up calcium from water with a low concentration of this ion. Although an enzyme transporter is presumably involved in the active transport of calcium across epithelia, very little is known about the cellular mechanism of the transepithelial movement of calcium in crustaceans.

Calcitonin-like immunoreactivity has been found in blood and tissues of the marine blue crab, Callinectes sapidus Rathbun. The activity in blood rises significantly during the immediate premolt (D4) stage, but tissue immunoreactivity does not vary significantly with molt stage. The immunoreactivity to antisalmon calcitonin serum is due to a 27.2 kDa protein that shows strong similarities in amino acid composition to a similar protein in a lobster and to human calcitonin precursor. The protein is most abundant in the midgut glands (hepatopancreas), but is also found in significant quantities in several other tissues. Immunoreactivity in the blood appears to be primarily due to the same molecular weight fraction, with secondary contributions from smaller molecules, closer in size to vertebrate calcitonin. A physiological function of the calcitonin-like substance in calcium transport during or after molt has yet to be demonstrated.

The blood acid-base status of blue crabs. Callinectes sapidus, was assessed at temperatures ranging from 10 to 30 degrees C. Blood pH varied inversely with temperature, with a slope (dpH/tT) of - 0.012. The PaCO rose only slightly between 10 and 27 degrees C, from 2.09 torr to 2.91 torr, with the result that the total dissolved CO2 actually fell slightly due to the decrease in solubility. In vitro the blood behaved like a conventional Rosenthal system, with a rise in PCO2 at constant CT which was much greater than the observed in vivo increase. I vivo the CT of the blood decreased significantly in order to maintain the OH/H ratio. The ratio of ventilation to oxygen consumption (and presumably carbon dioxide production) was not significantly different at 10 and 27 degrees C, indicating that ventilation is not participating in the acid-base adjustment to temperature. The principal acid-base regulating mechanisms in the crab are probably ionic exchanges in the gills rather than ventilatory control of PaCO2.

In the water-breathing fishes, rising temperatures are accompanied by progressive reduction in pH, reductions in bicarbonate concentration, and slight rises in CO2 partial pressure. The pH-temperature slope of both intra- and extracellular compartments varies considerably, from -0.009 to -0.033/degrees C, with a rather consistent pattern of red muscle greater than white muscle greater than heart. Three different approaches to acid-base analysis, the imidazole-alphastat model, the strong-ion difference analysis, and the delta-bicarbonate approach, were applied to a set of data from the fresh-water channel catfish (Ictalurus punctatus). A principal difficulty encountered in using all three approaches was that assumptions were required regarding the chemical behavior of the intracellular buffers, but the delta-bicarbonate approach has the practical advantage of emphasizing parameters that can be measured directly. Closed-system models are not generally applicable to fish, and the interest for future work lies in deciphering the significance of tissue-to-tissue variations in pH regulation and in elucidating the mechanisms of the strong-ion transfers.

Ammonia excretion rates of channel catfish, Ictalurus punctatus, little skate (Raja erinacea), and blue crab (Callinectes sapidus) were measured in experimental regimes which permitted simultaneous assessment of the partial pressure gradients for nonionized NH3 and the chemical concentration gradients of NH4+. Under conditions of low external ammonia, the average ammonia excretion was +295 microM kg-1 h-1 for catfish, +149 microM kg-1 h-1 for blue crabs, and +59 microM kg-1 h1 for skates with partial pressure gradients of +72.5 mu Torr, +413 mu Torr, and +24.4 mu Torr, respectively; and [NH4+] gradients of +189 microM l-1, +643 microM l-1, and +107 microM l-1 (positive indicating greater from inside to medium). When the external ammonia was increased to 1.15 mM l-1, both gradients were reversed, and the net ammonia movement was initially from the external water into all three species. In the catfish the inward movement ceased, however, and ammonia excretion eventually resumed in the face of reversed gradients of both NH3 partial pressure and [NH4+]. Unidirectional Na+ influx, indicative of a Na+/NH4+ exchange, did not increase. The ammonia data, changes in titratable acidity, and net apparent H+ efflux were all consistent with a linked extrusion of internal NH4+ for external H+. Incorporation of such an exchange into a computer simulation model of the ammonia equilibrium and exchange system duplicated the experimental data. Other hypotheses failed to match experimental data, or failed to predict internal ammonia levels lower than outside. In the crab, internal ammonia levels rose rapidly to concentrations and partial pressures above the external medium until excretion was reestablished, with no evidence of maintenance of a reversed gradient. In the skate, internal concentrations rose appreciably in the first hour and continued to rise for 6-8 h, with no resumption of ammonia excretion. The interspecies differences appear to be due at least partly to differences in ammonia permeability of the gills.

Acid and base loads infused into the dorsal aorta of the freshwater channel catfish (Ictalurus punctatus Rafinesque) were excreted by both gills and kidneys. The gills excreted 2-3 times as much as the kidneys. After a 2 mmol . kg-1 load of NaHCO3, the gills excreted 50% of the net OH- load in the first 5 h, while the kidneys excreted 18% in the first 6 h. After a 2 mmol . kg-1 load of NH4Cl, the gills excreted 32% of the load in 6 h, and 16% was excreted renally in 20 h. There was no evidence of tissue damage after either NaHCO3 or NH4Cl infusions, whereas infusion of 2 mmol . kg-1 HCl or 1 mmol . kg-1 of L(+)-lactic acid caused significant kidney damage and extensive tissue necrosis within 24 h. After both NaHCO3 and NH4Cl infusions, the majority of the load had been transferred to the intracellular compartment within 2 h. From there it was excreted slowly, presumably by transfer back through the extracellular compartment. Due to the relative compartment volumes and buffer values, the change in intracellular pH was less than 0.05 units, while the blood pH was changed by as much as 0.3 units.

Carbonic anhydrase (CA) activity was assayed in lysed erythrocytes and in branchial cytoplasm, mitochondria and microsomes of the channel catfish, Ictalurus punctatus. Branchial CA activity was highest in the cytoplasmic fraction, but activity was very low in mitochondria and microsomes. Erythrocyte CA activity was over four-fold greater than that in the gills. Intact animals were injected with the CA inhibitors acetazolamide and benzolamide. Slow, intra-arterial injection of both inhibitors elicited transient side effects of apnoea, bradycardia and hypoxaemia. Acetazolamide and benzolamide induced a mixed but primarily respiratory acidosis. The onset and the time course of the acidosis were correlated with the inhibition of erythrocyte CA; acetazolamide acted faster because it is more freely diffusible than benzolamide. The acid-base disturbance in the blood reached its maximum after 2 h; compensation was delayed until 24 h, when CA inhibition began to disappear. We conclude from these results that there is very little, if any, membrane-associated CA in the gill, and that the branchial enzyme is not quantitatively important in directly converting plasma HCO3- to CO2 for excretion. Rather, CO2 excretion is accomplished via the traditional chloride shift, followed by intracellular dehydration of HCO3- by erythrocyte CA. These results also suggest that branchial cytoplasmic CA inhibition might impair ion transport processes that are used to compensate blood acid-base disturbances and thus delay compensation of the respiratory acidosis.

The interaction of isovaleraldehyde, an attractant, with zoospores of the fungus Phytophthora palmivora was investigated by using binding techniques. The amount of isovaleraldehyde bound diminished with time, an effect that may be related to sensory adaptation. In addition to non-specific binding, specific and saturable isovaleraldehyde binding was demonstrated. Cooperativity occurred at intermediate but not at low and high ligand concentrations. [3H]isovaleraldehyde was displaced by unlabelled isovaleraldehyde and by a number of chemically related ligands known to be chemotactic agents.l Their dissociation constants as calculated from the displacement experiments paralleled their potency as attractants and it is suggested that these attractants act through the same receptor. Some other chemotactic agents did not displace [3H]isovaleraldehyde, and these presumably act through one or more other receptors.

The bowfin, Amia calva is a facultative air breathing fish which uses its respiratory swimbladder to augment oxygen uptake in normoxia at 30 degrees C. It does not die however, when denied access to the surface at this temperature. The bladder RQ is 0.21 while the gill RQ is 1.61 and thus most of the CO2 is excreted into the water across the gills. In aquatic hypoxia some of the oxygen taken up via the swimbladder is lost to the water across the gills. However CO2 excretion across the gills is maintained at the same rate as that found in normoxia.

1. Techniques for the measurement of unidirectional flux rates in fish which require no anaesthesia or surgery are described. 2. Resting values for Cl- uptake at 10 and 17 degrees C were 8-03 +/- 1-11 and 13-52 +/- 0-95 mu-equiv. 200 g-1 h-1 (+/- S.E.), respectively; and for Na+ the rates were 15-49 +/- 0-40 and 26-30 +/- 0-36, respectively. 3. Hypercapnic acidosis caused an increase in Na+ uptake, presumably through Na+/H+ (or NH+4) exchange. It is suggested that this is a compensation mechanism leading to the increase in blood buffering observed in response to hypercapnia. 4. Alkalosis was observed following acute temperature increase and was accompanied by an increase in the rate of Cl-/HCO-3 exchange and also by an increase in Na+/H+ exchange. 5. The role of these branchial ion exchange mechanisms in overall acidbase regulation is discussed.

An estimate of the total mass of bone in the Channel catfish Ictalurus punctatus Rafinesque, was obtained by dissection. The wet weight of bone constituted 16.3 +/- 1.9% (+/- S.D.) of the total (live) wet weight, and 25.0 +/- 2.1% of the dry weight. Of the dry skeletal material, 66.3 +/- 11.1% was soluble in strong acid. The acid-soluble material was about half mineral salts, consisting of 19.5 +/- 2.21% Ca2+ and 27.6 +/- 3.22% PO4(3-), with minor fractions of Mg2+ (0.33%) and CO3(2-) (1.67%). The pH values of fluid compartments associated with skull and vertebral bone tissues were 7.420 +/- 0.026 and 7.444 +/- 0.017 (+/- S.E.), respectively, at a normocapnic plasma pH of 7.868 +/- 0.020. In response to external hypercapnia (7.5 Torr), the blood response consisted of an immediate decrease in pH, and a subsequent compensatory rise in both pH and [HCO3-]. This compensatory phase was accompanied by a net apparent H+ excretion to the water. The participation of the mineral salts of the bone compartment in compensation appeared to be negligible, since there was no significant change in either blood [Ca2+] or [PO4(3-)], nor any significant increase in calcium efflux to the water. The intracellular pH values of the bone compartments were only slightly higher than other tissues, and the changes in pHi during hypercapnia were similar in bone and white muscle. Thus, the bone compartment in the fish appears to be well regulated, relatively refractory to acute acid-base disturbance, and does not serve as an ion source during acid-base compensation.

The relationship between acid-base status and temperature was studied in the channel catfish, Ictalurus punctatus. The change in blood pH with temperature had a slope of -0.0132/degrees C and involved both a decrease in total CO2 at higher temperatures, and a significant rise in arterial PCO2. The acid-base changes in the intracellular compartment were similar to those in the blood, except that for red and white muscle the slope of the change in pH with temperature had a slightly higher value (-0.0185 and -0.0147, respectively), and for heart muscle it had a smaller value (-0.0117). The net whole-body excretion of acid or base in response to temperature change was relatively small: 0.40 m-mole . kg-1 net OH- was excreted in response to an increase from 22 to 31 degrees C, and 0.31 m-mole . kg-1 net H+ was excreted in response to change from 25 to 15 degrees C. In both cases approximately half was excreted renally and half branchially. Using information on the volumes and buffer capacities of the various body fluid compartments as well as the information above, the ratio of imidazole to phosphate intracellular buffers was calculated to be 5.1 to 1. The amount of intercompartmental (active) transfer required to make temperature adjustments is strongly dependent on the buffer ratio, and on the PCO2. Without the observed changes in PCO2 with temperature, the transfer requirement would have been 3 to 4 times larger.

The nature of pH changes with temperature is similar in both air-breathing and water-breathing poikilotherms having a pH-temperature slope of -0.015 to 0.020 U/degrees C. The means by which this is accomplished are quite different in the two groups. The air-breather behaves in vivo as a Rosenthal, or constant CO2 content system, with PaCO2 increasing at higher temperatures. The increase in PaCO2 is brought about by a reduction in the ration VE/MCO2. The water-breather, on the other hand, does not change VG/MO2, so as not to sacrifice oxygen delivery, and consequently does not control PaCO2 by ventilation and perhaps does not control it at all. Instead, the ratio of CT/SCO2 is controlled by altering blood bicarbonate concentration. Since alteraction of Na+ and Cl- uptake rates affects blood pH, and alterations of blood pH affect uptake of Na+ and Cl- at the gills, the carrier-mediated Na+/H+(NH4+) and Cl-/HCO3-(OH-) mechanisms now known to occur in gills appear to be the primary pH-regulating mechanism in water-breathers. Our knowledge of the role of gut and kidney in pH regulation is incomplete, but on the basis of preliminary information the kidney does not appear to respond to acid challenge.